Alcohol oligomerization

Abstract

The present invention is 1~3 Regarding the process for converting alcohol to higher alcohol, the process comprises the steps of: 1~3 a. premixing an alcohol, a catalyst, and a multicomponent solvent system to form a liquid mixture; and b. heating the liquid mixture, thereby obtaining a higher alcohol, wherein the multicomponent solvent system comprises at least a basic aqueous hydrocarbon solvent phase comprising at least two different hydrocarbons, the solvent comprising a base selected from the group comprising potassium hydroxide, sodium hydroxide, potassium ethoxide, sodium ethoxide, potassium t-butoxide, sodium t-butoxide, or a combination thereof, e.g., a eutectic mixture of sodium hydroxide and potassium hydroxide, and the catalyst is (HL)M(OH) n (H2O) m type complexes and activated carbon.

Description

[Technical Field]

[0001] FIELD OF THE INVENTION The present invention relates to the technical field of catalytic oligomerization of lower alcohols to produce higher alcohols, in particular the production of n-butanol from oligomerized ethanol. [Background technology]

[0002] Background of the Invention Several processes exist to form alcohols (C3 and above), but they all have certain drawbacks, as detailed in Figure 1. They are typically derived from crude oil, resulting in a huge carbon footprint.

[0003] The synthesis of n-butanol uses ethanol as the starting molecule and employs a catalytic reaction process. Two catalytic reaction mechanisms have been proposed in the literature: the direct dimerization of two ethanol molecules and a multi-step tandem synthesis route known as the Guerbet reaction. The "direct mechanism" requires high reaction temperatures (>350 °C), while the indirect route operates at lower reaction temperatures. Given the many advantages of upgrading ethanol to n-butanol (and other higher alcohols), the search for homogeneous and heterogeneous catalysts has attracted significant attention in recent years in both scientific and industrial fields.

[0004] The main types of homogeneous catalysts for upgrading ethanol to n-butanol are complexes of iridium, manganese, gold, copper, niobium, platinum, palladium, vanadium, titanium, zirconium, iron, ruthenium, molybdenum, osmium, or nickel in combination with strong bases, such as sodium hydroxide, potassium hydroxide, or sodium ethoxide. These reactions are believed to proceed via the Guerbet mechanism. Transition metals are involved in ethanol dehydrogenation and aldehyde hydrogenation, while strong bases are involved in aldol condensation. Although literature has documented n-butanol selectivity of 80% at over 50% ethanol conversion, numerous issues with homogeneous catalysts prevent their use in industrial processes. These issues include very high air sensitivity, low water tolerance, rapid decomposition of the ligands, and the difficulty of their recovery from the reaction product. This not only causes processing discontinuities and catalyst loss, but most importantly, impairs the scalability of the reaction.

[0005] Considering the shortcomings of homogeneous catalysts, heterogeneous catalysts, processes, and corresponding reaction mechanisms have been widely explored in recent years as solutions for the conversion of ethanol to n-butanol. These heterogeneous catalysts include metal oxides, zeolites, hydroxyapatite catalysts, mixed metal oxides, and supported metal catalysts. However, each reported type of heterogeneous catalyst has its own drawbacks: low n-butanol selectivity, low conversion rate, and harsh reaction conditions. Other problems that can arise with these catalysts include low water resistance and high cost. Because water is typically present in the reaction mixture and is produced during the dehydration reaction of the reaction process, sufficient water resistance is crucial.

[0006] Today, n-butanol is industrially synthesized directly from petroleum feedstocks via energy-intensive processes or via fermentation processes, which are time-consuming and have very low yields, as summarized above. An alternative process is the synthesis of n-butanol from bioethanol using a wide variety of catalysts. This has been extensively studied and documented in both scientific papers and patents. However, current limitations in the industrialization of catalytic bioethanol / n-butanol conversion using synthesized catalysts include low n-butanol selectivity, low conversion, harsh reaction conditions (high temperature and / or pressure), poor catalyst water resistance, catalyst cost, and low scalability. These are the reasons why catalytic n-butanol production from ethanol is currently uneconomical.

[0007] WO 2015 / 031561 discloses a method for converting a lower alcohol (e.g., ethanol) to a higher alcohol (e.g., butanol) in the presence of a water-stable transition metal catalyst comprising a Group VIII transition metal and a multidentate nitrogen donor ligand.

[0008] WO 2019 / 193079 discloses a process for obtaining higher aliphatic alcohols starting from aliphatic primary alcohols by a condensation reaction. Specifically, the process involves contacting the aliphatic primary alcohol with a catalyst mixture containing a transition metal, a base, and an additive in a homogeneous phase. Summary of the Invention [Problem to be solved by the invention]

[0009] It is therefore an object of the present invention to provide a process that overcomes one or more of the above-mentioned problems, particularly in the conversion of (bio)ethanol to (bio)n-butanol and higher alcohols. [Means for solving the problem]

[0010] SUMMARY OF THE INVENTION The inventors have discovered that one or more of the above objectives may be achieved using the presently claimed process and its (preferred) embodiments.

[0011] The present invention provides for the conversion of C1, C2, C3, and C5 alcohols from renewable feedstocks to higher (C4 and higher) alcohols, which can be further upgraded by known industrial processes.

[0012] An advantage of the present invention is that this type of catalyst is air and water stable, therefore the reaction mixture can be easily prepared in air.

[0013] A further advantage of the present invention is that very high ethanol conversions can be achieved. A further advantage of the present invention is that little or no by-products such as acetaldehyde, crotonaldehyde, or any other aldol condensation products are formed.

[0014] A further advantage of the present invention is that no additional hydrogen supply is required. A further advantage of the present invention is that the products can be controlled by the reaction time, for example, longer reaction times will give higher alcohols as C6 and C8 homologues.

[0015] A further advantage of the present invention is that it provides an economically viable ethanol oligomerization by providing an efficient combination of both a high n-butanol selectivity reaction process and efficient catalyst recycling to minimize catalyst leaching.

[0016] A further advantage of the present invention is that the application of a specific solvent system allows for optimal reaction conditions and optimal catalyst recycling conditions.

[0017] A further advantage of the present invention is that it uses only water, which can be purified by simple distillation using molecular sieves. Additional impurities, such as fusel alcohols, resulting from the fermentation process do not interfere with the process.

[0018] A further advantage of the present invention is that it avoids the complexities of prior art processes. A further advantage of the present invention is that no synthesis gas feed or hydrogen input is required, and therefore no specific partial pressure control is required.

[0019] A further advantage of the present invention is that there is no requirement for n-selectivity: only n-butanol is obtained.

[0020] A further advantage of the present invention is that the mixture can be prepared in air and have catalytic stability for several months under ambient conditions, without the need for complicated procedures as in the prior art.

[0021] A further advantage of the present invention is that it results in a relatively simple and pure single product resulting in overall process simplicity.

[0022] A further advantage of the present invention is that the process produces C4, C6, and C8 alcohols, but favors C4 products, with prolonged heating increasing the conversion to C6 and C8.

[0023] A further advantage of the present invention is that it can start from bioethanol, which is environmentally friendly and works below 200°C, making it very simple and commercially attractive.

[0024] A further advantage of the present invention is that the process is not limited to co-located alumina production sites and pyrophoric catalysts.

[0025] A further advantage of the present invention is that the process requires approximately 6 hours compared to ABE fermentation, resulting in a high turnover rate.

[0026] A further advantage of the present invention is that while collocation may be beneficial, it is not required for economic success.

[0027] A further advantage of the present invention is that the conversion and selectivity to n-butanol are high enough to ensure profitability without reliance on sidestreams.

[0028] The present invention allows for the use and retrofitting of existing infrastructure of fossil fuel-based commercial plants.

[0029] According to a first aspect, the present invention provides a method for producing a medicament for the treatment of a medicament comprising: 1~3 The present invention relates to a process for converting alcohols into higher alcohols, the process preferably comprising: aC 1~3 premixing an alcohol, a catalyst, and a multi-component solvent system to form a liquid mixture; and b. Heating the liquid mixture, thereby obtaining a higher alcohol.

[0030] The multi-component solvent system preferably comprises at least a basic aqueous hydrocarbon solvent phase comprising at least two different hydrocarbons, the solvent comprising a base selected from the group comprising potassium hydroxide, sodium hydroxide, potassium ethoxide, sodium ethoxide, potassium t-butoxide, sodium t-butoxide, or combinations thereof, e.g., a eutectic mixture of sodium hydroxide and potassium hydroxide.

[0031] The catalyst is (HL)M(OH) n (H2O) m The compound includes a complex of the type, and preferably includes activated carbon. M is preferably a metal selected from the group comprising Ru, Co, Ir, Rh, Os, Mo, W, Sc, Tc, Pt, Pd, Fe, or Ni.

[0032] HL is preferably indole, maleimide, maltol, 5-hydroxymaltol, kojic acid, tropolone, thujaplicin, hinokitiol, stipitatic acid, 2,6-bis[4-isopropyl-2-oxazolin-2-yl]pyridine, imidazole, 2,6-bis[4-phenyl-2-oxazolin-2-yl]pyridine, 2,6-bis[(3,8)-8H-indeno[1,2-d]oxazolin-2-yl)pyridine, pyrrole, pyrazole, 4-hydroxypyrazole, pyrazole-3-carboxaldehyde, pyrazole Pyrazole-3-carboxylic acid, pyrazole-4-carboxylic acid, pyrazole-3,5-dicarboxylic acid, 4-alkyl / arylpyrazoles, 3-alkyl / arylpyrazoles, 5-alkyl / arylpyrazoles, 3,5-alkyl / arylpyrazoles, 1-benzylpyrazole, 3,5-di(2-pyridyl)pyrazole, 2-(1H-pyrazol-3-yl)phenol, 2-(1H-pyrazol-5-yl)aniline, 3-alkylpyrazole-5-carboxylic acid, indazole, 5-hydroxypyrazole, tris(1-pyrazolyl)methan Benzimidazole, tris(3,5-dimethyl-1-pyrazolyl)methane, bis(pyrazolyl)methane, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole, 4-amino Aryl imidazole, 5-alkylimidazole, 5-arylimidazole, 4-methylimidazole, 1-benzylpyrazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 5-methylimidazole, 2-(1H-imidazol-2-yl)pyridine, 2-(1-hydroxyethyl)benzimidazole, 5-methylimidazole, 2-(2-pyridyl)benzimidazole, 2-(2-hydroxyphenyl)-1H-benzimidazole, 1H-pyrazol-3-ylboronic acid hydrate, 3,5-dimethyl-4-hydroxypyrazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(2-pyridyl)benzothiophene, 2-aryl-4H-(1,2,4)triazoles, 2-(4-methyl-2-pyridyl)-1H-benzimidazole, 2-arylbenzothiazoles, 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-5,5'-dicarboxylic acid, 2,2'-bipyridine-3,3'-dicarboxylic acid, 4-imidazolecarboxylic acid, 4-pyrrozolecarboxylic acid, pyrrole-3-carboxylic acid, 5-oxazolecarboxylic acid, 2,2'-bis(4,5-dimethylimidazole), 2, The protic monodentate organic ligand, the protic bidentate organic ligand, or the protic bidentate organic ligand is selected from the group consisting of 2'-bisimidazole, imidazole-4-carboxaldehyde, imidazole-4,5-dicarboxylic acid, 4,4'-bisimidazole, 4,4'-bisbenzimidazole, 2,2'-bisbenzimidazole, 4,5-bis(hydroxymethyl)imidazole, trisodium 3,3',3''-phosphanetriyltri(benzene-1-sulfonate), 2-(diphenylphosphino)benzenesulfonic acid, bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt, and 4,4'-(phenylphosphinidene)bis(benzenesulfonic acid) dipotassium salt hydrate, and 2-[di(2-methoxyphenyl)phosphino]benzenesulfonic acid.

[0033] m and n are integers. In some preferred embodiments, C 1~3 The alcohol is ethanol, preferably bioethanol. In some preferred embodiments, the solvent / ethanol ratio is at least 2.0, preferably at least 3.0. In some preferred embodiments, the ethanol is fuel-grade ethanol.

[0034] In some preferred embodiments, the ligand HL is selected from the group consisting of imidazole, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 4-methylimidazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 5-methylimidazole, 2-(1H-imidazol-2-yl)pyridine, 2-(1-hydroxyethyl)benzoyl Imidazole, 5-methylimidazole, 2-(2-pyridyl)benzimidazole, 2-(2-hydroxyphenyl)-1H-benzimidazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(4-methyl-2-pyridyl)-1H-benzimidazole Preferably, the ligand HL is selected from the group comprising imidazole, 2,2'-bis(4,5-dimethylimidazole), 2,2'-bisimidazole, imidazole-4-carboxaldehyde, imidazole-4,5-dicarboxylic acid, 4,4'-bisimidazole, 4,4'-bisbenzimidazole, 2,2'-bisbenzimidazole, 4,5-bis(hydroxymethyl)imidazole, and

[0035] In some preferred embodiments, the metal is Ru. In some preferred embodiments, the catalyst further comprises a skeletal or sponge metal catalyst, preferably Raney nickel.

[0036] In some preferred embodiments, the basic aqueous solvent phase comprises an alkali hydroxide, preferably KOH.

[0037] In some preferred embodiments, step a. is carried out at ambient temperature. In some preferred embodiments, step b. b1. Heating the mixture to a temperature T1 within a time frame Δt1; b2. Heating the mixture to a temperature T2 within a time frame Δt2; and b3. Maintaining the mixture at temperature T2 for a time period Δt3.

[0038] In some preferred embodiments, T2 is at least 140°C and up to 500°C, preferably at least 150°C and up to 400°C, preferably at least 160°C and up to 300°C, preferably at least 170°C and up to 260°C, preferably at least 180°C and up to 240°C, preferably at least 190°C and up to 220°C, preferably about 200°C.

[0039] In some preferred embodiments, C 1~3 The alcohol is converted to n-butanol. In some preferred embodiments, 1~3 Alcohol is C 6~8 Converted to alcohol.

[0040] In some preferred embodiments, the reaction vessel acts as an intrinsic catalyst. In some preferred embodiments, the process comprises: a. Further comprising distilling the higher alcohol.

[0041] According to a second aspect, the present invention provides a method for producing a medicament for the treatment of a medicament comprising: 1~3 The present invention relates to the use of the catalysts described herein in the conversion of alcohols to higher alcohols.

[0042] The dependent and dependent claims set out particular and preferred features of the invention. Features from the dependent claims may be combined with features of the independent claims or with features of other dependent claims as appropriate.

[0043] These and other characteristics, features, and advantages of the present invention will become apparent from the following detailed description. [Brief explanation of the drawings]

[0044] [Figure 1] FIG. 1 shows multiple cascade reactions for producing oxo alcohols (underlined) from crude oil. [Figure 2] Figure 1 shows the proposed cascade reaction to form n-butanol (underlined), but the products produced from side reactions are not underlined. [Figure 3] FIG. 1 is a schematic diagram showing possible deprotonation of a ligand by a base. [Figure 4] 1 is a schematic diagram of phase separation according to one embodiment of the present invention, where the lower region is the aqueous phase and the upper region is the hydrocarbon phase. [Figure 5] FIG. 1 illustrates reaction rates according to one embodiment of the present invention. [Figure 6] FIG. 1 shows the octanol / water partition coefficients at 25° C. of molecules in the reaction pathway. [Figure 7] FIG. 1 is a schematic diagram of phase separation in 1-propanol conversion. [Figure 8] 1 shows a schematic diagram of a gas chromatograph (GC) of crude phase conversion of ethanol. [Figure 9] 1 shows a gas chromatographic schematic of the crude phase conversion of ethanol and 1-propanol. DETAILED DESCRIPTION OF THE INVENTION

[0045] Detailed Description of the Invention In describing the present invention, terms used should be construed in accordance with the following definitions, unless the context dictates otherwise.

[0046] Unless otherwise defined, all terms used in disclosing the present invention, including technical and scientific terms, have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs. By way of further guidance, term definitions are included to better understand the teachings of the present invention.

[0047] In the following description, different aspects of the invention are defined in more detail. Each aspect so defined can be combined with any other aspect, unless expressly indicated otherwise. In particular, any feature indicated as being preferred or advantageous can be combined with any other feature indicated as being preferred or advantageous.

[0048] Throughout this specification, references to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrase "in one embodiment" or "in an embodiment" in various places throughout this specification do not necessarily all refer to the same embodiment, although they may. Furthermore, in one or more embodiments, particular features, structures, or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure. Furthermore, while some embodiments described herein include some features that are not included in other embodiments, it is understood by one of ordinary skill in the art that combinations of features from different embodiments are within the scope of the present invention and are meant to form different embodiments.

[0049] As used herein, the terms "comprising," "comprises," and "comprised of" are synonymous with "including," "includes," or "containing," "contains," and are inclusive or open-ended and do not exclude other unrecited elements, elements, or method steps. As used herein, the terms "comprising," "comprises," and "comprised of" will be understood to include the terms "consisting of," "consists," and "consists of."

[0050] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. By way of example, "a step" means one step or more than one step.

[0051] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All publications referenced herein are incorporated herein by reference.

[0052] The recitation of numerical ranges by endpoints includes all integers and, where appropriate, fractions subsumed within the range (e.g., 1 to 5 can include 1, 2, 3, and 4, e.g., when referring to several elements, and can also include 1.5, 2, 2.75, and 3.80, e.g., when referring to measurements). The recitation of endpoints also includes the endpoint values ​​themselves (e.g., 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical range recited herein is intended to include all subranges subsumed therein. When used as indicators of chemical structures, integers are typically positive, non-zero integers.

[0053] The term "about," as used herein when referring to a measurable value such as a parameter, amount, duration, etc., is meant to encompass a variation of no more than ±10%, preferably no more than ±5%, and more preferably no more than ±1% of the particular value, provided that such variation is appropriate for practicing the disclosed invention. It is to be understood that the value to which the modifier "about" refers is itself specifically, preferably, and disclosed.

[0054] In describing the present invention, terms used should be construed in accordance with the following definitions, unless the context dictates otherwise.

[0055] Whenever the term "substituted" is used in this invention, it means that one or more hydrogens of the atom designated by the term "substituted" are replaced with a group selected from the designated group, provided that the normal valence of the atom is not exceeded and the substitution results in a chemically stable compound, i.e., a compound that is sufficiently robust that it can be isolated in a useful purity from a reaction mixture.

[0056] Preferred embodiments of the present invention are described below. Each embodiment of the invention so defined can be combined with any other embodiment unless expressly indicated otherwise. In particular, any feature indicated as being preferred or advantageous can be combined with any other feature or description indicated as being preferred or advantageous.

[0057] According to a first aspect, the present invention provides a method for producing a medicament for the treatment of a medicament comprising: 1~3 The present invention relates to a process for converting alcohols into higher alcohols, the process preferably comprising: aC 1~3 premixing an alcohol, a catalyst, and a multi-component solvent system to form a liquid mixture; and b. Heating the liquid mixture, thereby obtaining a higher alcohol.

[0058] The catalyst is (HL)M(OH) n (H2O) mtype complexes (where m and n each independently represent an integer, for example, 1, 2, or 3), and preferably also includes activated carbon.

[0059] M is preferably a metal selected from the group including Ru, Co, Ir, Rh, Os, Mo, W, Sc, Tc, Pt, Pd, Fe, or Ni. In some preferred embodiments, the metal is Ru, Co, Ni, or V. In some preferred embodiments, the metal is Ru or Co. In some preferred embodiments, the metal is Ru.

[0060] The selection of the ligand (HL) (Figure 3) was found to be important in this invention because the addition of a strong base, such as KOH, to any transition metal halide can result in the formation of an insoluble, unreactive black precipitate (presumably an oxide). Most importantly, the processes involved in this invention are thermal operations, such as the conversion of ethanol to n-butanol, distillation, and rectification, processes that typically result in thermal stress on the catalyst, potentially causing decomposition reactions and gradual deactivation over the catalyst's lifetime. Thermal separation processes rarely result in quantitative catalyst recovery, resulting in reduced productivity through metal loss. The ligand confers high polarity to the catalyst, making it insoluble in the organic phase and minimizing metal loss.

[0061] In some preferred embodiments, the HL is preferably indole, maleimide, maltol, 5-hydroxymaltol, kojic acid, tropolone, thujaplicin, hinokitiol, stipitatic acid, 2,6-bis[4-isopropyl-2-oxazolin-2-yl]pyridine, imidazole, 2,6-bis[4-phenyl-2-oxazolin-2-yl]pyridine, 2,6-bis[(3,8)-8H-indeno[1,2-d]oxazolin-2-yl)pyridine, pyrrole, pyrazole, 4-hydroxypyrazole, pyrazole-3-carbohydrate, 4-hydroxypyrazole, 4-hydroxybenzoyl ... Alkyl aldehyde, pyrazole-3-carboxylic acid, pyrazole-4-carboxylic acid, pyrazole-3,5-dicarboxylic acid, 4-alkyl / aryl pyrazoles, 3-alkyl / aryl pyrazoles, 5-alkyl / aryl pyrazoles, 3,5-alkyl / aryl pyrazoles, 1-benzylpyrazole, 3,5-di(2-pyridyl)pyrazole, 2-(1H-pyrazol-3-yl)phenol, 2-(1H-pyrazol-5-yl)aniline, 3-alkylpyrazole-5-carboxylic acid, indazole, 5-hydroxypyrazole, tris(1- (pyrazolyl)methane, tris(3,5-dimethyl-1-pyrazolyl)methane, bis(pyrazolyl)methane, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole , 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 4-methylimidazole, 1-benzylpyrazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 5-methylimidazole, 2-(1H-imidazol-2-yl)pyridine, 2-(1-hydroxyethyl)benzimidazole, 5-methylimidazole, 2-(2-pyridyl)benzimidazole, 2-(2-hydroxyphenyl)-1H-benzimidazole, 1H-pyrazol-3-ylboronic acid hydrate, 3,5-dimethyl-4-hydroxypyrazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(2-pyridyl)benzothiophene, 2-aryl-4H-(1,2,4)triazoles, 2-(4-methyl-2-pyridyl)-1H-benzimidazole, 2-arylbenzothiazoles, 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-5,5'-dicarboxylic acid, 2,2'-bipyridine-3,3'-dicarboxylic acid, 4-imidazolecarboxylic acid, 4-pyrrozolecarboxylic acid, pyrrole-3-carboxylic acid, 5-oxazolecarboxylic acid, 2,2'-bis(4,5-dimethylimidazole), 2, The protic monodentate organic ligand, the protic bidentate organic ligand, or the protic bidentate organic ligand is selected from the group including 2'-bisimidazole, imidazole-4-carboxaldehyde, imidazole-4,5-dicarboxylic acid, 4,4'-bisimidazole, 4,4'-bisbenzimidazole, 2,2'-bisbenzimidazole, 4,5-bis(hydroxymethyl)imidazole, trisodium 3,3',3''-phosphanetriyltri(benzene-1-sulfonate), 2-(diphenylphosphino)benzenesulfonic acid, bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt, and 4,4'-(phenylphosphinidene)bis(benzenesulfonic acid) dipotassium salt hydrate, 2-[di(2-methoxyphenyl)phosphino]benzenesulfonic acid.

[0062] In some preferred embodiments, the ligand HL is selected from the group consisting of indole, maleimide, maltol, 5-hydroxymaltol, kojic acid, tropolone, thujaplicin, hinokitiol, stipitatic acid, 2,6-bis[4-isopropyl-2-oxazolin-2-yl]pyridine, imidazole, 2,6-bis[4-phenyl-2-oxazolin-2-yl]pyridine, 2,6-bis[(3,8)-8H-indeno[1,2-d]oxazolin-2-yl)pyridine, pyrrole, pyrazole, 4-hydroxypyrazole, pyrazole-3-carboxylate, 4-hydroxypyrazole, 4-hydroxybenzoyl ... Aldehydes, pyrazole-3-carboxylic acid, pyrazole-4-carboxylic acid, pyrazole-3,5-dicarboxylic acid, 4-alkyl / arylpyrazoles, 3-alkyl / arylpyrazoles, 5-alkyl / arylpyrazoles, 3,5-alkyl / arylpyrazoles, 1-benzylpyrazole, 3,5-di(2-pyridyl)pyrazole, 2-(1H-pyrazol-3-yl)phenol, 2-(1H-pyrazol-5-yl)aniline, 3-alkylpyrazole-5-carboxylic acid, indazole, 5-hydroxypyrazole, tris(1-pyrazol-3-yl)phenol, (pyrazolyl)methane, tris(3,5-dimethyl-1-pyrazolyl)methane, bis(pyrazolyl)methane, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole, 4-Arylimidazole, 5-Alkylimidazole, 5-Arylimidazole, 4-Methylimidazole, 1-Benzylpyrazole, 4-Arylimidazole, 5-Alkylimidazole, 5-Arylimidazole, 5-Methylimidazole, 2-(1H-Imidazol-2-yl)pyridine, 2-(1-Hydroxyethyl)benzimidazole, 5-Methylimidazole, 2-(2-Pyridyl)benzimidazole, 2-(2-Hydroxyphenyl)-1H-benzimidazole, 1H-Pyrazol-3-ylboronic acid hydrate, 3,5-dimethyl-4-hydroxypyrazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(2-pyridyl)benzothiophene, 2-aryl-4H-(1,2,4)triazole, 2-(4-methyl-2-pyridyl)-1H-benzimidazole, 2-arylbenzothiazole, 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-5,5'-dicarboxylic acid, 2,2'-bipyridine-3,3'-dicarboxylic acid, The compound is selected from the group consisting of 4-imidazolecarboxylic acid, 4-pyrrolecarboxylic acid, pyrrole-3-carboxylic acid, 5-oxazolecarboxylic acid, 2,2'-bis(4,5-dimethylimidazole), 2,2'-bisimidazole, imidazole-4-carboxaldehyde, imidazole-4,5-dicarboxylic acid, 4,4'-bisimidazole, 4,4'-bisbenzimidazole, 2,2'-bisbenzimidazole, 4,5-bis(hydroxymethyl)imidazole, 2-(diphenylphosphino)benzenesulfonic acid, and 2-[di(2-methoxyphenyl)phosphino]benzenesulfonic acid.

[0063] In some preferred embodiments, the ligand HL is selected from the group consisting of imidazole, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 4-methylimidazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 5-methylimidazole, 2-(1H-imidazol-2-yl)pyridine, 2-(1- hydroxyethyl)benzimidazole, 5-methylimidazole, 2-(2-pyridyl)benzimidazole, 2-(2-hydroxyphenyl)-1H-benzimidazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(4-methyl 4,5-bis(hydroxymethyl)imidazole, ...

[0064] Preferably, the ligand HL is imidazole. In some preferred embodiments, the aqueous hydrocarbon solvent is added under elevated temperature (eg, at least 40° C.) conditions in the presence of at least one "additional" catalyst.

[0065] "Additional catalyst" means that the catalyst is complementary to the reaction components, i.e., C 1~3It will be understood to be separate from components that are inherently present with the reaction components, such as the alcohol, the catalyst of claim 1, the aqueous solvent, and / or the walls of the reactor apparatus. In other words, the "additional" catalyst contemplated herein may be considered to be an "exogenous" catalyst in the sense that it is provided to the reaction as an individual reaction component.

[0066] Additional catalysts contemplated herein can be selected from the following non-limiting examples: base catalysts, acid catalysts, alkali metal hydroxide catalysts, transition metal hydroxide catalysts, alkali metal formate catalysts, transition metal formate / acetate catalysts, reactive carboxylic acid catalysts, transition metal catalysts, transition metal carbonyl halide catalysts, transition metal halide or carbonyl or sulfide or phosphine or imidazole or pyrazole or acetate or butrate catalysts, noble metal catalysts, water gas shift catalysts, and combinations thereof.

[0067] The process of the present invention can be carried out using an "additional" catalyst in combination with an "intrinsic" catalyst.

[0068] The optimal amount of additional catalyst used in the method of the present invention is determined, for example, by the type or source of ethanol to be treated, the first generation (G1:1 st generation), second generation (G2:2 nd generation), CO2-derived, and / or fossil fuel-derived, the volume of ethanol to be treated, the aqueous solvent utilized, the particular temperature and pressure employed during the reaction, the type of catalyst and desired properties of the final product, n-butanol or higher alcohol mixture selectivity, and the nature of the reactor equipment.

[0069] In some preferred embodiments, the additional catalyst or combination of additional catalysts may be used in an amount (relative to the ethanol feedstock) of about 0.01% to about 50% by weight of catalyst, about 0.1% to about 20% by weight of catalyst, about 0.1% to about 10% by weight of catalyst, about 0.1% to about 5% by weight of catalyst, about 0.1% to about 2.5% by weight of catalyst, about 0.1% to about 1% by weight of catalyst, or about 0.1% to about 0.5% by weight of catalyst.

[0070] In some embodiments, the hydrolysis catalyst may be a base catalyst. Any suitable additional base catalyst may be used.

[0071] In some preferred embodiments, aluminosilicates, including hydrated forms (e.g., zeolites), may be used to aid in water dehydration (desorption). Non-limiting examples of zeolites include ZSM-5, mordenite, Y, USY, and beta zeolites, SAPO-11, SAPO-34, molecular sieves, phosphates, zirconates, kaolinite, montmorillonite, pillared clays, hydrotalcites, and acidic ion exchange resins such as Amberlyst-15® and -35®, Nafion SAC-13®, and the like.

[0072] In some preferred embodiments, oxygen removal can be facilitated by thermal means, including decarbonylation, e.g., to aldehydes (to produce RC-H and CO gas or CH) and decarboxylation of carboxylic acids in the material being treated (to produce RC-H and CO gas). The rates of these reactions can be enhanced by the addition of acid catalysts and / or transition (noble) metal catalysts. Any suitable transition or noble metal can be used, including those supported on solid acids, or simply as a reactor surface. Non-limiting examples include Pt / Al2O3 / SiO2, Pd / Al2O3 / SiO2, Ni / Al2O3 / SiO2, Ru / Al2O3 / SiO2, Os / Al2O3 / SiO2, Cr / Al2O3 / SiO2, Co / Al2O3 / SiO2, Fe / Al2O3 / SiO2, W / Al2O3 / SiO2, Mo / Al2O3 / SiO2, Re / Al2O3 / SiO2, Cu / Al2O3 / SiO2, and mixtures thereof.

[0073] In some preferred embodiments, a combined acid / base and hydrogenation catalyst may be used to facilitate oxygen removal, for example, by hydrodeoxygenation, i.e., water elimination via the acid / base component and double bond saturation via the metal component. Any suitable combined acid / base and hydrogenation catalyst may be used, including those supported on solid acids or in combination with ion exchange resins. Non-limiting examples include Pt / Al2O3 / SiO2, Pd / Al2O3 / SiO2, Ni / Al2O3 / SiO2, NiO / MoO3, CoO / MoO3, NiO / WO2, zeolites loaded with precious metals (e.g., ZSM-5, Beta, ITQ-2), and mixtures thereof.

[0074] In some preferred embodiments, a water gas shift (WGS) catalyst may be used to increase the hydrogen concentration in the reaction, i.e., via the water gas shift reaction. Any suitable water gas shift (WGS) catalyst may be used, including, for example, transition metals, transition metal oxides, and mixtures thereof, such as magnetite, platinum-based WGS catalysts, finely divided copper and nickel, Raney® nickel, or copper, and components of reactor materials, and mixtures thereof.

[0075] In some preferred embodiments, particularly advantageously suitable catalysts for use in the process according to the invention are skeletal or sponge metal catalysts, known as "Raney® catalysts." These include Raney® nickel, cobalt, or copper, and copper-containing metal alloys in the form of Raney® catalysts. Raney® catalysts are preferred, with at least 70%, and especially at least 99%, of their metal components being stainless steel. Raney nickel may also be referred to as sponge nickel.

[0076] In some preferred embodiments, the catalyst further comprises a skeletal or sponge metal catalyst, preferably Raney nickel. Raney nickel is a nickel-aluminum alloy. Preferably, the alloy has a Ni:Al ratio of about 1:1.

[0077] In some embodiments, the catalyst is provided as a single-site catalyst. In some embodiments, the catalyst is supported, preferably supported on an aluminosilicate structure.

[0078] In some preferred embodiments, the catalyst is provided in step a. at least 0.01 mol % and up to 1.00 mol %, preferably at least 0.02 mol % and up to 0.10 mol %, preferably about 0.05 mol %.

[0079] In some embodiments, any type of activated carbon, such as medical-grade activated carbon, may be used. Preferably, the activated carbon is peat-sourced. Preferably, the activated carbon is steam-activated. Preferably, the activated carbon is in powder form. For example, peat-derived, steam-activated, powdered activated carbon, Norit® Environmentally Friendly Alternative Norit® SA2, manufactured by Merck, may be used. Advantageously, it has been found that the processes disclosed herein, including a catalyst comprising activated carbon, improve reaction rates while reducing the amount of by-products and impurities, thereby facilitating the desired coupling of alcohol compounds.

[0080] The multi-component solvent system preferably comprises at least a basic aqueous hydrocarbon solvent phase comprising at least two different hydrocarbons. In some embodiments, the solvent system comprises at least 1 and up to 10, preferably at least 2 and up to 5, preferably about 3 solvent / C. 1~3 The alcohol ratio is provided in step a.

[0081] In some preferred embodiments, processing with a subcritical aqueous hydrocarbon solvent (compared to a supercritical aqueous solvent) may be advantageous in that it requires less energy to carry out the process and may better preserve the aqueous hydrocarbon solvent during the reaction. When utilizing a subcritical aqueous hydrocarbon solvent, it is contemplated that the additional use of one or more catalysts may be particularly beneficial in increasing yield and / or n-butanol selectivity. Furthermore, the cost-effectiveness of reducing input energy, i.e., maintaining subcritical rather than supercritical conditions and preserving the solvent state, may significantly outweigh the additional costs incurred by further including one or more of the catalysts described herein.

[0082] The solvent preferably contains a base selected from the group consisting of potassium hydroxide, sodium hydroxide, potassium ethoxide, sodium ethoxide, potassium t-butoxide, sodium t-butoxide, or combinations thereof, such as a eutectic mixture of sodium hydroxide and potassium hydroxide. In some preferred embodiments, the basic aqueous solvent phase contains an alkali hydroxide, preferably KOH. In some embodiments, an alkoxide of a higher alcohol may be used as the base.

[0083] The solvent comprises a multi-component solvent system comprising at least two different hydrocarbons. In some preferred embodiments, the solvent system is a thermomorphic multi-component solvent system, preferably comprising a high-boiling hydrocarbon solvent phase.

[0084] The additional high-boiling hydrocarbon solvent understood herein may be any solvent that enhances n-butanol selectivity as an extractant, co-extracting intermediates with n-butanol as outlined in Figure 2, thereby enabling reactor equipment heating and catalyst stabilization within safe operating ranges while suppressing higher alcohol formation from ethanol using the method of the present invention. Because ethanol has a critical temperature (Tc) of 240.95°C and a boiling point of 78.37°C, heating ethanol alone under the reaction conditions of the present invention would result in dangerous reaction conditions. Alternatively, the boiling point of ethanol can be appropriately increased by adding a hydrocarbon solvent with a higher boiling point. Preferably, the hydrocarbon solvent has at least two components with different polarities and a high-temperature-dependent miscibility gap. Preferably, the reaction components are immiscible at low temperatures and completely miscible at high reaction temperatures. High dilutions, such as those containing aqueous hydrocarbon solvents, also dissociate acetaldehyde hydrate CH3CH(OH)2 or semiacetal CH3CH(OH)(OEt) back to acetaldehyde water and ethanol. This promotes the subsequent aldol condensation to produce n-butanol. Similarly, it affects the rapid dissociation of n-butanal hydrate and subsequent hydrogenation to form n-butanol. Preferably, the hydrocarbon solvent can also act as an entrainer for the efficient distillation of azeotropes, resulting in reaction mixtures such as ethanol / water and n-butanol / water.

[0085] The area and shape of the "phase separation zone" in the applied thermomorphic multicomponent solvent system depend on various parameters, such as the water-to-alcohol ratio, temperature, and the type of alcohol (ethanol or n-butanol). Ethanol is the only solvent with high water solubility, in contrast to butanol (73 g / L at 25 °C). As the conversion increases, its solubility decreases, thereby reducing the interaction of the active catalyst with the aqueous phase and thereby increasing n-butanol selectivity. As the reaction progresses, the liquid phase consists of unreacted ethanol, water, n-butanol, intermediates, and hydrocarbon solvent. By appropriately selecting the water / alcohol / hydrocarbon ratio based on the corresponding distribution coefficients according to the reaction conditions, this regime, and thereby n-butanol selectivity, can be carefully controlled. Figures 4 and 7 show the relationship between the water / alcohol / hydrocarbon ratio and the n-butanol selectivity.

[0086] In some preferred embodiments of the present invention, the feedstock may contain one or more different aqueous alcohols, such as fusel alcohols. However, it is emphasized that the inclusion of an alcohol is optional and not a requirement. For example, depending on availability, it may be convenient or even preferable to use a higher boiling alcohol as the solvent.

[0087] In some preferred embodiments, the solvent comprises a mixture of two or more aqueous alcohols. Suitable alcohols include C3 to C6 20 Non-limiting examples of suitable alcohols include straight-chain or branched alcohols such as 1-propanol, isopropyl alcohol, isobutyl alcohol, pentyl alcohol, amyl alcohol, hexanol, and isohexanol.

[0088] In some preferred embodiments, the high boiling hydrocarbon solvent phase is selected from the group consisting of poly(ethylene glycol) (PEG) monoalkyl ethers, aliphatics (linear or branched), aromatics, aromatics with aliphatic substituents, xylene, cycloalkanes, substituted cycloalkanes, naphthenes, indenes, fluorenes, biphenyls, Petrosolv 200-300, Petroflux ND, Petrosolv 250-450, SOLGAD 150, SOLGAD 200, SOLGAD 200 ULN, and SOLGAD 150. ULN, sulfolane, dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone, N,N-dimethylacetamide, 1,4-dioxane, anisole, propylene carbonate, benzyl alcohol, N-methylpyrrolidone, N-ethylpyrrolidone, N-cyclohexylpyrrolidone, N-octylpyrrolidone, ethyl lactate, butyl lactate, morpholine, glycerin, glycerin-mono-tert-butyl ether, glycerin-di-tert-butyl ether, glycerin-tri-tert-butyl ether, acetonitrile, propionitrile, di-tert-butyl ether Aryl ether, alkyl aryl ether, ionic liquid, dicarboxylic acid / tricarboxylic acid ester plasticizer, bis(2-ethylhexyl) phthalate, diisononyl phthalate, bis(n-butyl) phthalate, butyl benzyl phthalate, diisodecyl phthalate, di-n-octyl phthalate, diisooctyl phthalate, diethyl phthalate, diisobutyl phthalate, di-n-hexyl phthalate, trimellitate, trimethyl trimellitate, tri-(2-ethylhexyl) trimellitate, tri-(n-octyl, n-decyl) trimellitate, tri-(heptyl) trimellitate,Nonyl), n-octyl trimellitate, bis(2-ethylhexyl) adipate, dimethyl adipate, monomethyl adipate, dioctyl adipate, sebacic acid plasticizers, dibutyl sebacate, maleates, dibutyl maleate, diisobutyl maleate, benzoates, epoxidized vegetable oils, sulfonamides, N-ethyltoluenesulfonamide (ortho and para isomers), N-(2-hydroxypropyl)benzenesulfonamide, N-(n-butyl)benzenesulfonamide, organic phosphates, tricresyl phosphate, tributyl phosphate, glycols, polyethers, triethylene glycol dihexanoate, tetraethylene glycol diheptanoate, polybutene, acetylated monoglycerides, alkyl citrates, triethyl citrate, acetyltriethyl citrate, tributyl citrate, acetyltributyl citrate, trioctyl citrate, quercetin The high boiling hydrocarbons include those selected from the group consisting of acetyl trioctyl citrate, trihexyl citrate, acetyl trihexyl citrate, butyryl trihexyl citrate, trihexyl o-butyryl citrate, trimethyl citrate, alkyl sulfonic acid phenyl esters, vinyl chloride copolymers, 1,2-cyclohexanedicarboxylic acid diisononyl ester, biphenyl, triphenylmethane, polycyclic aromatic hydrocarbons, tetralin, naphthalene, tetrahydroanthracene, anthracene, hexahydropyrene, trihydropyrene, pyrene, phenanthrene, chrysene, paraffin, paraffin intermediate, light naphtha, intermediate naphtha, light gas oil, intermediate gas oil, heavy gas oil, light vacuum gas oil, intermediate vacuum gas oil, heavy vacuum gas oil, vacuum resid, linear alkyl benzene, vegetable oil, fatty acid methyl ester, animal fat / tallow, optionally substituted derivatives thereof, and combinations thereof.

[0089] In some preferred embodiments, the solvent comprises an aromatic compound with an aliphatic substituent, such as mesitylene, which boils at 164°C. In some preferred embodiments, the solvent comprises a Petrosolv solvent, which boils at 250°C. Petrosolv 200-300 is not a single molecule, but a distillate obtained by distillation, and has particular utility as a solvent. It consists of over 200 molecules in varying proportions, as analyzed by gas chromatography (GC). In some preferred embodiments, the solvent comprises mesitylene and Petrosolv. In some preferred embodiments, the solvent comprises xylene. In some preferred embodiments, the solvent comprises xylene and mesitylene. In some preferred embodiments, the solvent comprises xylene and Petrosolv solvent. In some preferred embodiments, the solvent comprises xylene, mesitylene, and Petrosolv solvent. In some preferred embodiments, the solvent comprises 1-propanol.

[0090] In some preferred embodiments, the hydrocarbon solvent according to the present invention may be recycled for use in a subsequent reaction to convert ethanol to n-butanol. The recycled solvent may be reused in the cooling / depressurization process, and subsequent distillation may be facilitated by carrying out the method of the present invention in a continuous flow system. This may be particularly advantageous in embodiments of the present invention relating to long-term operation at pilot plant scale or larger. In general, it is believed that recycling of solvent present in the reaction components may allow for situations requiring additional solvent / ethanol supply during start-up operations.

[0091] In some embodiments, the high-boiling hydrocarbon solvent phase comprises a high-boiling hydrocarbon in a ratio of 1:1 to 1:1000. Preferably, the ethanol to solvent ratio is 1:100, 1:10, 1:5, 1:3, 1:2, or 1:1. Higher reaction temperatures (>250°C) favor larger solvent volumes, while temperatures below 250°C favor smaller solvent volumes. The feedstock may contain greater than about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of hydrocarbon solvent or alcohol, and combinations thereof.

[0092] In some preferred embodiments, C 1~3 The alcohol is ethanol, preferably bioethanol. In some preferred embodiments, the solvent / ethanol ratio is at least 2.0, preferably at least 3.0. Preferably, the bioethanol is obtained from fermentation.

[0093] It is understood that "ethanol feedstock" encompasses any ethanol, including two-carbon alcohols, including both fossil fuel and non-fossil fuel or biomass fuel forms. There is no limitation as to the specific type of ethanol utilized in the methods of the present invention, although it is believed that certain forms of ethanol (e.g., bio-based ethanol) may be more suitable than others.

[0094] In some preferred embodiments, the ethanol may be rectified spirit, i.e., the first product of a distillery collected from a rectification column and containing 94.5% alcohol. Alternatively, it may be classified as ordinary denatured spirit (ODS) or special denatured spirit (SDS). Impurities or fusel alcohols may be part of the feedstock. Such impurities may be aldehydes, acids, esters, higher alcohols, or amyl alcohols. They may be purified or used as crude feedstock directly from the fermentation process.

[0095] In some preferred embodiments, the ethanol may be extra neutral alcohol (ENA) or neutral spirit (NS).

[0096] In some preferred embodiments, the ethanol may be fuel-grade ethanol, also known as absolute alcohol (AA), which includes a blend of fusel alcohols and / or denaturants.

[0097] In some preferred embodiments, the ethanol may be derived from first generation (food-based), second generation (waste-based), or obtained via CO / CO recycling or other sources. There are no limitations regarding the proportions of different ethanol sources. For example, the ethanol may comprise more than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, or 95% by weight of the feedstock. Preferably, the ethanol is high-grade ethanol, such as fuel-grade ethanol or G1 ethanol.

[0098] In some preferred embodiments, the ethanol concentration in the feedstock may be greater than about 98%, greater than about 95%, or greater than about 90% by weight, and the water concentration may be greater than about 10%, greater than about 8%, greater than about 6%, greater than about 5%, greater than about 4%, or greater than about 3% by weight.

[0099] In some preferred embodiments, the water concentration is about 1% to about 10% by weight. In particularly preferred embodiments, water is recycled from the product obtained in the process. For example, some water present after completion of the reaction can be removed as a substream and recycled to the feedstock. It has been observed that if the water concentration is too high, the conversion rate decreases.

[0100] In some preferred embodiments, fusel alcohols may be present in the ethanol feedstock. Fusel alcohols are present because they have a higher boiling point and are more volatile than ethanol, resulting from the fermentation mash. These may be a mixture of alcohols, primarily including activated amyl alcohol (2-methyl-1-butanol), isoamyl alcohol, isobutyl alcohol, 1-propanol, and n-amyl alcohol, n-butyl alcohol, and methionol. Less volatile alcohols present in the mash that are difficult to extract by distillation, including phenethyl alcohol and tyrosol, may also be present. Thus, the concentration of fusel alcohols may be greater than about 10% by weight, greater than about 5% by weight, or greater than about 3% by weight. Increased conversion has been observed with the presence of fusel alcohols.

[0101] In some preferred embodiments, ethanol may be fed to the reactor as a liquid stream.

[0102] In some preferred embodiments, the ethanol stream is substantially free of external hydrogen, e.g., less than 0.5 wt.%, less than 0.1 wt.%, or less than 0.01 wt.% hydrogen. The feed stream may also contain other molecules, such as high-boiling hydrocarbon solvents. An inert gas may be present in the gas stream, and thus may include methane, argon, nitrogen, or helium. Preferably, hydrogen is not introduced simultaneously with the gas stream, so that the gas stream is substantially free of hydrogen. The hydrogen required for the intermediate reaction may be generated in situ using, for example, sodium formate, potassium formate, or ammonium formate.

[0103] The catalyst system is such that no additional hydrogen is required. The catalyst can be added to the ethanol, aqueous hydrocarbon solvent before heating / pressurizing to the target reaction temperature and target reaction pressure, while heating / pressurizing to the target reaction temperature and target reaction pressure, and / or after the reaction temperature and target reaction pressure are reached. The timing of catalyst addition can depend on the desired products. For example, for highly selective n-butanol formation, adding the catalyst near or at the target reaction temperature and target reaction pressure can be beneficial, while for mixtures of higher alcohols, there is a flexibility in the timing of catalyst addition; i.e., the catalyst can be added before the target reaction temperature and target reaction pressure are reached.

[0104] In some preferred embodiments, the aqueous hydrocarbon solvent is added under conditions of elevated temperature and pressure in the presence of at least one "additional" catalyst, which, as noted above, is understood to refer to the provision of a catalyst supplemental to that inherently present in the reaction.

[0105] In some preferred embodiments, step a. is carried out at ambient temperature. In some preferred embodiments, step b. b1. Heating the mixture to a temperature T1 within a time frame Δt1; b2. Heating the mixture to a temperature T2 within a time frame Δt2; and b3. Maintaining the mixture at temperature T2 for a time period Δt3.

[0106] In some preferred embodiments, T2 is at least 140°C and up to 500°C, preferably at least 150°C and up to 400°C, preferably at least 160°C and up to 300°C, preferably at least 170°C and up to 260°C, preferably at least 180°C and up to 240°C, preferably at least 190°C and up to 220°C, preferably about 200°C.

[0107] The particular time during which conversion to n-butanol can be achieved when the target temperature and pressure are reached, i.e., the "retention time or residence time," can depend on a variety of factors, including, for example, the type of hydrocarbon solvent used, the percentage of ethanol in the solvent, the amount of water, the type of catalyst (as defined herein) in the mixture and its various concentrations, and / or the type of reactor equipment described above in which the process is carried out. These and other factors can be varied to maximize yield and / or reduce processing time by optimizing a given process. Preferably, the retention time is sufficient to convert all or substantially all of the ethanol used as a feedstock to n-butanol.

[0108] In some preferred embodiments, T1 is at least 60°C and up to 80°C, preferably about 70°C.

[0109] In some preferred embodiments, T2 is at least 140°C and up to 500°C, preferably at least 150°C and up to 400°C, preferably at least 160°C and up to 300°C, preferably at least 170°C and up to 260°C, preferably at least 180°C and up to 240°C, preferably at least 190°C and up to 220°C, preferably about 200°C.

[0110] In some embodiments, Δt1 is at least 90 to 180 minutes, preferably about 120 minutes.

[0111] In some embodiments, Δt2 is at least 30-90 minutes, preferably about 60 minutes.

[0112] In some embodiments, Δt3 is at least 120-360 minutes, preferably about 240 minutes.

[0113] Reaction mixtures that do not have a high proportion of hydrocarbon solvent may require very rapid initial conversion to generate any solvent in situ. However, as described herein, the incorporation of a high-boiling hydrocarbon component into the reaction mixture allows that component to act as a solvent, thereby reducing the need for rapid heating / pressurization.

[0114] In a continuous flow system, the pressure generally changes from atmospheric to the target pressure in the time it takes for the pump to pass, i.e., nearly instantaneously, whereas in a batch system, the pressure reflects the time it takes for the mixture to heat up.

[0115] In some preferred embodiments, the reaction mixture can be brought to the target temperature and / or pressure in a time period ranging from about 30 seconds to about 360 minutes.

[0116] In some preferred embodiments, the reaction mixture can be brought to the target temperature and / or pressure in less than about 15 minutes, less than about 10 minutes, less than about 5 minutes, or less than about 2 minutes.

[0117] In some preferred embodiments, the reaction mixture can be brought to the target pressure substantially instantaneously and to the target temperature in less than about 20 minutes, less than about 10 minutes, or less than about 5 minutes. Preferably, the reaction mixture can be brought to the target pressure substantially instantaneously and to the target temperature in less than about 2 minutes. In other embodiments, the reaction mixture can be brought to the target pressure substantially instantaneously and to the target temperature in about 1 to about 2 minutes.

[0118] In some preferred embodiments, the residence time Δt1 is less than about 360 minutes, 240 minutes, 180 minutes, 120 minutes, 60 minutes, 45 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, 10 minutes, or about 5 minutes. Preferably, the residence time is less than about 120 minutes, 60 minutes, 45 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, 10 minutes, or more than about 5 minutes.

[0119] In some preferred embodiments, the retention times Δt2 and Δt3 are from about 1 minute to about 360 minutes. Preferably, the retention times are from about 10 minutes to about 120 minutes, from about 20 minutes to about 140 minutes, from about 30 minutes to about 180 minutes, or from about 40 minutes to about 240 minutes. Preferably, the retention time / retention time is from about 20 minutes to about 30 minutes.

[0120] Additionally or alternatively, after completion of the hold period, the reaction mixture may be cooled to about 140°C to about 200°C, about 150°C to about 200°C, preferably about 160°C to about 190°C, more preferably about 150°C, in a time of less than about 10 minutes, preferably less than about 7 minutes, more preferably less than about 6 minutes, preferably about 4 to about 6 minutes, more preferably about 5 minutes. After the initial cooling period, the temperature can be further reduced to ambient temperature by simultaneous depressurization with rapid release into a cold aqueous medium, such as cooling water.

[0121] It has been found that the conversion of ethanol to n-butanol advantageously occurs at temperatures between 140° and 300° C., in particular between 170° and 220° C., most preferably between 190° and 200° C. The pressure may range from 1 to 300 bar, in particular between 5 and 100 bar, most preferably between 10 and 80 bar.

[0122] The heating / pressurization and cooling / depressurization processes can be facilitated by carrying out the method of the present invention in a continuous flow system, which can be a continuous stirred tank reactor (CSTR) or a tubular reactor or a microchannel reactor apparatus.

[0123] The present invention utilizes an alcohol feedstock (ethanol) that is converted to another alcohol (n-butanol).

[0124] Similarly, the required hold time is affected by the proportions of various components (eg, water, solvent, alcohol catalyst, etc.) in the reaction mixture.

[0125] In some preferred embodiments, step b. is carried out at a pressure of at least 2 bar and up to 250 bar, which keeps the mixture in the liquid phase rather than the gas phase, ensuring selectivity. The higher the pressure, the more likely it is to remain in the liquid phase.

[0126] The inventors have found that this component results in a uniform dispersion. In some embodiments, step b. comprises an agitation speed adjusted to between 0 rpm and 5000 rpm, preferably between 200 rpm and 1200 rpm.

[0127] It is understood that "dispersed" refers to a state in which the reaction mixture is thoroughly mixed. Thorough dispersion may depend on the nature of the reactor. Batch and flow reactors have different mixing mechanisms, and compared to batch reactors, tube reactors inherently allow for significantly shorter diffusion times and very rapid mixing (larger surface-to-volume ratios). This, combined with reaction kinetics, is often used to evaluate whether flow conditions are beneficial based on the reaction Reynolds number (Re). Preferably, the mixture is stirred vigorously enough to be beneficial in a thermomorphic multicomponent hydrocarbon solvent system (i.e., one in which the temperature dependence of the miscibility gap is as high as possible, allowing for two-phase separation from a homogeneous mixture with minimal energy consumption and eliminating the liquid-liquid interface so that the reactants can combine). Additionally, a single solvent is preferred that can homogenize the catalyst phase, the ethanol feedstock phase, and, preferentially, the n-butanol phase upon cooling without requiring additional separation units for product purification and solvent recovery.

[0128] In some preferred embodiments, a bubble column reactor mechanism may be used to ensure good heat and mass transfer rates, resulting in excellent dispersion, compactness, easy operation with no moving parts, and reduced maintenance and operating costs.

[0129] In some preferred embodiments, one skilled in the art may use an overhead stirring unit with a variable speed of 0-1200 rpm in a batch reactor. Alternatively, a Teflon-coated stir bar can be used in conjunction with a hot stir plate equipped with a suitably sized aluminum metal block equipped with a temperature probe and controlled stirring, although this may be used with limited efficiency.

[0130] In some embodiments, step b. is carried out in a batch reactor, a flow reactor, a continuous flow reactor, a tubular reactor, or a microchannel reactor; preferably, step b. is carried out in a batch reactor or a tubular reactor.

[0131] In the present invention, heat and mass transfer or mixing limitations, rather than fundamental reaction kinetics, control the reaction rate. The conversion of 2 equivalents of ethanol to 1 equivalent each of n-butanol and water at ambient conditions is −46.6 kJ / mol; thus, such an exothermic reaction can take several hours when carried out in a batch reactor, not because of reaction rate limitations, but because of the time required to remove the heat of reaction and operate safely.

[0132] In some preferred embodiments, the reactor may be any suitable batch reactor or combination of reactors. Preferably, the reactor comprises a fixed bed reactor or a series of such reactors.

[0133] In some preferred embodiments, the reactor is a gas flow catalytic reactor or a series of such reactors.

[0134] In some preferred embodiments, the reactor is a continuous stirred tank reactor or a fluidized bed reactor or a tubular reactor.

[0135] Although the methods of the present invention do not need to be carried out under continuous flow conditions, doing so may provide several advantages. For example, continuous flow may increase the rate at which heating and / or pressurization of the mixture can be applied and / or removed. This may facilitate achieving desired mass and heat transfer rates, heating / cooling, and / or pressurization / depressurization.

[0136] Continuous flow may also allow for tight control over the retention time of the reaction mixture. While not limited to a particular mode of action, it is hypothesized that the ability to tightly adjust retention / residence times, along with the increased heating / cooling and / or pressurization / depressurization rates facilitated by continuous flow conditions, reduces the occurrence of undesirable side reactions, such as those referenced in Figure 2, as the reaction mixture is heated / pressurized and / or cooled / depressurized.

[0137] Continuous flow is also believed to enhance the reactions involved in the conversion of ethanol to n-butanol by creating mixing and shear forces that are believed to promote emulsification, which may be an important mechanism involved in the transport and "storage" of the produced n-butanol away from the reactive surface of the catalyst, creating an interfacial surface area involved in so-called "on-water catalysis."

[0138] Thus, in a preferred embodiment, the process of the present invention is carried out under continuous flow conditions. As used herein, the term "continuous flow" refers to the process in which ethanol mixed with a high boiling point aqueous hydrocarbon solvent in a mixture (with or without an additional catalyst) is (a) heating and pressurization to reach a set target operating temperature and pressure; (b) treatment at a target operating temperature and pressure for a specified time (i.e., "hold / residence time"), and (c) refers to a process in which the material is subjected to cooling and pressure reduction followed by distillation; The mixture is maintained in a continuously moving stream along the entire length (or portion) of a given surface. It will be understood that the "continuous flow" conditions contemplated herein are defined by the starting point of heating and pressurization (i.e., (a) above) and the ending point of cooling and depressurization (i.e., (c) above).

[0139] The continuous flow conditions envisioned herein do not imply any particular limitation on the flow rate of the mixture, so long as it is maintained in a continuously moving stream.

[0140] Preferably, the minimum (volume-independent) flow velocity of the mixture along a given surface is faster than the settling velocity of the solid catalyst components within the mixture, i.e., the terminal velocity at which suspended particles, being denser compared to the surrounding solution, move (due to gravity) towards the bottom of the mixture flow, thereby spreading uniformly.

[0141] For example, the minimum flow velocity of the mixture can be greater than about 0.001 cm / s, greater than about 0.05 cm / s, preferably greater than about 0.5 cm / s, and more preferably greater than about 5 cm / s. The overhead flow velocity can be influenced by factors such as volumetric flow rate and / or retention / residence time, which in turn can be influenced by the components of the particular reactor equipment utilized to maintain continuous flow conditions.

[0142] Continuous flow conditions can be facilitated, for example, by carrying out the process of the present invention in a suitable reactor apparatus, which generally includes a heating / cooling section, a pressurization / depressurization section, and a reaction section, through which a continuous flow of the reaction mixture is maintained.

[0143] Utilizing a suitable flow rate (under continuous flow conditions) may be advantageous for example to inhibit scaling or catalyst deposition along the entire length of the particle surface as the reaction mixture moves along the vessel wall of the reactor apparatus, and / or to create an effective mixing regime for efficient heat transfer into the reaction mixture.

[0144] In batch processes, cooling occurs only at the surface of the reactor. The formation of hot spots or accumulation of reaction heat can promote undesired side reactions or decomposition, as depicted in Figure 2. This becomes even more pronounced when scaling up production routines. The surface-to-volume ratio is a function of the size of the reactor. The larger the reactor, the smaller the surface-to-volume ratio. For example, the surface / volume (cm) of a 100 mL flask is: 2 / cm 3 ) is 1, but for a 189 L (50 gallon) reactor it is 0.08, and for a 1 m 3 It is 0.06 for the reactor and 200 for a flat microchannel reactor with a width of about 100 μm.

[0145] In some preferred embodiments, continuous stirred tank reactors or tubular reactors are preferred over batch or CSTR reactors.

[0146] Therefore, a synthetic procedure that works well in small glass inserts during the research and development (R&D) stage can cause major problems if it is carried out directly in a kilo lab or pilot plant, and then in larger vessels in a commercial plant. In flow chemistry, the surface-to-volume ratio of a single flow reactor (e.g., a microreactor) is large. Scaling up from the gram scale to the kilogram scale to the multi-ton scale only extends the run time of the microreactor system and does not require further process development.

[0147] In some preferred embodiments, a continuous stirred tank reactor (CSTR) or a fixed-bed reactor may be used to facilitate continuous production. Preferably, several specialized reactors may be used: (1) a microreactor, (2) a continuous tubular reactor / plug flow reactor, (3) a bubble column reactor (BCR), (4) a countercurrent reactor, and (5) a CSTR in combination with a continuous tubular reactor. Additionally or alternatively, the heat exchange of the countercurrent reactor for heating the feed stream and cooling the product stream can be combined with the fixed-bed reactor section to save on heat exchanger costs. Additionally or alternatively, the reactor may be a high-pressure reactive distillation (RD) reactor, where improved separation of unreacted ethanol from products such as water, n-butanol, and higher alcohols can be achieved through reaction (e.g., overcoming azeotropes, reacting to remove contaminants, avoiding difficult separations), and catalyst components can be embedded in the column packing to improve efficiency or improve the reaction through separation (e.g., increasing overall rate, overcoming reaction equilibrium constraints, improving selectivity). The benefits are greatest when both aspects are applied.

[0148] In some preferred embodiments, flow reactors (e.g., microreactors) with large surface-to-volume ratios can be used to absorb the heat generated from the reaction much more efficiently than batch reactors. In large batch reactors, there is a strong temperature gradient from the cooled surface of the reactor to its center. In microreactors, heat is generated much less, so the flow can cool to operating temperature in a few millimeters of path length. This is due to the high heat transfer in flow reactors compared to batch reactors. For example, typical heat transfer coefficients for different reactor types are: volumetric heat transfer coefficient (MW / m) for jacketed batch reactors, and volumetric heat transfer coefficient (MW / m) for jacketed batch reactors. 3 K) is 10 -2 ~10 -3 , while the shell-and-tube type has a power output of 0.2, and the plate or glass fluidic module has a power output of 1.3-1.7 MW / m 3K. Microreactors can therefore further reduce the carbon footprint of the overall process.

[0149] To further exploit the characteristics and advantages of continuous flow reactors, miniature flow reactors can be designed in a variety of shapes, lengths, diameters, and materials. A key feature of each design unit of a flow reactor is the ability to maintain a steady flow rate through the reactor over the process time. Other features can incorporate the implementation of baffles to promote mixing and / or static mixers to increase turbulence. Flow reactors are typically designed to reduce reactor volume, physical footprint, and energy requirements compared to their batch reactor counterparts. Such designs and sizes allow these reactors to be operated in a safer environment and are ideal for the production of C6, C8, and C8 fractions of ethanol and n-butanol. 10 Benefits include increased reaction rates (e.g., at higher temperatures than in batch reactors) due to more efficient heat transfer capacity and well-defined reaction concentration profiles, allowing for controlled conversion to alcohol; operation without solvent or at low solvent / ethanol ratios; enhanced mixing; and effective removal of heat generated by the exothermic reaction. The ability to precisely control residence time in the reaction zone increases the reproducibility of product distribution and process robustness with respect to operating conditions to facilitate flow processes. Several other specialized reactors have also been designed for this invention, such as spinning disk reactors (SDRs), spinning tube-in-tube reactors, and tubular reactors designed for multiphase catalytic reactions. These can be used as single units or in combination to optimize conversion and selectivity to n-butanol.

[0150] In some preferred embodiments, C 1~3 The alcohol is converted to n-butanol. In some preferred embodiments, 1~3 Alcohol is C 6~8 Converted to alcohol.

[0151] In some embodiments, the reaction achieves favorable conversion of ethanol and favorable n-butanol selectivity and productivity. For purposes of this invention, the term "conversion" refers to the amount of ethanol in the feedstock that is converted to compounds other than ethanol. Conversion is expressed as a percentage based on the ethanol in the feedstock. Ethanol conversion can be at least 20%, e.g., at least 30%, at least 40%, or at least 60%, or at least 80%.

[0152] Selectivity, as it refers to the formation of n-butanol, is expressed as the ratio of the amount of carbon in the desired product to the amount of carbon in all products. Preferably, the n-butanol selectivity is at least 30%, e.g., at least 40%, or at least 60%, or at least 90%. In some embodiments, the catalyst has a C6 or higher alcohol selectivity of at least 5%, e.g., at least 10%, at least 20%, or at least 25%. In preferred embodiments of the process, the selectivity to undesired products, such as diethyl ether, methane, ethane, and ethene, is low, as shown in Figure 2. The selectivity to these undesired products is preferably less than 20%, e.g., less than 5% or less than 1%. More preferably, these undesired products are undetectable. More preferably, these undesired products are not formed.

[0153] In some preferred embodiments, the production of n-butanol from ethanol by the methods of the present invention may be facilitated by the presence of an "intrinsic" catalyst that is inherently present in a given reaction component, such as, for example, the ethanol, the aqueous solvent, and / or the vessel walls of the reactor apparatus in which the reaction mixture may be processed.

[0154] Thus, the process of the present invention can be carried out using an "additional" catalyst in combination with an "intrinsic" catalyst, or an "intrinsic" catalyst alone, depending on the type and materials of reactor equipment.

[0155] The optimum amount of endogenous catalyst used in the process of the present invention can depend on a variety of factors, including, for example, the type of ethanol being treated, the volume of ethanol being treated, the aqueous hydrocarbon solvent used, the particular temperature and pressure employed during the reaction, the type of catalyst and desired conversion, and n-butanol selectivity.

[0156] In some preferred embodiments, the intrinsic catalyst or a combination of the intrinsic catalyst and the additional catalyst may be used in an amount (relative to ethanol) of about 0.1% to about 20% by weight of catalyst, about 0.1% to about 10% by weight of catalyst, about 0.1% to about 5% by weight of catalyst, about 0.1% to about 2.5% by weight of catalyst, about 0.1% to about 1% by weight of catalyst, or about 0.1% to about 0.5% by weight of catalyst.

[0157] In some preferred embodiments, the "intrinsic" catalyst used in the reaction process can be an alkali metal salt and / or an alkaline earth metal salt, such as a potassium salt, a calcium salt, and / or a sodium salt. For example, alkali metal hydroxides and alkali metal carbonates can be effective in reducing the oxygen content of the aldol condensation product. In one embodiment, the optimal catalyst concentration (in the reaction itself) of the alkali metal hydroxide catalyst and / or alkali metal carbonate catalyst under a set of otherwise substantially constant reaction conditions can range from about 0.1 molar to about 5 molar. In some preferred embodiments, the concentration can range from about 0.1 molar to about 2 molar. Preferably, the concentration of the alkali metal hydroxide catalyst and / or alkali metal carbonate catalyst is less than about 25% by weight and is between about 5% and about 15% by weight.

[0158] For example, bioethanol derived from a distillery may contain variable amounts of impurities, e.g., 0.1% to about 2%, and the impurities may include various amounts of alkali salts, such as potassium, sodium, and / or calcium salts resulting from the extraction of fusel alcohol. Other metals present in fuel-grade ethanol may include manganese, iron, lead, cobalt, cadmium, zinc, copper, and nickel in varying amounts. These may be catalysts used in a series of reactions under the reaction conditions of the present invention, including the reactions described in Figure 2. Additionally or alternatively, the aqueous hydrocarbon solvent used in the method of the present invention may provide an intrinsic catalyst for the reaction. Non-limiting examples of these catalysts include the hydronium ions and / or hydroxide ions of water. Additionally or alternatively, an "intrinsic" catalyst may be provided by the vessel wall of the reactor apparatus in which the reaction is conducted. Non-limiting examples of materials commonly used in reactor construction, i.e., including the reactor vessel wall, are alloys of iron with other metals, including chromium, nickel, manganese, vanadium, molybdenum, titanium, and silicon.

[0159] In some preferred embodiments, the "intrinsic" catalyst, which may be provided by the vessel wall of the reactor apparatus, is a transition metal / noble metal.

[0160] Non-limiting examples of "intrinsic" catalysts include iron metal, iron hydroxide, iron oxide, iron carbonate, iron bicarbonate, iron acetate, nickel metal, nickel hydroxide, nickel oxide, nickel carbonate, nickel bicarbonate, chromium metal, chromium hydroxide, chromium oxide, chromium carbonate, chromium bicarbonate, manganese metal, manganese metal hydroxide, manganese metal oxide, manganese metal carbonate, and / or manganese metal bicarbonate. Hydroxides may be present by reacting the metal with water and an alkaline "additional" catalyst. Oxides may be present as a passivation layer by reacting the metal with an oxygen-containing compound. Carbonates and bicarbonates may be present by reacting the metal, metal oxide, and / or metal hydroxide with carbon dioxide generated in situ by a decarboxylation reaction. Metal acetates can exist by reacting metals, metal oxides, metal hydroxides, metal bicarbonates, and metal carbonates with acetic acid generated in situ by hydrolysis. Metals and metal compounds associated with surfaces made of steel and similar materials can catalyze a variety of reactions, including, but not limited to, one or more of the reactions described in Figure 2.

[0161] By way of non-limiting example only, endogenous catalysts, e.g., alkali salts such as potassium, sodium, and calcium salts, can be transferred to the aqueous hydrocarbon phase during the reaction. Because significant concentrations of such catalysts, e.g., alkali salts of potassium, sodium, and calcium, can be present in ethanol processed by the methods of the present invention, in certain embodiments, the aqueous hydrocarbon phase containing dissolved catalysts, e.g., potassium, sodium, and / or calcium salts, can be recycled.

[0162] In some preferred embodiments, in-situ regeneration of intrinsic catalyst from various reaction components, e.g., either by-product water, or the ethanol feedstock, or the aqueous hydrocarbon solvent, and / or the reactor apparatus vessel walls, reduces or eliminates the need to provide "extra" catalyst in subsequent ethanol conversion. This can be particularly advantageous in embodiments of the invention involving long-term operation at pilot plant scale or above. In general, it is believed that recycling of intrinsic catalyst present in reaction components, e.g., alkali salts, can allow for situations where "extra" catalyst is required only during start-up operations.

[0163] In some preferred embodiments, the "intrinsic" catalyst and catalyst components may be preformed and assayed or added as individual components in molar amounts equivalent to the ethanol feedstock. This may be particularly advantageous in embodiments of the invention associated with long-term commercial-scale operation and long-term storage of the catalyst.

[0164] In some preferred embodiments, the reaction vessel acts as an intrinsic catalyst. In some preferred embodiments, reactor equipment can be used to promote ethanol conversion. Any reactor equipment made from 316 stainless steel, an alloy of Fe, Cr (12-20%), Ni (10-14%), Mo (2-3%), Mn (≦2%), and possibly lesser amounts of Si (≦1%), P (≦0.045%), and S (≦0.03%) (e.g., generally considered inert and highly corrosion-resistant because it passivates itself by building up a mechanically strongly adherent chromium oxide layer ≦100 Å thick), when treated with an appropriate strong base or acid, can be used to promote oxygen removal, i.e., desorption of water from ethanol. Non-limiting examples of austenitic, martensitic, or ferritic stainless steels include: In some preferred embodiments, the process comprises: c. Further comprising distilling the higher alcohol.

[0165] Subsequent distillation of the reaction mixture to purify n-butanol is the preferred step in this process. Traditional steam cracker or catalytic cracker procedures involving distillation also have significant drawbacks in that the equipment used is large, resulting in high capital costs, and in low energy efficiency, resulting in high operating costs.

[0166] The separation of multicomponent mixtures preferably involves the use of at least two distillation columns in direct or indirect sequence. A vertical dividing-wall column (DWC) may be used. Compared to classical distillation designs, DWC offers several significant advantages: increased thermodynamic efficiency due to reduced remixing effects, 25-40% lower energy requirements, higher purity of all product streams, reduced maintenance costs, a smaller footprint, and up to 30% lower investment costs due to a reduced number of equipment units.

[0167] Achieving n-butanol purity targets requires several energy-intensive separation steps, primarily due to the existence of well-known binary azeotropes: ethanol-water (95.63 wt % ethanol) and n-butanol-water. Unlike ethanol, n-butanol and water form a heterogeneous azeotrope with a composition of 76.33 mol % water at 364.6 K. Therefore, the first step may be performed in a pre-concentration distillation column (PDC) to recover up to 92.4–94 wt % ethanol. The second step is ethanol dehydration to concentrations above the azeotropic composition. This is typically performed in an extractive distillation column (EDC) followed by a solvent recovery column (SRC). Although the energy cost of extractive distillation is relatively high, it remains an option for large-scale bioethanol fuel production and is preferred over pervaporation, adsorption, pressure swing distillation, azeotropic distillation, or hybrid methods combining these options. This may be applicable when an n-butanol production facility is co-located with an ethanol production facility. A vertical extractive dividing-wall column (E-DWC) system can be used for extractive distillation with or without a pre-concentration distillation column (PDC).

[0168] In some preferred embodiments, molecular sieve distillation may then be performed to further purify the butanol using an MFI-type zeolite membrane (e.g., silicalite-1) due to its well-defined pore structure (approximately 0.5 nm) and high hydrophobicity, resulting in n-butanol with a purity of 99.99%.

[0169] According to a second aspect, the present invention provides a method for producing a medicament for the treatment of a medicament comprising: 1~3 The present invention relates to the use of the catalysts described herein in the conversion of alcohols to higher alcohols.

[0170] The dependent and dependent claims set out particular and preferred features of the invention. Features from the dependent claims may be combined with features of the independent claims or with features of other dependent claims as appropriate. [Example]

[0171] Example material Commercially available reagents were used as received from the appropriate commercial supplier, such as VWR, Merck, etc., without further purification.

[0172] 1-Propanol (technical grade), zinc fine powder, technical grade xylene mixture, and anhydrous K2CO3 were purchased from VWR Chemicals, Ni / Al 50 / 50% and KOH (>85%) were purchased from Carl Roth GmbH, cobalt(II) chloride (anhydrous) 97%, bromopentacarbonylmanganese(I) ≥ 98%, benzimidazole, and imidazole 99% were purchased from Thermo Scientific. Petrosolv 200-300 was purchased from Raincarbon Inc. and dried over 3Å molecular sieves purchased from Carl Roth GmbH. Iron(II) chloride tetrahydrate, sodium metal, triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (TPPTS), and mesitylene were purchased from Merck. 2-(2-pyridylbenzimidazole), Ba(OH) 94-98%, and sodium formate (98%) were purchased from Alfa Aesar. CsCO >98% and pyrazole were purchased from TCI Chemicals. Triphenylphosphine was purchased from Acros Organics. Merck peat-derived, steam-activated, powdered activated carbon, Norit® environmentally friendly alternative Norit® SA2, was used. RuCl3.3H2O was purchased from Pressure Chemicals and Celite 535 was purchased from Macherey-Nagel GmbH & Co. KG.

[0173] method All reactions were carried out using either a 10 mL stainless steel reactor, a Parr 100 mL stainless steel reactor vessel, or a Parr 600 mL stainless steel reactor vessel with or without a glass insert. All of these are typically made of the same material as the reactor body itself. We have found that the use of a glass liner may not be sufficient to prevent the reactor from operating in a catalytic process, as it does not limit exposure of the lid, drive shaft, and impeller used to stir the reaction to the reaction solution. This is especially true at high speeds, such as when gaseous reactants must be dissolved in the reaction mixture, or at high temperatures, when substantial mass transport by convection and distillation occurs within the enclosed reactor space. However, in the present invention, this minimizes exposure to reagents occurring in the solution / liquid phase, thereby providing a rational and reasonable basis for conversion with or without the influence of reactor metals. Furthermore, the 10 mL high-pressure reactor, lacking an overhead stirrer and Teflon stir bar, minimizes exposure and generally allows for better control of reaction parameters. This was also tested in a Parr 600 mL stainless steel reactor vessel heated on an aluminum block.

[0174] Unless otherwise stated, all trials were carried out in air. All components were found to be stable in air.

[0175] analysis In-house gas chromatogram-flame ionization detector (GC-FID) and gas chromatogram-mass spectra (GC-MS) analyses were performed on an Agilent 8890 using an HP-5ms column. All crude solutions were prepared in diethyl ether in 2 mL vials with polytetrafluoroethylene (PTFE) screw caps.

[0176] [Table 1]

[0177] ethanol All experiments employed industrial grade fuel grade ethanol (G1) and neutral ethanol (G2), as listed below: G1: Ethanol feedstock of ASTM D4806 standard for denatured fuel ethanol for blending with gasoline for use as automotive spark ignition engine fuel, with the specifications shown in Table 2 below.

[0178] [Table 2]

[0179] G2: Specifications of ethanol used in the test as neutral ethanol obtained by fermenting grains and sugar-containing juice of sugar beet and / or sugar cane, having the specifications shown in Tables 3 and 4.

[0180] [Table 3]

[0181] [Table 4]

[0182] Comparative Example 1 G1-grade ethanol, iron(II) chloride tetrahydrate salt, imidazole, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of (681.0:1.0:2.9:177.2) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integration of the GC signal for 1-butanol compared to all other components except ethanol in the product. GC traces showed a conversion of 5% and selectivity of >98%.

[0183] Comparative Example 2 G1-grade ethanol, cobalt(II) chloride salt, imidazole, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of 444.7:1.0:1.9:115.7 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integration of the GC signal for 1-butanol compared to all other components except ethanol in the product. GC traces showed a conversion of 5% and a selectivity of >98%.

[0184] Comparative Example 3 G1-grade ethanol, bromopentacarbonylmanganese(I) salt, KOH, and 2 mL of Petrosolv 200-300 solvent were premixed in air at ambient temperature in a molar ratio of 138.5:1.0:115.3 and then heated to 70 °C (2 h). The temperature was then increased to 180 °C in 20 °C increments over 1 h. The time at temperature T was 10 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal for 1-butanol relative to all other components except ethanol in the product. GC traces showed a conversion of 5% and selectivity of >99%. Pentacarbonylmanganese(I) was found to be air-sensitive. Addition of imidazole also resulted in an air-sensitive catalyst.

[0185] Comparative Example 4 G1-grade ethanol, bromopentacarbonylmanganese(I) salt, PPh3, KOH, and 2 mL of Petrosolv 200-300 solvent in a molar ratio of 138.5:1.0:1.54:115.3 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 180 °C in 20 °C increments over 1 h. The time at temperature T was 10 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integration of the GC signal for 1-butanol compared to all other components except ethanol in the product. GC traces showed a conversion of 4% and selectivity of >99%.

[0186] Comparative Example 5 G1-grade ethanol, bromopentacarbonylmanganese(I) salt, imidazole, KOH, and 2 mL of Petrosolv 200-300 solvent in a molar ratio of 138.5:1.0:2.8:115.3 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 180 °C in 20 °C increments over 1 h. The time at temperature T was 10 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol compared to all other components except ethanol in the product. The GC trace showed evidence of conversion.

[0187] Comparative Example 6 G1-grade ethanol, ruthenium(III) chloride hydrate salt, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of 710.5:1.0:184.8 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal for 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 10.1% and a selectivity of 66.7%.

[0188] Comparative Example 7 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of (710.5:1.0:3.0:184.8) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 24.6% and a selectivity of 63.5%.

[0189] Comparative Example 8 G1-grade ethanol, ruthenium(III) chloride hydrate salt, benzimidazole, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of (710.5:1.0:1.76:184.8) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 4% and a selectivity of 85.8%.

[0190] Comparative Example 9 G1-grade ethanol, ruthenium(III) chloride hydrate salt, 2-(2-pyridylbenzimidazole), KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of 710.5:1.0:1.1:184.8 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 5.1% and a selectivity of 85.1%.

[0191] Comparative Example 10 G1-grade ethanol, ruthenium(III) chloride hydrate salt, pyrazole, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of (710.5:1.0:3.0:184.8) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 11.1% and a selectivity of 71.2%.

[0192] Comparative Example 11 G1-grade ethanol, ruthenium(III) chloride hydrate salt, TPPTs, KOH, and 3 mL of Petrosolv 200-300 solvent in a molar ratio of (710.5:1.0:0.74:184.8) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal for 1-butanol compared to all other components except ethanol in the product. The GC trace showed a conversion of 15.1% and a selectivity of 69.2%.

[0193] Comparative Example 12 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Zn, and 1 mL of mesitylene and 2 mL of Petrosolv 200-300 solvent in a molar ratio of 710.5:1.0:12.2:184.8:31.7 were premixed under nitrogen at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 18.6% and a selectivity of 79.8%.

[0194] Comparative Example 13 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Zn, and 2 mL of mesitylene and 1 mL of Petrosolv 200-300 solvent in a molar ratio of (710.5:1.0:12.2:184.8:31.7) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 6 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 14.8% and a selectivity of 82.3%.

[0195] Comparative Example 14 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, 1 mL of mesitylene, and 2 mL of Petrosolv 200-300 in a molar ratio of 177.6:1.0:0.76:46.2:2.42 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal for 1-butanol compared to all other components except ethanol in the product. The GC trace showed a conversion of 27.5% and a selectivity of 75.0%.

[0196] Example 15 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 1 mL of mesitylene, and 2 mL of Petrosolv 200-300 in a molar ratio of (177.6:1.0:0.76:46.2:2.42:43.2) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 49% and a selectivity of 72.7%.

[0197] Comparative Example 16 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, sodium formate, 1 mL of mesitylene, and 2 mL of Petrosolv 200-300 in a molar ratio of 177.6:1.0:0.76:46.2:6.2 were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 20.8% and a selectivity of 77.2%.

[0198] Example 17 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 50 mL of mesitylene, and 100 mL of Petrosolv 200-300 in a molar ratio of (1973.6:1.0:5.1:410.8:13.4:96.0) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 1-butanol compared to all other components except ethanol in the product. GC tracing showed that the conversion was 36.9% and the selectivity was 82.48%.

[0199] Example 18 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 50 mL of mesitylene, and 100 mL of Petrosolv 200-300 in a molar ratio of (1973.6:1.0:5.1:410.8:13.4:96.0) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 170 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 1-butanol compared to all other components except ethanol in the product. GC tracing showed that the conversion was 44.9% and the selectivity was 77.7%.

[0200] Example 19 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 50 mL of mesitylene, and 100 mL of Petrosolv 200-300 in a molar ratio of (1973.6:1.0:5.1:410.8:13.4:96.0) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 180 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 1-butanol compared to all other components except ethanol in the product. GC tracing showed that the conversion was 44.1% and the selectivity was 74.47%.

[0201] Example 20 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 50 mL of mesitylene, and 100 mL of Petrosolv 200-300 in a molar ratio of (1973.6:1.0:5.1:410.8:13.4:96.0) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 190 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 1-butanol compared to all other components except ethanol in the product. GC tracing showed that the conversion was 60.4% and the selectivity was 79.2%.

[0202] Example 21 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 50 mL of mesitylene, and 100 mL of Petrosolv 200-300 in a molar ratio of (1973.6:1.0:5.1:410.8:13.4:96.0) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 200 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 1-butanol compared to all other components except ethanol in the product. GC tracing showed that the conversion was 54.4% and the selectivity was 79.2%.

[0203] Example 22 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 50 mL of mesitylene, and 100 mL of Petrosolv 200-300 in a molar ratio of (1973.6:1.0:5.1:410.8:13.4:96.0) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 210 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 1-butanol compared to all other components except ethanol in the product. GC tracing showed that the conversion was 60.4% and the selectivity was 80.2%.

[0204] Comparative Example 23 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, and 3 mL of mesitylene were premixed in a molar ratio of 177.6:1.0:0.76:35.1 in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 7 h. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 22.0% and a selectivity of 77.4%.

[0205] Comparative Example 24 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, and 2 mL of mesitylene were premixed in a molar ratio of 177.6:1.0:0.76:35.1 in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 7 h. The solvent / ethanol ratio was 2. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 13.1% and a selectivity of 78.6%.

[0206] Comparative Example 25 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, and 1 mL of mesitylene were premixed in a molar ratio of 177.6:1.0:0.76:35.1 in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 7 h. The solvent / ethanol ratio was 1. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 4.9% and a selectivity of 91.0%.

[0207] Comparative Example 26 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, and 0.5 mL of mesitylene were premixed in air at ambient temperature in a molar ratio of 177.6:1.0:0.76:35.1 and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 7 h. The solvent / ethanol ratio was 0.5. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 5.2% and a selectivity of 86.5%.

[0208] Comparative Example 27 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, and KOH in a molar ratio of (177.6:1.0:0.76:35.1) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 7 h. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 2.6% and a selectivity of 81.8%.

[0209] Comparative Example 28 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, NaCl, and Petrosolv 200-300 solvent in a molar ratio of (88.8:1.0:1.5:46.0) were premixed in air at ambient temperature and then heated to 70 °C (1 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 3 h. The solvent / ethanol ratio was 4.0. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 22.4% and a selectivity of 84.2%.

[0210] Comparative Example 29 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, K2CO3, and Petrosolv 200-300 solvent in a molar ratio of 88.8:1.0:1.5:46.0 were premixed in air at ambient temperature and then heated to 70 °C (1 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 3 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol compared to all other components except ethanol in the product. No conversion was observed in the GC trace.

[0211] Comparative Example 30 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, Cs2CO3, and Petrosolv 200-300 solvent in a molar ratio of 88.8:1.0:1.5:46.0 were premixed in air at ambient temperature and then heated to 70 °C (1 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 3 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. Traces of GC traces showed only minor conversion.

[0212] Comparative Example 31 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, Ba(OH)2, and Petrosolv 200-300 solvent in a molar ratio of 88.8:1.0:1.5:46.0 were premixed in air at ambient temperature and then heated to 70°C (1 h). The temperature was then increased to 150°C in 20°C increments over 1 h. The time at temperature T was 3 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol compared to all other components except ethanol in the product. Traces of GC traces showed only minor conversion.

[0213] Comparative Example 32 G2-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, 5 mL of tap water, and 140 mL of mesitylene were premixed in air at ambient temperature in a molar ratio of (1973.6:1.0:5.1:492.9:13.4) and then heated to 70 °C (2 h). The temperature was then increased to 160 °C in 20 °C increments over 1 h. The time at temperature T was 4 h. The solvent / ethanol ratio was 2.8. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal for 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 16.3% and a selectivity of 85.8%.

[0214] Comparative Example 33 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, and 100 mL of xylene in a molar ratio of (1973.6:1.0:6.8:821.0:10.8) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 180 °C in 20 °C increments over 1 h. The time at temperature T was 2 h. The solvent / ethanol ratio was 4. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal for 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 23.6% and a selectivity of 81.6%.

[0215] Comparative Example 34 G1-grade ethanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, and 30 mL of Petrosolv 200-300 in a molar ratio of (710:5:1.0:12.2:184.8:7.3) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 210 °C in 20 °C increments over 1 h. The time at temperature T was 2 h with stirring. The solvent / ethanol ratio was 3. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by, for example, integrating the GC signal of 1-butanol relative to all other components except ethanol in the product. The GC trace showed a conversion of 52.9% and a selectivity of 88.7%.

[0216] Comparative Example 35 1-Propanol conversion was tested under similar conditions as ethanol. 1-Propanol produces propionaldehyde. Under our reaction conditions, aldol condensation of propionaldehyde produces 2-methylpent-2-enal, which is hydrogenated to produce 2-methylpentan-1-ol. The distribution coefficients for 1-propanol and the resulting intermediates and final products are listed in Figure 6. Technical grade 1-propanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, and 140 mL of mesitylene were premixed in a molar ratio of (2948.6:1.0:5.5:786.6:7.7) in air at ambient temperature and then heated to 70°C (2 hours). The temperature was then increased to 200°C in 20°C increments over 1 hour. The time at temperature T was 2 hours. The solvent / 1-propanol ratio was 2.8. Upon reaction completion, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed by integrating the GC signal of 2-methylpentan-1-ol relative to all other components except 1-propanol in the product. The GC trace showed a conversion of 46.95% and a selectivity of >99%.

[0217] Comparative Example 36 Technical-grade 1-propanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, and 140 mL of mesitylene were premixed in air at ambient temperature in a molar ratio of 2948.6:1.0:5.5:786.6:7.7 and then heated to 70°C (2 h). The temperature was then increased to 180°C in 20°C increments over 1 h. The time at temperature T was 2 h. The solvent / 1-propanol ratio was 2.8. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal for 2-methylpentan-1-ol compared to all other components in the product except for 1-propanol. The GC trace showed a conversion of 37.47% and a selectivity of >99%.

[0218] Comparative Example 37 Technical-grade 1-propanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, and 140 mL of mesitylene were premixed in air at ambient temperature in a molar ratio of 2948.6:1.0:5.5:786.6:7.7 and then heated to 70°C (2 h). The temperature was then increased to 160°C in 20°C increments over 1 h. The time at temperature T was 2 h. The solvent / 1-propanol ratio was 2.8. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal for 2-methylpentan-1-ol compared to all other components in the product except for 1-propanol. The GC trace showed a conversion of 33.67% and a selectivity of >99%.

[0219] Comparative Example 38 G1-grade 1-propanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, and 2 mL of mesitylene solvent were premixed in a molar ratio of (88.8:138.6:1.0:1.5:36.9:6.1) in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 7 h. The solvent / alcohol ratio was 1.34. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. A representative GC trace is shown in Figure 9.

[0220] Example 39 Technical-grade 1-propanol, ruthenium(III) chloride hydrate salt, imidazole, KOH, Raney® Ni, activated carbon, 1 mL of mesitylene, and 1 mL of Petrosolv 200-300 in molar ratios (554.3:1.0:18.3:184.8:9.7; 172.8) were premixed in air at ambient temperature and then heated to 70 °C (2 h). The temperature was then increased to 150 °C in 20 °C increments over 1 h. The time at temperature T was 2 h. The solvent / 1-propanol ratio was 2. Upon completion of the reaction, the reactor was cooled in an ice bath and the pressure was released. The reaction mixture was filtered through celite and analyzed by GC-FID and GC-MS. Selectivity was assessed, for example, by integration of the GC signal of 2-methylpentan-1-ol compared to all other components except 1-propanol in the product. GC tracing showed a conversion of 11.2% with a selectivity of >99%.

[0221] Example 40 Distillation A representative crude sample reaction mixture (300 mL) from a GC-FID test, as shown in Figure 8, was transferred to a 1000 mL round-bottom flask equipped with a stir bar and a 50 cm long fractionating column packed with iron or copper wool to increase the number of theoretical plates. Distillation is preferably carried out at atmospheric pressure, although operation at subatmospheric or superatmospheric pressures is possible if desired under certain circumstances. Generally, the number of trays in the fractionating column and the amount of heat transferred to the material being purified in the fractionating column are sufficient to produce a purified n-butanol liquid stream containing at least about 97-99% n-butanol.

[0222] The composition of the distilled product was determined by GC-FID as follows: Fraction 1: 78.5℃, 12.4g (ethanol) Fraction 2: 78.5-116.5°C, 7.2g (2:1:0.1 mixture of ethanol, n-butanol, and acetaldehyde diethyl acetal) Fraction 3: 116.5-118.5°C, 14.2g (n-butanol) Fraction 4: The residue remains.

[0223] This example demonstrates that we were successful in distilling the sample. Example 41 The catalyst according to the invention, ethanol, and solvent were premixed at ambient temperature and then heated at 70°C (2 hours). The temperature was then increased by 20°C over 1 hour to a temperature of #°C. The time at temperature T was 4 hours. The catalyst was present at 0.0494 mol% and the solvent / ethanol ratio was 3. The results are shown in Table 5 below.

[0224] Run 1 corresponds to the description in Example 22. Run 2 and Run 3 correspond to the description in Example 21. Run 4 corresponds to the description in Example 20. Run 5 corresponds to the description in Example 19. Run 6 corresponds to the description in Example 18. Run 7 and Run 8 correspond to the description in Example 17. Runs 2 and 3 were identical except that Run 3 was conducted after exposing the catalyst to the natural environment for 4 months. Run 7 and Run 8 were identical except that Run 8 was conducted after exposing the catalyst to the natural environment for 6 months, demonstrating that the catalyst system is relatively stable in air / water.

[0225] [Table 5]

[0226] In the examples according to the present invention, no intermediates were formed as observed by GC. In the examples according to the present invention, only n-butanol was formed, and no other butanol isomers were observed. As shown in Figure 5, in the examples with longer run times, more C6 and C8 were formed from n-butanol.

Claims

1. a. C １～３ premixing an alcohol, a catalyst, and a multi-component solvent system to form a liquid mixture; and b) heating the liquid mixture, thereby obtaining a higher alcohol; the multi-component solvent system comprises at least a basic aqueous hydrocarbon solvent phase comprising at least two different hydrocarbons, the solvent comprising a base selected from the group comprising potassium hydroxide, sodium hydroxide, potassium ethoxide, sodium ethoxide, potassium t-butoxide, sodium t-butoxide, or combinations thereof, e.g., a eutectic mixture of sodium hydroxide and potassium hydroxide; The catalyst is (HL)M(OH) n (H ２ O) m complexes and activated carbon, C １～３ A process for converting alcohol into higher alcohols wherein M is a metal selected from the group comprising Ru, Co, Ir, Rh, Os, Mo, W, Sc, Tc, Pt, Pd, Fe, or Ni; HL is a protic monodentate organic ligand, a protic bidentate organic ligand, or a polydentate organic ligand; where m and n are integers.

2. HL is indole, maleimide, maltol, 5-hydroxymaltol, kojic acid, tropolone, thujaplicin, hinokitiol, stipitatic acid, 2,6-bis[4-isopropyl-2-oxazolin-2-yl]pyridine, imidazole, 2,6-bis[4-phenyl-2-oxazolin-2-yl]pyridine, 2,6-bis[(3,8)-8H-indeno[1,2-d]oxazolin-2-yl)pyridine, pyrrole, pyrazole, 4-hydroxypyrazole, pyrazole-3-carboxaldehyde, pyrazole-3-carboxylic acid, pyrazole pyrazole-4-carboxylic acid, pyrazole-3,5-dicarboxylic acid, 4-alkyl / arylpyrazole, 3-alkyl / arylpyrazole, 5-alkyl / arylpyrazole, 3,5-alkyl / arylpyrazole, 1-benzylpyrazole, 3,5-di(2-pyridyl)pyrazole, 2-(1H-pyrazol-3-yl)phenol, 2-(1H-pyrazol-5-yl)aniline, 3-alkylpyrazole-5-carboxylic acid, indazole, 5-hydroxypyrazole, tris(1-pyrazolyl)methane, tris(3,5-dimethyl-1- (pyrazolyl)methane, bis(pyrazolyl)methane, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole, 4-arylimidazole, 5-alkylimidazole , 5-arylimidazole, 4-methylimidazole, 1-benzylpyrazole, 4-arylimidazole, 5-methylimidazole, 2-(1H-imidazol-2-yl)pyridine, 2-(1-hydroxyethyl)benzimidazole, 2-(2-pyridyl)benzimidazole, 2-(2-hydroxyphenyl)-1H-benzimidazole, 1H-pyrazol-3-ylboronic acid hydrate, 3,5-dimethyl-4-hydroxypyrazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(2-pyridyl)benzothiophene, 2-aryl-4H-(1,2,4)triazole, 2-(4-methyl-2-pyridyl)-1H-benzimidazole, 2-arylbenzothiazole, 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-5,5'-dicarboxylic acid, 2,2'-bipyridine-3,3'-dicarboxylic acid, 4-imidazolecarboxylic acid, 4-pyrrolecarboxylic acid, pyrrole-3-carboxylic acid, 5-oxazolecarboxylic acid, 2,2' 2. The process of claim 1, wherein the protic monodentate organic ligand is selected from the group consisting of 4,5-dimethylimidazole, 2,2'-bisimidazole, imidazole-4-carboxaldehyde, imidazole-4,5-dicarboxylic acid, 4,4'-bisimidazole, 4,4'-bisbenzimidazole, 2,2'-bisbenzimidazole, 4,5-bis(hydroxymethyl)imidazole, 2-(diphenylphosphino)benzenesulfonic acid, and 2-[di(2-methoxyphenyl)phosphino]benzenesulfonic acid.

3. Said C １～３ 3. The process according to claim 1, wherein the alcohol is ethanol, preferably bioethanol and / or fuel-grade ethanol.

4. 4. The process of claim 3, wherein the solvent / ethanol ratio is at least 2.0, preferably at least 3.

0.

5. The ligand HL is imidazole, 4-hydroxybenzimidazole, 1-benzylimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 2-alkylimidazole, 2-arylimidazole, 4-alkylimidazole, 2-aminobenzimidazole, 2-alkylbenzimidazole, 4,5-diarylimidazole, 4,5-dialkylimidazole, 2,4,5-triarylimidazole, 2,4,5-trialkylimidazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 4-methylimidazole, 4-arylimidazole, 5-alkylimidazole, 5-arylimidazole, 5-methylimidazole, 2-(1H-imidazol-2-yl)pyridine, 2-(1-hydroxyethyl)benzimidazole, 5-methylimidazole , 2-(2-pyridyl)benzimidazole, 2-(2-hydroxyphenyl)-1H-benzimidazole, 2-(2-pyridyl)benzimidazole, 2-(1H-imidazol-2-yl)pyridine, 2,6-bis(2-benzimidazolyl)pyridine, 2-(3-pyridyl)-1H-benzimidazole, 2-(4-methyl-2-pyridyl)-1H-benzimidazole, 2,2'-bis(4,5-dimethyl 5. The process according to any one of claims 1 to 4, wherein the ligand HL is selected from the group comprising imidazole), 2,2'-bisimidazole, imidazole-4-carboxaldehyde, imidazole-4,5-dicarboxylic acid, 4,4'-bisimidazole, 4,4'-bisbenzimidazole, 2,2'-bisbenzimidazole, 4,5-bis(hydroxymethyl)imidazole, preferably wherein the ligand HL is imidazole.

6. The process of any one of claims 1 to 5, wherein the metal is Ru.

7. The process of any one of claims 1 to 6, wherein the catalyst further comprises a skeletal or sponge metal catalyst, preferably Raney nickel.

8. The process of any one of claims 1 to 7, wherein the basic aqueous solvent phase comprises an alkali hydroxide, preferably KOH.

9. The process of any one of claims 1 to 8, wherein step a. is carried out at ambient temperature.

10. Step b. b1. Heating the mixture to a temperature T1 within a time frame Δt1; b2. Heating the mixture to a temperature T2 within a time frame Δt2; and b3. maintaining the mixture at temperature T2 for a time period Δt3.

11. 11. The process of claim 10, wherein T2 is at least 140°C and up to 500°C, preferably at least 150°C and up to 400°C, preferably at least 160°C and up to 300°C, preferably at least 170°C and up to 260°C, preferably at least 180°C and up to 240°C, preferably at least 190°C and up to 220°C, preferably 200°C.

12. Said C １～３ 12. The process of any one of claims 1 to 11, wherein the alcohol is converted to n-butanol.

13. Said C １～３ Alcohol is C ６～８ The process of any one of claims 1 to 12, wherein the hydroxybenzoate is converted to an alcohol.

14. 14. The process of any one of claims 1 to 13, wherein the process is carried out in a reaction vessel, the reaction vessel acting as an intrinsic catalyst.

15. c) Distilling the higher alcohol The process of any one of claims 1 to 14, further comprising:

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