Production of nitrile compounds

Abstract

The present invention relates to a process for producing nitrile compounds via chain extension of alkyleneamine compounds containing three or more amine units, where at least two amine units are protected by cyclic urea units and at least one amine unit is unprotected. The chain extension is carried out by reacting at least one unprotected amine unit with glycolonitrile or a combination of formaldehyde and a cyanide selected from HCN and inorganic cyanide salts to add at least one acetonitrile group to the at least one unprotected amine unit. The process according to the present invention allows for the production of nitrile compounds with high selectivity and high yield. The nitrile compound can be treated as desired.

Description

[Technical field]

[0001] The present invention relates to a process for producing nitrile compounds via selective chain extension of alkyleneamine compounds having three or more amine units. [Background technology]

[0002] The production of nitrile compounds via chain extension of alkyleneamine compounds is known in the art. This can be carried out, for example, by reacting alkyleneamines with glycolonitrile or with a combination of hydrogen cyanide and formaldehyde to form chain-extended nitrile compounds. Hydrogenation of the nitrile compounds results in the formation of amine compounds. Such a process is disclosed, for example, in US2010 / 0121064 for the reaction of EDA with glycolonitrile (referred to as FACH in this state of the art document). However, as shown in this reference, the process produces undesirable secondary products. Summary of the Invention [Problem to be solved by the invention]

[0003] The amount of secondary components increases with the amount of amine moieties present in the amine molecule, and therefore the amount of secondary components is greater starting with larger molecules containing more amine units than those disclosed in US2010 / 0121064. [Means for solving the problem]

[0004] It has now been found that it is possible to protect the primary and secondary amine groups in alkyleneamine compounds containing three or more amine units with cyclic urea units and selectively react the alkyleneamines on the amine groups that are not part of such cyclic urea units with glycolonitrile or with a combination of formaldehyde and a cyanide selected from HCN and inorganic cyanide salts, thereby allowing for the formation of fewer by-products.

[0005] Thus, the present invention relates to a process for producing nitrile compounds via chain extension of alkyleneamine compounds containing three or more amine units, at least two of which are protected by cyclic urea units and at least one amine unit is unprotected, wherein the chain extension is by reacting at least one unprotected amine unit with glycolonitrile or with a combination of formaldehyde and a cyanide compound selected from HCN and an inorganic cyanide salt to add at least one acetonitrile group to the at least one unprotected amine unit.

[0006] It should be noted that chain-extended alkyleneamines in which part of the amine is protected with a cyclic urea group are not known. Such processes are disclosed, for example, in US2015 / 0065679, EP078169, US5,399,706, US2,785,176, GB972,003. The processes in these documents are based either on the Michael addition reaction of an amine compound with a substance having an activated double bond, such as acrylonitrile or butenenitrile, or on its reaction with an epoxide or chloride, such as 2-chloroethylamine.

[0007] With the exception of reaction with 2-chloroethylamine, which results in the formation of a salt, the Michael addition reaction leads to molecules in which no ethyleneamine chain extension is observed. More specifically, the reaction leads to either the incorporation of propylene or larger alkylene chains, or to compounds terminating in alkyl units. Reaction with epoxides also introduces additional hydroxy groups.

[0008] Surprisingly, it has been found that in the process of the present invention, an acetonitrile chain is selectively added to an amine group or groups in an alkyleneamine compound that is not part of a cyclic urea unit, without salt formation and without introducing additional functional groups.

[0009] An additional advantage of the process of the present invention is that due to the presence of cyclic urea units that render the amine units unable to react with each other, in many embodiments, it is possible to prevent cyclization or polymerization reactions that can occur when hydrogenating acetonitrile-terminated compounds, such as, for example, when hydrogenating ethylenediaminoacetonitrile. Also, due to the presence of urea groups, there are fewer amino groups. As a result, there are fewer side reactions in which the nitrile groups react with other amino groups, resulting in the formation of fewer by-products, thereby increasing selectivity.

[0010] The process of the present invention allows for the preparation of nitrile compounds in a more selective manner, thus allowing for the application of more stringent reaction conditions resulting in higher conversions and the production of the desired nitrile compounds in higher yields.

[0011] Furthermore, it has been found that when glycolonitrile is used as a reactant, it is possible to selectively add one or more acetonitrile units to an unprotected amine group, and that when cyanide and formaldehyde are used, it is possible to selectively add two acetonitrile units to an amine group or groups that are not part of a cyclic urea unit.

[0012] Thus, the process of the present invention provides many options for preparing selectively chain extended alkylene amines. As a result of the selective reaction, less effort is required to separate the reaction mixture, resulting in reduced costs for both processing and equipment.

[0013] The process of the present invention results in the formation of a compound comprising at least one acetonitrile group and at least two amine units protected by cyclic urea units, which can be further processed as desired, as described below. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] The process according to the invention is discussed in more detail below.

[0015] The starting compound in the process according to the invention is an alkyleneamine compound containing three or more amine units, at least two of which are protected by a cyclic urea unit and at least one of which is unprotected.

[0016] The phrase two amine units protected by a cyclic urea unit refers to a unit of formula I. [ka] wherein A is selected from the group of C2-C4 alkylene units, optionally substituted with one or more C1-C3 alkyl groups. In this cyclic alkylene urea group, A is preferably a C2-C3 alkylene unit, optionally substituted with one or two C1 alkyl groups. It is preferably selected from the group of ethylene, propylene, and isopropylene, specifically ethylene. When multiple A's are present in the molecule, each A can be independently selected.

[0017] In one embodiment, the starting compound is an alkylene urea compound comprising at least one primary or secondary amine group of formula I and at least one cyclic alkylene urea group of formula I. The (unprotected) amine group is preferably a primary amine group or a cyclic secondary amine group. It is particularly preferred that the amine group is a primary amine group.

[0018] The alkyleneamine compound used as starting material in the present invention contains at least one cyclic urea unit of formula I. Generally, the alkyleneamine compound contains up to 10 cyclic urea units of formula I. In practice, the alkyleneamine compound often contains up to 5 cyclic urea units of formula I. The alkyleneamine compound contains at least one unprotected amine unit. Generally, the alkyleneamine compound contains up to 5 unprotected amine units. In practice, the alkyleneamine compound often contains up to 3 unprotected amine units, particularly 1 or 2, particularly 1.

[0019] The alkylene units in the alkyleneamine compounds generally have from 1 to 10, particularly from 1 to 8, carbon atoms. In one embodiment, the alkylene units meet the requirements of A above.

[0020] In one embodiment, the alkyleneamine compound is free of moieties other than amine units and alkylene units.

[0021] In another embodiment, the alkyleneamine compound comprises moieties other than amine and alkylene units. Such moieties may be selected, for example, from C1-C6 alkyl groups optionally substituted with -OH, -COOH, and / or COO-alkyl, and ether moieties (-O-).

[0022] The alkyleneamine compounds generally have a molecular weight in the range of 115 to 10.000 g / mol, particularly 115 to 1000 g / mol, and in some embodiments 115 to 500 g / mol.

[0023] In one embodiment, the alkylene urea compound is a compound of formula II: Formula II: R2-[-XA-] q -N(A)(CO)N-[AX-] p -A-NH2 During the ceremony, R2 is selected from H and a C1-C6 alkyl group optionally substituted with one or more groups selected from -OH, -NH2, and -COOR4, particularly with zero, one or two groups selected from -OH, -NH2, and COOR4, particularly with zero, one or two groups selected from -OH and -NH2, and R4 is H or a C1-C6 alkyl group. X is independently selected at each occurrence from -O-, -NR2-, a group of formula I, and a group of formula III. [ka] [ka] A has the meaning discussed above, and when more than one A is present in a molecule, each A may be independently selected; p is an integer ranging from 0 to 8; q is an integer ranging from 0 to 8.

[0024] For the avoidance of doubt, the structure -N(A)(CO)N- in formula II corresponds to formula I.

[0025] The above choices for A also apply here. It is particularly preferred that A is ethylene.

[0026] X is preferably selected from -NH-, a group of formula III, and a group of formula I. When it is desired to produce a linear alkylene amine, X is preferably selected from NH and a group of formula I.

[0027] R2 is preferably selected from H, ethyl, propyl, and isopropyl, in particular ethyl, optionally substituted by one or two groups selected from -OH and -NH2. R2 is particularly preferably ethyl or propyl, in particular ethyl, substituted by -NH2 at the second carbon atom (aminoethyl or aminoisopropyl) or, in the case of propyl, at the third carbon atom, counting from the connection to X.

[0028] Since reactions of large molecules to form even larger molecules are not necessarily of interest, it may be preferred that the sum of p and q be at most 8, and in some embodiments at most 4, or at most 2.

[0029] Examples of preferred compounds of formula II are the urea adduct of diethylenetriamine (U-DETA), the monourea adduct of triethylenetetramine (U1-TETA and U2-TETA) in which the urea group can be at the terminal ethylene moiety or at the central ethylene moiety, and the mono- and diurea adducts of tetraethylenepentamine with primary amine groups (U1-TEPA, DU1,3-TEPA).These compounds are particularly attractive when it is desired to make linear polyethyleneamine nitrile compounds and their respective urea products.

[0030] Examples of other compounds that may be used in one embodiment of the process according to the invention are compounds consisting of an ethyleneamine chain with a urea group on the nitrogen atom on each side of a terminal ethylene moiety and an ethylene chain on the nitrogen atom on each side of another ethylene moiety, e.g., U1P3-TEPA and U1P4-TEPA.

[0031] Generally, compounds are named herein as follows:

[0032] The letter code refers to the longest linear ethyleneamine chain.

[0033] U refers to the presence of a cyclic urea group resulting from the presence of urea groups on two adjacent nitrogen atoms connected through an ethylene moiety, ie, the presence of a group of formula I where A is an ethylene group.

[0034] P refers to the presence of a piperazine moiety resulting from the presence of ethylene moieties on two adjacent nitrogen atoms connected via ethylene moieties, ie, the presence of a group of formula III where both A are ethylene groups.

[0035] The numbers after the U or P prefix refer to each nitrogen atom in the chain to distinguish between the different possible structures.

[0036] The letter before the U or P prefix refers to the number of the group, with D representing di, or 2 groups, and T representing tri and tetra, or 3 and 4 groups, respectively. When T is used, it will be clear from the context whether tri or tetra is meant.

[0037] In another embodiment, the alkylene urea compound is a compound of formula IV: Formula IV:R2-[-XA-] q -N(A)(CO)N-[AX-] p -AN(A)(A)N-[-AX-] r -R3 wherein R2, X, A, q and p have the meanings given above. The preferences given above also apply here.

[0038] R3 is selected from H and C1-C6 alkyl groups optionally substituted with one or more groups selected from -OH and -NH2, especially zero, one or two groups selected from -OH and -NH2. R3 is preferably selected from H, ethyl, propyl and isopropyl, especially ethyl, optionally substituted with one or two groups selected from -OH and -NH2. R3 is especially preferably ethyl or propyl, especially ethyl, substituted with -NH2 at the second carbon atom (aminoethyl or aminoisopropyl) or, in the case of propyl, at the third carbon atom, counting from the connection to X.

[0039] In formula IV, r is an integer between 0 and 8, particularly between 0 and 4, and more particularly 0, 1, or 2. Because reaction of larger molecules to form even larger molecules is not always of interest, it may be preferred that the sum of p, q, and r is at most 8, in some embodiments at most 4, or at most 2.

[0040] For the avoidance of doubt, the structure -N(A)(CO)N- in formula IV corresponds to formula I. The structure -N(A)(A)N- in formula IV corresponds to formula III.

[0041] An example of a preferred compound of formula IV is the urea adduct of piperazinoethylethylenediamine (UP-TETA). Also preferred are U1P3-TEPA and U1P4-TEPA.

[0042] Mixtures of alkylene urea compounds may also be used.

[0043] In a preferred embodiment, the starting compound in the process of the present invention, an alkyleneamine containing three or more amine units, at least two of which are protected by cyclic urea units and at least one amine unit is unprotected, is selected from the group of U-DETA, U1-TETA, UP-TETA, U2-TETA, DU1,3-TEPA, DU1,4-TEPA, U1P3-TEPA, and U1P4-TEPA.

[0044] The starting compounds described above are reacted with glycolonitrile or with a combination of formaldehyde and a cyanide selected from HCN and inorganic cyanide salts, the reactions of which are described below.

[0045] In one embodiment, the starting compound described above is reacted with glycolonitrile, also known as hydroxyacetonitrile or formaldehyde cyanohydrin. Below is an example of this reaction using U-DETA as the starting material. Water (not shown) is also formed in the reaction. [ka]

[0046] The reaction between the starting compound and glycolonitrile is generally carried out at a temperature of 0 to 100°C, in particular 0 to 50°C, in particular 0 to 35°C. The reaction is generally carried out at a pressure of 0.5 to 10 bar. Since high pressure is not required, it may be attractive to carry out the reaction at a pressure of 0.5 to 5 bar, in particular 0.5 to 3 bar. Atmospheric pressure is considered to be preferred. In this specification, when pressure is referred to in bar, bar(a) is meant.

[0047] The reaction may be carried out in a solvent. Water is a suitable solvent, but other solvents in which the reactants can dissolve under the reaction conditions but do not substantially react under the reaction conditions may be considered. Other suitable solvents include organic solvents, such as amides, such as N-methylpyrrolidone (NMP) and dimethylformamide (DMF), aromatic and aliphatic hydrocarbons, such as benzene and xylene, alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, secondary butanol and tertiary butanol, amines, such as ethyleneamines, alkylamines, ammonia, esters, such as methyl acetate or ethyl acetate, and ethers, such as diisopropyl ether, diisobutyl ether, glycol dimethyl ether, diglycol dimethyl ether, dioxane and tetrahydrofuran (THF). The use of ethers, particularly cyclic ethers, especially tetrahydrofuran, is considered more preferred. Alternatively, alcohols, particularly methanol, as the organic solvent may be preferred. The use of amines and ammonia, although possible, is less attractive due to their possible involvement in the reaction.

[0048] As will be apparent to those skilled in the art, the reaction can be carried out as a batch or continuous process. Suitable reactor and process configurations are known in the art and do not require description here.

[0049] The molar ratio of starting compound to glycolonitrile depends on the desired chain extension and the number of reactive amine groups in the starting compound. In general, the molar ratio of glycolonitrile to reactive amine groups in the starting material is in the range of 0.25:1 to 4:1. Since an excess of glycolonitrile is in principle not required, it is preferred that the molar ratio of glycolonitrile to reactive amine groups in the starting material is at most 3:1, in particular at most 2:1, more in particular at most 1.5:1.

[0050] When the starting compound contains one reactive amine group, generally, the complete conversion of the reactive amine group to the monocyanomethylated product is desired.Therefore, in this case, it is preferred that the molar ratio of glycolonitrile to reactive amine group (which is the same as the starting compound in this case) is at least 0.5:1, in particular at least 0.75:1, more in particular at least 0.9:1, in particular at least 1:1.

[0051] If the starting compound contains more than one reactive amine group, the molar ratio of glycolonitrile to primary amine groups in the reaction mixture depends on the desired degree of chain extension and therefore on the desired degree of conversion. If it is desired to react all amine groups to obtain a complete conversion, the abovementioned values ​​of the molar ratio of glycolonitrile to reactive amine groups apply. If only a partial conversion of the amine groups is desired, lower ratios apply. In this case, it may be preferred that the molar ratio of glycolonitrile to reactive amine groups is in the range of 0.25:1 to 1:1, in particular in the range of 0.25:1 to 0.9:1, or 0.25:1 to 0.7:1, or 0.25:1 to 0.5:1.

[0052] For example, U2-TETA can react with one or two glycolonitrile molecules to form mono- or dicyanomethylated U2-TETA or a mixture thereof. Lower glycolonitrile to amine group ratios lead to the formation of more mono-cyanomethylated U2-TETA, while higher glycolonitrile to primary amine group ratios lead to the formation of more dicyanomethylated U2-TETA.

[0053] As the skilled artisan will recognize, there is often a trade-off between the conversion of starting materials and the selectivity to the desired product, where an increase in the conversion of starting materials may be accompanied by an increase in the formation of by-products, resulting in a decrease in the selectivity to the desired product. With this in mind, it is within the skill of the skilled artisan to select the reaction conditions (reaction time, reaction temperature, ...) and the ratio between the reactants to obtain the desired balance between the conversion and the selectivity to the desired product.

[0054] In another embodiment, the starting compound described above is reacted with a combination of formaldehyde and a cyanide selected from HCN and an inorganic cyanide salt. Below is an example of this reaction using U-DETA as the starting material. [ka]

[0055] In one embodiment, the cyanide is HCN. In this case, the reaction is preferably carried out at a temperature in the range of -5°C to 90°C, in particular 0°C to 60°C, and at a pressure of 0.5 to 10 bar. Since high pressure is not required, it may be attractive to carry out the reaction at a pressure of 0.5 to 5 bar, in particular 0.5 to 3 bar. Atmospheric pressure may be preferred.

[0056] The reaction can be carried out in a solvent. Water is a suitable solvent, but other solvents in which the reactants are soluble under the reaction conditions can also be considered. The solvents mentioned above for the reaction with glycolonitrile can also be applied here.

[0057] As will be apparent to those skilled in the art, the reaction can be carried out as a batch or continuous process. Suitable reactor and process configurations are known in the art and do not require description here.

[0058] The reaction is preferably carried out at a pH in the range of from 1 to 9, more specifically at a pH of from 2 to 7. If necessary, a pH adjuster can be added.

[0059] In this process, among other features, the addition of formaldehyde and hydrocyanic acid can be used as tools to control the balance between selectivity and conversion.

[0060] In another embodiment, the cyanide is an inorganic cyanide salt. In this case, the cyanide salt is preferably selected from alkali metal cyanide salts and alkaline earth metal cyanide salts. Suitable alkali metal salts include sodium, potassium, and lithium salts, with sodium and potassium being preferred, and sodium being particularly preferred. An example of a suitable alkaline earth metal salt is calcium cyanide. In general, it is preferred that the cyanide is soluble in the reaction medium under the reaction conditions.

[0061] When a cyanide salt is used, the end product obtained depends on the pH of the reaction medium. When the reaction is carried out under acidic conditions, the end product will be a nitrile. In this case, the pH is preferably kept within the range of 1 to 7. If desired, an acid, for example a strong inorganic acid, can be added to maintain the pH in the desired range. When the reaction is carried out under strongly basic conditions, the nitrile formed in the reaction will further react to form a carboxylate salt. A base, in particular a strong inorganic base such as NaOH or KOH, can be added to promote the formation of carboxylate groups. In this case, the reaction may be preferably carried out at a pH of 10 to 14.

[0062] The reaction of the starting compound with the combination of formaldehyde and an inorganic cyanide salt is preferably carried out at a temperature of from 30 to 150°C, in particular from 50 to 130°C.

[0063] In one embodiment, the ammonia produced by hydrolysis of the nitrile group is preferably distilled off from the reaction mixture simultaneously with reagent dosing, allowing for higher product purity.

[0064] The reaction is generally carried out at a pressure of 0.5 to 10 bar(a). Since high pressure is not required, it may be attractive to carry out the reaction at a pressure of 0.5 to 5 bar, in particular 0.5 to 3 bar. Atmospheric pressure may be preferred.

[0065] The reaction can be carried out in a solvent. Water is a suitable solvent, but other solvents in which the reactants are soluble under the reaction conditions can also be considered. The solvents mentioned above for the reaction with glycolonitrile can also be applied here.

[0066] As will be apparent to those skilled in the art, the reaction can be carried out as a batch or continuous process. Suitable reactor and process configurations are known in the art and do not require description here.

[0067] The formaldehyde and cyanide may be provided to the reaction mixture simultaneously or sequentially, in a single dose or in a series of doses. They may be provided separately to the starting material or may be combined before reacting with the starting material. Combinations of the various embodiments are also envisioned. Simultaneous addition of the reagents may be preferred.

[0068] The molar ratio between formaldehyde and cyanide is in the range of 0.5:1 to 2:1, in particular 0.7:1 to 1.4:1, more in particular 0.9:1 to 1.1:1, for example equimolar.

[0069] The desired ratio between the starting compound and the cyanide depends on the desired chain extension, the number of reactive amine groups in the starting compound, and whether the reactive amine groups are primary or secondary amines. In general, one cyanide molecule is required per NH bond to be reacted for complete conversion. Thus, in general, the molar ratio of cyanide to reactive NH bonds of reactive amines in the starting material ranges from 0.25:1 to 4:1. Since an excess of cyanide is not required in principle, this ratio is preferably at most 3:1 or at most 2.5:1, or at most 2:1, or at most 1.5:1, in particular at most 1.2:1. Since partial conversion is generally unattractive, the molar ratio of cyanide to reactive NH bonds of reactive amines in the starting material is preferably at least 0.5:1, more preferably at least 0.8:, more particularly at least 1:1.

[0070] The process according to the invention results in the formation of acetonitrile-substituted alkyleneamine compounds. Examples of starting materials and nitrile products that can be obtained therefrom are given in the table below.

[0071] [Table 1A]

[0072] [Table 1B]

[0073] Other combinations of starting materials and the nitrile products that can be obtained are given in the table below. [Table 2A]

[0074] [Table 2B]

[0075] [Table 2C]

[0076] [Table 2D]

[0077] [Table 2E]

[0078] [Table 2F]

[0079] [Table 2G]

[0080] [Table 2H]

[0081] [Table 2I]

[0082] [Table 2J]

[0083] [Table 2K]

[0084] [Table 2L]

[0085] [Table 2M]

[0086] In one embodiment, in a next step, the acetonitrile group resulting from the process of the present invention is further reacted. For example, in one embodiment, the nitrile unit is hydrogenated to provide an amine group. For example, in another embodiment, the nitrile unit is hydrolyzed to provide a terminal amide (under neutral or weakly acidic conditions) or a carboxylic acid group (under alkaline conditions). For example, in a further embodiment, the nitrile group can be reacted with a Grignard reagent to form an imine salt, which can be hydrolyzed to produce a ketone.

[0087] If desired, the cyclic urea protecting group can be removed from the product obtained by the process according to the invention. In one embodiment, this can be done by reaction under alkaline conditions. In that case, if the acetonitrile groups have not already been converted to another group in the formed product, they are also saponified to carboxylic acid groups under alkaline conditions. Thus, the removal of the cyclic urea unit and the saponification of the acetonitrile group to a carboxymethyl group can be carried out simultaneously. However, if it is desired to convert the nitrile group to an amine unit by reacting it with another chemical, in some embodiments it may be preferred to carry out such a reaction first, before the cyclic urea unit is removed. This will be explained in more detail below.

[0088] The following reaction schemes show possible further reactions starting from the U-DETA derived products.

[0089] [ka]

[0090] [ka]

[0091] [ka]

[0092] In one embodiment, the nitrile product of the process according to the invention is subjected to a catalytic hydrogenation step in which the nitrile compound is reacted with hydrogen to convert the nitrile to the corresponding amine.

[0093] The catalytic hydrogenation of the acetonitrile product of the present invention is preferably carried out using a hydrogenation catalyst, such as Raney cobalt or Raney nickel, a supported catalyst containing an element of group 8 of the periodic table, such as Fe, Co, Ni, Cu, Ru, Rh, Pd, Os, Ir, Pt, preferably Fe, Co, Ni, Ru or Rh, especially Co or Ni. The catalyst may be supported on an inorganic oxide support, for example based on alumina, silica, titania, zirconia, or combinations thereof, or on a porous carbon support.

[0094] The reaction may be carried out at a temperature of 40-150° C., preferably 70-140° C., in particular 80-140° C., and at a pressure of 5-300 bar, preferably 30-250 bar, in particular 40-160 bar. The catalytic hydrogenation of the acetonitrile product is known in the art and does not require further explanation here.

[0095] The hydrogenation process leads to the formation of alkyleneamine compounds which have acquired additional ethyleneamine groups compared to the starting compounds of the process according to the invention, which makes it possible to obtain chain-extended alkyleneamine compounds.

[0096] The following table provides examples of starting materials, nitriles, and resulting amine products. [Table 3]

[0097] In another embodiment, the nitrile product of the process according to the invention is subjected to a saponification step in which the nitrile compound reacts with a base to form a carboxylate salt, which can be carried out subsequent to the nitrile formation, but can also be carried out simultaneously with the nitrile formation if the latter is carried out using an inorganic cyanide salt as discussed above.

[0098] When saponification of the acetonitrile product is carried out as a separate step, it is preferably carried out by adding a base such as an aqueous solution of sodium hydroxide or potassium hydroxide. In a further preferred embodiment, the base is used in an amount of 0.7 to 1.5 molar equivalents per acetonitrile group. As with the use of aqueous media, it is preferred to use KOH or NaOH as the base. Saponification processes are known in the art and do not require further explanation here.

[0099] The product from the saponification step is a salt of a carboxylic acid.

[0100] The following table lists some preferred starting material-nitrile intermediate-saponification product combinations. [Table 4]

[0101] In one embodiment, the nitrile group can be reacted with a Grignard reagent to form an imine salt, which can then be hydrolyzed to give the ketone.

[0102] Grignard reagents are compounds of formula R-Mg-X, where X is a halogen and R is an organic group, usually alkyl or aryl. X is generally selected from Cl, Br, and I. Examples of suitable R grounds include C1-C10 alkyl and C5-C10 aryl, alkylaryl, and arylalkyl. R is selected from, for example, methyl, ethyl, propyl, and phenyl. Examples include methylmagnesium chloride and phenylmagnesium bromide. Reaction with a Grignard reagent results in the formation of an imine compound. The imine can be converted to a ketone by reaction with water, preferably under acidic conditions. It is important to add water only after the imine has been formed, as the presence of water leads to the destruction of the Grignard reagent.

[0103] The reaction of a nitrile group with a Grignard reagent to form an imine which is subsequently hydrolyzed to form a ketone is known in the art and does not require further explanation here.

[0104] In a further embodiment, the aminonitrile compound obtained by the process of the present invention is subjected to a hydrolysis step to produce the corresponding amide. This reaction can be carried out in a solvent, particularly a protic solvent, preferably water, using an acid catalyst. Suitable catalysts include conventional acid catalysts such as inorganic acids, such as sulfuric acid, nitric acid, hydrochloric acid, and hydrobromic acid, and organic acids, such as formic acid, citric acid, acetic acid, trifluoroacetic acid, and combinations thereof.

[0105] The hydrolysis of aminonitrile compounds to form the corresponding amide compounds is known in the art and does not require further explanation here.

[0106] The following table lists some preferred starting materials, the corresponding nitrile intermediates, and amide product combinations. [Table 5]

[0107] In one embodiment, the cyclic urea protecting group is removed from the product obtained by the process according to the invention. Depending on the reaction conditions in the urea removal step, this can be done on the nitrile product or on the product from the further reaction discussed above. It is within the skill of the art to select the appropriate reaction sequence, taking into account the reactivity of the end groups and the general reaction conditions in the urea removal step.

[0108] Herein, compounds containing a cyclic urea protecting group may also be referred to as U-compounds or U-alkyleneamine compounds to reflect that removal of the cyclic urea protecting group results in the liberation of two amine groups that were previously protected by incorporation into the cyclic urea group. This process may also be referred to as a CO2 elimination step. It can be carried out in different ways.

[0109] In one embodiment, U-alkyleneamine compounds are reacted with water in liquid phase to form corresponding alkyleneamine compounds under removal of CO2. The reaction with water generally occurs at a temperature of at least 150°C. If the reaction temperature is less than 150°C, U-compounds do not react very much. The reaction is preferably carried out at a temperature of at least 180°C, particularly at least 200°C, more particularly at least 230°C, or even at least 250°C. Preferably, the temperature during this step does not exceed 400°C, particularly at most 350°C, more particularly at most 320°C.

[0110] The pressure during the process is not critical, as long as the reaction medium is in the liquid phase. As a general range, values ​​from 0.5 to 100 bar can be mentioned, depending on the desired temperature. In order to maintain a sufficient amount of amine and water in the medium, it is desirable to carry out the CO2 removal step at a pressure of at least 5 bar, in particular at least 10 bar. In view of the high costs associated with high-pressure equipment, a pressure of up to 50 bar, in particular up to 40 bar, may be preferred.

[0111] The amount of water depends on the desired degree of conversion and the process conditions. In general, the amount of water is at least 0.1 moles of water per mole of urea moiety in the feedstock. Often, larger amounts are used, for example at least 0.1 moles of water per mole of urea moiety, in particular at least 0.5 moles of water per mole of urea moiety. The maximum value is not critical for the process according to the invention, but too much water will require unnecessarily large equipment. As a general maximum value, we can mention an amount of water of up to 500 moles, in particular up to 300 moles, more particularly up to 200 moles, in some embodiments up to 100 moles, or up to 50 moles per mole of cyclic ethylene urea moiety.

[0112] It is preferred to carry out CO2 removal during the reaction, for example by venting the reaction vessel, preferably by providing a stripping gas such as nitrogen or steam.

[0113] In one embodiment, the U-alkyleneamine compound is reacted in the liquid phase with water in an amount of 0.1 to 20 moles per mole of urea moiety while removing CO2 at a temperature of at least 230° C. It has been found that the use of small amounts of water in combination with relatively high temperatures and CO2 removal results in an efficient process that results in good conversion and low formation of by-products.

[0114] In one embodiment, a U-alkyleneamine compound is reacted with an alkyleneamine from which a carbonyl moiety can be removed to result in the conversion of the U-alkyleneamine compound to its corresponding alkyleneamine compound and the simultaneous conversion of the alkyleneamine from which a carbonyl moiety can be removed to a U-alkyleneamine. This process can be described as a carbonyl transfer reaction.

[0115] In a further embodiment, the U-alkyleneamine compound reacts with a strong base, i.e., a base with a pKb of less than 1, to form the corresponding alkyleneamine compound and carbonate. In this embodiment, the use of a strong inorganic base is considered to be preferred. In one embodiment, the strong inorganic base is selected from the group of metal hydroxides, in particular the group of hydroxides of alkali and earth alkali metals, in particular from the group of sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, and barium hydroxide. In one embodiment, the strong inorganic base is selected from the group of metal oxides, in particular the group of oxides of alkali and earth alkali metals, in particular from the group of calcium oxide, magnesium oxide, and barium oxide. It may be preferred to select a strong inorganic base from the group of sodium hydroxide, potassium hydroxide, magnesium (hydr)oxide, and calcium (hydr)oxide. The use of sodium hydroxide and potassium hydroxide may be considered to be particularly preferred. Other strong inorganic bases, such as ammonium hydroxide, may also be used. As will be clear to the skilled person, mixtures of various inorganic bases may be used. Compounds containing a base in addition to other components may also be used, as is the compound that is converted into an inorganic base in the reaction medium. The molar amount of base can be calculated relative to the molar amount of alkylene urea moiety to be converted. A value of at least 0.2:1 can be mentioned. If it is desired to obtain complete conversion of the alkylene urea moiety to the corresponding alkylene amine compound, the use of a larger amount may be preferred, for example at a molar ratio of at least 1:1, in particular at least 1.5:1. To increase the reaction rate, it may be preferred to use a larger amount, for example at a molar ratio of at least 2:1, in particular at least 2.5:1. Since a large amount of base does not contribute to further conversion but leads to additional costs, it is preferred that the molar ratio of the molar amount of base to the alkylene urea moiety is at most 20:1, in particular at most 15:1, more in particular at most 10:1. It has been found that a smaller amount of inorganic base may be sufficient. More specifically, it has been found that good results are obtained with a molar ratio of base to alkylene urea moiety of at most 7.5:1, in particular at most 6.5:1, more in particular at most 5.5:1.It has been found that the use of a molar ratio of up to 5.5: 1 results in complete conversion of the alkylene urea moiety and a high yield of the resulting alkylene amine compound. It may be preferable to use less base per mole of alkylene urea moiety, for example, in a molar ratio of up to 5: 1, particularly up to 4: 1, more particularly up to 3: 1.

[0116] The treatment with a base can be carried out, for example, by contacting the material to be treated with a concentrated aqueous solution of an inorganic base. Depending on the nature of the base and the further composition of the reaction mixture, it is also possible to add the base in solid form and dissolve it in the reaction medium. As will be clear to the skilled artisan, the aim is to have the base in solution so that the hydroxyl groups can react with the CO2 adduct, while avoiding unnecessary dilution of the reaction medium.

[0117] The reaction can be carried out at temperatures between room temperature and 400°C. The temperature and pressure must be selected so that the reaction mixture is in the liquid phase. Higher temperatures are advantageous since they lead to shorter reaction times. It may be preferred to carry out the reaction at a temperature of at least 100°C, in particular at least 140°C, in particular at least 170°C. On the other hand, higher temperatures may lead to the undesired formation of by-products. It may therefore be preferred to carry out the reaction at a temperature of up to 350°C, in particular up to 290°C.

[0118] Depending on the reaction temperature, the reaction time may vary within a wide range, for example, between 15 minutes and 24 hours. It may be preferable for the reaction time to vary between 1 hour and 12 hours, in particular between 1 hour and 6 hours. If a smaller amount of base is used, a longer reaction time may be required to obtain the desired degree of conversion.

[0119] Once the reaction is complete, a reaction mixture is obtained containing the ethyleneamine compound and the carbonate salt of the inorganic base, which can be removed by methods known in the art, such as by filtration if the salt is in solid form, or more commonly, by phase separation.

[0120] Combinations of various CO2 removal steps are also possible, for example treatment with water with CO2 removal followed by treatment with base, optionally with an intermediate product removal step.

[0121] It will be apparent to one skilled in the art that the various preferred embodiments described herein can be combined, unless they are mutually exclusive. The present invention includes the following aspects. Section 1. 1. A process for producing nitrile compounds via chain extension of an alkyleneamine compound containing three or more amine units, at least two of which are protected by cyclic urea units and at least one of which is unprotected, said chain extension being by reacting said at least one unprotected amine unit with glycolonitrile or with a combination of formaldehyde and a cyanide compound selected from HCN and an inorganic cyanide salt to add at least one acetonitrile group to said at least one unprotected amine unit. Section 2. Item 1. The process of item 1, wherein the at least one unprotected amine unit is reacted with glycolonitrile. Section 3. Item 1. The process of item 1, wherein the at least one unprotected amine unit is reacted with a combination of formaldehyde and a cyanide selected from HCN and an inorganic cyanide salt. Section 4. Item 4. The process of item 3, wherein the cyanide is HCN. Section 5. Item 4. The process according to item 3, wherein the cyanide compound is an inorganic cyanide salt, in particular a salt selected from the group consisting of sodium cyanide, potassium cyanide, calcium cyanide, and combinations thereof. Section 6. Item 6. The process of item 5, wherein the reaction is carried out in the presence of an acid. Section 7. Item 6. The process according to item 5, wherein the reaction is carried out under conditions such as in the presence of a base to react the nitrile group to form a carboxylate. Section 8. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subjected to a further reaction step, which is a hydrogenation step in the presence of hydrogen and a catalyst, in which the nitrile group is at least partially converted to an amine group. Section 9. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subjected to a further reaction step, which is a saponification step to a carboxylate group in the presence of an aqueous base. Section 10. 7. The process according to any one of paragraphs 1 to 6, wherein the product containing at least one acetonitrile group is subjected to a further reaction step of reaction with a Grignard reagent to form an imine salt, which is then hydrolyzed to obtain a ketone. Section 11. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subsequently subjected to a further reaction step, which is a hydrolysis step in the presence of an acid catalyst, to form the corresponding amide. Section 12. Item 11. The process of any one of the preceding paragraphs, wherein the alkyleneamine compound containing three or more amine units, at least two amine units being protected by cyclic urea units and at least one amine unit being unprotected, is selected from the group of U-DETA, U1-TETA, UP-TETA, U2-TETA, DU1,3-TEPA, DU1,4-TEPA, U1P3-TEPA, and U1P4-TEPA. Section 13. The process according to any one of the preceding clauses, wherein the cyclic urea unit is removed from the nitrile compound obtained by the process according to any one of clauses 1 to 6 or, optionally, if the nitrile compound is subjected to a further reaction step, during or after said further reaction step, which may be a reaction step according to any one of clauses 7 to 11. Section 14. Item 13. The process of item 12, wherein the step of removing the cyclic urea units comprises one or more of reaction with water in a liquid phase, reaction with an alkylene amine capable of removing a carbonyl moiety, and reaction with a strong base.

[0122] The present invention is illustrated by the following examples, but is not limited thereto or by them. EXAMPLES

[0123] Example 1 Chain extension of U-DETA to U-DETA monoacetonitrile followed by saponification and removal of the cyclic urea group Example 1A: Synthesis of monocyanomethyl-U-DETA by reaction of U-DETA with glycolonitrile A solution of U-DETA (68.5 g, 0.5 mol) in water (109 g) and a 58.8% glycolonitrile solution (47.6 g, 0.5 mol) were simultaneously charged to a 1 L reactor containing water (101 g) at 20° C. Glycolonitrile was dosed slightly faster. The dosing temperature was 18° C. The dosing time was 35 min. The reaction mixture was maintained at room temperature for 18 h. NMR analysis showed complete conversion to the product. [ka]

[0124] Example 1B: Synthesis of monocarboxymethyl-U-DETA by saponification of monocyanomethyl-U-DETA The solution monocyanomethyl-U-DETA (304 g) prepared in the 1 L reactor described above was added to a mixture of 50% NaOH (44.7 g) and water (128 g) in a stainless steel reactor at 20° C. After stirring for 1 h, the reactor temperature was gradually increased to boiling point (104° C.) and maintained at this temperature for 3 h to allow the ammonia-water mixture to distill off. NMR analysis showed complete hydrolysis to the product. [ka]

[0125] Example 1C: Synthesis of 1-(carboxymethyl)-diethylenetriamine by removal of the cyclic urea group from monocarboxymethyl-U-DETA Hydrolysis experiments were carried out using a 50 ml Parr bomb. A 50% NaOH solution was added to the reaction mixture containing monocarboxymethyl-U-DETA sodium salt obtained as described in Example 1B above. NMR analysis showed incomplete conversion at about 2 equivalents of NaOH at 180° C. for 20 hours. Addition of an additional equivalent of NaOH resulted in complete hydrolysis at 180° C. for 18 hours. [ka]

[0126] Example 2 Chain extension of U-DETA to U-DETA diacetonitrile followed by saponification Example 2A: Synthesis of dicyanomethyl-U-DETA by reaction of U-DETA with formaldehyde and HCN Concentrated sulfuric acid (3 g) was added to a solution of U-DETA (68.5 g, 94.5% purity, 0.5 moles) in water (293 g) in a 1 liter double-walled reactor equipped with a heating / cooling bath and stirrer to lower the pH from 11.7 to 9.5. 44.2% formaldehyde solution (34 g, 0.5 moles) was added to the resulting solution, which resulted in a further reduction in pH to 5.5. This was followed by the simultaneous addition of 44.2% formaldehyde solution (36 g, 0.5 moles) and hydrogen cyanide (27 g, 1 moles) over a period of 90 minutes. A precipitate formed in about 75 minutes and water (100 g) was added to improve stirrability. After stirring for 1 hour, the product was discharged from the reactor, but a substantial amount of water rinsing was required. The product was filtered off and dried. [ka]

[0127] Example 2B: Synthesis of dicarboxymethyl-UDETA by saponification of dicyanomethyl-U-DETA Dry dicyanomethyl-U-DETA (70.4 g) prepared as described above was added to a stirred mixture of water (400 g) and 50% NaOH (57 g, 0.6 moles) at 35° C. The mixture was stirred overnight at 35° C. to obtain a clear solution. The temperature of the reactor was gradually increased to 105° C. and maintained at this temperature for 2 hours to distill off the ammonia-water mixture. Water was added to maintain the temperature at 105° C. A yellow solution (260 g) containing 31.6% (NMR analysis) of the disodium salt of dicarboxymethyl-U-DETA was obtained, which corresponds to a yield of 57% based on the starting UDETA. [ka]

[0128] Example 3: Chain extension of U-DETA to U-DETA diacetate by reaction of U-DETA with formaldehyde and alkali metal cyanide Example 3A: Synthesis of dicarboxymethyl-U-DETA via reaction of U-DETA with formaldehyde and alkali metal cyanide A 30% solution of sodium cyanide was dosed at 98° C. into a 1 L stainless steel reactor containing water (250 g), U-DETA (90.3 g, 94%, 0.7 mol), and 50% NaOH (17 g, 0.2 mol). Two minutes after the start of NaCN dosing, the simultaneous dosing of 44% formaldehyde solution was started. The dosing rate of NaCN solution was 3.18 g / min for the first 33 minutes, 1.25 g / min for the next 49 minutes, and 1.01 g / min for the remaining time. The total amount of NaCN solution dosed was 230 g. The dosing rates of formaldehyde solution were 1.31, 0.51, and 0.42 g / min, respectively. The total amount of formaldehyde solution dosed was 97 g. Dosing of formaldehyde was stopped when the amount of free cyanide was below 100 ppm. The reaction mixture was boiled for an additional hour while removing the ammonia-water mixture and adding water so that the temperature did not rise above 104° C. After cooling, 576.5 g of reaction solution was discharged from the reactor containing 30.3% (NMR analysis) of dicarboxymethyl-U-DETA disodium salt, corresponding to a yield of 86% based on U-DETA. [ka]

[0129] Example 3B Removal of the urea group to form 1,1-bis(carboxymethyl)-diethylenetriamine A 50% NaOH solution (3.5 equiv.) was added to the reaction mixture resulting from the Singer process containing dicarboxymethyl-U-DETA sodium salt, and the mixture was heated at 180° C. for 40 h. High conversion to product was obtained according to NMR analysis. [ka]

Claims

1. 1. A process for producing nitrile compounds via chain extension of an alkyleneamine compound containing three or more amine units which are primary or secondary amine groups, at least two of which are protected by cyclic urea units and at least one amine unit is unprotected, comprising: The cyclic urea unit has the structure of Formula I, 【Chemistry 1】 In formula I, A is selected from the group of C2-C4 alkylene units optionally substituted by one or more C1-C3 alkyl groups; wherein said chain extension is by reacting said at least one unprotected amine unit with glycolonitrile or with a combination of formaldehyde and a cyanide selected from HCN and an inorganic cyanide salt to add at least one acetonitrile group to said at least one unprotected amine unit.

2. 2. The process of claim 1, wherein the at least one unprotected amine unit is reacted with glycolonitrile.

3. 2. The process of claim 1, wherein the at least one unprotected amine unit is reacted with a combination of formaldehyde and a cyanide selected from HCN and an inorganic cyanide salt.

4. 4. The process of claim 3, wherein the cyanide is HCN.

5. 4. The process of claim 3, wherein the cyanide compound is an inorganic cyanide salt.

6. The process of claim 5 , wherein the reaction is carried out in the presence of an acid.

7. 6. The process of claim 5, wherein the reaction is carried out under conditions to react the nitrile group to form a carboxylate.

8. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subjected to a further reaction step, which is a hydrogenation step in the presence of hydrogen and a catalyst, in which the nitrile group is at least partially converted to an amine group.

9. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subjected to a further reaction step which is a saponification step to a carboxylate group in the presence of an aqueous base.

10. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subjected to a further reaction step of reaction with a Grignard reagent to form an imine salt which is then hydrolyzed to give a ketone.

11. 7. The process according to any one of claims 1 to 6, wherein the product containing at least one acetonitrile group is subsequently subjected to a further reaction step, which is a hydrolysis step in the presence of an acid catalyst to form the corresponding amide.

12. 12. The process of any one of claims 1 to 11, wherein the alkyleneamine compound containing three or more amine units, at least two amine units being protected by cyclic urea units and at least one amine unit being unprotected, is selected from the group of U-DETA, U1-TETA, UP-TETA, U2-TETA, DU1,3-TEPA, DU1,4-TEPA, U1P3-TEPA, and U1P4-TEPA. 【Chemistry 2】

13. The process according to any one of claims 1 to 12, wherein the cyclic urea units are removed from the nitrile compound obtained by the process according to any one of claims 1 to 6 or, optionally, if the nitrile compound is subjected to a further reaction step, during or after said further reaction step, which may be a reaction step according to any one of claims 7 to 11.

14. 13. The process of claim 12, wherein the step of removing the cyclic urea units comprises one or more of reaction with water in a liquid phase, reaction with an alkylene amine capable of removing a carbonyl moiety, and reaction with a strong base.

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