Production of Nitrile Compounds

Abstract

The present invention relates to a process for producing a nitrile compound by chain extension of an alkyleneamine compound containing three or more amine units, wherein at least two amine units are protected by cyclic urea units and at least one amine unit is unprotected, by reacting the at least one unprotected amine unit with glycolonitrile or with 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 invention allows the production of nitrile compounds with high selectivity and high yield. The nitrile compounds can be processed as required.

Description

[0001] The present invention relates to a method for producing a nitrile compound by selective chain elongation of an alkyleneamine compound having three or more amine units.

[0002] Production of nitrile compounds by chain elongation of alkyleneamine compounds is known in the art. For example, it can be carried out by reacting an alkyleneamine with glycolonitrile or with a combination of hydrogen cyanide and formaldehyde to form a chain - elongated nitrile compound. After hydrogenating the nitrile compound, an amine compound will be formed. For example, such a method is disclosed in US2010 / 0121064 for the reaction of EDA with glycolonitrile (referred to as FACH in this prior art document). However, as pointed out in this document, this method produces undesired secondary components.

[0003] The amount of secondary components increases with the amount of amine moieties present in the amine molecule. Thus, when the starting material is a larger molecule containing more amine units than the starting material disclosed in US2010 / 0121064, the amount of secondary components will be even greater.

[0004] It has now been found that the primary and secondary amine groups in an alkyleneamine compound having three or more amine units can be protected with cyclic urea units and the alkyleneamine on the amine group that is not part of such cyclic urea units can be selectively reacted with glycolonitrile or with a combination of formaldehyde and a cyanide selected from HCN and inorganic cyanide salts. This will reduce the formation of by - products.

[0005] Accordingly, the present invention provides a method for producing a nitrile compound by chain elongation of an alkyleneamine compound having three or more amine units, wherein at least two amine units are protected with cyclic urea units and at least one amine unit is unprotected, by reacting the at least one unprotected amine unit with glycolonitrile or with 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.

[0006] It should be noted that chain - elongated alkyleneamines in which a portion of the amine is protected by cyclic urea groups are not unknown. For example, such methods are disclosed in US2015 / 0065679, EP078169, US5,399,706, US2,785,176, GB972,003. The methods in these documents are either based on Michael addition reactions of amine compounds with materials having active double bonds such as acrylonitrile or butenenitrile, or on reactions with epoxides or chlorides such as 2 - chloroethylamine.

[0007] In addition to the reaction with 2-chloroethylamine to form salts, the Michael addition reaction produces molecules in which no ethyleneamine chain extension occurs. More specifically, the result of the reaction is the incorporation of a propylene or larger alkylene chain, or a compound capped with alkyl units is obtained. The reaction with epoxides will also introduce additional hydroxyl groups.

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

[0009] An additional advantage of the process of the present invention is that due to the presence of the cyclic urea unit, the amine units cannot react with each other, and in many embodiments, cyclization or polymerization reactions that may occur during the hydrogenation of acetonitrile-capped compounds, such as during the hydrogenation of ethylenediaminoacetonitrile, can be prevented. In addition, due to the presence of the urea group, there are fewer amino groups. Therefore, there will be fewer side reactions of the nitrile group reacting with another amino group, resulting in fewer by-products and thus higher selectivity.

[0010] Since the process of the present invention allows the production of nitrile compounds in a more selective manner, it is possible to employ more stringent reaction conditions, which results in higher conversion rates and allows the production of the desired nitrile compounds in high yields.

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

[0012] Therefore, the process of the present invention provides many options for the preparation of selectively chain-extended alkyleneamines. As a result of the selective reaction, less effort is required to separate the reaction mixture, thereby reducing both processing and equipment costs.

[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. This compound can be further processed as needed, which will be discussed below.

[0014] The process according to the present invention will be discussed in more detail below.

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

[0016] The so-called two amine units protected by cyclic urea units refer to units of formula I.

[0017] Formula I

[0018]

[0019] wherein A is selected from C2 - C4 alkylene units, optionally substituted by one or more C1 - C3 alkyl groups. In the cyclic alkyleneurea group, preferably A is a C2 - C3 alkylene unit, optionally substituted by one or two C1 alkyl groups. A is preferably selected from ethylene, propylene, and isopropylidene, especially ethylene. In the case where there is more than one A in the molecule, each A can be independently selected.

[0020] In one embodiment, the starting compound is an alkyleneurea compound that contains at least one primary or secondary amine group and at least one cyclic alkyleneurea group of Formula I. Preferably, the (unprotected) amine group is a primary amine group or a cyclic secondary amine group. Particularly preferably, the amine group is a primary amine group.

[0021] The alkyleneamine compound used as a starting material in the present invention contains at least one cyclic urea unit of Formula I. Generally, the alkyleneamine compound will contain up to 10 cyclic urea units of Formula I. In practice, the alkyleneamine compound usually contains up to 5 cyclic urea units of Formula I. The alkyleneamine compound contains at least one unprotected amine unit. Generally, the alkyleneamine compound will contain up to 5 unprotected amine units. In practice, the alkyleneamine compound usually contains up to three, especially one or two, particularly one unprotected amine unit.

[0022] The alkylene unit in the alkylamine compound usually has 1 to 10, especially 1 to 8 carbon atoms. In one embodiment, the alkylene unit meets the above requirements for A.

[0023] In one embodiment, in addition to the amine unit and the alkylene unit, the alkyleneamine compound does not include other moieties.

[0024] In another embodiment, in addition to the amine unit and the alkylene unit, the alkyleneamine compound does indeed include other moieties. Such moieties can be selected, for example, from C1 - C6 alkyl groups, optionally substituted by -OH, -COOH, and / or COO - alkyl, and ether moieties (-O-).

[0025] The molecular weight of the alkylamine compound is usually in the range of 115 to 10,000 g / mol, especially 115 to 1000 g / mol, and in some embodiments in the range of 115 - 500 g / mol.

[0026] In one embodiment, the alkyleneurea compound is a compound of Formula II:

[0027] Formula II: R2 - [-X-A-] q -N(A)(CO)N-[A-X-] p -A-NH 2

[0028] wherein

[0029] R2 is selected from H and C1-C6 alkyl, said C1-C6 alkyl being optionally substituted by one or more groups selected from -OH, -NH 2 and -COOR4, especially zero, one or two groups selected from -OH, -NH 2 and COOR4, especially zero, one or two groups selected from -OH and -NH 2 groups, where R4 is H or C1-C6 alkyl;

[0030] X is independently selected, each time it appears, from -O-, -NR2-, groups of formula I and groups of formula III:

[0031]

[0032] A has the meaning discussed above, where when there is more than one A in the molecule, each A can be independently selected,

[0033] p is an integer in the range from 0 to 8, and

[0034] q is an integer in the range from 0 to 8.

[0035] For the avoidance of doubt, the structure -N(A)(CO)N- in formula II corresponds to formula I.

[0036] The preferred options given above for A also apply here. Particularly preferred is that A is ethylene.

[0037] Preferably, X is selected from -NH-, groups of formula III and groups of formula I. When it is desired to produce linear alkylamines, preferably X is selected from NH and groups of formula I.

[0038] Preferably, R2 is selected from H, ethyl, propyl and isopropyl, especially ethyl, optionally substituted by one or two groups selected from -OH and -NH 2 groups. Particularly preferred is that R2 is ethyl or propyl, especially ethyl, substituted by -NH 2 at the second carbon atom counted from the connection point with X (aminoethyl or aminopropyl), or in the case of propyl substituted by -NH 2 at the third carbon atom.

[0039] Since the reaction of macromolecules to form even larger molecules is not always the goal, it may be more preferred that the sum of p and q is at most 8, in some embodiments at most 4, or at most 2.

[0040] Examples of preferred compounds of formula II are the urea adduct of diethylenetriamine (U-DETA), the mono-urea adduct of triethylenetetramine, where the urea group can be at the terminal ethylene moiety or at the central ethylene moiety (U1-TETA and U2-TETA), and the mono-urea and di-urea adducts of tetraethylenepentamine having primary amine groups (U1-TEPA, DU1,3-TEPA). These compounds are particularly attractive if it is desired to produce nitrile compounds of linear polyethylenamines and their respective urea products.

[0041] Examples of other compounds that can be used in one embodiment of the process according to the invention are compounds consisting of an ethylenamine chain having urea groups provided on the nitrogen atoms on each side of a terminal ethylene moiety and an ethylene chain provided on the nitrogen atoms on each side of another ethylene moiety, for example, U1P3-TEPA and U1P4-TEPA.

[0042] Generally, in this specification, compounds are named as follows.

[0043] The letter code refers to the longest linear ethylenamine chain.

[0044] U refers to the presence of a cyclic urea group, which results from the presence of urea groups on two adjacent nitrogen atoms connected by an ethylene moiety, i.e., a group of formula I (where A is ethylene).

[0045] P refers to the presence of a piperazine moiety, which results from the presence of ethylene moieties on two adjacent nitrogen atoms connected by an ethylene moiety, i.e., a group of formula III (where both As are ethylene).

[0046] The number after the U or P prefix refers to the corresponding nitrogen atom in the chain to distinguish different possible structures.

[0047] The letter before the U or P prefix represents the number of groups, D represents two or two groups, and T represents 3 and 4, or three and four groups, respectively. When using T, it will be clear from the context whether 3 or 4 is meant.

[0048] In another embodiment, the alkylene urea compound is a compound of formula IV

[0049] Formula IV: R2-[-X-A-] q -N(A)(CO)N-[A-X-] p -A-N(A)(A)N-[-A-X-] r -R3

[0050] wherein R2, X, A, q and p have the meanings given above. The preferred options given above also apply here.

[0051] R3 is selected from H and C1-C6 alkyl, and the C1-C6 alkyl is optionally substituted by one or more groups selected from -OH and -NH 2 groups, especially substituted by zero, one or two groups selected from -OH and -NH 2 groups. Preferably, R3 is selected from H, ethyl, propyl and isopropyl, especially ethyl, optionally substituted by one or two groups selected from -OH and -NH 2 groups. Particularly preferably, R3 is ethyl or propyl, especially ethyl, substituted by -NH at the second carbon atom counted from the connection point with X (aminoethyl or aminopropyl) or at the third carbon atom in the case of propyl 2 substituted.

[0052] In formula IV, r is an integer between 0 and 8, especially an integer between 0 and 4, more especially 0, 1 or 2. Since the reaction of large molecules to form even larger molecules is not always the goal, the sum of p, q and r can preferably be at most 8, in some embodiments at most 4, or at most 2.

[0053] 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.

[0054] Examples of preferred compounds of formula IV include the urea adduct of piperazinyl ethyl ethane-1,2-diamine (UP-TETA). U1P3-TEPA and U1P4-TEPA are also preferred.

[0055] Mixtures of alkyleneurea compounds can also be used.

[0056] In a preferred embodiment, the alkyleneamine having 3 or more amine units in which at least 2 amine units are protected by cyclic urea units and at least 1 amine unit is unprotected as the starting compound in the method of the present invention is selected from U-DETA, U1-TETA, UP-TETA, U2-TETA, DU1,3-TEPA, DU1,4-TEPA, U1P3-TEPA and U1P4-TEPA.

[0057] The starting compound as described above is reacted with glycolonitrile or with formaldehyde and a cyanide selected from HCN and inorganic cyanide salts. These reactions will be discussed below.

[0058] In one embodiment, the starting compound as described above reacts with glycolonitrile. Glycolonitrile is also known as hydroxyacetonitrile or formaldehyde cyanohydrin. The following is an example of this reaction, where U-DETA is used as the starting material. Water is also formed in the reaction (not shown).

[0059]

[0060] The reaction between the starting compound and glycolonitrile is typically carried out at a temperature between 0 - 100 °C, particularly between 0 and 50 °C, more particularly between 0 and 35 °C. The reaction is usually carried out at a pressure of 0.5 - 10 bar. Since elevated pressure is not required, it may be attractive to carry out the reaction at a pressure of 0.5 - 5 bar, particularly 0.5 - 3 bar. Atmospheric pressure is considered to be preferred. When referring to pressure in bar in this specification, it means bar (absolute pressure).

[0061] The reaction can be carried out in a solvent. Water would be a suitable solvent, but other solvents can also be considered in which the reactants are soluble under the reaction conditions but do not react substantially under the reaction conditions. Other suitable solvents include organic solvents such as amides like N-methylpyrrolidone (NMP) and dimethylformamide (DMF), aromatic and aliphatic hydrocarbons such as benzene and xylene, alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, sec-butanol and tert-butanol, amines such as ethylamine, alkylamines, ammonia, esters such as methyl acetate or ethyl acetate, and ethers such as diisopropyl ether, diisobutyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, dioxane and tetrahydrofuran (THF). The use of ethers is preferably considered, particularly cyclic ethers, more particularly tetrahydrofuran. Alternatively, alcohols, particularly methanol, may be preferred as organic solvents. The use of amines and ammonia, although possible, may be less attractive as they may participate in the reaction.

[0062] It will be apparent to those skilled in the art that the reaction can be carried out by batch or continuous methods. Suitable reactors and process configurations are known in the art and need not be elucidated here.

[0063] The molar ratio between the starting compound and glycolonitrile will depend on the desired chain extension and the number of reactive amine groups in the starting compound. Generally, the molar ratio of glycolonitrile to reactive amine groups in the starting material ranges from 0.25:1 to 4:1. Since in principle an excess of glycolonitrile is not required, it is preferred that the molar ratio of glycolonitrile to reactive amine groups in the starting material is at most 3:1, particularly at most 2:1, more particularly at most 1.5:1.

[0064] When the starting compound contains a reactive amino group, it is generally desirable to completely convert the reactive amino group into a monocyanomethylated product. Thus, in such cases, the molar ratio of glycolonitrile to the reactive amino group (which is the same as the starting compound in this case) is preferably at least 0.5:1, particularly at least 0.75:1, more particularly at least 0.9:1, especially at least 1:1.

[0065] When the starting compound contains more than one reactive amino group, the molar ratio of glycolonitrile to the primary amino group in the reaction mixture will depend on the desired degree of chain extension and thus on the desired degree of conversion. When it is desired that all amino groups react to obtain complete conversion, the molar ratio values of glycolonitrile to the reactive amino group given above are applicable. When it is desired to convert only some of the amino groups, lower ratios will be applicable. In such cases, the molar ratio of glycolonitrile to the reactive amino group may preferably be in the range of 0.25:1 to 1:1, particularly 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.

[0066] For example, U2-TETA can react with one or two glycolonitrile molecules to form mono- or dicyanomethylated U2-TETA or mixtures thereof. Lower ratios of glycolonitrile to amino groups will result in the formation of more mono-cyanomethylated U2-TETA, while higher ratios of glycolonitrile to the primary amino group will result in the formation of more dicyanomethylated U2-TETA.

[0067] As is known to the person skilled in the art, there is often a trade-off between the conversion of the starting materials and the selectivity to the desired product, where an increase in the conversion of the starting materials may be accompanied by an increase in the formation of by-products, leading to a decrease in the selectivity to the desired product. Taking this into account, the reaction conditions (reaction time, reaction temperature...) and the ratios between the reactants are selected within the capabilities of the person skilled in the art so as to obtain a balance between the desired conversion and the selectivity to the desired product.

[0068] In another embodiment, the starting compound as described above is reacted with a combination of formaldehyde and a cyanide selected from HCN and inorganic cyanide salts. The following are examples of such reactions, where U-DETA is used as the starting material.

[0069]

[0070] 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, particularly in the range of 0°C to 60°C, and a pressure of 0.5 - 10 bar. Since elevated pressures are not required, it may be attractive to carry out the reaction at a pressure of 0.5 - 5 bar, particularly 0.5 - 3 bar. Atmospheric pressure may be preferred.

[0071] The reaction can be carried out in a solvent. Water would be a suitable solvent, but other solvents in which the reactants are soluble under the reaction conditions can also be considered. The above-mentioned solvents used for the reaction with glycolonitrile can also be used here.

[0072] It is clear to those skilled in the art that the reaction can be carried out batchwise or continuously. Suitable reactors and process configurations are known in the art and need not be described in detail here.

[0073] The reaction is preferably carried out at a pH in the range of 1 to 9, more particularly 2 to 7. If necessary, a pH regulator can be added.

[0074] For this process, among other features, the addition of formaldehyde and hydrocyanic acid can be used as a means to control the balance between selectivity and conversion.

[0075] 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 salts, potassium salts and lithium salts, preferably sodium salts and potassium salts, particularly preferably sodium salts. An example of a suitable alkaline earth metal salt is calcium cyanide. Generally, it is preferred that the cyanide is soluble in the reaction medium under the reaction conditions.

[0076] In the case of using a cyanide salt, the final product obtained will depend on the pH value of the reaction medium. If the reaction is carried out under acidic conditions, the final product will be a nitrile. In this case, the pH value is preferably maintained in the range of 1 to 7. If necessary, an acid, such as a strong inorganic acid, can be added to maintain the pH value within the desired range. If 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, particularly a strong inorganic base such as NaOH or KOH, can be added to promote the formation of the carboxyl group. In this case, the reaction is preferably carried out at a pH value of 10 - 14.

[0077] The reaction of the starting compounds with the combination of formaldehyde and an inorganic cyanide salt is preferably carried out at a temperature of 30 to 150 °C, particularly 50 to 130 °C.

[0078] In one embodiment, ammonia produced by the hydrolysis of the nitrile group is preferably distilled off from the reaction mixture while dosing the reagents. This allows for a higher product purity.

[0079] The reaction is generally carried out at a pressure of 0.5 - 10 bar (absolute pressure). Since elevated pressure is not required, it may be attractive to carry out the reaction at a pressure of 0.5 - 5 bar, particularly 0.5 - 3 bar. Atmospheric pressure may be preferred.

[0080] The reaction can be carried out in a solvent. Water would be a suitable solvent, but other solvents in which the reactants are soluble under the reaction conditions can also be considered. The above solvents used for the reaction with glycolonitrile can also be used here.

[0081] It is clear to those skilled in the art that the reaction can be carried out batchwise or continuously. Suitable reactors and process configurations are known in the art and need not be described in detail here.

[0082] Formaldehyde and cyanide can be provided to the reaction mixture simultaneously or sequentially in a single dose or a series of doses. They can be provided separately to the starting materials, or they can be combined before reacting with the starting materials. Combinations of various embodiments are also contemplated. The simultaneous addition of the various reagents is preferred.

[0083] The molar ratio between formaldehyde and cyanide will be in the range of 0.5:1 to 2:1, particularly 0.7:1 to 1.4:1, more particularly 0.9:1 to 1.1:1, for example equimolar.

[0084] The required ratio between the starting compound and cyanide will depend on the desired chain extension, the number of reactive amino groups in the starting compound, and whether the reactive amino group is primary or secondary. Generally, for complete conversion, one molecule of cyanide is required for each NH-bond to be reacted. Thus, generally, the molar ratio of cyanide to the reactive NH-bonds of the reactive amine in the starting material is in the range of 0.25:1 to 4:1. Since in principle an excess of cyanide is not required, 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, specifically at most 1.2:1. Since partial conversion is generally not attractive, the molar ratio of cyanide to the reactive NH-bonds of the reactive amine in the starting material is preferably at least 0.5:1, more preferably at least 0.8:1, more particularly at least 1:1.

[0085] The method according to the invention forms acetonitrile-substituted alkyleneamine compounds. Examples of starting materials and the nitrile products obtainable therefrom are listed in the table below.

[0086]

[0087]

[0088]

[0089] Other combinations of starting materials and the nitrile products obtained therefrom are listed in the table below.

[0090]

[0091]

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100]

[0101]

[0102]

[0103]

[0104] In one embodiment, in the next step, the acetonitrile groups produced by the method of the present invention continue to react. For example, in one embodiment, the nitrile unit is hydrogenated to provide an amino group. For example, in another embodiment, the nitrile unit is hydrolyzed to obtain a terminal amide (under neutral or weakly acidic conditions) or a carboxylic acid group (under basic conditions). For example, in a further embodiment, the nitrile group reacts with a Grignard reagent to form an imine salt, which can then be hydrolyzed to produce a ketone.

[0105] If desired, the cyclic urea protecting group can be removed from the product obtained from the method according to the present invention. In one embodiment, this can be accomplished by reaction under basic conditions. In this case, if the acetonitrile groups have not been converted to another group in the product formed, they will also be saponified to carboxylic acid groups under basic conditions. Thus, the removal of the cyclic urea unit and the saponification of the acetonitrile groups to carboxymethyl groups can be carried out simultaneously. However, in some embodiments, if it is desired to react the nitrile groups with another chemical to convert them to amine units, it may be preferable to first carry out such a reaction before removing the cyclic urea unit. This will be discussed in more detail below.

[0106] The following reaction scheme illustrates possible further reactions, where a product derived from U-DETA is used as the starting compound.

[0107] Catalytic hydrogenation of acetonitrile groups

[0108]

[0109] Saponification of the acetonitrile group

[0110]

[0111] Removal of the cyclic urea unit from the hydrogenation product

[0112]

[0113]

[0114] In one embodiment, the nitrile product of the process according to the invention undergoes a catalytic hydrogenation step, in which the nitrile compound reacts with hydrogen to convert the nitrile into the corresponding amine.

[0115] The catalytic hydrogenation of the acetonitrile product of the invention is preferably carried out using a hydrogenation catalyst such as Raney - cobalt or Raney - nickel, a supported catalyst containing Group 8 elements 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 can be supported on an inorganic oxide support (such as based on alumina, silica, titania, zirconia or a combination thereof), or on a porous carbon support.

[0116] The reaction can be carried out at a temperature of 40 to 150 °C, preferably 70 to 140 °C, especially 80 to 140 °C and a pressure of 5 to 300 bar, preferably 30 to 250 bar, especially 40 to 160 bar. The catalytic hydrogenation of the acetonitrile product is known in the art and does not need to be further elaborated here.

[0117] The hydrogenation process results in the formation of an alkylenediamine compound which has acquired an additional ethylenediamine group compared to the starting compound of the process according to the invention. Thus, an extended alkylenediamine compound can be obtained by the process according to the invention.

[0118] The following table shows examples of starting materials, nitriles and resulting amine products:

[0119]

[0120]

[0121] In another embodiment, the nitrile product of the process according to the invention undergoes a saponification step, in which the nitrile compound reacts with a base to form a carboxylate. If an inorganic cyanide salt is used as described above to form the nitrile, this reaction can be carried out after the formation of the nitrile, but can also be carried out simultaneously with the formation of the nitrile.

[0122] If the saponification of the acetonitrile product is carried out as a separate step, it is preferably accomplished by adding an aqueous solution of a base such as sodium hydroxide or potassium hydroxide. In a further preferred embodiment, the amount of base used is 0.7 to 1.5 molar equivalents per acetonitrile group. It is preferred to use KOH or NaOH as the base, and the same applies to the use of an aqueous medium. The saponification process is known in the art and does not need to be further detailed here.

[0123] The product from the saponification step is a salt of a carboxylic acid.

[0124] The following table lists some preferred starting material-nitrile intermediate-saponification product combinations:

[0125]

[0126] In one embodiment, the nitrile group reacts with a Grignard reagent to form an imine salt, which can then be hydrolyzed to produce a ketone.

[0127] A Grignard reagent is a compound of the formula R-Mg-X, where X is a halogen and R is an organic group, typically an alkyl or aryl group. X is usually selected from Cl, Br, and I. Examples of suitable R groups include C1-C10 alkyls and C5-C10 aryls, alkylaryls, and arylalkyls. R is, for example, selected from methyl, ethyl, propyl, and phenyl. Examples include methylmagnesium chloride and phenylmagnesium bromide. The reaction with the Grignard reagent results in the formation of an imine compound. By reaction with water, preferably under acidic conditions, the imine can be converted to a ketone. It is important to add water only after the formation of the imine, as the presence of water will cause the destruction of the Grignard reagent.

[0128] The reaction of a nitrile group with a Grignard reagent to form an imine, followed by hydrolysis to form a ketone, is known in the art and does not need to be further detailed here.

[0129] In a further embodiment, the aminonitrile compound obtained by the method of the present invention undergoes a hydrolysis step to produce the corresponding amide. The reaction can be carried out in a solvent, particularly a protic solvent, preferably in water, using an acidic catalyst. Suitable catalysts include conventional acidic catalysts such as inorganic acids, for example 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.

[0130] The hydrolysis of an aminonitrile compound to form the corresponding amide compound is known in the art and does not need to be further detailed here.

[0131] The following table lists many preferred combinations of starting materials, corresponding nitrile intermediates, and amide products:

[0132]

[0133]

[0134] 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 for the nitrile product or for the product from the further reactions described above. Selecting a suitable reaction sequence is within the scope of those skilled in the art, taking into account the reactivity of the end groups and the reaction conditions prevailing in the urea removal step.

[0135] In this specification, a compound containing a cyclic urea protecting group may also be denoted as a U-compound or a U-alkyleneamine compound to reflect that removal of the cyclic urea protecting group results in the release of the two amine groups that were previously protected by being incorporated in the cyclic urea group. This process may also be denoted as a CO 2 elimination step. It can be carried out in different ways.

[0136] In one embodiment, the U-alkyleneamine compound reacts with water in the liquid phase in the presence of removal of CO 2 to form the corresponding alkyleneamine compound. The reaction with water typically occurs at a temperature of at least 150 °C. If the reaction temperature is lower than 150 °C, the U-compound will not react to a significant extent. Preferably the reaction is 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.

[0137] The pressure during the process is not critical as long as the reaction medium is in the liquid phase. As a general range, values of 0.5 to 100 bar can be mentioned, depending on the desired temperature. The CO 2 removal step is preferably carried out at a pressure of at least 5 bar, particularly at least 10 bar, to maintain a sufficient amount of amine and water in the medium. Given the high costs associated with high-pressure equipment, the pressure may preferably be at most 50 bar, particularly at most 40 bar.

[0138] The amount of water depends on the desired degree of conversion and the process conditions. Generally, the amount of water is at least 0.1 mole of water per mole of the urea moiety in the feed. Higher amounts are usually used, such as at least 0.1 mole of water per mole of the urea moiety, particularly at least 0.5 mole of water per mole of the urea moiety. The maximum value is not critical for the process according to the invention, but an excessive amount of water will result in the need for unnecessarily large equipment. As a general maximum, amounts of up to 500 moles of water per mole of the cyclic ethyleneurea moiety, particularly up to 300 moles, more particularly up to 200 moles, and in some embodiments up to 100 moles, or up to 50 moles can be mentioned.

[0139] Preferably, CO is removed during the reaction 2 , for example, by venting the reaction vessel and preferably by providing a stripping gas such as nitrogen or steam.

[0140] In one embodiment, the U-alkyleneamine compound reacts with water in the liquid phase at a temperature of at least 230 °C in an amount of 0.1 - 20 moles of water per mole of urea moiety while removing CO 2 . It has been found that the use of a small amount of water in combination with a relatively high temperature and CO 2 removal results in an effective method with good conversion and little by-product formation. In one embodiment, the U-alkyleneamine compound reacts with an alkyleneamine capable of seizing a carbonyl moiety, resulting in the conversion of the U-alkyleneamine compound to its corresponding alkyleneamine compound and simultaneously converting the alkyleneamine capable of seizing a carbonyl moiety to a U-alkyleneamine. This process can be described as a carbonyl transfer reaction.

[0141] In a further embodiment, the U-alkyleneamine compound is reacted with a strong base (i.e., a base with a pKb less than 1) to form the corresponding alkyleneamine compound and a 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 metal hydroxides, particularly hydroxides of alkali metals and alkaline earth metals, particularly sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, magnesium hydroxide, and barium hydroxide. In one embodiment, the strong inorganic base is selected from metal oxides, particularly oxides of alkali metals and alkaline earth metals, particularly calcium oxide, magnesium oxide, and barium oxide. It may be preferred to select the strong inorganic base from sodium hydroxide, potassium hydroxide, (hydro)magnesium hydroxide, and (hydro)calcium hydroxide. The use of sodium hydroxide and potassium hydroxide is considered to be particularly preferred. Other strong inorganic bases such as ammonium hydroxide may also be used. It will be apparent to those skilled in the art that mixtures of various inorganic bases may be used. Blends containing a base in addition to other components may also be used, and these blends may be blends that are converted to an inorganic base in the reaction medium. The molar amount of the base can be calculated relative to the molar amount of the alkyleneurea moiety to be converted. A value of at least 0.2:1 may be mentioned. If it is desired to completely convert the alkyleneurea moiety to the corresponding alkyleneamine compound, a larger amount may be preferably used, for example, at a molar ratio of at least 1:1, particularly at least 1.5:1. A larger amount may be preferably used to increase the reaction rate, for example, at a molar ratio of at least 2:1, particularly at least 2.5:1. Since a large amount of the base does not promote further conversion but results in additional costs, the molar ratio of the base to the molar amount of the alkyleneurea is preferably at most 20:1, particularly at most 15:1, more particularly at most 10:1. It has been found that even smaller amounts of the inorganic base may be sufficient. More particularly, it has been found that good results can be obtained when the molar ratio of the base to the alkyleneurea moiety is at most 7.5:1, particularly at most 6.5:1, even more particularly at most 5.5:1. It has been found that using a molar ratio of at most 5.5:1 results in complete conversion of the alkyleneurea moiety and a high yield of the resulting alkyleneamine compound. Preferably, even less base may be used per mole of the alkyleneurea moiety, for example, at a molar ratio of at most 5:1, particularly at most 4:1, more particularly at most 3:1.

[0142] The base treatment 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, a base in solid form may also be added and dissolved in the reaction medium. It will be clear to those skilled in the art that the aim is to have the base in a dissolved state so that the hydroxyl groups can react with the CO 2 adduct, while avoiding unnecessary dilution of the reaction medium.

[0143] The reaction can be carried out at a temperature between room temperature and 400 °C. The temperature and pressure should be selected such that the reaction mixture is in the liquid phase. Higher temperatures are advantageous as they result in reduced reaction times. The reaction may preferably be carried out at a temperature of at least 100 °C, particularly at least 140 °C, particularly at least 170 °C. On the other hand, higher temperatures may lead to the formation of unwanted by-products. Therefore, the reaction may preferably be carried out at a temperature of at most 350 °C, particularly at most 290 °C.

[0144] Depending on the reaction temperature, the reaction time can vary within a wide range, for example between 15 minutes and 24 hours. The reaction time may preferably vary between 1 hour and 12 hours, particularly between 1 hour and 6 hours. When using a smaller amount of base, a longer reaction time may be required to achieve the desired degree of conversion.

[0145] After completion of the reaction, a reaction mixture containing the ethylenediamine compound and the carbonate of the inorganic base is obtained. The salt can be removed by methods known in the art, for example by filtration, where the salt is in solid form, or generally by phase separation.

[0146] Various combinations of CO 2 It is also possible to combine the elimination steps, for example treatment with water to simultaneously remove CO 2 , followed by treatment with a base, optionally in combination with steps to remove intermediate products.

[0147] It will be apparent to those skilled in the art that the various preferred embodiments described herein can be combined unless mutually exclusive.

[0148] The present invention is illustrated by the following examples, but is not limited thereto or thereby. Examples

[0149] Example 1 Extension of U-DETA to U-DETA monoacetonitrile, followed by saponification and removal of the cyclic urea group

[0150] Example 1A: Synthesis of monocyano-methyl-U-DETA by reaction of U-DETA with glycolonitrile

[0151] 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 added to a 1 L reactor containing water (101 g) at 20 °C. The glycolonitrile was added slightly faster. The addition temperature was 18 °C. The addition time was 35 minutes. The reaction mixture was kept at room temperature for 18 hours. NMR analysis showed complete conversion to the product.

[0152]

[0153] Example 1B: Synthesis of Mono-carboxymethyl-U-DETA by Saponification of Mono-cyanomethyl-U-DETA

[0154] The solution of mono-cyanomethyl-U-DETA (304 g) prepared in a 1 L reactor as 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 raised to the boiling point (104 °C) and maintained at this temperature for 3 h to distill off the ammonia-water mixture. According to NMR analysis, it was completely hydrolyzed to the product.

[0155]

[0156] Example 1C: Synthesis of 1-(Carboxymethyl)-diethylenetriamine by Removal of the Cyclic Urea Group from Mono-carboxymethyl-U-DETA

[0157] Hydrolysis experiments were carried out using a 50 ml Parr bomb. A 50% NaOH solution was added to the reaction mixture containing the sodium salt of mono-carboxymethyl-U-DETA obtained as described in Example 1B above. According to NMR analysis, incomplete conversion occurred within 20 h at 180 °C using 2 equivalents of NaOH. When an additional equivalent of NaOH was added, complete hydrolysis occurred within 18 h at 180 °C.

[0158]

[0159] Example 2 Chain-extension of U-DETA to U-DETA Diacetonitrile, Followed by Saponification

[0160] Example 2A: Synthesis of Dicyano-methyl-U-DETA by Reaction of U-DETA with Formaldehyde and HCN

[0161] Concentrated sulfuric acid (3 g) was added to a solution of U-DETA (68.5 g, purity 94.5%, 0.5 mol) in water (293 g) in a 1 L double-walled reactor equipped with a heating / cooling bath and a stirrer to lower the pH value from 11.7 to 9.5. A 44.2% formaldehyde solution (34 g, 0.5 mol) was added to the resulting solution, which caused the pH to further drop to 5.5. Then, a 44.2% formaldehyde solution (36 g, 0.5 mol) and hydrogen cyanide (27 g, 1 mol) were added simultaneously over 90 min. A precipitate formed within about 75 min, and water (100 g) was added to improve stirrability. After stirring for 1 h, the product was discharged from the reactor, which required a large amount of rinsing water. The product was filtered out and dried.

[0162]

[0163] Example 2B: Synthesis of Dicarboxymethyl-UDETA by Saponification of Dicyanomethyl-U-DETA

[0164] The dried dicyanomethyl-U-DETA (70.4 g) prepared as above was added to a stirred mixture of water (400 g) and 50% NaOH (57 g, 0.6 mol) at 35 °C. The mixture was stirred overnight at 35 °C to obtain a clear solution. The reactor temperature was gradually raised to 105 °C and maintained at this temperature for 2 hours while the ammonia-water mixture was distilled off. 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, corresponding to a 57% yield based on the starting UDETA.

[0165]

[0166] Example 3: Chain Extension of U-DETA to U-DETA Diacetate via the Reaction of U-DETA with Formaldehyde and Alkali Metal Cyanide

[0167] Example 3A: Synthesis of Dicarboxymethyl-U-DETA via the Reaction of U-DETA with Formaldehyde and Alkali Metal Cyanide

[0168] A 30% sodium cyanide solution was added to 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) at 98 °C. Two minutes after the start of the addition of NaCN, the addition of a 44% formaldehyde solution was started simultaneously. The addition rate of the 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 the added NaCN solution was 230 g. The addition rates of the formaldehyde solution were 1.31, 0.51 and 0.42 g / min, respectively. The total amount of the added formaldehyde solution was 97 g. When the amount of free cyanide ions was below 100 ppm, the addition of formaldehyde was stopped. The reaction mixture was refluxed for 1 hour while removing the ammonia-water mixture and adding water to prevent the temperature from rising above 104 °C. After cooling, 576.5 g of a reaction solution containing 30.3% (NMR analysis) of the disodium salt of dicarboxymethyl-U-DETA was discharged from the reactor, corresponding to an 86% yield based on U-DETA.

[0169]

[0170] Example 3B Formation of 1,1-Bis(carboxymethyl)-diethylenetriamine by Removal of Urea Groups

[0171] 50% NaOH solution (3.5 equivalents) was added to the reaction mixture produced by the Singer method, which contained dicarboxymethyl-U-DETA sodium salt and the mixture was heated at 180 °C for 40 hours. A high conversion to the product was obtained according to NMR analysis.

[0172]

Claims

1. A method for producing a nitrile compound by chain extension of an alkyleneamine compound containing three or more amine units, wherein at least two amine units are protected by cyclic urea units and at least one amine unit is unprotected, by reacting the at least one unprotected amine unit with glycolonitrile or with 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, wherein the alkyleneamine compound containing three or more amine units in which at least two amine units are protected by cyclic urea units and at least one amine unit is unprotected is selected from: U-DETA, U1-TETA, UP-TETA, U2-TETA, DU1,3-TEPA, DU1,4-TEPA, U1P3-TEPA, U1P4-TEPA, U2-TEPA, U1-T-TEPA, U3-PEHA, U2-T-PEHA, U3-T-HEHA, U1P3-PEHA, U1P3-T-HEHA and U3-T-HEOA.

2. The method according to claim 1, wherein the at least one unprotected amine unit reacts with glycolonitrile.

3. The method according to claim 1, wherein the at least one unprotected amine unit reacts with a combination of formaldehyde and a cyanide selected from HCN and inorganic cyanide salts.

4. The method according to claim 3, wherein the cyanide is HCN.

5. The method according to claim 3, wherein the cyanide is an inorganic cyanide salt.

6. The method according to claim 3, wherein the inorganic cyanide salt is selected from sodium cyanide, potassium cyanide, calcium cyanide, and combinations thereof.

7. The method according to claim 5, wherein the reaction is carried out in the presence of an acid.

8. The method according to claim 5, wherein the reaction is carried out under conditions such that the nitrile group reacts to form a carboxylate salt.

9. The method according to claim 8, wherein the reaction is carried out in the presence of a base.

10. The method according to any one of claims 1 to 7, wherein the product containing the at least one acetonitrile group is subjected to a further reaction step, the further reaction step being a hydrogenation step in the presence of hydrogen and a catalyst, wherein the nitrile group is at least partially converted to an amino group.

11. The method according to any one of claims 1 to 7, wherein the product containing the at least one acetonitrile group is subjected to a further reaction step, the further reaction step being a saponification step for forming a carboxylate group in the presence of an aqueous base.

12. The method according to any one of claims 1 to 7, wherein the product containing the at least one acetonitrile group is subjected to a further reaction step, the further reaction step being a reaction of forming an imine salt with a Grignard reagent and subsequent hydrolysis of the imine salt to produce a ketone.

13. The method according to any one of claims 1 to 7, wherein the product containing the at least one acetonitrile group is subsequently subjected to a further reaction step, and the further reaction step is a hydrolysis step for forming a corresponding amide in the presence of an acidic catalyst.

14. The method according to any one of the preceding claims 1 to 7, wherein the cyclic urea unit is removed from the nitrile compound obtained by the method according to any one of claims 1 - 7, or optionally, in the case where the nitrile compound is subjected to a further reaction step, the cyclic urea unit is removed from the nitrile compound during or after the further reaction step, and the further reaction step may be the reaction step according to any one of claims 8 to 13.

15. The method according to claim 14, wherein the step of removing the cyclic urea unit comprises one or more of reacting with water in a liquid phase, reacting with an alkyleneamine capable of abstracting a carbonyl moiety, and reacting with a strong base, and the strong base is a base with a pKb of less than 1.

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