WO1992012962A1

WO1992012962A1 - Process for the production of cyanoacetic acid

Info

Publication number: WO1992012962A1
Application number: PCT/US1992/000588
Authority: WO
Inventors: A. Ray Bulls; Jere D. Fellmann; Roy A. Periana
Original assignee: Catalytcca Inc.
Priority date: 1991-01-24
Filing date: 1992-01-24
Publication date: 1992-08-06
Also published as: EP0568621A1; EP0568621A4; AU1255492A; JPH06507154A

Abstract

This is a process for preparing cyanoacetic acid (CAA) or its esters by further oxidizing a partially oxidized propionitrile compound of the following formula: N}C-CHx-CHy-AB, where A is -H, -OH, or -OR; and B is -OH, -OR, or = O; x=1 or 2, y=0 or 1 (depending upon the selection of A and B); but where B is =O, A is -H, and x=0; and where y=1, x=0, B is -OH or -OR. Especially preferred partially oxidized propionitrile compounds include cyanoacetaldehyde (CA), its hydrate (CAH) or acetal (CADA). Suitable oxidants include oxygen, ozone, hydrogen peroxide, peracids, nitrites, and the like. The partially oxidized propionitrile compound is preferably produced from acrylonitrile. An optional step is the esterification of the cyanoacetic acid.

Description

PROCESS FOR THE PRODUCTION OF CYANOACETIC ACID

Field of the Invention

This is a process for preparing cyanoacetic acid (CAA) or its esters by further oxidizing a partially oxidized propionitrile compound of the following formula:

N) C-CH_x-CH_y-AB where A is -H, -OH, or -OR; and B is -OH, -OR, or =O; x=1 or 2, y=0 or 1 (depending upon the selection of A and B); but where B is =0, A is - H, and x=0; and where y=1, x=0, B is -OH or -OR. Especially preferred partially oxidized propionitrile compounds include cyanoacetaldehyde (CA), its hydrate (CAH) or acetal (CADA). Suitable oxidants include oxygen, ozone, hydrogen peroxide, peracids, nitrites, and the like. The partially oxidized propionitrile compound is preferably produced from acrylonitrile. An optional step is the esterification of the cyanoacetic acid.

Background of the Invention

The current technology for the preparation of CAA involves the reaction of chloroacetic acid (or its ester) with NaCN. Although this technology has been practiced commercially for some time, it suffers from high cost due to the chloroacetic acid and the environmental concerns surrounding the use of NaCN.

CAA is of interest since it has application as a raw material for the pharmaceutical and specialty chemical industry. It can also be used for the preparation of mafonic acid and its esters, which acids and esters are also used in the synthesis of pharmaceuticals.

The art does not teach that CAA or its esters can be made from ACN. Smidt teaches (Angew. Chem., 71. Jahr. 1959, Nr. 19, p 626) that ACN can be oxidized by PdCI₂ to 2-ketopropionitrile. In contrast, Lioyd suggests (US 3,410,807) that oxidation of ACN in an alcoholic media produces CADA but fails to exemplify it further. CADA is the acetal of cyanoacetaldehyde (CA), not 2-ketopropionitrile. In agreement with Lioyd, Hosokawa et. al. (Bull. Chem. Soc. Jpn., 63, 166-169, 1990 and Ace. Chem. Res., 23(2),49-54, 1990) shows that ACN can be oxidized to the corresponding cyclic acetal in a 1 ,3-propandiol/DME media using a PdCI₂(CH₃CN)₂ with CuCl₂ or BiCI₃-LiCI as a co-catalyst. Ube also shows in two independent and non-related disclosures that ACN can be oxidized to the acetal of cyanoacetic acid (CADA) using alkylnitrite esters (US 4,504,422) and CADA can be oxidized to CAE using hydroxylamine as a stoichiometric oxidant (US 4,438,041). Hydroxylamine is not a conventional oxidant. Hydroxylamine is typically used in combination with aldehydes in their conversion to the corresponding nitrite. Ube, consequently, was apparently attempting to prepare malononrtrile from CADA.

It is important to point that several potential intermediates in our process have been prepared by indirect means. Ube teaches (J 57-0,203,052) that CADA can be hydrolyzed to CA using an acid catalyst. There are several references (US 4,277,418, DE 3,641,604, DE 3,222,519, DE

3,211,679, JP 83-26,855, JP 58-26,855) which teach either the conversion of CADA to the corresponding alkoxyacrylonitrile (ROCH=CHCN) or vice versa. Additionally, CA is commonly obtained from ACN as the acetal (CADA). Typically a PdCI₂/CuCI₂ catalyst in an alcoholic media has been used.

CH₂=CHCN + 1/2 O₂ + 2 ROH - - -> (RO)₂CHCH₂CN (ACN) (CADA)

The only reported oxidation of a cyanoacetaldehyde we have found has come from Ube. There, it was reported that CADA can be oxidized to CAA-ester (CAE) by reaction with hydroxylamine:

(RO)₂CHCH₂CN + HONH₂ - - -> ROCOCH₂CN

The oxidation of aldehydes or acetals by oxygen and of acetlas by ozone and peracids has been described but never with a deactivated acetal such as CADA.

None of the prior art shows the oxidation of the listed partially oxidized propionitrlile compounds to directly produce CAA. The prior art similarly does not show the combination of theat step with either the esterification of the CAA to its ester or the production of the listed partially oxidized propionitrlile compounds from ACN.

Summary of the Invention

N) C-CH_x-CH_y-AB where A is -H, -OH, or -OR; and B is -OH, -OR, or =O; x=1 or 2, y=0 or 1 (depending upon the selection of A and B); but where B is =O, A is -

H, and x=0; and where y=1, x=0, and B is -OR or -OH. Especially preferred partially oxidized propionitrile compounds include

cyanoacetaldehyde (CA), its hydrate (CAH) or acetal (CADA). Suitable oxidants include oxygen, ozone, hydrogen peroxide, peracids, nitrites, and the like. The partially oxidized propionitrile compound is preferably produced from acrylonftriie. An optional step is the esterification of the product cyanoacetic acid. This overall reaction scheme is outlined as follows:

[O] [O] esterify

ACN - - - - - - - - > CAH - - - - - - - > CAA - - - - - - - - - -> ECA

CA CADA RACN CADA/CAH.

Description of the Invention

This is a process for preparing cyanoacetic acid [CAA] (or it esters) by further oxidizing a partially oxidized propionitrile compound of the following formula:

N) C-CH_x-CH_y-AB where A is -H, -OH, or -OR; and B is -OH, -OR, or =O; x=1 or 2, y=0 or 1 (depending upon the selection of A and B); but where B is =O, A is - H, and x=0; and where y=1, x=0, and B is not =O, with selected oxidants. Especially preferred partially oxidized propionitrile compounds include cyanoacetaldehyde (CA), its hydrate (CAH) or acetal (CADA). Additionally, the inventive process includes the optional steps of:

a.) producing the partially oxidized propionitrile by oxidizing acetonitrile (ACN), and

b.) esterifiying the product CAA to produce alkylcyanoacetates. Oxidation of Partially oxidized propionitrile compounds

The oxidation of partially oxidized propionitrile compounds with oxygen, ozone, peracids (RCOOOH, where R is H or C_nH_n+2), alkyl nitrites (RONO, where R is C_nH_n+2) and hydrogen peroxide or mixtures thereof requires the stoichiometric use of the oxidant. An especially preferred oxidant is an equimolar combination of carboxylic acids (RCOOH), particularly formic acid (HCOOH) and hydrogen peroxide. This combination forms peracids (RCOOOH), including performic acid (HCOOOH) when formic acid is the carboxylic acid is the acid, in situ.

In the case of ozone, we have some evidence that it has been used catalytically in combination with oxygen but not with CA. This invention deals only with the use of stoichiometric ozone as an oxidant. The use of oxygen is quite novel since oxygen is a considerably less potent oxidant than a peroxide or peracid is.

The oxidative conversion of either CAH or CADA to CAA or ECA is generally described in the following equations:

N) C-CH₂-CH-(OH)₂ + [O] - - -> N) C-CH₂-C-OOH N) C-CH=CH-(OH) + [O] - - -> N) C-CH₂-C-OOH N) C-CH₂-CH-(OR)₂ + [0] - - -> N) C-CH₂-C-OOR N) C-CH=CH-(OR) + [O] - - -> N) C-CH₂-C-OOR

Conversion of CAA to the corresponding ester

CAA is also easliy converted to the ester by acid catalyzed hydrolysis using alcohols.

N) C-CH₂-COOH + ROH - - -> N) C-CH₂-C-OOR + H₂O where R is C_nH_{2n +1}. Suitable acids include strong mineral acids such as H₂SO₄, glacial acetic acid, HCI, etc. Sulfuric acid is easpecially preferred because of its cost and ready acailability but others are suitable. Strong acidic ion exchange resins (Dowex, Amberlyst, etc.) are also suitable. The reaction may be carried out in an appropriate solvent such as toluene, benzene, and similar materials. Toluene is a desirable solvent since it is tolerant of the strong acid catalyst and (when

ethylcyanoacetate is the product of ethanol and CAA) may be separated from the reaction mixture by distillation of an azeotrope of

H₂O/ethanol/toluene.

Formation of partially oxidized propionitrile bv oxidation of acetonitrile Acetonitrilθ is a fairly inexpensive feedstock. Using any of a variety of oxidation catalysts such as Wacker-type catalysts (PdCI₂/CuCI₂), FeCI₃ PdCI₂, Na₂PdCl₄, HPA's (especially H5PMo10V25O40), platinum group metals and their salts (palladium, platinum, rhodium, ruthenium, iridium, ond osmium and the halides, sulfates, nitrates, phosphates, and acetates thereof) or other soluble oxidation catalysts in a suitable polar reaction media (H₂O; short chain alcohols, (CH₃OH to C₁₂H₂₅OH) such as methanol, ethanol, propanol, isopropanol, etc.; ethers, aldehydes, etc.) will result in oxidation of the ACN to the partially oxidized propionitrile compound described above: N) C-CH_x-CH_y-AB. The catalyst need be present in a catalytic amount which often is between 1 ppm and 10% by weight of the catalyst in the solution.

The oxidants used in this step may the same as those used in the step of oxidizing the partially oxodixzed propionitrile to CAA, e.g., oxygen, ozone, peracids (RCOOOH, where R is H or C_nH_n+2), alkyl nitrites

(RONO, where R is C_nH_n+2) and hydrogen peroxide or mixtures thereof. The invention has been disclosed by direct description. Below may be found a number of examples showing various aspects of the invention. The examples are only examples of the invention and are not to be used to limit the scope of the invention in any way.

EXAMPLES

Procedures

In examples 1-8, the Pd and co-catalyst were added to a 300 cc autoclave. The total volume of reactants, diluents, feedstocks, and catalysts was about 150 cc. The pressure varied between atmospheric and 100 psi. The materials were added to the reactor, the reactor was heated to the reaction temperature, stirring at 1000-2000 rpm was commenced, and samples were periodically taken.

In example 9, the feedstocks, catalysts, and solvents were added to a glass reactor having magnetic stirring. The total volume was about 30 cc.

In examples 11-17, the various feeds (ethyl-CADA, methyl-CADA, or ethoxyacrylonitrile), acid, and H₂O were added to round bottom flasks. The flasks were heated under reduced pressure to remove the alcohol as formed. The yield and purity of the aqueous solutions was

determined by high pressure liquid chromatography.

In examples 18 and 19, the reactants (CACA or CAH) were dissolved in an appropriate solvent (H₂O or glacial acetic acid) and loaded into a 250 cc 3-neck Morton flask equipped with a magnetic stir bar and

thermometer. A stream of O₃ (0.08 to 2%) in oxygen or air was generated with a Polymetrics ozone generator and passed through the solution (at 200-2000 cc/min) with stirring at a temperature between 0# and 25#C. The progress of the reaction was monitored via high pressure liquid chromatography.

In examples 20-22, water or aqueous carboxylic acid was loaded into a 500 cc 3-neck Morton flask equipped with an overhead mechanical stirrer and a reflux condenser. Addition acid was used to increase the acidity. Equimoiar amounts of substrate (CADA or EACN) and 50% H₂O₂ were fed into the stirred solution over a period of 1 to 6 hours at 40#-6Q#C. The solution was stirred an additional 1-2 hours at temperature. The product mixture was analyzed using high pressure liquid chromatography and GC analysis.

In examples 23-25, a solution of CAH in H₂O or acetic acid (typically from 1 to 10% CAH by weight) was added to a 100 cc stainless steel reactor equipped with an internal stirrer, a sample port, and an external heating jacket. Acid (e.g., H_s4) was added to the solution as needed to help stabilize the CAH. The appropriate catalyst was then added to the solution to a concentration between 10 and 100mM. Oxygen or air was charged to the reactor to a pressure of 5 to 100 psig. The solution was heated to a temperature of 50-120# C with stirring. Samples of the reaction solution were collected periodically and the progress of the reaction was determined by high pressure liquid chromatography.

In example 26, the ethyl ester of CAA was added to an aqueous solution with H₂SO₄ and heated to 55# C for 16 hr.

In example 27, CAA was dissolved with the acid in absolute ethanol and refluxed for eight hours. The following examples illustrate the oxidation of ACN to CA derivatives, CADA, CAH and RACN.

Examples 1-3: Oxidation of ACN using Na₂PdCl₄/CuCl₂ in alcoholic media.-

These examples show the use of this catalyst with a variety of alcohols to make CADA and CAH.

Examples 4-5: Oxidation of ACN to CADA using Na₂PdCl₄/CuCl₂ in EtOH/water media. This example shows the use of this catalyst in EtOH/water media.

Example 6: Oxidation of ACN to CAH using Na₂PdCl₄/CuCl₂ in

Examples 7-8: Oxidation of ACN using Na₂PdCI₄/HPA In alcoholic media.

Example 9: Oxidation of ACN to CADA using PdCI₂ and EtONO in EtOH.

Example 10: Oxidation of ACN to CAA using PdCI₂/CuCl₂ in water.

This example shows the one-step oxidation of ACN to CAA.

Examples 11-15: Hydrolysis of ethyl-CADA using various acids.

These examples show the hydrolysis of CADA and alkoxyacrylonitrile to CAH.

(All reactions were conducted at 70# C for 75 minutes under 200 mm Hg. The reduced pressure was used to remove the EtOH as it formed in order to drive the equilibrium to favor CAH formation.)

Example 16: Hydrolysis of methyl-CADA using liquid acids.

Example 17: Hydrolysis of ethoxyacrylonitrile (EACN).

The following examples illustrate the oxidation of CAH or CADA to CAA or CAE using non-oxygen based oxidants (i.e. ozone, peracids, hydrogen peroxide)

Example 18: Oxidation of CAH using ozone.

Example 19: Oxidation of CACA (where CACA = ethylene glycol CADA) using ozone.

Examples 20 and 21: oxidation of CA and derivatives using hydrogen peroxide alone or In combination with carboxylic acids.

Exampie 22- Oxidation of CA and derivatives using hydrogen peroxide in combination with carboxylic acids

The following examples illustrate the oxidation of CAH to CAA using oxygen as the oxidant.

Example 23: Oxidation of CAH with oxygen using various free radical initiation catalysts.

Example 24: Oxidation of CAH with oxygen using a non-free radical catalysts (Na₂PdCl₄/HPA).

Example 25: Oxidation of CAH with oxygen using a non-free radical cataivsts ( Na₂PdCl₄/CuCl₂).

The following examples illustrate the hydrolysis of CAE and the

esterification of CAA.

Example 26: Hydrolysis of ethyl ester of CAA.

Example 27: Esterification of CAA with ethanol.

Procedures

The following procedures were used in the following examples to oxidize various partially oxidized propionitriles using hydrogen peroxide, ozone, and peracids.

Reactions of O₃ with CA equivalents:

The reactant (CACA, CAH, or CADA) was dissolved in an appropriate solvent (H₂O or glacial acetic acid) and loaded into a 250 cc 3-neck Morton flask equipped with a magnetic stir bar and thermometer. A stream of O₃ (0.08 to 2%) in oxygen (or air) was generated with a Polymetrics ozone generator and passed through the solution (at 200- 2000 cc/min) with stirring at a temperature between 0 and 25#C. The progress of the reaction was monitored by high pressure liquid chromatography.

Reaction of hydrogen peroxide/carboxylic acid with CA equivalents:

The aqueous carboxylic acid (formic, CAA, or acetic acid), was loaded in a 500 cc 3-neck Morton flask equipped with an overhead mechanical stirrer and a reflux condensor. Additional acid (i.e. H₂SO₄) can be added to the solvent to increase the acidity. Equimolar amounts of substrate (i.e. CADA or EtOACN [EACN]) and 50% H₂O₂ were fed into the stirred solution over a period of 1 to 6 hours at 40#C to 60#C. The solution was stirred an additional 1-2 hours at temperature. The product mixture was determined by high pressure liquid chromatography and GC analysis.

Reaction of hydrogen peroxide with CA equivalents in H₂O:

The feed material (CAH, CACA, or CADA), H₂O, and H₂SO₄ were added to a 100 cc 3-neck Morton flask equipped with a mechanical stir bar. Approximately 1 equivalent of hydrogen peroxide was charged into the solution with stirring. The temperature of the solution was kept between 25°C and 60°C. The solution was stirred an additional 1-2 hours at temperature. The product mixture was determined by high pressure liquid chromatography and GC analysis.

EΞxample 28 Ozone Oxidation of CAH

Ozone reacts with CAH at room temperature to give CAA. The Table below shows results at pH = 1 and low ozone (0.08%) concentration.

We examined the influence of pH and ozone concentration on the CAA yield obtained from the oxidation of CAH by ozone. This was done by setting the desired pH by titration with Na₂CO₃ or NaHCO₃. The ozone concentrations were variable: 2%, 0.4% and 0.08%. The results from these experiments are shown in the following Table.

The five general trends observed are:

╌ The rate of oxidation dramatically increased as a function of both ozone concentration and pH. The fastest rates were observed with the highest ozone concentrations and highest pH.

╌ The selectivity to CAA slightly increased as the ozone concentration decreased.

╌ The selectivity to CAA increased as the pH increased.

╌ Generally, the selectivity to CAA decreased as the conversion increased.

Example 29 Ozone Oxidation of CADA

The open literature shows the oxidation of alkyl and aromatic acetals to the corresponding esters. Although no literature was found describing the oxidation of deactivated acetals such as CADA, it seemed reasonable that the oxidation of CADA was possible only through the use of potent oxidants. It is known that the selectivity to the corresponding ester is somewhat poor with noncyclic acetals (such as those derived from ethanol), whereas the selectivity improves with cyclic acetals (such as those derived from ethyiene glycol). We prepared ethylene glycol-CADA [or the cyclic acetal of cyanoacetaldehyde (CACA), characterized it by NMR and obtained a response factor for high pressure liquid chromatography] for use in ozone oxidation experiments.

Ozonolysis of CACA with a 2 % O₃/O₂ mixture produced the

corresponding ester. The reaction rate was found to increase

significantly when 2% versus 0.08 % ozone was used. The data show that this is a highly selective reaction below 70% conversion. Above a 70 % conversion level, unidentified products were preferentially formed.

The use of stoichiometric ozone likely would only be considered only if an inexpensive ozone generator were to be available. However, we believe that the hydroxyethyl ester of CAA is difficult to make by any other route.

Example 30 Peracid Oxidation of CADA and CAH

The high yield and fast reaction rate obtained from the oxidation of the acetal with ozone suggested that a more fruitful approach to CAA could potentially be achieved through the oxidation of CADA with peracids. The reaction of peracids with acetals yields the corresponding esters.

The reaction of ethyl-CADA with 30% peracetic acid in acetic acid showed, after 13 hr at ambient temperature, a 12 % selectivity to CAA-ester at 60% conversion. Surprisingly, a large amount (48 % selectivity) of CAA was found in the reaction mixture. Since CADA hydrolyses readily under these conditions this suggested that the small amount of H₂O₂ and H₂O present in peracetie acid must have been responsible for the production of CAA from the intermediacy of CAH. Therefore a new approach was attempted for the conversion of CADA (via CAH) directly into CAA using a mixture of water and a peracid.

To test this concept, an aqueous mixture containing CAH was reacted with an excess amount of 30% peracetie acid. This gave a rapid reaction and high selectivity to CAA (after 1 hr at ambient temperature CAH conversion - 90% with a mol % selectivity to CAA = 77%) was obtained. The increased reaction rate of CAH over CADA (in the absence of added water) suggested that CAH was an intermediate in the oxidation of CADA to CAA.

Example 31 Hydrogen peroxide Oxidation of CADA and CAH

The oxidation of an acetal to a carboxylic acid with hydrogen peroxide or a peracid has little precedence in the literature. Generally, acetals are oxidized with a peracid to the corresponding carboxylic acid ester.

Our data suggest that CADA is first hydrolyzed to CAH which is in turned oxidized by the peracid. The use of the peracid is desired since our control experiments showed that when CAH was oxidized with H₂O₂ alone, the yields were somewhat lower than with a peracid (mol % seiectivity_H2O2 = 50% versus mol % selectivity_{Peracatic acid} = 80%).

An economical way of generating performic acid, in the presence of large amounts of water, is by combining H₂O₂ and formic acid. Formic acid is commercially available in 96% and 88% aqueous mixtures. Additionally, since it forms an azeotrope with water it can be conveniently distilled to a 77% concentration. We examined both 96% and 77% formic acid in combination with near stoichiometric quantities of H₂O₂ and found similar results.

We examined the oxidation of CADA in H₂O₂/formic acid media for the effectiveness of CAA synthesis. Ethyl-CADA reacts cleanly with about one equivalent of H₂O₂ (1.04 mol H₂O₂/mol CADA) in 96% formic acid. A small amount of acid catalyst (such as H₂SO₄ or HCI) can be added to speed the reaction rate at 40#C. Alternatively, simply heating the solution in the absence of added acid to about 60#C results in similar reaction rates (rate was about 1×10^-7 mol cc^-1 sec^-1).

For the H₂O₂ oxidation of ethyl-CADA at 100 % conversion, the selectivity to CAA was approximately 88 mol % by high pressure liquid

chromatography. The only major byproduct identified was CAH (ca. 10 mol%) which can likely be recovered and recycled. A small amount of CAA-ester (ca. < 1%) and CO₂ was also detected. A minor byproduct may be formic acid. However, since formic acid was the major constituent in the solvent, it was impossible to accurately quantify any small increase.

In one experiment, we obtained a crude CAA product (78 % isolated yield) by removal of the solvent and washing with methylene chloride. The melting point was measured at 66-68#C, in accordance with the literature for CAA. The product was analyzed by ¹H and ¹³C NMR and FTIR and compared with standard CAA. We found that the CAA prepared by this procedure was > 99⁺ % pure by ¹H NMR.

Recrystallization of the crude product from ether/heptane afforded 60% of CAA as pure white crystals (mp 66.5-67.5#C). This demonstrated the feasibility of product separation and purification for this step. Similar results have been achieved with methyl-CADA in 77% formic acid. The principle difference appears to be that the rate of hydrolysis of methyl-CADA is approximately 4.5 times slower than the ethyl derivative. In order to achieve a comparable rate, we increased the acid catalyst concentration from ca. 0.2 M to 0.8 M. At 100% conversion of methyl- CADA (reaction time = 200 min) the CAA yield was 84 mol %. The principle byproduct was CAH (which can potentially be recycled).

Another byproduct was CAA-ester (ca. 3%) which may represent additionai yield of CAA. The H₂O₂ utilization was found to be 86%.

We found that the yield of CAA was a function of the amount of H₂O₂ present in 77% formic acid. The excess H₂O₂ needed (1.38 mol

H₂O₂/mol CADA) to achieve 98 mol % CAA yield was indicative of a less than stoichiometric utilization of the H₂O₂ in the water-formic acid-performic acid system. Although the highest yields were achievable with the excess H₂O₂, quite acceptable yields were obtained with

stoichiometric amounts of H₂O₂ (ca. 82%).

A measure of H₂O₂ utilization was obtained by comparing the mole ratio of CAA (produced)/H₂O₂ (initial) against the CAA yield. Approximately 70 to 80 % of the H₂O₂ was utilized for the production of CAA. There was still evidence of active peroxide after 5.5 hours, suggesting that the reaction had not come to completion.

The CAA yield was also found to be H₂O₂ concentration dependent. The yield of CAA peaked at a H₂O₂ solution concentration of about 1.6 wt %. At higher H₂O₂ concentrations, the utilization dropped and the CO₂ production increased. At a low H₂O₂ concentration the reaction rate decreased giving lower CAA yields after the same reaction time. We have found acceptable results when charging 50 % H₂O₂ to the reactor. However, after dilution with the reaction solvent the actual H₂O₂ concentration in the reaction media was only about 1 to 2 wt %.

Therefore low initial H₂O₂ concentrations can be employed provided the solution concentration is not less than 1 wt% H₂O₂.

Example 32 Use of other Carboxylic Acids

The carboxylic acid used to generate the peracid in-situ can also be varied. We have demonstrated the use of not only formic but acetic and CAA acids in combination with hydrogen peroxide. The table below shows examples of these results using various CA derivatives.

Procedures

The following procedure was used in example 33 set out below in which CAH is oxidized to CAA using O₂.

To a 100 cc stainless steel reactor equipped with an internal stirrer, a sampling port, and an external heating jacket was added a solution of CAH in H₂O or acetic acid (typically from 1 to 10% CAH by weight). Acid (e.g. H₂SO₄) can be added to the solution to help stabilize the CAH. The appropriate catalyst was then added to the solution (catalyst

concentrations are typically between 10 and 100 mM). Oxygen (or air) was charged to the reactor to a pressure of 5 to 100 psig. The solution was heated to a temperature of 50 to 120#C with stirring. Samples of the reaction solution were collected periodically and the progress of the reaction was determined by high pressure liquid chromatography.

Example 33

This example investigated the use of free radical initiation catalysts in aqueous and acetic acid solvents. The table details the results of some of the experiments from the free radical initiated oxidation of CAH to CAA using oxygen.

Clearly, these results showed that CAH can be oxidized under these conditions to CAA. In general, the selectivity declined as conversion increased. The best results showed a selectivity of 66% at 10% conversion, the selectivity dropped to 45% at 28% conversion.

Generally, the metal catalyzed oxidation of aldehydes is carried out commercially in a carboxylic acid solvent utilizing the free aldehyde and not the hydrate. Since water is a more convenient solvent for our process we attempted to find a water based oxidation catalyst for this conversion. Using either a manganese or cobalt catalyst, in water, has thus far led to complete oxidation of the CAH. However, using a heteropolyacid (HPA) as the catalyst provided the improved results shown in Table 1. This suggests that the HPA is acting as a free radical initiator but is much milder than either manganese or cobalt.

Due to the low selectivity obtained from oxidation of CAH in this manner, a non-free radical catalyst was sought. We have found that the electrophilic oxidation of CAH (in water at 75#C) to CAA could be accomplished with the use of a stoichiometric amount of palladium (+2). With this oxidant greater selectivities of CAA were obtained even in water and under acidic conditions, similar to the HPA experiment. This verified that a non-radical oxidation of CAH to CAA is preferred over a free radical oxidation.

Even though stoichiometric use of palladium is economically impractical, this experiment shows that much higher yields are obtainable with an electrophilic oxidant as compared to a free radical initiator. The data appears to show that the radical pathway leads to higher losses than the electrophilic mechanism. Therefore several non-radical approaches were investigated.

A Pd/HPA catalyst gave results somewhat better than HPA alone but far less than for stoichiometric palladium.

Assuming first order kinetics for all three cases (stoichiometric Pd, HPA and Pd/HPA) we found that the rates of oxidation of CAH using HPA and Pd/HPA catalysts are quite similar. However, the stoichiometric palladium oxidation rate is notably slower (the relative rates for stoichiometric palladium, HPA and Pd/HPA are 1:1.5:1.7). Therefore the product distribution is largely being controlled by the HPA free radical oxidation of CAH, with very little contribution from palladium. In order to develop a highly selective catalyst for this step was necessary to minimize the free radical pathway and favor the electrophilic pathway. ln order to minimize the fosses due to free radical oxidation a less oxidizing co-catalyst was sought to replace the HPA. We selected CuCI₂ as that cocatalyst. CuCI₂ was less oxidizing than HPA and that the relative rate of free radical consumption of CAH was approximately 15 times slower than HPA.

These data indicated that a PdCI₂/CuCI₂ catalyst would perform considerably better than the corresponding PdCI₂/HPA catalyst. This was found to be the case.

Although the Pd/HPA catalyst displayed 1.5 times the reaction rate, the mol % yield of CAA was considerably higher with the Pd/Cu catalyst. At 100% conversion, we anticipate that the CAA yield could reach 45%. This is reasonable since the selectivity was a constant 45% throughout the experiment. The reaction rate was about 10^-9 mol cc^-1 sec^-1).

It should be dear that one having ordinary skill in this art would envision equivalents to the processes found in the claims that follow and that these equivalents would be within the scope and spirit of the claimed invention.

Claims

WE CLAIM AS OUR INVENTION:

1. A process for producing cyanoacetic acid by further oxidizing a partially oxidized propionitrile compound of the following formula:

N) C-CH_x-CH_y-AB where A is -H, -OH, or -OR; and B is -OH, -OR, or =O; x= 1 or 2, y=0 or 1 (depending upon the selection of A and B); but where B is =O, A is -H, and x=0; and where y=1, x=0, and B is not =O.

2. The process of claim 1 where the partially oxidized propionitrile compounds are selected from cyanoacetaldehyde, its hydrate, or acetal.

3. The process of daim 1 where the oxodation takes place with with oxygen, ozone, peracids (RCOOOH, where R is H or C_nH_n+2), alkyl nitrites (RONO, where R is C_nH_n+2) and hydrogen peroxide or mixtures thereof.

4. The process of claim 1 including the step of oxidizing

acetonitrile to produce the partially oxidized propionitrile

compounds.

5. The process of claim 1 including the step of esterifying the product cyanoacetic acid.