WO1995032183A1

WO1995032183A1 - Process for the preparation of 2-cyanoacryloyl chloride and use of the compound so prepared for the preparation of esters of 2-cyanoacrylic acid

Info

Publication number: WO1995032183A1
Application number: PCT/IE1995/000017
Authority: WO
Inventors: Valery Alexandrovich Dyatlov; Viktor Maleev
Original assignee: Saldane Limited
Priority date: 1994-05-24
Filing date: 1995-02-08
Publication date: 1995-11-30
Also published as: AU1671495A

Abstract

A process for the preparation of 2-cyanoacryloyl chloride in pure form comprises reacting 2-cyanoacrylic acid with a chlorinating agent, said reaction being carried out under side-reaction and polymerisation inhibiting conditions. A preferred chlorinating agent is a volatile chlorinating agent which forms only volatile by-products during the course of the reaction. Suitable volatile chlorinating agents include oxalyl chloride, sulfur oxychloride, trifluoroacetyl chloride and phosgene. Various methods can be used to inhibit polymerisation initiating conditions such as the use of a catalyst which forms an intermediate complex with the chlorinating agent, thereby preventing the formation of a mixed anhydride. The 2-cyanoacryloyl chloride formed can be used to form esters useful in the manufacture of adhesives and which esters are free of contaminants which would otherwise affect the setting time of the adhesives.

Description

Process for the preparation of 2-cyanoacryloyl chloride and use of the compound so prepared for the preparation of esters of 2-cyanoacrylic acid

Technical Field

This invention relates to a process for the preparation of 2- cyanoacryloyl chloride and to the use thereof in the preparation of esters of 2-cyanoacrylic acid. 2-Cyanoacryloyl chloride which has the formula:

CN / H₂C= C \ C-Cl

II o

can potentially be used to prepare a wide range of cyanoacrylate monomers.

Background Art

The ability of 2-cyanoacrylates to polymerise rapidly under the influence of moisture or nucleophilic substances has led to their exploitation as instantaneous adhesives. However, the inherent ability of 2-cyanoacrylates to undergo rapid anionic polymerisation gives rise to complications as regards the synthesis of free 2-cyanoacryloyl chloride. Accordingly, whereas esters of 2-cyanoacrylic acid are known and well characterised since the 1940s, 2-cyanoacryloyl chloride has not been isolated and characterised. 2-Cyanoacryloyl chloride has been observed in solution only. The first reported observation of 2-cyanoacryloyl chloride in solution by NMR was described in 1990 by Kandror, I.I. et al. However, all efforts to isolate 2-cyanoacryloyl chloride from solution were unsuccessful. Kandror, LI. et al. ((1990) Zh. Obsch. Khemii., Vol. 60, No. 9, p. 2160-8) have described two methods for the preparation of 2- cyanoacryloyl chloride-containing solutions.

The first method involved the reaction of 2-cyanoacrylic acid with phosphorus pentachloride at a temperature of 110°C using a toluene-xylene mixture as a solvent, followed by distillation off of phosphorus oxychloride and a portion of the solvent. The resulting solution contained a mixture of 2-cyanoacryloyl chloride, polyphosphoric acid and polymers formed from 2-cyanoacrylic acid in the form of a solution in xylene. Conversion of 2-cyanoacrylic acid to 2-cyanoacryloyl chloride together with polymer was reported by NMR to be 95-99%, the yield of 2-cyanoacryloyl chloride was not estimated. ¹³C and ³¹P NMR analysis of 2-cyanoacryloyl chloride prepared by this method shows that deleterious by-products which are formed include those resulting from chlorination of, and addition of hydrogen chloride to, the olefinic bond of cyanoacryloyl chloride, and from the addition of phosphorus oxychloride to its nitrile group to yield substances containing the -C(Cl)=N-P(0)Cl₂ function. 2- Cyanoacryloyl chloride obtained by this method cannot be isolated from the mixture and polymerises spontaneously once the solvent is distilled off in vacuo. Vacuum distillation or precipitation of the product with an inert solvent also leads to instantaneous polymerisation.

The second method involved the reaction of 2-cyanoacrylic acid with thionyl chloride in toluene or toluene-xylene solution at a temperature of 110°C followed by distillation off of hydrochloric acid, sulfur dioxide and a portion of the solvent to give a mixture of 2-cyanoacryloyl chloride, 2-cyanoacrylic acid and polymers formed from 2-cyanoacrylic acid in the form of a solution in xylene. No yield or conversion has been estimated. NMR analysis shows that the product of the reaction is a solution of a mixture of 2-cyanoacryloyl chloride and 2-cyanoacrylic acid in a ratio of 65:35, together with mixed anhydride by-products resulting from the side and polymerisation reactions. Attempts to complete the reaction and convert residual 2-cyanoacrylic acid and mixed anhydrides into 2- cyanoacryloyl chloride resulted in polymerisation of the mixed anhydrides, 2-cyanoacryloyl chloride and 2-cyanoacrylic acid. The 2-cyanoacryloyl chloride could not be isolated in pure form from the reaction mixture using this method and the yield could not be estimated. However, according to NMR data, the yield is less than 65% and it appears that a significant amount of polymeric and side reaction products were not taken into account.

Thus, pure 2-cyanoacryloyl chloride was not obtained and chemically characterised in accordance with either of the two methods described above. In the case of each method, 2- cyanoacryloyl chloride can only be obtained in the form of a solution contaminated with non- volatile by-products.

2-Cyanoacryloyl chloride is used as a starting material for obtaining esters of 2-cyanoacrylic acid. Because of the contamination of the 2-cyanoacryloyl chloride referred to above this necessitates that any resulting ester be purified to remove the contaminants formed during 2-cyanoacryloyl chloride production. If such contaminants, which are generally of an acidic nature, are not removed, these can affect the setting times of adhesives formed from the esters. The highest level of strongly acidic contamination tolerable in cyanoacrylate adhesive compositions is generally less than 1 p.p.m. As regards the contaminants, the most undesirable contaminants are traces of residual phosphorus oxychloride, non- volatile strong acids such as phosphoric and polyphosphoric acids, and the deleterious chlorinated by-products mentioned supra. These by-products can slowly release hydrochloric acid via hydrolysis by atmospheric moisture during, for example, storage of a cyanoacrylate adhesive composition, leading to loss of adhesive properties by acid inhibition of the anionic polymerisation pathway. Complicated procedures are required to purify the esters from the non- volatile mixtures of contaminants, in particular in the case of non-distillable liquid esters which cannot be purified by either distillation or by recrystallisation. Accordingly, a process for the preparation of pure 2- cyanoacryloyl chloride which is not contaminated with non volatile contaminants such as phosphoric, polyphosphoric, poly(2- cyanoacrylic) and other acids is required.

Disclosure of Invention

The invention provides a process for the preparation of 2- cyanoacryloyl chloride, which comprises reacting 2-cyanoacrylic acid with a chlorinating agent, said reaction being carried out under side-reaction and polymerisation inhibiting conditions.

The process according to the invention allows for the preparation of 2-cyanoacryloyl chloride in pure form or in the form of a solution which is uncontaminated with non- volatile acids or precursors therefor or mixtures thereof.

Preferably, the process according to the invention comprises reacting 2-cyanoacrylic acid with a chlorinating agent under side- reaction and polymerisation inhibiting conditions to give a solution of 2-cyanoacryloyl chloride, optionally followed by isolation of 2- cyanoacryloyl chloride under polymerisation inhibiting conditions.

By non- volatile acid herein is meant any acid or polyacid or precursor thereof which cannot be removed by sparging of an inert gas into the reaction mixture in vacuo at a temperature of less than 40°C.

In the case of the above prior art method which involves phosphorus pentachloride, the by-products are typically hydrochloric acid, phosphorus oxychloride and acids formed from phosphorus oxychloride such as phosphoric acid and polyphosphoric acid.

The chlorinated by-products referred to hereinabove are those of structural formulae:

(I) (H)

which arise via the addition of chlorine to 2-cyanoacrylic acid or 2- cyanoacryloyl chloride; those of structural formulae

(πi) (iv)

which arise via the addition of hydrogen chloride to 2-cyanoacrylic acid or 2-cyanoacryloyl chloride; and those of structural formula

(V)

which arise via the addition of phosphorus oxychloride to the nitrile function of 2-cyanoacryloyl chloride.

The products of polymerisation and side-reactions referred to hereinabove are typically polyacids and polyanhydrides formed from 2-cyanoacrylic acid, 2-cyanoacryloyl chloride and an intermediate mixed anhydride formed from the acid and the chloride.

The use of a chlorinating agent in accordance with the invention under the conditions described, prevents contamination of the 2-cyanoacryloyl chloride formed with residual amounts of the chlorinating agent typical of the prior art process. Preferably, a volatile chlorinating agent is used which does not form non-volatile by-products during the reaction.

In order to prevent contamination with non-volatile acidic by¬ products formed from the chlorinating agent as is typical of the prior art processes, preferably chlorinating agents which form only volatile by-products are employed.

In order to prevent the formation of chlorinated by-products which arise via chlorination of the olefinic bond of 2-cyanoacrylic acid or 2-cyanoacryloyl chloride, or via reaction of the nitrile function of either of the above with the chlorinating agent, a chlorinating agent is suitably chosen which will not effect any of these transformations under the conditions of the process.

In order to prevent the formation of chlorinated by-products which arise via the addition of hydrogen chloride to the olefinic bond of 2-cyanoacrylic acid or of 2-cyanoacryloyl chloride, hydrogen chloride is driven off by sparging with an inert gas during the process.

In order to prevent the mixed anhydrides, which are subject to a side-reaction involving cyclisation and also to spontaneous polymerisation, from initiating the polymerisation of both 2- cyanoacrylic acid and 2-cyanoaryloyl chloride, chlorinating agents which do not lead to the formation of mixed anhydrides are employed.

The chlorinating agent in accordance with the invention is preferably any chlorinating agent unable to form a mixed anhydride and which forms volatile by-products during the chlorination reaction such as oxalyl chloride which forms carbon dioxide, carbon monoxide and hydrogen chloride, sulfur oxychloride which forms sulfur dioxide and hydrogen chloride, trifluoroacetyl chloride which forms trifluoroacetic acid and hydrogen chloride, phosgene which forms carbon dioxide and hydrogen chloride or 1 , 1 -dichloromethyl methyl ether which forms methyl formate. Particularly suitable chlorinating agents for use in accordance with the invention are oxalyl chloride and 1,1 -dichloromethyl methyl ether.

Preferably, the reaction conditions are such as to inhibit the formation of acidic or acidogenic by-products.

Representative of the acidogenic by-products herein are the chlorinated by-products of the formulae II, IV and V hereinabove depicted.

In order to prevent contamination by non- volatile polymeric products of side reactions, such side reactions are typically inhibited by one of the methods hereinafter described.

Accordingly, in a first embodiment, the polymerisation inhibiting conditions result from the use of a solvent which dissolves the reactants and any intermediate mixed anhydride formed but not the 2-cyanoacryloyl chloride which precipitates out on cooling.

Suitably the solvent can be an excess of the chlorinating agent. A prefened solvent is oxalyl chloride.

According to a second embodiment of the invention, the polymerisation inhibiting conditions are achieved by lowering the reaction temperature to a temperature lower than the polymerisation initiating temperature.

Suitably the temperature is in the range of from -10 to 110°C, more especially 0 to 70°C.

According to a third embodiment of the invention, the polymerisation inhibiting conditions are achieved by driving off any by-products capable of initiating polymerisation. Suitably the volatile by-products can be driven off by sparging with an inert gas.

The inert gas can be any inert gas, but is suitably argon or nitrogen.

By driving off volatile by-products the equilibrium of the reaction is moved in the direction of the 2-cyanoacryloyl chloride which it is desired to form.

According to a fourth embodiment of the invention, the polymerisation inhibiting conditions are achieved by the use of a catalyst which forms an intermediate complex with the chlorinating agent, thereby preventing the formation of a mixed anhydride.

A suitable catalyst is N, N-dimethylformamide.

Preferably, the catalyst is added to the 2-cyanoacrylic acid followed by addition of the chlorinating agent dropwise to a mixture of 2-cyanoacrylic acid and the catalyst. Further, preferably, the chlorinating agent is used in excess relative to the amount of catalyst used.

The invention thus provides substantially pure 2-cyanoacryloyl chloride which can be directly used in the preparation of esters for use in the formation of adhesives without the disadvantages of contaminants characteristic of the prior art. For example, the process according to the invention can be used to prepare many of the esters described in International Publication WO 94/15907.

Furthermore, the invention provides a solution of 2- cyanoacryloyl chloride which is free of acidic non-volatile contaminants and mixtures thereof. Modes of Carrying out the Invention

The invention will be further illustrated by the following Examples.

Example 1

Preparation of pure, solid 2-cyanoacryloyl chloride using oxalyl chloride as reagent

To 0.25 g (2.5 mmol) of 2-cyanoacrylic acid under intensive stirring 0.75 ml (0.6 mg; 5 mmol) of oxalyl chloride was added at room temperature. The suspension of the 2-cyanoacrylic acid in oxalyl chloride was vigorously stirred for 15 min. at room temperature and was then heated to 40°C. At this temperature the acid slowly dissolved in oxalyl chloride. Once the acid was completely dissolved a stream of argon was bubbled through the solution and the reaction mixture was cooled with liquid nitrogen. The solid frozen mixture thereby obtained was heated slowly to give a melt of oxalyl chloride containing a solid precipitate. The liquid was decanted and the precipitate dried in vacuo to give 0.15 g (1.9 mmol) of solid 2-cyanoacryloyl chloride, m.p. 46-49°C dec. Yield 50% Calculated for C₄H₂N0C1 C=41.39%, 1^*1=1.72%, N=12.07%, Cl=30.6%, Found C=40.93%, H=1.84%, N=11.67%, Cl=31.8%, NMR(C₆D₆ δ ppm) 5.76d; 5.2d; (2H, CH₂=) 7=l_27Hz.

Example 2

Preparation of pure 2-cyanoacryloyl chloride as a solution in toluene using oxalyl chloride as reagent

To 2-cyanoacrylic acid (2.0 g; 20 mmol) under intensive stirring was added at room temperature oxalyl chloride (10 ml; 117 mmol). The resulting suspension of 2-cyanoacrylic acid in oxalyl chloride was then stirred at 40°C during 15 min. after which time it was cooled to room temperature. The cyanoacrylic acid slowly dissolved in the oxalyl chloride. When solution was complete the mixture was filtered and dry toluene (250 ml) was added to the filtrate. A stream of argon was bubbled through the resulting solution to remove by-product gases hydrogen chloride, carbon monoxide and carbon dioxide. Excess oxalyl chloride was then removed by co-distillation with toluene (100 ml) at 35°C in vacuo to give a colourless solution (150 ml) of 2-cyanoacryloyl chloride in toluene. *H NMR in 1 : 3 C₆D₆ : toluene δ 5.90 and 5.35 (each 1H, 2d, 7=1.27 Hz, H_aH_bC=C-) p.p.m.

Example 3

Preparation of pure 2-cyanoacryloyl chloride as a solution in p - xylene using oxalyl chloride as reagent and N. N-dimethylformamide as catalyst

2-Cyanoacrylic acid (2.0 g; 20 mmol) was dissolved with heating in dry /---xylene (250 ml) containing γ-propanesultone (1 mg). -Xylene (50 ml) was removed by distillation in order to ensure anhydrous conditions, and the mixture was filtered into a 300 ml flask provided with a condenser, a dosing funnel, a mechanical stirrer and an argon inlet adaptor. The solution was cooled to 40°C and N, N-dimethylformamide (5 mg) was added using a stock solution of N, N-dimethylformamide in benzene. The mixture was stirred and oxalyl chloride (6 ml; 70 mmol) was added dropwise with continuous sparging by argon. The mixture was stirred at room temperature during 12 hr and conversion to 2-cyanoacryloyl chloride was monitored by H ΝMR. If residual 2-cyanoacrylic acid was detected, additional small portions of oxalyl chloride were added in order to complete its transformation into 2-cyanoacryloyl chloride. Ethyl furfurylidenecyanoacetate (5 mg) was then added to the mixture, and excess of oxalyl chloride together with volatile gaseous by-products were removed by distillation in vacuo together with p- xylene (100 ml) to give a yellow transparent solution (100 ml) of 2- cyanoacryloyl chloride in p -xylene. H NMR in CgDg : -xylene 1 : 3 δ 5.97 and 5.42 (2s, each 1H, 2d, H_aH_bC=C-) p.p.m.

Example 4

Preparation of 2-cyanoacryloyl chloride as a solution in toluene using phosgene as reagent and N. N-dimethylformamide as catalyst

2-Cyanoacrylic acid (2.0 g; 20 mmol) was dissolved in warm dry toluene (250 ml) containing γ-propanesultone (1 mg). Toluene (50 ml) was distilled off in order to ensure anhydrous conditions. The mixture was filtered into a 500 ml flask provided with a mechanical stirrer, an argon inlet adaptor, a dosing funnel provided with a cooling system and a dry ice condenser arranged for reflux. The mixture was cooled to 10°C and N, N-dimethylformamide (5 mg) was added using a stock solution of N, N-dimethylformamide in benzene. Phosgene (9.9 g; 100 mmol), dissolved in toluene (200 ml), was added dropwise from the cooled dosing funnel with constant stirring and sparging of argon. The mixture was stirred at room temperature during 12 hr, and conversion to 2-cyanoacryloyl chloride was monitored by *H ΝMR. If residual 2-cyanoacrylic acid was detected, additional small portions of phosgene in toluene were added in order to complete its transformation into 2-cyanoacryloyl chloride. The excess of phosgene together with volatile by-products were removed by the distillation of toluene (300 ml) in vacuo at

30°C to leave a yellow transparent solution (100 ml) of 2- cyanoacryloyl chloride in toluene. H ΝMR in CgDg : toluene 1 : 3 δ 5.40 and 5.92 (2s, each 1H, 2d, H_aH_bC=C-) p.p.m.

Example 5

Preparation of the 2-cvanoacrylate ester of 1 ,4-butanediol monomethacrylate

A solution of 2-cyanoacryloyl chloride in jp-xylene prepared from 2-cyanoacrylic acid (2.0 g) according to Example 3 was continuously sparged with dry nitrogen and stirred at 40°C. To this was added dropwise a solution of 1,4-butanediol monomethacrylate (2.9 g) in dry benzene (100 ml). The mixture was stirred at 40°C with continuous sparging of nitrogen during 5 hr. The nitrogen was then replaced by sulfur dioxide and solvent (100 ml) was removed at 55°C by distillation in vacuo. Dry charcoal (0.1 g) was added and the mixture was filtered. γ-Propanesultone (0.1 mg) was added using a stock solution in benzene and remaining solvent was distilled off in vacuo to give a yellow oil. Benzene (50 ml) and dry charcoal (0.1 g) were added, the mixture was filtered, and solvent was again distilled off in vacuo to give the title compound as a colourless oil (4.3 g). -^*H NMR in C₆D₆ δ 1.48 (4H, m, -OCH₂C#2C /2CH₂0-). 1.91 (3H, s,

CH₃C=C-), 3.98 (4H, m, OC//2CH₂CH₂C//₂O-), 5.37 (1H, s, CH_a=C(CH₃)), 5.79 (1H, s, CH_a=C(CN), 6.18 (1H, s, CH_b=C(CH₃) and 6.46 (1H, s, CH_b-C(CN)) p.p.m.

Example 6

Preparation of the 2-cyanoacryloyl chloride as a solution in benzene using 1.1 -dichloromethyl methyl ether as reagent

2-Cyanoacrylic acid (0.5 g; 5.15 mmol) was dissolved with heating in dry benzene (50 ml). Benzene (10 ml) was removed by distillation in order to ensure anhydrous conditions. The resulting solution was filtered into a 100 ml flask provided with a mechanical stiiTer, an argon inlet adaptor and a condenser. The solution was cooled to 40°C and 1,1 -dichloromethyl methyl ether (6.35 g; 5.6 mmol) was added with stirring. The mixture was refluxed during 4 hr with continuous stirring and sparging of argon. Conversion to 2- cyanoacryloyl chloride was monitored by ^!H NMR. If residual 2- cyanoacrylic acid was detected, additional small portions of 1,1- dichloromethyl methyl ether were added in order to complete its transformation into 2-cyanoacryloyl chloride. Ethyl furfurylidenecyanoacetate (5 mg) was then added, and excess 1,1- dichloromethyl methyl ether together with volatile by-products were removed by the distillation of benzene (20 ml) in vacuo to give a transparent solution (20 ml) of 2-cyanoacryloyl chloride in benzene. ^XH NMR in C₆D₆ : C₆H₆ 1 : 1 δ 5.30 and 5.84 (each IH, 2d, 7 = 1.27

Hz, H_aH_bC=C-) p.p.m., 13c NMR 112.8 (CN), 119.5 (=C(CN)COCl), 146.0 (CH₂=) and 161.8 (C=0) p.p.m.

Claims

Claims: -

1. A process for the preparation of 2-cyanoacryloyl chloride, which comprises reacting 2-cyanoacrylic acid with a chlorinating agent, said reaction being carried out under side- reaction and polymerisation inhibiting conditions.

2. A process according to Claim 1, wherein the reaction of 2-cyanoacryhc acid with the chlorinating agent is carried out under side-reaction and polymerisation inhibiting conditions to give a solution of 2-cyanoacryloyl chloride, optionally followed by isolation of 2-cyanoacryloyl chloride under polymerisation inhibiting conditions.

3. A process according to Claim 1 or 2, wherein a volatile chlorinating agent is used which does not form non- volatile by¬ products during the reaction.

4. A process according to Claim 3, wherein the volatile chlorinating agent is oxalyl chloride, sulfur oxychloride, trifluoroacetyl chloride, phosgene or 1,1 -dichloromethyl methyl ether.

5. A process according to Claim 4, wherein the volatile chlorinating agent is oxalyl chloride or 1,1 -dichloromethyl methyl ether.

6. A process according to any preceding claim, wherein the reaction conditions are such as to inhibit the formation of acidic or acidogenic by-products.

7. A process according to any preceding claim, wherein the polymerisation inhibiting conditions are such as to inhibit the formation of non- volatile polymeric products otherwise resulting from a side or polymerisation reaction.

8. A process according to Claim 7, wherein the polymerisation inhibiting conditions result from the use of a solvent which dissolves the reactants and any intermediate mixed anhydride formed but not the 2-cyanoacryloyl chloride which precipitates out on cooling.

9. A process according to Claim 8, wherein the solvent is an excess of the volatile chlorinating agent.

10. A process according to any one of Claims 1-7, wherein the polymerisation inhibiting conditions are achieved by lowering the reaction temperature to a temperature lower than the polymerisation initiating temperature.

11. A process according to Claim 10, wherein the reaction is carried at a temperature in the range -10°C to 110°C.

12. A process according to Claim 10 or 11, wherein the reaction is carried out at a temperature in the range 0 to 70°C.

13. A process according to any one of Claims 1-7, wherein the polymerisation inhibiting conditions are achieved by driving off any by-products capable of initiating polymerisation.

14. A process according to Claim 13, wherein the volatile by-products are driven off by sparging with an inert gas.

15. A process according to Claim 14, wherein the inert gas is argon or nitrogen.

16. A process according to any one of Claims 1-7, wherein the polymerisation inhibiting conditions are achieved by the use of a catalyst which forms an intermediate complex with the chlorinating agent, thereby preventing the formation of a mixed anhydride.

17. A process according to Claim 16, wherein the catalyst is N, N-dimethylformamide.

18. Substantially pure 2-cyanoacryloyl chloride.

19. A solution of 2-cyanoacryloyl chloride uncontaminated with non-volatile acids or mixtures thereof.