GB1570319A - Process for the manufacture of cyclopropanecarbonitrile - Google Patents

Abstract

Cyclopropanecarbonitrile is prepared from 4-halobutyronitrile in the presence of alkali metal oxides, alkali metal hydroxides, alkaline earth metal oxides or alkaline earth metal hydroxides by employing 4-halobutyronitrile and alkali metal oxide, alkali metal hydroxide, alkaline earth metal oxide or alkaline earth metal hydroxide in a molar ratio of 1:1 to 1:3.5 and carrying out the reaction in an inert solvent in the presence of a phase transfer catalyst at temperatures between 40 and 150 DEG C. Cyclopropanecarbonitrile is a valuable intermediate in the preparation of agrichemicals.

Description

(54) PROCESS FOR THE MANUFACTURE OF CYCLOPROPANECARBONITRILE (71) We, CIBA-GEIGY AG, a body corporate organised according to the laws of Switzerland, of Basle, Switzerland, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to a new process for the manufacture of cyclopropanecarbonitrile.

Cyclopropanecarbonitrile has proven to be a valuable as well as a versatile compound.

Its primary function has been a source of the cyclopropyl group in the preparation of agricultural chemicals, such as N-cycloalkyl anilines, whose performance characteristics are improved by the presence thereon of the cyclopropyl group.

Prior art methods for preparing cyclopropanecarbonitrile have involved reacting, at generally high reaction temperatures, a halobutyronitrile with an alkali metal hydroxide or sodium amide. For example, the use of potassium and sodium hydroxides has been disclosed in Nicolet et al., Journal of the American Chemical Society, 49,2068 (1927), and Cloke, Journal of the American Chemical Society, 51,1180 (1929), while the use of sodium amide has been disclosed in Schlatter, Journal of the American Chemical Society, 63,1734 (1941). However, certain difficulties have been encountered with these procedures.

Thus, sub-standard yields of product have generally been recovered, the reaction with the hydroxides generally showing yields of 4055% and the reaction with the amide showing yields around 60%. Such low yields of product have generally resulted from troublesome side reactions as well as difficult and prolonged distillation operations.

In addition, the prior art procedures have not been readily adaptable to commercial scale-up, due, in part, to the potentially violent reaction with sodium amide and to the previously noted involved distillation operations. United States Patent 3,853,942 discloses a process for preparations of cyclopropanecarbonitrile by reacting at elevated temperatures halobutyronitrile with an alkali metal alkoxide in an inert solvent and removing the alcohol formed, but the alkali metal alkoxide is a comparatively expensive and difficult to handle reactant and therefore where possible it is desirable to avoid the use of this material.

In accordance with this invention there is provided a process for preparing cyclopropanecarbonitrile comprising reacting a 4 - halobutyronitrile with an alkaline metal or alkaline earth metal oxide or hydroxide in a molar ratio of said nitrile to said oxide or hydroxide of about 1:1 to about 1:3.5, the reaction being carried out in the presence of a phase transfer catalyst, the reaction medium being an inert organic solvent and the reaction temperature being maintained at about 400 C. to about 1500C.

The novel process of this invention is seen to proceed according to the following equation:

wherein X is selected from chlorine or bromine; and M is an alkali metal or alkaline earth metal.

Thus, 4 - chlorobutyronitrile, 4 - bromo butyronitrile and mixtures thereof are applic able for use in the process of this invention.

The 4-chlorobutyronitrile is the preferred halobutyronitrile. Methods for preparing such nitriles are known; reference in this regard may be made to the JACS articles and U.S.

Patent 3.853,942 noted hereinabove. These nitriles are typically prepared bv the anhy drous free radical reaction of allyl chloride and hydrogen halide in the presence of benzovl peroxide, followed by the reaction of the resulting trimethylenechlorohalide in 50% excess, with sodium cyanide, in ethanol-water medium.

The second reactant utilized in the process of this invention is an alkali metal or alkaline earth metal oxide or hydroxide selected from the first and second columns of the Periodic Table. The useful alkali metals of the first column are lithium, sodium, potassium and rubidium with sodium and potassium being particularly preferred. Useful alkaline earth metals of column 2 include magnesium, calcium, strontium, and barium. Useful oxides include calcium oxide, sodium oxide and potassium oxide. Preferred as second reactants are potassium hydroxide and sodium hydroxide. In carrying out this process particularly useful results are obtained when the ratio of nitrile reactant to oxide or hydroxide reactant is in the range of from about 1:1 to about 1:3.5 and more preferably from about 1:1.2 to about 1:2.5 moles. A very useful molar ratio of nitrile to oxide or hydroxide is about 1:1.5 to about 1:2. Since there is a need to avoid hydrolysis of the cyclopropanecarbonitrile final product (which is often called cyclopropylnitrile for convenience) it is beneficial to employ larger than stoichiometric amounts of the hydroxide or oxide in order to increase the reaction rate. In carrying out the process of this invention the oxide or hydroxide can be in any of the usual forms commercially available, e.g. flake, pellet, or powder, and especially beads or pellets. Liquid forms of the hydroxide can also be employed.

The reaction is conducted in an inert organic solvent, the choice of solvent being dependent upon the temperature at which it is desired to conduct the reaction. Optionally, the process can be conducted with or without the removal of water formed in the reaction as is shown in the examples. Suitable solvents for use in the process of this invention include non-fused ring aromatics such as benzene, toluene, and xylene; lower haloalkanes and lower haloalkylenes having 1 to 6 carbon atoms such as methylene chloride, trichloro trifluoroethane, 1,2-dichloroethylene, carbontetrachloride, trichloroethylene, and tetrachlorodifluoroethane; alkanes of 5 to 8 carbon atoms such as pentane, hexane, heptane, octane and petroleum ethers which are various hydrocarbon mixtures of the foregoing alkanes, as well as cycloalkanes and cycloalkenes such as cyclohexane, cyclohexene, and cyclopentane. Combinations of these solvents may be employed to achieve a particular combination of reaction temperatures such as a mixture of toluene and methylene chloride. Particularly preferred inert organic solvents are benzene, toluene and methylene chloride, with methylene chloride being the solvent of choice.

The amount of solvent can vary over a large range with the least amount of solvent being that sufficient to have a workable reaction slurry and sufficient volume to dissipate the heat generated by the reaction. For instance when benzene, toluene or methylene chloride is the solvent, as little as one volume of solvent can be successively employed to three volumes of the nitrile reactant, and a volume ratio of one to one is quite suitable with larger amounts such as three to one hundred volumes of solvent per volume of nitrile reactant being useable although the volumes of solvent are less convenient to handle.

The phase transfer catalyst is an essential component required in the practice of the present invention. The concept of phase transfer catalysts has been reported in the literature for a number of reactions, and a large number of catalytic compounds known to be useful for the production of alkyl nitriles can be used herein. Examples include quaternary ammonium, phosphonium, sulphonium, arsonium salts, of which quaternary ammonium halides are preferred. Examples of specific compounds useful as phase transfer catalysts are tetramethylammonium chloride, tributylmethylammonium chloride, tetrabutylammonium bromide, cetyltrimethylammonium bromide, benzyltrimethylammonium bromide, tricaprylylmethylammonium chloride, octyltrimethylammonium chloride, dodecyltri methylammonium chloride, benzyltriethylammonium chloride, dibenzyldiethylammonium nitrate, diethyldipropylammonium sulfate, dihexyldimethylammonium iodide, tetrabutylammonium hydrogen sulfate, tetrabutylphosphonium bromide, tetraethylphosphonium chloride, dioctadecenyldimethylammonium chloride, ethyltribenzylphosphonium fluoride, cetyltrimethylphosphonium acetate, tricaprylylethylphosphonium nitrate, tributylhexadecylphosphonium bromide, tributylsulphonium bromide, tetrabutylphosphonum bromide and diethyldibenzylarsonium nitrate. Particularly preferred are tributylmethylammonium chloride, tricaprylylmethylammonium chloride and tetrabutvlammonium bromide.

The amount of phase transfer catalyst which can be used can vary from a small amount such as 0.002 mole or less per mole of the nitrile reactant up to an amount exceeding the stoichiometric amount required to displace the halogen component of the nitrile reactant.

The amount of catalyst preferably used because of economic considerations is from about 0.002 to about 0.10 mole and more preferably 0.002 to about 0.02 mole per mole of nitrile reactant.

The conditions under which the reaction of the above reactants can be conducted can vary depending upon the reactants employed. Since reaction pressures can vary from superatmospheric to subatmospheric, the reaction temperatures can be substantially higher than 100"C. or as low as 40"C. Careful selection of reaction temperatures and pressures can minimize the formation of undesirable byproducts, and such selection of optimum reaction temperatures, pressures and other operating conditions therefore constitutes a preferred embodiment of this invention. Preferred reaction temperatures for halobutyronitrile and alkali metal oxides are from about 500 to about 1200 C. A reaction temperature of from about 60 to about 1100 C. is particularly preferred. Reaction pressures are most conveniently maintained at atmospheric pressure, but pressures from 0.1 or less up 10 or more atmospheres are included within the scope of this invention.

From the foregoing discussion it will be seen that the time of conducting the reaction will vary over a considerable time span depending upon the temperature employed which will generally be from a few minutes to up to about 10 hours. It is an advantage of the process of this invention that as soon as all of the nitrile reactant has been consumed in the reaction, the reaction can be terminated without a post-holding or treating period which is typical of many other reactions. In fact the elimination of this post-holding period has a beneficial effect, namely further reducing the possibility of hydrolysis of the cyclopropanecarbonitrile final product obtained. In general, the formation of a high proportion of cyclopropanecarbonitrile can be obtained by conducting the reaction at a temperature below llO"C.

Two preferred combinations of reactants and reaction conditions are as follows:- A: The 4-halobutyronitrile is a mixture of 4-chlorobutyronitrile and 4-bromobutyronitrile, the molar ratio of said nitrile reactant to said hydroxide is about 1:1.5, and the reaction is carried out in the presence of about 0.003 mole of tricaprylylmethyl ammonium chloride phase transfer catalyst, the reaction medium being benzene and the reaction temperature being between 75"C and 80"C.

B: The 4-halobutyronitrile is a mixture of 4-chlorobutyronitrile annd 4-bromobutyronitrile, the alkali metal hydroxide is sodium hydroxide, the molar ratio of said nitrile reactant to said hydroxide being about 1:2, the reaction being carried out in the presence of about 0.01 mole of tributylmethylammonium chloride as phase transfer catalyst, the reaction medium being methylene chloride, and the reaction temperature being maintained at 600 to 70"C.

As previously indicated, this process ensures the formation of pure cyclopropanecarbonitrile in high yields. The resulting compound may then be further synthesized into biologically active materials for agricultural and pharmaceutical application. For example, the cyclopropanecarbonitrile may be reacted with n-propylamine in the presence of a platinum metal catalyst to form cyclopropylmethylpropylamine which can then be reacted according to the disclosures of U.S. Pat. No.

3,546,295 to prepare N-cycloalkylaniline herbicidal compounds. Alternatively, the cyclopropanecarbonitrile may be converted to cyclopropylamine which may, in turn, be reacted with cyanuric chloride to form cyclo proDylamino-substituted-s-triazine herbicides.

The following examples are included to illustrate the process of the present invention, but are not to be considered limiting. Unless otherwise specified, all parts are parts by weight and all temperatures are expressed as to degrees centigrade.

A typical reaction was carried out in a oneliter, round-bottom flask fitted with a stirrer, thermometer, Dean-Stark trap, and reflux condenser. The flask was charged with .250 ml of benzene, 1.5 moles of MOH (M = Na, K), and the desired quantity of tricaprylyl methyl ammonium chloride, a phase transfer catalyst commercially available under the name Aliquat 336. The mixture was heated to reflux and 1.0 mole of mixture (in a weight ratio of about 3:1) of 4-chlorobutyronitrile and 4-bromobutyronitrile added rapidly from a dropping funnel. Refluxing was continued until all the halobutyronitrile had been consumed as indicated by gas chromatograph analysis. At this point, the mixture is cooled to ambient temperature and 250 ml of water added to dissolve all salts present. The phases are separated and the aqueous phase extracted with 100 ml of benzene to obtain additional cyclopropanecarbonitrile dissolved in the water.

The benzene solutions are combined and distilled at 200 mm mercury to give pure cycloprooanecarbonitrile, hereinafter referred to as CPN, in vields of 90% or greater. The benzene forecut containing small amounts of CPN is recycIed to a subsequent reaction.

The distillation was accomplished using a 2' X 1" column packed with 1/4" Intalox saddles and reflux ratio of 3:1.

The results from various reactions are summarized in Table I below. All gas chromatograph analyses were carried out on a "Varian 1700" gas chromatograph equipped with a 10% "Reoplex 400" on Chromasorb W column (6' X 1/4") at 160"C. Results are based on a weight standard of an authentic sample of CPN. "VARIAN" and "REO PLEX" are Registered Trade Marks.

By way of comparison U.S. Pat. No.

3,853,942 at Example IV shows a product yield of cyclopropanecarbonitrile of 84 to 85% and Example III shows a product yield of cyclopropanecarbonitrile of 87 to 88% when potassium methoxide and sodium ethoxide, respectively, are used in the process claimed by that patent. The patent further shows in Example VI that when 4-chlorobutyronitrile is reacted with potassium hydroxide in a toluene slurry, no catalyst being present, that the product yield of cyclopropanecarbonitrile is 64 to 65%.

PREPARATION OF CYCLOPROPYLNITRILE (CPN) Example Base Time (hrs) a Yield (%) b Catalyst Level c 1 NaOH Powdered Technical Flakes - Only 20% complete after 4 hrs None 2 NaOH Technical Flakes - Only 7% complete after 5 hrs None 3 NaOH Powdered Technical Flakes - Only 28% complete after 6 hrs None 4 KOH Reagent Pellets 3.5 96 None initially 2% after 2.5 hrs 5 NaOH Reagent Pellets 6 90 None initially 2% after 2.5 hrs 6 NaOH Technical Beads 4 92 0.3% initially 1.0% after 1 hrs 2.0% after 2 hrs 7 NaOH Powdered Technical Flakes 4 91 0.3% initially 1.0% after 1 hr 2.0% after 2 hrs 8 NaOH Technical Flakes 4.5 93 0.9% initially 1.8% after 1.5 hrs a) Time required for complete conversion of starting material. b) Yield by gas chromatograph assay. c) Catalyst charge is percent by weight of the halobutyronitrile charged.

Additional series of experiments both in the laboratory and in the pilot plant were conducted with different phase transfer agents and solvents and otherwise varying reaction conditions to further support the scope of this invention. The effect of these variations and modifications is shown in the following illus trative examples.

Example 9.

A 1-liter 5-neck round-bottom flask fitted with a stirrer, thermometer, a Dean-Stark trap with a condenser, an addition funnel and a sampler served as a reactor. A vacuum take off was attached to the top of the condenser.

There was charged to the reactor 250 g. of toluene, 5.7 g. of catalyst (Aliquat 336), 114.3 g. of NaOH beads and then a vacuum was turned on and when 115 mm of pressure was reached the reaction mixture was heated to 60 and 188.6 g. of 4-chlorobutyronitrile/ 4 - bromobutyronitrile (CBN/BBN - 3:1) was charged from the addition funnel. The reaction was maintained at reflux, azeotropically removing the water formed in the reaction.

After all the halobutyronitriles had reacted as determined by sampling the reaction mixture and analyzing by G.C., the mixture was cooled to 2530 and the vacuum was broken. 343 g. water was charged to the reactor and the mixture was stirred to dissolve the salts. The lavers were senarated and samples were submitted for G.C. analysis. Yield of product in the organic layer was 95.7%.

Example 10.

A liter 5-neck round-bottom flask fitted with a stirrer, thermometer, condenser, addition funnel, and sampler served as a reactor.

There was charged to the reactor 160 g. of NaOH (beads), 144 g. of methylene chloride, 8 g of Aliquat 336 and 254 g. of CBN/BBN (3:15. This reaction mixture was then heated to reflux ( 650) until all the CBN/BBN had reacted. After completion, the mixture was cooled to 450 and 480 g. of water was added and the mixture was stirred to dissolve the salts formed. The layers were separated and each was sampled for G.C. assay. The yield of desired product in the organic layer was 99.3%.

Example 11.

The procedure of Example 10 was repeated except that 7.4 g. of a 74% aqueous solution of tributylmethylammonium chloride as catalyst, and 210 g. of distilled CBN/BBN (48:1) were used. The yield was close to quantitative.

Example 12.

The procedure of Example 10 was repeated except that 2 g. of Aliquat 336 was employed.

The reaction time was 8.5 hours and the yield was close to quantitative.

Example 13.

The procedure of Example 9 was repeated except that 4 g. of tetrabutylammonium bromide, 80 g. of NaOH pellets and 130 g. of CBN/BBN (3:1) were used. The yield was 94.7%.

Example 14.

The best mode of carrying out the subject process on a large scale which was determined after a series of pilot plant experiments, can be exemplified bv the following procedure: To a 300 gallon reaction vessel (PV-3 1), equipped with a variable speed turbine agitator, is charged 19 lobs of a 74% aqueous solution of tributylmethylammonium chloride, 506 Ibs of methylene chloride and 851 Ibs of CBN/BBN (3:16.53 moles). With the agitator on slow steed 539 lbs of sodium hvdroxide pellets (13.48 moles) is charged.

The vessel is set for total reflux and the agitator turned on full speed. The vessel is then heated to reflux (62670) rapidly with hot water on the jacket. The reaction mixture is held at reflux until the reaction is complete (usually in about 3-5 hours) as determined by G.C. analysis of 1 ounce samples taken every hour. Then the mixture is rapidly cooled to 45" or less with cold water. Water (1615 lbs-195 gallons) is then charged to the vessel under moderate agitation. This agitation is continued for about 20 minutes. The agitator is then turned off and the mixture allowed to settle for 30 minutes. The organic layer is then separated from the water layer. The solvent is then distilled off and the product recovered. Yield: about 95%.

This procedure, which employs tributylmethylammonium chloride as catalyst, solid sodium hydroxide in the form of pellets, methylene chloride and is carried out under total reflux at a temperature of about 63 67" and thus without removal of water during the reaction and with vigorous agitation (which is very important), exhibits important advan tages in large-scale manufacture over prior art procedures in terms of higher yields (about 95%), increased capacity, decreased manu facturing costs, improved safety and reduced effluent loads.

Summarizing, it is seen that this invention provides a vastly improved process for the preparation of cyclopropanecarbonitrile. The foregoing examples and methods have been described in the foregoing specification for the purpose of illustration and not limitation.

Many other modifications and ramifications will naturally suggest themselves to those skilled in the art based on this disclosure.

These are intended to be comprehended as within the scope of this invention.

Claims (24)

WHAT WE CLAIM IS:

1. A process for preparing cyclopropane carbonitrile comprising reacting a 4-halobutyronitrile with an alkali metal or alkaline earth metal oxide or hydroxide in a molar ratio of said nitrile to said oxide or hydroxide of about 1:1 to about 1:3.5, the reaction being carried out in the presence of a phase transfer catalyst, the reaction medium being an inert organic solvent and the reaction temperature being maintained at about 400 C. to about 1500C.

2. The process of Claim 1 wherein said hydroxide is an alkali metal hydroxide.

3. The process of Claim 2 wherein said hydroxide is sodium hydroxide.

4. The process of Claim 2 wherein said hydroxide is potassium hydroxide.

5. The process of any preceding Claim wherein said nitrile reactant is 4-chiorobutyro- nitrile.

6. The process of any one of Claims 1 to 4 wherein said nitrile reactant is a mixture of 4-chlorobutyronitrile and 4-bromobutyronitrile.

7. The process of any preceding Claim wherein said phase transfer catalyst is a quaternary ammonium or phosphonium compound.

8. The process of Claim 7 wherein said phase transfer catalyst is a quaternary ammonium halide.

9. The process of Claim 8 wherein said quaternary ammonium halide is tributylmethyl ammonium chloride.

10. The process of Claim 8 wherein said quaternary ammonium halides is tricaprylylmethyl ammonium chloride.

11. The process of any preceding Claim wherein said reaction temperature is from about 500 to about 1200C.

12. The process of Claim 11 wherein said reaction temperature is from about 600 to about llO"C.

13. The process of any preceding Claim wherein said molar ratio is from about 1:1.2 to about 1:2.5.

14. The process of Claim 13 wherein said molar ratio is from about 1:1.5 to about 1:2.

15. The process of any preceding Claim wherein said solvent is an aromatic solvent.

16. The process of Claim 15 wherein the solvent is benzene.

17. The process of Claim 15 wherein the solvent is toluene.

18. The process of any one of Claims 1 to 14 wherein said solvent is a halo (lower) alkane.

19. The process of Claim 18 wherein said solvent is methylene chloride.

20. The process of Claim 1 wherein the 4-halobutyronitrile is a mixture of 4-chlorobutyronitrile and 4-bromobutyronitrile, the molar ratio of said nitrile reactant to said hydroxide is about 1:1.5, and the reaction is carried out in the presence of about 0.003 mole of tricapyrylmethyl ammonium chloride phase transfer catalyst, the reaction medium being benzene and the reaction temperature being between 750 and 80"C.

21. The process of Claim 1 wherein the 4-halobutyronitrile is a mixture of 4-chlorobutyronitrile and 4-bromobutyronitrile, the alkali metal hydroxide is sodium hydroxide, the molar ratio of said nitrile reactant to said hydroxide being about 1:2, the reaction being carried out in the presence of about 0.01 mole of tributylmethylammonium chloride as phase transfer catalyst, the reaction medium being methylene chloride, and the reaction temperature being maintained at 600 to 700C.

22. The process of any one of Claims 1 to 4 wherein said nitrile reactant is 4-bromobutyronitrile.

23. The process of Claim 1 substantially as described in any one of Examples 4 to 10.

24. Cyclopropanenitrile when prepared by the process of any of Claims 1 to 23.