DE69616005T2 - METHOD FOR PRODUCING 3,3,5-TRICHLORGLUTARIMIDE - Google Patents

Description

The present invention relates to a process for the preparation of 3,3,5-trichloroglutarimide, wherein a 2,2,4-trichloro-4-cyanobutyric acid derivative is converted to the desired glutarimide compound.

2,3,5,6-Tetrachloropyridine and 3,5,6-trichloropyridin-2-ol, which can be obtained from it by hydrolysis, are valuable intermediates in the preparation of various active substances, in particular insecticides, herbicides and fungicides (see, for example, U.S. Patent Nos. 4,133,675, 3,244,586, 3,355,278 and 3,751,421; French Patent No. 2,171,939 and also J. Agr. Food Chem. 14, 304 (1966)). The known processes for the preparation of 2,3,5,6-tetrachloropyridine are unsatisfactory in various respects. 2,3,5,6- Tetrachloropyridine can be obtained by high temperature chlorination (about 200-600°C, preferably about 350-600°C) of pyridine or pyridine derivatives such as 3,5-dichloropyridine. Such high temperature processes are usually not selective since they lead to the formation of other highly chlorinated by-products which must be removed. One such by-product is pentachloropyridine, which can be converted to 2,3,5,6-tetrachloropyridine by selective reduction of the chlorine atom in the 4-position, either with zinc or electrolytically. However, zinc is expensive and large amounts of zinc salts are typically formed, a factor that is undesirable from an ecological point of view. In addition, high temperature chlorination, electrolytic reduction and the production of zinc require large amounts of energy.

US Patent No. 4,327,216 (Martin) describes a process for preparing 2,3,5,6-tetrachloropyridine and 3,5,6-trichloropyridin-2-ol by reacting trichloroacetyl chloride with acrylonitrile in the presence of a catalyst. Apparently 2,2,4-trichloro-4-cyanobutanoyl chloride is formed as an intermediate, but it is not isolated. The series of reactions responsible for the formation of the final products is carried out in a single operation and the combined yield of 2,3,5,6-tetrachloropyridine and 3,5,6-trichloropyridin-2-ol is not very high. Furthermore, the reaction typically produces a mixture of the two products which must be treated in subsequent operations to obtain only one of these products.

U.S. Patent No. 4,996,323 (Pews) discloses a process for preparing 3,5,6-trichloropyridin-2-ol by carrying out the following three separate reactions: trichloroacetyl chloride is added to acrylonitrile in the presence of a catalytic amount of copper or a cuprous salt to form 2,2,4-trichloro-4-cyanobutanoyl chloride; the 2,2,4-trichloro-4-cyanobutanoyl chloride is cyclized by contacting it with acidic reagents, preferably in an anhydrous state, to form 3,3,5,6-tetrachloro-3,4-dihydropyridin-2-one, and hydrogen chloride can be eliminated from this dihydropyridinone compound to give 3,5,6-trichloropyridin-2-ol in an aromatization reaction. However, the dihydropyridinone compound can alternatively lose water to give 2,3,5,6-tetrachloropyridine. The water produced as a byproduct during the formation of 2,3,5,6-tetrachloropyridine contributes significantly to yield losses due to numerous side reactions.

U.S. Patent No. 5,017,705 (Becker) discloses a process for preparing 3,5,6-trichloropyridin-2-ol by cyclizing an aryl 4-cyano-2,2,4-trichlorobutyrate of the formula I:

NC-CHCl-CH2 -CCl2 -COOAr (I)

wherein Ar represents an optionally substituted aryl or heteroaryl radical, by heating the compound of formula I to between 100°C and 180°C in an inert organic solvent in the presence of anhydrous hydrogen chloride to form 3,5,6-trichloropyridin-2-ol. It is taught that the presence of dry hydrogen chloride gas in the reaction medium is essential to effect cyclization.

US-A-4,360,676 (Martin et al.) discloses that 2,3,5,6-tetrachloropyridine can be prepared by cyclization of 2,2,4-trichloro-4-cyanobutanecarboxamide or 2,2,4-trichloro-4-cyanobutyronitrile (2,2,4-trichloroglutaronitrile) in an aqueous acidic medium to give 3,3,5-trichloroglutarimide and converting this imide compound to the desired 2,3,5,6-tetrachloropyridine product (via an aromatization reaction with dehydration of the dicarboxylic acid imide functions and simultaneous elimination of a hydrogen chloride group and a chlorination reaction). The cyclization reaction is carried out at temperatures between about -10°C and 120°C, preferably between about 60°C and 110°C, using an acid such as acetic acid, hydrochloric acid or sulfuric acid. The following materials are described as suitable dehydrating, chlorinating agents for the conversion of 3,3,5-trichloroglutarimide to 2,3,5,6-tetrachloropyridine: phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride, phenylphosphonic acid dichloride and phosgene. Under certain circumstances, catalytic amounts of N,N-dimethylformamide are also added to the aromatization reaction mixture.

The present invention relates to a process for the preparation of 3,3,5-trichloroglutarimide by cyclization of 4-cyano-2,2,4-trichlorobutanoyl chloride. More particularly, the invention relates to a process for the preparation of 3,3,5-trichloroglutarimide, which is characterized by combining 4-cyano-2,2,4-trichlorobutanoyl chloride with a nearly stoichiometric amount of water sufficient to react with all of the 4-cyano-2,2,4-trichlorobutanoyl chloride and any impurities in an inert organic solvent at a temperature between 20°C and 50°C to obtain a mixture of 3,3,5-trichloroglutarimide and 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one, and heating the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one in the presence of water and an inert organic solvent to between 90°C and 100°C, wherein the 3,3,5,6-Tetrachloro-5,6-dihydropyridin-2-one is converted to 3,3,5-trichloroglutarimide.

The process according to the invention represents a different approach to the preparation of 3,3,5-trichloroglutarimide. The invention requires fewer and simpler process steps to prepare 3,3,5-trichloroglutarimide than the processes from the known prior art. 3,3,5-trichloroglutarimide can be prepared in high yield and without significant amounts of by-products. using starting materials that are relatively inexpensive compared to prior art processes for the preparation of 3,3,5-trichloroglutarimide.

The cyclization reaction of the present invention is carried out using nearly stoichiometric amounts of 4-cyano-2,2,4-trichlorobutanoyl chloride and water, although water is preferably used in slight excess. The stoichiometric amount of water is 1 mole for each mole of 4-cyano-2,2,4-trichlorobutanoyl chloride used. The amount of water used is important because sufficient water must be added to react with all of the 4-cyano-2,2,4-trichlorobutanoyl chloride and any impurities in the reaction mixture that can react with water. The water required to convert 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one to 3,3,5-trichloroglutarimide can be added before and during the cyclization reaction, or after the cyclization reaction is complete. In general, higher molar ratios of water result in faster and more complete conversions of 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one to 3,3,5-trichloroglutarimide, but excessive amounts of water can result in reduced purity of the isolated 3,3,5-trichloroglutarimide product and unidentified impurities that are difficult to separate from the 3,3,5-trichloroglutarimide. Typically, a total amount of 1 to 5 moles of water (for both reactions) is used for each mole of 4-cyano-2,2,4-trichlorobutanoyl chloride used. Preferably, 1.2 moles of water is used for each mole of 4-cyano-2,2,4-trichlorobutanoyl chloride used. This water is preferably added slowly to the solution of 4-cyano-2,2,4-trichlorobutanoyl chloride in the organic solvent, i.e. before and during the cyclization reaction. This slow water addition maximizes the yield and purity of the final product 3,3,5-trichloroglutarimide.

The cyclization reaction and the reaction of 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one with water to produce additional glutarimide product generally takes place in an inert organic solvent. In general, the term "inert organic solvent" is intended to mean a solvent which does not react with acid chlorides, other starting components of the reaction mixture, or any of the reaction products. It has been found that xylenes and tetrachloroethylene are particularly suitable solvents.

The cyclization reaction and the subsequent reaction of 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one with water are carried out under suitable reaction conditions. The term "suitable reaction conditions" is used herein to mean a pressure and temperature at which these two reactions can proceed to substantial completion. Although pressure is not believed to be a critical parameter, atmospheric pressure is typically used. The cyclization reaction, which is exothermic, should also preferably be carried out slowly and the reaction mixture should be cooled so that the pot temperature can be maintained at a temperature between 20°C and 50°C. The duration of the cyclization reaction is generally a function of the reaction temperature and, in particular, the amount of water present in the reaction vessel. However, temperatures for the cyclization reaction and molar ratios of water higher than those given above can be detrimental to the yield and/or purity of the final product. On the other hand, a temperature that is too low during the cyclization reaction can lead to phase separation of the reactants, which results in the absence of any reaction.

The conversion step of the process from 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one to 3,3,5-trichloroglutarimide typically requires 10 hours or more to achieve high conversions. Typically, after cyclization of 4-cyano-2,2,4-trichlorobutanoyl chloride to yield a mixture of 3,3,5-trichloroglutarimide and 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one, the resulting mixture is heated to between 90°C and 100°C to convert the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one to 3,3,5-trichloroglutarimide. However, it is conceivable that the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one and/or the 3,3,5-trichloroglutarimide could be separated from the mixture using known separation techniques (e.g., recrystallization), and the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one could be heated to between 90°C and 100°C with water and inert organic solvent to convert the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one to 3,3,5-trichloroglutarimide.

The 3,3,5-trichloroglutarimide prepared by the process of the invention can be recovered or used as an intermediate without recovery and/or purification in a subsequent chemical process. For example, after the reaction of 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one with water, the reaction mixture is typically cooled, e.g. to 20°C, and filtered to give a wet cake which is typically washed and dried to give 3,3,5-trichloroglutarimide in high yield and purity.

The 3,3,5-trichloroglutarimide can be converted to 2,3,5,6-tetrachloropyridine, according to methods known in the art, for example, by treating the 3,3,5-trichloroglutarimide with a dehydrating chlorinating agent, e.g., phosphorus oxychloride, as disclosed in US-A-4,360,676. If desired, 3,5,6-trichloropyridin-2-ol can be prepared by the hydrolysis of 2,3,5,6-tetrachloropyridine, as known in the art.

The following examples are given to illustrate the invention. All solvents and reagents were purchased from commercial suppliers without further purification except as indicated. All parts or percentages listed are by weight unless otherwise stated.

Preparation example of 4-cyano-2,2,4-trichlorobutanoyl chloride

Acrylonitrile, trichloroacetyl chloride, and copper were purchased from Aldrich Chemical Company. The reaction vessel was a 250 mL (milliliter) three-necked round bottom flask equipped with a magnetic stirrer, reflux condenser, nitrogen inlet, heating mantle, and temperature probe. To this reaction vessel were added 45.3 g (grams) (0.86 moles) of acrylonitrile, 164.1 g (0.9 moles) of trichloroacetyl chloride, and 0.36 g (0.0057 moles) of copper. This mixture was heated under a nitrogen blanket for 28 hours at reflux temperature (the pot temperature increased with increasing conversion; when the percent conversion was in the mid twenties as determined by gas liquid chromatography ("GLC"), the reflux temperature was about 90ºC, and when the percent conversion was in the mid thirties as determined by GLC, the reflux temperature was about 95-100ºC). When the Determining percent conversion to be about 40% as determined by GLC, the system was set up for short path vacuum distillation and 27 g of o-xylene was added. An additional dry ice trap was placed immediately adjacent to the distillation head to catch any material that did not condense out in the distillation head. Distillation was carried out for about 1.5 hours. The pot temperature was maintained at about 50-60°C by steadily reducing the vacuum from about 1513 kPa (kilopascals) to about 2.0 kPa. The total distillate collected (collected distillate plus amounts in the ice trap) weighed 126.9 g. The distillate comprising acrylonitrile and trichloroacetyl chloride could have been recycled to improve the overall yield. The sediment was analyzed by GLC to ensure that no acrylonitrile was detected and was then diluted with 30.1 g of o-xylene and filtered.

The cake was air dried to yield 1.5 g of gray solids. The filtrate weighed 131.4 g and was assayed to contain 29.2% o-xylene, 2.3% trichloroacetyl chloride, 62.7% 4-cyano-2,2,4-trichlorobutanoyl chloride, and 1.8% various organic heavy components. The yield of recovered 4-cyano-2,2,4-trichlorobutanoyl chloride was 39%.

Preparation example of 3.3.5-trichloroglutarimide

To a 250 mL flask was added 30 g of o-xylene and 81 g of a crude mixture comprising 64.0% 4-cyano-2,2,4-trichlorobutanoyl chloride (0.22 mole), 24.2% o-xylene and various impurities and unreacted starting materials. This mixture was maintained at about 40-47°C while 4.8 g (0.27 mole) of water was slowly added thereto over a period of about 105 minutes. This resulting mixture comprised 3,3,5-trichloroglutarimide and 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one, respectively, in a weight ratio of 1.3:1. The resulting mixture was heated and maintained at 100°C for about 14 hours. The mixture was then cooled to about 17°C and filtered. The cake was washed with cold o-xylene and dried to give 38.4 g of a tan powder which assayed to contain 98.2% 3,3,5-trichloroglutarimide and 0.4% 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one, resulting in a 79% yield of isolated 3,3,5-trichloroglutarimide product. Yield losses in the filtrate were 8.8% as 3,3,5-trichloroglutarimide, 0.35% as trichloropyridinol, and 11.6% as 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one. The filtrate could have been recycled to improve the overall yield.

Claims (5)

1. A process for the preparation of 3,3,5-trichloroglutarimide, characterized by: (a) combining 4-cyano-2,2,4-trichlorobutanoyl chloride with a nearly stoichiometric amount of water sufficient to react with all of the 4-cyano-2,2,4-trichlorobutanoyl chloride and any impurities in an inert organic solvent at a temperature between 20°C and 50°C to obtain a mixture of 3,3,5-trichloroglutarimide and 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one, and (b) heating the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one in the presence of water and an inert organic solvent to between 90°C and 100°C, whereby the 3,3,5,6-tetrachloro-5,6-dihydropyridin-2-one is converted to 3,3,5-trichloroglutarimide. 2. The method of claim 1, further characterized in that the solvent is xylene or tetrachloroethylene. 3. Process according to claim 1 or 2, further characterized in that 1 to 5 moles of water are used for each mole of 4-cyano-2,2,4-trichlorobutanoyl chloride used. 4. Process according to claim 1 or 2, further characterized in that 1.2 moles of water are used for each mole of 4-cyano-2,2,4-trichlorobutanoyl chloride used. 5. A process according to any one of the preceding claims, further characterized in that the water is slowly added to the 4-cyano-2,2,4-trichlorobutanoyl chloride.