MXPA97008460A - A procedure to reduce the accumulation of diithocarbazinate in the preparation of di diocyte barbazinate - Google Patents

Abstract

The present invention relates to an improved process for preparing methyl dithiocarbazinate by reaction of carbon disulfide and hydrazine in an effective ratio to form hydrazinium dithiocarbazinate, followed by methylation of dithiocarbazinate hydrazinium with methyl bromide. The improvement lies in carrying out the reaction of carbon disulfide and hydrazine in the presence of a specified amount of a non-alcoholic solvent to reduce the accumulation of dithiocarbazine

Description

A PROCEDURE TO REDUCE THE ACCUMULATION OF DITIOCHARBAZINATE IN THE PREPARATION OF METHYL DIOCYACHARBAZINATE CROSS REFERENCE TO RELATED APPLICATION This application is a continuation in part of the US application. serial number 08 / 743,775, filed November 7, 1996. BACKGROUND OF THE INVENTION Field of the Invention: The present invention relates to an improved process for the preparation of methyl dithiocarbazinate. More specifically, the invention relates to an improved process for increasing the yield and / or purity of methyl dithiocarbazinate. Brief Description of the Prior Art: Prior art descriptions of the procedures for preparing methyl dithiocarbazinate are limited by shortage. of information on published experimental procedures and the excessive cost of commercial-scale procedures. The laboratory reports present little information on how the reaction temperatures would affect the production of unwanted by-products, yield and purity, the impact on waste treatment operations and the like. Commercial scale methods are expensive because they involve the use of expensive reagents and / or expensive techniques, such as separation of intermediates and recrystallization of the final product. Audrieth et al., J. Organic Chem., Vol. 19, pp. 733-741 (1954) describe a process for the preparation of methyl dithiocarbazinate and its conversion to thiocarbohydrazide. The process consists of a dropwise addition of 1.04 mole of carbon disulfide to 1.18 mole of potassium hydroxide and 1.1 mole of 85% hydrazine in 200 ml of ethanol, in an ice bath. During the addition, a heavy yellow oil containing potassium dithiocarbazinate is separated. The resulting mixture is stirred and cooled and two volumes of ether are added to produce the separation of more desired product (potassium dithiocarbazinate). The oil layer is separated from the ether-alcohol layer and filtered to remove a small amount of an unidentified solid that is formed. The clear yellow solution is then dissolved in 300 ml of water. The resulting solution is cooled in an ice bath and 1.05 moles of methyl iodide are added in about 10 batches. The reaction vessel is agitated and cooled alternately after each such addition, until the methyl iodide is consumed. The reaction mixture is allowed to stand for several hours, being stirred occasionally to allow a complete reaction. The methyl dithiocarbazinate is collected and recrystallized from ethanol. Methyl dithiocarbazinate (24.4 g, 0.2 mole) was dissolved in 200 ml of absolute ethanol and 18 ml (0.3 mole hydrazine) of 85% hydrazine hydrate was added. The resulting solution was subjected to reflux until no more solid thiocarbohydrazide precipitated (approximately 45 minutes). A small amount of 3-hydrazino-4-amino-5-mercapto-1,2,4-triazole which had been formed was removed as follows. The reaction mixture was cooled and the resulting solid product was collected and recrystallized from acidified water with a few drops of hydrochloric acid. U.S. Pat. No. 4,696,938 describes a process for preparing and using methyl hydrazinecarbodi-thioate as an intermediate in the preparation of 6-arylpyridine thiosemicarbazones. Methyl dithiocarbazinate is prepared as follows. Hydrazine hydrate (150 g) is added to a cooled (0 ° C) solution of potassium hydroxide in water (240 ml) and 2-propanol (200 ml). Pre-cooled carbon disulfide (182 ml) is then added dropwise to the stirred reaction mixture, while maintaining an internal temperature below 10 ° C. After the addition is complete, stirring is continued for another hour. Methyl iodide (426 g) is added dropwise over 11/2 hours. The resulting white precipitate is collected by filtration and washed with cold water. The crude product is recrystallized from methylene chloride. To form 6-arylpyridine thiosemicarbazone, methyl dithiocarbazinate is reacted in a suitable solvent such as alcohol. The reaction product is treated with selenium dioxide in a suitable ethereal solvent such as tetrahydrofuran or 1,4-dioxane. S. Losanitch, J. Chem. Soc, Vol. 119, pp. 763-765 (1921) describes a process for preparing methyl dithio-carbazinate by first obtaining ammonium dithiocarbazinate and reacting it with methyl iodide. The ammonium dithiocarbazinate is obtained as follows. A solution of hydrazine hydrate in alcohol is slowly treated, containing a large excess of ammonia, with cooling, with the corresponding amount of carbon disulfide. Methyl dithiocarbazinate is formed by treating the ammonium salt in an alcoholic solution diluted with methyl iodide. Sandstrom et al., Arkiv Fór Kemi, 4 (1952) 297, describe a process for preparing ethyl dithiocarbazinate. The process includes the separation of hydrazinium dithiocarbazinate from an ethanol-water mixture and the reaction of hydrazinium dithiocarbazinate with ethyl bromide in an ethanol-water mixture. U.S. Pat. No. 3,284,482 describes a process for the preparation of chlorobenzyl esters of dithiocarbazinic acid as follows. To a solution consisting of 85% of hydrazine, 25% of sodium hydroxide and 300 ml of water, carbon disulfide is added, by dripping, at a temperature of 10 to 15 ° C and for 20 minutes. The external cooling is removed and the reaction mixture is stirred for one hour at a temperature of 25 to 30 ° C. Trichlorobenzyl chloride is then added in one portion to the reaction mixture, which is stirred for 24 hours at a temperature of 25 to 30 ° C to produce the corresponding trichlorobenzyl dithiocarbazinate. The product is then extracted with ethyl ether. The ether solution is washed with water until neutral, dried over sodium sulfate and the ether is removed in vacuo. The British Patent Description 1,274,521 discloses dithiocarbazin ester derivatives by reaction of esters of dithiocarbazinic acid with an oxo compound. The dithiocarbazinic acid is prepared by reacting hydrazine hydrate with carbon disulfide in an alcoholic medium in the presence of excess potassium hydroxide, ammonia or hydrazine hydrate. After isolation, the salt of dithiocarbazinic acid is converted into an ester by an alkylation or aralkylation step. This stage is carried out in water, a mixture of water and alcohol or in alcohol. Alternatively, the ester can be prepared in a single reactor. The alkylating or aralkylating agent is added to the dithiocarbazinic acid salt solution prepared by the above method. The alkylating or aralkylating agents described by the patent are: dimethyl sulfate, diethyl sulfate, allyl chloride, n-butyl iodide, n-octyl ester, n-dodecyl bromide, cetyl bromide, benzyl chloride, p-chlorobenzyl, p-isopropylbenzyl bromide, pn-butylbenzyl bromide and alpha-methylbenzyl chloride. As will be seen from the foregoing, an economical process, ie, an easier and more efficient procedure in terms of cost, is needed for the preparation of methyl dithiocarbazinate. By the present invention, said improved process for the preparation of methyl dithiocarbazinate is provided. SUMMARY OF THE INVENTION According to the above, the present invention includes an improved process for the preparation of methyl dithiocarbazinate by reaction of carbon disulfide and hydrazine to form hydrazinium ditocarbazinate, followed by methylation of dithiocarbazinate with methyl bromide. The improvement consists in carrying out the reaction of the carbon disulfide and the hydrazine in the presence of a non-alcoholic solvent to reduce the accumulation of dithiocarbazinate on a surface to which it is exposed. The molar ratio of solvent to carbon disulfide is about 0, 4: 1 to about 3: 1 and is preferably from about 0.5: 1 to about 3: 1. Water is also preferably added. The amount of solvent significantly exceeds the amount ordinarily employed in the prior art preparation of hydrazinium dithiocarbazinate. Typically, the molar ratio of solvent to carbon disulfide in the prior art processes was 0.3: 1 or less. It is relatively easy to determine the reduction of surface accumulation of dithiocarbazinate, typically on the walls of reaction vessels, vessels, conduits or an apparatus therein. It has been found that approximately an increase of twice the amount of solvent ordinarily employed can provide a reduction in accumulation. Quantities of solvent greater than what is needed to reduce buildup can have an adverse effect on the recovery of the reaction product or result in undue impoverishment of the solvent. This accumulation is observed more clearly in equipment on a pilot scale or on an industrial scale, but it can be observed in equipment at laboratory scale whose style and intensity of agitation correspond closely with the equipment at industrial scale. The use of an increase in solvent also provides the ability to produce a much more concentrated product suspension than is possible with water alone or with water and lower levels of solvent. In the prior art, suspensions of DTCM with a concentration of 25% or less were all that could be handled and transferred on an industrial scale. With the use of higher levels of solvent, suspensions of 30 to 40% DTCM can be handled and transferred on an industrial scale. This provides a dramatic increase in the volumetric efficiency of the production equipment, with a corresponding reduction in product costs and waste generation. By this method, products of high purity (up to about 98%) and high yields (up to about 87%) with a suspension concentration of 30 to 40% can be obtained unexpectedly. On the contrary, the prior art could not ordinarily achieve product purity of greater than 90 to 92% without further purification and yields that were 83% or higher and a suspension concentration of DTCM were needed for industrial use. of 25% or less. Without inclining to any particular theory of the invention, we think that this procedure effects the suspension of the solid product in a form that is easily mixed and transported. Apparently, the prior art process can not effect easy suspension and transport of the solid product without excessive dilution. The invention is described in more detail below. DETAILED DESCRIPTION OF THE INVENTION As indicated above, the claimed invention relates to an improved process for preparing methyl dithiocarbazinate by reaction of carbon disulfide with hydrazine in a non-alcoholic solvent for the hydrazinium dithiocarbazinate form. This is followed by methylation of hydrazinium dithiocarbazinate with methyl bromide to form methyl dithiocarbazinate. The improvement here consists in reducing the accumulation of dithiocarbazinate on the surface of the container by providing a higher level of solvent to reduce the accumulation. The highest level of solvent can be added before or after the addition of carbon disulfide. In the embodiment of the invention, referred to as the "DTCH process", the invention consists in the reaction of carbon disulfide with hydrazine in an effective ratio to form a reaction product containing hydrazinium dithiocarbazinate. The resulting product containing dithiocarbazinate reacts with methyl bromide to produce high yields of methyl dithiocarbazinate. When preparing hydrazinium dithiocarbazinate by the DTCH procedure, hydrazine can typically react in the form of hydrazine hydrate and carbon disulfide in a molar ratio of from about 4: 1 to about 2: 1 and, preferably, from about 2: 1 to about 2.4: 1. The DTCH procedure can be represented by the following reaction scheme.

S / "\ 2H, N-NH7 + CS2? H2N-N S ~ + H3N-NH2 (I) H S S / "\ /" \ H2N-N S ~ + H N-NH2 + CH3Br? H2N-N S-CH3 + H2N-NH3 + ~ Br (II) H H DTCH DTCM It is a distinctive feature of the invention that the reaction medium can be utilized to obtain an improved process for the preparation of methyl dithiocarbazinate. As a reaction medium, a reducing amount of the accumulation of a non-aqueous solvent can be employed. Preferably, the reaction mixture also contains water. When used, the molar ratio of water to carbon disulfide is from about 2: 1 to about 10: 1 and is preferably from about 2: 1 to about 5: 1. The aprotic solvents are useful non-alcoholic solvents. Illustratively, an aliphatic or aromatic hydrocarbon solvent may be employed. The aliphatic hydrocarbon can be selected from the group consisting of alkanes, such as pentane, hexane and heptane. The aromatic hydrocarbon can be selected from the group consisting of toluene, benzene and xylenes. Toluene is preferred. The molar ratio of solvent to carbon disulfide ranges from about 0.4: 1 to about 3: 1 and, preferably, from about 0.5: 1 to about 3: 1. Unlike many prior art methods, the reaction mixture (which may contain water) does not contain alcoholic solvents. The above reactions can be carried out at a temperature of about 0 to 35 ° C and, preferably, 5 to 25 ° C, for a period of about 1 to 4 hours and, preferably, 1 to 2 hours, to a pH of about 8 to 14 and, preferably, 9 to 14. The resulting dithiocarbazinate reacts (is methylated) with methyl bromide. The molar ratio of methyl bromide to dithiocarbazinate may be from about 1.5 to 1.02: 1 and, preferably, 1.05: 1. Typically, methyl bromide is introduced into the reaction vessel containing the hydrazinium dithiocarbazinate by bubbling through it. Although this reaction can be conducted in another reaction vessel, it is typically conducted in the same reaction vessel as that used in the preparation of dithiocarbazinate. The reaction medium used in the methylation reaction is essentially the same as the reaction medium described above. The reaction conditions for the preparation of methyl dithiocarbazinate can be as follows. The pH range of the reaction mixture may be from about 8 to about 14 and, preferably, 14 to 9, at a temperature of from about 0 to 35 ° and, preferably, from 5 to 25 ° C, for about 0, 5 to 3 hours and, preferably, 1 to 2 hours. The reaction can be carried out without isolating the dithiocarbazinate salts. It is also a distinctive feature of the invention that the methylation reaction can be carried out without the use of expensive reaction catalysts such as sodium iodide. According to this invention, the methylation reaction consists essentially of the reaction of the reaction product containing dithiocarbazinate with methyl bromide. The resulting product containing methyl dithiocarbazinate can be isolated by any convenient means. Illustratively, methyl dithiocarbazinate can be isolated as a wet cake by filtration or centrifugation. The wet cake can be collected on a vacuum filter and washed with water to remove impurities such as bromide salts. The resulting cake can be used as such cake or dried by any convenient means. Illustratively, the cake can be dried by exposure to temperatures that would effect drying without causing decomposition. More specifically, the cake can be dried in a vacuum oven, using a nitrogen spray at a temperature of about 30 ° to 40 ° C. In general, the purity of methyl dithiocarbazinate can be up to about 95%, the variation being attributable to the washing and / or drying steps. As you would see from the above, methyl dithiocarbazinate can be obtained without recrystallization of the reaction product containing it. It is, therefore, a distinctive feature of the invention that methyl dithiocarbazinate can be prepared without separating the intermediate dithiocarbazinate from the reaction medium. As such, the invention encompasses a process for the preparation of methyl dithiocarbazinate consisting essentially of the reaction of carbon disulfide and hydrazine in a non-alcoholic solvent, followed by methylation of hydrazinium dithiocarbazinate. By the process of the invention, high yields of methyl dithiocarbazinate are obtained in high purity without the associated drawback of the accumulation of dithiocarbazinate on the surface of the reaction vessel and with a suspension significantly more concentrated than what was previously practical at scale industrial. The elimination of the accumulation of solids in the wall of the reaction vessel solved several problems. The reaction temperature can be more closely controlled due to a better heat transfer through the wall of the reaction vessel. Secondly, the reduction of the available dithiocarbazinate increases the local concentration of methyl bromide beyond the desired limits, leading to a greater formation of by-products and then to lower yield and purity. Also by this method the use of undesirable solvents, such as ethanol, and methylating agents, such as methyl iodide, can be eliminated. The procedure does not require isolation of intermediate dithiocarbazinate. The advantages of this invention, particularly with respect to the yield and purity and the ability to transfer the product suspension for further processing on an industrial scale are clear when comparing the examples described below. These and other aspects of the invention are further illustrated, although not intended to be limited, by the following examples, wherein all parts and percentages are by weight unless otherwise specified. EXAMPLES Example 1 Carbon disulfide (38 g, 0.5 mole) was added slowly (with cooling) to a mixture of toluene (30 ml, ie about 0.3 mole), water (72 ml, 4 moles) and hydrazine monohydrate (50 g, 1.0 mole) at 25 ° C. The molar ratio of solvent to carbon disulfide was about 0.6: 1. After the additions were complete, the reaction was stirred for 1 hour and then methyl bromide gas (52.3 g, 0.55 mol) was bubbled into the mixture over 2 hours. The resulting white suspension was stirred for a further 30 minutes at 25 ° C, then cooled to 5 ° C and filtered at any time during the batch. The batch was very fluid and easy to transfer from the reactor. The batch mixture was easy to make. Methyl dithiocarbazinate was isolated (yield 87%, purity 98%) as white powder. Example 2 (Comparative) A batch was made using the above procedure, but without the presence of toluene. The batch had large amounts of solids deposited in the vessel wall during the addition of the carbon disulfide. The batch had a very high viscosity, which made the mixture difficult. The batch could not be poured out of the reactor and had to be extracted by hand. The yield was 79% and the purity was 87%. Example 3 A batch was made using the above procedure, but with the presence of 15 ml of toluene (i.e., about 0.15 mols). The molar ratio of solvent to carbon disulfide was about 0.3: 1. The batch had large amounts of solids deposited in the container wall during the addition of carbon disulfide, but not as many as in Comparative Example 5. The batch had a high viscosity which made mixing difficult. The yield was 81% and the purity was 88%. Although the invention has been described in detail in the foregoing for illustrative purposes, it is to be understood that said detail has only that purpose and that those skilled in the art will be able to make variations therein without departing from the spirit and scope of the invention, except as may be limited by the claims.

Claims (6)

CLAIMS 1. In a process for the manufacture of methyl dithiocarbazinate consisting of the reaction of carbon disulfide and hydrazine to form hydrazinium dithiocarbazinate and the methylation of said dithiocarbazinate hydrazinium with methyl bromide, the refinement in which the reaction of said carbon disulfide and hydrazine is carried out in the presence of a non-alcoholic solvent to reduce the accumulation of dithiocarbazinate, the molar ratio of said solvent being to carbon disulfide of about 0.4: 1 to about 3: 1. 2. The process according to Claim 1, wherein said solvent is an aromatic or aliphatic hydrocarbon. 3. The process of Claim 2, wherein said solvent is toluene. 4. The method of Claim 1, wherein said molar ratio is from about 0.5: 1 to about 3: 1. 5. The process of Claim 1, wherein the methylating reaction is followed by isolation of methyl dithiocarbazinate as a wet cake by filtration or centrifugation. 6. The process of Claim 1, wherein said reaction is also carried out in the presence of water, the molar ratio of water to carbon disulfide being from about 2: 1 to about 10:

1.