Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2000-07-31
2001-07-17
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S278000
Reexamination Certificate
active
06262304
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing 1,1,3,3-tetramethylguanidine which is useful as intermediates or raw materials for manufacturing medicines and chemical products, and also relates to a process for producing dimethylcyanamide which is important as the intermediate for 1,1,3,3-tetramethylguanidine.
2. Description of the Prior Art
It is known that dimethylcyanamide can be produced by reacting cyanogen chloride with dimethylamine in an organic solvent which is immiscible with water (British Patent No. 1267318), by reacting cyanogen halide with dimethylamine in an aqueous solvent (Japanese Patent Application Laid-Open No. 55-133352), or by treating sodium or potassium cyanide and dimethylamine with chlorine in an aqueous solvent (Japanese Patent Application Laid-Open No. 61-280463). The dimethylcyanamide thus obtained is used as an intermediate for the synthesis of 1,1,3,3-tetramethylguanidine. 1,1,3,3-Tetramethylguanidine has been produced by reacting dimethylcyanamide with dimethylamine hydrochloride in a water-immiscible organic solvent at high temperature under pressure (British Patent No. 1267318), or by reacting dimethylcyanamide with dimethylamine and dimethylamine hydrochloride in an aqueous solvent (Japanese Patent Application Laid-Open Nos. 61-280463 and No. 55-133352).
A method of producing 1,1,3,3-tetramethylguanidine from dimethylcyanamide in a water-immiscible organic solvent generally involves several problems. The method requires a complicated reaction apparatus because the reaction is carried out at high temperatures under pressure. The reaction conditions are corrosive to the reaction apparatus. Further, the method does not produce 1,1,3,3-tetramethylguanidine in satisfactory yields. In consequence, 1,1,3,3-tetramethylguanidine is produced from dimethylcyanamide preferably in an aqueous solvent as taught by Japanese Patent Application Laid-Open No. 55-133352.
Therefore, the method of British Patent No. 1267318, in which dimethylcyanamide is produced in a water-immiscible organic solvent, is unsuitable because solid matters such as dimethylamine hydrochloride are precipitated during the reaction and the water-immiscible organic solvent must be changed to an aqueous solvent in the subsequent synthesis of 1,1,3,3-tetramethylguanidine in an aqueous solvent.
A method of mixing an aqueous solution of cyanogen chloride with an aqueous solution of dimethylamine is also unsatisfactory in the yields as described in Comparative Example 1. Japanese Patent Application Laid-Open No. 55-133352 discloses in Example 3 that the final yield of 1,1,3,3-tetramethylguanidine amounts to 85.1 mol % by feeding a cyanogen chloride gas into an aqueous solution of dimethylamine. The low yield of 1,1,3,3-tetramethylguanidine of the proposed method would be attributable mainly to a low yield of dimethylcyanamide intermediate.
The method of Japanese Patent Application Laid-Open No. 61-280463 is favorable for producing 1,1,3,3-tetramethylguanidine in an aqueous solvent because dimethylcyanamide is obtained as an aqueous solution. However, the reaction procedures are complicated because chlorine as an oxidant should be blown into a solution containing a reductive organic compound. Further, as described below, the results of applicants' replication of the proposed reaction procedures showed that the reaction involved possible danger of causing fire.
Therefore, an object of the present invention is to provide a simple process for producing dimethylcyanamide safely in high yields. Another object of the present invention is to provide a simple process for producing 1,1,3,3-tetramethylguanidine safely in high yields via dimethylcyanamide.
SUMMARY OF THE INVENTION
All the reported methods for producing dimethylcyanamide by reacting cyanogen chloride with dimethylamine in the presence of water have failed to produce dimethylcyanamide in high yields due to side reactions of cyanogen chloride. Only capable of producing dimethylcyanamide in relatively high yields even in the presence of water is the method disclosed in Japanese Patent Application Laid-Open No. 61-280463. However, as mentioned above, the proposed method requires complicated and strictly controlled procedures such as the blowing of chlorine under strictly controlled pH. Thus, any known methods for the production of dimethylcyanamide inevitably involve drawbacks such as low yield and complicated procedures.
The inventors have now found that dimethylcyanamide is safely produced in high yields by mixing a solution of cyanogen chloride in an organic solvent which is immiscible with water and an aqueous solution of dimethylamine to allow cyanogen chloride to react with dimethylamine. It has been further found that the dimethylcyanamide produced by the above method is free from precipitated solid matters, thereby facilitating the subsequent treatments. In addition, it has been found that the above method does not require complicated procedure and strict control.
Thus, in a first aspect of the present invention, there is provided a process for producing dimethylcyanamide, comprising a step of mixing a solution of cyanogen chloride in an organic solvent which is immiscible with water and an aqueous solution of dimethylamine, thereby allowing cyanogen chloride to react with dimethylamine.
The reaction product solution containing dimethylamine obtained in the above process is used as a raw material for producing 1,1,3,3-tetramethylguanidine after simple procedure of removing the organic solvent by distillation. By adding dimethylamine to a solution after removing the organic solvent and heating, 1,1,3,3-tetramethylguanidine hydrochloride is easily synthesized. Free 1,1,3,3-tetramethylguanidine is recovered by neutralizing hydrogen chloride with alkali such as sodium hydroxide and potassium hydroxide, and treating the resulting solution with usual methods such as extraction, salting out and distillation.
Thus, in a second aspect of the present invention, there is provided a process for producing 1,1,3,3-tetramethylguanidine, comprising a step of mixing a solution of cyanogen chloride in an organic solvent which is immiscible with water and an aqueous solution of dimethylamine to allow cyanogen chloride to react with dimethylamine, thereby obtaining a dimethylcyanamide solution; a step of removing the organic solvent from the dimethylcyanamide solution by distillation; and a step of heating the resulting solution after adding dimethylamine.
DETAILED DESCRIPTION OF THE INVENTION
In the process of the present invention, one mole of cyanogen chloride is reacted with one mole of dimethylamine to produce one mole of dimethylcyanamide together with hydrogen chloride. To neutralize the generated hydrogen chloride, one mole of a base such as sodium hydroxide and dimethylamine is required, thereby producing one mol of a hydrochloride of the base. Since dimethylamine is generally used as the base, 2 moles of dimethylamine is added per one mole of cyanogen chloride to complete the reaction.
Cyanogen chloride and dimethylamine may be used in another molar ratio other than the above. An excess portion remains unreacted in the reaction product solution. Therefore, the use of excess dimethylamine is preferred to prevent cyanogen chloride from remaining unreacted, because care must be taken in handling a reaction product solution containing the remaining cyanogen chloride due to its high toxicity and corrosive properties. However, the use of a large excess dimethylamine is disadvantageous, because the remaining dimethylamine is distilled together with the organic solvent during the distillation prior to the subsequent synthesis of 1,1,3,3-tetramethylguanidine, thereby requiring an additional step for separating dimethylamine from the organic solvent. Therefore, the amount of dimethylamine to be used is preferably about 2 to 2.2 moles per one mole of cyanogen chloride.
The solution of cyanogen chloride in water-immiscible organic solvent may be mixed with the aqueous solution of dimethyl
Hashimoto Toshihiro
Motoi Takashi
Antonelli Terry Stout & Kraus LLP
Davis Brian J.
Mitsubishi Gas Chemical Company Inc.
Richter Johann
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