DD299292A5 - PROCESS FOR THE PREPARATION OF AMIDINOTHIOROUS SUBSTANCE - Google Patents

Abstract

The invention relates to a process for the preparation of amidinothiourea. Amidinothiourea can be prepared industrially easily and in good yields by reacting dicyandiamide with dimethylthioformamide and concentrated hydrochloric acid. dicyandiamide; dimethylthioformamide; Intermediate for drugs}

Description

For this 1 page formulas

Field of application of the invention

The invention relates to a process for the preparation of amidinothiourea of the formula I, which is a valuable intermediate in the preparation of medicaments such as famotidine.

Characteristic of the known technical solutions

It is known to amidinothiourea by reacting dicyandiamide with hydrogen sulfide either under pressure (Chem. Ber. 62 (1929), 1402) or depressurised while passing a stream of H ₂ S through an aqueous solution of dicyandiamide (Org. Synth. 35 [1955 ], 69, F. Kurzer, J. Chem. Soc., 1955, 1).

In the latter case, a yield of 60% is given, at the same time 10% of 2,4-Dithiobiuret formed as a byproduct.

It is also known to carry out the reaction between dicyandiamide and hydrogen sulfide under pressure in various alcohols and in the presence of a catalyst (JP-A 69.13692KTK, 71.06044KTK, 71.19938KTK, 71.19939KTK and 71.19940KTK).

It is also known to produce amidinothiourea by reacting dicyandiamide with carbon disulfide in the presence of caustic potash or aqueous methylamine solution (J. Chem. Soc., 1948, 1653, JP-OS 82.46960KTK).

A further possibility for the preparation of amidinothiourea consists in the reaction of dicyandiamide with thioacetamide and concentrated hydrochloric acid, where I is obtained as the hydrochloride in 80% yield (Chem.% Ind. 1974, 301; Austr. J. Chem. 1974, 2627). As a by-product formed in this reaction s-triazine.

All of these methods are associated with considerable disadvantages such as the use of highly toxic and safety difficult to handle starting materials (H ₂ S, CS ₂ ), long reaction times when working with carbon disulfide or a very complex and non-productive production of the starting material thioacetamide from acetamide and phosphorus pentoxide (Chem Berger 11, 340 [1878]; Liebigs Ann. 250, 264).

Object of the invention

The invention makes it possible to produce amidinothiourea technically easily, in good yields and starting from readily available raw materials, the amidinothiourea being obtained in such a pure form that it can be further processed without any further purification.

Explanation of the essence of the invention

The present invention has the object, amidinothiourea technically easy to produce in good yields and starting from readily available raw materials.

According to the present invention, this is achieved by reacting a mixture of dicyandiamide, dimethylthioformamide of the formula II and concentrated hydrochloric acid. It is advantageous to use all the reactants in approximately equimolar amount.

A particular embodiment of the invention consists in adding the concentrated hydrochloric acid as quickly as possible to a mixture of dicyandiamide and dimethylthioformamide. In this case, the reaction sets in under intense heating and there is a solution of amidinothiourea hydrochlorides. After the reaction has ended, the reaction mixture is mixed with water and the amidinothiourea is precipitated.

A particular advantage of the invention consists in the use of Dimethylthioformamid, which is for example technically very well after Willstatter (Chem. Ber. 42 [1909], 1920) produced by reacting dimethylformamide with phosphorus pentasulfide in benzene or toluene.

The success of the process according to the invention is completely surprising and unforeseeable for the skilled person. In Joshua et al. (Austr. J. Chem. 1974, 2627) is in fact given for the reaction. Dicyandiamide and thioacetamide the Scheme outlined in the formula sheet as Scheme 1.

However, this means that the thioacetamide has to react in its tautomeric form (formula III). However, such tautomerism is excluded in dimethylthioformamide.

Thus, the process of the invention offers the possibility of a technologically unpretentious process by the completely surprising substitutability of Dimethylthioformamids for the production of amidinothiourea, with its particular advantage is that Dimethylthioformamid is very easily accessible in contrast to thioacetamide.

embodiment

84 g (1 mol) of dicyandiamide and 89 g (1 mol) of dimethylthioformamide are mixed, whereby a clear solution is formed with stirring. This is mixed as quickly as possible with 100 ml (1 mol) of concentrated hydrochloric acid (37%). In this case, the temperature of the mixture rises within a few minutes to 80 ° C. The mixture is stirred for 15 minutes, mixed with 150 ml of water and the solution is cooled to 1O ⁰ C. Sucked from a little insoluble and the filtrate with stirring and further cooling dropwise with 100 ml of sodium hydroxide solution (33 ml of concentrated sodium hydroxide with 722g / l NaOH and 66ml of water). The thereby precipitated amidinothiourea is filtered off, washed twice with 70 ml of water and dried. Yield: 82.5 g of amidinothiourea (S 70% of theory)

Mp .: 165-172 ⁰ C.

C-NH-C

GH II

SH H ₃ G - O

, MH III

Scheme 1

^l 2 ^u \ + HGl "2" \

_y G-FH-GN ~> ^ G-NH-GH.HCl

HN ^ IW

HN

, C-NH-C-Ol II

NH

* S

+ CH ₃ -C:

^X 2

- HGl

NH II C-M-O-S-G-GH

! I

C-NH-C-In

HN

+ CH ₃ -GN

Claims (3)

1. A process for the preparation of amidinothiourea of the formula I _1, characterized in that reacting a mixture of dicyandiamide, dimethylthioformamide and concentrated hydrochloric acid with each other. 2. The method according to claim 1, characterized in that the three reactants are used in approximately equimolar amounts. 3. Process according to claims 1 and 2, characterized in that the concentrated hydrochloric acid is added to a mixture of dicyandiamide and Dimethylthioformamid.