DD202534A5 - METHOD OF PREPARING DIMETHYL (N-CYANIMIDO) CARBONATE - Google Patents

Abstract

The invention relates to a process for the preparation of dimethyl (N-cyanimido) carbonate for use as an intermediate for the synthesis of hystamine antagonists at H & ind2! Receptors. The object of the invention is to provide an improved process which avoids the use of toxic and unsuitable for industrial use cyanogen chloride or Bromcvan. According to the invention, dimethyl (N-cyanimido) carbonate of the formula (CH 2) 2) C = NCN is obtained by reacting sodium cyanide in an aqueous solution of sodium hydroxide and methanol with chlorine to give dimethyliminocarbonate and then reacting the dimethyliminocarbonate formed with cyanamide.

Description

Berlin, 22 · 12.1982 Δ? C 07 C / 241 513/6

Process for the preparation of dimethyl (Ef-cyaiiirni do) carbonate

Field of application of the invention

The present invention relates to a novel process for the preparation of dimethyl (ω-cyanimido) carbonate of the formula

(CH ₃ O) ₂ G = UGlT.

Dimethyl (H-ayanimido) carbonate has proven to be a preferred reagent in the synthesis of compounds which are histamine antagonists at Ho receptors, e.g. As gimetidine proved.

Characteristic of the known technical solutions

From J. Org. Chem. 1974, 39, 1522 is known and described therein, a process for the preparation of dimethyl (U-cgcanimido) carbonate from dimethyl (U-cyanimido) dithiocarbonate. It is also known and described in the literature, the synthesis of diethyl (U-cyanimido) carbonate with cyanamide in a non-aqueous medium at 0 ⁰ C (Chem · Ber · 1967, 100, 2604). In EP-AI-OO14O64 a process for the preparation of (If-cyanimido) carbonates is described ftei which the reaction in the system water / water-immiscible organic solvent, preferably toluene, takes place. The reaction proceeds in such a way that the intermediate disubstituted imidocarbonate is formed in situ from cyanogen chloride or cyanogen bromide and the corresponding alcohol in the presence of a base. Before adding cyanamide, the reaction mixture must be neutralized to pH 7 with cone.HCl.

Because of the known properties of the starting compound

AP G 07 C / 241 513/6 61 124/11

24

Cyanogen chloride or bomcyan, both of which are extremely toxic so that they can only be used under special safety measures (The Herck Indes, Mnth Edition, 1976, 2700-01), the described implementation is not technically applicable; a large-scale design would require special, appropriately adapted technology and equipment as well as special environmental protection measures ·

Object of the invention

Object of the invention int the provision of an improved process for the preparation of dimethyl (IT cyanimido) carbonate, which avoids the use of toxic and not suitable for industrial use cyanogen chloride or cyanogen bromide

Explanation: of the invention of the invention

The invention has for its object to find a new reaction mechanism using easy to handle reactants.

The inventive method is based on use of Hatriumcyanid as starting material · According to the method dissolved in water followed by excess sodium hydroxide and 'the corresponding alcohol, preferably methanol, · is Into the formed at 0 ⁰ C cooled solution an equivalent amount of sodium cyanide, an equivalent amount of chlorine initiated at such a rate that the temperature of 5 ⁰ C is not exceeded. After completion of the introduction of chlorine and neutralization of the reaction mixture with cone. Hydrochloric acid is mixed with methylene chloride and

AP G 07 C / 241 513/6 61 124 11

241513 8

- 2a -

Thereafter, mixed with an aqueous solution of gyananiid and cone · hydrochloric acid.

Other alkyl derivatives of the Gyanimidocarbonats with 1-4 C-atoms can be prepared by the process according to the invention, if one proceeds as described above and ethanol, propanol or butanol used instead of methanol.

Bin further advantage of the process of the invention is that the Bndprodukt is obtained in high yield and with a purity level which allows it without additional purification (z · example, by recrystallization) directly in the synthesis of lT-cyano-li ^t - / 2- / t4 ~ 2is ^ hyl-5-imidazolyl) -methylthio7-ethyl <-0 ~ methyl-isourea, which is an intermediate in the synthesis of ^N-t CyazLO-N-methyl-N ⁿ - / 2- (4-methyl -5-imidazolyl) methylthio7-ethyl ( -guanidine (cimetidine) is to use.

embodiment

The invention will be explained by the following embodiment.

AP G 07 G / 241 513/6 61 124 11

^ iOiJ D - 3 -

example

170 g (3.47 mol) of sodium cyanide, 152.6 g (3.8 mol) of sodium hydroxide and 443 ml (11.1 mol) of methanol are dissolved in 750 ml of Y / a, cooled to 0 ⁰ G and the solution 246.3 g (3.47 mol) of chlorine introduced, wherein the temperature of the reaction solution must not exceed 5 ⁰ G · After completion of the chlorination, the reaction mixture with cone. HGl adjusted to pH 7, with 870 ml of methylene chloride and then with 104 g (2.48 mol) of cyanamide, dissolved in 280 ml of water, and with 132 ml of cone. HCl added. After completion of the addition, the reaction mixture is heated to 15 ⁰ G and the organic and aqueous phases are separated. The aqueous phase is extracted twice with methylene chloride, the combined extracts with Ua, p50. dried and evaporated to dryness. There v / ground 254 g (90% based on Cyanamid) dimethyl (U-cyanimido) carbonate in Porm of white crystals, mp. 53 G ⁰ is obtained.

Claims (2)

AP G 07 C / 241 513/6 61 124 11 241513 δ _4_ invention ^ anapruch 1. A process for the preparation of dimethyl (U-cyanimido) carbonate of the formula characterized by reacting sodium cyanide in an aqueous Hatriumhydroxyd- and methanol solution with chlorine to Dimethylimidocarbonat and this then with cyanamide to dimethyl (ii-cyanimido) carbonate. 2 · "A method according to item 1, characterized in that the reaction at a temperature between -5 ° un 20 ⁰ C, preferably at + 5 ⁰ C is performed. '