IE970595A1

IE970595A1 - A process for preparing isothiocyano compounds

Info

Publication number: IE970595A1
Application number: IE970595A
Authority: IE
Inventors: Michael Hilary Burke
Original assignee: Michael Hilary Burke
Priority date: 1997-08-12
Filing date: 1997-08-12
Publication date: 1999-06-16

Abstract

A process for preparing isothiocyano compounds Nitroscanate is prepared by forming an amide, hydrolysing the amide, preparing a thiourea from the hydrolysed product and converting the thiourea thus formed into nitroscanate. The process may be used on a commercial scale with high yield and without the use of hazardous chemicals.

Description

This process is not, however, satisfactory as it involves the use of hazardous chemicals, especially thiophosgene.

This invention is therefore directed towards providing an improved process for preparing nitroscanate.

According to the invention, there is provided a process 15 for manufacturing an isothiocyano derivative of the formula NCS IV comprising the steps of:- - 2 IE 970595 forming an amide of the formula wherein R2 is Ac; hydrolysing the amide of formula I to form a compound of formula II II wherein R2 is HCI; preparing a thiourea of the formula from the compound of formula II; and converting the thiourea of formula III to the desired compound of formula IV.

In a preferred embodiment of the invention, the amide of formula I is prepared by reacting a compound of the formula V with a compound of formula VI VI - 3 Preferably, the reaction is carried out in the presence of dimethylformamide and potassium carbonate. Preferably, the process includes the step, after reaction, of removing phenolic impurities. In this case preferably the phenolic impurities are removed by addition of a base, preferably sodium hydroxide. i In one embodiment of the invention, the hydrolysis is carried out using hydrogen chloride.

Preferably, the thiourea is prepared by reacting a 10 compound of formula II with ammonium thiocyanate, NH^SCN.

In a preferred embodiment of the invention, the thiourea of formula III is converted to the desired compound of formula IV by releasing ammonia (NH3) from the thiourea of formula III.

Preferably, in this case ammonia is released by reacting the thiourea of formula III with chlorobenzene.

The invention also provides the compound nitroscanate whenever manufactured by the process of the invention.

The advantages of the invention are in providing a process 20 for manufacturing nitroscanate on a commercial scale a high yield without the use of hazardous chemicals.

The invention will be more clearly understood from the following description thereof given by way of example only.

Stage 1 Nitroscanate amide Cl HO oo NHAc 140.4 Kg l-chloro-4-Nitrobenzene 136.4 Kg 4-Acetamidophenol 477.20 litres Dimethylformamide were charged into a reaction vessel. The reaction mixture was stirred at ambient temperature. 69.5 Kg of potassium carbonate was then introduced into the vessel and the contents were stirred and heated to a temperature above 130°C for approximately 4 hours. The mixture was cooled to -20°C. The mixture was quenched with 1092 litres of water forming a yellow solid precipitate. To remove any phenolic impurities 73 litres of 25% sodium hydroxide solution was added. After stirring, the solid was filtered giving 350-400 Kgs of crude damp solid. The compound was recrystallised using IMS and after drying, substantially pure amide of Formula II in a yield of 8092% was achieved.

Stage 2 218 Kg of the compound formed in Stage 1 909 litres of water 454.5 litres of concentrated hydrochloric acid, and 227.3 litres of IMS - 5 IE 970595 were charged into a vessel and stirred and heated at reflux for approximately 4 hours. On cooling, a white solid was precipitated which was filtered resulting in approximately 196 Kg of dry product of formula III.

Stage 3 i 980 litres water 163.3 Kg Ammonium Thiocyanate were charged into a vessel and, after stirring for 30 minutes, the product of Stage 2 was added. The mixture was stirred and heated to reflux (approximately 100°C) for about 6 hours. The mixture was then cooled and a yellow granular solid was filtered at approximately 80°C. After washing and recrystallisation, a yield of 170 Kg (80%) of the compound of formula III was produced.

Stage 4 169 Kg of the product of Stage 3 and 1690 litres chlorobenzene were charged into a vessel. A stream of nitrogen was maintained during the reaction. The mixture was stirred and heated to reflux giving off ammonia. 4050 litres of chlorobenzene were distilled from the mixture which was then refluxed for 16 hours. A further 1200 litres of chlorobenzene was distilled out under vacuum. The mixture was cooled to 20°C, filtered and concentrated. 120 Kg of crude dry nitroscanate representing a yield of 75% was extracted. The crude nitroscanate was crystallised, filtered and dried giving a yield of 64-80Kg (40-50%) of pure nitroscanate as a cream coloured solid.

Many variations on the process described will be readily apparent.

The invention is not limited to the embodiments hereinbefore described which may be varied in detail.

Claims

1. A process for manufacturing an isothiocyano derivative of the formula 0-N· NCS IV comprising the steps of:5 forming an amide of the formula wherein R[ is Ac; hydrolysing the amide of formula I to form a compound of formula II Ό'Ό·' II wherein R 2 is HCI; 10 preparing a thiourea of the formula III - 7 IE 970595 from the compound of formula II; and converting the thiourea of formula III to the desired compound of formula IV.

2. A process as claimed in claim 1 wherein the amide of 5 formula I is prepared by reacting a compound of the formula V with a compound of formula VI

3. A process as claimed in claim 2 wherein the reaction is carried out in the presence of dimethyl formamide and potassium carbonate. 10

4. A process as claimed in claim 3 including the step, after reaction, of removing phenolic impurities.

5. A process as claimed in claim 4 wherein the phenolic impurities are removed by addition of a base, preferably sodium hydroxide. 15

6. A process as claimed in any preceding claim wherein the hydrolysis is carried out using hydrogen chloride .

7. A process as claimed in any preceding claim wherein the thiourea is prepared by reacting a compound of 20 formula II with ammonium thiocyanate, NH^SCN.

8. A process as claimed in any preceding claim wherein the thiourea of formula III is converted to the - 8 desired compound of formula IV by releasing ammonia (NH 3 ) from the thiourea of formula III.

9. A process as claimed in claim 8 wherein ammonia is released by reacting the thiourea of formula III with 5 chlorobenzene. I

10. A process for preparing an isothiocyano derivative substantially as hereinbefore described with reference to the examples.

11. Nitroscanate whenever manufacture by a process as 10 claimed in any preceding claim.