GB2328435A - A process for preparing isthiocyano compounds - Google Patents

A process for preparing isthiocyano compounds Download PDF

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Publication number
GB2328435A
GB2328435A GB9717468A GB9717468A GB2328435A GB 2328435 A GB2328435 A GB 2328435A GB 9717468 A GB9717468 A GB 9717468A GB 9717468 A GB9717468 A GB 9717468A GB 2328435 A GB2328435 A GB 2328435A
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United Kingdom
Prior art keywords
formula
compound
thiourea
preparing
amide
Prior art date
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Granted
Application number
GB9717468A
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GB9717468D0 (en
GB2328435B (en
Inventor
Michael Hilary Burke
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Individual
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Individual
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Filing date
Publication date
Priority to IE970596A priority Critical patent/IES970596A2/en
Application filed by Individual filed Critical Individual
Priority to GB9717468A priority patent/GB2328435B/en
Publication of GB9717468D0 publication Critical patent/GB9717468D0/en
Publication of GB2328435A publication Critical patent/GB2328435A/en
Application granted granted Critical
Publication of GB2328435B publication Critical patent/GB2328435B/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
    • C07C331/16—Isothiocyanates
    • C07C331/28—Isothiocyanates having isothiocyanate groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C335/18—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Nitroscanate of formula (IV) 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

"A process for preparing isothiocyano compounds The invention relates to a process for preparing isothiocyano compounds and in particular l-isothiocyanate- 4-(4-nitrophenoxy)benzene which is known as nitroscanate.
Nitroscanate is described in GB-1,136,76 and has known anthelmintic properties. GB-1,136,760 and 1,228,516 describe processes for preparing nitroscanate by reacting a compound of the formula
with thiophosgene in an organic solvent medium in the presence of an alkali.
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 for manufacturing an isothiocyano derivative of the formula
comprising the steps of: forming an amide of the formula
wherein R1 is Ac; hydrolysing the amide of formula I to form a compound of formula II
wherein R2 is HC1; 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
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.
In one embodiment of the invention, the hydrolysis is carried out using hydrogen chloride.
Preferably, the thiourea is prepared by reacting a compound of formula II with ammonium thiocyanate, NH4SCN.
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 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
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 130cm for approximately 4 hours. The mixture was cooled to 15-20 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 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 3 980 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 1000C) for about 6 hours. The mixture was then cooled and a yellow granular solid was filtered at approximately 800C. 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 ref fluxed 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 (11)

1. A process for manufacturing an isothiocyano derivative of the formula
comprising the steps of:forming an amide of the formula
wherein R1 is Ac; hydrolysing the amide of formula I to form a compound of formula II
wherein R2 is HC1; 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.
2. A process as claimed in claim 1 wherein the amide of 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 dimethylformamide and potassium carbonate.
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.
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 formula II with ammonium thiocyanate, NH4SCN.
8. A process as claimed in any preceding claim wherein the thiourea of formula III is c..verted to the desired compound of formula IV by releasing ammonia (NH3) 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 chlorobenzene.
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 claimed in any preceding claim.
GB9717468A 1997-08-12 1997-08-18 A process for preparing isothiocyano compounds Expired - Fee Related GB2328435B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
IE970596A IES970596A2 (en) 1997-08-12 1997-08-12 A process for preparing isothiocyano compounds
GB9717468A GB2328435B (en) 1997-08-12 1997-08-18 A process for preparing isothiocyano compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IE970596A IES970596A2 (en) 1997-08-12 1997-08-12 A process for preparing isothiocyano compounds
GB9717468A GB2328435B (en) 1997-08-12 1997-08-18 A process for preparing isothiocyano compounds

Publications (3)

Publication Number Publication Date
GB9717468D0 GB9717468D0 (en) 1997-10-22
GB2328435A true GB2328435A (en) 1999-02-24
GB2328435B GB2328435B (en) 2001-09-05

Family

ID=26312084

Family Applications (1)

Application Number Title Priority Date Filing Date
GB9717468A Expired - Fee Related GB2328435B (en) 1997-08-12 1997-08-18 A process for preparing isothiocyano compounds

Country Status (2)

Country Link
GB (1) GB2328435B (en)
IE (1) IES970596A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103113309A (en) * 2013-02-07 2013-05-22 江西师范大学 Bipyrimidyl dibenzene/diether/diamine and synthesis method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103113309A (en) * 2013-02-07 2013-05-22 江西师范大学 Bipyrimidyl dibenzene/diether/diamine and synthesis method thereof

Also Published As

Publication number Publication date
IES78453B2 (en) 1998-02-11
GB9717468D0 (en) 1997-10-22
GB2328435B (en) 2001-09-05
IES970596A2 (en) 1998-02-11

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PCNP Patent ceased through non-payment of renewal fee

Effective date: 20140818