Process for manufacture of N-alkoxy(or aryloxy)carbonyl...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters

Reexamination Certificate

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C560S148000, C558S019000

Reexamination Certificate

active

06184412

ABSTRACT:

TECHNICAL FIELD OF THE INVENTION
The field of the present invention is the manufacture of carbonyl isothiocyanate derivatives. More particularly, the present invention pertains to an improved process for preparing N-alkoxy(or aryloxy)carbonyl isothiocyanate derivatives, wherein the improvement comprises the presence of a N,N-dialkylarylamine as a catalyst in the reaction process, and the presence of an aqueous solvent in the reaction process.
BACKGROUND OF THE INVENTION
Derivatives of carbonyl isothiocyanates are well known in the art, and various methods for their production are also known in the art.
U.S. Pat. No. 4,659,853 discloses a process for producing derivatives of alkoxy, aryloxy and alkene isothiocyanates by reacting a haloformate, an alkali, alkaline earth metal, lead or ammonium thiocyanate and a compound having the formula R
1
—Y—H wherein R
1
is an alkyl, aryl or alkoxy, Y is oxygen, sulfur or N—R
2
, and R
2
is hydrogen or R
1
; in the presence of a solvent or water and a catalyst. Suitable catalysts include pyridine, quinoline, pyrimidine, pyrazine, quinoxaline and the like.
U.S. Pat. No. 4,778,921 describes a process for the preparation of alkoxy and aryloxy isothiocyanates which includes the reaction of a haloformate and an alkali or alkaline earth metal thiocyanate in the presence of water and a catalyst. The catalyst comprises a six-membered mononuclear or ten-membered fused polynuclear aromatic, heterocyclic compound having one or two nitrogen atoms as the only hetero atoms in the ring.
U.S. Pat. No. 5,194,673 discloses a process for producing alkoxy and aryloxy isothiocyanates by the reaction of a haloformate and an alkali or alkaline earth metal thiocyanate in the presence of water and a catalyst. A co-catalyst is also used in the process to accelerate the reaction rate, increase product purity, and reduce the adverse effects of impurities in the thiocyanate reactants.
In the publication, Chem. Ber. 116, 2044, (1983), it is reported that the use of an aromatic heterocyclic nitrogen catalyst such as pyridine in carbon tetrachloride produced an alkoxythiocarbonyl isothiocyanate wherein the yield was only about 52%.
The most prevalent prior art methods comprise (i) the formation of the carbonyl isothiocyanate, (ii) the recovery and purification thereof, and (iii) the final reaction thereof with the appropriate co-reactant to produce the desired derivative. However, the known methods result in carbonyl isothiocyanate of low yield and purity. Thus, there is a need in the art for a process to produce carbonyl isothiocyanate derivatives in high yield and purity.
BRIEF SUMMARY OF INVENTION
The present invention provides a process for the preparation of N-alkoxy(or aryloxy)carbonyl isothiocyanate derivatives which includes reacting a chloroformate compound of the general formula (I)
wherein R
1
represents a C
1
-C
8
alkyl radical, a C
2
-C
4
alkenyl radical, or a C
6
-C
10
aryl radical; and X represents a halogen atom; with a thiocyanate of the general formula (II)
MSCN  (II)
wherein M represents an alkali or alkaline earth metal, lead, or NH
4
, in the presence of an aqueous solvent, and in the presence of a catalytic amount of a N,N-dialkylarylamine of the general formula (III)
wherein R
2
each represents a C
1
-C
8
alkyl radical or a C
3
-C
6
alkenyl radical, or R
2
together represents a C
5
saturated heterocyclic ring or a C
4
saturated heterocylic ring wherein O may be part of the ring; and R
3
represents an aryl group that can be a phenyl, a naphthyl, a substituted phenyl or a substituted naphthyl; to produce a N-alkoxy(or aryloxy)carbonyl isothiocyanate intermediate product of the general formula (IV)
wherein R
1
is as defined above in formula (I); and reacting a compound of the general formula (V)
R
4
—Y—H  (V)
wherein R
4
represents a C
1
-C
10
alkyl radical, a C
6
-C
10
aryl radical or a C
1
-C
8
alkoxy radical, and Y represents oxygen, sulfur or NR
5
, wherein R
5
represents hydrogen or R
4
, with the intermediate product (IV) to produce a N-alkoxy(or aryloxy)carbonyl isothiocyanate derivative of the general formula (VI)
wherein R
1
is as defined above in formula (I), and R
4
and Y are as defined above in formula (V).
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a process for producing carbonyl isothiocyanate derivatives. In particular, the present process is used to produce N-alkoxy(or aryloxy)carbonyl isothiocyanate derivatives in high yield and purity. The process comprises reacting a chloroformate compound of the general formula (I)
wherein R
1
represents a C
1
-C
8
alkyl radical, a C
2
-C
4
alkenyl radical or a C
6
-C
10
aryl radical; and X represents a halogen atom, with a thiocyanate of the general formula (II)
MSCN  (II)
wherein M represents an alkali or alkaline earth metal, lead, or NH
4
, in the presence of an aqueous solvent, and in the presence of a catalytic amount of a N,N-dialkylarylamine of the general formula (III)
wherein R
2
each represents a C
1
-C
8
alkyl radical or a C
3
-C
6
alkenyl radical, or R
2
together represent a C
5
saturated heterocyclic ring or a C
4
saturated heterocyclic ring wherein O may be part of the ring; and R
3
represents an aryl group that can be a phenyl, a naphthyl, a substituted phenyl or a substituted naphthyl; to produce a N-alkoxy(or aryloxy)carbonyl isothiocyanate intermediate product of the general formula (IV)
wherein R
1
is as defined above in formula (I); and reacting a compound of the general formula (V)
R
4
—Y—H  (V)
wherein R
4
represents a C
1
-C
10
alkyl radical, a C
6
-C
10
aryl radical or a C
1
-C
8
alkoxy radical, and Y represents oxygen, sulfur or NR
5
, wherein R
5
represents hydrogen or R
4
, with the intermediate product (IV) to produce a N-alkoxy(or aryloxy)carbonyl isothiocyanate derivative of the general formula (VI)
wherein R
1
is as defined above in formula (I), and R
4
and Y are as defined above in formula (V).
The process of the present invention may be conducted in a one-pot process.
The process according to the invention is generally carried out at atmospheric pressure. The reaction of the chloroformate (formula I) with the thiocyanate (formula II) is carried out at a temperature of from about −10° C. to about 40° C.; and preferably at a temperature of from about 0° C. to about 10° C. The chloroformate is added to the reaction mixture at a rate such that the temperature of the reaction remains in the desired range. The reaction time for this step in the process of the invention is up to about 16 hours; and preferably the reaction time is from about 1 hour to about 4 hours. The progress of the reaction is monitored by liquid chromatography analysis of the reaction mixture to determine the amount of unreacted thiocyanate.
Suitable chloroformates for use in the process of the present invention include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, hexyl, 2-ethylhexyl, benzyl, phenyl, and allyl chloroformates. In a preferred embodiment, the chloroformate is either methyl chloroformate or propyl chloroformate.
Suitable thiocyanates for use in the process of the present invention include metal, lead and ammonium thiocyanates. Suitable thiocyanates include sodium, lithium, potassium, rubidium, cesium, beryllium, magnesium, calcium, strontium, and barium thiocyanates. In a preferred embodiment, the thiocyanate is sodium thiocyanate.
The reaction of the chloroformate and thiocyanate is carried out in the presence of a catalytic amount of a N,N-dialkylarylamine (formula III), and in the presence of an aqueous solvent.
Suitable N,N-dialkylarylamines for use as a catalyst in the reaction of the present invention include N,N-dimethylaniline, N,N-dimethyl-1-naphthylamine, N,N-dimethyl-p-toluidine, N,N-diethylaniline, N,N-diallylaniline, 1-phenylpiperidine and 4-phenylmorpholine. In a preferred embodiment, the N,N-dialkylarylamine catalyst is N,N-dimethylaniline. The amount of catalyst present in the reaction mixture is such that it comprises from about 0.1% to abou

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