Preparation of carbamates

Carbamates are prepared in one step by reacting an alcohol, phosgene, and an amine in the absence of an acid scavenger.

BACKGROUND OF THE INVENTION 
This invention is in the field of chemical processes; more specifically, 
this invention is an improvement in a known process for making carbamates, 
organic compounds of the general formula: 
##STR1## 
Carbamates are well known compounds having established utilities as drugs, 
insecticides, and as polymer precursors, for example. Carbamate 
insecticides are listed in various indexes; for example, "Chemical Week 
Pesticides Register,"McGraw-Hill Book Co., New York, N.Y., 1977 and 
"Pesticide Index," The Entomological Society of America, College Park, 
Md., 1976. Such insecticides include, for example, butacarb, carbofuran, 
carbaryl, terbucarb, ethiofencarb, bufencarb, isoprocarb, aminocarb, 
bendiocarb, dioxacarb, formetanate, methiocarb, promecarb, propoxur, 
dicresyl, and MPMC, which are common names for carbamates of the aforesaid 
formula wherein R.sup.1 is methyl, R.sup.2 is 3,5-di-tert-butylphenyl, 
2,3-dihydro-2,2-dimethyl-7-benzofuranyl, 1-naphthyl, 
2,6-di-tert-butyl-4-methylphenyl, 2-ethylthiomethylphenyl, 
3-(1-methylbutyl)phenyl and 3-(1-ethylpropyl)phenyl (i.e., a mixture), 
2-isopropylphenyl, 4-dimethylamino-3-methylphenyl, 
2,2-dimethyl-1,3-benzodioxol-4-yl, 2-(1,3-dioxolan-2-yl)phenyl, 
3-dimethylaminomethyleneiminophenyl, 3,5-dimethyl-4-(methylthio)phenyl, 
3-isopropyl-5-methylphenyl, 2-(1-methylethoxy)phenyl, 3-methylphenyl, and 
3,4-dimethylphenyl, respectively, and R.sup.3 is hydrogen. 
The aforesaid carbamates are prepared in several ways. For example, they 
are prepared by condensing an alcohol or phenol, R.sup.2 OH, with a 
previously prepared isocyanate, R.sup.1 NCO, or carbamoyl chloride, 
R.sup.1 NHCOCl, or with phosgene first and subsequent reaction of the 
chloroformate thus produced with an amine, R.sup.1 NH.sub.2. 
U.S. Pat. No. 4,086,246 discloses a process for making carbamates in one 
step from commercially available materials, wherein the phenol, R.sup.2 
OH, phosgene, and an amine, R.sup.1 NH.sub.2, are all reacted in a common 
water-immiscible organic solvent in the same reaction vessel at the same 
time in the presence of an acid binding agent to yield the carbamate. The 
acid binding agent, generally a tertiary amine, is a scavenger for the 
by-product hydrogen chloride. 
The scavenged hydrogen chloride salt is a troublesome by-product, difficult 
to remove from the reaction mixture and costly to dispose of without 
contaminating the environment. Furthermore, in order to avoid the 
formation of 1,3-dimethylurea, the prior art has employed large amounts of 
phosgene, creating further separation and disposal problems as well as 
higher costs. Thus, the aforesaid requirements in the one-step process of 
the prior art seriously limit the commercial utility of that process. The 
economic advantage of a one-step process over two steps via an isocyanate, 
carbamoyl chloride, or chloroformate intermediate will be evident. 
SUMMARY OF THE INVENTION 
According to this invention, neither an acid scavenger nor substantial 
excess phosgene are required, thereby avoiding the above-cited 
disadvantages of the known one-step process and providing an economically 
and environmentally attractive method to prepare carbamates. 
This invention is a process for making a carbamate of the formula 
##STR2## 
wherein R.sup.1, R.sup.2, and R.sup.3 can be any substituent organic 
radicals or groups which are not detrimentally affected by the process, 
and R.sup.3 can also be hydrogen, which comprises adding phosgene and an 
amine, R.sup.1 NHR.sup.3, to an alcohol or phenol, R.sup.2 OH, in a 
water-immiscible organic solvent in the absence of an acid binding agent. 
In terms of the prior art one-step process for making compounds of the 
formula 
##STR3## 
wherein 
R.sup.1 is alkyl, alkyl substituted by halogen, alkyl substituted by 
alkoxy, aryl, aryl substituted by halogen, aryl substituted by alkyl, aryl 
substituted by alkoxy, aralkyl, aralkyl substituted by halogen, aralkyl 
substituted by alkyl, aralkyl substituted by alkoxy, cycloalkyl 
substituted by halogen, cycloalkyl substituted by alkyl or cycloalkyl 
substituted by alkoxy, and 
R.sup.2 is an aromatic group, an aromatic group substituted by alkyl, an 
aromatic group substituted by halogen, an aromatic group substituted by 
alkoxy, a heteroaromatic group, a heteroaromatic group substituted by 
alkyl, a heteroaromatic group substituted by halogen, or a heteroaromatic 
group substituted by alkoxy, by the reaction of phosgene with a phenol of 
the formula: 
EQU R.sup.2 --OH 
and further by reaction of a primary amine of the formula: 
EQU R.sup.1 -NH.sub.2 
by reacting all three of the above-mentioned reactants in a common 
water-immiscible organic solvent in the same reaction vessel at the same 
time in the presence of an acid binding agent, this invention is the 
improvement which comprises omitting the acid binding agent. 
Among the carbamates which are produced by this invention, it is preferred 
that the process be employed to make those insecticidal carbamates wherein 
R.sup.1 is methyl, and R.sup.2 is selected from 3,5-di-tert-butylphenyl, 
2,3-dihydro-2,2-dimethyl-7-benzofuranyl, 1-naphthyl, 
2,6-di-tert-butyl-4-methylphenyl, 2-ethylthiomethylphenyl, 
3-(1-methylbutyl)phenyl, 3-(1-ethylpropyl)phenyl, 2-isopropylphenyl, 
4-dimethylamino-3-methylphenyl, 2,2-dimethyl-1,3-benzodioxol-4-yl, 
2-(1,3-dioxolan-2-yl)phenyl, 3-dimethylaminomethyleneiminophenyl, 
3,5-dimethyl-4-(methylthio)phenyl, 3-isopropyl-5-methylphenyl, 
2-(1-methylethoxy)phenyl, 3-methylphenyl, and 3,4-dimethylphenyl. Further, 
it is most preferred that R.sup.2 be selected from 
2,3-dihydro-2,2-dimethyl-7-benzofuranyl, 1-naphthyl, 3,4-dimethylphenyl, 
and 3-methylphenyl. The process of this invention is most especially 
preferred in the case that R.sup.1 is methyl, R.sup.2 is 
2,3-dihydro-2,2-dimethyl-7-benzofuranyl and the product is carbofuran. 
DETAILED DESCRIPTION 
Various water-immiscible organic solvents may be employed in the process, 
but it is preferred that aprotic solvents, such as hydrocarbons, be used. 
For example, aliphatic hydrocarbons, such as hexane, cyclohexane, heptane, 
and octane, and aromatic solvents, such as benzene, toluene, xylene, and 
mesitylene, as well as halogen-substituted analogs of any of these, can be 
used. Toluene is the preferred solvent when the process is used to prepare 
carbofuran. 
Although the process may be conducted at temperatures in the range 
50.degree.-150.degree. C., temperatures between 85.degree. C. and 
125.degree. C. are preferred. 
In carrying out the process, the phosgene and amine are added at the same 
time, i.e. concurrently, but as separate streams, to the stirred R.sup.2 
OH and solvent. It is further preferred that the addition be done 
gradually. The term, "gradually," herein means not all at once, but over 
the course of the reaction, either continuously or discontinuously. 
The course of the reaction is followed conveniently by gas chromatography 
or by monitoring the evolution of HCl; for example, by trapping the 
evolved HCl in a standardized NaOH solution and back titrating; two moles 
of HCl are evolved for every mole of R.sup.2 OH reacted to form carbamate. 
The process of making carbamate formally requires equimolar amounts of 
amine, R.sup.2 OH, and phosgene, but it is preferred to employ a slight 
excess of phosgene, to about a 20% molar excess of phosgene over amine. 
Very close to equimolar amounts of amine and R.sup.2 OH are preferred in 
general. 
It is especially preferred, however, in making carbofuran, to terminate the 
reaction before all of the 2,3-dihydro-2,2-dimethyl-7-benzofuranol has 
reacted. As complete conversion of the benzofuranol is approached, the 
following side reaction, producing an allophanate and consuming the 
desired product, becomes more pronounced. 
EQU R.sup.1 NHCOOR.sup.2 +COCl.sub.2 +R.sup.1 NH.sub.2 .fwdarw.R.sup.1 
NHCONR.sup.1 COOR.sup.2 +HCl 
Thus, it is desirable to monitor the reaction mixture, e.g., with gas 
chromatography. When the allophanate concentration is about 1-20%, 
preferably about 2-5%, of the carbofuran concentration, the reaction is 
terminated by stopping the addition of phosgene and methylamine. At such 
termination, the conversion of 2,3-dihydro-2,2-dimethyl-7-benzofuranol is 
generally about 80%. The crystalline carbofuran is isolated by filtration, 
and the filtrate, containing unreacted 
2,3-dihydro-2,2-dimethyl-7-benzofuranol, is recycled as the solvent in a 
subsequent batch run. In this way the overall yield is improved.

The manner in which the process of this invention is carried out is 
illustrated in the following Examples, the specific details of which 
should not be regarded as limitations. 
EXAMPLE 1 
PREATION OF CARBOFURAN 
A stirred solution of 2,3-dihydro-2,2-dimethyl-7-benzofuranol (100.0 g, 0.6 
mole) in 500 g of toluene was heated to 95.degree. C. under nitrogen. 
Gaseous phosphene (approximately 15 g/hr) and monomethylamine 
(approximately 3-4 g/hr) were metered into the flask concurrently and 
gradually until gas chromatographic analysis indicated that the amount of 
allophanate by-product was 3% of the carbofuran present. At this point, 
the addition of phosgene and monomethylamine was stopped, but heating was 
continued for 1.25 hours to ensure complete reaction. In this run, the 
point at which the reaction was terminated corresponded to the addition of 
73.0 g (0.74 mole) of phosgene and 19.0 g (0.61 mole) of monomethylamine, 
which resulted in an 80% conversion of 
2,3-dihydro-2,2-dimethyl-7-benzofuranol and a 73% yield of carbofuran. 
After a total reaction time of 5.75 hours, the reaction mixture was 
filtered hot. After cooling the filtrate to room temperature, the 
carbofuran which had crystallized was isolated by filtration and dried. 
The dried carbofuran weighed 79.5 g and was assayed to be 98% pure, 
representing a 60% isolated yield. The filtrate was then recycled in the 
next carbamoylation run. 
The same procedure was used for runs 2 through 10 in in which the filtrate 
was similarly recycled. Data appear in Table I. The overall yield of 
carbofuran having a purity of 95-98% was 90%. 
TABLE I 
__________________________________________________________________________ 
Yield 
R.sup.2 OH R.sup.2 OH 
Carbo- 
Total 
Fresh 
COCl.sub.2 
CH.sub.3 NH.sub.2 
Time 
Temp. 
Conver. 
furan 
Run 
(mole).sup.1 
(mole) 
(mole) 
(mole) 
(hr) 
(.degree.C.) 
(%) (%) 
__________________________________________________________________________ 
1 0.60 
0.60 
0.74 
0.61 5.75 
95 80 73 
2 0.61 
0.48 
0.72 
0.55 5.0 
96 77 69 
3 0.62 
0.48 
0.73 
0.52 4.5 
96 76 66 
4 0.63 
0.46 
0.73 
0.63 5.75 
97 75 63 
5 0.60 
0.43 
0.70 
0.48 4.5 
96 78 70 
6 0.59 
0.49 
0.67 
0.54 4.5 
97 78 63 
7 0.61 
0.48 
0.72 
0.61 5.0 
97 80 70 
8 0.60 
0.46 
0.75 
0.64 5.5 
96 80 65 
9 0.59 
0.46 
0.77 
0.48 5.0 
97 85 73 
10 0.59 
0.49 
0.75 
0.52 4.5 
97 80 76 
__________________________________________________________________________ 
.sup.1 Includes unreacted R.sup.2 OH from previous run. 
EXAMPLE 2 
PREATION OF CARBARYL 
A stirred solution of 1-naphthol (86.5 g, 0.6 mole) in 500 g of toluene was 
heated under nitrogen to 98.degree. C. Phosgene (79.9 g, 0.8 mole) and 
methylamine (22.0 g, 0.7 mole) were then metered into this solution 
concurrently and gradually over a period of approximately 6.5 hours. The 
reaction mixture was filtered hot. The filtrate was then allowed to cool 
to room temperature, and the crystallized carbaryl was recovered by 
filtration. The yield of 1-naphthyl methylcarbamate was 78%. 
EXAMPLE 3 
PREATION OF 3,4-DIMETHYLPHENYL METHYLCARBAMATE 
A solution of 3,4-dimethylphenol (73.3 g, 0.600 mole) in 500 g of toluene 
was heated under nitrogen to 99.degree. C. Phosgene (71 g, 0.72 mole) and 
methylamine (20 g, 0.64 mole) were metered into the stirred solution as 
gases concurrently and gradually over a period of four hours, while the 
temperature was maintained at 97.degree.-99.degree. C. After an additional 
half hour at the same temperature, the hot mixture was filtered; the 
filtrate was concentrated to yield 102.7 g of an oil which contained 
3,4-dimethylphenyl methylcarbamate in a 70% yield. 
EXAMPLE 4 
PREATION OF 3-METHYLPHENYL METHYLCARBAMATE 
A solution of 3-methylphenol (64.9 g, 0.600 mole) in 500 g of toluene was 
heated under nitrogen to 95.degree. C. Phosgene (76.0 g, 0.77 mole) and 
methylamine (16.0 g, 0.52 mole) were metered into the stirred solution as 
gases concurrently and gradually over a period of 4.5 hours, while the 
temperature was maintained at 96.degree.-98.degree. C. After an additional 
half hour at the same temperature, the hot mixture was filtered; the 
filtrate was concentrated to yield 103.5 g of an oil which contained 
3-methylphenyl methylcarbamate in a 78% yield.