1-chloroalkyl carbamate

Table 3-14 Preparation of 1-alkenyl carbamates from 1-chloroalkyl carbamates.

Table 3-20 Preparation of 1-chloroalkyl carbamates by reaction of Tchloroalkyl chloroformates with primary and secondary amines.

Some examples of 1-chloroalkyl carbamates obtained through N-dealkylation of tertiary amines are gathered in table 3-21 (Ref. 127, 193). 

Since the -NR R2 group makes center A and B both much less harder than does the OR group, we expect some differences between the reactivities of 1-chloroalkyl carbamates and 1-chloroalkyl carbonates. For example the reaction of the hard-soft borderline nucleophiles phenoxide type anions with 1-chloroalkyl-N,N-dilakyl carbamates proceeds selectively through B mechanism to give exclusively alkylation instead of acylation as shown in scheme 136. 

In the course of our studies dedicated to the reactivity of 1-chloroalkyl carbamates toward primary and secondary amines, we discovered that the easy to prepare 1,2,2,2-tetrachloroethyl carbamates are valuable versatile intermediates for the synthesis of N-nitrosoureas (Ref. 198). 

Chloroalkyl carbonates and carbamates are easily made from reaction of 1-chloroalkyl chloroformates with alcohols and amines through standard processes (see section 3-2-2-3, this volume) or original methods developed by 5NPE research teams (section 3-3). If a simple method for the (i-elimination could be devised, the ready availability of 1-chloroalkyl carbamates and carbonates would seem to make these compounds attractive precursors to vinylic carbamates and carbonates. 

While studying the reactivity of carbamoyl chlorides, we found that they react easily with aldehydes in the presence of a Lewis acid as the catalyst to afford 1-chloroalkyl carbamates in good yield as shown in scheme 123 (Ref. 176). The chemical properties of 1-chloroalkyl carbamates which can be obtained by other routes are discussed in section 3-3-2. 

I-3- Reactions n i hloroethyl khloroformates with amines synthesis I and useful Applications of I 1-chloroalkyl carbamates... 

As already discussed in section 3-2-2-3, 1-chloroalkyl carbamates present two electrophilic centers which may be attacked by nucleophiles following differents pathways as shown in scheme 134. 

Similar to he case of reaction with 1-chloroalkyl carbonates studied in section 3-2-2-3, carboxylates anions react with 1-chloroalkyl carbamates to give alkylation derivatives... 

According to the H5AB theory, secondary and primary amines react as hard nucleophiles through A attack mechanism with 1-chloroalkyl carbamates to affords ureas. However, the reaction is slower and less easy than the reaction of amines with 1-chloroalkyl carbonates and strong nucleophilic amines are generally required to reach good yields. 

Chloroalkyl carbamates, prepared with phosgene (see Section 4.3.2 Carbamates ), react with hard nucleophiles such as methoxymethyl amine to afford known ureas such as the herbicide Linuron [219]. 

Alternatively, ethyl A-(/J-chloroalkyl)carbamates can be obtained by the addition of ethyl N.N-dichlorocarbamate to alkenes, followed by a reduction step with sodium bisulfite or sodium metabisulfite (Na,S205). The same mixture of diastereomeric adducts (antijsyn 62 38) was obtained from (E)- and (Z)-2-butene under UV irradiation74, and the thermal addition by a radical mechanism to cyclohexene, cycloheptene, and cyclooctene was unsatisfactory because of the low yield and/or the low diastereoselectivity72,142. However, the addition to cyclopentene, indene, and acenaphthene in benzene as solvent was stereoselective in all cases the <7.s-adducts were formed initially at 0 C, but on heating the m-ad ducts or performing the reaction at 25 °C the tram-adducts were exclusively obtained142. 

Scheme 134 Possible types of nucleophilic attacks to I chloroalkyl carbamates.

Table 3-21 Preparation of l-chloroalkyl carbamates by reaction of R-CHCI-0C(=O)CI with tertiary amines.

A classical procedure for the synthesis of the A-(1-chloroalkyl)amides1 or carbamates68 involves substitution of the hydroxy group in stable A-( 1-hydroxyalkyl)amides (or carbamates) by a halogen function with reagents such as thionyl chloride, phosphorus pentachloride, phosphorus pentabromide, etc. In certain cases merely heating in concentrated hydrochloric or hydrobromic acid suffices1. 

Reaction of 1-chloroalkyl chioroformates with amines, synthesis and useful applications of 1-chloroethyl carbamates. 115... 

The use of a trialkyl amine, for example triethyl amine, as a scavenger is not recommended because 1-chloroalkyl chloroformates react very easily with tertiary alkyl amines to afford N,N-disubsituted carbamates (Ref. 68) as discussed in section 3-3. 

Scheme 82 1-Chloroalkyl carbonates as reagents for the synthesis of carbamates.

Therefore, 1-chloroalkyl carbonates have been proposed as new acylating agents and thus are valuable precursors to carbamates, thiocarbamates and unsymmetrical ureas as outlined in section 3-3, this volume. 

In contrast to the carbamate chemistry, thermal elimination of hydrochloric acid from 1-chloroalkyl carbonates requires much higher temperature and is accompanied by major yield destructive side reactions. The key to an economical route to vinylic carbonates was discovered by Olofson and coworkers (Ref. 129). This discovery was the consequence of a beautiful observation made by Dang, Olofson s student, on the formation of neopentyl fluoroformate and, unexpectably of vinyl neopentyl carbonate while heating 1-chloroethyl neopentyl carbonate with KF in benzonitrile (Ref. 130). 

In opposition to the preceding case, the reaction of phenoxides anions with 1-chloroalkyl-N-monoalkyl carbamates leads to acylation instead of alkylation as shown in scheme 137. 

Chloroalkyl chloroalkyi carbonates to afford carbamates in high yield... 

The reaction was also performed with various types of amines using different kinds of 1-chloroalkyl carbonates (Ref. 64) and was proved to be quite general except with weakly nucleophilic amines. Some examples of carbamates obtained by the reaction of 1-chloroethyl carbonates with primary and secondary amines are given in table 3-27. 

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