Process for the manufacture of 1-bromoalkyl hydrocarbyl carbonates

The invention relates to a new process for the preparation of 1-bromoalkyl hydrocarbyl carbonates. The carbonates according to the invention are prepared by reacting an alpha-chlorinated carbonate of formula ##STR1## with an anhydrous brominated compound of formula ZBr in which Z represents hydrogen, the group (CH.sub.3).sub.3 -Si-, the group ##STR2## or bromine if R.sub.2 is other than an aromatic radical, in the presence of a catalyst chosen from the group consisting of heteroaromatic amines, quaternary ammonium or phosphonium halides, hexasubstituted guanidinium halides, alkaline earth metal halides or alkali metal halides in combination with a complexing agent for their cation. The carbonates according to the invention find their preferential applications as blocking agents for some antibiotics or as agents for the synthesis of phosphorus-containing carbonates which can be used as insecticides.

The invention relates to a new process for the preparation of 1-bromoalkyl 
hydrocarbyl carbonates. The invention also relates to new 1-bromoalkyl 
hydrocarbyl carbonates. 
Very few alpha-brominated carbonates are known because the preparation 
thereof had remained difficult until recent years. 
It is possible to prepare 1-bromoethyl ethyl carbonate by reacting a 
1-bromoethyl haloformate with ethanol according to the reaction scheme: 
##STR3## 
X representing chlorine or bromine. 
The difficulty of this process lies in the preparation of the starting 
haloformate: 
##STR4## 
According to European Patent Application EP 108, 547, a free radical 
bromination of ethyl chloroformate or of ethyl bromoformate is carried 
out. 
This free radical bromination has disadvantages. The UV lamps employed in 
preference to free radical initiators consume large amounts of energy and 
the amount of energy consumed increases with increasing reaction periods 
used in implementing this method. Different brominated by-products are 
always obtained. 
It is also possible to prepare 1-bromoethyl bromoformate by reacting 
acetaldehyde with bromophosgene as described in French Patent Application 
FR 2,532,933. However, in this case, it is essential to use catalysts, and 
bromophosgene is not a reagent which is available on the market. It is not 
very stable and is very difficult to prepare. It is manufactured, for 
example, by reacting carbon monoxide with bromine, but this reaction 
requires very specific industrial plants. 
Another process for the preparation of 1-bromoethyl ethyl carbonate 
consists in brominating diethyl carbonate by the free radical method. The 
same disadvantages of the free radical methods as described above are 
encountered: production of by-products and high energy requirement. 
Additionally, this process cannot be suitable for the production of a 
number of 1-bromoethyl carbonates because, depending on the structure of 
the carbonate used as the starting material, bromine will be attached in a 
larger quantity with the hydrocarbon group other than the ethyl group; for 
example, when the attachment of bromine to ethyl isopropyl carbonate is 
attempted, ethyl 1-bromoisopropyl carbonate is the preponderant product 
obtained. 
It is also possible to use 1-chloroethyl ethyl carbonate as the starting 
material and to carry out a substitution of chlorine by bromine using a 
large excess of a bromine salt such as lithium or ammonium bromide, as 
mentioned in European Patent Application No. 108,547. This method also has 
disadvantages because, as this is an equilibrium reaction, the reaction is 
incomplete. 
For example, as mentioned in Example 12 of this application, with a 300% 
excess of lithium bromide, a mixture of brominated carbonate and 35% of 
1-chloroethyl ethyl carbonate, and not the pure product, is obtained and 
the separation of the alpha-chlorinated carbonate and the alpha-brominated 
carbonate is very difficult, as in the case of all other lower alkyl 
carbonates. 
A new process for the preparation of 1-bromoethyl hydrocarbyl carbonates 
has very recently been proposed in French Patent N.degree. 2 573 756. 
According to this process, hydrobromic acid is added to a vinyl 
hydrocarbyl carbonate; however, this process does not make it possible to 
obtain alpha-brominated carbonates other than 1-bromoethyl carbonates, and 
vinyl chloroformate which is useful in the preparation of the carbonate 
used as the starting material is not very easy to obtain. 
Consequently, there was a need for a new process for the preparation of a 
large variety of 1-bromoalkyl hydrocarbyl carbonates, which does not have 
the disadvantages described above. 
The object of the invention is precisely to provide such a process. 
According to this new process, 1-bromoalkyl hydrocarbyl carbonates, of 
formula: 
##STR5## 
in which R.sup.1 represents a straight-chain or branched, C.sub.1 
-C.sub.20 aliphatic or C.sub.5 -C.sub.15 alicyclic radical and R.sup.2 
represents a substituted or unsubstituted, C.sub.1 -C.sub.12 aliphatic, 
C.sub.5 -C.sub.20 alicyclic or C.sub.6 -C.sub.14 aromatic radical, are 
prepared by reacting an alpha-chlorinated carbonate of formula 
##STR6## 
in which R.sup.1 and R.sup.2 have the above meanings, with an anhydrous 
compound of formula ZBr in which Z represents a hydrogen atom, the group 
(CH.sub.3).sub.3 -Si- or 
##STR7## 
and may also represent a bromine atom when R.sup.2 is other than an 
aromatic radical, in the presence of a catalyst chosen from amongst 
heteroaromatic amines, quaternary ammonium or phosphonium halides, 
hexasubstituted guanidium halides, alkali metal halides in combination 
with a complexing agent for their cation or alkaline earth metal halides, 
in a quantity of between 0.5 and 10 mole per cent relative to the 
alpha-chlorinated carbonate and at a temperature of between 40.degree. C. 
and 150.degree. C. 
The reaction scheme is as follows: 
##STR8## 
The alpha-chlorinated carbonates used as the starting material are 
available on the market or may be prepared by known methods, for example 
by reacting alpha-chlorinated chloroformates with alcohols or phenols as 
mentioned in the Patent Applications FR 2 559 764 and EP 185,578. 
The radical R.sup.1 is preferably a C.sub.1 -C.sub.8 aliphatic or a C.sub.5 
-C.sub.10 alicyclic radical. 
R.sup.2 is preferably a substituted or unsubstituted, C.sub.1 -C.sub.8 
aliphatic, C.sub.5 -C.sub.10 alicyclic or C.sub.6 -C.sub.10 aromatic 
radical. 
The substituent(s) for R.sup.2 is (are) preferably chosen from the group 
comprising aryl, aryloxy and alkoxy radicals and chlorine, fluorine and 
bromine atoms. 
The compound ZBr must be anhydrous. It is generally employed in a quantity 
of between 1 and 2 moles per mole of alpha-chlorinated carbonate, 
preferably between 1.1 and 1.5 moles. 
HBr, (CH.sub.3).sub.3 -Si-Br or 
##STR9## 
is preferably employed as the compound ZBr. 
A catalyst is essential for obtaining high yields. 
Pyridine, 4-dimethylaminopyridine, quaternary ammonium or phosphonium 
chlorides and bromides, hexabutylguanidinium chloride, potassium chloride 
in combination with 18-crown-6 crown ether and magnesium bromide may be 
mentioned as examples of catalysts. 
The quantities of catalysts employed are preferably between 1 and 5 mole 
per cent relative to the quantity of the alpha-chlorinated carbonate. 
The reaction mixture is generally heated and preferably to a temperature of 
between 60.degree. and 120.degree. C. 
The reaction may be carried out with or without a solvent. Aromatic 
solvents such as toluene and aliphatic solvents such as 2-bromobutane or 
ethyl acetate may be mentioned as solvents which are well suited. 
The process of the invention is simple. The implementation thereof does not 
require expensive plants or the use of high amounts of energy. The raw 
materials are easily available. It enables many alpha-brominated 
carbonates, and especially alpha-brominated carbonates which could never 
be prepared previously, to be obtained with a high purity and with high 
yields. 
The 1-bromoalkyl hydrocarbyl carbonates prepared according to the process 
of the invention are intermediates of synthesis which may, for example, 
advantageously replace their less reactive chlorinated homologues or more 
unstable iodinated homologues in many reactions. 
One of their important applications is the modification the carboxylic acid 
groups by the introduction of a carbonate group, in various compounds. The 
reaction may be outlined as follows: 
##STR10## 
This application is described especially in U.S. Pat. No. 4,426,391 and in 
the Patent Applications EP 54,512, EP 108,547, FR 2,532,933 and FR 
2,387,988. 
Thus, according to the teaching of the French Patent Application No. 
2,532,933, alpha-brominated carbonates find a preferential application as 
blocking agents for some antibiotics such as bac-ampicillin. 
They may also react with phosphoric acid derivatives, as mentioned in the 
Patent Application DE 2,628,410: 
##STR11## 
The compounds obtained according to this reaction scheme find a useful 
application as insecticidal products. 
As the C--Br bond is much more labile than the C--Cl bond, alpha-brominated 
carbonates could be used in a much smaller quantity than the corresponding 
alpha-chlorinated carbonates. The reaction conditions will be milder and a 
certain degradation of the starting compound will therefore be avoided. 
The yields will be higher. 
Moreover, the alpha-brominated carbonates are much more stable than the 
corresponding iodinated carbonates and this will enable, when they are 
used for replacing them, products of higher purity to be obtained in a 
larger quantity. 
The examples which follow illustrate the invention without, however, 
limiting it.

EXAMPLE 1 
Preparation of 1-bromoethyl isopropyl carbonate 
13.11 g (78.7 mmol) of alpha-chloroethyl isopropyl carbonate and 0.35 g 
(1.09 mmol; 0.014 eq.) of tetra-n-butylammonium bromide are introduced 
into a reactor equipped with a stirrer, a thermometer, a condenser and a 
gas inlet tube. The mixture is heated to 80.degree. C. and a gas stream 
containing 38 g of anhydrous hydrobromic acid is passed through it over 6 
hours. 
The reaction medium is degassed with argon and distillation is carried out 
under reduced pressure. 
13.63 g (yield: Yld=82%) of the carbonate expected, with the following 
characteristics, are thereby collected: 
Boiling point 80.degree.-83.degree. C./18 mm Hg 
IR D (C=0): 1760 cm.sup.-1 
.sup.1 H NMR (CDCl.sub.3, .delta. ppm): 6.60 (q, J=6 Hz, 1 H); 4.91 (sept, 
J=6 Hz, 1 H); 2.00 (d, J=6 Hz, 3 H); 1.3 (d, J=6 Hz, 6 H). 
EXAMPLE 2 
Preparation of 1-bromoethyl ethyl carbonate 
The catalyst MgBr.sub.2.(Et.sub.2 O).sub.x is prepared starting with 0.15 g 
(0.006 mol) of magnesium and 1.18 g (0.006 mol) of 1,2-dibromoethane in 10 
ml of ether. When the magnesium is used up, the lower phase is added to 
20.2 g (0.13 mol) of 1-chloroethyl ethyl carbonate. The mixture is heated 
to 60.degree.-65.degree. C. and 36.6 g (0.23 mol) of bromine is slowly 
introduced over 5 h. 
After stirring for 20 h at 60.degree. C., the mixture is allowed to cool, 
25 ml of CH.sub.2 Cl.sub.2 are added and washing is carried out with water 
and then with an aqueous Na.sub.2 S.sub.2 O.sub.3 solution. 
Drying over MgSO.sub.4, filtration, concentration and distillation under 
reduced pressure are carried out and 11.2 g (yield=43%) of the carbonate 
expected are collected. 
Boiling point: 62.degree.-66.degree. C./18 mm Hg 
IR D (C=0): 1760 cm.sup.-1 
.sup.1 H NMR (CDCl.sub.3, .delta. ppm): 6.58 (q, J=6 Hz, 1 H); 4.20 (q, J=7 
Hz, 2 H); 1.97 (d, J =6 Hz, 3 H); 1.30 (t, J=7 Hz, 3 H) 
EXAMPLES 3 AND 4 
Preparation of 1-bromoethyl ethyl carbonate and of 1-bromopentyl methyl 
carbonate 
The reaction is carried out as in Example 1. The reagents employed and the 
results obtained are given in the table below: 
__________________________________________________________________________ 
EX. 
##STR12## Catalyst HBr T.degree. C. 
Period 
Yld 
__________________________________________________________________________ 
##STR13## MgBr.sub.2.(Et.sub.2 O).sub.x.sup.b 0.0093 
35.1 g; 0.434 mol 
70.degree. C. 
24 h 
76%.sup. 
4 
##STR14## 
##STR15## 19.4 g; 0.24 mol 
80- 85.degree. C. 
7 h 
34%.sup.a 
__________________________________________________________________________ 
.sup.a non-optimized yield 
.sup.b MgBr.sub.2.(Et.sub.2 O).sub.x prepared starting with Mg + 
BrCH.sub.2 CH.sub.2 Br in ether as in Example 2. 
EXAMPLE 5 
Preparation of 1-bromoethyl phenyl carbonate 
15.4 g (0.077 mol) of 1-chloroethyl phenyl carbonate, 0.44 g (0.0014 mol) 
of tetrabutylammonium bromide and 13.7 g (0.090 mol) of trimethylsilane 
bromide are introduced into a distillation apparatus equipped with a 15 cm 
Vigreux column, a thermometer and a stirrer. The mixture is heated at 
90.degree. C. for 24 h and the trimethylsilane chloride released is 
removed by distillation. The product expected is then distilled. 17.2 g 
(Yld=91%) are obtained. 
Boiling point: 72.degree.-77.degree. C./0.04 mm Hg 
IR D (C=0) 1775 cm.sup.-1 
.sup.1 H NMR (CDCl.sub.3, .delta. ppm); 7.6-6.9 (m, 5 H); 6.56 (q, J=6 Hz, 
1 H); 1.98 (d, J=6 Hz, 3 H) 
EXAMPLES 6 TO 8 
Preparation of 1-bromoethyl ethyl carbonate 
The reaction is carried out as in Example 5 starting with 1-chloroethyl 
ethyl carbonate in the presence of various catalysts and replacing the 
trimethylsilane bromide with acetyl bromide. The quantities of free agents 
employed and the results obtained are given in the table below. 
__________________________________________________________________________ 
EX 
##STR16## 
Catalyst 
##STR17## 
T.degree. C. 
Period 
##STR18## 
__________________________________________________________________________ 
6 20.5 g; (C.sub.8 H.sub.17).sub.3 NMe.sup..sym. Cl.sup..crclbar. 
19.7 g; 
100- 
26 h 
73% 
0.13 mol 
0.67 g; 0.16 mol 
105 
0.0017 mol 
7 20.1 g; 0.13 mol 
##STR19## 
21.6 g; 0.18 mol 
95 24 h 
63% 
8 20.1 g; KCl - 18-C-6 
20.4 g; 
95 24 h 
55% 
0.13 mol 
0.80 g; 0.011 mol 
0.17 mol 
1.20 g; 0.0045 mol 
__________________________________________________________________________ 
EXAMPLE 9 
Preparation of 1-bromoethyl isopropyl carbonate 
35.2 g (0.21 mol) of 1-chloroethyl isopropyl carbonate, 0.71 g (0.0022 mol) 
of tetrabutylammonium bromide and 40 ml of 2-bromobutane are introduced 
into an apparatus equipped with a thermometer, a stirrer and a Soxhlet 
extractor filled with CaCl.sub.2 and fitted with a condenser cooled by dry 
ice and ethyl acetate (in order to recycle the excess HBr) and a gas inlet 
tube from above. 
The mixture is heated to 95.degree.-104.degree. C. and a gas stream 
containing 26.1 g (0.32 mol) of anhydrous hydrobromic acid is passed 
through it over 8 hours. 
The reaction medium is degassed with argon, the 2-bromobutane is removed, 
distillation is carried out under reduce-d pressure and 40 g of the 
product expected are obtained (Yld=90%). 
Boiling point: 82.degree./18 mm Hg 
EXAMPLE 10 
Preparation of 1-bromoethyl isopropyl carbonate 
A solution of 1-chloroethyl isopropyl carbonate (16.7 g; 0.10 mol) and 
hexabutylguanidinium chloride (0.43 g; 0.0011 mol) in toluene (40 ml) is 
heated to 115.degree. C. and a gas stream containing 15 g (0.186 mol) of 
anhydrous hydrobromic acid is passed through it over 7 hours. 
The reaction medium is degassed with argon, the toluene is removed, the 
product is distilled under reduced pressure and 16.0 g of the expected 
product is obtained (Yld=76%).