Process for the preparation of substituted diphenyl ethers

This invention relates to certain phenoxybenzoates having excellent selective herbicidal properties. The compounds of the present invention are defined by the formula ##STR1## wherein L, M and N are independently hydrogen, halogen, trihalomethyl, nitro, cyano, C.sub.1-4 alkyl, C.sub.1-4 alkoxy and ##STR2## and A is selected from the group of radicals defined by the formulae: ##STR3##

The present process provides an efficient and economical method for the 
synthesis of certain substituted phenyl ethers, having the formula 
##STR4## 
wherein L, M and N are independently hydrogen, halogen, trihalomethyl, 
nitro, cyano, C.sub.1-4 alkyl, C.sub.1-4 alkoxy and 
##STR5## 
and A is selected from the group of radicals defined by the formulae: 
##STR6## 
wherein 
R is an unsaturated, straight chain or branched aliphatic radical having 
from 2 to 8 carbon atoms; 
R.sub.1 and R.sub.2 are independently hydrogen or alkyl of 1 to 4 carbon 
atoms; 
R.sub.3 and R.sub.4 are independently hydrogen, or a saturated or 
unsaturated straight or branched chain C.sub.1-8 aliphatic radical 
optionally substituted with halogen, hydroxy, alkoxy, cyano or nitro; 
R.sub.5 is a saturated or unsaturated, straight chain or branched aliphatic 
hydrocarbon radical of from 1 to 18 carbon atoms wherein one or more of 
the --CH.sub.2 --groups can be replaced with --O--, --S--, --S--S--, 
--SO-- or --SO.sub.2 -- and said hydrocarbon radical is optionally 
substituted with halogen, trihalomethyl, cyano, aryl, hydroxy, alkoxy, 
nitro or cycloalkyl having 3 to 6 carbon atoms; 
R.sub.6 is a saturated or unsaturated straight chain or branched aliphatic 
radical containing from 1 to 8 carbon atoms, optionally substituted with 
halogen, trihalomethyl, cyano, hydroxy, nitro, acetoxy, alkoxy, thioalkoxy 
or aryl; an aryl radical optionally substituted with halogen, 
trihalomethyl, hydroxy, cyano, nitro, alkyl or alkoxy; a cyclic 3-6 
membered alkylene ring or a 5-6 membered alkenylene ring or benzyl 
optionally substituted with halogen, trihalomethyl, alkyl, hydroxy, alkoxy 
or cyano; 
##STR7## 
each R.sub.9 is independently an alkylene diradical having from 1 to 4 
carbon atoms; 
X, X' and X" are independently --O--, --S-- or --NR.sub.4 --; 
Z and Z" are independently, --O-- or --S--, Z" additionally can be thiol or 
--SO.sub.3 --; and Z' is --S--, --S--S--, --SO-- or --SO.sub.2 --; 
p has a value of 2-6; n in each instance, has a value of 0 or 1; and 
m has a value of 1-6. The synthesis of these compounds is defined by a 2-, 
3- or 4-step process wherein the first 2 steps involve reacting a 
substituted phenoxybenzoic acid having the formula 
##STR8## 
with a diacylating agent having the formula HXA'X'H wherein A' is R.sub.5, 
##STR9## 
at a temperature between about 20.degree. and about 200.degree. C. under 
from about 1 to about 5 atmospheres pressure for a period of from about 1 
to about 40 hours; preferably at a temperature between about 100.degree. 
and 150.degree. C. under atmospheric pressure for a period of from about 
10 to about 40 hours, to produce the corresponding bis-compound having the 
formula 
##STR10## 
and then nitrating the bis-compound with a conventional nitrating agent at 
a temperature between about -5.degree. and about +70.degree. C. under 
atmospheric pressure for a period of from about 1 to about 10 hours; 
preferably at a temperature between about 0.degree. C. and about 
30.degree. C. for a period of from about 1 to about 5 hours, to produce 
the corresponding nitrated compound having the formula: 
##STR11## 
It will be appreciated that when A' is R.sub.5, the product of formula 1 
A-IV is directly produced by the second step, i.e. nitration step C. 
Examples of suitable acylating agents include ethylene glycol, 
2-hydroxyethyl ether, 2,2'-thiodiethanol, 1,2-ethanedithiol, 
ethylenediamine, 2-mercaptoethanol, 1,4-butenediol, 2-hydroxyethyl 
sulfide, and the like. 
The above nitration step can be carried out in the absence or in the 
presence of an inert solvent, such as methylene dichloride, ethylene 
dichloride, chloroform, carbon tetrachloride, etc. Suitable nitrating 
agents include nitric acid/sulfuric acid, potassium nitrate/sulfuric acid, 
nitric acid/sulfuric acid/acetic anhydride and other conventional 
nitrating mixtures. When a solvent is employed, the concentration of the 
bis compound can be varied over a wide range limited only by economic 
considerations; however, it is found that concentrations between about 10 
and about 80 weight percent provides good results. 
The mole ratio of diacylating agent to the phenoxybenzoic acid is most 
preferably about 1:2. The mole ratio of NO.sub.2.sup.+ in the nitrating 
agent is most preferably 2:1 with respect to the intermediate 
bis-compound; although a greater excess of nitrating agent, can be 
employed if desired. 
When compounds of formula 1 having A group I, III and V are desired, the 
nitrated product of the 2 step process described above is transacylated by 
reacting it with at least an equimolar amount of an above-described 
diacylating agent at a temperature of between about 20.degree. and about 
250.degree. C. under from about 1 to about 5 atmospheres pressure for a 
period of 0.5 to about 20 hours; preferably at a temperature between about 
140.degree. and about 200.degree. C. under atmospheric pressure for a 
period of from about 1 to 10 hours. The reaction is generally defined by 
the equation: 
##STR12## 
The transacylating step is preferably carried out in a presence of a 
transacylating catalyst such as sulfuric acid, p-toluene sulfonic acid, 
hydrogen halide, hydrate manganese acetate, boron trifluoride etherate, 
phosphoric acid, calcium oxide, barium oxide, lead oxide, sodium oxide, 
lead nitrate, zinc acetate, manganese borate, zinc borate or an acidic ion 
exchange resin. Of these transesterification catalysts, manganese acetate 
tetrahydrate has been found to be very effective. The mole ratio of 
diacylating agent employed in this third step of the reaction is between 
about 1:1 and 50:1, preferably between about 3:1 and about 20:1 with 
respect to the nitrated product of Step C. The excess and unreacted 
diacylating agent in this stage functions as a solvent for the 
transacylation reaction and is preferably separated from the product for 
recycle. 
When the 3-step process is carried out in batch operation the various 
coreactants in each step are added sequentially after substantial 
completion of the preceding reaction. However, the synthesis may also be 
effected in separate reactors operated in series with heating and/or 
cooling devices between the various stages, as required. Also unreacted 
components may be separated from product and recycled to the appropriate 
stage. 
To obtain the products of A groups II and VI, the product of equation D is 
reacted with a carbonyl-containing compound of the formula 
##STR13## 
or the acid halide or anhydride of such carbonyl-containing compounds 
wherein X, X" and n are as defined above and F is (X").sub.n R.sub.6 or 
R.sub.8, according to the reaction defined by equation E; 
##STR14## 
Reaction E is effected at a temperature of between about 0.degree. C. and 
about 200.degree. C. under a pressure of from atmospheric to about 5 
atmospheres over a period of from 0.5 to 20 hours; preferably at between 
about 25.degree. C. and about 75.degree. C. under atmospheric pressure 
over a period of from about 1 to 10 hours. 
Suitable carbonylating agents include acetic acid, chloroacetic acid, 
thioacetic acid, N,N-dimethylcarbamyl chloride, pyruvic acid, propionic 
acid, methoxyacetyl chloride, acetic anhydride, phthalic anhydride, and 
the like. 
The carbonyl-containing reactant is employed in a mole ratio of from about 
1:1 to about 20:1 with respect to the product of reaction D. If desired 
the carbonylation can be effected in the presence of an inert solvent, 
e.g. tetrahydrofuran, and any of those previously given for the nitration 
reaction C. However, this reaction can be effected in the absence of 
solvent or in the presence of excess carbonyl-containing compound which 
excess may function as a recyclable solvent to this stage of the reaction. 
The product compounds of the present invention are those named in Tables I 
of co-pending patent applications, Ser. Nos. 239,286 filed Mar. 2, 1981; 
266,675 filed May 22, 1981; 283,402 filed July 15, 1981; 292,320 filed 
Aug. 12, 1981; 301,664 filed Sept. 14, 1981 and 310,663 filed Oct. 13, 
1981 which disclosures are incorporated herein by reference. As described 
in the foregoing applications the present products of this invention are 
useful as herbicides and may have additional uses and applications 
depending upon the particular compound. 
Having generally described the process of this invention, reference is now 
had to specific preferred embodiments described in the following examples, 
in which all amounts and proportions are reported by weight unless 
otherwise indicated. It is to be understood that the scope of this 
invention is not to be limited to these examples and is instead defined by 
the foregoing disclosure and the appended Claims.

EXAMPLE 1 
Preparation of 
1,2-Bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]ethane 
A. In a 250 ml glass flask, xylene (100 cc), 
3-(2-chloro-4-trifluoromethylphenoxy) benzoic acid (131.6 g., 0.1 mole), 
ethylene glycol (6.2 g., 0.1 mole) and conc. sulfuric acid (2 g.) were 
heated to reflux (130.degree. C.) while azeotroping off about 2 cc of a 
water-glycol mixture. The temperature was maintained for 30 hrs., after 
which the mixture was cooled to room temperature. The product mixture was 
then analyzed by thin layer chromatography (10:1 toluene/ethyl acetate on 
silica) and the following product separations were reported: R.sub.f =0.71 
(major spot-product), 0.47 (monoester), and 0.13 (starting material). The 
reaction mixture was partitioned between ethyl acetate and a 5% sodium 
bicarbonate solution. The organic phase was reduced in volume by 
evaporation leaving 25.4 g of crude bis-ester, which was subjected to 
column chromatography eluting with a 3:1 toluene/CH.sub.2 Cl.sub.2 solvent 
mixture. The product fractions averaged 20.6 g. (62.6%) upon evaporation. 
Recrystallization from 5:1 hexane/toluene yielded 16.2 g. of 
1,2-bis[5-(2-chloro-4-trifluoromethylphenoxy)benzoyloxy]ethane; m.p. 
98.degree. C.; nmr (CDCl.sub.3); .delta. 8.1-6.9 (7, m, CH--Ar), 4.7 (4, 
s, CH.sub.2); ir (neat) 1726 cm.sup.-1 (C.dbd.O). 
B. A solution of 
1,2-bis[5-(2-chloro-4-trifluoromethylphenoxy)benzoyloxy]ethane (6.6 g., 
0.01 mole) in 15 cc of dichloroethane was treated with 10.4 g. of ca. 
33/67 nitric/sulfuric acid at 2.degree.-4.degree. C. for 1.75 hours. Thin 
layer chromatography (3:1 toluene/CH.sub.2 Cl.sub.2 on silica) analysis 
indicated a product with R.sub.f =0.39. Water (15 cc) was added dropwise 
at 0.degree.-5.degree. C. The layers were separated and the organic phase 
was washed sequentially with 5% sodium bicarbonate and water. The solvent 
was removed by rotary evaporation leaving 6.3 g. of 
1,2-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]ethane 
(84%); nmr (CDCl.sub.3).delta. 8.1-7.0 (10, m, CH--Ar), 4.6 (4, s, 
CH.sub.2); ir (neat) 1750 (C.dbd.O), 1530 cm.sup.-1 (NO.sub.2). 
Other compounds having the general formula 1 where A is group IV are 
prepared by the above procedure A. and B. except for substitution of the 
ethylene glycol reactant in step A. 
Accordingly, 
1,3-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]propane is 
prepared by substituting 1,3-propandiol for ethylene glycol in Step A; 
1,5-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]3-oxapenta 
ne is prepared by substituting 2-hydroxyethyl ether for ethylene glycol in 
Step A; and 
1,6-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]3,4-dithia 
hexane is prepared by substituting 2-hydroxyethyl disulfide for ethylene 
glycol in Step A. 
EXAMPLE 2 
Preparation of [2-Hydroxy 
ethyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate 
The reaction product of Example 1 B, 
1,2-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]ethane 
(6.1 g, 0.008 mole) was mixed with ethylene glycol (10.1 g., 0.16 mole) 
and manganese acetate tetrahydrate (0.4 g.) and heated at 
165.degree.-185.degree. C. for 5 hours, and then cooled to room 
temperature. The product mixture was then subjected to thin layer 
chromatographic analysis (5:1 toluene/ethyl acetate on a silica gel 
support); which showed a single spot with R.sub.f =0.2 identified as 
2-hydroxyethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate. This 
indicated that complete transacylation had taken place. 
The mixture was partitioned between water and toluene/ethyl acetate and the 
volume of the organic phase was reduced by rotary evaporation. The 
resulting product was then subjected to high pressure liquid 
chromatography purification employing a 5:1 toluene/ethyl acetate solvent 
system. The product fractions (4.2 g, 65%) were identified by Thin Layer 
Chromatography, nmr and ir. High pressure liquid chromatography analysis 
revealed a 88.3% purity with a trace of bis-nitro ester and less than 1% 
5-[2-chloro-4-trifluoromethylphenoxy]-2-nitrobenzoic acid. 
The reaction of this example can be employed to make other nitrobenzoates 
by proper substitution of 
1,2-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]ethane. 
For example, [3-hydroxy 
propyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate is prepared 
by substituting 
1,3-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]propane; 
[5-hydroxy-3-oxapentyl]5-(2-chloro-4-trifluoromethylpehnoxy)-2-nitrobenzoa 
te is prepared by substituting 1,5 
bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]-3-oxapentane; 
[5-hydroxy-3-thio-pentyl] 
5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate is prepared by 
substituting 
1,5-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]-3-thiapen 
tane and 
[4-hydroxy-2-buten-1-yl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzo 
ate is prepared by substituting 
1,4-bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]-2-butene 
for 1,2 bis[5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyloxy]ethane 
in this example. 
EXAMPLE 3 
Preparation of [2-Chloroacetoxyethyl]5-(2 
chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate 
Chloroacetyl chloride (3 g, 0.027 mole) was added dropwise to a stirred 
solution of 
[2-hydroxyethyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate (8.1 
g, 0.02 mole), triethylamine (2.5 g), and ether (150 ml). The heat given 
off during the reaction raised the temperature of the ether solution to 
reflux. After completion of addition, the mixture was kept at reflux for 
10 min. The mixture then was allowed to cool to room temperature, poured 
into 200 ml of water, and 400 ml of ether was added. The ether extract was 
washed three times with water, dried CaSO.sub.4 and condentrated to 8.6 g 
of yellowish oil. The oil was column chromatographed through silica gel 
with 20% ethyl acetate-80% hexane as eluent to afford 3.2 g of pure 
[2-chloroacetoxyethyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoat 
e, as a pale yellow gummy material; nmr (CDCl.sub.3) .delta. 4.16 (S, 2H), 
4.50 (S, 4H), 6.98-8.18 (m, 6H); ir (CHCl.sub.3) 1752, 1765. 
Other carbonylated compounds can be prepared by the procedure of this 
example by proper substitution of chloroacetyl chloride. Thus, 
[2-(methoxyacetoxy)ethyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenz 
oate is prepared by substituting methoxyacetyl chloride for chloroacetyl 
chloride; 
[2-acetoxyethyl]5-(2-chloro-4-trifluoromethylphenoxy)-nitrobenzoate is 
prepared by substituting acetic anhydride for chloroacetyl chloride; 
[2-(propionyloxy)ethyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoa 
te is prepared by substituting propionyl chloride for chloroacetyl chloride 
and [2-(N,N-dimethylcarbamyloxy) 
ethyl]5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate is prepared by 
substituting N,N-dimethylcarbamyl chloride for chloroacetyl chloride.