PROCESS FOR THE PREPARATION OF 4-TRIFLUOROMETHOXYPHENOL
Field of the Invention
The present invention provides the process for the preparation of 4-trifluoromethoxyphenol
of Formula I. The present invention also provides the process for the preparation of
intermediates used in preparing 4-trifluoromethoxyphenol
Background of the invention
4-trifluoromethoxyphenol and its intermediates are extremely useful in pharmaceuticals,
pesticides, dyes, liquid crystal materials and electronic chemicals.
OCF3
OH
Formula I
The Chinese Patent Application No. 103553884 provides method for preparing
trifluoromethoxybenzene. The method comprises the following steps: (1) introducing
chlorine into the raw material of benzaldehyde or a mixture of benzaldehyde and parylene for
chlorination; (2) carrying out fluoridation on the chlorination product prepared in the step (1)
with anhydrous hydrogen fluoride to obtain trifluoromethoxybenzene and paradibenzenyl.
The Chinese Patent Application No. 1390820A describes the use of carbon tetrachloride as a
solvent for introducing chlorine into methoxybenzene, however, the use of carbon
tetrachloride is restricted due to its ozone depleting nature. The Chinese Patent Application
No. 102557895A alternatively provides tetrachloroethane, pentachloroethane,
hexachloroethane, bis (trichloromethyl) carbonate resin as solvent instead of carbon
tetrachloride. However, in these solvents, it is difficult to separate anisole chlorinated
products.
The J. Am. Chem. Soc. 1987, 109, 3708-3713 provides a process for nitration of α, α, α-
trifluoromethoxybenzene in the presence of nitronium tetrafluoroborate. The reaction takes
place in nitromethane as solvent.
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The process of the present invention is simple, uses mild reaction conditions such as nonhazardous
and nontoxic reagents and solvents, economical and hence is suitable for industrial
production.
Summary of the Invention
The present invention provides a process for the preparation of 1-nitro-4-
trifluoromethoxybenzene of Formula V comprising;
a) reacting a compound of Formula II with a chlorinating agent and a catalyst to obtain a
compound of Formula III,
OCH3
OCCl3
Formula II Formula III
b) reacting the compound of Formula III with hydrogen fluoride to obtain a compound
of Formula IV,
OCF3
Formula IV
c) reacting the compound of Formula IV with nitric acid and a chlorinated solvent to
obtain 1-nitro-4-trifluoromethoxybenzene, and
OCF3
NO2
Formula V
d) isolating 1-nitro-4-trifluoromethoxybenzene from step c).
Detailed description of the Invention
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The present invention provides a process for the preparation of 1-nitro-4-
trifluoromethoxybenzene of Formula V comprising;
a) reacting a compound of Formula II with a chlorinating agent and a catalyst to obtain a
compound of Formula III,
OCH3
OCCl3
Formula II Formula III
b) reacting the compound of Formula III with hydrogen fluoride to obtain a compound
of Formula IV,
OCF3
Formula IV
c) reacting the compound of Formula IV with nitric acid and a chlorinated solvent to
obtain 1-nitro-4-trifluoromethoxybenzene, and
OCF3
NO2
Formula V
d) isolating 1-nitro-4-trifluoromethoxybenzene from step c).
The compound of Formula II is commercially obtained. The chlorinating agent in step a) is
selected from chlorine, sulfuryl chloride or N-chlorosuccinimide. The catalyst in step a) is
selected from the group consisting of phosphorus trichloride, azobisisobutyronitrile,
derivatives of azobisisobutyronitrile and benzoyl peroxide or mixture thereof. The step a)
may take place in the presence of solvent. The solvent may be selected from the group
4
consisting of benzotrifluoride, 4-chlorobenzotrifluoride, chlorobenzene and dichlorobenzenes or mixture thereof.
The step b) may take place at a temperature in the range of about 50oC to about 120oC, for example, about 60oC to about 100oC for about 1 hour to about 12 hours, for example, for about 5 hours to about 9 hours.
The step c) may take place in the presence of sulphuric acid. The step c) may take place in the presence of a solvent. The solvent may be a chlorinated solvent, for example, dichloromethane, chloroform and carbon tetrachloride or mixture thereof. The step c) may take place at a temperature in the range of about 2oC to about 35oC, for about 2hour to about 5 hours. The 1-nitro-4-trifluoromethoxybenzene may be isolated by any of the methods in the art, for example, evaporation, distillation, filtration and layer separation or mixture thereof.
In another aspect, use of 1-nitro-4-trifluoromethoxybenzene, as prepared by present invention, for the preparation of compound of 4-trifluoromethoxyphenol of Formula I.
The 4-trifluoromethoxyphenol of Formula I may be prepared from 1-nitro-4-trifluoromethoxybenzene by any method known in the art.
The 4-trifluoromethoxyphenol of Formula I may be isolated by any of the methods in the art, for example, evaporation, distillation, filtration and layer separation or mixture thereof.
The 4-trifluoromethoxyphenol of Formula I, as obtained by present invention, has purity of about 99% to about 99.5%.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Examples:
Step 1: Anisole (150g) and radical initiator (7.5g) and 4-Chlorobenzotrifluoride (750g) added together for 4-5 hrs at 90-100°C which is illuminated with polychromatic UV. Then 15 to 20 LPH of chlorine flow rate is maintained simultaneously with the addition at 90 to 100°C. After addition, the mixture is further maintained the chlorine flow of about 20LPH for 2 h for reaction completion and total about 345g chlorine is used. Reaction mass is purged with nitrogen gas to expel the dissolved chlorine and HCl followed by solvent removal to get the step 1 crude (296g). Crude as such used in step 2. 5
Step 2: Trifluoromethoxy benzene is prepared from Trichloromethoxy benzene with anhydrous HF at 80°C for 4-6 hrs, by product from this reaction is hydrochloric acid. Observed 30-35kg/cm2 Maximum as pressure in this reaction. The crude material is distilled at atm pressure for isolating the pure Trifluoromethoxy benzene.
Procedure: Trichloromethoxy benzene (265g) and AHF (252g) are charged in an SS 316 autoclave and heated to 80°. Maintained for 4 to 6 Hrs at the temp. under pressure conditions. After completion of the reaction – HCl & AHF are vented and expelled the dissolved HCl & AHF by heating and purging with Nitrogen gas. Crude (190g) trifluoromethoxy benzene is then boiled off to get the pure product in the initial cuts (About 120g).
Step 3: Trifloromethoxybenzene is nitrated with concentrated Sulphuric acid + concentrated nitric acid at 00c (Nitration mixture) to 35°C.The reaction produces mixture of isomers having close boiling points. Between ortho and para isomer, para isomer was formed as major and is about 90%. And the by-product formed during the reaction is Sulphuric acid and water. The crude product isolated by using DCM layer separation followed by the evaporation of DCM solvent.
Procedure: Trifluoromethoxy benzene(118g) and solvent (DCM - 590g) are charged in glass RB and cooled to about 0°C. Added nitration mixture(HNO3-58.24+H2SO4-174.24g) from top at temp. at about 5° to 10c for about 1Hr. Raised the temp. slowly to 30°C maintained for another hour. After completing of the reaction – mass quenched into ice cold water and separated the solvent layer. Aq. layers extracted with the solvent and combined the solvent layers followed by dried and evaporated the solvent to the crude 1-Nitro-4-trifluromethoxy-benzene (135g) with about 90% selectivity and about 80 to 85% yield.

We claim:
1. A process for the preparation of 1-nitro-4-trifluoromethoxybenzene of Formula V
comprising;
a) reacting a compound of Formula II with a chlorinating agent and a catalyst to obtain a
compound of Formula III,
OCH3
OCCl3
Formula II Formula III
b) reacting the compound of Formula III with hydrogen fluoride to obtain a compound
of Formula IV,
OCF3
Formula IV
c) reacting the compound of Formula IV with nitric acid and a chlorinated solvent to
obtain 1-nitro-4-trifluoromethoxybenzene, and
OCF3
NO2
Formula V
d) isolating 1-nitro-4-trifluoromethoxybenzene from step c).
2. The process of claim 1, wherein the chlorinating agent in step a) is selected from
chlorine, sulfuryl chloride or N-chlorosuccinimide.
3. The process of claim 1, wherein the catalyst in step a) is selected from the group
consisting of phosphorus trichloride, azobisisobutyronitrile, derivatives of
azobisisobutyronitrile and benzoyl peroxide or mixture thereof.
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4. The process of claim 1, wherein the step a) takes place in the presence of a solvent selected from the group consisting of benzotrifluoride, 4-chlorobenzotrifluoride, chlorobenzene and dichlorobenzenes or mixture thereof.
5. The process of claim 1, wherein the step c) takes place in the presence of sulphuric acid.
6. The process of claim 1, wherein the step c) takes place in the presence of solvent selected from the group consisting of dichloromethane, chloroform and carbon tetrachloride or mixture thereof.
7. The process of claim 1, wherein the step c) takes place at a temperature in the range of about 2oC to about 35oC.
8. The process of claim 1, wherein the 1-nitro-4-trifluoromethoxybenzene is isolated by evaporation, distillation, filtration and layer separation or mixture thereof.
9. A process of preparation of 4-trifluoromethoxyphenol of Formula I by using 1-nitro-4-trifluoromethoxybenzene, wherein 1-nitro-4-trifluoromethoxybenzene is prepared as in claim 1.
10. The process of claim 9, wherein 4-trifluoromethoxyphenol of Formula I so obtained has purity of about 99 % to about 99.5%.