DE1256639B - Process for the production of 2-pentafluorophenylaethanol - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. CL: C 07 c

German class: 12 ο -5/04

Number: 1256 639

File number: J 29637IV b / 12 ο

Filing date: December 17, 1965

Opened on: December 21, 1967

The invention relates to an improved process for the production of 2-pentafluorophenyl ethanol (C ₈ F ₅ CH ₂ CH ₂ OH).

It is known in hydrocarbon chemistry that solutions of Grügnard reagents either in diethyl ether or in a mixture of diethyl ether and benzene react with ethylene oxide to give primary alcohols of the RCH ₂ CH ₂ OH type, where R is an alkyl or aryl radical (MS Kharasch and O. Reinmuth, "Grignard Reactions of Nonmetallic Substances", Constable & Co, London, 1954, p. 961). For example, phenylmagnesium bromide reacts with ethylene oxide in these solvents, with 2-phenylethanol in 58% ^e! "Yield results.

In contrast, a solution of pentafluorophenybnagnesium bromide reacts in diethyl ether not with ethylene oxide; it is only pentafluorobenzene when acidifying the reaction mixture and when Distillation of the ether layer obtained.

In contrast, a solution of pentafluorophenyl magnesium bromide reacts in diethyl ether not with ethylene oxide; it is only pentfluorobenzene when Acidification of the reaction mixture and obtained in the distillation of the ether layer. In Russian Literature describes that pentafluorophenyl magnesium chloride does not react with ethylene oxide, when diethyl ether is used as a solvent; only pentafluorobenzene was obtained when you look at that The reaction mixture is acidified and the ether layer is distilled. If, however, benzene is added to the reaction mixture and this under for 5 hours Is heated to reflux, 2-pentafluorophenyl ethanol is obtained in 26% yield (N. N. Vorozhtsov et al., "Tetrahedron Letters", 1964, No. 47, p. 3575).

The invention therefore relates to a process for the preparation of 2-pentafluorophenyl ethanol by Implementation of a pentafluorophenyl Grignard compound with ethylene oxide in the presence of an organic Solvent and subsequent hydrolysis and is characterized in that it is used as a Grignard compound Pentafluorophenyl magnesium bromide

C ₉ F ₅ MgBr

and tetrahydrofuran used as the solvent. This reaction must be described as surprising, especially since the 2-pentafluorophenyl ethanol is obtained in high yield. This result can in no way be predicted from the previously published literature. The yield of 2-Pentafluorphenyläthanol in this case is 79 ° / ₀ of theory.

Process for the production of
2-pentafluorophenyl ethanol

Applicant:

Imperial Smelting Corporation (NSC)
Limited, London

Representative:

Dr. D. Thomsen and Dipl.-Ing. H. Tiedtke,

Patent Attorneys, Munich 2, Tal 33

Named as inventor;

George Fuller, Gloucestershire (Great Britain)

Claimed priority:

Great Britain December 18, 1964 (51532)

Because of the thermal instability of pentafluorophenyl magnesium bromide in refluxing tetrahydrofuran, the Grignard reagent is best prepared and used at low temperature, for example at -30 to + 2O ⁰ C, preferably between 0 and ^{-10 0} C. To ensure that no unchanged When bromopentafluorobenzene is present, it is advisable that a large excess of magnesium be used (usually at least one

two-fold excess) if the pentafluorophenyl magnesium bromide will be produced.

2-Pentafluorophenyl ethanol is a valuable intermediate. It gets dehydrated easily, for example with phosphorus oxide, resulting in monomeric 2,3,4,5,6-pentafluorostyrene; the homopolymerization this product leads to poly (pentafluorostyrene); this product shows improved light and heat stability compared to polystyrene. Other useful polymers are made by interpolymerization of Pentafluorostyrene made with other vinyl monomers, e.g. B. with styrene. Oxidation of alcohol gives pentafluorophenylacetic acid; this is for the production of therapeutically active compounds useful (see British Patent 901 880).

2-Pentafluorophenylethanol is also easily converted into 2-pentafluorophenylethyl bromide and then into 3-pentafluorophenylpropionic acid converted; here acts

709 709/468

it is also a useful intermediate for the preparation of therapeutically active compounds (see British patent specification 977,961).

According to the invention, 2-Pentafiuorphenyläthanol is in high yield after a one-step Process made from the easily accessible bromopentafluorobenzene. This alcohol used to be after produced from hexafluorobenzene in a multistage process (see A. K. B arbor et al., »J. Chem. Soc ", 1961, p. 808). So offers the procedure according to the invention a significant technical advance in the chemistry of fluorinated aromatics.

Eib ρ ie 1
Production of 2-Pentafiuorphenyläthanol

Bromopentanuobenzene (740 g, 3 mol) was added to a suspension of magnesium turnings (200 g, 8.2 mol) in tetrahydrofuran (1300 ecm) at a temperature of 0 to -10 "C. The reaction was initially started by adding 1.2 mol. Dibromoethane (1 ecm) was initiated, and the bromopentanuobenzene was added at such a rate that the temperature of the reaction mixture ^{did not exceed 0 °} C. After two thirds of the bromopentanuobenzene had been added, the reaction was no longer exothermic (100 g, 4] mol) and 1,2-dibromoethane (1 cc) added, and then the remaining one-third of the Brompentafluorbenzols was added. the mixture was kept for 1 hour at ⁰ C, then was cooled to -10 "C cooled and ethylene oxide (300 ecm, 6 mol) added. When the reaction had subsided, the temperature was allowed the mixture to 20 ⁰ C increase and kept the mixture for 16 hours at 20 ° C. Then the organic liquid was decanted from the excess magnesium, the magnesium was washed with fresh tetrahydrofuran and the Washing waters were added to the bulk of the organic layer. Hydrochloric acid was added to the tetrahydrofuran solution, and then the organic layer was separated and washed with water. After most of the tetrafuran was removed through a 30.48 cm packed column filled with Dixon gauze (1.6 1.6 cm), the residue was distilled to give (1) a mixture (29 g) with a boiling point of 28 to 90 ° C / 15 mm, (2) 2-Pentafiuorphenyläthanol (360.4 g) with a boiling point of 90 to 106 ⁰ C / 15 mm, «0 = 1.4458 °, determined by gas chromatography , a 97% purity had, and (3) 2-Pentanuorphenyläthanol (182.7 g) having a boiling point of 106 to J09 ° C / 15 mm, which had a 78 ° / _o sodium purity.

The infrared spectrum of the alcohol was identical to that of an authentic sample obtained by reduction of ethyl pentafluorophenyl acetate with liciumaluminum hydride.

For further identification, 2-pentafluorophenyl ethanol (1.83 g) and 3,5-dinitrobenzoyl chloride (2 g) were refluxed for 20 minutes to give the 3,5-dinitrobenzoate derivative with a melting point of 93 to 93.5 ^C C (from ethanol). (Found: C 44.4, H 1.8%. The theoretically calculated values for C ₁₅ H ₇ F ₅ N ₂ O ₆ are: C 44.3, H 1.7%.)

Claims (2)

Patent claims: 1. A process for the preparation of 2-pentafluorophenyl ethanol by reacting a pentafluorophenyl - G rignard compound with Ä ethylene oxide in the presence of an organic solvent and subsequent hydrolysis, characterized in that the Grignard compound used is pentafluorophenyl _{magnesium bromide C 6} F ₅ MgBr and tetrahydrofuran as the solvent . 2. The method according to claim 1, characterized in that the molar ratio between C ₈ F ₅ MgBr and ethylene oxide is 1: 1 to 1: 3. 709 7D9 / 468 12.67 ® Bundesdruckerei Berlin