Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
1999-01-12
2001-04-03
Padmanabham, Sreeni (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S309000, C568S323000, C568S335000, C568S324000
Reexamination Certificate
active
06211413
ABSTRACT:
The invention relates to a process for the preparation of compounds of formula I
wherein:
X is H or F,
Y is CF
3
or F and
R
1
is hydrogen or C
1
-C
2
alkyl; in which process
(1) a compound of formula II, wherein X and Y are as defined for formula I, is reacted with an organic or inorganic nitrite or nitrous acid;
(2) the resulting diazonium compound of formula III is reacted with an aldoxime of formula V
R
1
—CH═NOH (V)
wherein R
1
is as defined for formula I, in presence of copper powder or a copper salt; and
(3) the resulting oxime of formula IV is hydrolyzed with aqueous acid to the compound of formula I.
The compounds of formula I are important intermediates for the preparation of pharmaceuticals, dyestuffs, perfumes, pesticides and other products; e.g. WO 97/19912.
It is known that trifluoromethylphenyl alkyl ketones can be prepared from trifluoromethylphenyl halogenides and alkane carboxylic acid derivatives by Grignard reaction, for example the preparation of 3-trifluoromethyl acetophenone in Research Dislosure RD 38614, June 1996.
Furtheron, 3-trifluoromethyl acetophenone has been prepared by Grignard reaction of 3-trifluoromethylbenzonitrile, which in turn has been obtained from 3-trifluoromethyl aniline by diazotization and cyanation (J. Am. Chem. Soc. 70, p.4020,1948).
However, for an industrial process the Grignard reaction has serious disadvantages: the reaction may be difficult to start and the reaction mixture is thermally unstable which may therefore constitute a safety risk. Due to the equimolar amounts of magnesium needed, an undesirable amount of material has to be handled.
The general synthetic principle of preparing phenyl alkyl ketones and benzaldehydes by diazotization of an aniline, reaction of diazonium salts with an aldoxime and subsequent hydrolysis of the oxime is described, e.g in J. March, Advanced Organic Chemistry, 2nd Ed., p. 663, 1977; the yields are in general only 40-60%. For example, the yields of halo- and acetyl substituted acetophenones prepared by this reaction are only 30-45% (J. Chem. Soc. 1954, p.1297-1302).
The known processes for the preparation of compounds of formula I are accordingly unsatisfactory for economic, ecological and safety reasons.
It has been found that phenyl alkyl ketones and benzaldehydes of formula I can be obtained from the corresponding anilines according to this invention in yields of up to 80% and in good qualities. The method provided herewith is distinguished by ready availability of the raw materials, good technical feasibility and is economically and ecologically favorable.
DETAILED DESCRIPTION OF THE INVENTION
Reaction step (1): The diazotization reaction is carried out in an organic solvent with an organic nitrite, e.g. an alkyl nitrite as isoamyl nitrite, or an aryl nitrite, as phenyl nitrite; or, more preferably, in aqueous solution with nitrous acid or a salt thereof, in presence of an acid. Preferred nitrites are sodium nitrite, potassium nitrite, magnesium nitrite, particularly preferred is sodium nitrite. Preferred acids are hydrochloric acid, sulfuric acid and nitrosulfuric acid.
Advantageous is a temperature of −10 to +30° C. and a pH 0-3.
Reaction step (2): The diazonium compound of formula III is preferably reacted in the presence of CuCl or CuSO
4
at −10 to +40° C., more preferably −10 to +15° C., and at pH 2-7, more preferably at pH 3-5.
The amount of the copper salt is 1 to 20 mol %, more preferably 3 to 6 mol %, in relation to the aniline of formula II.
In a preferred mode of running the reaction step (2), an aqueous suspension of the diazonium compound of formula III and an aqueous solution of the copper salt are simultaneously added to an aqueous suspension of the aldoxime of formula V, maintaining a pH of 3-5 by simultaneously adding a base to the reaction mixture.
Reaction step (3): The phenone oxime of formula IV is hydrolyzed with aqueous acid, preferably diluted mineral acid, as hydrochloric acid, sulfuric acid, phosphoric acid, at pH <2, optionally in mixture with a solvent, wherein the product is soluble.
The temperature is not critical and may vary from 30° C. to +170° C., more preferably from 30 to 120° C.
It may be advantegeous for working up and purification of intermediates and products to run the reaction steps, in particular steps (2) and/or (3), in presence of a hydrophobic solvent, as hydrocarbons, halogenated hydrocarbons, ethers and ketones, for example hexane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, mineral oil, kerosene, methylene chloride, chloroform, ethylenechloride, chlorobenzene and dichlorobenzene.
Particularly preferred is the preparation of 3-(trifluoromethyl)acetophenone and 3-(trifluoromethyl)propiophenone from 3-(trifluoromethyl)aniline according to the reaction scheme
wherein R
1
is methyl or ethyl.
A further aspect of the invention is a process for the preparation of a compound of formula IV
wherein:
X is H or F,
Y is CF
3
or F and
R
1
is hydrogen or C
1
-C
2
alkyl; in which process
(1) a compound of formula II, wherein X and Y are as defined for formula I, is reacted with an organic or inorganic nitrite or nitrous acid;
(2) the resulting diazonium compound of formula III is reacted with an aldoxime of formula V
R
1
—CH═NOH (V)
wherein R
1
is as defined for formula I, in presence of copper powder or a copper salt.
REFERENCES:
patent: 3652632 (1972-03-01), Vacek
patent: 4537780 (1985-08-01), Sanborn et al.
patent: 26 04 207 (1976-08-01), None
patent: WO 97/19912 (1997-06-01), None
patent: WO 98/50335 (1998-11-01), None
Humphlett et al, Journal of American Chemical Society, vol. 70, pp. 4020-4023, 1948.*
March, Advanced Organic Chemistry,third edition, pp. 313, 649 and 784, 1985.*
Research Disclosure, 706/Oct. 1997, No. 40221.
Research Disclosure, 348/Jun. 1996, No. 38614.
Advanced Organic Chemistry, J. March, Second Ed., 1977, p. 663.
J. Chem. Soc., 1954, pp. 1297-1302.
Derwent Abstract 98-595928 (of WO 98/50335) (1998).
Derwent Abstract 76-61958X (of DE 2604207) (1976).
Moore Terry Lee
Wang Linhua
Wegmann Arthur
Bayer Aktiengesellschaft
Gil Joseph C.
Padmanabham Sreeni
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