Chemistry: electrical and wave energy – Processes and products – Processes of treating materials by wave energy
Reexamination Certificate
1999-04-07
2001-01-30
Gorgos, Kathryn (Department: 1741)
Chemistry: electrical and wave energy
Processes and products
Processes of treating materials by wave energy
C204S157420, C204S157430, C204S157480, C204S157940, C204S157990, C204S158110
Reexamination Certificate
active
06179970
ABSTRACT:
This invention relates to the preparation of fluoro compounds from amines by replacement of the amino group by a fluorine atom.
It is known to produce fluoro compounds from corresponding amines, particularly aromatic amines, by conversion of the latter into a diazonium tetrafluoroborate salt which is then decomposed thermally to produce the fluoro compound. It is also known to carry out the diazotization of aromatic amines in anhydrous hydrofluoric acid with subsequent heating to produce the corresponding fluoro compound. Neither of these methods is entirely satisfactory. The first involves isolation of the tetrafluoroborate salt which is hazardous and time consuming. The latter method gives poor yields when substituted aromatic amines are used, especially if the substitution is in the ortho position. Also, the reaction has to be carried out under pressure because anhydrous hydrofluoric acid is volatile.
There have been a number of proposals of methods for the production of fluoro compounds which are said to give improved results. For example, European Specification EP-A-0430434 (Imperial Chemical Industries plc.) describes a process for the preparation of fluoro aromatic and fluoro heteroaromatic compounds by reaction of corresponding aromatic or heteroaromatic amines with a nitrosyl polyfluoro salt in an inert liquid followed by decomposition of the diazonium polyfluoro salt obtained in situ. It has also been proposed (M{umlaut over (u)}eller et al Z. Chem. 26 (1986) pp 169-170) to bring about the decomposition of aromatic diazonium fluoroborates in a fluorinated hydrocarbon reaction medium in the presence of Et
3
N.3HF under the influence of ultrasound at 40° C. It is stated that high yields may be obtained. However, this method like other known methods involving the use of diazonium tetrafluoroborates, requires isolation of the tetrafluoroborate salt.
It has now been found that compounds containing a primary amino group can be converted into compounds containing a fluorine atom in place of the amino group without isolation of any intermediate diazonium salt and with excellent yields of the desired product, if the reaction is carried out with ultrasound.
The present invention accordingly provides a process for converting a compound containing a primary amino group into a compound containing a fluorine atom in place of the said amino group which comprises contacting the said amino group containing compound with hydrogen fluoride, or with a complex thereof with a base, and with a nitrosating agent, at a temperature in the range of −20° to +100° C. while the reagents are subjected to the action of ultrasound having a frequency of 10-100 kHz and an intensity of at least 20 watts/cm
2
and/or microwaves having a frequency of 300 MHz to 3 GHz and an intensity of 100 W to 5 kW.
This process is applicable to a wide variety of amino group containing compounds including more particularly aromatic and heteroaromatic primary amines and alpha-amino acids.
The invention may be, for example, applied to aromatic amino-compounds of the formula
A(NH
2
)
n
where A is an unsubstituted or substituted aromatic or heteroaromatic radical and n is an integer, e.g. from 1 to 4. A may be for example a residue of benzene, naphthalene, diphenyl, acetonaphthene, fluorene, or pyrene or a heteroaromatic compound such as pyridine or quinoline.
The invention may also be applied to &agr;-amino acids such as alanine, valine, phenylalanine, isoleucine, tyrosine, and threonine, and to aralkylamines such as phenylethylamine.
Examples of suitable aromatic and heteroaromatic amines which may be subjected to the process of the present invention may be represented by the general formula:
where Ar is phenyl, &agr;- or &bgr;-naphthyl, pyridyl, quinolyl, thienyl, or diphenyl, n is 0, 1, 2 or 3 and R is halogen, alkyl, hydroxy, alkoxy, COOH, CHO, alkoxycarbonyl, nitro, cyano, trifluoromethyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulphonamido, alkanoyl, or aroyl.
Preferred aromatic primary amines which may be used in the process of the invention conform to the general formula:
where n is 0, 1, 2 or 3 and the radicals R, which may be the same or different when n is 2 or 3, are each halogen, e.g. fluorine or chlorine, alkyl of 1 to 4 carbon atoms, e.g. methyl or ethyl, hydroxy, alkoxy of 1 to 4 carbon atoms, e.g. methoxy or ethoxy, alkylthio of 1 to 4 carbon atoms, e.g. methylthio, carboxy, alkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy, nitro, cyano or trifluoromethyl.
The hydrogen fluoride is preferably introduced into the reaction mixture in the form of a complex with a base which is preferably a secondary or tertiary aliphatic amine, a heterocyclic aromatic amine, or an ether. Examples of suitable compounds are triethylamine, diisopropylamine, pyridine, tetrahydrofuran, diethyleneglycol dimethyl ether, 1,3-dioxolane, and dioxane.
The nitrosating reagent is preferably an alkali metal nitrite, e.g. sodium nitrite, or a nitrite ester, e.g. ethyl nitrite. It is also possible to use other nitrosating agents, for example nitrosyl fluoroborate or nitrogen oxides.
In some cases improved yields are obtained by incorporating boron trifluoride etherate into the reaction mixture.
The amount of nitrosating reagent which is used in the process can be varied within wide limits. Preferably from 1.0 to 5.0, especially from 1.0 to 2.0 and more especially from 1.1 to 1.5, mole of nitrosating reagent is used per mole of primary amine.
The amount of hydrogen fluoride complex to primary amine can be carried within wide limits. Preferably 5 to 200, especially 10 to 50 and more especially 10 to 25, parts of liquid are used per part of primary amine.
The reaction may be carried out at any temperature in the range −20° C. to +150° C., but it is preferably carried out at 0 to 70° C., and especially at 0 to 50° C. The pressure is not critical and it is ordinarily convenient to carry out the reaction at ambient pressure.
The ultrasound or microwaves may be provided using commercially available sources, e.g. an ultrasonic cleaning bath or a microwave oven. The frequency of the ultrasound should be chosen to maximise absorption of energy by the reaction medium. Typically, the ultrasound should have an intensity of at least 20, preferably 50, more preferably 100 and especially 200 W/cm
2
. Microwaves should have a frequency of 300 MHz to 3GHz and a power of 200 W to 5 kw. (In some countries, the maximum frequency is fixed by law.)
Following completion of the reaction (shown by disappearance of the starting amine and the intermediate diazonium salt from the reaction medium) the desired fluoro compound may be worked up in the usual way.
The fluoro compounds obtained are useful as intermediates in the manufacture of a wide range of products including pharmaceuticals, herbicides, pesticides, dyestuffs and plastics.
The following Examples illustrate the invention.
REFERENCES:
patent: 3481850 (1969-12-01), Petterson et al.
patent: 5354439 (1994-10-01), Forat et al.
patent: 141750 (1930-10-01), None
patent: 0 430 434 A2 (1991-06-01), None
patent: 0 467 742 A1 (1992-01-01), None
N. Yoneda et al., “Preparation of Aromatic Fluorides by Photochemical Diazotization and Decomposition of Aromatic Amines”, Chemical Abstracts, 110(3):23510v (1989) no month available.
M{umlaut over (u)}eller et al., “Ultraschallforcierte Balz-Schiemann-Reaktion Unter Thermisch Milden Bedingungen”, Z. Chem. 26, pp. 169-170 (1986) no month available.
Coe Paul
Mercier Claude
Waring Tony
Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Gorgos Kathryn
Rhodia Limited
Wong Edna
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