Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1992-08-18
1995-01-17
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564221, C07C23315, C07C23366
Patent
active
053826825
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel aryloxy-nitroanilides and a process for preparing them.
Certain nitroanilides are suitable as intermediates which can be readily converted to their corresponding anilines, required in the preparation of useful photographic and pharmaceutical compounds. Previous methods of preparation have not been suitable for large scale synthesis of anilines particularly for those analogues which are ballasted. Selective reduction of dinitro analogues as in Anales de Fisica y Quimica (1966), 451, P. E Verkade and C. P. Van Dijk result in the formation of mixtures of isomers with consequent separation difficulties, whilst preparation of the required anilines from ethyl-4-chloro-3-nitrobenzoate is a protracted and expensive procedure.
A method of preparing 2-phenoxy-5-nitrotroacetanilide in low yield is already known (A. R. Fox and K. H. Pausacker, J Chem Soc. (1957), 295-301) in which 2-chloro-5-nitroacetanilide is reacted with a large excess of sodium phenoxide under molten conditions and in the presence of copper powder.
The present invention relates to a method of preparing aryloxy-nitroanilides which avoids this use of a large excess of phenol, is suitable for large scale synthesis end gives the anilides in good yields, and to the novel intermediates thereof. The anilides can be subsequently hydrolysed to the required anilines using known methods.
According to the present invention there are provided novel intermediates of formula (I). ##STR2## wherein R is alkyl from 1 to 5 carbon atoms or unsubstituted or substituted aryl of from 6 to 10 atoms, one of R.sup.1 and R.sup.2 is hydrogen and the other is aryloxy, wherein the aryl is unsubstituted or substituted with one or more alkyl of from 1 to 10 carbon atoms, with the proviso that when R is methyl, R.sup.1 may not be unsubstituted phenoxy and when R is 2-hydroxy-5-chlorophenyl, R.sup.2 may not be unsubstituted or chloro or methyl substituted phenoxy.
As used herein and throughout the specification the term alkyl denotes a straight or branched chain alkyl group.
When R is a substituted aryl group, it may be substituted, for example, by one or more halo, alkyl, ester or sulfonyl-containing groups. However, preferred intermediates are those wherein R is a phenyl group or most preferably a methyl group and especially those wherein one of R.sup.1 and R.sup.2 is a substituted phenoxy group. Particularly preferred compounds are
In a further aspect of the present invention there is provided a method of preparing intermediates of formula (I)' ##STR3## wherein R is alkyl from 1 to 5 carbon atoms or unsubstituted or substituted aryl of from 6 to 10 carbon atoms, one of R.sup.1 and R.sup.2 is hydrogen and the other is an aryloxy, wherein the aryl is unsubstituted or substituted with one or more alkyl of from 1 to 10 carbon atoms, comprising the step of reacting a compound of formula (II) ##STR4## wherein R is as defined above and one of L.sup.1 and L.sup.2 is a hydrogen and the other is a leaving group, with a compound of formula R.sup.3 OH, wherein R.sup.3 is aryl as defined for R.sup.1 and R.sup.2.
Preferably the reaction is carried out in the presence of a base, such as potassium carbonate or sodium hydride, and with a polar aprotic solvent, such as dimethylformamide or diglyme (bis-(2-methoxyethyl) ether, or a nonpolar hydrocarbon solvent, such as xylene. Although the most preferred solvent is dimethylformamide these other solvents work well at elevated temperatures, especially at their boiling points.
The leaving group is preferably a halogen atom, especially chloro or fluoro, or a sulphonate group.
The most suitable reaction temperature will vary according to the reactants involved and in particular the leaving group. When R is methyl and the leaving group is chloro, temperatures in excess of 140.degree. C. are advantageous, whilst the corresponding fluoro compound reacts more effectively at between room temperature to 100.degree. C. When R is phenyl, use of room temperature minimises the formation of by-products.
An extension of the method
REFERENCES:
patent: 3798258 (1974-03-01), Patchett et al.
patent: 5107022 (1992-04-01), de Besset
Journal Of The Chemical Society. 1957, Letchworth GB, pp. 295-301; A. R. Fox: `Oxidations With Phenyl Iodosoacetate. Part VI.` cited in the application, see p. 299.
Journal Of Medicinal Chemistry. vol. 20, No. 6, 1977, Washington US pp. 826-829; H. Singh: `Systhesis Of 5-Chloro-3-`Nitro-4'-Substituted Salicylanilides, A New Series Of Anthelmintic And Antimicrobial Agents` see p. 827.
Pharmazie, vol. 45, No. 1, Jan. 1990, Berlin D. D. pp. 34-37; R. P. Srivastava et al: `Synthesis Of 2,5-Distributed Benzimidazoles<1,3,4-Thiadiazoles And 3,5-Diiodosalicylanilides As Structural Congeners Of Rafoxanide And Closantel` see table 2.
Chemical Abstracts, vol. 57, No. 6, 17 Sep. 1962, Columbus, Ohio, US; abstract No. 727OG, col. 7270; see abstract & CAN. J. Chem. vol. 40, 1062, pp. 165-169; G. Frangatos: `The Synthesis Of Some Basic Diphenyl Ethers`.
Anales de Fisica y Quimica (1966), p. 451, P. E. Verkade and C. P. Van Dijk Abstract.
Buckland Paul R.
Latimer Lee H.
Bembenick B.
Eastman Kodak Company
Kluegel Arthur E.
Raymond Richard L.
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