Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-12-02
2000-01-18
Rotman, Alan L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546292, 546296, 546297, 546298, 546302, C07D21364, C07D21369, C07D21370, C07D21384
Patent
active
060159057
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a chemical process and, more particularly, to a process for preparing 2-(6-substituted pyrid-2-yloxymethyl)phenylacetates. These compounds are useful as intermediates for producing agricultural fungicides.
Some new agricultural fungicides, which are methyl 2-[2-(aryl- and heteroaryloxymethyl)phenyl]-3-methoxyacrylates, are described in EP-A-0278595 along with a variety of methods for their preparation.
One method of preparation involves the conversion of a methyl 2-halomethylphenylacetate to a methyl 2-aryl- or 2-heteroaryloxymethylphenylacetate by treatment with an alkali metal salt of a phenol or appropriate hydroxy heteroaromatic compound, followed by the transformation of the methyl acetate group into a methyl methoxyacrylate.
A disadvantage of this method is that in using it to prepare the compound methyl 2-(pyrid-2-yloxymethyl)phenylacetate by treating 2-bromomethylphenyl-acetate with 2-pyridone in the presence of an alkali metal hydroxide, substantial amounts of the unwanted N-alkylated product are obtained.
The N- and O-alkylation of pyridones and factors which influence their formation are discussed in "Pyridine and Its Derivatives, Part Three", Ed. E Klingsberg, 1962, John Wiley & Sons, pages 630-633 and in "Pyridine and Its Derivatives, Supplement Part Three", Ed. R A Abramovitch, John Wiley & Sons, pages 745-749. In particular, it is noted that the introduction of a 6-methyl substituent into 2-hydroxypyridine reduces the amount of N-benzylation from 50% to 16%.
Unfortunately, the presence of an acetate group in the 2-position of the benzylating agent can lead to the formation of unwanted dimeric material as a result of the interaction of two molecules of the benzylating agent. Although N-benzylation is reduced by the presence of a 6-methyl substituent, dimerisation predominates and very little of the desired O-benzylated product is obtained.
It has now been found that both N-alkylation and dimerisation can be substantially reduced, and N-alkylation even eliminated for all practical purposes, by including a substituent other than alkyl in the 6-position of the pyridine ring.
Accordingly, the present invention provides a process for the preparation of a compound of formula (I).sup.1 wherein A and D are independently selected from the group comprising halo (especially fluoro, chloro or bromo), hydroxy, C.sub.1-4 alkyl (especially methyl or ethyl), halo(C.sub.1-4)alkyl (especially halomethyl, particularly trifluoromethyl, difluoromethyl, fluoromethyl or trichloromethyl), C.sub.1-4 alkoxy (especially methoxy), thio(C.sub.1-4)alkoxy (especially thiomethoxy), halo(C.sub.1-4)alkoxy (especially trifluoromethoxy), phenyl, phenoxy, nitro, amino, acylamino (especially formamido or acetylamino), cyano, carboxy, C.sub.1-4 alkoxycarbonyl (especially methoxycarbonyl) and C.sub.1-4 alkylcarbonyloxy (especially acetoxy) and m is 0 or an integer of from 1 to 3, which comprises treating a compound of formula (II), wherein A, D and m are as defined above and M is a metal atom, with a compound of formula (III) wherein L is a leaving group. Where m is 2 or 3 so that D represents 2 or 3 substituents, these substituents may be the same or different.
Halo is typically fluoro, chloro or bromo.
Alkyl and the alkyl moiety of alkoxy, alkoxycarbonyl and alkylcarbonyloxy contain from 1 to 4 carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl. Examples of halo-substituted alkyl groups are halomethyl and haloethyl, which include trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, dichloromethyl, chloromethyl and pentafluoroethyl. Examples of haloalkoxy are trifluoro- and trichloromethoxy. Examples of alkoxycarbonyl and alkylcarbonyloxy are methoxycarbonyl and acetoxy.
Acylamino includes, in particular, C.sub.1-4 alkanoylamino, for example, formamido and acetylamino.
Phenyl and phenoxy groups may themselves be substituted by one or more substituents. Suitable substituents include, for example, halo, C.su
REFERENCES:
patent: 5008438 (1991-04-01), Schuetz et al.
patent: 5057146 (1991-10-01), Anthony et al.
patent: 5077303 (1991-12-01), Seele et al.
patent: 5157037 (1992-10-01), Schuetz et al.
patent: 5166216 (1992-11-01), Schuetz et al.
patent: 5194622 (1993-03-01), Brayer et al.
patent: 5334577 (1994-08-01), Wenderoth et al.
patent: 5606095 (1997-02-01), Pfiffner et al.
Comins, D. L., et al., Tetrahedron Letters, "N-vs. O-Alkylation in the Mitsunobu Reaction of 2-Pyridone," vol. 35, No. 18, 1994, pp. 2819-2822.
Hopkins, George C., et al., J. Org. Chem., "Alkylations of Heterocyclic Ambident Anions. II. Alkylation of 2-Pyridone Salts," vol. 32, 1967, pp. 4040-4044.
Shiao, Min-Jen et al., Heterocycles, "A Facile Synthesis of Bromo-2-Alkoxypyridines," vol. 31, No. 5, 1990, pp. 819-824.
Chemical Abstracts, No. 89133q, vol. 98, (1983).
Chemical Abstracts, No. 39238e, vol. 87, (1977).
Chemical Abstracts, No. 77781k, vol. 81, (1974).
Chemical Abstracts, No. 55938z, vol. 73, (1977).
Chemical Abstracts, No. 12505t, vol. 72, (1970).
Forrester Julie
Jones Raymond Vincent Heavon
Munns Gordon Richard
Ritchie David John
Standen Michael Charles Henry
LeCroy David P.
Rotman Alan L.
Zeneca Limited
LandOfFree
Process for the preparation of 2-(6-substituted pyrid-2-yloxymet does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of 2-(6-substituted pyrid-2-yloxymet, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of 2-(6-substituted pyrid-2-yloxymet will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-564310