Process for the preparation of pyridine derivatives

1. A process for the preparation of substituted pyridine derivatives of formula (I)

wherein

R 1 and R 2 independently represent H C 1-20 -alkyl (branched or straight chain or cyclic) or C 6-20 -aryl, each of which alkyl and aryl groups may be substituted with one or more of the following groups: F, Cl, Br, I, C 1-20 -alkoxy or C 6-20 -aryloxy each of which alkoxy or aryloxy groups may be substituted with amino, F, Cl, Br or I;

R 3 represents C 1-20 -alkyl (branched or straight chain or cyclic) or C 6-20 -aryl, each of which alkyl and aryl groups may be substituted with one or more of the following groups: F, Cl, Br, I, C 1-20 -alkoxy or C 6-20 -aryloxy, each of which alkoxy or aryloxy groups may be substituted with amino, F, Cl, Br, or I;

R 4 represents E n R 6 m in which

if n=m=1, then E represents S and R 6 represents C 1-20 -alkyl (branched or straight chain or cyclic) or C 6-20 -aryl, each of which may be substituted with one or more of the following groups: F, Cl, Br, I, C 1-20 -alkoxy or C 6-20 -aryloxy, each of which alkoxy or aryloxy groups may be substituted with amino, F, Cl, Br or I;

if n=0 and m=1 than R 6 =H, C 1-20 -alkyl (branched or straight chain or cyclic) or C 6-20 -aryl, each of which alkyl and aryl groups may be substituted with one or more of the following groups: F, Cl, Br, I, C 1-20 -alkoxy or C 6-20 -aryloxy, each of which alkoxy or aryloxy groups may be substituted with amino, F, Cl, Br or I;

E 1 represents O or N;

R 5 represents H; and

n=1 when E 1 represents O and n=2 when E 1 =N

which comprises:

i) reacting an α-β-unsaturated carbonyl compound of formula (II)

R 3 —C(O)—C(R 1 )═C(R 2 )-G  (II)

wherein

R 1 , R 2 and R 3 are as previously defined; and

G represents —NH 2 or a leaving group

with a Wittig reagent or Horner-Wadsworth-Emmons reagent of formula (III)

wherein

(P) represents P(Ar) 3 , in which Ar represents a substituted or preferably unsubstituted C 6-20 aryl, R′ independently represents C 1-20 alkyl (branched or straight or cyclic) or C 6-20 aryl;

M represents an alkaline metal (Li, Na, K, Rb or Cs);

E n R 6 m is as previously defined;

Y represents —CN; —C(O)NH 2 ; —C(O)OR 7 in which R 7 is as defined for R 3 above in the presence of a base to provide a mixture of intermediates; and

ii) cyclizing the mixture of intermediates to the substituted pyridine of formula (I) by:

a) catalysis with acid, catalysis with zeolites or catalysis with base when Y represents —CN or C(O)NH 2 , G represents a leaving group and the base is an alcoholate; or

b) catalysis with base in the presence of ammonia when Y represents —C(O)—OR 7 , G represents a leaving group and the base is an alcoholate.

2. The process according to claim 1 , wherein R 1 and R 2 both represent H and R 3 represents an electron withdrawing group.

3. The process according to claim 1 , wherein R 1 and R 2 both represent H and R 3 represents a partially or fully fluorinated C 1-6 -alkyl group.

4. The process according to claims 1 , wherein R 3 represents —CF 3 .