Processes for preparing aminophenylsulfonylureas, and intermediates therefor
View Patent ↗The invention relates to the preparation of compounds (I) in which A=H or acyl and R 1 , R 2 , R 3 , R, n, X, Y and Z are as defined in claim 1 by halogenation and rearrangement of compounds (II) (optionally salt) to give compounds (III) R*═OH, R**═NR 1 R 2 (II) R*═NR 1 R 2 , R**═Cl (III) R*═NR 1 R 2 , R**═NH 2 (IV) a) ammonolysis of (III) to (IV), reduction of the nitro group and reaction with carbamate (salts) (VI) of the formula Ar—OCO—N(M)-Het, where Ar=phenyl, M=H or cation and Het=heterocycle from formula (I), to give compounds (I) (A=H), or b) ammonolysis of (III) to (IV), reaction with carbamate (salt) (VI) and reduction of resulting compounds (VII) at the NO 2 group to give compounds (I) (A=H), or c) reaction of (III) with cyanates and amines (V) of the formula HNR 3− Het and reduction of the resulting compound (VII) at the NO 2 group to give compounds (I) (A=H) and optional acylation if A is to be other than H. Compounds of the formulae (I) (A=H), (III), (IV), (V), (VI) (M=cation) and (VII) are novel.
1. A compound of formula (VII) or salt thereof:
wherein
(R) n is n identical or different radicals from the group consisting of halogen, alkyl and alkoxy,
n is 0 or 1,
R 1 is H, C 1 –C 6 -alkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 1 –C 6 -alkoxy, C 2 –C 6 -alkenoxy, C 2 –C 6 -alkynoxy or C 5 –C 6 -cycloalkyl, each of the 7 latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl)-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl, or is phenyl which is unsubstituted or substituted by radicals from the group consisting of halogen, C 1 –C 4 -alkyl, C 1 –C 4 -alkoxy, C 1 –C 4 -hatoalkyl, C 1 –C 4 -haloalkoxy and nitro,
R 2 is H, C 2 –C 6 -alkyl, C 2 –C 6 -alkenyl or C 2 –C 6 -alkynyl, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl)-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl,
or the group
NR 1 R 2 is a heterocyclic ring of 4, 5 or 6 ring atoms which may contain up to two further ring heteroatoms from the group consisting of N and O in the ring and which is unsubstituted or substituted by one or more radicals from the group consisting of C 1 –C 4 -alkyl,
R 3 is hydrogen or methyl,
X and Y independently of one another are halogen, C 1 –C 6 -alkyl, C 1 –C 6 -alkoxy, C 1 –C 6 -alkylthio, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy and C 1 –C 4 -alkylthio, or are C 3 –C 6 -cycloalkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 3 –C 6 -alkenyloxy or C 3 –C 6 -alkynyloxy, and
Z is CH.
2. The compound or salt thereof of claim 1 , wherein
(R) n is halogen, C 1 –C 4 -alkyl or C 1 –C 4 -alkoxy,
n is 0 or 1,
R 1 is H, C 1 –C 6 -alkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 1 –C 6 -alkoxy, C 2 –C 6 -alkenoxy, C 2 –C 6 -alkynoxy or C 5 –C 6 -cycloalkyl, each of the 7 latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl)-carbonyl, (Ci -C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl, or is phenyl which is unsubstituted or substituted by radicals from the group consisting of halogen, C 1 –C 4 -alkyl, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkyl, C 1 –C 4 -haloalkoxy and nitro,
R 2 is H, C 2 –C 6 -alkyl, C 2 –C 6 -alkenyl or C 2 –C 6 -alkynyl, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl )-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl,
or the group
NR 1 R 2 is a heterocyclic ring of 4, 5 or 6 ring atoms which may contain up to two further ring heteroatoms from the group consisting of N and O in the ring and which is unsubstituted or substituted by one or more radicals from the group consisting of C 1 –C 4 -alkyl,
R 3 is H or CH 3 ,
one of the radicals X and Y is halogen, C 1 –C 2 -alkyl, C 1 –C 2 -alkoxy, C 1 –C 2 -alkylthio, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 2 -alkoxy and C 1 –C 2 -alkylthio, or is mono- or di-(C 1 –C 2 -alkyl)amino, and
the other of the radicals X and Y is C 1 –C 2 -alkyl, C 1 –C 2 -haloalkyl, C 1 –C 2 -alkoxy, C 1 –C 2 -haloalkoxy or C 1 –C 2 -alkylthio,
Z is CH.
3. A process for preparing a compound or salt thereof of claim 1 , which comprises:
(1) reacting the compound of formula (II) or salt thereof
in the presence of a halogenating agent, with formation of the carbonyl halide and its rearrangement to form the compound of formula (III)
wherein
(R) n is n identical or different radicals from the group consisting of halogen, alkyl and alkoxy,
n is 0 or 1,
R 1 is H, C 1 –C 6 -alkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 1 –C 6 -alkoxy, C 2 –C 6 -alkenoxy, C 2 –C 6 -alkynoxy or Cs-C 6 -cycloalkyl, each of the 7 latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (Ci-C 4 -alkyl)-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl, or is phenyl which is unsubstituted or substituted by radicals from the group consisting of halogen, C 1 –C 4 -alkyl, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkyl, C 1 –C 4 -haloalkoxy and nitro,
R 2 is H, C 2 –C 6 -alkyl, C 2 –C 6 -alkenyl or C 2 –C 6 -alkynyl, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl)-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkyisulfinyl and C 1 –C 4 -alkylsulfonyl,
or the group NR 1 R 2 is a heterocyclic ring of 4, 5 or 6 ring atoms which may contain up to two further ring heteroatoms from the group consisting of N and O in the ring and which is unsubstituted or substituted by one or more radicals from the group consisting of C 1 –C 4 -alkyl,
(2a) reacting the compound of formula (III) to ammonolysis at the SO 2 Cl group to give the a compound of formula (IV)
wherein (R) n , n, R 1 and R 2 is as defined above;
and then reacting the compound of formula (IV) with the compound of formula (VI)
wherein
X and Y independently of one another are halogen, C 1 –C 6 -alkyl, C 1 –C 6 -alkoxy, C 1 –C 6 -alkylthio, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy and C 1 –C 4 -alkylthio, or are C 3 –C 6 -cycloalkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, alkenyloxy or C 3 –C 6 -alkynyloxy, and
Z is CH; and
M is H, C 1 –C 4 -alkyl or a metal cation; or
(2b) reacting the compound of the formula (III) with cyanates and with the heterocyclic amine of the formula (VIII)
wherein
X and Y independently of one another are halogen, C 1 –C 6 -alkyl, C 1 –C 6 -alkoxy, C 1 –C 6 -alkylthio, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy and C 1 –C 4 -alkylthio, or are C 3 –C 6 -cycloalkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 3 –C 6 -alkenyloxy or C 3 –C 6 -alkynyloxy, and
Z is CH; and
R 3 is hydrogen or methyl.
4. The process of claim 3 , wherein
(R) n is halogen, C 1 –C 4 -alkyl or C 1 –C 4 -alkoxy,
n is 0 or 1,
R 1 is H, C 1 –C 6 -alkyl, C 2 –C 6 -alkenyl, C 2 –C 6 -alkynyl, C 1 –C 6 -alkoxy, C 2 –C 6 -alkenoxy, C 2 –C 6 -alkynoxy or C 5 –C 6 -cycloalkyl, each of the 7 latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl)-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl, or is phenyl which is unsubstituted or substituted by radicals from the group consisting of halogen, C 1 –C 4 -alkyl, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkyl, C 1 –C 4 -haloalkoxy and nitro,
R 2 is H, C 2 –C 6 -alkyl, C 2 –C 6 -alkenyl or C 2 –C 6 -alkynyl, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 4 -alkoxy, C 1 –C 4 -haloalkoxy, C 1 –C 4 -alkylthio, mono- and di-(C 1 –C 4 -alkyl)-amino, cyano, azido, formyl, (C 1 –C 4 -alkyl)-carbonyl, (C 1 –C 4 -alkoxy)-carbonyl, C 1 –C 4 -alkylsulfinyl and C 1 –C 4 -alkylsulfonyl,
or the group
NR 1 R 2 is a heterocyclic ring of 4, 5 or 6 ring atoms which may contain up to two further ring heteroatoms from the group consisting of N and O in the ring and which is unsubstituted or substituted by one or more radicals from the group consisting of C 1 –C 4 -alkyl,
R 3 is H or CH 3 ,
one of the radicals X and Y is halogen, C 1 –C 2 -alkyl, C 1 –C 2 -alkoxy, C 1 –C 2 -alkylthio, each of the three latter radicals being unsubstituted or substituted by one or more radicals from the group consisting of halogen, C 1 –C 2 -alkoxy and C 1 –C 2 -alkylthio, or is mono- or di-(C 1 –C 2 -alkyl)amino, and
the other of the radicals X and Y is C 1 –C 2 -alkyl, C 1 –C 2 -haloalkyl, C 1 –C 2 -alkoxy, C 1 –C 2 -haloalkoxy or C 1 –C 2 -alkylthio,
Z is CH; and
M is H, C 1 –C 4 -alkyl or a metal cation.