AU624123B2 - Process for the preparation of substituted difluorobenzo-1, 3-dioxoles - Google Patents

Abstract

The reaction of 2,2-difluorobenzo-1,3-dioxol with (a) an alkali metal or an alkali metal compound and then with (b) a compound R<1>-Z<1> where Z<1> has the meaning of a leaving group, or an aldehyde, gives compounds of the formula I <IMAGE> in which R<1> represents -OH, -SH, -CHO, -CN, -COOH, -B(OH)2, -COX where X represents Cl or Br, furthermore -COOR<2>, -SiR@ or -B(OR<2>)2 where R<2> has the meaning of a C1-C12-alcohol radical minus the hydroxyl group, in which R1 furthermore represents -CnH2nCOOR<2> where n has the meaning of a number from 1 to 4, or linear or branched C1-C12-hydroxyalkyl which is unsubstituted or substituted by -F, -CN, C1-C6-alkoxy, phenyl, fluorophenyl, C1-C4-alkoxyphenyl, C1-C4-alkylthiophenyl, C1-C4-alkylphenyl, C1-C4-fluoroalkylphenyl, nitrophenyl or cyanophenyl, or in which R1 represents a benzyl alcohol which is unsubstituted or substituted by F, C1-4-alkoxy, -alkylthio, -alkyl, -fluoroalkyl, nitro or cyano, or is C1-C12-acyl, or in which R1 represents a radical of the formula II <IMAGE> in which R<5> represents -CN, -CF3, -COOR<2>, -CONH2, -CO-NHR<2> or -CONR@, R<3> and R<4> represent a direct bond or in each case represent H, or R<3> is H and R<4> independently has the meaning of R<5>, or R<3> and R<4> together represent -CH2-NR<6>-CH2-, -CH2-NR<6>-CO- or -CO-NR<6>-CO- where R<6> is the radical of a protective group which can be eliminated, or where, furthermore, R<1> represents a radical of the formula III <IMAGE> Insecticides or fungicides can be prepared from the compounds of the formula I.

Description

/I

i r_ i FORM 10 &3 ef: 89191 COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952 COMPLETE SPECIFICATION

(ORIGINAL)

FOR OFFICE USE: Class Int Class Complete Specification Lodged: Accepted: Published: \Priority: Related Art: Name and Address of Applicant: Ciba-Geigy AG Klybeckstrasse 141 4002 Basle

SWITZERLAND

F I Address for Service: Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia r (9 Complete Specification for the invention entitled: Process for the Preparation of Substituted Difluorobenzo-1,3-dioxoles The following statement is a full description of this invention, including the best method of performing it known to me/us 5845/5 5-16949/= Process for the prepara-tion of substituted difluorobenzo-1,3-dioxoles Abstract The reaction of 2,2-difluorobenzo-1,3-dioxole with an alkali metal or an alkali metal compound and then a compound R'-Z 1 in which Z' is a leaving group, or with an aldehyde produces compounds of formula I 0/ wherein R 1 is -OH, -SH, -CHO, -CN, -COOH, -B(OH)2, -COX, with X being C1 0 or Br, or is -COOR 2 -SiRj or -B(0R 2 2 with R 2 being a C 1

-C-

12 alcohol Smoiety without the hydroxy group, wherein RI is further -C HCORwt n 2n CO ,wt S n being an integer from 1 to 4, or linear or branched Cl-Cl2hydroxyalkyl which is unsubstituted or is substituted by -CN, C 1 -Csalkoxy, phenyl, 00 fluorophenyl, Ci-Cz 4 alkoxy-phenyl, Cl-C 4 alkylthio-phenyl, G 1 -Ci 4 alkyl- 0 0 phenyl, Cl-Ci~fluoroalkyl-phenyl, nitrophenyl or by cyanophenyl, or wherein R' is a benzyl alcohol-which is unsubstituted or is substituted 0: by F, Cl-C~alkoxy, Cl-Cz~alkylthio, Cl-Ci~alkyl, Cl-C 4 fluoroalkyl, nitro or by cyano, or is C1-C1 2 acyl, or wherein R' is a radical of formula II -R (II), wherein R 5 is -CN, -GF 3 -COOR 2

-CONH

2

-CO-NHR

2 or -CONR R 3 and R' are a direct bond or each is H, or R 3 is H and R4~ independently has the 0 meanings of R 5 or R 3 and R4~ together are -CHZ-NR 6

-CH

2

-CH

2

-NR

6 -CO- or 00.: -CO-NR 6 -CO- wherein R 6 is the radical of a removable protecting group, or wherein further R1 is a radical of formula III -R Insecticides or fungicides can be prepared from the compounds of formula I.

5-16949/= Process for the preparation of substituted difluorobenzo-1,3-dioxoles The invention relates to a process for the preparation of 2,2-difluorobenzo-1,3-dioxoles that are substituted in the 4-position, by reaction of 2,2-difluorobenzo-1,3-dioxole with an alkali metal or with an alkali metal or alkaline earth metal compound and subsequent reaction with an aldehyde or a compound having a leaving group, and to novel 2,2-difluorobeno-1,3-dioxoles that are substituted in the 4-position.

SEP-A-O 206 999 describes unsubstituted or N-substituted 3-(2,2-difluoro- 0 benzo-1,3-dioxol-4-yl)-4-cyanopyrroles which are valuable agents for 0 controlling microorganisms. The compounds are prepared by a multi-stage 000 0000 synthesis. The 3-(2,2-difluorobenzo-1,3-dioxol-4-yl)-2-propenoic acid o00.000 nittile which is required as starting material is obtained by diazotisaoo 0 tion of 4-amino-2,2-difluorobenzo-1,3-dioxole, subsequent reaction with 0 0 acrylonitrile in the presence of CuCl and dehalogenation of the resulting 4-(2-thloro-2-cyano-eth-1-yl)-2,2-difluorobenzo-1, 3 dioxole. (2,2-Di- 000 :0 fluorobenzo-1,3-dioxol-4-yl)-methyl esters of pyrethroid or pyrethroid- 00,0 like carboxylic acids, for example, are described as insecticides in 0 00 DE-OS 2 819 788. The benzodioxolylmethyl alcohols are in this case o* prepared by customary methods, for example with the reduction of aldehydes. 2,2-Difluorobenzo-1 3-dioxole-4-carbaldehyde, however, is not mentioned.

SIn J. Org. Chem., Vol. 37, page 673 (1972), E.L. Stogryn describes the 0 0 preparation of 2,2-difluorobenzo-1,3-dioxole-5-carbaldehyde by formylation of 2,2-difluorobenzo-1,3-dioxol-5-yllithium with dimethylformamide.

The lithium compound is obtained by reaction of 5-bromo-2,2-difluorobenzo-1,3-dioxole with butyllithium.

9 2 It has now been found that 2,2-difluorobenzo-l,3-dioxole that is free of halogen at the benzene nucleus can be reacted with alkali metals or alkali metal or alkaline earth metal compounds'directly and with high specificity with regard to position to give 2,2-difluorobenzo-1,3-dioxole metallated in the 4-position which can be reacted further with electrophilic compounds to give corresponding benzenes substituted in the 4 -position.

The present invention relates to a process for the preparation of compounds of formula I /0 I ri CF 2 0/ 0 0 0 o 00 o 0 o a 000 0 0000 0000 0 0 0 0 0 wherein R 1 is -OH, -SH, -CHO, -CN, -COOH, -B(OH) 2 -COX, with X being Cl or Br, or is -COOR 2 -SiR or -B(OR 2 2 with R 2 being a C 1 -Czlalcohol moiety without the hydroxy group, wherein R 1 is further -CnH2nCOOR 2 with n being an integer from 1 to 4, or linear or branched C 1

-C

1 zhydroxyalkyl which is unsubstituted or is substituted by -CN, Ci-C 6 alkoxy, phenyl, fluorophenyl, Ci-C4alkoxy-phenyl, C 1 -C4alkylthio-phenyl, C 1 -Cialkyl-phenyl, Ci-Cifluoroalkyl-phenyl, nitrophenyl or by cyanophenyl, or wherein

R

1 is a benzyl alcohol or a Ci-C2iacyl moiety, each unsubstituted or substituted by F, Ci-C4alkoxy, Ci-C4alkylthio, Ci-C4alkyl, C 1

-C

4 fluoroalkyl, nitro or by cyano, or wherein R 1 is a radical of formula II *000 «l o ai n 0 0 0 00 0 o o o 0 00 00 0 0 0 00 g 0o 0

Q

0 6 0 000000 0 0 r3 4 R'

(II),

wherein R 5 is -CN, -CF3, -COOR 2

-CONH

2

-CO-NHR

2 or -CONR<, R 3 and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or R 3 and R 4 together are -CH 2

-NR

6 -CHz-, -CH 2

-NR

6 -CO- or

-CO-NR

6 -CO- wherein R 6 is the radical of a removable protecting group, or wherein further R 1 is a radical of formula III

(III)

which process comprises c I -3a) in an inert solvent, reacting 2,2-difluorobenzo-1,3-dioxole with an alkali metal or with an alkali metal or alkaline earth metal compound with a strong anion base to give a compound of formula IV S i CF 2

(IV)

0 wherein Y is an alkali metal or an alkaline earth metal, and optionally then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ2', NiZ 2 AlZ 3 SiZ 4 SnZ 2 SnZi4, TiZ 4

BZ

3 or ZrZ4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CUZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ 3 -TiZ 3

-BZ

2 or -ZrZ 3 and Z is -Cl, -Br or -I and, in the case of boron, is also -OC1-Ci~alkyl or -0-aryl, no, b) reacting the compound of formula IV with an electrophilic compound 004 from the group X-CN, C0 2

S

8

COX

2 B(0R 2 )3 R 2 0- ~o S XCOOR 2 with X being -Cl or -Br, or with a formylating reagent, CH 2 0, an 4040 epoxide, a benzaldehyde which is unsubstituted or is substituted by F, o CI-Cialkoxy, Ci-C 4 alkylthio, Cl-C~alkyl, Cl-C~fluoroalkyl, nitro or by cyano, a Ci-Ciialkyl-CH0 which is unsubstituted or is substituted by -F, -Cl, -CN, CI-C 6 alkoxy, phenyl, fluorophenyl, Cl-C 4 alkoxyphenyl, Cj-Ct 4 0 alkylthiophenyl, Cl-C~alkylphenyl, Cl-Ct~fluoroalkylphenyl, nitrophenyl or 000 by cyanophenyl, or with C1-Ci 2 acyl-X1 wherein X1 is -Cl, -Br, C1-C 6 alkoxy or the radical of a secondary amine, or with X 2 C nH 2nC00R', X 2

-C;R

3

'CR

4

R'

o 9 or a compound of formula Il~a H~ ~H(lIIa) 06 wherein X 2 is a leaving group, and c) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I.

A preferred process is that for the preparation of compounds of formula I 0 I II CF 2 \01 wherein R 1 is -CHO, -CN, -COOH, -B(OH) 2 -COX, with X being Cl or Br, or is -COOR 2 or -B(OR 2 2 with R 2 being a C 1

-C

1 2 -alcohol moiety without the hydroxy group, wherein RI is further -C H 2nCOOR 2 with n being an integer from 1 to 4, or linear or branched Ci-C1 2 hydroxyalkyl or Ci-Cz2acyl each unsubstituted or substituted by -CN, CI-C6alkoxy, phenyl, fluorophenyl, C1-C4alkoxyphenyl, Ci-C4alkylthiophenyl, Cl-C4alkylphenyl,

C

1 -Cifluoroalkylphenyl, nitrophenyl or by cyanophenyl, or wherein R 1 is a radical of formula II

(II),

43 wherein R 5 is -CN, -CF 3

-COOR

2

-CONH

2

-CONHR

2 or -CONR 2 R' and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the 0 meanings of R or R 3 and RI together are -CH 2

-NR

6

-CH

2

-CH

2

-NR

6 -CO- or o 0 -CO-NR 6 -CO- wherein R 6 is the radical of a removable protecting group, or wherein further R 1 is a radical of formula III H H (III) o which process comprises a) in an inert solvent, reacting 2,2-difluorobenzo-1,3-dioxole with an alkali metal or with an alkali metal or alkaline earth metal compound 0 0s°* with a strong anion base to give a compound of formula IV /o 11 CFz (IV) \0 I i c, wherein Y is an alkali metal or an alkaline earth metal, and optionally then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ 2 NiZ 2 AlZ 3 SiZi 4 SnZ 2 SnZ4, TiZ 4 BZ3 or ZrZ4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ3, -TiZ 3

-BZ

2 or -ZrZ 3 and Z is -Cl, -Br or -I and, in the case of boron, is also -0-Cl-Csalkyl, b) reacting the compound of formula IV with an electrophilic compound from the group X-CN, COz2, B(OR 2 3

COX

2 or XCOOR 2 with X being -Cl or -Br, or with a formylating reagent, CHO20, an epoxide, a Cj-Cj 1 alkyl-CHO which is unsubstituted or is substituted by -Cl, -CN, C1-Csalkoxy, phenyl, fluorophenyl, Cl-C 4 alkoxyphenyl, C 1

-C

4 -alkylthiophenyl, C 1 -C4alkylphenyl, C1-C4fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or with C1-C 12 acyl-X 1 wherein X1 is -Cl, -Br, C 1 -Csalkoxy or the radical of a secondary amine, or with X 2 C nH2nCOOR 2 X2-CR3=CR RS or a compound of 09 0 S* formula IIIa on a o a X2_ H th (IIIa) a wherein X 2 is a leaving group, and c) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I.

o ab A preferred process in this connection is considered to be that for the 0 0 preparation of compounds of formula I according to claim 2, 00

IF

a I CF2 wherein R1 is -CHO, -CN, -COOH, -COX, with X being Cl or Br, -COOR 2 with

R

2 being a C 1

-C

2 zalcohol moiety without the hydroxy group, -C H COOR 2 n 2n 1 with n being an integer from 1 to 4, linear or branched C 1

-C

12 hydroxyalkyl or Cl-Cl2acyl each unsubstituted or substituted by -CN, -6-

CI-C

6 alkoxy, phenyl, fluorophenyl, Cl-C*~alkoxyphenyl, Cl-C~alkylthiophenyl, Cl-CL~alkylphenyl, Cl-C~fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or is a radical of formula II 3II) wherein RS is -CN, -CF 3 -COOR 2 or -CONR R 3 and R4 are a direct bond or each is H, or R 3 is H and R4 independently has the meanings of R 5 or R 3 and R4~ together are -CH 2 -NR6-CH2-, -CH 2

-NR

6 -CO- or -CO-NR 6-CO- wherein R 6 is the radical of a removable protecting group, or wherein R1 is a radical of formula III which process comprises 0* a) in an inert solvent, reacting 2,2-difluorobenzo-1,3-dioxole with an 00 alkali metal or with an alkali metal compound with a strong anion base to Sgive a compound of formula IV I I CF 2

(IV)

00 1* wherein Y is an alkali metal, and optionally then reacting with an anhydrous metal halide from the group MgZ2, ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ 2 o 0 NiZ 2 AlZ 3 SiZ4, SnZ 2 SnZ*4, TiZi., or ZrZ 1 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ3, -SnZ, -SnZ 3 -TiZ 3 or -ZrZ3 and Z is -Cl, -Br or -I, Sb) reacting the compound of formula IV with an electrophilic compound from the group X-CN, C0 2

COX

2 or XCOOR 2 with X being -Cl or -Br, or with a forxnylating reagent, a C 2 -Cl 2 haloalcohol which is unsubstituted or is substituted by -CN, Cl-C 6 alkoxy, phenyl, fluorophenyl, C 1 -Ci 1 alkoxyphenyl, C 1 -Cialkylthiophenyl, C 1

-C

4 alkylphenyl, Cl-CL~fluoroalkylphenyl, nitrophemyl or by cyanophenyl, CH 2 O, a Cl-Cl 1 alkyl-CHQ which is unsubstituted or is substituted by -CN, Cl-C 6 alkoxy, phenyl, fluorophenyl, Cl-Ci 4 alkoxyphenyl, Cl-Ct~alkylthiophenyl, Cl-Ci 4 alkylphenyl,

I

7 C1-C 4 fluoroalkylphenyl, nitrophenyl or by cyanophenyl, an epoxide, a benzaldehyde which is unsubstituted or is substituted by Ci-C4alkoxy, Ci-C4alkylthio, Ci-Coalkyl, Cl-C4fluoroalkyl, nitro or by cyano, or with Ci-C12acyl-X 1 wherein X1 is -Cl, -Br, Ci-Csalkoxy or the radical of a secondary amine, or with X 2 Cn H2n COOR 2

X

2

-CR

3 =CR R 5 or a compound of formula IIa X2 _-Ra HC CH *IIIa) wherein X 2 is a leaving group, and c) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I.

e Also preferred is a process for the preparation of compounds of formula I wherein R' is -CHO, -CN, -COOH, -COX, with X being Cl or Br, or a radical ao of formula II 3 4 0 bre -R (II), r wherein R 5 is -CN, -CF3, -COOR 2 or -CONHz, R 3 and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or R 3 c and R 4 together are -CH 2

-NR

6 -CO- wherein R 6 is the radical of a removable S protecting group, or wherein R 1 is a radical of formula III C CH (III) g o o a un n .o which process comprises a) in an inert solvent, reacting 2,2-difluorobenzo-l,3-dioxole with an alkali metal or with an alkali metal compound with a strong anion base to give a compound of formula IV 0 *I I "l S-8- 8 wherein Y is an alkali metal, and optionally then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ 2 NiZ 2 AlZ 3 SiZ 4 SnZ 2 SnZ4, TiZu, BZ 3 or ZrZ4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ 3 -TiZ 3

-BZ

2 or -ZrZ 3 and Z is -Cl, -Br or -I, b) reacting the compound of formula IV with an electrophilic compound from the group X-CN, CO 2 or COX 2 with X being -Cl or -Br, a formylating reagent, X 2

-CR

3 =CR R 5 or a compound of formula IIa

X

2 HC CH (IIIa) wherein X 2 is a leaving group, and .0 0 0. c) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I.

a o S Prominence is to be given in this connection to that variant for the preparation of compounds of formula I wherein R 1 is -CHO or a radical of formula II o -R (II), a3 4 0 a 0 wherein R 5 is -CN, -COOR 2 or -CONH 2 each of R 3 and R 4 is H, or R 3 is H 00 or o and R 4 independently has the meanings of R A preferred embodiment of the process is that in which, in formula I, R 1 is -CHO or -COOR 2 in formula II R 3 and R 4 are a direct bond and R 5 is 00.. -CN, or R 3 is H, R 4 is -CN and R 5 is -COOR 2 -CONRJ or -CN, or R 3 and R together are -CHz-NR 6

-CH

2

-CO-NR

6 -CO- or -CH 2

-NR

6 -CO- and R 5 is -CN, and R 5 in formula III is -CN.

When R 2 is an alcohol moiety without a hydroxy group it can be, for example, linear or branched alkyl having pref-erably from 1 to 12, especially from 1 to 6, carbon atoms, or unsubstituted or C 1

-C

4 alkylsubstituted Cs- or CG-cycloalkyl or Cs- or C 6 -cycloalkyl-CmH2m- or phenyl-C H wherein m is 0 or an integer from 1 to 4, especially 0, 1 m 2m 1I .1

I-

9 or 2. Examples are methyl, ethyl, the isomers of propyl, butyl, pentyl, hexyl, octyl, decyl, dodecyl, cyclopentyl, cyclohexyl, methylcyclopentyl or methylcyclohexyl, (methyl- or ethyl-cyclohexyl)methyl, benzyl, methylor ethyl-benzyl, phenylethyl or (methylphenyl)ethyl.

When R 1 is C H 2nCOOR 2 n is an integer from 1 to 4, especially 1 or 2.

The -C H group may be linear or branched. Examples of this group are methylene, ethylene, ethylidene, propylidene, 1,2- or 1,3-propylene, butylidene, 1,3- or 1,4-butylene.

When R' is unsubstituted or substituted hydroxyalkyl, it contains preferably from 1 to 6, especially from 1 to 4, carbon atoms. The hydroxy group may be bonded to a primary, secondary or tertiary carbon atom.

Examples of hydroxyalkyl are hydroxymethyl, 1 or 2-hydroxyethyl, 1-, 2-or 3-hydroxyprop-1- or -2-yl, 3- or 4-hydroxybut-1- or -2-yl, hydroxypentyl, hydroxyhexyl, phenyl(hydroxymethyl), 1-phenyl-2-hydroxyethyl, fluorophenyl(hydroxymethyl), 1-methoxy-2-hydroxyeth-2-yl, 1,1,1trifluoro-2-hydroxyethyl and cyanophenyl(hydroxymethyl).

o 0 00 0 00 do oo 0s* 000090 0 0 0 0 When R' is unsubstituted or substituted acyl, it contains preferably from 1 to 6 and especially from 1 to 4 carbon atoms. The acyl radical may, for 0000 000 example, be one of formula R 7 -CO- wherein R7 is C 1 -Clialkyl, especially 0 Cl-Csalkyl, which is unsubstituted or is substituted by -CN, C 1 -C6alkoxy, phenyl, fluorophenyl, C 1

-C

4 alkoxyphenyl, C 1 -Cialkylphenyl, o C 1 -Calkylthiophenyl, C 1 -C4fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or may be phenyl which is unsubstituted or is substituted by -F, cyano, nitro, C 1 -Cialkyl, C 1 -C4alkoxy, C 1

-C

4 alkylthio or by C 1 -Czfluoro- V, alkyl. Examples ar- formyl, acetyl, fluoroacetyl, trifluoroacetyl, chlorodifluoroacetyl, propionyl, butyryl, benzoyl, phenylacetyl, 3-phenylpropionyl or fluorobenzoyl.

As the radical of a secondary amine, X 1 contains preferably from 2 to 12, especially from 2 to 8, carbon atoms. The radical may correspond to the formula R 8

R

9 N- wherein R 8 is C 1 -Csalkyl or C 1 -Csalkoxy and R 9 is C 1 -Csalkyl, or R' is C 1 -CLalkoxy-Cl-C3alkyl and R 9 is C 1 -Csalkyl or has the meaning of R 8 or R 8 and R together are tetra- or penta- methylene or tetra- or penta-methylene interrupted by or by a =N-C 1

-C

4 alkyl group.

p.

i ;I 1- 10 In a preferred embodiment, X 1 is C 1

-C

4 alkyl-k-0C-Calkyl, C1-Czalkyl-A-CHCH 2 0-C-lCr-alkyl, (C 1 -CialkylOC 2 CHz) 2 N- or the radical of a 5- or 6-membered heterocyclic amine which may contain a further hetero atom from the group and =N-C 1

-C

4 alkyl. Examples are dimethylamino, diethylamino, methoxymethylamino, ethoxymethylamino, methyl- (methoxyethyl)amino, di(methoxymethyl)amino, pyrrolidino, piperidino, morpholino and N-methylpiperazino.

is preferably -CN, -CF 3

-COOR

2 or -CONH 2 The removable protecting group R6 is generally a known radical. R 6 may, for example, be Cl-C4alkoxymethyl, or phenoxymethyl which is unsubstituted or substituted by Ca-Ctalkyl or C1-Cialkoxy. Suitable groups are also benzyl, diphenylmethyl and triphenylmethyl. In a preferred embodiment the protecting groups are trialkylsilyl groups having a total of from 1 to 18, preferably from 1 to 10, carbon atoms, Ci-Clzacyl, especially CI-Csacyl, groups or -COOR 2 groups in which R 2 has the meanings mentioned hereinbefore. The trialkylsilyl group may be, for example, trimethylsilyl, triethylsilyl, tri-n- or -iso-propylsilyl, tert.-butyldimethylsilyl or (1,1,2,2-tetramethylethyl)dimethylsilyl. Acyl groups have been mentioned hereinbefore for In the group -COOR 2

R

2 is preferably Cr-Csalkyl. Examples of these groups are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl.

*0p o a a o 00 o 00 o 0 00s a 0 V'*0 0 0* 00* 00 *1 0q *e 0 oI a 0 0( 00 00 00 0 The leaving group X 2 is preferably a halide, especially -Cl or -Br, CI-Csalkoxy, for example methoxy, ethoxy or propoxy, Cs-Cloaryloxy, for example phenoxy or naphthoxy, C1-C12-secondary amino, especially Cl-Ca*U secondary amino, for example dimethylamino, diethylamino, piperidino, 0: Cl-C8-acyloxy, especially C1-C+acyloxy, for example acetyloxy, or the radical of a sulfonic acid which may be an aliphatic sulfonic acid, for example methyl-, ethyl- or propyl-sulfonic acid, or an aromatic sulfonic acid, for example benzene- or p-toluene-sulfonic acid.

2,2-Difluorobenzo-1,3- ioxole is known and can be obtained, for example, by fluorination of 2,2-dichlorobenzo-1,3-dioxole.

:1 :i i i! i

I

1 thereof. Examples are pentane, isopentane, hexane, heptane, cyclohexane, 4 l 11 Reaction step a) is carried out in an inert solvent, for example in a non-polar or polar aprotic solvent. Suitable solvents are aliphatic or aromatic hydrocarbons, ethers, tertiary amines, N-alkylated acid amides, lactams or cyclic ureas, sulfoxides, sulfones, nitriles, or mixtures thereof. Examples'are pentane, isopentane, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, diethyl ether, dibutyl ether, tetrahydrofuran, dioxane, ethylehe glycol dimethyl ether, triethylamine, N,N,N',N'-tetramethylethylenediamine, hexamethylphosphoric acid triamide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, ethylenedimethylurea, propylenedimethylurea, dimethyl sulfoxide, tetramethylenesulfone, acetonitrile. Solvents that may at the same time be reactants in process step such as, for example, carboxylic acid So u amides, are not added until process step b) and are then added in the form of an excess of those reactants.

.g The r raction temperature may alyp rabl be from -150 to 150°C, especially from -100 to 80°C, in both process steps.

0 a If non-polar or weakly polar solvents are employed, it is advantageous for the reaction mixture to contain, in addition, a complexing agent, for °oo° 2 example in an amount of from 0.01 mol. up to a 10-fold excess, based on o0o the compound of formula IV. Such complexing agents may be, for example, tertiary amines or N-substituted acid amides, lactams or cyclic ureas, ethers or sulfoxides, such as those mentioned hereinbefore under solvents. Further suitable complexing agents 're crown ethers, such as, for example, 15-crown-5, 18-crown-6, dibenzo-18-crown-6, dicyclohexyl-18- So' crown-6, dibenzo-24-crown-8 or dicyclohexyl-24-crown-8. Alkali metal S B. halides, especially lithium, sodium and potassium halides, magnesium halide and copper halide are also suitable. Halide is preferably chloride, bromide and iodide.

Suitable ali'ali metals and alkaline earth metals, also in the alkali metal and alkaline earth metal compounds, for use in reaction step a) are, for example, Li, Na, K, Rb, Cs, Ca, Sr or Ba, with Li, Na ai. K

U

being preferred. The strongly basic anions may be, for example, linear or branched C1-Csalkyl 0 especially C1-Cnalkyl®, C6-CiLaryl 9 HO, H 2 He, ia i i, 12 Ca-C6alkoxy especially Ci-C alkoxy, C1-C 6 alkyl-NH, especially C1-Calkyl-NH or di(Ca-CSalkyl)N especially di(C1-C4alkyl)N or di(C3-Ccycloalkyl)N. In a preferred embodiment, the alkali metal is Li, Na or K and the alkali metal or alkaline earth metal compound is a Li-, Na-, Ca-, Sr- or Ba-alkyl, -arylhydride, -amide or -alcoholate.

The metallation of 2,2-difluorobenzo-1,3-dioxole is effected in a manner known per se by reaction thereof with an alkali metal or with an alkali metal or alkaline earth metal compound in an inert solvent at preferably from 20 to -80°C. In this reaction, the alkali metal, for example in the form of a suspension, or the alkali metal or alkaline earth metal compound can be introduced into the reaction vessel first and the benzodioxole can be slowly added thereto. The procedure may also be o reversed.

0 0 ,o Reaction b) can be carried out directly after reaction step It is also possible, however, for the alkali metal or alkaline earth metal 044 compound of formula IV to be reacted prior to reaction step b) with an anhydrous metal halide, for example MgZz, ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ 2 NiZ 2 A1Z 3 SiZ 4 SnZ 2 SnZ 4 TiZ 4

BZ

3 or ZrZ 4 wherein Z is Cl, Br or I, especially Cl or Br, to give a compound of formula IV wherein Y is -MgZ, S-ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ 3 -TiZ 3

-BZ

2 or o o -ZrZ 3 Z is especially Cl or Br. In this reaction, the metal halide can be added in solid form or in the form of a suspension in an inert 0o solvent. The reaction temperature is preferably from 0 to -80 0

C.

The electrophilic compounds used in reaction step b) are known or can be prepared by known processes. A few examples are cyanogen chloride or 0o:0 obromide, carbon dioxide, carboxylic acid dichloride or dibromide, methyl chlorocarbonate, ethyl bromocarbonate; formylating reagents preferably from the group Ci-C6alkoxymethyleneanilines, formyl halide, especially formyl chloride and bromide, formates having preferably from 1 to 6, especially from 1 to 4, carbon atoms in the alcohol moiety, for example methyl or ethyl formate, orthoformic acid esters having preferably from 1 to 6 carbon atoms in the alcohol moiety, N-disubstituted formamides having from 2 to 12, preferably from 2 to 6, carbon atoms and, optionally, or N-Ca-C4alkyl groups in the amide radical, for example di-

I

-"j 13 methyl-, diethyl-, methyl-methoxyformamide, formic acid morpholide or formic acid N-methylpiperazide; formaldehyde, acetaldehyde, benzaldehyde, acetyl chloride or bromide, propionyl chloride, methyl acetate, ethyl propionate, dimethylacetamide, N-methyl-N-methoxypropionic acid amide, ethyl benzoate, N,N-dimethylphenylacetic acid amide, ethyl chloroacetate or bromoacetate, 2-chloro- or 2-bromo-ethanol, 2-chloro- or 2-bromopropan-1-ol, 4-chlorobutan-1-ol, 3-chloro- or 3-bromo-propynoic acid nitrile, 1-chloro- or 1-bromo-3,3,3-trifluoropropyne, ethyl 3-chloropropynecarboxylate, ethoxyacetonitrile, 1-ethoxy-3,3,3-trifluoroprop-1ene, ethylene oxide, propylene oxide, ethyl f-dimethylaminoacrylate, B-p-toluenesulfonyloxyacrylonitrile, N,N-dimethyl-2-chloroacrylic acid amide, 8-ethoxy-acrylonitrile, a-p-toluenesulfonyloxy-a-cyanoacrylonitrile, ethyl N,N-dimethylaminomethylenecyanoacetate, a-trifluoro- S methyl-a-chloroacrylonitrile, ethyl ethoxymethylenecyanoacetate, ethyl a p-toluenesulfonyloxymethylenecyanoacetate, A 3-1-acetyl-3-cyano-4-chloropyrroline, A 3-1-trimethylsilyl-3-cyano-4-tosyloxy-pyrrolin- 2 -one, 1-acetyl-3-cyano-4-chloro-pyrrole, trimethyl borate, triphenyl borate, aaaaa trimethylchlorosilane, diphenylmethylchlorosilane, sulfur. Formylating an a reagents are described by Olah et al. in Chem. Rev. 1987, 87, page 671.

It may be of advantage to carry out reaction b) in the presence of Pd, Rh aaaa 9 or Ru compounds.

a a a The reaction temperature in step b) may, for example, be from -800C to Gr a S 10000, preferably from -80 0 C to 50 0 C. The electrophilic compound may be added in solid form or in the form of a solution, it being possible for the solvent to be the same as or different from that used in reaction o step a).

The isolation of the compounds of formula I is carried out by methods that are known per se by distilling, crystallising or chromatographing the filtrate obtained after filtration of the reaction mixture. It is generally advantageous to hydrolyse the reaction mixture, for example with dilute mineral acids, such as, for example, hydrochloric acid or sulfuric acid. If the electrophilic compound is COz, an aldehyde, an epoxide or a carboxylic acid amide or ester, salts will initially be

II

-14formed which make hydrolysis necessary in order to isolate the compounds of formula I. The hydrolysis conditions are so selected that the protecting group

R

6 is not split off.

The invention further relates to compounds of formula la R1 Ri 0 CF2 Oa), wherein R 1 is -OH, -SH, -CHO, -CN, -COOH, -B(OH) 2 -COX, with X being CI or Br, or is -COOR 2 -SiR2 or -B(OR 2 2 with R 2 being a Cj-C, alcohol moiety without the hydroxy group, wherein R' is further -CH2nCOOR 2 with n being an integer from 1 to 4, or linear or branched C,-C, 1 2 hydroxyalkyl which is 10 unsubstituted or is substituted by -CN, C -Calkoxy, phenyl, fluorophenyl, ,2 Cl-C 4 alkoxyphenyl, C-C 4 alkylthiophenyl, C,-C 4 alkylphenyl, C-C 4 fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or wherein R 1 is a benzyl alcohol which S" is unsubstituted or is substituted by F, C,-C 4 alkoxy, C 1

-C

4 alkylthio, C,-C 4 alkyl, Cl-C 4 fluoroalkyl, nitro or by cyano, or is R 7 -CO- wherein R 7 is C 1 -Cj 1 alkyl, :i 15 which is unsubstituted or is substituted by -CI, -CN, C,-C 6 alkoxy, phenyl, fluorophenyl, Cl-C 4 fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or may 0 be phenyl which is unsubstituted or is substituted by cyano, nitro,

C,-C

4 alkyl, 0 1

-O

4 alkoxy, Cl-C 4 alkylthio or by C,-C 4 fluoroalkyl; or wherein R 1 is a radical of formula II m 3R4 I), wherein R 5 is -CN, -CF, -COOR 2

-CONH

2

-CO-NHR

2 or -CONR2, R 3 and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or wherein further R 1 is a radical of formula III HC CH j6 with the proviso that R 5 in formula III is not -CN and R, is C,-Cealkoxymethyl;C phenoxymethyl which is unsubstituted or substituted by C 1

-C

4 alkyl or KXW/89191.doc j 14A-

C

1

-C

4 alkoxy; benzyl; diphenylmethyl; triphenylmethyl; trialkylsilyl having a total of from 1-18 carbon atoms; -COOR 2

R

7 in which R 2 and R 7 have the meanings mentioned hereinbefore and wherein said compound of formula la is not 2,3-(difluoromethylenedioxy)-cinnamonitril. The preferred meanings indicated hereinbefore for R' to R 6 XI and X 2 also apply here.

Among these compounds, there are preferred those in which R 1 is -CHO, -CN, -COOH, -B(OH) 2 -COX, with X being Cl or Br, or is -COOR 2 or -B(0R 2 2 with R 2 being a C 1

-C

12 alcohol moiety without the hydroxy group, wherein R 1 is further -CnH2nCOOR 2 with n being an integer from 1 to 4, 99 9 0 09 Wa 9 09 9 00 9 999 0 99', 9999 0 99494 99 94 09 0 9 4 0 09 9 99 9 9 9490 9 99 9 99 99 9 0 09 9 90 0 0 9 9 9 9 9990 0 99 99 9 99 9 9 90 999099 9 9 KXW8991do "r 15 or linear or branched C1-C12hydroxyalkyl or Ci-C 12 acyl each unsubstituted or substituted by -CN; Ci-Csalkoxy, phenyl, fluorophenyl, CI-C4alkoxyphenyl, C 1 -C4alkylthiophenyl, C 1 -C4alkylphenyl, C 1 -C4fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or wherein R 1 is a radical of formula II -R (II), wherein R 5 is -CN, -CF 3

-COOR

2

-CONH

2

-CONHR

2 or -CONR 2

R

3 and R are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or R 3 and R 4 together are -CHz-NR 6 -CHz-, -CH 2

-NR

6 -CO- or

-CO-NR

6 -CO- wherein R 6 is the radical of a removable protecting group, or wherein further R' is a radical of formula III

-R

H H (III).

S0 2n 0 o e 6o formula II wherein each of R 3 and R 4 is H and R 5 is -CN, -CF 3 -CONRz or -COOR 2 or wherein R 5 is -CN, -CF 3

-COOR

2 or -CONR R 3 and R" are S a direct bond, or R 3 is H and R 4 independently has the meanings of R 5 or 0o 0 R 3 and R 4 together are -CH 2

-NR

6

-CH

2 -CHa-NR 6 -CO- or -CO-NR 6 -CO- wherein

R

6 is the radical of a removable protecting group, or wherein RI is a a ^o 04 oa S" radical of formula III, with the proviso that R in formula III is not -CN. The preferred meanings indicated hereinbefore for RI to R 6

X

1 and

X

2 also apply here.

00 Another preferred embodiment is that in which, in formula Ia, R' is -CHO or -COOR 2 or is a radical of formula II wherein R 3 and R are a bond and

R

5 is -CN, or R 3 is H, R 4 independently has the meanings of R 5 and R 5 is -CN, -COOR 2 or -CONR, or R 3 and R 4 together are -Ciz-NR 6

-CH

2

I

-CO-NR

6 -CO- or -CH 2

-NR

6 -CO- and R 5 is -CN. R 2 is preferably a Ci-Csalkyl radical. The protecting group R 6 is preferably a trialkylsilyl protecting group having a total of from 1 to 18 carbon atoms, a C 1

-C

1 2 acyl group or a -COOR 2 group.

i i -CO-R6-O o -Cz-N -CO an R 5 is 2 i preeraly C -~alyl_ radca. Te rotctnggrop 6 i pefraby traylily potetig r

;'I

p" I 'I 16 Using the process of the invention, the compounds of formula I are obtained in high yield and purity whilst, in particular, position isomers are not formed or are formed only to an insignificant extent.

The compounds of formulae I and la are suitable for the preparation of insecticides and microbicides. The carboxylic acids and carboxylic acid derivatives, aldehydes and ketones can be reduced by customary methods of reduction to the corresponding alcohols. From ths alcohols it is possible to prepare with pyrethroid or pyrethroid-like carboxylic acids insecticidal esters, such as those described in DE-OS 2 819 788 (Example 1).

Compounds of formula I are furthermore used as intermediates for valuable herbicides of the sulfonylurea class, such as, for example, those described in European Application Publication No. 99 339.

Compounds in which R 1 is -CN, -COOH, COX and COOR 2 can be converted by customary methods into the aldehyde group. From the aldehydes of formula I it is possible to prepare by the process described in EP-A-0 206 999 (Example 1) the microbicidal 3-cyanopyrroles described therein.

op 0)( 04 0 0I40 004 004 0 00 00 0i 0 o 0 U0 In compounds having radicals of formulae II and III, the -CF 3 group can be converted by the process described in US-A-4 705 801 into the nitrile 00 S* o group. The conversion of ester and amide groups into nitrile groups is known, as is the hydrogenation of acetylenes to ethylenes. By using the known methods, it is possible to obtain compounds of formula I in which S the group R' is -CH=CR 4

R

5 wherein R 4 is H, -CN or -COOR 2 and R 5 is -CN ooa... or -COOR 2 These compounds are intermediates for the microbicides whose preparation using these intermediates is described in EP-A-0 206 999. The mentioned methods for conversion into the nitrile group and the dehydrogenation of compounds of formula I wherein R 3 and R 4 together are -CHz-NR 6

-CH

2 or -CH 2

-NR

6 -CO- also result in the microbicidal 3-cyanopyrroles mentioned. Compounds having the radical of formula III are themselves these 3-cyanopyrroles (R 5 is -CN) or can be converted into i 1' ii ri

I

w i i ii I .f 17 them, as mentioned, by known methods (R 5 is -CF3, -COOR 2 or -CONR2).

Methods of removing the protecting group.R 6 are widely described in the literature.

The following Examples il3ustrate the invention in detail.

Example 1: Preparation of 4 -(trifluoroacetyl)-2,2-difluoro-1,3-benzodioxole In a 250 ml 3-necked flask under argon, 7.9 g (50 mmol) of 2,2-difluoro- 1,3-benzodioxole are dissolved in a mixture of 30 ml of tetrahydrofuran and 30 ml of diethyl ether and, at -70 0 C, 40 ml (55 mmol) of tert.butyllithium (1.39M in pentane) are added dropwise thereto over a period of 20 minutes. When the dropwise addition is complete, the yellow S suspension is maintained at -70 0 C for 40 minutes. There is then added 4 4 dropwise at that temperature, over a period of 10 minutes, a solution of 9.8 g (50 mmol) of a,a,--trifluoroacetyl-N-methylpiperazide in 20 ml of diethyl ether. The turbid solution is then allowed to warm up to 0 0 C and is hydrolysed with 30 ml of 2N hydrochloric acid. The aqueous phase is separated off and extracted twice with 60 ml of diethyl ether each time.

The organic solutions are washed once with 50 ml of 2N HCI and once with ml of H 2 0, dried over MgS04 and concentrated in a vacuum rotary evaporator. Upon distillation of the residue, 9.1 g (72 of the product 2' distil over in the form of a colourless liquid at boiling point 108-110 0 C/40 mbar.

op So 1 H-NMR (CDCI 3 300 MHz): 7.62 (d x d; J 7.9; 1.5; 1H); 7.29 (d x d; J 7.9; 1.5; 1H); 7.16 J 7.9; 1H).

Example 2: Preparation of 2,2-difluoro-1,3-benzodioxole-4-carbaldehyde oo,.s a) Under nitrogen, 69 ml (110 mmol) of n-butyllithium (1.60M in hexane) are introduced into a 500 ml 3-necked flask and, while cooling with ice/sodium chloride, a solution of 13 g (110 mmol) of N,N,N',N'-tetramethylethyl nediamine (TMEDA) in 30 ml of hexane is added thereto over a period of 15 minutes. To the clear, pale yellow solution, 15.8 g (100 mmol) of 2,2-difluoro-1,3-benzodioxole dissolved in 120 ml of hexane are added dropwise, at -10 0 C, over a period of 30 minutes, during which 2,2-difluoro-1,3-benzodioxol-4-yllithium gradually separates in the form of a voluminous precipitate. After stirring vigorously at -10 0 C for I I I |i I i 18 minutes, 20 ml (260 mmol) of dimethylformamide (DMF) are added to the white suspension. The oily reaction mixture is stirred at -10 0 C for minutes and is then hydrolysed with 50 ml of 10 hydrochloric acid.

The aqueous phase is separated off and extracted twice with 100 ml of diethyl ether each time. The organic solutions are washed three times with 40 ml of IN HC1 each time, dried over MgSO4 and concentrated in a vacuum rotary evaporator at 50 0 C/200 mbar. Distillation yields 16.8 g of colourless product of boiling point 105-106 0 C/50 mbar.

b) The procedure of Example 3 is followed except that dimethylformamide is used instead of N-methyl-N-methoxy-acetamide. 2,2-Difluoro-1,3benzodioxole-4-carbaldehyde is obtained in a yield of 73 S c) 94.0 g (272 mmol) of n-butyllithium (18.5 in toluene) are added dropwise under a nitrogen atmosphere, at from -15° to -10 0 C, over a period of 1.5 hours, to 29.5 g (254 mmol) of N,N,N',N'-tetramethyl- .aoo« ethylenediamine and 40.0 g (253 mmol) of 2,2-difluoro-1,3-benzodioxole in o 35 ml of toluene, an orange suspension being formed. 19.7 g (270 mmol) of 0 0 DMF are then metered in at from -150 to -10°C over a period of j hour.

The pale yellow suspension is poured at +10 0 C onto 346 g (1.105 mol) of 11.6 aqueous hydrochloric acid and the whole is stirred for I hour to 0 complete the reaction. The aqueous phase is separated off and the organic phase is concentrated by evaporation in a vacuum rotary evaporator at S" 50 0 C/200 mbar under nitrogen to yield the desired product.

d) 39.3 g (339 mmol) of N,N,N',N'-tetramethylethylenediamine are added dropwise at from -150 to -10 0 C under a nitrogen atmosphere to 137.8 g (409 mmol) of n-butyllithium solution (19.0 in toluene). The resulting reaction mixture is metered into a solution of 53.3 g (337 mmol) of 2,2-difluoro-1,3-benzodioxole in 46 ml of toluene over a period of 31 hours at from -15° to -10 0 C under a nitrogen atmosphere. 30 g (410 mmol) of N,N-dimethylformamide are then added over a period of hour at from -15° to -10 0 C. The resulting solution is poured onto 461.1 g (1.472 mol) of 11.6 aqueous hydrochloric acid and the whole is stirred for j hour to complete the reaction. The aqueous phase is 1 19 separated off and the organic phase is concentrated by evaporation in a vacuum rotary evaporator at 50 0 C/200 mbar under nitrogen to yield the desired aldehyde.

1H-NMR (CDC1 3 300 MHz): 10.20 1H); 7.58 (d x d; J 7.9; 1.5; 1H); 7.34 (d x d; J 7.9; 1.5; 1H); 7.23 J 7.9; 1H).

Example 3: Preparation of 4-acetyl-2,2-difluoro-l,3-benzodioxole 6.2 g (55 mmol) of potassium tert.-butoxide dissolved in 40 ml of tetrahydrofuran (THF). are adde. dropwise at -30°C under argon, over a period of 20 minutes, to a solution of 8.0 g (50 mmol) of 2,2-difluoro- 1,3-benzodioxole in 10 ml of THF in a 250 ml 3-necked flask. The mixture s *is then cooled to -90 0 C (methanol/liquid nitrogen), and 35 ml (55 mmol) of n-butyllithium (1.58M in hexane) are added thereto over a period of O 1 a 30 minutes. The deep red solution of 2,2-difluoro-l,3-benzodioxol- 4 -ylo i potassium is maintained at -78 0 C for 20 minutes. Then, 5.2 g (50 mmol) of as .o N-methyl-N-methoxy-acetamide in 20 ml of THF are added thereto over a Se period of 15 minutes at -78 0 C. When the dropwise addition is complete, the beige reaction mixture is allowed to warm up to -10 0 C and is then hydrolysed with 40 ml of 10 hydrochloric acid. The hydrolysed mixture was S is extracted three times with 70 ml of diethyl ether each time. The o organic solutions are washed three times with 30 ml of 1N HC1 each time, dried over Na2S04 and concentrated in a vacuum rotary evaporator. Upon 0 o distillation of the residue, 7.1 g (79 of the product distil over in the form of a colourless oil at boiling point 114-116 0 C/30 mbar.

IH-NMR (CDCl 3 300 MHz): 7.65 (d x d; J 7.9; 1.5; 1H); 7.27 (d x d; J o7.9; 1.5; 1H); 7.18 J 7.9; 1H); 2.68 (s; -UW" 3H) Example 4: Preparation of 2,2-dimethyl-1-(2,2-difluoro-1,3-benzodioxol- 4-yl)-propan-l-ol a) 23.7 ml (33 mmol) of tert.-butyllithium (1.4M in pentane) are added dropwise at -60 0 C under argon, over a period of 20 minutes, to a solution of 4.75 g (30 mmol) of 2,2-difluoro-1,3-benzodioxole in 20 ml of tetrahydrofuran (THF) and 15 ml of diethyl ether in a 250 ml 3-necked flask.

The yellow, turbid solution is subsequently maintained at -65 0 C for i M a e- I 20 minutes and then a fine suspension of 6.45 g (35 mmol) of anhydrous magnesium bromide in 35 ml of THF (prepared from 1,2-dibromoethane and magnesium in THF) is added thereto over a period of 10 minutes. The greenish-blue solution is allowed to warm up to 0 C and then 2.6 g mmol) of pivalaldehyde dissolved in 10 ml of THF are added dropwise thereto. After stirring for 30 minutes at 25 0 C, the colourless reaction mixture is hydrolysed with 30 ml of 10 hydrochloric acid. The aqueous phase is separated off and extracted twice with 50 ml of diethyl ether each time. The organic solutions are washed once with 30 ml of 2N HCl and once with 30 ml of H 2 0, dried over MgSO4 and concentrated in a vacuum rotary evaporator. The crystalline yellow residue is recrystallised from hexane to yield 5.1 g (70 of colourless platelets of melting point 68-69 0

C.

00 0 So b) The procedure of Example 1 is followed except that pivalaldehyde is Soo used instead of trifluoroacetyl-N-methylpiperazide. 2,2-Dimethyl-l- (2,2-difluoro-1,3-benzodioxol-4-yl)-propan-l-ol is obtained in a yield of 0000 o 81 000000 0 0 00 00 O 0 1 H-NMR (CDCl 3 300 MHz): 7.13 (d x d x d; J 8.0; 1.5; 0.5; 1H); 7.07 (t; J 8.0; 1H); 6.97 (d x d; J 8.0; 1.5; 1H); 4.63 o00. 1H); 2.05 (bs; OH); 0.95 9H).

0 0 0 0 Example 5: Preparation of (E)-2-cyano-3-(2,2-difluoro-l,3-benzodioxol- S: 4-yl)-2-propenoic acid ethyl ester a) 7.9 g (50 mmol) of 2,2-difluoro-1,3-benzodioxole are metallated according to Example 2 at -15 0 C with 35 ml (55 mmol) of n-butyllithium (1.60M in hexane) and 6.5 g (55 mmol) of TMEDA in 60 ml of hexane. To the 2,2-difluoro-1,3-benzodioxol-4-yllithium which precipitates there is 0 added at -20C, over a period of 30 minutes, a solution of 9.3 g mmol) of ethoxymethylenecyanoacetic acid ethyl ester in 30 ml of tetrahydrofuran, an orange-red turbid solution being formed during the reaction, which is exothermic. After stirring for 20 minutes at -15 0

C,

the solution is hydrolysed with 50 ml of 2N hydrochloric acid. The aqueous phase is extracted twice with 80 ml of diethyl ether each time.

The organic solutions are washed twice with 50 ml of water each time, p t 4 I 21 dried over MgSO and concentrated to dryness by evaporation in a vacuum rotary evaporator. The residue is crystallised from ethanol/water 4:1, affording 10.1 g (72 of colourless platelets of m.p. 87-88 0

C.

b) 40.0 g (253 mmol) of 2,2-difluoro-1,3-benzodioxole in 29.5 g (254 mmol) of TMEDA and 35 ml of toluene are metallated analogously to Example 2r) at from -15 to -10 0 C with 106.2 g (307 mmol) of n-butyllithium solution (18.5 in toluene). 52.1 g (308 mmol) of ethoxymethylenecyanoacetic acid ethyl ester in 115 ml of toluene are added to the reaction mixture .at from -15 to -10 0 C over a period of 2 hours. The resulting suspension is poured, after 20 minutes at +10 0 C, into 350 ml of water, the aqueous phase is separated off and the organic phase is concentrated by evaporation in a vacuum rotary evaporator to yield the desired product.

o0 o c) 53.3 g (337 mmol) of 2,2-difluoro-l,3-benzodioxole in 46 ml of toluene ooo Sare metallated according to Example 2d), at from -15 to -10 0 C, with 0 0 .o BO 137.8 g (409 mmol) of n-butvllithium solution (19.0 in toluene) in the presence of 39.3 g (339 mmol) of TMEDA. 69.1 g (409 mmol) of ethoxymethylenecyanoacetic acid methyl ester in 150 ml of toluene are metered in at from -15 to -10 0 C over a period of 2- hours. The reaction mixture 00 0 is added at +10 0 C to 450 ml of water, the phases are separated and the organic phase is concentrated by evaporation in a vacuum rotary evaporator to yield the title compound.

'H-NMR (CDC1 3 300 MHz): 8.35 1H), 8.10 X of ABX; 1H); 7.25 (m; °o AB of ABX; 2H); 4.42 J 7.0; 2H); 1.42 J; S°7.0; 3H).

QQO'a o 0 Example 6: The procedure of Example 4 is followed except that B-ptoluenesulfonyloxyacrylonitrile is used instead of pivalaldehyde.

B-(2,2-Difluoro--1,3-benzodioxol-4-yl)acrylonitrile is obtained in a yield of 52 J 22 Example 7: The procedure of Example 1 is followed except that COz is passed in instead of adding trifluoroacetyl-N-methylpiperazide. 2,2-Difluoro-1,3-benzodioxole-4-carboxylic acid is obtained in a yield of 61 Example 8: Preparation of 4-hydroxy-2,2-difluoro-1,3-benzodioxole 15.8 g (100 mmol) of 2,2-difluoro-1,3-benzodioxole are metallated according to Example 2, at -20 0 C, with 70 ml (110 mmol) of n-butyllithium (1.58M in hexane) and 12.8 g (110 mmol) of TMEDA in 120 ml of hexane. To the white suspension there is added dropwise at -100°C, over a period of minutes, a solution of 10.4 g (100 mmol) of trimethyl borate in 50 ml of diethyl ether. When the reaction mixture has warmed up and has been stirred for 30 minutes at room temperature, there are added to the precipitated dimethoxy-(2,2-difluoro-1,3-benzodioxol-4-yl)borane, while cooling with ice, 35 ml of 3N sodium hydroxide solution, immediately e followed by the addition, over a period of 10 minutes, of 32 ml 310 mmol) of 30 hydrogen peroxide solution. The yellow-orange Semulsion is adjusted to pH 3 with 10 HC1. The aqueous phase is extrac- S ted three times with 150 ml of diethyl ether each time. The organic S solutions are washed three times with 100 ml of 2N FeSO4 solution each o° time, then twice with 100 ml of 20 sodium bisulfite solution each time and finally with 50 ml of brine, dried over MgS04 and concentrated in a vacuum rotary evaporator. Upon distillation of the residue, 8.4 g (48 of the product distil over in the form of a pale yellow oil at boiling S point 135-139 0 C/25 mbar.

1 H-NMR (CDC1 3 300 MHz): 6.93 J 8.1; 1H); 6.67 (d x d; J 8.1; 1H); 6.64 (d x d; J 8.1; 1.0; 1H); 6.15 (bs; V. OH).

Example 9: Preparation of 2,2-difluoro-1,3-benzodioxole- 4 -boric acid 7.9 g (50 mmol) of 2,2-difl-.)ro-1,3-benzodioxole are metallated according to Example 1, at C, with 40 ml of tert.-butyllithium (1.38M in pentane) in a mixture of 55 ml of diethyl ether and 30 ml of THF. 5.1 g mmol) of trimethyl borate in 25 ml of diethyl ether are then added to the aryllithium compound at -100 0 C over a period of 2 minutes. The clear, yellow reaction solution is then allowed to warm up to room temperature and, after being stirred for 30 minutE- while cooling with ice, is .ll jJJ* i. 00 a o 00a oo 0 00 0a a~ 0 o 0 od 0y 4 23 hydrolysed with 100 ml of 2N HC1. The aqueous phase is extracted three times with 75 ml of diethyl ether each time. The organic solutions are washed neutral with water and brine and, without being dried, are concentrated in a vacuum rotary evaporator. The yellow crystalline residue is recrystallised from petroleum ether. 7.4 g (73 of pale yellow prisms of melting point 103-104 0 C are obtained.

1H-NMR (CDC1 3 300 MHz): 7.51 X of ABX; 1H); 7.18 AB of ABX; 2H); 5.33 (bs; 2 x OH).

-4-merccop o-I 3-benzod\oo\e Example 10: Preparation of 2,2-difluorol,3 benzodioxolc-1:thiophonol 4.8 g (30 mmol) of 2,2-difluoro-1,3-benzodioxole are metallated as described in Example 1 with 24 ml (33 mmol) of tert.-butyllithium (1.38M in pentane) in a mixture of 35 ml of THF and 15 ml of diethyl ether.

1.1 g (34 mmol) of sulfur (S 8 are then added in portions, at -30 0 C, over a period of 10 minutes. The orange reaction solution is subsequently maintained at -30 0 C for a further 20 minutes and is then hydrolysed with 30 ml of 2N HC1. The aqueous phase is extracted twice with 50 ml of diethyl ether each time. The organic phases are washed neutral with water and brine, dried over MgSO4 and concentrated in a vacuum rotary evaporator. Fractional distillation of the residue yields 3.4 g (60 of colourless product of boiling point 72-74 0 C/20 mbar.

'H-NMR (CDCl 3 60 MHz): 6.85 3H); 3.49 SH).

Example 11: Preparation of 4-(chlorodifluoroacetyl)-2,2-difluoro-l,3benzodioxole 39.5 g (250 mmol) of 2,2-difluoro-1,3-benzodioxole are metallated according to Example 2, at -15 0 C, with 172 ml (275 mmol) of n-butyllithium (1.60M in hexane) and 32 g (275 mmol) of TMEDA in 300 ml of hexane. To the precipitated 2,2-difluoro-1,3-benzodioxol-4-yllithium, a solution of 50.0 g (250 mmol) of a-chloro-a,a-difluoroacetylmorpholide in 100 ml of THF is added at -15 0 C over a period of 40 minutes during which a voluminous white precipitate gradually forms. The suspension is stirred at 0 C for 1 hour, then hydrolysed with 120 ml of 10 HC1. The aqueous phase is extracted twice with 250 ml of diethyl ether each time. The organic solutions are washed twice with 100 ml of IN HC1 each time, dried r

I

ii ii i:- I:e f g -24over MgS04~ and concentrated at 50'C in a vacuum rotary evaporator.

Fractional distillation yields 41.3 g (61 of pale yellow product of boiling point 93-95'C/25 mbar.

'H-NMR (CDC1 3 300 MHz): 7.75 (d x d; J 8.0; 1.0; 1H); 7.39 (d x d; J 8.0; 1.0; IH); 7.27 .1 Example 12: The procedure of Example 1 is followed except that trimethylchlorosilane is used instead of trifluoroacetyl-N-methylpiperazide.

4-Trimethylsilyl-2,2-difluoro-1,3-benzodioxole 80-81'C/160 mbar) is obtained in a yield of 73 7%.

'H-NMR (CDC1 3 300 MHz): 7.09 (mn; X of ABX); 7.05 (in; AB of ABX; 2H); 0.3 (sa9

Claims (17)

1. A process for the preparation of compounds of formula I /0 S i CF 2 wherein R 1 is -OH, -SH, -CHO, -CN, -COOH, -B(OH)2, -COX, with X being C1 or Br, or is -COOR 2 -SiRs or -B(0R 2 2 with R 2 being a Cl-C, 2 alcohol moiety without the hydroxy group, wherein RI is further -C nH 2 nCOOR', with n being an integer from 1 to 4, or linear or branched Cl-Cl 2 hydroxyalkyl which is unsubstituted or is substituted by -CN, C 1 -C~alkoxy, phenyl, .fluorophenyl, Cl-C~alkoxy-phenyl, Cl-Ci~alkylthio-phenyl, C 1 -C~~alkyl-phe- 0nyl, Cl-Ct 4 fluornalkyl-phenyl, nitrophenyl or by cyanophenyl, or wherein R1 is a benzyl alcohol or a C1-C1 2 acyl unsubstituted or substituted by F, S Cl-Ct~alkoxy, C 1 -Cz~alkylthio, Cl-Cz~alkyl, Cl-C 4 fluoroalkyl, nitro or by cyano, or wherein RI is a radical of formula II wherein R 5 is -CN, -cF3, -COOR 2 -CONH2, -CO-NHR 2 or -CONR R 3 and R4 :~00 are a direct bond or each is H, or R 3 is H and R4 independently has the meanings of R 5 or R 3 and R4 together are -CH 2 -NR 6 -CH 2 -CH 2 -NR 6 -CO- or 0 -CO-NR 6 -CO- wherein R 6 is the radir-al of a removable protecting group, or 0 wherein further R1 is a radical of formula III which process comprises a) in an inert solvent, reacting 2,2-difluorobenzo-1,3-dioxole with an alkali metal or with an alkali metal or alkaline earth metal compound with a strong anion base to give a compound of formula IV -26- '0 i i Cr 2 (IV) 0 wherein Y is an alkali metal or an alkaline earth metal, and optionally then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CuZ2, PdZ 2 NiZ 2 AlZ 3 SiZ 4 SnZ 2 SnZ4, TiZ 4 BZ 3 or ZrZ4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ2, -SiZ 3 -SnZ, -SnZ3, -TiZ 3 -BZ 2 or -ZrZ 3 and Z is -Cl, -Br or -I and, in the case of boron, is also -0C 1 -C~+alkyl or -0-aryl, b) reacting the compound of formula IV with an electrophilic compound from the group X-CN, C0 2 S 8 COX 2 B(0R 2 X-SiR R 2 0-SiMj or S:XC0OR', with X being -Cl or -Br, or with a formylating reagent, CH 2 O, an S epoxide, a benzaldehyde which is unsubstituted or is substituted by F, ~'Cl-C~alkoxy, C 1 -C~alkylthio, C 1 -C~alkyl, Cl-C~fluoroalkyl, nitro or by 000 cyano, a C 1 -Cllalkyl-CH0 which is unsubstituted or is substituted by -F, o~-Cl, -CN, Cj-Cealkoxy, phenyl, fluorophenyl, Cl-C~alkoxyphenyl, C 1 -C4- alkyithiophenyl, C 1 -Ci 4 alkylphenyl, Cl-C 4 fluoroalkylphenyl, nitrophenyl or by cyanlophenyl, or with C 1 -C1 2 acyl-X' wherein X1 is -Cl, -Br, C 1 -C~alkoxy or the radical of a secondary amine, or with X 2 C nH 2nC00R', X 2 -CR 3 CR 4 0 :or a compound offormula TTTI 2 o fH H I a 0 0'6 wherein X 2 is a leaving group, and 0c) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I.

2. A process for the preparation of compounds of formula I according to claim 1, wherein R' is -CHO, -CN, -CO0H, -B(OH) 2 -COX, with X being Cl or Br, or is -COOR' or -B(0R 2 2 with R 2 being a C 1 -Cl 2 alcohol moiety without the hydroxy group, wherein R1 is further -C nH 2nCOOR 2 with n being an integer from 1 to 4, or linear or branched Cl-C 12 'hydroxyalkyl or C 1 -C 12 acyl each unsubstituted or substituted by -CN, CI.-C 6 alkoxy, -27- phenyl, fluorophenyl, Cl-Ci 4 alkoxyphenyl, C 1 -Ci~alkylthiophenyl, Cl'-Ci+- alkyiphenyl, Cl-C~fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or wherein R1 is a radical of formula II wherein R 5 is -CN, -CF 3 -COOR 2 -CONH2, -CO-NHR 2 or -CONR R 3 and R 4 are a direct bond or each is H, or R 3 is H and independently has the meanings of R 5 or R 3 and R' together are -CH 2 -NR 6 -CH 2 -CH 2 -NR 6 -CO- or -CO-NR 6 -CU- wherein R 6 is the radical of a removable protecting group, or wherein further R' is a radical of formula III 0 which process comprises O 0 Sa) in an inert solvent, reacting 2,2-difluorobenzo-1,3-dioxole with an alkali metal or with an alkali metal or alkaline earth metal compound 00with a strong anion base to give a compound of formula IV 0 0 weenY is an alkali metal or an alkaline earth metal, and optionally 0 144 0 then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CUZ 2 PdZ 2 NiZ 2 AlZ 3 SiZ4, SnZ 2 SnZ4, TiZ4, BZ 3 or ZrZ4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ3, -TiZ 3 -BZ 2 or -ZrZ3 and Z is -Cl, -Br or -I and, in the case of boron, is also -OCI-C~alkyl, b) reacting the compound of formula IV with an electrophilic compound fro th grup -CN C0, B0R)3, COX 2 or XCOOR, with X being -Cl or -Br, or with a formylating reagent, CH 2 Q, an epoxide, a C 1 -C 11 alkyl-CHO which is unsubstituted or is substituted by -Cl, -CN, C 1 -C~alkoxy, phenyl, fluorophenyl, Cl-Cz~alkoxyphenyl, C 1 -C4-alkylthiophenyl, CI-C 4 alkylphenyl, Cl-Ct~fluoroalkylphenyl, nitrophenyl oi by cyanophenyl, or with C1-C1 2 acyl-X1 wherein X 1 is -Cl, -Br, C 1 -C 6 alkoxy or the radical of a secondary amine, or with X 2 C H COOR2 X 2 -CR 3=CR4R 5 or a compound of X 2 t-h-en isR h cn f wherein X 2 is a leaving group, and c) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I. claim 2, I Hi CF 2 H (IIa) wherein RX is -CHO, -CN, -COOH, -COX, with X being Cl or Br, -COOR 2 with 0 R 2 being a Cl-C 12 alcohol moiety without the hydroxy group, -CnH 2nCOOR 2 nclaim 2,2n with n being an integer from 1 to 4, linear or branched Ci-C 12 hydroxy- alkyl or C1-C 1 2 acyl each unsubstituted or substituted by -CN, Ci-Csalkoxy, phenyl, fluorophenyl, Cl-C4alkoxyphenyl, Cl-C4alkylthio- cyanophenyl, or is a radical of formula II a or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or R and R 4 together are -CH2-NR 6 -CH 2 -CH 2 -NR 6 -CO- or -CO-NR -CO- wherein R 6 is the radical of a removable protecting group, or wherein RI is a radical of formula III H IIH (III) which process comprises which process comprises I1 L -29- a) in an inert solvent, reacting 2,2-difluorobenzo-l,3-clioxole with an alkali metal or with an alkali metal compound with a strong anion base to give a compound of formula IV wherein Y is an alkali metal, and optionally then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ 2 NiZ 2 AlZ 3 SiZ 4 SnZ 2 SnZ4, TiZ4 or ZrZ 4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ 3 -TiZ 3 or -ZrZ 3 and Z is -Cl, -Br or -I, b) reacting the compound of formula IV with an electrophilic compound 040 from the group X-CN, C0 2 COX 2 or XCOOR 2 with X being -Cl or -Br, or with a formylating reagent, a C 2 -Cl 2 haloalcohol which is unsubstituted or is substituted by -CN, C~Cakxpeyfurophenyl, C 1 -C4- CaCaloy phnlf f% lkoyphnyl C-Cz~alkylthiophenyl, C-C 4 alkylp'henyl, C-C 4 fluoroalkyl- phenyl, nitrophenyl or by cyanophenyl, CH 2 O, a Cl-Cl 1 alkyl-CHO which is unsubstituted or is substituted by -CN, CI-Csalkoxy, phenyl, fluoro- Sphenyl, Ca-Ci~alkoxyphenyl, C 1 -C~alkylthiophenyl, Cl-C~~alkylphenyl, ~XCl-Ci~fluoroalkylphenyl, nitrophenyl or by cyanophenyl, an epoxide, a benzaldehyde which is unsubstituted or is substituted by Cl-C 4 alkoxy, C-C 4 alkylthio, Cl-Ci 4 alkyl, C-Ci~fluoroalkyl, nitro or by cyano, or with Cl-Cl2acyl-X 1 wherein X 1 is -Cl, -Br, C 1 -C 6 alkoxy or the radical of a 41 secondary amine, or with X 2 C nH 2nCOOR', X 2 -CR 3 =CR 4 R 5 or a compound of 0 41 formula Il~a n2 0 x2- -R HaY (Ila) wherein X 2 is a leaving group, and C) isolating the compound of formula I or first hydrolysing the reaction mixture and then isolating the compound of formula I. 30

4. A process for the preparation of compounds of formula I according to claim I wherein R I is -CHO, -CN, -COOH, -COX, with X being Cl or Br, or a radical of formula II R(II), wherein R 5 is -CN, -CF 3 -COOR 2 or -CONH 2 R 3 and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R s or R 3 and R 4 together are -CH 2 -NR 6 -CO- wherein R 6 is the radical of a removable protecting group, or wherein R' is a radical of formula III HC CH (III) Y which process comprises o a a) in an inert solvent, reacting 2,2-difluorobenzo-1,3-dioxole with an o"'O alkali metal or with an alkali metal compound with a strong anion base to a give a compound of formula IV 0 Oo, I I CF 2 (IV) S00 S0v wherein Y is an alkali metal, and optionally then reacting with an anhydrous metal halide from the group MgZ 2 ZnZ 2 CdZ 2 CuZ, CuZ 2 PdZ 2 0 7 NiZ 2 AlZ 3 SiZq, SnZ 2 SnZ4, TiZ4, BZ 3 or ZrZ4 to give a compound of formula IV wherein Y is -Cu, -MgZ, -ZnZ, -CdZ, -CuZ, -PdZ, -NiZ, -AlZ 2 -SiZ 3 -SnZ, -SnZ 3 -TiZ 3 -BZ 2 or -ZrZ 3 and Z is -Cl, -Br or -I, 00 o 000 ooooo b) reacting the compound of formula IV with an electrophilic compound from the group X-CN, CO 2 or COX,, with X being -Cl or -Br, a formylating reagent, X2-CR3=CR 4 Rs or a compound of formula IIIa X 2 R 5 a HC tCH (IIIa) hr6 wherein X 2 is Y. leaving group, and i 0 a i Aooim Qhri X 2 is ij ji 1 S 31 c) isolating the compound of formula I or first hydrolysing the reaction S mixture and then isolating the compound of formula I. A process for the preparation of compounds of formula I according to claim I, i I /CF o wherein R 1 is -CHO or a radical of formula II (II), R3 3 R' wherein R 5 is -CN, -COOR 2 or -CONH 2 each of R 3 and R 4 is H, or R 3 is H Sand R independently has the meanings of R 5

6. A process according to claim-3, wherein, in formula I, R 1 is -CHO or -COOR 2 in formula II R 3 and R 4 are a direct bond and R 5 is -CN, or R 3 is "S R 4 is -CN and R 5 is -COOR 2 -CONR 2 or -CN, or R 3 and R! together are o o° -CH 2 -NR 6 -CH 2 -CH 2 -NR 6 -CO- or -CO-NR 6 -CO- and R 5 is -CN, and R 5 in formula III is -CN.

7. A process according to claim 3, wherein the reaction is carried out at U as from -150 0 C to 150 0 C. Co 4: 0 a 8. A process according to claim 3, wherein the solvent is a non-polar or polar aprotic solvent. 0

9. A process according to claim 8, wherein the solvent is an aliphatic or i' 0 aromatic hydrocarbon, an ether, a tertiary amine, an N-alkylated acid amide, a lactam or a cyclic urea, a sulfoxide, a sulfone, a nitrile, a ketone or mixtures thereof. A process according to claim 3, wherein the reaction mixture contains, in addition, a complexing agent. 32 32

11. A process accordiig to claim 10, wherein the complexing agent is a tertiary amine, an N-substituted carboxylic acid amide, lactam or cyclic urea, ether or a sulfoxide, a crown ether, an alkali metal halide, magnesium halide or copper halide.

12. A process according to claim 3, wherein the alkali metal is Li, Na or K, and the alkali metal or alkaline earth metal compound is a Li-, Na-, Ca-, Sr- or Ba-alkyl, -arylhydride, -amide or -alcoholate.

13. A process according to claim 3, wherein the formylating reagent is a formyl halide, a formic acid ester, an orthoformic acid ester, an alkoxymethyleneaniline or an N-disubstituted formamide.

14. A process according to claim 3, wherein, as the radical of a 0 secondary amine, X 1 is Ci-C4alkyl- -OCi-C4alkyl, Ci-C4alkyl- 2 CCH 2 0- S C 1 -C 4 alkyl, (CI-C4alkylOCH 2 CH2) 2 N- or the radical of a 5- or 6-membered heterocyclic amine which may contain a further hetero atom from the group S-0- and =N-Ci-C4alkyl. 0 0

15. A process according to claim 3, wherein X 2 as a leaving group is a halide, Ci-Csalkoxy, C6-Cioaryloxy, Ci-C 2 i-secondary amino, Ci-Ceacyloxy or the radical of a sulfonic acid. Do o

16. A process according to claim 3, wherein the protecting group R 6 is a S trialkylsilyl group having a total of from 1 to 18 carbon atoms, C 1 -C 2 z- acyl or -COOR 2 g, 17. Compounds of formula la /O I II CF 2 (Ia), \o wherein R' is -OH, -SH, -CHO, -CN, -COOH, -B(OH) 2 -COX, with X being Cl or Br, or is -COOR 2 -SiRj or -B(OR) 2 with R 2 being a CI-C-2alcohol moiety without the hydroxy group, wherein RI is further -CnH2nCOOR 2 with n being an integer from 1 to 4, or linear or branched CI-C12hydroxyalkyl which is unsubstituted or is substituted by -CN, CI-Csalkoxy, phenyl, -33- fluorophenyl, Cl-C 4 alkoxyphdnyl, Cl-C 4 alkylthiophenyl, Cl-C 4 alkylphenyl, Cj- C 4 fluoroalkyl-phenyl, nitrophenyl or by cyanophenyl, or wherein R 1 is a benzyi alcohol which is unsubstituted or is substituted by F, C 1 -C 4 alkoxy, Cj- C 4 alkylthio, C1-C 4 alkyI, rC 1 -C 4 fluoroalkyl, nitro or by cyano, or is R 7 -CO- wherien R 7 is Cl-Cl 1 alkyl, which is unsubstituted or is substituted by -Cl, -CN, Cl-C 8 a1 koxy, phenyl, fluorophenyl, C 1 -C 4 fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or may be phenyl which is unsubstituted or is substituted by F, cyano, nitro, Cl-C 4 alkyl, Cl-C 4 alkoxy, Cl-C 4 alkylthio or by Cl-C 4 fluorcalkyl; or wherein R 1 is a radical of formula 11 wherein R 5 is -CN, -C,3 -COO R 2 -CONH 2 -CO-NHR 2 or -CONR 2 R 3 and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or wherein further R 1 is a radical of formula Ill Ia. a -R HCNCH 15 with the proviso that R 5 in formula Ill is not -CN and R 6 is Cl-C 6 alkoxymethyl; ::aphenoxymethyl 'which is unsubstituted or substituted by C 1 -Calkyl or a C1-C 4 alkoxy; benzyl; diphenylmethyl; triphenylmethyl; trialkylsilyl having a total of from 1-18 carbon atoms; -COOR 2 R 7 in which R 2 and R 7 have the a~aaa meanings mentioned hereinbefore and wherein said compound of formula la is not 2,3-(difluoromethylenedioxy)-cinnamonitril.

18. Compounds of formula la according to claim 1 7, wherein RI is -CHO, -CN, -COOH, -B(OH) 2 -COX, with X being Cl or Br, or is -COOR 2 or 2 2 with R 2 being a Cl-C, 2 alcohol moiety without the hydroxy group, wherein R 1 is further -CnH2nCOOR 2 with n being an integer from 1 to 4,or linear or branched Cl-Cl 2 hydroxyalkyl or R 7 -CO- wherein R 7 is Cl-Cl,alkyl, which is unsubstituted or is substituted by -Cl, -CN, Cl-Cealkoxy, phenyl, fluorophenyl, Cl-C 4 fluoroalkylphenyl, nitrophenyl or by cyanophenyl, or may be phenyl which is unsubstituted or is substituted by cyano, nitro, Cl-C 4 alkyl, C 1 -C 4 alkoxy, Cl-C 4 alkylthio or by C 1 -C 4 fluoroalkyI; or wherein R 1 is 3 30 a radical or formula 11 KXW/89191.doc -34- C=C-R R 3 R 4 wherein R 5 is -CN, -CF 3 -COOR 2 -CONH 2 -CO-NHR 2 or -CONR 2 R 3 and R 4 are a direct bond or each is H, or R 3 is H and R 4 independently has the meanings of R 5 or wherein further R 1 is'a radical of formula III HC,>.CH (r) R 6 with the proviso that R 5 in formula III is not -CN and R 6 is Cl-Calkoxymethyl; phenoxymethyl which is unsubstituted or substituted by C,-C 4 alkyl or CC4alkoxy; benzyl;.diphenylmethyl; triphenylmethyl; trialkylsilyl having a total of from 1-18 carbon atoms; -COOR 2 R 7 in which R 2 and R 7 have the °0:0 10 meanings mentioned hereinbefore and wherein said compound of formula la is not 2,3-(difluoromethylenedioxy)-cinnamonitril. S- 19. Compounds of formula la according to claim 18, wherein R 1 is -CN, -CHO, -COOH, -COOR 2 and R 2 is an alcohol moiety without a hydroxy group, or R 1 is -CnH2nCOOR 2 with n being an integer from 1 to 4, or is a 15 radical of formula II wherein each of R 3 and R 4 is H and R 5 is -CF 3 -CONR 2 or -COOR 2 or R 5 is -CN, -CF 3 -COOR2 or -CONR2 R 3 and R 4 are a direct bond, or R 3 is H and R 4 independently has the mearings of R 5 or wherein R 1 is a radical of formula III C-- with the proviso that R 5 in formula III is not -CN. Compounds according to claim 19, wherein, in formula la, R' is S KXW 8919 1 KXW/89191.doc -CHO or -COOR 2 or is a radical of formula II wherein R 3 and R 4 are a bond and R 5 is -CN, or R 3 is H, R 4 independently has the meanings of R 5 and R 5 is -CN, -COOR 2 or -CONR 2 and R 5 is -CN and R 6 is Cl-C 6 alkoxymethyl; phenoxymethyl which is unsubstituted or substituted by C 1 -C 4 alkyl or C,-C 4 alkoxy; benzyl; diphenylmethyl; triphenylmethyl; trialkylsilyl having a total of from 1-18 carbon atoms; -COOR 2 R 7 in which R 2 and R 7 have the meanings mentioned hereinbefore.

21. Compounds according to claim 19, wherein R 2 is C 1 -Calkyl.

22. Process for the preparation of substituted difluorobenzo-1,3- dioxoles of formula as defined in claim 1, which process is substantially as hereinbefore described with reference to any one of the Examples.

23. Compounds of formula when produced by the process of any one of claims 1 to 16 or 22.

24. Compounds of formula (la) as defined in claim 17, substantially as herein described with reference to any one of the Examples. Process for the preparation of compounds of formula (la) as defined in claim 17, substantially as herein described with reference to any one of the Examples. 20 DATED this TENTH day of MARCH 1992 Ciba-Geigy AG Patent Attorneys for the Applicant a SPRUSON FERGUSON o 00 o a 0 a i a i