AU624806B2 - Process for the preparation of a pyrrole derivative - Google Patents

Process for the preparation of a pyrrole derivative Download PDF

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AU624806B2
AU624806B2 AU31467/89A AU3146789A AU624806B2 AU 624806 B2 AU624806 B2 AU 624806B2 AU 31467/89 A AU31467/89 A AU 31467/89A AU 3146789 A AU3146789 A AU 3146789A AU 624806 B2 AU624806 B2 AU 624806B2
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formula
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Peter Ackermann
Hans-Ruedi Kanel
Bruno Schaub
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Syngenta Participations AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
    • C07F1/02—Lithium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table

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  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
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Abstract

3-(2,2-Difluorobenzodioxol-4-yl)-4-cyanopyrrole can be prepared by reaction of 4-metallo-2,2-difluorobenzodioxole (III) with an unsaturated nitrile and then with a sulphonylmethyl isocyanide in a one-pot process. The compounds III are novel intermediates.

Description

r T 62 4 Oef68340 FORM 10 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
Spruson Ferguson, Patent Attorneys Level 33 St Martins Tower, 31 Market Street Sydney, New South Wales, 2000, Australia v Address for Service: Complete Specification for the invention entitled: Process for the Preparation of a Pyrrole Derivative The following statement is a full description of this invention, including the best method of performing it known to me/us 5845/10 L I 5-16952/+ Process for the preparation of a pyrrole derivative Abstract 3-(2,2--difluorobenzodioxol-4-yl)-4-cyanopyrrole can be prepared by reacting 4-metallo-2,2-difluorobenzodioxole (III) with an unsaturated nitrile and then with a sulfonylmethyl isocyanide in a one-pot process.
The compounds III are novel intermediates.
4 I 4 4* 1 I II II I 4* 4! o 4 I III III'S I
I
L _dW 1A- 5-16952/+ Process for the preparation of a pyrrole derivative The present invention relates to a process for the preparation of 3-(2,2-difluorobenzodioxol-4-yl)-4-cyanopyrrole of formula I 0
-CN
2oo H oe o F \F o to the 4-metallo-2,2-difluorobenzodioxoles involved as intermediates of O 0o, that process, and to a process for the preparation of those intermedi- I, oI c 0 ates.
0.0 It is known from DE-PS 2,927,480 that N-acyl-3-phenyl-4-cyanopyrroles S.e have a fungicidal activity. EP-A 206999 describes 3-(2,2-difluorobenzo- Q o S dioxol-4-yl)-4-cyanopyrrole as a fungicide.
00 00 A process for the preparation of 3-phenyl-4-cyanopyrroles starting from an a-cyanocinnamic acid (or from a suitable ester of such an acid) by r*o reaction with a substituted methyl isocyanide has been described in 0 000 DE-OS 3,601,285.
0 0 The disadvantage of that process is that the benzaldehydes, which, as the starting materials, form the basis of the a-cyanocinnamic acids, can be obtained only with difficulty in the case of certain substitutions in the nucleus. In such cases, a process based on that reaction sequence proves to be very difficult to carry out and uneconomical.
The aim of the present invention is to provide a process for the preparation of 3-(2,2-difluorobenzodioxol-4-yl)-4-cyanopyrrole which process is improved from the technical and economic point of view and can be applied generally.
14 7. A process according to claim 6, wherein the metallation and the subsequent reactions are carried out at from -25° to +80 0
C.
8. A process according to claim 3, wherein the complex-forming compound is selected from a group consisting of ethers, tert.-amines, L Surprisingly, it has now been found that 3-(2,2-difluorobenzodioxol-4yl)-4-cyanopyrrole of formula I
,-,CN
(I)
F F can be very readily prepared in a one-pot process when a 4-metallo-2,2difluorobenzodioxole of formula III, wherein Me is a metal, n is the valency of that metal and Y is an anionic radical which can also be a
C
1 -C14 organic basic radical, is reacted in a solvent phase, in the presence or absence of a complex-forming compound, first with an unsaturated nitrile of formula IV
Y-
I 4 n-1
/CN
0 2'0 RICH=C\ R2
\F
S' III
IV
wherein R is halogen, Ci-C 4 alkoxy, C6-Cioaryloxy, di-C1-C4alkylamino, C 1
-C
4 alkylsulfonyloxy, C6-Cloarylsulfonyloxy or C 1
-C
4 alkylcarbonyloxy (=acyloxy) and R 2 is a C 1 -C4alkoxycarbonyl radical, and then with an S isocyanide of formula V
R
3
-SO
2 CHzNC, (V) wherein R 3 is an open-chain or cyclic, unsubstituted or substituted Ci-Ciohydrocarbon.
It has also been found and is likewise a subject of the present invention that the compounds of formula III can be prepared very readily and regioselectively by reacting 2,2-difluorobenzodioxole of formula II in a suitable solvent phase, in the presence or absence of a complex-forming compound, with a metal or a metal compound, metallation not occurring to any appreciable extent in any position other than the 4-position.
i 3 /-Me n
Y
n-1 n 0 \0 F \F F/ \F (II) (III) In these formulae, Me, Y and n are as defined above, at least one Y being an organic basic radical. If a metal is used, n 0 and Y does not apply.
The nature of the metal Me used and also of the metal compound MenYn used is not in prijciple subject to any restriction but metals of the alkali or alkaline earth groups are preferred, especially Li, Na, K, Cs, Ca and Mg and their compounds with a C 1 -Ciohydrocarbon radical.
1 The reaction is carried out in a temperature range of from -700 to t +150 0 C, preferably at from -250 to +80 0
C.
Suitable solvents are, for example, hydrocarbons (such as petroleum ether, toluene, hexane, heptane, etc.) and ethers (such as diethyl ether, dioxane, tetrahydrofuran) in addition to those specified hereinafter. If non-polar or weakly polar solvents are used in the metallation, then the use of complexing agents is necessary or at least advantageous if a high regioselectivity is to be obtained and ensured.
Of the process conditions, the use of a complex-forming compound selected from a group consisting of tert.-amines, cyclic ureas, ethers and N-substituted acid amides is preferred. Of those, hexamethylphosphoric acid triamide, ethylene glycol dimethyl ether, 1,3-dimethyl-2-imidazolone, dimethylethyleneurea, dimethylpropyleneurea and N,N,N',N'-tetramethylethylenediamine are especially preferred.
The present invention relates also to the compounds of formula III which can be prepared by that process.
Conventional metallation processes, described in organic chemistry, for aromatic compounds generally take place non-selectively and result in a L 4 mixture of isomeric organometallic compounds. It is therefore surprising that the metallation of 2,2-difluorobenzodioxole takes place selectively in the 4-position.
Compounds of formula III can also be obtained by trans-metallation of a compound of formula IIla -(Me')ny S_ 'n-1 (liIa),
O,
F \F with a compound of formula Me Y Me' being a metal other than Me. The n meaning of the metal Me' and its compounds is limited essentially to metals of the alkali and alkaline earth group. Preferred are Li, Na, K, Cs and Mg, lithium being especially preferred. The present invention relates also to that transmetallation. Alkali metal and alkaline earth metal derivatives of 2,2-difluorobenzodioxole can generally be obtained by direct metallation, while metals from the other groups are advantageously obtained from the former group by transmetallation. The present invention relates also to the 4-metallo-2,2-difluorobenzodioxole derivatives of formula III obtainable by transmetallation or direct metallation, especially to those in which the metal is an alkali metal or an alkaline earth metal or is zinc, cadmium, copper, palladium, nickel, aluminium, silicon, tin, titanium or zirconium.
In such a transmetallation operation, for example 2,2-difluorobenzodioxole-lithium can be converted with magnesium bromide or with zinc chloride into -2,2-difluorobenzodioxole-magnesium bromide or 2,2-difluorobenzodioxole-zinc chloride, respectively.
Surprisingly, it has now been found that, starting from 2,2-difluorobenzodioxole of formula II, the complete process for the preparation of the compounds of formula I can be effected in a one-pot process via the stage of the compounds of formula III despite the fact that the reactants are completely different and are added gradually and possibly under changing conditions, likewise without isolation of further products formed intermediately.
II _Y CC-- 5 The present invention accordingly relates also to a process for the preparation of 3-(2,2-difluorobenzodioxol-4-yl)-4-cyanopyrrole, wherein the 2,2-difluorobenzodioxole of formula II is converted in a solvent phase, in the presence or absence of a complex-forming compound, with an organometal compound or with a metal into a 4-metallo-2,2-difluorobenzodioxole of formula III which is reacted, without being isolated, first with an unsaturated nitrile of formula IV and then with an isocyanide of formula V.
Metal compounds of formula III are therefore the direct intermediates for compounds of formula I and are either introduced as such into the preparation process or are formed in the first step thereof.
Using the process according to the invention, 3-(2,2-difluorobenzodi- Soxol-4-yl)-4-cyanopyrrole can be prepared in a high yield.
The C1-C4alkyl representing the individual radicals RI and Rz in formula IV as part of other radicals may be branched or straight-chained and is methyl, ethyl, propyl, isopropyl, butyl, sec.-butyl, isobutyl or tert.-butyl.
RI as a Cs-Cioaryloxy or a Cs-Co1arylsulfonyloxy radical may be phenoxy, Ci-C4alkylphenoxy, a- or B-naphtyloxy, further phenylsulfonyloxy, C 1 -C4alkylsulfonyloxy or a- or B-naphthylsulfonyloxy.
There may be mentioned as examples of the Ci-Ciohydrocarbon radical mentioned under R 3 in formula V, without these constituting a limitation, methyl, ethyl, isopropyl, heptyl, octyl, cyclopentyl, cyclohexyl, decyl, methylcyclohexyl, phenyl, p-tolyl, 1-naphthyl and 2-naphthyl.
In the metallation reagents Men Y for the 2,2-difluorobenzodioxole, as n mentioned, at least one Y is a strongly basic anion which may be C]-Cloalkyl preferably Ci-C4alkyl C 6
-C
1 4aryl Ci-Cioalkoxy preferably Ci-C 4 alkoxy NH 2 Ci-CiohydrocarbylNH or di(Ci-Clohydrocarbyl)N or also H.
Lr 6 Of these anions, alkyl aryl (such as phenyl di-(Ci-C4alkyl)N
(C
1 -Cialkyl)(Cs-Cscycloalkyl)N and di- (Cs-C 6 cycloalkyl)N are preferred. For transmetallation it is also possible to use metal compounds having anions such as halide, nitrate, sulfate, phosphate, acetate, formate, etc..
The following solvents are especially suitable for the preparation of the compounds of formula I in stepwise processes or in a one-pot process: Aliphatic or aromatic hydrocarbons, ethers, tertiary amines, N-alkylated acid amides, lactams or cyclic ureas, sulfoxides, sulfones, nitriles, Sketones, alcohols or mixtures thereof. Examples are pentane, isopentane, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, diethyl ether, dibutyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, triethylamine, N,N,N',N'-tetramethylethylenedi- S amine, hexamethylphosphoric acid triamide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, ethylenedimethylurea, propylenedimethylurea, dimethyl sulfoxide, tetramethylenesulfone, acetonitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, methanol, ethanol, 'isopropanol and tert.-butanol.
When non-polar solvents are used, in order to ensure that the reaction proceeds smoothly it is almost always necessary to add a complexing agent, and when weakly polar solvents are used such action is at least S advantageous. The complexing agent is added in an amount of from 0.01 mol. to a tenfold excess, based on the compound of formula II.
Tertiary amines, N-substituted acid amides, lactams, cyclic ureas, alcoholates, sulfoxides or ethers, some of which have already been mentioned among the above solvents or earlier among the preferred complexing agents, are generally suitable.
Included among the ethers in the broader sense are also crown ethers, for example 15-crown-5; 18-crown-6; dibenzo-18-crown-6; dicyclohexyl-18crown-6; dibenzo-24-crown-8; and dicyclohexyl-24-crown-8.
7 The processes according to the invention preferably take place under an inert gas in the presence of a complex-forming compound complexing agent) and in a solvent or a solvent mixture.
The preferred first step in each of the above-mentioned processes for the preparation of the compounds of formula III, liIa or I is the metallation of the 2,2-difluorobenzodioxole of formula II with lithium or, preferably, an organolithium compound. Accordingly, of the compounds of formula III, 2,2-difluorobenzodioxol-4-yl-lithium is especially preferred as intermediate.
One of the preferred forms of the complete process for the preparation of 3-,2,2-difluorobenzodioxol-4-yl)-4-cyanopyrrole is that wherein the 2,2-difluoro-l,3-benzodioxole dissolved in a hydrocarbon is added at from -250 to -5 0 C to a mixture of approximately equimolar amounts of tetramethylethylenediamine and n-butyllithium, and then an equimolar amount of ethoxymethylenecyanoacetic acid ethyl ester and subsequently an equimolar amount of p-toluenesulfonylmethyl isocyanide are added to the reaction mixture at from -250 to +25 0 C. Tetrahydrofuran is advantageously used as a further solvent. Methanol may be mentioned as the preferred solvent for the last reactant.
One of the especially preferred forms of the complete process for the preparation of 3-(2,2-difluorobenzodioxol-4-yl)-4-cyanopyrrole is that wherein n-butyllithium is added at from -250 to -5 0 C to a mixture, dissolved in a hydrocarbon, of approximately equimolar amounts of 2,2-difluorobenzodioxole and tetramethylethylenediamine, and then an equimolar amount of ethoxymethylenecyanoacetic acid ethyl ester and subsequently an equimolar amount of p-toluenesulfonylmethyl isocyanide are added to the reaction mixture at from -250 to +25 0
C.
The organometal compounds of formula III, both in solution and in suspension, are stable for a time at low temperatures in the form of their corresponding complexes. It is known that, for example, organolithium compounds are often in the form of dimers. In addition, solvents or complexing agents that have fiee electron pairs, for example ethers or tert.-amines, are coordinatively bonded to the metal.
-L 2^ 8 In the preparation according to the invention of the compounds of formula III from the compound of formula II, organometal compounds are to be given prominence as reactants. Of the organometal compounds, the organolithium compounds, especially methyllithium, n-butyllithium, sec.-butyllithium, tert.-butyllithium, phenyllithium, lithium diisopropylamide and lithium dicyclohexylamide, are particularly preferred.
The metal compounds used for the preparation of the compounds of formula III, and the compounds of formulae II, IV and V are known products which are commercially available or can be prepared by conventional methods.
The process according to the invention is illustrated by the following Examples: Example 1: Preparation of 2,2-difluoro-l,3-benzodioxol-4-yl-lithium S a) First 13 g (110 mmol) of N,N,N',N'-tetramethylethylenediamine in 30 ml of toluene/tetrahydrofuran and then 15.8 g (100 mmol) of 2,2-difluoro-1,3-benzodioxole, dissolved in 120 ml of toluene/tetrahydrofuran are added dropwise under a nitrogen atmosphere at from -15' to 0 C to 69 ml (110 mmol) of n-butyllithium (1.6 molar suspension in toluene), n-butane being formed.
A specimen of the resulting dissolved product of formula III is identified by NMR spectroscopy.
Signals 6 ppm: 6.83 d (J 7 Hz) corresponds to: H 7 7.10 dd (J 7 Hz) corresponds to: H 6 7.80 d (J 4 Hz) corresponds to: H b) 94.0 g (272 mmol) of n-butyllithium (18.5 in toluene) are added dropwise under a nitrogen atmosphere at from -150 to -10 0 C to 29.5 g (254 mmol) of N,N,N',N'-tetramethylethylenediamine and 40.0 g (253 mmol) of 2,2-difluoro-1,3-benzodioxole in 35 ml of toluene, n-butane being formed in addition to the title compound.
i 9 c) 39.3 g (339 mmol) of N,N,N',N'-tetramethylethylenediamine are added dropwise under a nitrogen atmosphere at from -150 to -10 0 C to 137.8 g (409 mmol) of n-butyllithium solution (19.0 in toluene). The resulting reaction mixture is added dropwise at from -150 to -10 0 C under a nitrogen atmosphere to a solution of 53.3 g (337 mmol) of 2,2-difluoro-1,3-benzodioxole in 46 ml of toluene, n-butane being formed in addition to the title compound.
t The following compounds of formula III are prepared analogously to I Example 1.
n "s Me Y n-i (ill) o 'i ii n-1 0 0
I
2 10 Table: Compounds of formula III compound no.
position H atom NMR: 6 (ppm) 6,83 (d) 7,10 (dd) 7,80 (d)
I,
4 444~~ 4 44 44 4 4 4 4 4444 4 5 6,85 7,05 7, 76 6,86 6,65 7,42 6,93 6,84 7,05 6,84 6,98 7,14 (d) (dd) (d) (d) (dd) (d) (d) (dd) (d) (d) (dd) (d) (J=7Hz) (J='7Hz) (J=4Hz) (J='7Hz) (J=7Hz) (J=4Hz) (J=7Hz) (J=7Hz) (J=4Hz) (J=7Hz) (J=7Hz) (J=4Hz) (J=7Hz) (J=7-z) (J=4Hz) Example 2: Preparation of 3-(2 ,2-difluorobenzodioxol-4-yl)- 4 -cyanopyrrole a) First 48.2 g of N,N,N',N'-tetramethylethylenediamine, and then, after stirring for 30 minutes, 60 g of 2,2-difluoro-1,3--benzodioxole dissolved in 200 ml of hexane are addedf under an inert gas atmosphere at to 261 ml of 1.6N n-butyllithium in hexane. After 15 minutes, 70.7 g of ethoxymethylenecyanoacetic acid ethyl ester dissolved in 250 ml of tetrahydrofuran are added at -15' within a period of 25 minutes. After a further 30 minutes, 81.5 g of p-toluenesulfonylmethyl isocyanide dissolv'--d in 220 ml of tetrahydrofuran are added to the resulting suspension at 00 over a period of 25 minutes. The solution is then heated to 250 and 400 ml of solvent are evaporated off in vacuo.
11 The residue is diluted with 500 ml of ethyl acetate and the resulting solution is washed twice with 300 ml of water and twice with 300 ml of saturated sodium chloride solution and dried over magnesium sulfate. The solvent is evaporated off in vacuo.
The residue is chromatographed over silica gel using hexane/ethyl acetate as eluant.
After evaporation of the solvent in vacuo, the title compound having a melting point of 193-195 0 C is obtained. Yield 70 of the theoretical yield, based on 2,2-difluorobenzo-l,3-dioxole.
b) 106.2 g (307 mmol) of n-butyllithium sulution (18.5 in toluene) are added dropwise under a nitrogen atmosphere at from -150 to -10 0 C to S 29.5 g (254 mmol) of N,N,N',N'-teLramethylethylenediamine and 40 g (253 mmol) of 2,2-difluoro-1,3-benzodioxole in 35 ml of toluene. 52.1 g (308 mmol) of ethoxymethylenecyanoacetic acid ethyl ester in 11 ml of toluene are then added within a period of 2 hours at from -150 to -10 0
C.
After 20 minutes, the resulting suspension is heated to 0 C ann 50 g (256 mmol) of p-toluenesulfonylmethyl isocyanide dissolved in 135 ml of tetrahydrofuran are added over a period of 30 minutes. The reaction mixture is then heated to 25 0 C, added to 150 ml of water and filtered to obtain the title compound.
c) 39.3 g (339 mmol) of N,N,N',N'-tetramethylethylenediamine are added dropwise under a nitrogen atmosphere at from -150 to -10 0 C to 137.8 g (409 mmol) of n-butyllithium solution (19.0 in toluene). The resulting re.action mixture is metered at from -150 to -10 0 C under a nitrogen atmosphere into a solution of 53.3 g (337 mmol) of 2,2-difluorobenzo- 2,3-dioxole in 46 ml of toluene. 69.1 F (409 mmol) of ethoxymethylenecyanoacetic acid ethyl ester in 150 ml of toluene are then metered in at from -150 to -10 0 C. The resulting suspension is subsequently heated to 0 0 C and 66.6 g (342 mmol) of p-toluenesulfonylmethyl isocyanide dissolved in 180 ml of tetrahydrofuran are added. The reaction mixture is then heated to 25 0 C, added to 200 ml of water and filtered to obtain the title compound.
-i

Claims (14)

1. A process for the preparation of 3-(2,2-difluorobenzodioxol-4-yl)- 4 -cyanopyrrole of formula I wherein a 4-metallo-2,2-difluorobenzodioxole of formula III, wherein Me is a metal, n is the valency of that metal and Y is an anionic radical, is reacted in a suitable solvent phase, in the presence or absence of a complex-forming compound, first with an unsaturated nitrile of formula IV 0 0 ~R 1 CH=C /C III IV *Wherein RI is halogen, Cl-C~alkoxy, Cs-Cloaryloxy, di-Cl-Ci~alkylamino, CI-Ci.- alkylsulfonyloxy, C6-Gloarylsulfonyloxy or Cl-Ci~alkylcarbonyloxy and R 2 is a Ca-G~alkoxycarbonyl radical, and then with an isocyanide of formula V R 3 -SO 2 CH 2 NC, wherein R 3 is an openL-chain or cyclic, unsubstituted or substituted Cl-Ci ohydrocarbon.
2. A process for the preparation of compounds of formula III according to claim 1, wherein 2,2-difluorobenzodioxole of formula II is reacted in a suitable solvent phase, in the presence or absence of a coi., '-x-forminL, compound, with a metal or a metal compound Me nYn -13 n I Men Y n n-1 Me" 1 \n (II) (III) wherein Me is a metal, n is the valency of the metal and Y is an anionic radical and, if Y is present, at least one Y is an organic basic radical.
3. A process for the preparation of 3-(2,2-difluorobenzodioxol-4-yl)-4- an cyanopyrrole, wherein, in a one-pot reaction, 2,2-difluorobenzodioxole is S converted in a solvent phase, in the presence or absence of a complex- S forming compound, with an organometal compound or with a metal into a 4 -metallo-2,2-difluorobenzodioxole of formula III according to claim 1 a which is reacted, without being isolated, first with an unsaturated S nitrile of formula IV according to claim 1 and then with an isocyanide of formula V according to claim 1. a ai 4. A process for the preparation of compounds of formula III according to claim 1, wherein a compound of formula IIa n n-1 (IIIa), F/ \F wherein Me' is a metal other than Me, is reacted with a compound of formula Meny A process according to claim 3, wherein the reaction is carried out under an inert gas atmosphere in a solvent selected from a group con- sisting of aliphatic and aromatic hydrocarbons, ethers, ketones and dipolar solvents.
6. A process according to claim 5, wherein the metallation and the subsequent reactions are carried out at from -700 to +150 0 C. 14
7. A process according to claim 6, wherein the metallation and the subsequent reactions are carried out at from -250 to +80 0 C.
8. A process according to claim 3, wherein the complex-forming compound is selected from a group consisting of ethers, tert.-amines, cyclic ureas and N-substituted acid amides.
9. A process according to claim 8, wherein the complex-forming compound is selected from a group consisting of ethylene glycol dimethyl ether, hexamethylphosphoric acid triamide, 1,3-dimethyl-2-imidazolone, dimethylethyleneurea, dimethylpropyleneurea and N,N,N',N'-tetramethyl- ethylenediamine, and an organolithium compound is used as the metal compound. A process according to claim 9, wherein 2,2-difluoro-l,3- benzodioxole is added to a mixture of approoriately equimolar amounts of tetramethylethylenediamine and butyllithium at from -250 to -5 0 C and the reaction mixture is reacted in succession with an approximately equimolar amount of ethoxymethylenecyanoacetic acid ethyl ester and then with an approximately equimolar amount of p-toluenesulfonylmethyl isocyanide at from -250 to +25 0 C.
11. A process according to claim 9, wherein n-butyllithium is added at from -25° to -5 0 C to a mixture, dissolved in a hydrocarbon, of approximately equimolar amounts of 2,2-difluoro-l,3-benzodioxole and tetramethylethylenediamine and the reaction mixture is reacted in succession with an approximately equimolar amount of ethoxymethylene- cyanoacetic acid ethyl ester and then with an approximately equimolar amount of p-toluenesulfonylmethyl isocyanide at from -25° to +25 0 C.
12. The compounds of formula III obtainable by a process according to claim 2 or claim 4.
13. Compounds according to claim 12, wherein Me is a metal selected from a group consisting of Li, Na, K, Cs, Mg, Ba, Zn and Cu, n being 1 or 2 and Y being chloride or bromide.
14. 2,2-difluoro-l,3-benzodioxol-4-yl-lithium. s;GSA/6850M 15 A process according to claim 2, wherein an organolithium compound is used as the metal compound Meny n
16. A process according to claim 15, wherein an organolithium compound selected from a group consisting of methyllithium, n-butyllithium, sec.-butyllithium, tert.-butyllithium, phenyllithium, lithium diisopropylamide and lithium dicyclohexylamide is used.
17. A process according to claim 2, wherein the compound of formula II is reacted with a complex prepared from equimolar amounts of an organometal compound and a tert.-amine or an amide.
18. A process according to claim 17, wherein the organometal compound is selected from a group consisting of organo-Li, -Na, -Cs and -Mg compounds. The product cf th przr^: cf Rjn' -OR Of Claim 1 tE 11 cr 19, A process for the preparation of 3-(2,2-diflorobenzodioxol-4- yl)-4-cyanopyrrole substantially as hereinbefore described with reference to any one of the Examples. DATED this FIFTEENTH day of MARCH 1989 Ciba-Geigy AG Patent Attorneys for the Applicant SPRUSON FERGUSON
AU31467/89A 1988-03-18 1989-03-17 Process for the preparation of a pyrrole derivative Expired AU624806B2 (en)

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US6204397B1 (en) 1991-03-08 2001-03-20 Bayer Aktiengesellschaft Process for the preparation of 3-substituted 4-cyano-pyrrole compounds

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AU5912086A (en) * 1985-06-21 1986-12-24 Syngenta Participations Ag Substituted 3-phenyl-cyanopyrrole derivatives
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US4680413A (en) * 1986-01-17 1987-07-14 Nippon Soda Co., Ltd. Process for the production of 3-phenyl-4-cyanopyrroles

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AU5912086A (en) * 1985-06-21 1986-12-24 Syngenta Participations Ag Substituted 3-phenyl-cyanopyrrole derivatives
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