WO2005105717A1 - Process for the production of cyclic diketones - Google Patents

Process for the production of cyclic diketones Download PDF

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WO2005105717A1
WO2005105717A1 PCT/EP2005/004655 EP2005004655W WO2005105717A1 WO 2005105717 A1 WO2005105717 A1 WO 2005105717A1 EP 2005004655 W EP2005004655 W EP 2005004655W WO 2005105717 A1 WO2005105717 A1 WO 2005105717A1
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formula
compound
halogen
alkyl
substituted
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PCT/EP2005/004655
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David Anthony Jackson
Andrew Edmunds
Martin Charles Bowden
Ben Brockbank
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Syngenta Participations Ag
Syngenta Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
    • C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/23—Preparation of halogenated hydrocarbons by dehalogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C23/00—Compounds containing at least one halogen atom bound to a ring other than a six-membered aromatic ring
    • C07C23/18—Polycyclic halogenated hydrocarbons
    • C07C23/20—Polycyclic halogenated hydrocarbons with condensed rings none of which is aromatic
    • C07C23/32—Polycyclic halogenated hydrocarbons with condensed rings none of which is aromatic with a bicyclo ring system containing eight carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
    • C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/42—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis
    • C07C45/43—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis of >CX2 groups, X being halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/417—Saturated compounds containing a keto group being part of a ring polycyclic
    • C07C49/423—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system
    • C07C49/427—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system having two rings
    • C07C49/443—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system having two rings the condensed ring system containing eight or nine carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/417—Saturated compounds containing a keto group being part of a ring polycyclic
    • C07C49/423—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system
    • C07C49/453—Saturated compounds containing a keto group being part of a ring polycyclic a keto group being part of a condensed ring system having three rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/487—Saturated compounds containing a keto group being part of a ring containing hydroxy groups
    • C07C49/507—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic
    • C07C49/513—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/385—Saturated compounds containing a keto group being part of a ring
    • C07C49/517—Saturated compounds containing a keto group being part of a ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/20—All rings being cycloaliphatic the ring system containing seven carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/44—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing eight carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/50—Spiro compounds

Definitions

  • the present invention relates to a novel process for the preparation of cyclic 1 ,3-diketones and to novel intermediates for use in that process.
  • Cyclic 1,3-diketones are valuable starting materials for the preparation of herbicides as are described, for example, in WO 01/94339.
  • the problem of the present invention is accordingly to make available a novel process for the preparation of cyclic 1 ,3-diketones which makes it possible to prepare those compounds at reasonable cost in high yields and good quality.
  • a 2 is oxygen, C(O), SO 2 or (CR 3 R 4 ) n ; n is 1 or 2; A 3 is CR 5 R 6 ;
  • R 2> R3, R , 5 and R 6 are each independently of the others C C 4 alkyl which may be mono-, di- or tri-substituted by C 1 -C 4 alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C C 4 alkoxycarbonyl, C 1 -C 4 alkylthio, C C 4 alkylsulfinyl, C C 4 alkyIsulfonyl, C 1 -C 4 alkyl- carbonyl, phenyl or by heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C C 4 alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C C 4 alkoxycarbonyl, C-
  • R 7 and R 8 are each independently of the other C C 4 alkyl, C C haloalkyl, d-C ⁇ lkylsulfonyl, CrC alkylcarbonyl or d-C 4 a!koxycarbonyl; comprises a) reacting a compound of formula II
  • a 1 ⁇ A 2 and A 3 are as defined for formula I, with a bromine or chlorine source to form a compound of formula III
  • A-,, A 2 and A 3 are as defined for formula I and X is chlorine or bromine; and b) treating that compound with water.
  • alkyl groups appearing in the above substituent definitions may be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl.
  • Alkoxy groups are derived from the mentioned alkyl groups.
  • An alkylene chain may be substituted by one or more d-C 3 a!kyl groups, especially by methyl groups; such alkylene chains and alkylene groups are preferably unsubstituted.
  • a C C 3 alkylene chain which may be interrupted by oxygen, sulfur, SO, SO 2 , OC(O), NR 8 or by C(O), which are separated at least by a carbon atom, is to be understood as being, for example, the chains -CH 2 -, -CH 2 CH 2 -, -CH 2 CH 2 CH 2 -, -CH 2 CH 2 CH 2 CH 2 -, -CH(CH 3 )-, -CH 2 CH(CH 3 )-, -CH 2 CH(CH 3 )CH 2 -, -CH 2 O-, -OCH 2 -, -CH 2 OCH 2 -, -OCH 2 CH 2 -, -OCH CH CH -, -CH OCH 2 CH 2 -, -CH 2 OCH(CH 3 )CH 2 -, -SCH 2 -, -SCH 2 CH 2 -, -SCH 2 CH 2 -, -SCH 2 CH 2 CH 2 -, -CH 2 S-, -
  • Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine. The same applies also to halogen in conjunction with other meanings, such as haloalkyl, halo- alkoxy or halophenyl.
  • Haloalkyl groups having a chain length of from 1 to 4 carbon atoms are, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-fluoroprop-2-yl, pentafluoro- ethyl, 1 ,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl, 2,2,2-trichloroethyl, penta- fluoroethyl and heptafluoro-n-propyl.
  • Preferred haloalkyl groups are fluoromethyl, difluoro- methyl, difluorochloromethyl, dichloromethyl, trifluoromethyl and pentafluoroethyl.
  • Alkoxy groups preferably have a chain length of from 1 to 4 carbon atoms.
  • Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert- butoxy; preferably methoxy or ethoxy.
  • Alkylthio groups preferably have a chain length of from 1 to 4 carbon atoms.
  • Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.
  • Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl; preferably methylsulfinyl or ethylsulfinyl.
  • Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutyl- sulfonyl, sec-butylsulfonyl or tert-butylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
  • Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert- butoxycarbonyl; preferably methoxycarbonyl, ethoxycarbonyl or tert-butoxycarbonyl.
  • Heteroaryl is to be understood as being 5- or 6-membered groups containing nitrogen, oxygen and/or sulfur, for example furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, triazinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, 4,5-dihydro-isoxazolyl, 2-pyranyl, 1 ,3-dioxoI-2-yl, oxiranyl, 3-oxetanyl, tetrahydrofuranyl or tetrahydropyranyl.
  • Suitable bromine and chlorine sources are bromine, chlorine, their succinimides such as N- bromosuccinimide (NBS), bromo- and chloro-acetamides and alkyl hypohalites.
  • a preferred bromine source is bromine or NBS, and a preferred chlorine source is chlorine.
  • an inert gas such as, for example, argon or nitrogen beneath the surface of the reaction mixture.
  • Incorporation of the halogens into the reaction mixture can be carried out by dropwise addition or direct introduction beneath the surface of the reaction mixture. In the case of direct introduction, the halogens can be diluted with an inert gas such as, for example, argon or nitrogen.
  • the reaction according to Process Step a) is preferably carried out in the presence of a free- radical initiator such as, for example, benzoyl peroxide or azoisobutyronitrile. Illumination of the reaction mixture is, moreover, advantageous.
  • the halogenation is preferably carried out in the presence of azoisobutyronitrile.
  • the reaction is preferably carried out in the presence of a solvent.
  • Suitable solvents are chlorobenzene, hexane, acetonitrile, tetrahydrofuran, methylcyclohexane or CCI and also mixtures thereof; special preference is given to chlorobenzene or CCI 4 .
  • the temperatures are generally from 0°C to 150°C; preference is given to a range from 80°C to 130°C.
  • Ai, A 2 and A 3 are as defined for formula I in claim 1 and X is either chlorine or bromine, are novel and were developed specifically for the process according to the invention, and the present invention accordingly also relates thereto.
  • An especially valuable intermediate is the compound of formula lllb
  • Process Step b) is preferably carried out with acid- or base-catalysis, preferably acid- catalysis.
  • Suitable acids are mineral acids such as sulfuric acid, hydrochloric acid or bromic acid or organic acids such as acetic acid. Special preference is given to sulfuric acid.
  • bases there may be used organic or inorganic bases such as, for example, quaternary ammonium hydroxides or sodium hydroxide.
  • bases for complete conversion at least 2 equivalents of water are used. In a preferred embodiment, first one equivalent of water is added to the compound of formula III until the monoketone of formula IV
  • Ai, A 2 and A 3 are as defined hereinbefore and X is chlorine or bromine, is formed and then, as a result of the addition of the second equivalent of water, the diketone of formula I is formed.
  • the selectivity of the reaction can be further increased using this preferred embodiment.
  • the reaction according to Process Step b) is preferably carried out in the presence of a solvent.
  • Suitable solvents are those mentioned for Process Step a), preferably chlorobenzene or acetonitrile.
  • the reaction is carried out at a temperature of from 20°C to 150°C, preferably from 20°C to 50°C.
  • the reaction is carried out in the presence of aqueous sulfuric acid in acetonitrile as solvent.
  • the process according to the invention can be carried out without isolation of intermediates, in a one-pot reaction procedure. This constitutes a considerable advantage especially for large-scale application of the process according to the invention.
  • Example P1 Preparation of 2.4,4-tribromo-bicyclor3.2.1loct-2-ene: To a suspension of 15 g (88.9 mmol) of bicyclo[3.2.1]oct-2-ene in 250 ml of CCI there are added, under a nitrogen atmosphere, 1.54 g (9.26 mmol) of azoisobutyronitrile. The reaction mixture is then illuminated with a strong lamp and heated to a temperature of 80°C, with stirring. 30 g (0.17 mol) of N-bromosuccinimide (NBS) are then added and stirring is carried out for 1.25 hours at a temperature of 80°C.
  • NBS N-bromosuccinimide

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  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to the preparation of compounds of formula (I); wherein the substituents are as defined in claim 1, by reacting a compound of formula (II); with a bromine or chlorine source to form a compound of formula (III); and subsequently treating that compound with water.

Description

Process for the production of cyclic diketones
The present invention relates to a novel process for the preparation of cyclic 1 ,3-diketones and to novel intermediates for use in that process.
Cyclic 1,3-diketones are valuable starting materials for the preparation of herbicides as are described, for example, in WO 01/94339.
A number of processes are known for the preparation of such 1 ,3-diketones. For example, bicyclic 1,3-diketones can be obtained from the corresponding salt forms by known methods.
Such a process for the preparation of bicyclic 1 ,3-diketones from the corresponding salts is described, for example, in JP-10-265441. The use of 3-acetyl-cyclopentanecarboxylic acid alkyl esters, which are obtained from 3-methylene-bicyclo[2.2.1]heptan-2-one, as starting material in that process makes it too uneconomical for the commercial preparation of bicyclo[3.2.1]octane-2,4-dione by way of the corresponding sodium salt because, during the oxidative ring opening in the presence of acids and alcohols, for example using sulfurous peroxo acid in the presence of methanol, in addition to the formation of the desired alkyl esters, the free 3-acetyl-cyclopentanecarboxylic acid may also be formed which then has to be converted back into the corresponding alkyl ester in an additional reaction step prior to cyclisation.
The problem of the present invention is accordingly to make available a novel process for the preparation of cyclic 1 ,3-diketones which makes it possible to prepare those compounds at reasonable cost in high yields and good quality.
The problem has been solved by making available the process according to the invention. This process for the preparation of compounds of formula I
Figure imgf000003_0001
wherein At JS CRTRZ;
A2 is oxygen, C(O), SO2 or (CR3R4)n; n is 1 or 2; A3 is CR5R6;
R1. R2> R3, R , 5 and R6 are each independently of the others C C4alkyl which may be mono-, di- or tri-substituted by C1-C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C C4alkoxycarbonyl, C1-C4alkylthio, C C4alkylsulfinyl, C C4alkyIsulfonyl, C1-C4alkyl- carbonyl, phenyl or by heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C C4alkoxycarbonyl, C-|-C4alkylsulfonyl or by C C4haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R1 t R2, R3, R , R5 and R6 are each independently of the others hydrogen, C C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, CrC alkoxycarbonyl, C C^lkylthio, Cι-C4alkylsulfinyl, CrC alkylsulfonyl, Crdalkylcarbonyl, phenyl or heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C-ι-C alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C C4alkoxycarbonyl, C dalkylsulfonyl or by Cι-C haloalkyI, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R-i and R2 together form a 3- to 5-membered carbocyclic ring which may be substituted by C C4alkyl and/or interrupted by oxygen, sulfur, S(O), SO2, OC(O), NR7 or by C(O); and/or R2 and R together or R2 and R5 together form a CrC3alkylene chain which may be interrupted by oxygen, sulfur, SO, SO2, OC(O), NR8 or by C(O); it being possible for that C C3alkylene chain in turn to be substituted by C C4aIkyl; and
R7 and R8 are each independently of the other C C4alkyl, C C haloalkyl, d-C^lkylsulfonyl, CrC alkylcarbonyl or d-C4a!koxycarbonyl; comprises a) reacting a compound of formula II
Figure imgf000003_0002
wherein A1 τ A2 and A3 are as defined for formula I, with a bromine or chlorine source to form a compound of formula III
Figure imgf000004_0001
wherein A-,, A2 and A3 are as defined for formula I and X is chlorine or bromine; and b) treating that compound with water.
The alkyl groups appearing in the above substituent definitions may be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. Alkoxy groups are derived from the mentioned alkyl groups.
An alkylene chain may be substituted by one or more d-C3a!kyl groups, especially by methyl groups; such alkylene chains and alkylene groups are preferably unsubstituted.
A C C3alkylene chain which may be interrupted by oxygen, sulfur, SO, SO2, OC(O), NR8 or by C(O), which are separated at least by a carbon atom, is to be understood as being, for example, the chains -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH(CH3)-, -CH2CH(CH3)-, -CH2CH(CH3)CH2-, -CH2O-, -OCH2-, -CH2OCH2-, -OCH2CH2-, -OCH CH CH -, -CH OCH2CH2-, -CH2OCH(CH3)CH2-, -SCH2-, -SCH2CH2-, -SCH2CH2CH2-, -CH2S-, -CH2SCH2-, -CH2S(O)CH2-, -CH2SO2CH2-, -CH2SCH2CH2-, -CH2S(O)CH2CH2-, -CH2SO2CH2CH2-, -CH2SO2NH-, -CH2N(CH3)SO2CH2CH2-, -N(SO2-CH3)CH2CH2-, -CH2C(O)NH- or -CH2NHC(O)CH2-.
Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine. The same applies also to halogen in conjunction with other meanings, such as haloalkyl, halo- alkoxy or halophenyl.
Haloalkyl groups having a chain length of from 1 to 4 carbon atoms are, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-fluoroprop-2-yl, pentafluoro- ethyl, 1 ,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl, 2,2,2-trichloroethyl, penta- fluoroethyl and heptafluoro-n-propyl. Preferred haloalkyl groups are fluoromethyl, difluoro- methyl, difluorochloromethyl, dichloromethyl, trifluoromethyl and pentafluoroethyl.
Alkoxy groups preferably have a chain length of from 1 to 4 carbon atoms. Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert- butoxy; preferably methoxy or ethoxy.
Alkylthio groups preferably have a chain length of from 1 to 4 carbon atoms. Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio. Alkylsulfinyl is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl; preferably methylsulfinyl or ethylsulfinyl. Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutyl- sulfonyl, sec-butylsulfonyl or tert-butylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.
Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert- butoxycarbonyl; preferably methoxycarbonyl, ethoxycarbonyl or tert-butoxycarbonyl.
Heteroaryl is to be understood as being 5- or 6-membered groups containing nitrogen, oxygen and/or sulfur, for example furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, triazinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, 4,5-dihydro-isoxazolyl, 2-pyranyl, 1 ,3-dioxoI-2-yl, oxiranyl, 3-oxetanyl, tetrahydrofuranyl or tetrahydropyranyl.
Process Step a):
Suitable bromine and chlorine sources are bromine, chlorine, their succinimides such as N- bromosuccinimide (NBS), bromo- and chloro-acetamides and alkyl hypohalites. A preferred bromine source is bromine or NBS, and a preferred chlorine source is chlorine. In the case of bromination it is advantageous for the HBr that is formed to be removed from the reaction mixture, which may be accomplished, for example, by introducing an inert gas such as, for example, argon or nitrogen beneath the surface of the reaction mixture. Incorporation of the halogens into the reaction mixture can be carried out by dropwise addition or direct introduction beneath the surface of the reaction mixture. In the case of direct introduction, the halogens can be diluted with an inert gas such as, for example, argon or nitrogen.
The reaction according to Process Step a) is preferably carried out in the presence of a free- radical initiator such as, for example, benzoyl peroxide or azoisobutyronitrile. Illumination of the reaction mixture is, moreover, advantageous. The halogenation is preferably carried out in the presence of azoisobutyronitrile.
The reaction is preferably carried out in the presence of a solvent. Suitable solvents are chlorobenzene, hexane, acetonitrile, tetrahydrofuran, methylcyclohexane or CCI and also mixtures thereof; special preference is given to chlorobenzene or CCI4.
The temperatures are generally from 0°C to 150°C; preference is given to a range from 80°C to 130°C.
Compounds of formula II are known, for example from Tetrahedron Letters (1976) 1257-58 or J. Org. Chem. 61, 1996, 7832-7847; they are commercially available in some cases or can be prepared by known methods. The compounds of formula III
Figure imgf000006_0001
wherein Ai, A2 and A3 are as defined for formula I in claim 1 and X is either chlorine or bromine, are novel and were developed specifically for the process according to the invention, and the present invention accordingly also relates thereto. An especially valuable intermediate is the compound of formula lllb
Figure imgf000006_0002
Process Step b):
Process Step b) is preferably carried out with acid- or base-catalysis, preferably acid- catalysis. Suitable acids are mineral acids such as sulfuric acid, hydrochloric acid or bromic acid or organic acids such as acetic acid. Special preference is given to sulfuric acid. As bases there may be used organic or inorganic bases such as, for example, quaternary ammonium hydroxides or sodium hydroxide. For complete conversion at least 2 equivalents of water are used. In a preferred embodiment, first one equivalent of water is added to the compound of formula III until the monoketone of formula IV
Figure imgf000007_0001
wherein Ai, A2 and A3 are as defined hereinbefore and X is chlorine or bromine, is formed and then, as a result of the addition of the second equivalent of water, the diketone of formula I is formed. The selectivity of the reaction can be further increased using this preferred embodiment.
The reaction according to Process Step b) is preferably carried out in the presence of a solvent. Suitable solvents are those mentioned for Process Step a), preferably chlorobenzene or acetonitrile. The reaction is carried out at a temperature of from 20°C to 150°C, preferably from 20°C to 50°C.
In a preferred embodiment of Process Step b), the reaction is carried out in the presence of aqueous sulfuric acid in acetonitrile as solvent.
The process according to the invention can be carried out without isolation of intermediates, in a one-pot reaction procedure. This constitutes a considerable advantage especially for large-scale application of the process according to the invention.
The process according to the invention will be explained in greater detail by means of the following Examples. Preparation Examples:
Example P1 : Preparation of 2.4,4-tribromo-bicyclor3.2.1loct-2-ene: To a suspension of 15 g (88.9 mmol) of bicyclo[3.2.1]oct-2-ene in 250 ml of CCI there are added, under a nitrogen atmosphere, 1.54 g (9.26 mmol) of azoisobutyronitrile. The reaction mixture is then illuminated with a strong lamp and heated to a temperature of 80°C, with stirring. 30 g (0.17 mol) of N-bromosuccinimide (NBS) are then added and stirring is carried out for 1.25 hours at a temperature of 80°C. Then, at intervals of about 1.5 hours, three further portions of 30 g (0.17 mol), 11.6 g (64.5 mmol) and 18.4 g (0.1 mol) of NBS are added and the reaction mixture is maintained at that temperature, with stirring, until conversion is complete. The reaction mixture is then cooled to ambient temperature and diluted with 100 ml of isohexane. After filtration and removal of the solvent in vacuo, 43.2 g (52 % of theory) of 2,4,4-tribromo-bicyclo[3.2.1]oct-2-ene are obtained as a red-brown oil.
MS: 265 (M+ - Br), 237, 183, 156, 119, 105, 89, 77, 63, 51 , 39
1H NMR (CDCIg): 1.55-1.65 (m, 1 H), 1.85-2.20 (m, 4H), 2.55-2.60 (d, 1 H), 2.70-2.80 (d, 1H),
3.20 (d, 1 H), 6.35 (s, 1 H)
Example P2: Preparation of 4-bromo-bicyclof 3.2.1 loct-3-en-2-one: To a solution of 89.9 g (7.9 % w/w, 100 % = 7.1 g, 20.6 mmol) of 2,4,4-tribromo- bicyclo[3.2.1]oct-2-ene in chlorobenzene there are added 100 ml of acetonitrile and 100 ml of 10 % sulfuric acid and stirring is carried out for 50 minutes at ambient temperature. The pH is then adjusted to 7 using aqueous sodium hydroxide solution and the aqueous phase is separated off. The organic phase is washed with 50 ml of water and then dried using magnesium sulfate. After filtration and removal of the acetonitrile using a rotary evaporator, 57.8 g (88 % of theory using quantitative 1H NMR) of 4-bromo-bicyc!o[3.2.1]oct-3-en-2-one are obtained as a 6.3 % solution in chlorobenzene.
MS: 200(M+), 172, 159, 146, 131 , 121 , 91 , 77, 65, 51 , 39
1H NMR (CDCIa): 1.60-1.70 (m, 2H), 1.85-1.95 (m, 1 H), 1.95-2.10 (m, 1H), 2.10-2.25 (m,
2H), 2.95 (t, 1H), 3.20 (t, 1 H), 6.20 (s, 1 H).
Example P3: Preparation of bicvclo[3.2.noctane-2,4-dione:
To a solution of 29 g (6.3 % w/w, .-. 100 % = 1.83 g, 9.1 mmol) of bromo-bicyclo[3.2.1]oct-3- en-2-one in chlorobenzene there are added 50 ml of acetonitrile and 100 ml of 10 % sulfuric acid and stirring is carried out for 90 minutes at reflux temperature (about 70°C). A further 50 ml of acetonitrile are then added and stirring is carried out for a further 17 hours until conversion is complete (monitored by HPLC). The acetonitrile and the major part of the chlorobenzene are then removed using a rotary evaporator. After extraction with ethyl acetate (100 ml) the aqueous phase is separated off. After drying the organic phase using magnesium sulfate, filtration and removal of the solvent in vacuo, 0.86 g (68 % of theory) of bicyclo[3.2.1]octane-2,4-dione is obtained.
MS: 138(M+), 109, 96, 81 , 68, 55, 39
1H NMR (CDCI. : 1.80-2.15 (m, 6H), 2.95 (s, 2H), 3.05-3.15 (d, 1 H), 3.20-3.30 (d, 1H).
The following compounds of Table 1 can also be prepared in accordance with the above Examples:
Figure imgf000009_0001
Comp. no. A_[ nι R 10
B1 CH2 CH2 0 H H B2 CH2 CH2 0 CH3 H B3 CH2 CH2 0 CH3 CH3 B4 (CH3)CH CH2 0 CH3 CH3 B5 (CH3)2C CH2 0 CH3 CH3 B9 CH2 CH2 0 CH3 CH3S B10 CH2 CH2 0 CH3 CH3SO B11 CH2 CH2 0 CH3 CH3SO2 B12 CH2 CH2 0 CH3 CH3O B13 CH2 CH2 0 CH3 CH3OC(O) B14 CH2 CH2 0 CH3 CH3CH2OC(O) Comp. no. A4 ni O B15 CH2 (CH3)2C 0 H H
Figure imgf000010_0001
B17 O CH2 0 H H
B18 A CH2 0 CH3 H
B19 CH2 0 CH3 CH3 \>
Figure imgf000010_0002
B23 (CH3)2C O 0 CH3 CH3 B24 CH2 O 0 CH3 CH3 B25 CHCH3 O 0 CH3 CH3 B26 (CH3)2C C=O 0 CH3 CH3 B27 (CH3)2C (OH)CH 0 CH3 CH3 B28 C* C=O 0 CH3 CH3
B29 c C=O 0 CH2 CH2
B30 (CH3)2C CH3O 0 CH3 CH3 CH30^ B31 CH O H CH2 B32 CH C=O H CH2 B33 CH CH2 H CH2 B34 CH CH2 H CHCHs B35 CH CH2 CH3 CH2 B36 CCH3 CH2 CH3 CH2 B37 CCH3 CH2 CH3 CHCH3 B38 CH CHCH3 H CH2 B39 CH C(CH3)2 H CH2 B40 CH CH2CH2 H CH2 Comp. no. ni O B41 CH C=O 2 H CH2 B42 CH CH2 2 H CH2 B43 CH2 CHCH3 0 CH3 H

Claims

What is claimed is:
1. A process for the preparation of a compound of formula I
Figure imgf000012_0001
wherein AT is CRTRZ;
A2 is oxygen, C(O), SO2 or (CR3R4)n; n is 1 or 2; A3 is CR5R6;
R-i, R2, R3, R4, R5 and R6 are each independently of the others d-C4alkyl which may be mono-, di- or tri-substituted by C C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, d-C4alkoxycarbonyl, d-C4alkylthio, C1-C4alkylsulfinyl, C1-C4alkylsulfonyl, d-C4alkyl- carbonyl, phenyl or by heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by d-C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, d-C4alkoxycarbonyl, C C4alkylsulfonyl or by C C4haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or Ri, R2, R3, R4, 5 and R6 are each independently of the others hydrogen, d-C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, d-C4alkoxycarbonyl , d-C4alkylthio, d-C4alkyl- sulfinyl, d-C alkylsulfonyl, d-C4alkylcarbonyI, phenyl or heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by Cι-C4alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, d-C4alkoxycarbonyl, C-ι-C alkyIsulfonyl or by C1-C4haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or
Ri and R2 together form a 3- to 5-membered carbocyclic ring which may be substituted by d-dalkyl and/or interrupted by oxygen, sulfur, S(O), SO2, OC(O), NR7 or by C(O); and/or R2 and R together or R2 and R5 together form a C C3alkylene chain which may be interrupted by oxygen, sulfur, SO, SO2, OC(O), NR8 or by C(O); it being possible for that d-C3alkylene chain in turn to be substituted by d-C4alkyl; and
R7 and R8 are each independently of the other C C4alkyl, d-C4-haloalkyl, Cι-C4alkylsulfonyl, C C alkylcarbonyl or C C alkoxycarbonyl; which comprises a) reacting a compound of formula II
Figure imgf000013_0001
wherein A1 t A2 and A3 are as defined for formula I, with a bromine or chlorine source to form a compound of formula III
Figure imgf000013_0002
wherein A^ A2 and A3 are as defined for formula I and X is chlorine or bromine; and b) treating that compound with water.
2. A process according to claim 1 , wherein in Step a) the compound of formula II is reacted with a bromine source.
3. A process according to claim 1 , wherein Step b) is carried out in the presence of an acid or base.
4. A process according to claim 1 , which is carried out without isolation of intermediates.
5. A compound of formula III
Figure imgf000013_0003
wherein A-i, A2 and A3 are as defined for formula I in claim 1 and X is either chlorine or bromine.
6. The compound of formula lllb
Figure imgf000014_0001
PCT/EP2005/004655 2004-04-30 2005-04-29 Process for the production of cyclic diketones WO2005105717A1 (en)

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WO2008145336A1 (en) 2007-05-29 2008-12-04 Syngenta Limited Herbicidally active bicyclic 1,3-dione compounds
WO2010089211A1 (en) 2009-02-04 2010-08-12 Syngenta Limited Novel herbicides

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DATABASE BEILSTEIN Institut zur Foerderung der Chemischen Wissenschaften; XP002345526, Database accession no. Reaction ID 2269527 *
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008145336A1 (en) 2007-05-29 2008-12-04 Syngenta Limited Herbicidally active bicyclic 1,3-dione compounds
US20100216638A1 (en) * 2007-05-29 2010-08-26 Syngenta Crop Protection, Inc. Herbicidally active bicyclic 1,3-dione compounds
US8828908B2 (en) 2007-05-29 2014-09-09 Syngenta Limited Herbicidally active bicyclic 1,3-dione compounds
WO2010089211A1 (en) 2009-02-04 2010-08-12 Syngenta Limited Novel herbicides

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