Title of Invention	A NOVEL CATALYTIC PROCESS FOR THE PREPARATION OF UNSATURATED ORGANIC HALIDES
Abstract	This invention relates to a novel catalytic process of preparation of unsaturated organic halides. Particularly, this invention relates to an improved catalytic process for the preparation of unsaturated halides of formula RX, where R represents alkenyl, alkynyl and aromatic groups using a metal salt or tetraalkylammonium salt in a halogenated salt

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This invention relates to a novel catalytic process of preparation of unsaturated organic halides. Particularly, this invention relates to an improved catalytic process for the preparation of unsaturated halides of formula RX, where R represents alkenyl, alkynyl and aromatic groups using a hitherto unknown modification of classical Hunsdiecker reaction. Vinyl halides, acetylenic halides and aromatic halides are key building blocks of various drug intermediates and biologically important natural products. In 1861 Borodin and in 1942 Hunsdiecker demonstrated that silver carboxylates, when reacted with bromine at elevated temperature, undergoes facile bromodecarboxylation to afford the corresponding alkyl bromides (Borodin, B.; Liebigs Ann. 1861, 119, 121; Hunsdiecker, H.C. Chem. Ber. 1942, 75, 291). In the intervening years the reaction has been further modified to include carboxylates of Hg(ll), Pb(IV) and Tl(l) and molecular halogen or halide (Chrich, D. Comprehensive Organic Synthesis; Trost, B. M.; Steven, V.L.; Pergamon: Oxford, 1991, 7, 723-734). This halodecarboxylation reaction, recently renamed as Hunsdiecker-Borodin-Cristol-Firth reaction (Hassner, A.; Stumer, C.; Organic Syntheses based on Name and Unnamed Reactions; Pergamon: Oxford, 1994, 183) is of proven utility for the synthesis of various organic halides notably alkyl (1°,2°,30) and aryl halides. The major limitations in the above processes include: (a) necessity to use high temperature; (b) the toxicity/hazard related to molecular bromine and salts of Hg, Tl, Pb, Ag, (c) very poor yields in cases of substrates such as a,p-unsaturated carboxylic acids and (d) stringent ex-situ protocol of isolating and purifying carboxylates in certain cases. Furthermore, the art has not, heretofore, suggested or taught a reagent system that is capable of mediating the Hunsdiecker reaction in a catalytic fashion. The principal object of the present invention is to provide a catalytic process for the preparation of unsaturated haiides from the reaction of corresponding carboxylic acids with N-halosuccinimides in the presence of various catalysts in organic or organic-aqueous solvent systems. This novel protocol thereby utilizes a catalytic metal-salt or phase transfer reagent in mediating an one-pot Hunsdiecker reaction. Accordingly, the present invention provides a novel catalytic process for the preparation of unsaturated organic haiides of formula RX where R represents alkenyl, alkynyl and aromatic groups, which comprises of reacting an organic unsaturated carboxylic acid of formula RCOOH wherein R is as stated above with N- haloacidimides in presence of a catalyst selected from group 1 metal salt or tetraalkyl ammonium salt of the kind such as herein described in halogenated solvent at ambient temperature for a period in the range of 25 wn to 24 h, recovering the unsaturated haiides of Formula RX by known methods wherein R is as stated above. In an embodiment of the present invention, unsaturated carboxylic acids used may be selected from alkyl or aryl substituted acrylic acid, alkyl or aryl substituted propiolic acid, alkyl or aryl substituted aromatic carboxylic acid. In yet another embodiment of the present invention, haloacidimides used may be selected from as N-bromosuccinimide, N-iodosuccinimide, N-chlorosuccinimide, N-bromophthalimide, N-iodophthalimide, N-Chlorophthalimide. In another embodiment of the invention the catalyst used may be group 1 metal salts or tetraalkylammonium salts. In another embodiment of the present invention the tetraalkylammonium salts used may be selected from tetrabutylammonium hydroxide, acetate, halide, trifluoroacetate. wherein tetraalkyl group may be such as tetramethyl, tetraethyl, tetrabutyl, tetrabenzyl, trimethylbenzyl, triethylbenzyl, cetyltriethyl. In another embodiment of the present invention the group 1 metal salts used may be such as lithium acetate, sodium acetate, potassium acetate, cesium acetate. In yet another embodiment of the present invention the solvent used may be such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrachloroethane, acetonitrile-water. More specifically, the present reaction describes a process for the preparation of unsaturated chlorides, bromides or iodides by reacting unsaturated carboxylic acids with N-chloro, N-bromo or N-iodosuccinimides respectively in the presence of Groupl metal salts or tetraalkylammonium salts in various organic or organic-aqueous solvent systems. Among all the catalysts screened, lithium acetate and tetrabutylammonium trifluoroacetate provides the best result. This is exemplified for the reaction of cinnamic acid with N-bromosuccinimide in presence of various catalysts (Table 1 and Table 2). Table 1: Conversion of cinnamic acid to bromostyrene in presence of various solvent and group-1 metal catalysts. (Table Removed) Table 2: Conversion of cinnamic acid to bromostyrene in presence of various solvent and tetraalkylammonium salts as catalysts (Table Removed) According to the present invention, the reaction of cinnamic acid (8 equiv.) with N-bromosuccinimide (11.5 equiv.) and tetrabutylammonium trifluoroacetate (1 equiv.) in dichloroethane (16 ml_) at ambient temperature for 6 h furnished after work-up p-bromostyrene in 73% isolated yield.. In contrast, uncatalysed reaction showed only 7-11% conversion. The methodology was extended to bromo, chloro and iododecarboxylation of various substituted cinnamic acids, propiolic acids and aromatic carboxylic acids as shown in Table 3, giving rise to good to excellent yields of corresponding halides. Table 3: Conversion of unsaturated carboxylic acid RCOOH to unsaturated halide RX [TBATFA = tetrabutylammonium trifluoroacetate] (Table Removed) Unsaturated organic halides are of potential importance in the synthesis of commercially significant organic intermediates. As an example, this invention also presents a short synthesis of the natural product piperine, a chief component of pepper. The strategy comprises of coupling the catalytic Hunsdiecker reaction with conventional Heck reaction. Reaction of piperonyl acrylic acid with N-iodosuccinimide under the invented protocol afforded 2-piperonyl-1-iodo-ethene in 73% isolated yield, the latter was coupled with 1-acryloxy piperidine under Heck condition to afford piperine in 51% isolated yield. Tsuboi and coworkers (Tetrahedron Letters 1979, 1043) described the synthesis of piperine using steps comprising of (i) reaction of piperonal with acetylene/KOH to generate 3-piperonyl-prop-1-yne-3-ol (ii) reaction of the latter with (2,2'-diethoxy)-N-ethylpyrrolidine in refluxing benzene. The invention is described in the examples given below which are produced by way of illustrations only and therefore should not be constrained to limit the scope of the invention. EXAMPLE-1: (2-PHENYL) VINYL BROMIDE: A mixture of N-bromosuccinimide (15.95 gm), cinnamic acid (11.85 gm) and LiOAC (10mol%) in MeCN\H2O (120 mL\4 mL) was stirred at ambient temperature for 4 h. Upon completion, solvent was evaporated and the residue was taken in ether and washed with brine and dried over magnesium sulfate and finally subjected to column chromatography (silica gel 60-12 mesh, eluent: ethylacetate\hexane:1:9) to furnish 9.7 gm of. 2-phenyl vinyl bromide EXAMPLE-2: (2-PHENYL) VINYL CHLORIDE: A mixture of N-chlorosuccinimide (1.4 gm), cinnamic acid (1.2 gm) and tetrabutylammonium trifluoroacetate (10mol%) in dichloroethane (12 mL) was stirred at ambient temperature for 16 h. Upon completion, solvent was evaporated and the residue was taken in ether and washed with brine and dried over MgSO4 and finally subjected to column chromatography (silica gel 60-12 mesh, eluent: ethylacetate\hexane:1:9) to furnish 940 mg of. 2-phenyl vinyl chloride. EXAMPLE-3: (2-PHENYL) VINYL IODIDE: A mixture of N-iodosuccinimide (2.0 gm), cinnamic acid (1.2 gm) and tetrabutylammonium trifluoroacetate (10mol%) in dichloroethane (12 mL) was stirred at ambient temperature for 20 h. Upon completion, solvent was evaporated and the residue was taken in ether and washed with brine and dried over MgSO4 and finally subjected to column chromatography (silica gel 60-12 mesh, eluent: ethylacetate\hexane:1:9) to furnish 225 mg of. 2-phenyl vinyl iodide. EXAMPLE-4: (4'-METHOXYPHENYL) VINYL BROMIDE: A mixture of N-bromosuccinimide (1.5 gm), 4'-methoxycinnamic acid (1.2 gm) and LiOAc (10 mol%) in MeCN\H20 (12 mL\0.5 mL) was stirred ambient temperature for 0.2 h. After solvent removal, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.1 gm 4'-methoxyphenyl vinyl bromide. EXAMPLE-5: (4'-METHOXYPHENYL) VINYL CHLORIDE: A mixture of N-chlorosuccinimide (1.4 gm), 4'-methoxycinnamic acid (1.2 gm) and tetrabutylammonium trifluroacetate (10 mol%) in chloroform (12 mL) was stirred ambient temperature for 6 h. After solvent removal, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.0 gm 4'-methoxyphenyl vinyl chloride. EXAMPLE-6: (4'-METHOXYPHENYL) VINYL IODIDE: A mixture of N-iodosuccinimide (1.5 gm), 4'-methoxycinnamic acid (1.2 gm) and tetrabutylammonium trifluroacetate (20 mol%) in dichloroethane (20 mL) was stirred at ambient temperature for 4 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.1 gm 4'-methoxy, phenyl vinyl iodide. EXAMPLE-7: 9-ANTHRACENYL VINYL BROMIDE: A mixture of N-bromosuccinimide (1.5 gm), 9-anthracenyl acrylic acid (1.9 gm) and tetrabutylammonium trifluroacetate (10 mol%) in chloroform (12 mL) was stirred ambient temperature for 4 h. After solvent removal, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.0 gm 9-anthracenyl vinyl bromide. EXAMPLE-8: 2-PIPERONYL VINYL IODIDE: A mixture of N-iodosuccinimide (5.5 gm), piperonyl acrylic acid (4.2 gm) and tetrabutylammonium trifluroacetate (10 mol%) in dichloroethane (60 mL) was stirred ambient temperature for 10 h. After solvent removal, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 4.2 gm 2-piperonylvinyl iodide. EXAMPLE-9: (2-PHENYL ) ACETYLENIC BROMIDE: A mixture of N-bromosuccinimide (8 gm), phenyl acetylenic acid (6.5 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (60mL) was stirred at ambient temperature for 0.5 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 6.2 gm. 2-phenyl acetylenic bromide. EXAMPLE-10: (2-PHENYL ) ACETYLENIC IODIDE: A mixture of N-iodosuccinimide (6 gm), phenyl acetylenic acid (3.0 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (30mL) was stirred at ambient temperature for 0.25 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 2.9 gm. 2-phenyl acetylenic iodide. EXAMPLE-11: (4-METHOXYPHENYL ) ACETYLENIC IODIDE: A mixture of N-iodosuccinimide (3 gm), 4-methoxyphenyl acetylenic acid (1.6 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (15mL) was stirred at ambient temperature for 0.25 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.3 gm. 4-methoxyphenyl acetylenic iodide. EXAMPLE-12: (4'-METHYLPHENYL ) ACETYLENIC BROMIDE: A mixture of N-bromosuccinimide (3 gm), 4-methylphenyl acetylenic acid (1.5 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (15mL) was stirred at ambient temperature for 0.25 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 930 mg. 4'-methylphenyl acetylenic iodide. EXAMPLE-13: (1-NAPHTHYL) ACETYLENIC IODIDE: A mixture of N-iodosuccinimide (1.12 gm), naphthyl acetylenic acid (6.5 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (60mL) was stirred at ambient temperature for 0.25 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.09 gm of 1-naphthyl acetylenic iodide. EXAMPLE-14: (2-FURYL ) ACETYLENIC IODIDE: A mixture of N-iodosuccinimide (3 gm), 2-furyl acetylenic acid (1.7 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (15mL) was stirred at ambient temperature for 0.25 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.1 gm. 2-furyl acetylenic iodide. EXAMPLE-15: (2-THI EN YL ) ACETYLENIC IODIDE: A mixture of N-iodosuccinimide (3 gm), 2-thienyl acetylenic acid (1.8 gm) and tetrabutylammonium trifluoroacetate (20 mol%) in dichloroethane (15ml_) was stirred at ambient temperature for 0.25 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:1:9) and afforded 1.5 gm. 2-thienyl acetylenic iodide. EXAMPLE-16: BROMOBENZENE A mixture of N-bromosuccinimide (3 gm), benzoic acid (2.2 gm) and tetrabutylammonium trifluororacetate (20 mol%) in dichloroethane (30 ml_) was stirred at ambient temperature for 24 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:2:8) and afforded 924 mg of. bromobenzene. EXAMPLE-17: (4-METHOXY) BROMOBENZENE A mixture of N-bromosuccinimide (3 gm), 4-methoxybenzoic acid (2.6 gm) and tetrabutylammonium trifluororacetate (20 mol%) in dichloroethane (30 ml_) was stirred at ambient temperature for 18 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:2:8) and afforded 2.34 gm of. 4-methoxybromobenzene. EXAMPLE-18: (4-METHYL) BROMOBENZENE A mixture of N-bromosuccinimide (3 gm), 4-methylbenzoic acid (2.4 gm) and tetrabutylammonium trifluororacetate (20 mol%) in dichloroethane (30 ml) was stirred at ambient temperature for 20 h. After evaporation of solvent, the mixture was subjected to column chromatography (silica gel 60-120 mesh, eluent: ethyl acetate\hexane:2:8) and afforded 1.2 gm of. 4-methylbromobenzene. The present invention provides, for the first time, a catalytic route to unsaturated organic halides utilizing reagents that are safe to handle. The good to excellent yields of the products are noteworthy. The process also does not use toxic halogens such as molecular bromine or iodine. The reactions are highly atom-economic, since the by-product of the reaction is succinimide, which is easily removable and could be re-used to synthesize N-halosuccinimides. WE CLAIM: 1. A novel catalytic process for the preparation of unsaturated organic halides of formula RX where R represents alkenyl, alkynyl and aromatic groups, which comprises of reacting an organic unsaturated carboxylic acid of formula RCOOH wherein R is as stated above with N- haloacidimides in presence of a catalyst selected from group 1 metal salt or tetraalkyl ammonium salt of the kind such as herein described in halogenated solvent at ambient temperature for a period in the range of 25 min to 24 h, recovering the unsaturated halides of Formula RX by known methods wherein R is as stated above. 2. A process as claimed in claim 1, wherein the unsaturated carboxylic acids used are selected from alkyl or aryl substituted alkenic acid, alkyl or aryl substituted alkynic acid, alkyl or aryl substituted aromatic carboxylic acid. 3. A process as claimed in claims 1-2, wherein the N-halosuccinimide used is selected from N- bromosuccinimide, N-iodosuccinimide, N-chlorosuccinimide, N-bromophthalimide, N- iodophthalimide, N-chlorophthalimide. 4. A process as claimed in claims 1-3, wherein the catalyst used is group 1 metal salt selected from lithium acetate, sodium acetate, potassium acetate, cesium acetate and tetraalkyl ammonium salt such as tetrabutylammonium hydroxide, acetate, halide, trifluoroacetate, wherein tetraalkyl group may be such as tetramethyl, tetraethyl, tetrabutyl, tetrabenzyl, trimethylbenzyl, triethylbenzyl, cetyltriethyl. 5. A process as claimed in claims 1-4, wherein the solvent used is halogenated solvent is selected from dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrachloroethane and acetonitrile-water. 6. A novel catalytic process for the preparation of unsaturated organic halides substantially as herein describe with reference to the examples.

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