Title of Invention	NOVEL α-HYDRAZINO-α,β-UNSATURATED NITRO COMPOUNDS AND METHODS OF PREPARATION THEREOF
Abstract	Novel α- hydrazino- α,β-unsaturated nitro compounds were synthesized from α,β- unsaturated nitro compounds and azo compounds and azo compounds in a one pot, atom economical operation in quantitave yield. The reaction catalyzed by an amine such as imidazole or 4-N,N-dimethlamino pyridine (DMAP) takes place at room temperatute in a variety of solvent and involves a novel C-N bond formation via coupling of the a-position of the α, β -unsaturated nitro compound with the azo compound. This method provides a novel route to natural/unnatural amino acids and other synthetically and biologically useful building blocks.

Title of Invention

NOVEL α-HYDRAZINO-α,β-UNSATURATED NITRO COMPOUNDS AND METHODS OF PREPARATION THEREOF

Abstract

Novel α- hydrazino- α,β-unsaturated nitro compounds were synthesized from α,β- unsaturated nitro compounds and azo compounds and azo compounds in a one pot, atom economical operation in quantitave yield. The reaction catalyzed by an amine such as imidazole or 4-N,N-dimethlamino pyridine (DMAP) takes place at room temperatute in a variety of solvent and involves a novel C-N bond formation via coupling of the a-position of the α, β -unsaturated nitro compound with the azo compound. This method provides a novel route to natural/unnatural amino acids and other synthetically and biologically useful building blocks.

Full Text	FORM - 2 THE PATENTS ACT 1970 39 OF 1970 COMPLETE SPECIFICATION (See Section 10) TITLE OF INVENTION A FACILE AND EFFICIENT SYNTHESIS OF a-HYDRAZINO-a,b-UNSATURATED NITRO COMPOUNDS (a) INDIAN INSTITUTE OF TECHNOLOGY BOMBAY (b) having administrative office at Powai, Mumbai 400 076, State of maharashtra, India and (c) an autonomous educational institute, and established in India under the Institutes of Technology Act 1961. The following specification particularly describes the nature of the invention and the manner in which it is to be performed. Field of invention This invention relates to the preparation of novel a-hydrazino-α,-unsaturated nitro compounds including process for their preparation. Background of invention and prior art The coupling of the a-position of activated alkenes (vinyl anion equivalents) with various carbon electrophiles mediated by a tertiary amine or tertiary phosphine, popularly known as the Morita-Baylis-Hillman (MBH) reaction, has emerged as an important C-C bond forming reaction in organic synthesis [Chem. Rev. 2003, 103, 811]. It provides a simple, convenient and one-pot methodology for the synthesis of densely functionalized molecules in a highly atom-economical fashion. However, O N bond formation via similar strategy has been scarcely investigated despite the fact that ON bond forming strategies offer convenient entry into natural/unnatural amino acids and other synthetically and biologically useful building blocks. Synthesis of a-hydraziona,β-unsaturated compounds via the above mentioned strategy is reported in publications Tetrahedron 2004, 60, 2083 for acrylates and acrylonitrile with azodicarboxylates and Tetrahedron Lett. 1998, 39, 7323 for vinyl ketones with azodicarboxylates, both in the presence of diazabicyclo-[2.2.2]-octane (DABCO) as the catalyst. 222222 nucleophilicity of the nitronate (arising from initial Michael type addition of the nucleophilic amine catalyst) and the propensity of the nitroalkenes to undergo polymerization, all previous attempts to carry out the MBH type reaction of nitroalkenes were fraught with difficulties. The publications in Ger. Offen. 1972, DE 2155113; Chem.Abstr. 1972, 77, 434174 and U. S. Patent 1973, US 3743669 disclose that nitroethylene reacts with an aldehyde (RCHO) in the presence of a cyclic tertiary amine such as DABCO to produce 2-(l-hydroxyalkyl) nitroethylene. The publication in Tetrahedron Lett. 2004, 45, 4745 describes reactions of β-aryl-α,β-unsaturated nitro compounds with formaldehyde in the presence of imidazole to yield α-hydroxymethyl-β-aryl-α,β-unsaturated nitro compounds. These compounds have been found to inhibit human cervical cancer cell proliferation by binding to microtubules/tubulins. It has been a long standing need in the industry and in the scientific community to provide facile methods for ON bond formation which have wide applications especially in the synthesis of amino acids and other biologically useful building blocks. Objects of the invention It is the object of this invention to provide novel α-hydrazino- α,β-unsaturated nitro compounds in high chemical yields. A further object of this invention is to provide commercially viable single pot process for the preparation of α-hydrazino-α,β-unsaturated nitro compounds from α,β-unsaturated nitro compounds in high yields. 3 Detailed description of the invention According to the present invention surprisingly a conjugated nitroalkene when reacted with an azo compound in the presence of a cyclic or acyclic amine as catalyst produces α-hydrazino- α,β-unsaturated nitro compound. A typical procedure involves stirring a solution of nitroalkene and azo compound in a solvent at room temperature (~25 °C) until the reaction goes to completion. The reaction mixture is then diluted with aqueous acid and the layers are separated. The aqueous layer is extracted with a suitable organic solvent, the combined organic layers are concentrated to yield a substantially pure α-hydrazino-α,β-unsaturated nitro compound. Typical nitroalkenes include those with substituents P to the nitro group. The substituent could be alkyl, aryl, aralkyl or alkaryl group. Further, The substituent could be cyclic or open chain, branched or straight chain, could contain or devoid of hetero atoms. Following are representative examples of nitroalkenes suitable for the present invention'- 2-(furan-2-yl) nitroethylene, 2-(thiophene-2-yl) nitroethylene, 2-(furan-3-yl nitroethylene, 2-(thiophene-2-yl) nitroethylene, 2-(indole-3-yl) nitroethylene, 2-(2, 3 or 4-pyridyl) nitroethylene, 2-(phenyl) nitroethylene, 2-(2, 3 or 4-substituted-phenyl) nitroethylene, 2-(l or 2-naphthyl) nitroethylene, 2-methyl nitroethylene, 2-heptyl nitroethylene, 2-cyclohexyl nitroethylene and their like. The azo compounds include those with two of the groups such as carboxylic acid (COOH), esters of carboxylic acid (COOR, where R = ethyl, iso-propyl etc), COR, CONR2, CN, CF3, RSO2 and their like attached to -N=N-. Typical amines are secondary or tertiary amines, cyclic or acyclic, containing one or more N atoms. Representative examples are imidazole and its substituted analogs, 4 4-N, N-dimethylamino pyridine (DMAP), its isomers and substituted analogs, amines in which these moieties are fused to other rings, e.g. a benzene ring. However, imidazole and DMAP are preferred. The reaction can be carried out in the absence or in the presence of a range of solvents or mixtures thereof selected from alkanols such as methanol, ethanol, cyclohexanol and their like, open chain and cyclic ether solvents such as diethyl ether, tetrahydrofuran (THF), 1,4-dioxan and their like, halogenated solvents such as dicholoromethane, chloroform and their like, hydrocarbon solvents such as toluene, benzene and their like. Other suitable solvents include acetonitrile, dimethyl formamide, dimethyl sulfoxide, acetone and ethyl acetate. These solvents do not react with either of the coupling partners, viz. nitroalkene or azo compound. Although the reaction can be carried out over a wide range of temperatures from -100 to 200 °C depending on the solvent used, the preferred temperature range is 20-30 °C. The ratio of nitroalkene to the azo compound may vary, but the preferred range is 1:1 to 1-1.5. The catalyst loading may vary from 10 to 200 mol %, with 100 mol % preferred. In an embodiment of the invention the reaction is preferably carried out in the dark. In another embodiment of the invention the reaction is carried out under inert atmosphere. The invention is now illustrated with a few representative but non-limiting examples (see Tables 1 and 2 below). 5 Example 1. Preparation of (E)-diisopropyl-(2-(furan-2-yl)-l-nitrovinyl) hydrazine-1,2- dicarboxylate 3a. To a stirred solution of 2-(furan-2-yl) nitroethylene la (139 mg, 1 mmol) in THF (2 ml), under N2 and in dark, was added imidazole (68 mg, 1 mmol) followed by diisopropyl azodicarboxylate 2a (303 mg, 1.5 mmol) and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HC1 (10 ml). The aqueous layer was extracted with ethyl acetate (3x10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3 x 5 ml) to afford pure (E)-diisopropyl-(2-(furan-2-yl)-r nitrovinyl)hydrazine-1,2-dicarboxylate 3a as a yellow solid. "Yield 334 mg, 98 %, m. p. 138°C. Example 2. Preparation of (E)-diethyl-(2-(4-methoxyphenyl)-l-nitrovinyl) hydrazine-1,2-dicarboxylate 4f. 6 To a stirred solution of 2-(4-methoxyphenyl) nitroethylene If (179 mg, 1 mmol) in THF (2 ml), under N2 and in dark, was added imidazole (68 mg, 1 mmol) followed by diethyl azodicarboxylate 2b (261 mg, 1.5 mmol) and the reaction mixture was stirred at room temperature for 3V& h. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HC1 (10 ml). The aqueous layer was extracted with ethyl acetate (3 x 10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3x5 ml) to afford pure CE)-diethyl-(2-(4-methoxyphenyl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 4f as a yellow solid. Yield 332 mg, 94 %, m. p. 110-112 °C. Example 3. Preparation of ($-diisopropyl-(2-(thiophene-2-yl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 3b. To a stirred solution of 2-(thiophene-2-yl) nitroethylene lb (155 mg, 1 mmol) in acetonitrile (2 ml), under N2 and in dark, was added DMAP (122 mg, 1 mmol) followed by diisopropyl azodicarboxylate 2a (263 mg, 1.3 mmol) and the reaction mixture was stirred at room temperature for 45 min. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HC1 (10 ml). The aqueous layer was extracted with ethyl acetate (3 x 10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3x5 ml) to afford pure (E)-diisopropyl-(2-(thiophene-2-yl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 3b as a yellow solid. Yield 307 mg, 86 %, m. p. 135-137 °C. 7 Example 4. Preparation of (.E)-Diisopropyl-(2-(benzo[d][l,3]dioxol-5-yl)-l-nitrovinyl)hydrazine-1,2dicarboxylate 3h. To a stirred solution of 2-(benzo[d][l,3]dioxol-5-yl) nitroethylene lh (193 mg, 1 mmol) in acetonitrile (2 ml), under Kb and in dark, was added DMAP (122 mg, 1 mmol) followed by diisopropyl azodicarboxylate 2a (263 mg, 1.3 mmol) and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HCl (10 ml). The aqueous layer was extracted with ethyl acetate (3 x 10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3x5 ml) to afford pure (J5)"Diisopropyl-(2-(benzo[d][l,3]dioxol-5-yl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 3h as a yellow solid. Yield 324 mg, 82 %, m. p. 98-99 °C. Other examples including those detailed above are listed in the following tables. 8 Table 2. The MBH reaction of nitroalkenes 1 with DEAD 2aa in the presence of 100 mol % imidazole in THF or 100 mol % DMAP in acetonitrile at room temperature. 9 10 We claim- 1. Novel vinylic nitro compounds of formula 5 possessing a hydrazino group at the a position and substituent R, β to the nitro group wherein R is alkyl, aryl, aralkyl, alkaryl and their like; E is a group such as COOR', COR', CONR2\ CN, CF3,R'S02 and their like. 2. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claim 1 comprising reaction of a vinylic nitro compound with an azo compound in the presence of an amine catalyst optionally in an inert solvent. 3. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claim 1 comprising stirring a solution of nitroalkene and azo compound optionally in a solvent until the reaction goes to completion, the said reaction mixture then diluted with aqueous acid and the layers separated, the said aqueous layer extracted with a suitable organic solvent, the combined organic layers being concentrated to yield the desired product. 4. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-3 wherein the reactant azo compound is an open chain or cyclic one with groups selected from COOR', COR', CONR2', CN, CF3) R'S02 and their like attached to -N=N-. 5. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-4 wherein the catalyst is selected from imidazole, DMAP and their like. 11 6. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-5 wherein the solvents if used is selected from alkanols, ethers, hydrocarbons, halogenated solvents, DMF, DMSO, acetone, acetonitrile and ethyl acetate. 7. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-6 wherein the molar ratio of the reactants, nitroalkene and azo compound, vary from 1:0.05 to 0.05:1 and the catalyst loading varying from 0.5 to 30 % of the combined weight of the reactants. 8. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-7 wherein the reaction is carried out at -100 to 200 °C, preferably at 20-30 °C. 9. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-8 wherein the preferred ratio of nitroalkene to the azo compound is 1^1 to 1^1.5. 10. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-9 wherein the catalyst loading is 10 to 200 mol %, with the preferred loading of 100 mol % . Dated: 10th Nov 2005 12 Abstract Novel α-hydrazino-α,β-unsaturated nitro compounds were synthesized from a,(3-unsaturated nitro compounds and azo compounds in a one pot, atom economical operation in quantitative yield. The reaction catalyzed by an amine such as imidazole or 4-N,N-dimethylamino pyridine (DMAP) takes place at room temperature in a variety of solvents and involves a novel ON bond formation via coupling of the a-position of the a,(3-unsaturated nitro compound with the azo compound. This method provides a novel route to natural/unnatural amino acids and other synthetically and biologically useful building blocks. 13

Full Text

FORM - 2
THE PATENTS ACT 1970
39 OF 1970
COMPLETE SPECIFICATION
(See Section 10)
TITLE OF INVENTION
A FACILE AND EFFICIENT SYNTHESIS OF
a-HYDRAZINO-a,b-UNSATURATED
NITRO COMPOUNDS
(a) INDIAN INSTITUTE OF TECHNOLOGY BOMBAY (b) having administrative office at Powai, Mumbai 400 076, State of maharashtra, India and (c) an autonomous educational institute, and established in India under the Institutes of Technology Act 1961.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

Field of invention
This invention relates to the preparation of novel a-hydrazino-α,-unsaturated nitro compounds including process for their preparation.
Background of invention and prior art
The coupling of the a-position of activated alkenes (vinyl anion equivalents) with various carbon electrophiles mediated by a tertiary amine or tertiary phosphine, popularly known as the Morita-Baylis-Hillman (MBH) reaction, has emerged as an important C-C bond forming reaction in organic synthesis [Chem. Rev. 2003, 103, 811]. It provides a simple, convenient and one-pot methodology for the synthesis of densely functionalized molecules in a highly atom-economical fashion. However, O N bond formation via similar strategy has been scarcely investigated despite the fact that ON bond forming strategies offer convenient entry into natural/unnatural amino acids and other synthetically and biologically useful building blocks. Synthesis of a-hydraziona,β-unsaturated compounds via the above mentioned strategy is reported in publications Tetrahedron 2004, 60, 2083 for acrylates and acrylonitrile with azodicarboxylates and Tetrahedron Lett. 1998, 39, 7323 for vinyl ketones with azodicarboxylates, both in the presence of diazabicyclo-[2.2.2]-octane (DABCO) as the catalyst.
222222

nucleophilicity of the nitronate (arising from initial Michael type addition of the nucleophilic amine catalyst) and the propensity of the nitroalkenes to undergo polymerization, all previous attempts to carry out the MBH type reaction of nitroalkenes were fraught with difficulties.
The publications in Ger. Offen. 1972, DE 2155113; Chem.Abstr. 1972, 77, 434174 and U. S. Patent 1973, US 3743669 disclose that nitroethylene reacts with an aldehyde (RCHO) in the presence of a cyclic tertiary amine such as DABCO to produce 2-(l-hydroxyalkyl) nitroethylene. The publication in Tetrahedron Lett. 2004, 45, 4745 describes reactions of β-aryl-α,β-unsaturated nitro compounds with formaldehyde in the presence of imidazole to yield α-hydroxymethyl-β-aryl-α,β-unsaturated nitro compounds. These compounds have been found to inhibit human cervical cancer cell proliferation by binding to microtubules/tubulins.
It has been a long standing need in the industry and in the scientific community to provide facile methods for ON bond formation which have wide applications especially in the synthesis of amino acids and other biologically useful building blocks.
Objects of the invention
It is the object of this invention to provide novel α-hydrazino- α,β-unsaturated nitro compounds in high chemical yields.
A further object of this invention is to provide commercially viable single pot process for the preparation of α-hydrazino-α,β-unsaturated nitro compounds from α,β-unsaturated nitro compounds in high yields.
3
Detailed description of the invention
According to the present invention surprisingly a conjugated nitroalkene when reacted with an azo compound in the presence of a cyclic or acyclic amine as catalyst produces α-hydrazino- α,β-unsaturated nitro compound.
A typical procedure involves stirring a solution of nitroalkene and azo compound in a solvent at room temperature (~25 °C) until the reaction goes to completion. The reaction mixture is then diluted with aqueous acid and the layers are separated. The aqueous layer is extracted with a suitable organic solvent, the combined organic layers are concentrated to yield a substantially pure α-hydrazino-α,β-unsaturated nitro compound.
Typical nitroalkenes include those with substituents P to the nitro group. The substituent could be alkyl, aryl, aralkyl or alkaryl group. Further, The substituent could be cyclic or open chain, branched or straight chain, could contain or devoid of hetero atoms. Following are representative examples of nitroalkenes suitable for the present invention'- 2-(furan-2-yl) nitroethylene, 2-(thiophene-2-yl) nitroethylene, 2-(furan-3-yl nitroethylene, 2-(thiophene-2-yl) nitroethylene, 2-(indole-3-yl) nitroethylene, 2-(2, 3 or 4-pyridyl) nitroethylene, 2-(phenyl) nitroethylene, 2-(2, 3 or 4-substituted-phenyl) nitroethylene, 2-(l or 2-naphthyl) nitroethylene, 2-methyl nitroethylene, 2-heptyl nitroethylene, 2-cyclohexyl nitroethylene and their like.
The azo compounds include those with two of the groups such as carboxylic acid (COOH), esters of carboxylic acid (COOR, where R = ethyl, iso-propyl etc), COR, CONR2, CN, CF3, RSO2 and their like attached to -N=N-.
Typical amines are secondary or tertiary amines, cyclic or acyclic, containing one or more N atoms. Representative examples are imidazole and its substituted analogs,
4
4-N, N-dimethylamino pyridine (DMAP), its isomers and substituted analogs, amines in which these moieties are fused to other rings, e.g. a benzene ring. However, imidazole and DMAP are preferred.
The reaction can be carried out in the absence or in the presence of a range of solvents or mixtures thereof selected from alkanols such as methanol, ethanol, cyclohexanol and their like, open chain and cyclic ether solvents such as diethyl ether, tetrahydrofuran (THF), 1,4-dioxan and their like, halogenated solvents such as dicholoromethane, chloroform and their like, hydrocarbon solvents such as toluene, benzene and their like. Other suitable solvents include acetonitrile, dimethyl formamide, dimethyl sulfoxide, acetone and ethyl acetate. These solvents do not react with either of the coupling partners, viz. nitroalkene or azo compound.
Although the reaction can be carried out over a wide range of temperatures from -100 to 200 °C depending on the solvent used, the preferred temperature range is 20-30 °C.
The ratio of nitroalkene to the azo compound may vary, but the preferred range is 1:1 to 1-1.5. The catalyst loading may vary from 10 to 200 mol %, with 100 mol % preferred.
In an embodiment of the invention the reaction is preferably carried out in the dark.
In another embodiment of the invention the reaction is carried out under inert atmosphere.
The invention is now illustrated with a few representative but non-limiting examples (see Tables 1 and 2 below).
5

Example 1.
Preparation of (E)-diisopropyl-(2-(furan-2-yl)-l-nitrovinyl) hydrazine-1,2-
dicarboxylate 3a.

To a stirred solution of 2-(furan-2-yl) nitroethylene la (139 mg, 1 mmol) in THF (2 ml), under N2 and in dark, was added imidazole (68 mg, 1 mmol) followed by diisopropyl azodicarboxylate 2a (303 mg, 1.5 mmol) and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HC1 (10 ml). The aqueous layer was extracted with ethyl acetate (3x10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3 x 5 ml) to afford pure (E)-diisopropyl-(2-(furan-2-yl)-r nitrovinyl)hydrazine-1,2-dicarboxylate 3a as a yellow solid. "Yield 334 mg, 98 %, m. p. 138°C.
Example 2.
Preparation of (E)-diethyl-(2-(4-methoxyphenyl)-l-nitrovinyl) hydrazine-1,2-dicarboxylate 4f.
6

To a stirred solution of 2-(4-methoxyphenyl) nitroethylene If (179 mg, 1 mmol) in THF (2 ml), under N2 and in dark, was added imidazole (68 mg, 1 mmol) followed by diethyl azodicarboxylate 2b (261 mg, 1.5 mmol) and the reaction mixture was stirred at room temperature for 3V& h. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HC1 (10 ml). The aqueous layer was extracted with ethyl acetate (3 x 10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3x5 ml) to afford pure CE)-diethyl-(2-(4-methoxyphenyl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 4f as a yellow solid. Yield 332 mg, 94 %, m. p. 110-112 °C.
Example 3.
Preparation of ($-diisopropyl-(2-(thiophene-2-yl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 3b.

To a stirred solution of 2-(thiophene-2-yl) nitroethylene lb (155 mg, 1 mmol) in acetonitrile (2 ml), under N2 and in dark, was added DMAP (122 mg, 1 mmol) followed by diisopropyl azodicarboxylate 2a (263 mg, 1.3 mmol) and the reaction mixture was stirred at room temperature for 45 min. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HC1 (10 ml). The aqueous layer was extracted with ethyl acetate (3 x 10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3x5 ml) to afford pure (E)-diisopropyl-(2-(thiophene-2-yl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 3b as a yellow solid. Yield 307 mg, 86 %, m. p. 135-137 °C.
7

Example 4.
Preparation of (.E)-Diisopropyl-(2-(benzo[d][l,3]dioxol-5-yl)-l-nitrovinyl)hydrazine-1,2dicarboxylate 3h.

To a stirred solution of 2-(benzo[d][l,3]dioxol-5-yl) nitroethylene lh (193 mg, 1 mmol) in acetonitrile (2 ml), under Kb and in dark, was added DMAP (122 mg, 1 mmol) followed by diisopropyl azodicarboxylate 2a (263 mg, 1.3 mmol) and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then diluted with water (10 ml) and acidified with 5N HCl (10 ml). The aqueous layer was extracted with ethyl acetate (3 x 10 ml), the combined organic layers were washed with brine (20 ml), dried over anhydrous Na2S04 and concentrated. The crude residue was rinsed with pet. ether (3x5 ml) to afford pure (J5)"Diisopropyl-(2-(benzo[d][l,3]dioxol-5-yl)-l-nitrovinyl)hydrazine-l,2-dicarboxylate 3h as a yellow solid. Yield 324 mg, 82 %, m. p. 98-99 °C.
Other examples including those detailed above are listed in the following tables.

8

Table 2. The MBH reaction of nitroalkenes 1 with DEAD 2aa in the presence of 100 mol % imidazole in THF or 100 mol % DMAP in acetonitrile at room temperature.

9

10

We claim-
1. Novel vinylic nitro compounds of formula 5 possessing a hydrazino group at the
a position and substituent R, β to the nitro group wherein R is alkyl, aryl,
aralkyl, alkaryl and their like; E is a group such as COOR', COR', CONR2\ CN,
CF3,R'S02 and their like.

2. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claim 1 comprising reaction of a vinylic nitro compound with an azo compound in the presence of an amine catalyst optionally in an inert solvent.
3. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claim 1 comprising stirring a solution of nitroalkene and azo compound optionally in a solvent until the reaction goes to completion, the said reaction mixture then diluted with aqueous acid and the layers separated, the said aqueous layer extracted with a suitable organic solvent, the combined organic layers being concentrated to yield the desired product.
4. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-3 wherein the reactant azo compound is an open chain or cyclic one with groups selected from COOR', COR', CONR2', CN, CF3) R'S02 and their like attached to -N=N-.
5. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-4 wherein the catalyst is selected from imidazole, DMAP and their like.
11

6. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-5 wherein the solvents if used is selected from alkanols, ethers, hydrocarbons, halogenated solvents, DMF, DMSO, acetone, acetonitrile and ethyl acetate.
7. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-6 wherein the molar ratio of the reactants, nitroalkene and azo compound, vary from 1:0.05 to 0.05:1 and the catalyst loading varying from 0.5 to 30 % of the combined weight of the reactants.
8. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-7 wherein the reaction is carried out at -100 to 200 °C, preferably at 20-30 °C.
9. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-8 wherein the preferred ratio of nitroalkene to the azo compound is 1^1 to 1^1.5.
10. A process for the preparation of novel vinylic nitro compounds of formula 5 as claimed in claims 1-9 wherein the catalyst loading is 10 to 200 mol %, with the preferred loading of 100 mol % .

Dated: 10th Nov 2005

12

Abstract
Novel α-hydrazino-α,β-unsaturated nitro compounds were synthesized from a,(3-unsaturated nitro compounds and azo compounds in a one pot, atom economical operation in quantitative yield. The reaction catalyzed by an amine such as imidazole or 4-N,N-dimethylamino pyridine (DMAP) takes place at room temperature in a variety of solvents and involves a novel ON bond formation via coupling of the a-position of the a,(3-unsaturated nitro compound with the azo compound. This method provides a novel route to natural/unnatural amino acids and other synthetically and biologically useful building blocks.
13

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1410-mum-2005-form-26.pdf

1410-mum-2005-form-3.pdf

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Patent Number

226803

Indian Patent Application Number

1410/MUM/2005

PG Journal Number

10/2009

Publication Date

06-Mar-2009

Grant Date

24-Dec-2008

Date of Filing

11-Nov-2005

Name of Patentee

INDIAN INSTITUTE OF TECHNOLOGY, BOMBAY

Applicant Address

Indian Institute of Techonolgy, Bombay, Powai, Mumbai 400 076,

Inventors:

#	Inventor's Name	Inventor's Address
1	NAMBOOTHIRI IRISHI N N	INDIAN INSTITUTE OF TECHNOLOGY, BOMBAY,POWAI, MUMBAI-400 076
2	DADWAL MAMTA	Flat No. 301 Bldg. A, Raheja Nest, Chandivil Rd, Powai, Mumbai 400 072

PCT International Classification Number

C07D7/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA