cyclohex-3-ene-1-carbaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Examples of suitable cyclic polyaldehydes are trans-1,3-cyclohexanedicarboxaldehyde; cis-1,3-cyclohexanedicarboxaldehyde; trans-1,4-cyclohexanedicarboxaldehyde; cis-1,4-cyclohexanedicarboxaldehyde; a mixture of 1,3-cyclohexanedicarboxaldehydes and 1,4-cyclohexanedicarboxaldehydes, preferably a 1-to-1 mixture thereof; exo,exo-2,5-norbornanedicarboxaldehyde; exo,exo-2,6-norbornanedicarboxaldehyde; exo,endo-2,5-norbornanedicarboxaldehyde; exo,endo-2,6-norbornanedicarboxaldehyde; endo,endo-2,5-norbornanedicarboxaldehyde; endo,endo-2,6-norbornanedicarboxaldehyde product (endo and exo mixture); 3-(3-formylcyclohexyl)propanal; 3-(4-formylcyclohexyl)propanal; 2-(3-formylcyclohexyl)propanal; 2-(4-formylcyclohexyl)propanal; and cyclododecane-1,4,8-tricarbaldehyde. The trans-1,3-cyclohexanedicarboxaldehyde; cis-1,3-cyclohexanedicarboxaldehyde; trans-1,4-cyclohexanedicarboxaldehyde; and cis-1,4-cyclohexanedicarboxaldehyde can be prepared by a process comprising hydroformylating 3-cyclohexene-1-carboxaldehyde using the hydroformylating conditions described later. The 1:1 mixture of 1,3- and 1,4-cyclohexanedicarboxaldehydes can be prepared by a process comprising reacting acrolein and 1,3-butadiene in a Diels-Alder reaction to give 3-cyclohexenecarboxaldehyde (also called 1,2,3,6-tetrahydrobenzaldehyde), and hydroformylating the 3-cyclohexenecarboxaldehyde. The exo,exo-2,5-norbornanedicarboxaldehyde; exo,exo-2,6-norbornanedicarboxaldehyde; exo,endo-2,5-norbornanedicarboxaldehyde; exo,endo-2,6-norbornanedicarboxaldehyde; endo,endo-2,5-norbornanedicarboxaldehyde; and endo,endo-2,6-norbornanedicarboxaldehyde product (endo and exo mixture) can be prepared by a process comprising reacting acrolein and cyclopentadiene in a Diels-Alder reaction to give a 2-norbornene-5-carboxaldehyde, and hydroformylating the 2-norbornene-5-carboxaldehyde. The 3-(3-formylcyclohexyl)propanal; 3-(4-formylcyclohexyl)propanal; 2-(3-formylcyclohexyl)propanal; and 2-(4-formylcyclohexyl)propanal can be prepared by a process comprising hydroformylating vinyl cyclohexene. The cyclododecane-1,4,8-tricarbaldehyde can be prepared by a process comprising trimerizing 1,3-butadiene to give 1,4,8-cyclododecatriene, and hydroformylating the 1,4,8-cyclododecatriene. in a Diels-Alder reaction

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 100 ml of methanol was dissolved 25.7 g of [2-methoxy-3-(methoxycarbonyl)allyl]triphenylphosphonium bromide, and to this solution was added dropwise 10.5 g of a 28% by weight solution of sodium methoxide in methanol with stirring at room temperature over 10 minutes. To the mixed solution was then further added 5 g of 1,2,3,6-tetrahydrobenzaldehyde at room temperature and the resulting mixture was subjected to reaction at the same temperature for 2 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and to the residue was added 50 ml of water. The resulting mixture was extracted with 50 ml of chloroform. The extract was dried with anhydrous magnesium sulfate, and the solvent was then removed by distillation under reduced pressure. The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-haxane (3:1 by volume) mixture) to obtain an oily substance. This oily substance was dissolved in 100 ml of dioxane, and to the solution was then added 100 ml of 0.1N sulfuric acid. The resulting mixture was subjected to reaction at 100° C. for 1.5 hours. The solvent was then removed by distillation under reduced pressure, and to the residue was added 100 ml of chloroform. The resulting mixture was washed with 100 ml of water. The organic layer was separated, and dried with anhydrous magnesium sulfate and then the solvent was removed by distillation under reduced pressure. The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-hexane (3:1 by volume) mixture) to obtain 7.5 g of oily methyl 5-(cyclohexen-4-yl)-3-oxo-4-pentenoate. After completion of the reaction the solvent was removed by distillation under reduced pressure to the residue was added 50 ml of water The resulting mixture was extracted with 50 ml of chloroform The extract was dried with anhydrous magnesium sulfate the solvent was then removed by distillation under reduced pressure The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-haxane (3:1 by volume) mixture) to obtain an oily substance The resulting mixture was subjected to reaction at 100° C. for 1.5 hours The solvent was then removed by distillation under reduced pressure to the residue was added 100 ml of chloroform The resulting mixture was washed with 100 ml of water The organic layer was separated dried with anhydrous magnesium sulfate the solvent was removed by distillation under reduced pressure The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-hexane (3:1 by volume) mixture)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 100 ml of methanol was dissolved 25.7 g of [2-methoxy-3-(methoxycarbonyl)allyl]triphenylphosphonium bromide, and to this solution was added dropwise 10.5 g of a 28% by weight solution of sodium methoxide in methanol with stirring at room temperature over 10 minutes. To the mixed solution was then further added 5 g of 1,2,3,6-tetrahydrobenzaldehyde at room temperature and the resulting mixture was subjected to reaction at the same temperature for 2 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and to the residue was added 50 ml of water. The resulting mixture was extracted with 50 ml of chloroform. The extract was dried with anhydrous magnesium sulfate, and the solvent was then removed by distillation under reduced pressure. The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-haxane (3:1 by volume) mixture) to obtain an oily substance. This oily substance was dissolved in 100 ml of dioxane, and to the solution was then added 100 ml of 0.1N sulfuric acid. The resulting mixture was subjected to reaction at 100° C. for 1.5 hours. The solvent was then removed by distillation under reduced pressure, and to the residue was added 100 ml of chloroform. The resulting mixture was washed with 100 ml of water. The organic layer was separated, and dried with anhydrous magnesium sulfate and then the solvent was removed by distillation under reduced pressure. The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-hexane (3:1 by volume) mixture) to obtain 7.5 g of oily methyl 5-(cyclohexen-4-yl)-3-oxo-4-pentenoate. After completion of the reaction the solvent was removed by distillation under reduced pressure to the residue was added 50 ml of water The resulting mixture was extracted with 50 ml of chloroform The extract was dried with anhydrous magnesium sulfate the solvent was then removed by distillation under reduced pressure The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-haxane (3:1 by volume) mixture) to obtain an oily substance The resulting mixture was subjected to reaction at 100° C. for 1.5 hours The solvent was then removed by distillation under reduced pressure to the residue was added 100 ml of chloroform The resulting mixture was washed with 100 ml of water The organic layer was separated dried with anhydrous magnesium sulfate the solvent was removed by distillation under reduced pressure The residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: benzene/n-hexane (3:1 by volume) mixture)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Examples of suitable cyclic polyaldehydes are trans-1,3-cyclohexanedicarboxaldehyde; cis-1,3-cyclohexanedicarboxaldehyde; trans-1,4-cyclohexanedicarboxaldehyde; cis-1,4-cyclohexanedicarboxaldehyde; a mixture of 1,3-cyclohexanedicarboxaldehydes and 1,4-cyclohexanedicarboxaldehydes, preferably a 1-to-1 mixture thereof; exo,exo-2,5-norbornanedicarboxaldehyde; exo,exo-2,6-norbornanedicarboxaldehyde; exo,endo-2,5-norbornanedicarboxaldehyde; exo,endo-2,6-norbornanedicarboxaldehyde; endo,endo-2,5-norbornanedicarboxaldehyde; endo,endo-2,6-norbornanedicarboxaldehyde product (endo and exo mixture); 3-(3-formylcyclohexyl)propanal; 3-(4-formylcyclohexyl)propanal; 2-(3-formylcyclohexyl)propanal; 2-(4-formylcyclohexyl)propanal; and cyclododecane-1,4,8-tricarbaldehyde. The trans-1,3-cyclohexanedicarboxaldehyde; cis-1,3-cyclohexanedicarboxaldehyde; trans-1,4-cyclohexanedicarboxaldehyde; and cis-1,4-cyclohexanedicarboxaldehyde can be prepared by a process comprising hydroformylating 3-cyclohexene-1-carboxaldehyde using the hydroformylating conditions described later. The 1:1 mixture of 1,3- and 1,4-cyclohexanedicarboxaldehydes can be prepared by a process comprising reacting acrolein and 1,3-butadiene in a Diels-Alder reaction to give 3-cyclohexenecarboxaldehyde (also called 1,2,3,6-tetrahydrobenzaldehyde), and hydroformylating the 3-cyclohexenecarboxaldehyde using the hydroformylating conditions described later. The exo,exo-2,5-norbornanedicarboxaldehyde; exo,exo-2,6-norbornanedicarboxaldehyde; exo,endo-2,5-norbornanedicarboxaldehyde; exo,endo-2,6-norbornanedicarboxaldehyde; endo,endo-2,5-norbornanedicarboxaldehyde; and endo,endo-2,6-norbornanedicarboxaldehyde product (endo and exo mixture) can be prepared by a process comprising reacting acrolein and cyclopentadiene in a Diels-Alder reaction to give a 2-norbornene-5-carboxaldehyde, and hydroformylating the 2-norbornene-5-carboxaldehyde using the hydroformylating conditions described later. The 3-(3-formylcyclohexyl)propanal; 3-(4-formylcyclohexyl)propanal; 2-(3-formylcyclohexyl)propanal; and 2-(4-formylcyclohexyl)propanal can be prepared by a process comprising hydroformylating vinyl cyclohexene. The cyclododecane-1,4,8-tricarbaldehyde can be prepared by a process comprising trimerizing 1,3-butadiene to give 1,4,8-cyclododecatriene, and hydroformylating the 1,4,8-cyclododecatriene using the hydroformylating conditions described later. in a Diels-Alder reaction

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Examples of suitable cyclic polyaldehydes are trans-1,3-cyclohexanedicarboxaldehyde; cis-1,3-cyclohexanedicarboxaldehyde; trans-1,4-cyclohexanedicarboxaldehyde; cis-1,4-cyclohexanedicarboxaldehyde; a mixture of 1,3-cyclohexanedicarboxaldehydes and 1,4-cyclohexanedicarboxaldehydes, preferably a 1-to-1 mixture thereof; exo,exo-2,5-norbornanedicarboxaldehyde; exo,exo-2,6-norbornanedicarboxaldehyde; exo,endo-2,5-norbornanedicarboxaldehyde; exo,endo-2,6-norbornanedicarboxaldehyde; endo,endo-2,5-norbornanedicarboxaldehyde; endo,endo-2,6-norbornanedicarboxaldehyde product (endo and exo mixture); 3-(3-formylcyclohexyl)propanal; 3-(4-formylcyclohexyl)propanal; 2-(3-formylcyclohexyl)propanal; 2-(4-formylcyclohexyl)propanal; and cyclododecane-1,4,8-tricarbaldehyde. The trans-1,3-cyclohexanedicarboxaldehyde; cis-1,3-cyclohexanedicarboxaldehyde; trans-1,4-cyclohexanedicarboxaldehyde; and cis-1,4-cyclohexanedicarboxaldehyde can be prepared by a process comprising hydroformylating 3-cyclohexene-1-carboxaldehyde using the hydroformylating conditions described later. The 1:1 mixture of 1,3- and 1,4-cyclohexanedicarboxaldehydes can be prepared by a process comprising reacting acrolein and 1,3-butadiene in a Diels-Alder reaction to give 3-cyclohexenecarboxaldehyde (also called 1,2,3,6-tetrahydrobenzaldehyde), and hydroformylating the 3-cyclohexenecarboxaldehyde using the hydroformylating conditions described later. The exo,exo-2,5-norbornanedicarboxaldehyde; exo,exo-2,6-norbornanedicarboxaldehyde; exo,endo-2,5-norbornanedicarboxaldehyde; exo,endo-2,6-norbornanedicarboxaldehyde; endo,endo-2,5-norbornanedicarboxaldehyde; and endo,endo-2,6-norbornanedicarboxaldehyde product (endo and exo mixture) can be prepared by a process comprising reacting acrolein and cyclopentadiene in a Diels-Alder reaction to give a 2-norbornene-5-carboxaldehyde, and hydroformylating the 2-norbornene-5-carboxaldehyde using the hydroformylating conditions described later. The 3-(3-formylcyclohexyl)propanal; 3-(4-formylcyclohexyl)propanal; 2-(3-formylcyclohexyl)propanal; and 2-(4-formylcyclohexyl)propanal can be prepared by a process comprising hydroformylating vinyl cyclohexene. The cyclododecane-1,4,8-tricarbaldehyde can be prepared by a process comprising trimerizing 1,3-butadiene to give 1,4,8-cyclododecatriene, and hydroformylating the 1,4,8-cyclododecatriene using the hydroformylating conditions described later. in a Diels-Alder reaction

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In another aspect, a process is described for preparing a compound, or a salt of a compound, or a solvate thereof, of Formula (III). The process comprises steps of: (a) condensing benzylamine with cyclohex-3-enecarbaldehyde to form (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine; (b) contacting (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine with potassium tert-butoxide present in an amount ranging from about 0.05 molar equivalents to about 0.2 molar equivalents of potassium tert-butoxide to (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine to form (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine; (c) contacting (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine with paraformaldehyde present in an amount ranging from about 2.0 molar equivalents to about 5.0 molar equivalents of paraformaldehyde to (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine, in presence of formic acid and a reaction medium comprising water present in an amount ranging from about 0.1% to about 6.5% of the reaction medium to form a compound of Formula (I); (d) contacting a compound of Formula (I) with a hydrogen bromide aqueous solution comprising about 43% to about 53% w/w of hydrogen bromide present in an amount ranging from about 1.0 molar equivalent to about 2.0 molar equivalents of the about 43% to about 53% w/w aqueous solution of hydrogen bromide to a compound of Formula (I), the acid addition salt is an HBr salt, and the salt of a compound of Formula (II) is In another aspect, a process is described for preparing a compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In another aspect, a process is described for preparing a compound, or a salt of a compound, or a solvate thereof, of Formula (III). The process comprises steps of: (a) condensing benzylamine with cyclohex-3-enecarbaldehyde to form (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine; (b) contacting (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine with potassium tert-butoxide present in an amount ranging from about 0.05 molar equivalents to about 0.2 molar equivalents of potassium tert-butoxide to (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine to form (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine; (c) contacting (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine with paraformaldehyde present in an amount ranging from about 2.0 molar equivalents to about 5.0 molar equivalents of paraformaldehyde to (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine, in presence of formic acid and a reaction medium comprising water present in an amount ranging from about 0.1% to about 6.5% of the reaction medium to form a compound of Formula (I); (d) contacting a compound of Formula (I) with a hydrogen bromide solution comprising about 43% to about 53% w/w of hydrogen bromide and where the inorganic salt of a compound of Formula (II) is an HBr salt; (e) contacting aminothiourea and benzoic acid in presence of polyphosphoric acid to form 2-amino-5-phenyl-1,3,4-thiadiazole H3PO4 salt; (f) contacting 2-amino-5-phenyl-1,3,4-thiadiazole H3PO4 salt, CuBr2 and iso-amyl nitrite, in presence of a acetonitrile, to form 2-bromo-5-phenyl-1,3,4-thiadiazole; and (g) contacting a compound of Formula (II) with 2-bromo-5-phenyl-1,3,4-thiadiazole, in presence of a sodium bis(trimethylsilyl)amide and tetrahydrofuran, to form a reaction mixture, and optionally contacting the reaction mixture with citric acid. In another aspect, the reaction mixture comprises In another aspect, a process is described for preparing a compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In another aspect, a process is described for preparing a compound, or a salt of a compound, or a solvate thereof, of Formula (III). The process comprises steps of: (a) condensing benzylamine with cyclohex-3-enecarbaldehyde to form (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine; (b) contacting (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine with potassium tert-butoxide present in an amount ranging from about 0.05 molar equivalents to about 0.2 molar equivalents of potassium tert-butoxide to (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine to form (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine; (c) contacting (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine with paraformaldehyde present in an amount ranging from about 2.0 molar equivalents to about 5.0 molar equivalents of paraformaldehyde to (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine, in presence of formic acid and a reaction medium comprising water present in an amount ranging from about 0.1% to about 6.5% of the reaction medium to form a compound of Formula (I); (d) contacting a compound of Formula (I) with an a hydrogen bromide solution and where the inorganic salt of a compound of Formula (II) is an acid addition salt; (e) contacting aminothiourea and benzoic acid in presence of polyphosphoric acid to form a 2-amino-5-phenyl-1,3,4-thiadiazole H3PO4 salt; (f) contacting 2-amino-5-phenyl-1,3,4-thiadiazole H3PO4 salt, CuBr2 and iso-amyl nitrite, in presence of acetonitrile, to form 2-bromo-5-phenyl-1,3,4-thiadiazole; and (g) contacting a compound of Formula (II) with 2-bromo-5-phenyl-1,3,4-thiadiazole, in presence of a sodium bis(trimethylsilyl)amide and a polar aprotic solvent, to form a reaction mixture, and optionally contacting the reaction mixture with citric acid. In another aspect, the reaction mixture comprises In another aspect, a process is described for preparing a compound

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In another aspect, a process is described for preparing a compound, or a salt of a compound, or a solvate thereof, of Formula (III). The process comprises steps of: (a) condensing benzylamine with cyclohex-3-enecarbaldehyde to form (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine; (b) contacting (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine with potassium tert-butoxide present in an amount ranging from about 0.05 molar equivalents to about 3.0 molar equivalents of potassium tert-butoxide to (E)-N-(cyclohex-3-en-1-ylmethylene)-1-phenylmethanamine to form (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine; (c) contacting (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine with paraformaldehyde present in an amount ranging from about 2.0 molar equivalents to about 5.0 molar equivalents of paraformaldehyde to (E)-N-benzylidene-1-(cyclohex-3-en-1-yl)methanamine, in presence of formic acid and a reaction medium to form a compound of Formula (I); (d) contacting a compound of Formula (I) with an a hydrogen halide solution to form an acid addition salt of a compound of Formula (II); (e) contacting aminothiourea and benzoic acid in presence of polyphosphoric acid to form a 2-amino-5-phenyl-1,3,4-thiadiazole phosphate salt; (f) contacting a 2-amino-5-phenyl-1,3,4-thiadiazole salt, CuBr2 and iso-amyl nitrite, in presence of acetonitrile, to form 2-bromo-5-phenyl-1,3,4-thiadiazole; and (g) contacting the acid addition salt of a compound of Formula (II) with 2-bromo-5-phenyl-1,3,4-thiadiazole, in presence of a sodium bis(trimethylsilyl)amide and a reaction medium, to form a reaction mixture, and optionally contacting the reaction mixture with citric acid. In another aspect, the reaction mixture comprises In another aspect, a process is described for preparing a compound