1,3-diazepane-2-thione

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: A solution of 6.35 g of iodine and 11 g of potassium iodide in 50 ml of water is added dropwise to a mixture of 4.9 g of 5-bromoindole in 35 ml methanol and 3.25 g of 4,5,6,7-tetrahydro-1H-1,3-diazepine-2-thione in 50 ml of methanol. The reaction mixture is allowed to be stirred at room temperature for 2 hours. The crystalline precipitate formed is filtered off and recrystallized from a mixture of methanol and ethyl acetate to yield 5-bromo-3-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-ylthio)indole hydriodide which melts at 243°-246° (with decomposition). The crystalline precipitate formed is filtered off recrystallized from a mixture of methanol and ethyl acetate

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

Procedure: A solution of 6.35 g of iodine and 11 g of potassium iodide in 50 ml of water is added dropwise to a mixture of 4.9 g of 5-bromoindole in 35 ml methanol and 3.25 g of 4,5,6,7-tetrahydro-1H-1,3-diazepine-2-thione in 50 ml of methanol. The reaction mixture is allowed to be stirred at room temperature for 2 hours. The crystalline precipitate formed is filtered off and recrystallized from a mixture of methanol and ethyl acetate to yield 5-bromo-3-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-ylthio)indole hydriodide which melts at 243°-246° (with decomposition). The crystalline precipitate formed is filtered off recrystallized from a mixture of methanol and ethyl acetate

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

Procedure: Methyl iodide (0.55 ml, 1.15 mmol) was added to a solution of 1,3-diazepane-2-thione (1.00 g, 7.68 mmol) in acetone (8 ml). The reaction mixture was refluxed for 15 min. EtOH was added to the hot solution to dissolve the solids. After cooling to r.t. hex. was added and the precipitate was collected by filtration, washed with hex. and dried to give 1.79 g (86%) crude title compound which was used directly in the next step. The reaction mixture was refluxed for 15 min to dissolve the solids was added the precipitate was collected by filtration washed with hex and dried

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

Procedure: Methyl iodide (0.55 ml, 1.15 mmol) was added to a solution of 1,3-diazepane-2-thione (1.00 g, 7.68 mmol) in acetone (8 ml). The reaction mixture was refluxed for 15 min. EtOH was added to the hot solution to dissolve the solids. After cooling to r.t. hex. was added and the precipitate was collected by filtration, washed with hex. and dried to give 1.79 g (86%) crude title compound which was used directly in the next step. The reaction mixture was refluxed for 15 min to dissolve the solids was added the precipitate was collected by filtration washed with hex and dried

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

Procedure: A mixture consisting of 12 g. of piperonal 8.4 ml. of p-fluorobenzaldehyde, 6 g. of potassium cyanide, and 80 ml. of 65% ethanol is reacted as described in Example 20, giving 11.7 g. of 4'-fluoro-3,4-methylenedioxybenzoin as an uncrystallizable oil. 9.0 g. of this benzoin is converted to its methanesulfonate ester by the procedure of Example 20, yielding 9.8 g. of ester as an uncrystallizable oil. The reaction of 4.9 g. of the crude methanesulfonate ester, and 1.16 g. of hexahydro-2H-1,3-diazepin-2-thione in 80 ml. of acetone, followed by treatment with 5 ml of 2 N ethanolic hydrogen chloride gives the title compound melting at 211°-213° C. giving 11.7 g yielding 9.8 g The reaction of 4.9 g

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

Procedure: A mixture consisting of 16.6 g. of veratraldehyde, 12.5 g. of o-fluorobenzaldehyde, 8 g. of potassium cyanide, and 100 ml of 65% ethanol is reacted as described in Example 20, yielding 12.5 g. of 3,4-dimethoxy-2'-fluorobenzoin, m.p. 126°-128° C. A 5.8 g. portion of the benzoin derivative is converted to its methanesulfonate ester by the procedure of Example 20, giving 6.7 g. of the ester melting at 111°-113° C. 2.58 g. of the methanesulfonate ester, 0.91 g. of hexahydro-2H-1,3-diazepin-2-thione, and 55 ml. of acetone are mixed and left at room temperature for three days. 7 ml. of 2 N ethanolic hydrogen chloride are added, yielding 2.2 g. of the title compound, melting at 192°-194° C. yielding 12.5 g giving 6.7 g yielding 2.2 g

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

Procedure: A mixture of 9.2 ml. of 2-thiophenecarboxaldehyde, 11.3 ml. of o-chlorobenzaldehyde, 8 g. of potassium cyanide and 100 ml. of 65% ethanol is refluxed for 2 hours and then refrigerated. A 30 ml. portion of water is added, refrigeration is continued, the oil is separated by decantation, added to toluene, washed with water, dried and concentrated giving 12.7 g. of an oil. A 9.0 g. portion of this oil is mixed with 8.4 ml. of triethylamine and 100 ml. of toluene and stirred as a mixture of 2.4 ml. of methanesulfonyl chloride in 100 ml. of toluene is added. The mixture is stirred overnight then 100 ml. of water is added. The toluene layer is separated, washed with water, dried and concentrated, giving 10.6 g. of oily 2-thienyl α-hydroxy(2-chlorophenyl)ketone. This oil is combined with 3.9 g. of hexahydro-2H-1,3-diazepin-2-thione in 150 ml. of acetone and allowed to stand 48 hours. The solvent is removed, 100 ml. of water and 2 ml. of ammonium hydroxide are added and the aqueous layer is decanted. Ethanol is added, the mixture is cooled and the solid is collected, giving 3.4 g. of the desired product, m.p. 120°-122° C. A mixture of 9.2 ml the oil is separated by decantation added to toluene washed with water dried concentrated giving 12.7 g portion of this oil is mixed with 8.4 ml The toluene layer is separated washed with water dried concentrated giving 10.6 g to stand 48 hours The solvent is removed of ammonium hydroxide are added the aqueous layer is decanted Ethanol is added the mixture is cooled the solid is collected giving 3.4 g

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

Procedure: A mixture of 9.2 ml. of thiophene-2-carboxyaldehyde, 8 g. of potassium cyanide and 10.1 ml. of benzaldehyde in 100 ml. of 65% ethanol is reacted as described in Example 20, giving 6.2 g. of 2-thienyl-α-hydroxybenzyl ketone. A 4.36 g. portion of this ketone is reacted with methanesulfonyl chloride as described in Example 20, giving 3.2 g. of the methanesulfonate ester. A 2.64 g. portion of this ester and 1.30 g. of hexahydro-2H-1,3-diazepine-2-thione in 100 ml. of acetone are allowed to stand 48 hours, the solid is collected, washed with ether and dried in vacuo, giving 2.8 g. of the desired product, m.p. 149°-151° C. A mixture of 9.2 ml giving 6.2 g giving 3.2 g the solid is collected washed with ether dried in vacuo giving 2.8 g

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

Procedure: A mixture of 7.75 ml. of methanesulfonyl chloride in 200 ml. of toluene is added, over a period of one hour, to a stirred mixture of 21.2 g. of benzoin, 28 ml. of triethylamine and 100 ml. of toluene. The mixture is allowed to stand 2 hours, 100 ml. of water is added and the emulsion is filtered giving a solid which is washed with water and dried, giving 14.5 g. of benzoin methanesulfonate esters. A 2.90 g. portion of benzoin methanesulfonate esters and 1.30 g. of hexahydro-2H-1,3-diazepin-2-thione are suspended in 50 ml. of warm acetone and heated at reflux for 4 hours. The mixture is cooled, the solid is collected, washed with acetone then ether and dried in vacuo at 60° C., giving 3.9 g. of the desired product, m.p. 176°-178° C. A mixture of 7.75 ml the emulsion is filtered giving a solid which is washed with water dried giving 14.5 g at reflux for 4 hours The mixture is cooled the solid is collected washed with acetone ether and dried in vacuo at 60° C. giving 3.9 g

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

Procedure: A mixture of 22.6 ml. of o-chlorobenzaldehyde, 8 g. of potassium cyanide and 100 ml. of 65% ethanol is refluxed for 2 hours and then refrigerated. Water (30 ml.) is added, refrigeration is continued, then the water layer is decanted and the oil dissolved in toluene, washed with water, dried and concentrated to an oil. The crude 2,2'-dichlorobenzoin is converted to the methanesulfonate ester as described in Example 1, giving an oil. A 14.6 g. portion of this oil is reacted with 2.6 g. of hexahydro-2H-1,3-diazepin-2-thione in 100 ml. of acetone as described in Example 13, giving 1.4 g. of the desired product, m.p. 224°-226° C. A mixture of 22.6 ml the water layer is decanted the oil dissolved in toluene washed with water dried concentrated to an oil giving an oil portion of this oil is reacted with 2.6 g giving 1.4 g