N,N’-Bis-(benzothiazol-3-yl)piperazine; 3,3'-(Piperazine-1,4-diyl)bis(1,2-benzothiazole)

• CAT Number: R027326
• CAS Number: 223586-82-1
• Molecular Formula: C18H16N4S2
• Molecular Weight: 352.474
• Purity: ≥95%
• Synonyms: 1,4-Bis(benzo[d]isothiazol-3-yl)piperazine; 3-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]-1,2-benzothiazole; Lurasidone Impurity 1.
• Appearance: White to Off-White Solid
• Storage: -20°C
• IUPAC Name: 3-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]-1,2-benzothiazole
• InChI: InChI=1S/C18H16N4S2/c1-3-7-15-13(5-1)17(19-23-15)21-9-11-22(12-10-21)18-14-6-2-4-8-16(14)24-20-18/h1-8H,9-12H2
• InChIKey: UGYNLCWENVIDFA-UHFFFAOYSA-N
• SMILES: C1CN(CCN1C2=NSC3=CC=CC=C32)C4=NSC5=CC=CC=C54

N,N’-Bis-(benzothiazol-3-yl)piperazine; 3,3′-(Piperazine-1,4-diyl)bis(1,2-benzothiazole) (Cat.No:R027326) is a complex chemical compound with potential applications in materials science and pharmaceutical research. Its unique structure, incorporating benzothiazole and piperazine moieties, suggests versatile reactivity for various synthetic endeavors. 

Reference

[1]. New Disulfide Route to 3-(1-Piperazinyl)-1,2-benzisothiazole. Nucleus for Atypical Antipsychotic Drugs Stanley W. Walinsky, Darrell E. Fox, John F. Lambert, and Terry G. Sinay
Organic Process Research & Development 1999 3 (2), 126-130

A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new, “atypical antipsychotic” drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120−140 °C for 3−24 h in the presence of small amounts of DMSO and 2-propanol formed 3-(1-piperazinyl)-1,2-benzisothiazole in 75−80% yields. The DMSO oxidized the liberated 2-mercaptobenzonitrile to regenerate bis(2-cyanophenyl) disulfide, thereby enabling the utilization of both halves of the symmetrical disulfide to generate product. The reaction mechanism for the conversion of the bis(2-cyanophenyl) disulfide to 3-amino-1,2-benzisothiazole involves the formation of ring-opened sulfenamide and benzamidine intermediates and then their subsequent ring closure to regenerate the 1,2-benzisothiazole nucleus. A safe, efficient, and robust process to prepare 3-(1-piperazinyl)-1,2-benzisothiazole under very concentrated reaction conditions was developed and successfully scaled up in the pilot plant to support the development of ziprasidone. AB – A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new, “atypical antipsychotic” drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120−140 °C for 3−24 h in the presence of small amounts of DMSO and 2-propanol formed 3-(1-piperazinyl)-1,2-benzisothiazole in 75−80% yields. The DMSO oxidized the liberated 2-mercaptobenzonitrile to regenerate bis(2-cyanophenyl) disulfide, thereby enabling the utilization of both halves of the symmetrical disulfide to generate product. The reaction mechanism for the conversion of the bis(2-cyanophenyl) disulfide to 3-amino-1,2-benzisothiazole involves the formation of ring-opened sulfenamide and benzamidine intermediates and then their subsequent ring closure to regenerate the 1,2-benzisothiazole nucleus. A safe, efficient, and robust process to prepare 3-(1-piperazinyl)-1,2-benzisothiazole under very concentrated reaction conditions was developed and successfully scaled up in the pilot plant to support the development of ziprasidone.

DOI: 10.1021/op980210k