Cl₂ (g) Free Synthesis of syn-(Me,Me)bimane

syn-(Me,Me)Bimane 3 is a fluorescent molecule with high emission quantum yield of 90%.¹ Owing to its low toxicity and MW it is used as fluorescent probes for biological applications. Although expensive, 4 and some of its derivatives are commercially available. The only reported practical synthesis of 3 includes a hazardous chlorination step using gaseous Cl₂.² The wider use of 3 seems limited by the facts mentioned above. In our Lab, we developed a method for the facile synthesis of 4-chloropyrazlolinone (2), the key intermediate in syn bimane synthesis, circumventing the need for gaseous Cl₂. Following our simple procedures 2 can be produced in very good yields. As a source of Cl⁺, we use relatively cheap commercially available materials such as: trichloroisocyanuric acid, N-chlorosuccinimide, tert-butyl hypochlorite, among others.. (Scheme 1). The most important derivative of 3 is monobromo bimane (4) which is prepared using liquid Br₂.² We found that 4 can also be prepared in good yields using N-bromosuccinimide, avoiding the need of handling liquid Br₂. Our convenient methods for chlorinations of pyrazolinone 2 to access syn-(Me,Me)bimane 3 and monobromo bimane 4 will be discussed.

Reference:

1. S. Kosower, E. M. Kosower, G. L. Newton, and H. M. Ranney. Proc. Natl. Acad. Sci. USA, 1979, 76, 3382-3386.
2. M. Kosower, B. Pazhenchevsky. J. Am. Chem. Soc. 1980, 102, 4983-4993.
3. P. J. Das, I. Neogi, F. Grynszpan, Patent application submitted, 2017.