Efficient atom and step economic (EASE) synthesis of the “smart drug” Modafinil

Efficient atom and step economic (EASE) synthesis of the “smart drug” Modafinil

Green Chem., 2017, Advance Article
DOI: 10.1039/C6GC02623K, Communication
Shivam Maurya, Dhiraj Yadav, Kemant Pratap, Atul Kumar
We developed a post-sulfoxidation protocol for the synthesis of Modafinil that exhibits improved sustainability credentials, utilizing the recyclable heterogeneous catalyst Nafion-H.

Efficient atom and step economic (EASE) synthesis of the “smart drug” Modafinil

Shivam Maurya,ab   Dhiraj Yadav,a   Kemant Pratapab and  Atul Kumar*ab  
 *Corresponding authors
aMedicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow 226031, India
E-mail: dratulsax@gmail.com, atul_kumar@cdri.res.in
bAcademy of Scientific and Innovative Research, New Delhi 110001, India
Green Chem., 2017, Advance Article

DOI: 10.1039/C6GC02623K

Atul Kumar

Atul Kumar

Professor, Academy of Scientific and Innovative Research (AcSIR)/ Senior Principal Scientist at CSIR-CDRI

Central Drug Research Institute

Modafinil (2-[(diphenylmethyl)sulfinyl]acetamide, MOD) is a key psychostimulant drug used for the treatment of narcolepsy and other sleep disorders that has a very low addiction liability. Recently, MOD has been clinically investigated for the treatment of cocaine addiction and used by astronauts in long-term space missions. We have developed a synthetic strategy for “smart drug” Modafinil. An efficient atom and step economic (EASE) synthesis has been carried out by the direct reaction of benzhydrol and 2-mercaptoacetamide using the recyclable heterogeneous catalyst Nafion-H along with post-sulfoxidation. This protocol exhibits improved sustainability credentials. We have also developed a superior pre-sulfoxidation approach for the synthesis of Modafinil.

Modafinil Physical State – White solid; M.p. 158-159ºC,
IR (KBr): 3383, 3314, 3256, 1690, 1 1616, 1494, 1376, 1027, 702 cm-1;
H NMR (CDCl3) δ(ppm): 3.14(d, J=14.3 Hz, 1H); 3.48(d, J=14.3 Hz, 1H); 5.24(s, 1H); 5.88(br s, 1H); 7.09(br s, 1H); 7.29-7.43(m, 7H); 7.43-7.51(m, 3H);
13C NMR (CDCl3) δ(ppm): 52.00, 71.61, 128.80, 128.98, 129.10, 129.58, 129.62, 134.30, 134.74, + 166.46; Molecular formula C15H15NO2S;
ESI-MS (m/z): 274.1 (M+H) .

Dr. Atul Kumar

Senior Principal Scientist