Process Design and Scale-Up of the Synthesis of 2,2‘:5‘,2‘ ‘-Terthienyl

• Published in: Organic process research & development 2003-01, Vol.7 (1), p.10-16
• Main Authors: Smeets, B. J. J, Meijer, R. H, Meuldijk, J, Vekemans, J. A. J. M, Hulshof, L. A
• Format: Article
• Language: English
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/op020044n

The objective of this study was the design of a scaleable process for the synthesis of 3−4 mol of α-terthienyl from 2,5-dibromothiophene and thienylmagnesium bromide in a 10-L stirred tank reactor. In THF the Grignard reagent, thienylmagnesium bromide, was readily formed from 2-bromothiophene and magnesium. To avoid crystallization the maximal concentration was limited to 1.4 M. Furthermore, the novel combination of THF and NiCl2[bis(diphenylphosphino)benzene] allows for fast double coupling of the Grignard reagent with 2,5-dibromothiophene. The concentration of catalyst could be limited to 0.5 mol % based on the amount of 2,5-dibromothiophene. An adapted workup procedure was developed, in which n-octane was used to separate the magnesium salts from the desired product. The reaction was performed in a (semi)batch-wise operated reactor. A global model for the coupling step proved to predict the results at 0.1-, 1-, and 10-L scales very accurately. The heat of reaction evolved in the coupling step was valorized and could be handled easily. Mixing of the feed stream and the reactor content proved to be another important factor in the scaling-up of the α-terthienyl synthesis.