I need N-methylpyrrole,I was trid pyrrole reaction with Methyl iodide, and Dimethyl Sulphate,methanol/Acid not given good yields. so please suggest best process for N-methyl pyrrole synthesis
Dear Suman Suthoju, apparently the problem is that you are working under acidic conditions. However, the N-methylation of pyrrole using methyl iodide or dimethyl sulfate requires the presence of a strong base. Here is a statement I found in the literature:
"N-Alkylated indole and pyrrole produced by regioselective synthesis belong to an extremely attractive domain in heterocyclic chemistry as a result of their unusual bioactivities. One possible way of accomplishing the N-alkylation is by using a stoichiometric amount of a strong base. The established methods of accomplishing this include the use of alkali metals,5 alkali metal alkoxides,6 or potassium hydroxide in DMSO,7 potassium super oxide in crown ethers,8 sodium hydroxide in DMF,9 NaH or KH in DMF,10 HMPA,11 Cs2CO3 in DMPU12 and phase-transfer catalytic conditions.13
Here are the respective references:
5 C.F. Hobbs, C.K. McMillin, E.P. Papadopoulos, C.A. VanderWerf, J. Am. Chem. Soc., 84 (1962), pp. 43-51.
6 R.A. Jones, G.P. BeanA.T. Blomquist, H.H. Wasserman (Eds.), The Chemistry of Pyrroles, Vol. 34, Academic Press, London (1977), p. 173.
7 H. Heaney, S.V. Ley, J. Chem. Soc., Perkin Trans. 1, 5 (1973), pp. 499-500.
8 E.S. Yim, M.K. Park, B.H. Han, Ultrason. Sonochem., 4 (1997), pp. 95-98.
9 (a) Szmuzkovicz, J. Belg. Pat. 621,047, 1963. (b) P.R. Giles, M. Rogers-Evans, M. Soukup, J. Knight, Org. Process Res. Dev., 7 (2003), pp. 22-24.
10 M. Girard, P. Hamel, J. Org. Chem., 65 (2000), pp. 3123-3125.
11 (a) H. Normant, T. Cuvigny, Bull. Soc. Chim. Fr. (1965), pp. 1866-1872. (b) G.M. Rubottom, J.C. Chabala, Org. Syn., 54 (1974), pp. 60-62.
12 D.M. Fink, Synlett (2004), pp. 2394-2396.
13 (a)V. Bocchi, G. Casnati, A. Dossena, F. Villani, Synthesis (1976), pp. 414-416.(b) E. Santaniello, C. Farachi, F. PontiSynthesis (1979), pp. 617-618.
Just one personal remark: Try to avoid working with dimethyl sulfate because of its high toxicity!
N-methyl pyrrole synthesis can be synthesized by refluxing pyrrole91mole) with methyl iodide(1 mole) in acetone using K2CO3 as a base catalyst for 10 hrs..,cooled & the solvent removed under reduced pressure to get N-Methyl pyrrole.
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