General Papers ARKIVOC 2014 (v) 365-375 Page 365 © ARKAT-USA, Inc Lateral lithiation and substitution of N'-(2-methylphenyl)- N,N-dimethylurea Keith Smith,* a Gamal A. El-Hiti,* b Sadiq A. Al-Mansury, c Mohammed B. Alshammari, d and Asim A. Balakit e a School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK b Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia c Department of Chemistry, College of Veterinary Medicine, Al-Qasim Green University, Babil, Iraq d Chemistry Department, College of Sciences and Humanities, Salman bin Abdulaziz University, P.O. Box 83, Al-Kharij 11942, Saudi Arabia e College of Pharmacy, Babylon University, Babylon, Iraq E-mail: smithk13@cardiff.ac.uk, gelhiti@ksu.edu.sa DOI: http://dx.doi.org/10.3998/ark.5550190.p008.800 Abstract Lithiation of N'-(2-methylphenyl)-N,N-dimethylurea with three molar equivalents of tert-butyl- lithium at 40 to 30 C takes place on the nitrogen and on the methyl group at position 2 of the phenyl group. The lithium intermediate thus obtained reacts with a variety of electrophiles to give the corresponding side-chain substituted derivatives in high yields. Keywords: Lateral lithiation, N'-(2-methylphenyl)-N,N-dimethylurea, lithium intermediate Introduction Lateral lithiation, followed by reactions with electrophiles, provides a convenient route for the production of substituted aromatics and heterocycles. Such lateral lithiation requires a group that stabilizes an organolithium either by coordination or by delocalizing a negative charge. 1,2 Various heteroatom-based stabilizing groups, located at an ortho-position, have been used successfully for lateral lithiations. 3-16 In the course of our own studies of lithiation reactions 17 we have synthesized various substituted aromatics and heterocycles via efficient lateral lithiation procedures. 18-22 For example, we have successfully laterally lithiated and substituted N'-(2-methylbenzyl)-N,N-