Indian Journal of Chemistry Vol. 49B, June 2010, pp. 771-775 A fast and highly efficient method for the synthesis of tertiary amines in aqueous medium Subbarayappa Adimurthy* & Girdhar Joshi Analytical Science Division, Central Salt and Marine Chemicals Research Institute (CSIR), Gijubhai Badheka Marg, Bhavnagar 364 002, India E-mail: sadimurthy@yahoo.com Received 8 September 2009; accepted (revised) 7 December 2009 A facile and highly efficient method for the synthesis of tertiary amines by the reaction of secondary amines with benzylic bromides and 1,1′-dibromo p/o-xylenes in aqueous dioxane and NaOH is described. The reactions are dually promoted by the base in short time (15 min.) at ambient conditions in aqueous medium. Keywords: Secondary amines, benzylic bromides, dibromoxylenes, sodium hydroxide, tertiary amines N-Alkylation of secondary amines continues to be focus for numerous studies 1 . Amines are of fundamental interest in many fields of chemistry, as evidenced by rapid increase in modern methods now available for their synthesis 2-5 . The direct alkylation of secondary amines with alkyl halides or alcohols is a straight forward method for the synthesis of tertiary amines 6-8 . These methods receive less attention due to the requirement of the specialized microwave equipment 6 or formation undesired products 7 . Although some significant achievements in the copper and palladium catalyzed arylation of amines have been made 3,4,9 , the drawbacks of these catalyst systems, such as requirement of extremely anhydrous conditions, air sensitivity, high cost and toxicity, limits their applications. Use of solid supports are an alternate methods have been reported 10 . While these methods are apparently useful for constructing libraries of secondary and tertiary amines, they are obviously not practical for large scale preparations. Other alternate and general methods include reductive amination 11 , Mannich and Petasis reactions 12 , and metal induced amination of alkenes and alkynes 13 . Perhaps these methods are quite reliable, but practical success has been relatively limited since concomitant over alkylations are the common impediment. Therefore, the search for milder and more efficient systems for N-alkylation of primary and secondary amines is the subject of recent focus 3,14 . In continuation of our recent work on synthesis of 2,3- dihydro-1H-isoindole, under aqueous conditions 15 , we found that tertiary amines can be efficiently synthesized under the same conditions in a short reaction time of 15 min. Therefore we report herein, an efficient base promoted synthesis of tertiary amines by the reaction of benzyl bromides with various secondary amines at RT are described. Results and Discussion Initially, the reactivity of p-nitrobenzylbromide 1 with various secondary amines 2a-f in presence of aqueous NaOH was screened out and results are summarized in Table I. Under the optimized conditions the reactions were completed with in 15 minutes when 1.2 equivalents of NaOH is used at room temperature (Table I, entries 1-3). The progress of the reaction was monitored by TLC, which shows intense spot of tertiary amines in iodine. These results are very significant compared to the reported procedures which normally need long reaction time. All the reactions proceeded smoothly, without significant loss of yields except in 2d (Table I, entries 4) at RT rather than the microwave irradiation 6 where it needs high energy to promote reactions. The reaction of 1 with diphenyl amine 2e (Table I, entries 5) is sluggish under the same conditions even reaction continued up to 60 minutes. However, the reaction with diisopropyl amine 2f (Table I, entries 6) showed 33% desired product formation by GC analysis after 3 hr. Encouraged by the results of Table I, the present methodology was extended to a wide range of benzylic