Monatsh Chem 139, 267–270 (2008) DOI 10.1007/s00706-007-0776-1 Printed in The Netherlands A High Yielding, One-pot Synthesis of Substituted Ureas from the Corresponding Amines Using Mitsunobu’s Reagent # Devdutt Chaturvedi 1; , Nisha Mishra 2 , and Virendra Mishra 2 1 Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow, U.P., India 2 Synthetic Research Laboratory, Department of Chemistry, B.S.A. College, Mathura, U.P., India Received July 28, 2007; accepted August 2, 2007; published online February 12, 2008 # Springer-Verlag 2008 Summary. A Mitsunobu-based protocol has been developed for the synthesis of symmetrically and unsymmetrically substituted ureas from a variety of primary and secondary amines using gaseous carbon dioxide, in good to excellent yields. This protocol is mild and efficient compared to other reported methods. Keywords. Mitsunobu’s reagent; Carbon dioxide; Amines; Substituted ureas. Introduction Substituted ureas are very important class of com- pounds that display a wide range of interesting appli- cations [1]. They have extensively been used as agrochemicals [2], pharmaceuticals [3], intermedi- ates in organic synthesis [4], for protection of amino groups [5], and as linkers in combinatorial chemistry [6]. These uses require their preparation by conve- nient and safe methodology. Traditionally, their syn- thesis involves a reaction of amines with phosgene [7], its derivatives [8], carbonyl-imidazoles [9], or carbon monoxide [10] using various kinds of metal and non-metal catalysts. Moreover, a process for pre- paring 1,3-disubstituted ureas through reacting a cy- clic carbonic acid ester with an amine over a proper catalyst was disclosed [11]. However, This method is too expensive to use on a large scale. The transfor- mation of amines through catalytic carbonylation to produce disubstituted ureas provides an alternative en- vironmental benign method and has been investigated over many years using various kinds of metallic cat- alysts [12]. However, these methods failed due to the problems of regenerating the catalysts from the prod- ucts. Moreover, their formation using CO 2 employed harsh reaction conditions, such as long reaction times, use of expensive strongly basic reagents, tedious work-up, and low yields [13]. Consequently, there is continued interest in developing new and convenient methods for the synthesis of substituted ureas using mild reaction conditions. Our group [14] has been engaged over several years with the development of new methods for the syn- thesis of carbamates, dithiocarbamates and related compounds using cheap, abundantly available, and safe reagents like CO 2 and CS 2 . Recently, we have reported [15] the synthesis of carbamates, dithiocar- bamates, O,S-dialkyl-dithiocarbonates (xanthates), and dialkyl carbonates from the corresponding alco- hols using Mitsunobu’s reagent. Based on our recent work, we report herein a chemoselective, highly effi- cient, and mild synthesis of symmetrical and unsym- metrical ureas from corresponding amines using Mitsunobu’s reagent. Results and Discussion We carried out the synthesis of substituted sym- metrical and unsymmetrical ureas by mild carba- # This paper is dedicated to Dr. Nitya Anand for his constant inspiration for research.  Corresponding author. E-mail: ddchaturvedi002@yahoo. co.in