Spectrochimica Acta Part A 61 (2005) 1321–1326 Conformation of some biologically active aromatic ureas Boriana Hadjieva, Sonia Ilieva, Diana Cheshmedzhieva, Boris Galabov ∗ Department of Chemistry, University of Sofia, 1 James Bourchier Avenue, 1164 Sofia, Bulgaria Received 15 July 2004; accepted 15 September 2004 Dedicated to Prof. J.R. Dung on the occasion of his 70th birthday. Abstract Experimental IR spectroscopic data for the N–H stretching mode frequencies for several types of tri-substituted ureas containing benzyl and/or phenyl substituents as well as theoretical results from B3LYP/6–31G(d,p) computations on selected compounds provide sufficient evidence to determine the conformational state of these molecules. Two types of N–H bands may be found the spectra: (a) A type band due to a classical trans conformation (trans I) of the CO NH structure; (b) B type band arising from an alternative trans form (trans II), in which the N–H band is involved in a hydrogen bond like interaction with the aromatic ring at the neighbouring nitrogen atom (benzyl or phenyl substituents). The N–H band of trans I CO NH structure is observed at frequencies higher than 3460 cm -1 , the actual position depending on weather the non-substituted N–H group is linked to aryl or alkyl substituents. The N–H band of the trans II rotameric structure is observed at 3430–3420 cm -1 . © 2004 Elsevier B.V. All rights reserved. Keywords: Substituted ureas; Conformation; DFT calculations; IR spectroscopy 1. Introduction A number of substituted urea and thiourea derivatives were shown to possess pronounced herbicidal, plant growth reg- ulating and cytokine activity [1–3]. A number of 1-alkyl- 1-benzyl-3-aryl(or alkyl) ureas were recognized as cytokine antagonists (anticytokinins) [4,5]. It has been shown that the biological activity of urea and thiourea derivatives is strongly correlated with their conformational state [6]. The present study aims at establishing the dependencies between IR spec- tral characteristics and conformational state of biologically active tri-substituted ureas containing a benzyl moiety as well as aryl and alkyl substituents. For comparison analo- gous structures with phenyl instead of benzyl moiety were also investigated. This work is an extension of our previous studies on the relationship between structure and biological activity as plant-growth regulators of substituted ureas and thioureas [1–5]. There has been a continuous interest in applying IR and NMR spectroscopies in characterizing the conforma- ∗ Corresponding author. Tel.: +359 2 6256421; fax: +359 2 9621913. E-mail address: galabov@chem.uni-sofia.bg (B. Galabov). tional equilibrium in different types of substituted ureas and thioureas [7–27]. The interest is determined by the biological activities of many representatives of these classes of com- pounds as well as because of the closeness of their structure with amides and thioamides. Ab initio and density functional theory computations on selected urea derivatives were also reported [28–30]. The electronic structure results provided a clear framework for analysing the relationship between spec- troscopic data and conformation. 2. Experiments and computational details The aromatic ureas studied were synthesized by the re- action of isocyanates with amines [31]. The structural for- mulas of the compounds are given in Table 1. The infrared spectra were recorded on a Perkin-Elmer 983 G spectrometer at a slow speed in dilute tetrachloromethane solutions. The recorded frequencies are accurate to ±1 cm -1 . Density functional theory computations at B3LYP/6– 31G(d,p) level [32–34] were carried out to optimise the ge- ometry and evaluate properties of the conformers for several compounds from the series studied. A scaling factor k = 0.946 1386-1425/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.saa.2004.09.020