J. Chem. Soc. Pak., Vol. 10, No. 2, 1988. 235 Synthesis of some 3,5-Oxadiazines from Aroyl Isothiocyanates and 1-Phenylsemicarbazides MOHAMED EB, SHABAN Chemistry Department, Faculty of Seience, Ain Shams University, Abbassia, Cairo, Egypt. (Received 26th November, 1986, revised 25th August, 1987) Summary; The hitherto unknown 2-ary!-5,6-dihydro-6-phenylhydrazono-4-thiono- 1,3,S-oxadiazines (Vla-g) were synthesized by addition of arcyl isothiocya- nates (1a-g) to 1-phenylsemicarbazide. Products were based on The reaction of thiosemicarbazide [1] or semicarbazide hydrochloride [2] with benzoyl isothiocyanate has been reported to give the acyclie adduct ap. Ar-CONCS + NHo-NH-C-NH) —> qa) an ArCONHCSNHNH-C-NHy " (iy = Soro Ar = CgH,- Recently, it has been demonstrat- ed [3] that the addition of a number of aroyl isothiocyanates to urea or N-arylurea gave the mono-adducts of thiobiuret or 5-aryl thiobiuret (IV), respectively: Ar-CONCS + RNH-C-NH» ~> 3 RNHCONHCSNHCOAr (WD R = H or aryl In the present investigation, 1-phenylsemicarbazide (V), a relatively weaker nucleophile, was chosen for this study to react with some aroyl The structural assignments of the HNMR, infrared spectra and analytical data. isothiocyanate (la-g) of varying electrophilicity in order to obtain more precise information about the mode of addition of V to >C=S and/or >C=0 of I. Thus, (la-g) react with’ (V) to give 2-aryl-5,6-dihydro-6-phenyl- hydrazono-4-thiono-1,3,5-oxadiazines (Via-g), in good yields. Formation of Via-g has occurred most probably via a fucleophilic attack of the primary amido entity of V to the De ‘S function of the aroyl isothio¢yanate (1), (ef. Scheme-1). This mode of addition was found to be in contrast to that previously reported [1,2] for the addition of I to thiosemicarbazide or semicarbazide hydrochloride. It was believed that the steric as well as the electronic factors play an important role in such mode of addition of the aroyl isothiocyanates (la-g) to (V). Therefore, the primary amide group of V is expected to have a greater nucleophilicity as compared with the secondary amido or phenyl- amino grouping. A similar observation can also be concluded from the results of the previous work [3] where, N,N!- diphenyl- and N,N'-di-p-tolylureas were recovered unchanged (ca. 100% recovery) on being treated with benzoyl isothiocyanate, under the same236 MOHAMED €. SHABAN N=C=S + NH; C-NHNHPh —>- AG NHG NEG NENHED 0 aM ™) i (A) aN = AP-CEN-C-NH-C-NHNHPh An? “es by i 0 HO N HO-C7 NHNHPA |" ey rs ey" NHNHPh N-NHPh. N-NHPh (8) (Cc) (D) (vl) a, Ar= CgHe- by Ar =CgH, CH=CH- gear Coach HBr p ears C SHANO>- p Cety(NGa) 35 g-Ar= 3-Pyridyl Scheme 1 experimental conditions used in the present investigation and that N-aryl- ureas attack with the unsubstituted amido group. Therefore, the _ alternative adducts such as (A') were ruled out: 9 Ph-NH-N-C-NH» or ca'y Q Ph-N-NH-C-NH) | S=C-NHCOAr S=C-NHCOAr The structure of VI was sub- stantiated from analytical data (cf.Table-1), infrared spectra which showed similarities were devoid of any absorption at the frequency range of Yozq and exhibited “stretching frequencies correlated with secondary amino NH and thioamido NH groupings, (cf.Table-1). The | NMR spectra (DMSO) gave further support for theSYNTHESIS OF 3,5-OXADIAZINES structure of VI. Thus, the spectrum of Via showed from low to high field the following signals at 6 12.1-11.8 (broad singlet, thioamido NH or thiolo SH of the tautomers C and D; dis- appeared upon addition of D,0); 67.85-7.45 (multiplet, aromatic protons) and 63.25-3.18 (singlet, phenylhydrazono NH; disappeared upon shaking with D,0) with the integrated proton areas of 1:10:1, respectively, The spectrum of VIb showed signals at § 14.3-14,.1 (broad singlet, attributable to SH of the tautomer D; disappeared upon addition of D0); 6 7.85-7.40 (multiplet, aromatic protons); 6 7.15,6.8 (two doublets, two symmetrical ethylenic protons); 53.31-3.20 (singlet, phenyl- hydrazono NH; disappeared by addtion of D,0) with’ the integrated proton areas of 1:10:2:1, respectively. 237 The compounds (Vla-g) can exist in more than one tautomeric forms (B,C and D). The tautomer (D) is the more predominant as inferred from 1H NMR spectra. ‘This is further supported by the formation of a black precipitate upon shaking with alkaline sodium plumbite [3] at room tem- perature, which confirms the thio! form, i.e., (D) of the -NHCS- group. Experimental All melting points are uncorrect- ed. Infrared spectra (KBr discs) were measured on a Unicam SP 1200 spectro- photometer. 1H NMR spectra were run on EM-390 90 MHz NMR spectro- meter and all chemical shifts were reported relative to tetramethyl silane as an internal standard. Table-1: Characterization Data of VIa-9. Compourd m.p.*C Yield Formula Analysis(Found/Cale. }& IR spectra (solvent) % " N s (om) ni, V CoN Via 160-62 72 Cig gNOS 61-2 4.2 19-41? - 3340-3353, (B+) 60.8 4.1 18.9 10.8 1585-1595 vib, 213-14 69 Cp gNeOS 68.0 4,514.7 10.3 - 3380-3440, (A) 67.6 4.8 14,4 10.0 1590 vig 185-87 15 Ce N,OSCI $4.7 3.9 17.4 9.9 10.6" 3180-3200, (8) 54.6 3.3 16.9 9.7 10,7 1860-1590 vid 240-42 3 Cy_H, N,0S8r 48.4 2,9 15.8 9,0 21.7” 3380-2410, (B+) 48.0 2.9 14.9 €.5 21.3 1580-1600 Vie 262-64 79 Cig Ng0,8 85.5 3.6 21.00 9,7 - 3350-3380, (a) 58.0 3.4 20.8 9.4 1570-1580 vit, 185-57 86 Cay Neg 46.9 2.8 22,3 8.6 = 3300-3330, (8) 46.6 2.6 21.8 8.3 1985-1600 vig 245-47 84 Cyahy NeOS 87-0 3.60 2h TL = 3180-3220, (mw) $6.6 3.7 23.6 © 10.8 1580-1590 B= Benzene, B+P= benzene-petr.ether( 60-80"), As dilute acetic acid, M-methanol. Aye Clot X= Br238 3,5-Dinitrobenzoyl —_isothiocya- nate (If) was prepared according to Murav' eva method [4], b.p. 130-33/2 mmHg; yield 80% (Found: C,37.53; H,1.34; N,16.24; $,12.51. CgH,N,0,S 833 requires C,37.94; H,1.19; N,16.60; $,12.65%). Addition of aroyl isothiocyanates (Ia-g) to t-phenylsemicarbazide (V): Formation of Via-g: To a solution of V (0.01 mol) in dry acetone (150 ml) was added with stirring a solution of aroyl isothiocya- nate (0.01 mol) in dry acetone (100 ml) dropwise during 15 min. The reaction mixture was refluxed on a water-bath for 3 hr. On evaporation of the acetone solution followed by addition of water (250 ml), a solid product separated which was filtered MOHANED E. SHABAN and dried. Reerystallisation of the solid product from an appropriate solvent gave 2-aryl-5,6-dihydro-6- phynylhydrazono-4-thiono-1,3,5- oxadiazines (VJa-g). The results are given in Table-1. References 1. A. Sugii, J. Pharm. Soc. dapan, 78, 306 (1958). | 2. A. Sugii, J. Pharm. Soc. Japan, 79, 100 (1959). 3. M. N. Basyouni and A. E. Khamry, Bull, Chem. Soc. Japan, 58(12), 3728 (1979). 4. K.M, Murav' eva and T.P. Sydreva, thur. Obschei Khim., 26, 898 (1986).