CROATICA CHEMICA ACTA CCACAA, ISSN 0011-1643, e-ISSN 1334-417X Croat. Chem. Acta 87 (3) (2014) 201–206. http://dx.doi.org/10.5562/cca2381 Original Scientific Article Direct and Facile Synthesis of Acyl Isothiocyanates from Carboxylic Acids Using Trichloroisocyanuric Acid/Triphenylphosphine System Najmeh Entezari, Batool Akhlaghinia,* and Hamed Rouhi-Saadabad Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran RECEIVED NOVEMBER 7, 2013; REVISED JUNE 3, 2014; ACCEPTED AUGUST 27, 2014 Abstract. A mild, efficient, and practical method for one-step synthesis of alkanoyl and aroyl isothiocyanates from carboxylic acids using a safe and inexpensive mixed reagent, trichloroisocyanuric acid/triphenyl- phosphine is described at room temperature. Availability of the reagents and easy workup of the reaction make this method attractive for organic chemists. Keywords: acyl isothiocyanates, carboxylic acids, trichloroisocyanuric acid (TCCA), triphenylphosphine (TPP), potassium thiocyanate INTRODUCTION azides from carboxylic acids and sulfonic acids under mild and neutral reaction conditions by using the above Acyl isothiocyanates have found wide application in the mentioned mixed reagents.19–21 Herein we wish to report synthesis of various acyclic and heterocyclic compounds, a simplified, rapid and one-step method for the conver- including those possessing biological activity.1–3 sion of carboxylic acids to acyl isothiocyanates in the The methods of preparation of isothiocyanates are presence of TPP/TCCA as a mild, efficient and inex- limited.2 many methods have been described for the pensive reagent system at room temperature. 4–14 preparation of acyl isothiocyanates. which are main- ly based on the reaction of acyl halides with thiocyanate EXPERIMENTAL ion.2,6 Acyl halides are not always easy to access or store. As acyl halides are highly sensitive to moisture General and require care in handling, these methods need to anhydrous conditions and long reaction time.6 The reac- The products were purified by column chromatography. tion of carbonimidoyl dichloride with metal thiocyanate The purity determinations of the products were accom- is also another reported method of preparation of acyl plished by TLC on silica gel polygram STL G/UV 254 isothiocyanates, but the starting material is not easily plates. The melting points of products were determined available and the yield of the reaction is too low.15 with an Electrothermal Type 9100 melting point appa- There are few reports on the direct conversion of car- ratus. The FT-IR spectra were recorded on an Avatar boxylic acids to acyl isothiocyanates using acid activa- 370 FT-IR Therma Nicolet spectrometer. The NMR tors such as Ph3P(SCN)2 (Ref. 16) and PO(NCS)3 (Ref. spectra were provided on Brucker Avance 100 and 400 17). Preparation of the reagents in these methods suffers MHz instruments in CDCl3 and DMSO. Mass spectra from difficult procedures and the reactions take long were recorded with a CH7A Varianmat Bremem in- time. Conversion of trialkylsilyl carboxylates to acyl strument at 70 eV; in m/z (rel %). Elemental analyses isothiocyanates was also reported by using Ph3P(SCN)2 were performed using an Elementar, Vario EL III and (Ref. 18). This methodology cannot be considered as a Thermofinnigan Flash EA 1112 Series instrument. Most direct preparation of acyl isothiocyanates and also needs of the products were known compounds and character- initial preparation of reagents. ized by the IR and comparison of their melting points By considering the activity of trichloroisocyanuric with authentic samples. The structure of unknown prod- acid (TCCA) and N-chlorobenzotriazole (NCBT) to- ucts and some selected known products was further wards triphenylphosphine, recently we reported direct confirmed by 1H NMR, 13C NMR spectroscopy, mass preparation of acyl azides, esters, thioesters and sulfonyl spectrometry and elemental analysis. * Author to whom correspondence should be addressed. (E-mail: [email protected]) 202 N. Entezari et al., Direct Synthesis of Acyl Isothiocyanates from Carboxylic Acids Preparation of Benzoyl Isothiocyanate from Benzoic 1012, 861, 840, 738, 666, 532; MS m/z: 197 (M+, 2.5 %); Acid 138 (M+–NCS, 100 %); 110 (M+–CONCS, 92.5 %); 75 (Ph, 95 %). To a cold solution of triphenylphosphine (0.262 g, 1 mmol) in toluene (3 mL), trichloroisocyanuric acid (0.069 g, 4-Bromobenzoyl Isothiocyanate (Table 2, entry 7) 0.3 mmol) was added with continuous stirring. Benzoic Solid; m.p. 53–55 °C (Ref. 26) 54–55 °C; IR (KBr) –1 acid (0.097g, 0.8 mmol) was added and stirring was ῡmax /cm : 3088, 2197, 2039, 1985 (N=C=S), 1687 continued for 15 min. Potassium thiocyanate (0.193 g, (C=O), 1587, 1482, 1397, 1269, 1172, 1100, 1066, 2 mmol) was added and the temperature was raised up 1010, 860, 837, 734, 665, 510, 459; 1H NMR (400 to room temperature. Stirring was continued for 40 min MHz, CDCl3) δ/ppm: 7.67 (d, 2H, J = 8.8 Hz, ArH), at room temperature. The progress of the reaction was 7.94 (d, 2H, J = 8.8 Hz, ArH); 13C NMR (100 MHz, followed by TLC. Upon completion of the reaction, CDCl3) δ/ppm: 161.4 (C=O), 149.1 (N=C=S), 132.4, the concentrated residue passed through a short silica- 131.8, 130.7, 129.8, 129.7; MS m/z: 243 (M++2, gel column using n-hexane / ethyl acetate mixture (vol. 25 %); 241 (M+, 25 %); 183 (M+–NCS, 100 %); 155 ratio: 60:1) as the eluent. Benzoyl isothiocyanate was (M+–CONCS, 85 %). obtained with 95 % yield after removing the solvent 4-Methylbenzoyl Isothiocyanate (Table 2, entry 8) under reduced pressure. 27 –1 Oil; IR (neat) ῡmax /cm : 3043, 2986, 2913, 2847, Benzoyl Isothiocyanate (Table 2, entry1) 1974 (N=C=S), 1931, 1696 (C=O), 1607, 1511, 1446, 22 –1 Oil; IR (neat) ῡmax /cm : 2964, 2932, 2876, 1978 1405, 1256, 1175, 1082, 861, 785, 747, 677, 597. (N=C=S), 1694 (C=O), 1597, 1451, 1253, 1239, 1175, 3,5-Dimethylbenzoyl Isothiocyanate (Table 2, entry 9) 1083, 1067, 855, 693, 670, 648. 6 –1 Oil; IR (neat) ῡmax /cm : 3015, 2925, 2864, 1973 4-Nitrobenzoyl Isothiocyanate (Table 2, entry2) (N=C=S), 1697 (C=O), 1606, 1453, 1379, 1301, 1182, Solid; m.p. 90–92 °C (Ref. 13) 92–93 °C; IR (KBr) 1164, 1100, 937, 865, 762, 735, 669, 547, 449; 1 HNMR –1 ῡmax /cm : 3268, 3096, 3072, 3039, 1993 (N=C=S), (400 MHz, CDCl3) δ/ppm: 2.41 (s, 6H, 2CH3), 7.30 (d, 1956, 1690 (C=O), 1601, 1523, 1346, 1321, 1270, 1103, 1H, J=10 Hz, ArH), 7.69 (s, 2H, ArH); 13C NMR (100 + 874, 839, 709, 669, 510; MS m/z: 206 (M , 5 %); 149 MHz, CDCl3) δ/ppm: 161.9 (C=O), 147.40 (N=C=S), (M+–NCS, 72.5 %); 121 (M+–CONCS, 7.5 %); 75 (Ph, 138.8, 138.3, 136.9, 136.2, 133.7, 130.7, 128.3, 126.2, 95 %); Anal. Calcd. mass fractions of elements, w/%, for 125.2, 21.3, 21.2. C H N O S (M = 208.19) are: C 46.15, H 1.94, N 13.46, 8 4 2 3 r 4-Methoxybenzoyl isothiocyanate (Table 2, entry 10) S 15.40; Found: C 46.36, H 1.66, N 14.08, S 16.05. 4 –1 Oil; IR (neat) ῡmax /cm : 2961, 2932, 2839, 2160, 1973 3-Nitrobenzoyl Isothiocyanate (Table 2, entry 3) (N=C=S), 1930, 1690 (C=O), 1603, 1577, 1506, 1423, Solid; m.p. 94–95 °C (Ref. 23) 95–96 °C; IR (KBr) 1330, 1250, 1164, 1085, 1023, 863, 785, 750, 681, 599. ῡ /cm–1: 3370, 3244, 3092, 3080, 2929, 2855, 1991 max 4-(Isothiocyanatocarbonyl) phenyl acetate (Table 2, (N=C=S), 1723, 1684 (C=O), 1613, 1537, 1525, 1351, entry 11) 1290, 1265, 1127, 927, 820, 709, 690; MS m/z: 206 Oil; IR(neat) ῡ /cm–1: 2956, 2916, 2848, 1981 (M+, 15 %); 149 (M+–NCS, 100 %); 121 (M+–CONCS, max (N=C=S), 1936, 1774 (C=O), 1703, 1598, 1503, 1417, 25 %); 75 (Ph, 80 %); Anal. Calcd. mass fractions 1370, 1249, 1198, 1161, 1017, 910, 882, 850, 681, 645, of elements, w/%, for C H N O S (M = 208.19) are: 8 4 2 3 r 592; 1H NMR (400 MHz, DMSO-d6) δ/ppm: 2.26 (s, C 46.15, H 1.94, N 13.46, S 15.40; Found: C 46.28, 3H, Me), 7.22 (d, 2H, J = 8.4 Hz, ArH), 7.95 (d, 2H, J = H 1.62, N 13.40, S 15.55. 8.4 Hz, ArH); 13C NMR (100 MHz, DMSO-d6) δ/ppm: 3,4-Dichlorobenzoyl Isothiocyanate (Table 2, entry 4) 161.9 (O-C=O), 161.4 (N-C=O), 148.2 (N=C=S), 133.2, 24 –1 + Oil; IR (neat) ῡmax /cm : 3362, 3166, 3084, 3060, 132.4, 132.2, 129.9, 22.3; MS m/z: 221 (M , 5 %); 163 2018, 1955 (N=C=S), 1693 (C=O), 1658, 1583, 1458, (M+–NCS, 8 %); 104 (PhCO, 100 %); Anal. Calcd. mass 1383, 1266, 1232, 1106, 1030, 898, 837, 764, 734, 706, fractions of elements, w/%, for C10H7NO3S (Mr = 681, 547. 221.23) are: C 54.29, H 3.19, N 6.33, S 14.49; Found: C 54.08, H 3.29, N 6.48, S 14.92. 2-Chlorobenzoyl Isothiocyanate (Table 2, entry 5) 4 –1 Oil; IR (neat) ῡmax /cm : 3076, 1981 (N=C=S), 1948, 4-Acetamidobenzoyl Isothiocyanate (Table 2, entry 12) 28 –1 1790 (C=O), 1728, 1691, 1590, 1473, 1439, 1319, 1203, Oil; IR (neat) ῡmax /cm : 3460, 3264, 3182, 3096, 1132, 1077, 932, 997, 775, 742, 620, 477. 2953, 2921, 2851, 1989 (N=C=S), 1697 (C=O), 1594, 1536, 1413, 1315, 1253, 1170, 1021, 955, 869, 751, 677.