Synthesis and characterization of derived imines from 4-imino-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-3(4H)-amine

ICC Original Research Article Iranian Chemical Communication Payame Noor University of Ilam http://icc.journals.pnu.ac.ir Synthesis and characterization of derived imines from 4-imino-5,6,7,8tetrahydro-1-benzothieno[2,3-d]pyrimidin-3(4H)-amine Mehdi Soleimany *, Jalil Lari, Hooshang Vahedi Department of Chemistry, Payame Noor University, P.O. BOX 19395-4697, Tehran, Iran Received: 22 October 2013 , Accepted: 11 November 2013, Published: 1 February 2014 Abstract The synthesis and characterization of derived imines from 4-imino-5,6,7,8-tetrahydro-1-benzo thieno[2,3-d]pyrimidin-3(4H)-amine 3 have been developed in three steps through the reaction of heteroaromatic o-aminonitrile 1 with triethyl orthoformate. The process afforded the corresponding of imido ester 2 and was followed by cyclization with hydrazine hydrate to furnish iminothienopyrimidineamine 3 and, finally, the imination of 3 with aromatic aldehydes generated the corresponding imines (5a-5h). It is worth mentioning that the process was done at room temperature. The new products were obtained in high yield with an easy work-up in simple reaction along with the purification of products by non-chromatographic method. This general synthetic procedure which can be extended to the preparation of wide variety of imines using o-aminonitrile bifunctional derivatives can also be synthesized by Gewald reaction. Keywords: Thieno[2,3-d]pyrimidines, o-aminonitrile, imination, Gewald reaction Introduction Thieno[2,3-d]pyrimidines are a large inflammatory [1,5,10], antiatherosclerotic [6], group of heterocycles with diverse and antihistaminic interesting These depressant [9] and ulcerogenic index [10] compounds are reported to possess significant activities. Various methods have already been analgesic proposed biological [1,5,10], activities. antifungal [2], anti- bacterial [2,3], antimicrobial [4,9], anti- for [7], the antitumor synthesis [8], of CNS these compounds. One of the most general ones *Corresponding author: Mehdi Soleimany Fax number: +98 (511) 7273358,Tel number: +98 (915) 5070940 E-mail: Mehdi Page | 18 Iran. Chem. Commun. 2 (2014) 18-26 M. Soleimany et al. / Iranian Chemical Communication 2 (2014) 18-26 involves cyclocondensation suitably Kieselgel different accomplished by iodine Flask or UV Lamp. electrophiles such as chloroformamidine [11], The IR spectra were recorded on a Shimadzu α-substituted acetonitriles [12], formic acid 8400 instrument (the samples as KBr disks [13], phosgene [14], ethyl chlorofor- mate [14] for the range 400-4000 cm-1).1H and 13C and guanidine [15]. It is worth mentioning that NMR spectra were measured (CDCl3 and the synthesis of derived imines from 4-imino- DMSO-d6 as solvents) with a BRUKER DRX- 5,6,7,8-tetrahydro-1-benzothieno [2,3-d] py- 400 AVANCE spectrometer. Chemical shifts rimidin-3(4H)-amine 3 has not been reported were reported in δ unit (ppm) with reference in the literature. to TMS as an internal standard. Elemental functionalizedthiophenes of with Prompted by these findings, and due to our interest heterocyclic in the synthesis compounds with of new potential biological activities [16], as well as in continuation of our works on the synthesis of GF254 analysis was and visualization performed on a was Thermo Finnigan (San Jose, CA, USA) Flash EA microanalyzer, and the results were found to match satisfactorily with the calculated and observed values. thieno [2,3-d]pyrimidine derivatives [16], we Procedure for the synthesis of 2- (ethoxyme- N- thylideneamino)-4,5,6,7-tetrahydrobenzo-1- report, herein, the synthesis of (arylmethylene)-4-imino-5,6,7,8-tetrahydro-1benzothieno[2,3-d]pyrimidin-3(4H)-amines thiophene-3-carbonitrile (2) A mixture of compound 1 (10 mmol) and trie- (5a–5h) in 3 steps through the imina- tion of 3 at room temperature with aromatic aldehydes. thyl orthoformate (20 mmol) in ethanol (10-15 mL) was refluxed for 9 h with continuous stirring. The progress of the reaction was monitored by TLC (ethyl acetate: n-hexane, 1:1, Experimental v/v) on silica gel and showed complete con- General version of the reactant to the product. After Melting with completing the reaction, the excess triethyl Electrothermal 9100 apparatus. Evaporation of orthoformate and ethanol was removed by dis- solvents reduced tillation under reduced pressure, and then Pe- pressure on a Buchi rotary evaporator. Thin troleum ether (10-20 mL) was added and layer chromatography was performed on boiled for a short period of time and, then, was points were performed recorded under Page | 19 Synthesis and characterization of derived imines from 4-imino-5,6,7,8-tetrahydro-1- … left to cool at 0 oC overnight. The generated 184 °C. IR (υ, cm-1): 3100-3400 (NH, NH2), solid was collected by filtration, dried and 2939 (CH- aliphatic), 1630 (C=N) cm-1. 1H crystallized from Petroleum ether in order to NMR (CDCl3) δ ppm: 1.84-1.98 (m, 4H, afford 2 in good yield. 2CH2), 2.77-2.85 (m, 2H, CH2), 2.85-2.94 (m, Orange crystals, Yield: 74 %, (1.73 g), mp 51-52 °C. IR (υ, cm-1): 2931 (CH-aliphatic), 2214 (CN), 1620 (C=N), 1257, 1211 (C-O) cm-1. 1H NMR (CDCl3) δ ppm: 1.39 (t, 3H, 2H, CH2), 4.16 (br s, 2H, NH2), 6.53 (br s, 1H, NH), 8.45 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3) δ ppm: 22.44, 22.49, 25.41, 26.25, 115.45, 125.34, 134.06, 152.62, 158.93, 165.10. Anal. calcd. for C10H12N4S CH3), 1.77-1.92 (m, 4H, 2CH2), 2.55-2.72 (m, (220.29): C (54.52), H (5.49), N (25.43), S 4H, 2CH2), 4.40 (q, 2H, CH2), 7.94 (s, 1H, (14.56). Found: C (54.45), H (5.60), N N=CH). 13 C NMR (CDCl3) δ ppm: 14.01, 21.55, 22.23, 23.03, 25, 58, 64.10, 101.66, 114.79, 128.50, 134.11, 157.31, 157.40. Anal. calcd. for C12H14N2OS (234.32): C (61.51), H (6.02), N (11.96), O (6.83), S (13.68). Found: (25.36), O (25.31), S (14.49) (%). General procedure for the synthesis of N(Arylmethylene)-4-imino-5,6,7,8– tetrahydro-1- benzothieno[2,3-d]pyrimidin3(4H)-amine (5a-5h) C (61.44), H (6.10), N (11.87), O (6.75), S (13.61) (%). Procedure for the synthesis of 4-imino5,6,7,8-tetrahydro-1-benzothieno[2,3d]pyrimidin-3(4H)-amine (3) A mixture of compound 2 (10 mmol) and hydrazine hydrate (20 mmol) in dioxane (1015 mL) was refluxed for 12 h with continuous stirring. After completing the reaction (monitored by TLC, chloroform: methanol, A mixture of compound 3 (2 mmol) and aromatic aldehydes 4a-4h (3 mmol) in ethanol (15 mL) was mixed at room temperature for 24 h with continuous stirring. The progress of the reaction was monitored by TLC (chloroform: methanol, 9:1, v/v) on silica gel and showed complete conversion of the reactant to the product. The precipitated solid was, then, filtered off, dried and recrystallized from ethanol to give derivatives (5a-5h) in good yield. 9:1, v/v), and cooling at 0 oC, the separated solid was collected by filtration, dried and N-(4-toluenemethylene)-4-imino-5,6,7,8- crys (...truncated)