TMSCl mediated highly efficient one-pot synthesis of octahydroquinazolinone and 1,8-dioxo-octahydroxanthene derivatives

Page  136 General Papers ARKIVOC 2006 (xvi) 136-148 TMSCl mediated highly efficient one-pot synthesis of octahydroquinazolinone and 1,8-dioxo-octahydroxanthene derivatives Srinivas Kantevari,* Rajashaker Bantu, and Lingaiah Nagarapu Organic Chemistry Division-II, Indian Institute of Chemical Technology, Uppal Road, Hyderabad-500007, India E-mail: [email protected] Abstract A simple, efficient and cost-effective method for the synthesis of octahydroquinazolinone and 1,8-dioxo-octahydroxanthene derivatives by a one-pot cyclocondensation of dimedone and aldehydes, with and without urea or thiourea respectively in the presence of Trimethylsilyl chloride (TMSCl) in MeCN/DMF has been described. Keywords: Octahydroquinazolinone, trimethylsilyl chloride, 1,8-dioxo-octahydro xanthene, cyclocondensation, one pot multi-component synthesis Introduction Octahydroquinazolinone derivatives have attracted considerable attention in recent years owing to their potential antibacterial activity against Staphylococcus aureus, Escherichiacoli, pseudomonas aeruginosa1, and also as a calcium antagonist2. Methods employed for their synthesis are the variant classical one pot multi-component Biginelli reaction involving dimedone, aromatic aldehydes and urea3. Although various Lewis acid catalysts are employed1,3,4a-c in the extension of the Biginelli reaction, they are expensive, harmful and are difficult to handle especially on large scale. Most of these procedures are sluggish, require longer reaction times, use strongly acidic conditions, give unsatisfactory yields and also suffer from the formation of many side products 4a. In continuation of our work on the use of silica-supported reagents5, TMSCl has attracted our interest. Among the various silicon-based acidic reagents, TMSCl has received considerable attention as an inexpensive and readily available reagent for various organic transformations6. Advantages such as its compatibility with many synthetically valuable nucleophiles (e.g., organometalic reagents, and cuprates) and its non-aggregation nature substantially simplify the analysis of the reaction mechanisms. Because of this, it has been extensively used as a protecting ISSN 1424-6376 Page 136 ©ARKAT

Page  137 General Papers ARKIVOC 2006 (xvi) 136-148 group for various functional groups such as hydroxy and amino group6a,7 and as a promoter for cycloadddition and conjugate addition reactions6a under mild and convenient conditions to offer the products in excellent yield and high selectivity. However, to the best of our knowledge, there is no report on the synthesis of octahydroquinazolinone using TMSCl as a reagent. In this communication, we report a TMSCl mediated simple, efficient and environmentally benign synthesis of octahydroquinazolinone (Schemes 1 & 2). During our study we also observed the formation of 1,8-dioxo-octahydroxanthene in excellent yields by one-pot Knoevenagel condensation, Michael addition and cyclodehydration of dimedone with various aldehydes in the presence of TMSCl (Scheme 3). O O H O H2N NH2 O NH N H O O + TMSCl MeCN / DMF(4:1) Scheme 1 O O O H2N NH2 X NH N H X O + TMSCl MeCN / DMF(4:1) R R 12 3 H 4 Scheme 2 O O O O + TMSCl CH3CN/DMF 1 2 5 O ArCHO Ar Scheme 3 ISSN 1424-6376 Page 137 ©ARKAT

Page  138 General Papers ARKIVOC 2006 (xvi) 136-148 Initially, a pilot reaction was attempted using benzaldehyde (1), dimedone (2) and urea (3) in the presence of TMSCl (0.5 equiv) with out any solvent (Scheme-I). After 3 hours only 27% of octahydroquinazolinone product was isolated. Increasing the amount of TMSCl (1.5 equiv) did not improve the product yield to a considerable amount. Subsequently, we investigated the effect of different solvents on the reaction rate and as well as yields of the products (Table 1). In protic solvents such as MeOH or EtOH, the reaction was very slow and resulted in lower product yield. Similar results were obtained in coordinating solvents such as THF, diethyl ether and dimethy ether. On the other hand, conducting the reactions in chlorinated solvents such as dichloromethane and chloroform improved both the reaction rates as well as product yields. After screening for different solvents, acetonitrile / DMF (6.0 ml + 1.5 ml) came out as the solvent of choice, which not only afforded the products in good yield, but also with higher reaction rates (95% yield in 1.5 h). It is also noticed that the condensation using TMSCl proceeds rapidly and is superior to the reported procedures1,3,4a-c with respect to reaction time, temperature and yield. This claim is justified through the representative examples, illustrated in Table- 2, in which the efficiency of TMSCl has been compared with those of recently reported supported Lewis / protic acid catalysts (Table 2). Table 1. Effect of solvents in the condensation dimedone, benzaldehyde and urea in the presence of TMSCl Entry a Solvent Time (h) Yield (%)b 1 Neat 3 27 2 Methanol 5 36 3 Ethanol 4 42 4 THF 3 45 5 Et2O 4 49 6 DME 3 52 7 CH2Cl2 2 63 8 CHCl3 2 65 9 CH3CN / DMF 1.5 95 a All reactions were performed using benzaldehyde (10 mmol), urea (15 mmol), thiourea (15 mmol), dimedone (10 mmol) and TMSCl (20 mmol) in CH3CN/DMF(4:1 ratio). b Isolated yields. ISSN 1424-6376 Page 138 ©ARKAT

Page  139 General Papers ARKIVOC 2006 (xvi) 136-148 Table 2. Synthesis of octahydroquinazolinone 4a using different reagents and reaction conditions S.No Reagent Solvent Temp (oC) Time (h) Yield (%) 4a Ref 1 Conc.H2SO4 Ethanol 80 9.0 -4a 2 Conc.H2SO4 H2O RT 3.0 85 3 3 HClO4-SiO2 (50 CH3CN Reflux 6.0 54 - mg, 0.025 mmol) 4 Conc. HCl Ethanol Reflux 6.5 -4b 5 Acid Alumina Neat Reflux 6.0 -1 6 VCl3 CH3CN Reflux 2.0 67-92 4c 7 TMSCl CH3CN Reflux 5.0 15 - 8 TMSCl CH3CN/DMF Reflux 1.5 95 - In order to evaluate the generality of the process, several diversified examples illustrating the present method for the synthesis of octahydroquinazolinone 4 was studied (Scheme 2, Table 3). The reaction of dimedone 2 with various aromatic aldehydes 1 bearing electron withdrawing groups (such as nitro, halide) or electron releasing groups (such as N,N-dimethylamino, methyl, hydroxyl; mono, di, or tri methoxy groups), and urea or thiourea 3 was carried out in the presence of TMSCl. The yields obtained were good to excellent without formation of any side products such as 1,8-dioxo-Octahydroxanthenes, which are normally observed under the influence of strong acids4a. The reaction of aromatic aldehydes having electron-withdrawing groups reacted very well at faster rate compared with aromatics aldehydes substituted with electron releasing groups, unlike those of urea, the reactions of thiourea proceeded at lower rate less efficiently to give octahydroquinazolinone (entry 1 and 15, 2 and 16). The results obtained in the current method are illustrated in Table 3. All the products obtained were fully characterized by spectroscopic methods such as IR, 1H NMR, 13C NMR and mass spectroscopy and also by comparison with the reported 2a, 4a spectral data. The simplicity, together with the use of inexpensive, non-toxic and environmentally benign nature of TMSCl under CH3CN/DMF solvent is a remarkable feature of the procedure. Encouraged by these results we were delighted to observe that the present protocol could safely be extended to the condensation reaction involving equimolar quantity of aldehyde 1, dimedone 2. 1-8-dioxo-octahydroxanthenes were obtained in excellent yields (Scheme 3, Table 4) with out the formation of any side products. ISSN 1424-6376 Page 139 ©ARKAT

Page  140 General Papers ARKIVOC 2006 (xvi) 136-148 Table 3. TMSCl-Mediated synthesis of various octahydroquinazolinone Entry R X Produc Time Yield Mp ( 0C) Ref. tb (h) %a,c Found Reported 1 C6H5 O 4a 1.5 95.0 292-295 290-291 2a 2 3-Cl C6H4 O 4b 2.0 91.8 281-282 282-283 2a 3 4-Cl C6H4 O 4c 2.0 94.1 >300 >300 2a, 12 4 2,4-Cl2C6H3 O 4d 2.0 82.5 268-270 -- 5 4-BrC6H4 O 4e 1.5 93.2 >300 >300 2a 6 4-MeC6H4 O 4f 2.0 87.3 >300 >300 4a 7 NMe2C6H4 O 4g 2.0 80.7 231-232 -- 8 3-OMeC6H4 O 4h 1.5 86.2 247-248 247-248 4a 9 3,4,5-(OCH3)3 C6H2 O 4i 2.0 80.5 139-140 -- 10 (CH3)2CH O 4j 1.5 75.8 >300 -- 11 4-Pyridyl O 4k 2.0 71.2 >300 -- 12 4-NO2C6H4 O 4l 1.5 84.6 304-305 -- 13 3-NO2C6H4 O 4m 1.5 78.8 299-300 300-301 4a 14 4-OHC6H4 O 4n 2.5 71.7 300-302 -- 15 C6H5 S 4o 2.5 76.0 284-285 -- 16 3-ClC6H4 S 4p 2.5 71.6 275-276 275-276 2a 17 4-BrC6H4 S 4q 2.5 78.4 285-286 -- 18 4-OMeC6H4 S 4r 2.5 82.0 272-275 -- 19 3-OMeC6H4 S 4s 3.0 77.5 270-272 -- 20 4-MeC6H4 S 4t 2.5 81.8 273-275 -- 21 4-NMe2C6H4 S 4u 3.0 70.0 275-276 -- a All reactions were performed at 10mmol scale using 20mmol of TMSCl in CH3CN/DMF (6ml / 1.5ml-) at reflux temperature (80oC) b All the products were well characterized by 1H NMR, IR and Mass spectral data. c Isolated yields. Trimethylsilyl chloride showed remarkable reactivity as a “hard-soft” reagent and considerably accelerated the reactions. On the basis of all our experimental results, together with literature reports6,10, we have proposed the plausible mechanism13 for the formation of octahydroquinazolinone 4 in the presence of TMSCl (Scheme 4). The reaction is believed to precede through the formation of an N-acyliminium ion intermediate 7 from the urea or thiourea and aldehyde 1 precursor in the presence of TMSCl, leading to the formation of octahydroquinazolinone 4. ISSN 1424-6376 Page 140 ©ARKAT

Page  141 General Papers ARKIVOC 2006 (xvi) 136-148 Table 4. TMSCl-Mediated synthesis of various 1,8-dioxo-octahydroxanthenes a Entry Ar Productb Time (h) Temp ( 0C) Yieldc Mp ( 0C) Ref. (%) Found Reported 1 C6H5 5a 8 Reflux 84.1 201-203 202-204 11 2 4-Cl C6H4 5b 8 Reflux 81.0 230-232 228-230 11 3 2,4-Cl2C6H3 5c 8 Reflux 74.3 254-255 253-254 11 4 4-Br C6H4 5d 10 Reflux 79.2 240-242 -- 5 3-OMeC6H4 5e 10 Reflux 71.9 160-162 -- a All reactions were performed at 10mmol scale using 20mmol of TMSCl in CH3CN (5ml) b All the products were well characterized by 1H NMR, IR and Mass spectral data. c Isolated yields H2N NH2 H2N NHTMS X N H NHTMS X R TMSCl RCHO + O O O N H NH R X O OH NH TMSHN X R 3 6 7 84 2 O N TMS NH R X OH -TMSOH 9 X Scheme 4. Plausible mechanism for the formation of Octahydroquinazolinone 4. In conclusion, a series of octahydroquinazolinone and 1-8-dioxo-octahydroxanthenes were synthesized efficiently by the condensation of aldehydes 1, dimedone 2 and urea or thiourea 3 respectively in the presence of TMSCl (20 mmol) in CH3CN/DMF conditions. The current protocol was also applied successfully for the synthesis of 1,8-dioxo-octahydroxanthenes from aromatic aldehyde and dimedone. The method has ability to tolerate structurally and electronically divergent substituents in aldehydes; variable reaction conditions, shorter reaction times and simple work-up procedure are other advantages. Further, the present procedure is ISSN 1424-6376 Page 141 ©ARKAT

Page  142 General Papers ARKIVOC 2006 (xvi) 136-148 readily amenable to large-scale synthesis and the generation of combinatorial octahydroquinazolinones and 1,8-dioxo-octahydroxanthenes. Experimental Section General Procedures. All the commercial reagents and solvents were used without further purification unless otherwise stated. Melting points were recorded on Buchi 535 melting point apparatus and are uncorrected. All the reactions were monitored by thin layer chromatography performed on precoated silica gel 60F254 plates (Merck). Compounds were visualized with UV light at 254nm and 365nm, iodine and heating plates after dipping in 2% phosphomolybdic acid in 15% aq. H2SO4 solution. NMR spectra were recorded on Varian Unity-400 MHz and BRUKER AMX 300 MHz spectrometers using tetra methyl silane as an internal standard. 13C NMR was recorded on Varian Unity 100 MHz using CDCl3 as internal standard. Mass spectra were recorded on a VG Micromass 7070H and Finnigan Mat 1020B mass spectrometers operating at 70ev. Typical procedure for the synthesis of octahydroquinazolinone A solution of benzaldehyde 1a (10 mmol), dimedone 2a (10 mmol) and urea or thiourea (15mmol), and MeCN/DMF (6ml/1.5ml) containing TMSCl (20 mmol) was refluxed (80oC) till the reaction was completed (monitored by TLC). The solid product 4a obtained was filtered through a Buchner funnel, washed with MeCN (3x 5 ml) and dried. The compound was recrystallized in ethanol to give pure crystalline product. The representative spectral data of octahydroquinazolinone derivatives 4a-4u are given below. 7,7-Dimethyl-4-phenyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4a). Mp 292-295 0C, (Lit.2a mp 290-2910C); IR (KBr) .max 3317(br), 3258(br), 2961(br), 1709(s), 1673(s), 1608(vs), 1445(w), 1371(s), 1230(s), 761(s), 692(w), 562(w), 486(w), 427(w) cm-1. 1H NMR (300MHz, CDCl3 + DMSO-d6), d 0.97(s, 3H, CMe); 1.10(s, 3H, CMe); 2.18 (q, J=16.1Hz, 2H, CH2); 2.39(q, J=16.8Hz, 2H, CH2 ); 5.27 (d, J=2.8Hz,1H, CH); 7.32-7.21 (m, 5H, Ar ); 7.45(s, 1H, NH); 9.38(s, 1H, NH ); MS (ESI) m/z 271 ([M+H])+; Anal. Calcd for C16 H18 N2 O2: C, 71.09; H, 6.71, N, 10.36. Found: C, 71.16, H, 6.69; N 10.33. 4-(3-Chloro-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4b). Mp 281-282 0C, (Lit.2a mp 282-2830C); IR (KBr) .max 3248(br), 2955(br), 1700(vs), 1618(vs), 1471(sh), 1376(s), 1236(s), 1048(w), 804(w), 724(br), 563(s), 508(s) cm-1;1H NMR (400MHz,CDCl3+DMSO-d6), d 0.96(s, 3H, CMe); 1.09(s, 3H, CMe); 2.18 (q, J=16.5Hz, 2H, CH2); 2.39(q, J=18.0Hz, 2H, CH2 ); 5.23 (d, J=2.8Hz,1H, CH); 7.17-7.28 (m, 4H, Ar ); 7.66(s, 1H, NH); 9.44(s, 1H, NH ); MS (ESI) m/z 305 ([M+H])+ . Anal. Calcd for C16 H17 Cl N2 O2: C, 63.05; H, 5.62, N, 9.19. Found: C, 63.11, H, 5.62; N 9.23. 4-(4-Chloro-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4c). Mp >300 0C (Lit.2a mp >300 0C) ; IR (KBr) .max 3249(br), 2961(br), 1699(vs), 1612(vs), 1488(s), ISSN 1424-6376 Page 142 ©ARKAT

Page  143 General Papers ARKIVOC 2006 (xvi) 136-148 1375(s), 1238(s), 809(w), 763(w), 566(s), 509(w) cm-1; 1H NMR (400MHz,CDCl3+DMSO-d6), d 0.96(s, 3H, CMe); 1.09(s, 3H, CMe); 2.19(q, J=17.5Hz, 2H, CH2); 2.37(q, J=17.5Hz, 2H, CH2 ); 5.31 (d, J=2.9Hz, 1H, CH); 7.19-7.30 (m, 4H, Ar); 7.54(s, 1H, NH); 9.36(s, 1H, NH ); MS (ESI) m/z 305 ([M+H])+; Anal. Calcd for C16 H17 Cl N2 O2: C, 63.05; H, 5.62, N, 9.19. Found: C, 63.11, H, 5.61; N 9.20. 4-(2,4-Dichloro-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4d). Mp 268-270 0C; IR (KBr) .max 3325(br), 3103(br), 2956(br), 1701(vs), 1627(vs), 1450(m), 1375(s), 1236(s), 862(m), 755(w), 521(w), 464(w), 417 cm-1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 0.99(s, 3H, CMe); 1.04(s, 3H, CMe); 2.10(q, J=16.1Hz, 2H, CH2); 2.35(q, J=17.6Hz, 2H, CH2 ); 5.57(d, J=2.9Hz, 1H, CH); 7.08-7.19 (m, 3H, Ar ); 7.28(s, 1H, NH); 9.45(s, 1H, NH ); 13C NMR (75MHz, DMSO-d6): d 192.9 (C=O), 153.3 (NC=O), 151.0 (NC=C), 140.2, 132.9, 132.5, 131.0, 128.9, 127.5 (ArC), 105.4 (OC-C=C), 50.6 (C-NH), 49.8 (CH2), 32.2 (>C<, CH2), 28.6, 27.1 (CH3); MS (ESI) m/z 340 ([M+H])+ ; Anal. Calcd for C16 H16 Cl2 N2 O2: C, 56.63; H, 4.75, N, 8.26. Found: C, 56.63, H, 4.74; N 8.26. 4-(4-Bromo-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4e). Mp >300 0C (Lit.2a mp >300 0C); IR (KBr) .max 3249(br), 2961(br), 1708(s), 1612(vs), 1488(sh), 1375(s), 1231(s), 1011(s), 840(w), 762(br), 562(w), 491(w) cm-1; 1H NMR (400MHz,CDCl3+DMSO-d6), d 0.95(s, 3H, CMe); 1.08(s, 3H, CMe); 2.16(q, J=16.3Hz, 2H, CH2); 2.37(q, J=17.8Hz, 2H, CH2); 5.22(d, J=2.9Hz, 1H, CH); 7.21-7.39 (m, 4H, Ar); 7.56(s, 1H, NH); 9.41(s, 1H, NH); MS (ESI) m/z 350 ([M+H])+; Anal. Calcd for C16 H17 Br N2 O2: C, 55.03; H, 4.91, N, 8.02. Found: C, 55.10, H, 4.99; N 8.02. 7,7-Dimethyl-4-p-tolyl-4,6,7,8-tetrahydro-1H, 3H-quinazoline-2,5-dione (4f). Mp. >300 0C,(Lit.4a mp >300 0C); IR (KBr) .max 3252(br), 2960(br), 1711(s), 1673(vs), 1613(vs), 1420(w), 1374(s), 1233(s), 1045(w), 760(br), 563(w) cm-1.1H NMR (500MHz,CDCl3 + DMSO-d6), d 0.97(s, 3H, CMe); 1.09(s, 3H, CMe); 2.16(q, J=16.3Hz, 2H, CH2); 2.37(q, J=17.9Hz, 2H, CH2); 2.30(s, 1H, CH3), 5.22(d, J=1.8Hz, 1H, CH); 7.04-7.18 (m, 4H, Ar); 7.29(s, 1H, NH); 9.28(s, 1H, NH); MS (ESI) m/z 285 ([M+H])+. Anal. Calcd for C17 H20 N2 O2: C, 71.81; H, 7.09, N, 9.85; Found: C, 71.82, H, 7.11; N 9.84. 4-(4-Dimethylamino-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4g). Mp. 231-232 0C; IR (KBr) .max 3343(br), 3231(br), 2958(br), 1638(m), 1615(vs), 1461(sh), 1375(s), 1242(s), 1191(m), 1146(w), 567 cm-1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 0.98(s, 3H, CMe); 1.09(s, 3H, CMe); 2.18(q, J=16.1Hz, 2H, CH2); 2.38(q, J=16.8Hz, 2H, CH2); 2.54(s, 6H, NMe2), 5.25(d, J=2.9Hz, 1H, CH); 7.32-7.40 (m, 4H, Ar); 7.80(s, 1H, NH); 9.34(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 193.0 (C=O), 152.8 (NC=O), 151.6 (NC=C), 143.6, 127.6, 119.1 (6xArC), 106.9 (OCC=C), 51.4 (C-NH), 49.7(CH2), 44.4, 40.2(2xNCH3), 32.2(>C<, CH2) , 28.6, 27.0 (CH3); MS (ESI) m/z 314 ([M+H])+ Anal. Calcd for C18 H23 N3 O2: C, 68.98; H, 7.40, N, 13.41; Found: C, 68.97, H, 7.39; N 13.42. 4-(3-Methoxy-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4h). Mp. 247-248 0C (Lit.4a mp 247-248 0C); IR (KBr) .max 3251(br), 3117(br), 2956(br), 1697(vs), 1618(vs), 1376(s), 1233(sh), 1154(m), 1040(w), 788(w), 732(w), 565, 514 cm-1; 1H NMR ISSN 1424-6376 Page 143 ©ARKAT

Page  144 General Papers ARKIVOC 2006 (xvi) 136-148 (400MHz,CDCl3 + DMSO-d6), d 0.98(s, 3H, CMe); 1.09(s, 3H, CMe); 2.17(q, J=16.4Hz, 2H, CH2); 2.38(q, J=17.9Hz, 2H, CH2); 3.75(s, 3H, OCH3), 5.22(d, J=2.9Hz, 1H, CH); 6.71(dd, J=8.22Hz, 1H, Ar); 6.87(m, 2H, Ar), 7.18(t, J=8.22Hz, 1H, Ar) 7.28(s, 1H, NH); 9.35(s, 1H, NH); MS (ESI) m/z 301 ([M+H])+. Anal. Calcd for C17 H20 N2 O3: C, 68.98; H, 6.71, N, 9.33; Found: C, 68.97, H, 6.74; N 9.33. 7,7-Dimethyl-4-(3,4,5-trimethoxy-phenyl)-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4i). Mp 139-140 0C; IR (KBr) .max 3371(br), 3236(br), 3114(br), 2943(br), 1639(vs), 1377(s), 1240(s), 1128(s), 100(m)2, 760(w), 577 cm-1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 1.03(s, 3H, CMe); 1.10(s, 3H, CMe); 2.20(q, J=16.9Hz, 2H, CH2); 2.39(q, J=16.9Hz, 2H, CH2); 3.77(s, 3H, OCH3), 3.78(s, 6H, OCH3), 5.20(d, J=2.9Hz, 1H, CH); 6.53(s, 2H, Ar); 7.28(s, 1H, NH); 9.33(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 192.9(C=O), 162.9 (NC=O), 152.6 (NC=C), 139.8, 136.6, 114.1, 106.8, 105.3 (6xArC), 103.4(OC-C=C), 59.8 (2xOCH3), 55.6 (OCH3), 51.7 (C-NH), 49.7(CH2), 32.1(>C<, CH2), 28.8, 26.5 (CH3); MS (ESI) m/z 361 ([M+H])+. Anal. Calcd for C19 H24 N2 O5: C, 63.32; H, 6.71, N, 7.77; Found: C, 63.31, H, 6.71; N 7.76. 4-Isopropyl-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4j). Mp >300 0C; IR (KBr) .max 3235(br), 3127(br), 2960(br), 1696(vs), 1615(vs), 1380(s), 1239(s), 1151(m), 1062(w), 802 cm-1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 0.79(d, J=7.1Hz, 3H), 0.90(d, J=7.1Hz, 3H), 1.06(s, 3H, CMe); 1.08(s, 3H, CMe); 2.17(q, J=16.4Hz, 2H, CH2); 2.32(q, J=17.1Hz, 2H, CH2 ); 4.08(s, 1H, CH); 7.01(s, 1H, NH); 9.10(s, 1H, NH ); 13C NMR (75MHz, CDCl3 + DMSO-d6): d 191.6(C=O), 151.5 (NC=O), 151.3 (NC=C), 104.8 (OCC=C), 52.3 (C- NH) , 48.6 (CH2), 31.9 (CH2) 30.4(>C<), 27.5(CH3, CH) , 25.3, 16.9, 14.0 (3xCH3); MS (ESI) m/z 237 ([M+H])+. Anal. Calcd for C13 H20 N2 O2: C, 66.07; H, 8.53, N, 11.85; Found: C, 66.08, H, 8.53; N 11.84. 7,7-Dimethyl-4-pyridin-4-yl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4k). Mp >300 0C; IR (KBr) .max 3122(br), 2962(br), 1689(s), 1637(vs), 1375(s), 1245(s), 1169(m), 786(w), 563 cm-1; 1H NMR (400 MHz, CDCl3+DMSO-d6), d 0.88(s, 3H, CMe); 1.04(s, 3H, CMe); 2.03(q, J=16.4Hz, 2H, CH2); 2.38(q, J=17.9Hz, 2H, CH2); 5.22(s, 1H, CH); 7.12-7.74(m, 4H, Ar), 8.45(s, 1H, NH); 9.47(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 192.9 (C=O), 153.1( NC=O), 152.5 (ArC), 151.8 (NC=C), 149.5, 121.3 (4 x ArC) ,106.2 (OCC=C), 59.4 (C-NH), 50.8, 49.4 (CH2), 32.1(>C<), 28.3, 26.5 (CH3); MS (ESI) m/z 272 ([M+H])+. Anal. Calcd for C15 H17 N3 O2; C, 66.40; H, 6.32, N, 15.41; Found: C, 66.40, H, 6.33; N 15.41. 7,7-Dimethyl-4-(4-nitrophenyl)-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4l). Mp 304-305 0C; IR (KBr) .max 3323(br), 3244(br), 2963(br), 1671(s), 1623(vs), 1375(m), 1230(s), 829(w), 761 cm-1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 0.89(s, 3H, CMe); 1.06(s, 3H, CMe); 2.16(q, J=16.7Hz, 2H, CH2); 2.35(q, J=17.4Hz, 2H, CH2); 5.39(d, J=2.8Hz, 1H, CH); 7.52(d, J=8.36Hz, 2H, Ar); 8.09(d, J=8.36Hz, 2H, Ar); 7.56(s, 1H, NH); 9.44(s, 1H, NH); 13C NMR (50MHz, DMSO-d6): d 193.2 (C=O), 153.3 (NC=O), 151.8 (NC=C), 151.7, 146.7, 127.7, 123.8 (6x ArC), 106.5(OCC=C), 51.9 (C-NH), 49.8 (CH2), 32.4 (>C<,CH2), 28.7, 26.9 (CH3); MS (ESI) m/z 316 ([M+H])+. Anal. Calcd for C16 H17 N3 O4; C, 60.94; H, 5.43, N, 13.33; Found: C, 60.94, H, 5.44; N 13.32. ISSN 1424-6376 Page 144 ©ARKAT

Page  145 General Papers ARKIVOC 2006 (xvi) 136-148 7,7-Dimethyl-4-(3-nitro-phenyl)-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4m). Mp 299-300 0C (Lit.4a 300-302 0C) IR (KBr) .max 3117, 2956, 1697, 1618, 1377, 1233, 1153, 788 cm1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 1.06(s, 3H, CMe); 1.12(s, 3H, CMe); 2.18(q, J=16.6Hz, 2H, CH2); 2.43(q, J=16.6Hz, 2H, CH2); 5.84(d, J=2.3Hz, 1H, CH); 7.37-7.80(m, 4H, Ar); 7.86(s, 1H, NH); 9.58(s, 1H, NH); MS (ESI) m/z 316 ([M+H])+. Anal. Calcd for C16 H17 N3 O4; C, 60.94; H, 5.43, N, 13.33; Found: C, 60.94, H, 5.44; N 13.34. 4-(4-Hydroxyphenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-dione (4n). Mp 300-302 0C; IR (KBr) .max 3414(br), 3242(br), 2967(br), 1646(vs), 1614(s), 1463(s), 1373(s), 1225(s), 1170(m), 1106(w), 762(w), 504 cm-1; 1H NMR (400MHz,CDCl3 + DMSO-d6), d 0.98(s, 3H, CMe); 1.09(s, 3H, CMe); 2.14(q, J=15.8Hz, 2H, CH2); 2.33(q, J=17.3Hz, 2H, CH2); 5.14(d, J=2.2Hz, 1H, CH); 6.65(d, J=8.65Hz, 2H, Ar), 7.06(d, J=8.65Hz, 2H, Ar), 7.45(s, 1H, NH); 9.27(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 192.9 (C=O), 156.3 (NC=O), 151.99 (NC=C), 151.94, 135.1, 127.3, 114.9 (6x ArC), 107.8 (OCC=C), 51.3 (C-NH), 49.8 (CH2), 32.2 (>C<, CH2), 28.7, 26.8(CH3); MS (ESI) m/z 287 ([M+H])+. Anal. Calcd for C16 H18 N2 O3; C, 67.12; H, 6.34, N, 9.78; Found: C, 67.12, H, 6.33; N 9.77. 7,7-Dimethyl-4-phenyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H- quinazolin-5-azone (4o). Mp. 284-285 0C; IR (KBr) .max 3259(br), 3175(br), 2957(br), 1618(vs), 1566(s), 1459(s), 1373(s), 1145(m), 1100(sh), 158(w), 690, 553, 516, 427 cm-1; 1H NMR (200MHz, CDCl3 + DMSO-d6), d 0.94(s, 3H, CMe); 1.09(s, 3H, CMe); 2.27 (q, J=16.4Hz, 2H, CH2); 2.37(s, 2H, CH2 ); 5.25 (d, J=3.1Hz,1H, CH); 7.18-7.29 (m, 5H, Ar ); 9.46(s, 1H, NH); 10.37(s, 1H, NH ); 13C NMR (75MHz, DMSO-d6): d 193.4 (C=O), 174.5 (NC=O), 148.5 (NC=C), 143.2, 128.3, 127.3, 126.2 (6xArC), 108.0 (OCC=C), 52.0 (C-NH), 49.7 (CH2), 32.1(CH2, >C<), 28.6, 26.6 (CH3); MS (ESI) m/z 287 ([M+H])+. Anal. Calcd for C16 H18 N2 O S; C, 67.10; H, 6.33, N, 9.78; Found: C, 67.11, H, 6.33; N 9.77. 4-(3-Chlorophenyl)-7,7-dimethyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5-one (4p). Mp 275-276 0C (Lit.2a 275-276 0C) IR (KBr) .max 3236(br), 2950(br), 1611(vs), 1415(w), 1376(s), 1200(m), 1078(w), 804(w), 713(w), 559 cm-1; 1H NMR (200MHz,CDCl3 + DMSO-d6), d 0.97(s, 3H, CMe); 1.10(s, 3H, CMe); 2.16 (q, J=16.4Hz, 2H, CH2); 2.38(s, 2H, CH2); 5.28 (d, J=3.9Hz, 1H, CH); 7.27-7.16 (m, 4H, Ar); 9.46(s, 1H, NH); 10.41(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 193.5(C=O), 174.6 (NC=O), 148.9 (NC=C), 145.4, 132.8, 130.4, 127.3, 126.1, 124.8 (6x ArC), 107.4 (OCC=C), 51.6 (C-NH), 49.6 (CH2), 32.1 (>C<, CH2), 28.5, 26.6 (CH3); MS (ESI) m/z 321.5 ([M+H])+. Anal. Calcd for C16 H17 Cl N2 O S; C, 59.90; H, 5.34, N, 8.73; Found: C, 59.90, H, 5.34; N 8.72. 4-(4-Bromophenyl)-7,7-dimethyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5-one (4q). Mp 285-286 0C; IR (KBr) .max 3163(br), 2956(br), 1626(vs), 1570(s), 1459(s), 1375(s), 1201(sh), 1176(m), 1102(m), 1008(m), 781(w), 556 cm-1; 1H NMR (200MHz,CDCl3 + DMSOd6), d 0.88(s, 3H, CMe); 1.03(s, 3H, CMe); 2.09(q, J=16.6Hz, 2H, CH2); 2.29(s, 2H, CH2); 5.22(d, J=2.9Hz, 1H, CH); 7.16 (d, J=8.7Hz, 2H, Ar); 7.35(s, J=8.7Hz, 2H, Ar); 9.28(s, 1H, NH); 10.30(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 193.4 (C=O), 174.5 (NC=O), 148.7 (NC=C), 142.5, 131.7, 131.2, 128.4, 120.4 (6x ArC), 107.6 (OCC=C), 51.6(C-NH), 49.6 (CH2), ISSN 1424-6376 Page 145 ©ARKAT

Page  146 General Papers ARKIVOC 2006 (xvi) 136-148 32.1(>C<, CH2), 28.5, 26.6 (CH3); MS (ESI) m/z 366 ([M+H])+. Anal. Calcd for C16 H17 Br N2 O S: C, 52.61; H, 4.69, N, 7.67; Found: C, 52.60, H, 4.69; N 7.66. 4-(4-Methoxyphenyl)-7,7-dimethyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5-one (4r). Mp 272-275 0C; IR (KBr) .max 3261(br), 3164(br), 2956(br), 1640(vs), 1584(vs), 1375(s), 1252(m), 1168(s), 1023(m), 827(w), 768(w), 551 cm-1; 1H NMR (200MHz,CDCl3 + DMSO-d6), d 0.96(s, 3H, CMe); 1.10(s, 3H, CMe); 2.14(q, J=16.0Hz, 2H, CH2); 3.11(s, 2H, CH2); 3.75(s, 3H, OCH3), 5.17(d, J=2.9Hz, 1H, CH); 6.81(d, J=8.7Hz, 2H, Ar); 7.20(d, J=8.7Hz, 2H, Ar); 9.42(s, 1H, NH); 10.34(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 194.0 (C=O), 174.8 (NC=O), 159.0 (ArC), 148.8 (NC=C), 136.0, 128.0, 114.2, 108.7 (5x ArC), 100.3 (OCC=C), 55.5 (OCH3), 52.0 (C-NH), 50.3 (CH2), 32.7 (>C<, CH2), 29.2, 27.2 (CH3) ; MS (ESI) m/z 317 ([M+H])+. MS (ESI) m/z 317 ([M+H])+. Anal. Calcd for C17 H20 N2 O2 S: C, 64.53; H, 6.37, N, 8.85; Found: C, 64.52, H, 6.36; N 8.86. 4-(3-Methoxyphenyl)-7,7-dimethyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5-one (4s). Mp 270-272 0C; IR (KBr) .max 3340(br), 3181(br), 2956(br), 1611(vs), 1572(s), 1374(s), 1245, 1147, 1040, 769(w), 704, 567 cm-1.1H NMR (400MHz,CDCl3 + DMSO-d6), d 0.97(s, 3H, CMe); 1.11(s, 3H, CMe); 2.22(q, =16.1Hz, 2H, CH2); 2.39(s, 2H, CH2); 3.77(s, 3H, OCH3), 5.22(d, J=3.6Hz, 1H, CH); 6.76-7.22(m, 4H, Ar); 9.51(s, 1H, NH); 10.41(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 193.5 (C=O), 174.6(NC=O), 159.1(N-C=C), 148.6, 144.6, 130.0, 129.4, 118.2, 112.3 (6x ArC), 107.8(OCC=C) , 54.8 (OCH3), 51.7(C-NH), 49.7 (CH2), 32.1(>C<, CH2), 28.6, 26.5 (2xCH3); MS (ESI) m/z 317 ([M+H])+. Anal. Calcd for C17 H20 N2 O2 S; C, 64.53; H, 6.37, N, 8.85; Found: C, 64.54, H, 6.36; N 8.85. 7,7-Dimethyl-2-thioxo-4-p-tolyl-2,3,4,6,7,8-hexahydro-1H-quinazolin-5-one (4t). Mp. 273275; IR (KBr) .max 3278(br), 2957(br), 1606(vs), 1572(s), 1374(vs), 1261, 1097(m), 816, 759(w), 580 cm-1; 1H NMR (500MHz,CDCl3 + DMSO-d6), d 0.95(s, 3H, CMe); 1.10(s, 3H, CMe); 2.14(q, J=16.4Hz, 2H, CH2); 2.36(s, 2H, CH2); 2.30(s, 3H, CH3), 5.23(d, J=3.1Hz, 1H, CH); 7.18-7.04 (m, 4H, Ar); 9.32(s, 1H, NH); 10.29(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 193.4 (C=O), 174.4 (N-C=O), 148.3 (N-C=C), 140.3, 136.5, 128.8, 126.1 (6x ArC), 108.1(OCC=C), 51.7 (C-NH), 49.7(CH2), 32.1(>C<, CH2), 28.6, 26.6, 20.5 (CH3); MS (ESI) m/z 301 ([M+H])+. Anal. Calcd for C17 H20 N2 O S: C, 67.97; H, 6.71, N, 9.32; Found: C, 67.96, H, 6.72; N 9.32. 4-(4-Dimethylamino-phenyl)-7,7-dimethyl-2-thioxo-2,3,4,6,7,8-hexahydro-1H-quinazolin-5one (4u). Mp. 275-276 0C; IR (KBr) .max 3278(br), 3180(br), 2957, 1616(vs), 1454(s), 1371, 1235, 807, 764, 556(m), 499 cm-1; 1H NMR (200MHz,CDCl3 + DMSO-d6), d 0.97(s, 3H, CMe); 1.10(s, 3H, CMe); 2.25(q, J=16.0Hz, 2H, CH2); 2.37(s, 2H, CH2); 2.97(s, 6H, NMe2), 5.18(d, J=2.9Hz, 1H, CH); 6.89-7.20 (m, 4H, Ar); 9.37(s, 1H, NH); 10.33(s, 1H, NH); 13C NMR (75MHz, DMSO-d6): d 193.5 (C=O), 174.6 (N-C=O), 159.1(N-C=C), 148.7, 144.6, 129.5, 118.3, 112.3 (6x ArC), 107.8 (OCC=C), 54.8 (C-NH), 51.7(CH2), 34.7 (CH2), 32.1(>C<), 28.6, 26.6 (CH3), 18.4 (2x NCH3); MS (ESI) m/z 330 ([M+H])+. Anal. Calcd for C18 H23 N3 O S; C, 65.62; H, 7.04, N, 12.75; Found: C, 65.63, H, 7.03; N 12.75. ISSN 1424-6376 Page 146 ©ARKAT

Page  147 General Papers ARKIVOC 2006 (xvi) 136-148 Typical procedure for the synthesis of 1,8-dioxooctahydroxanthene A solution of benzaldehyde 1a (10mmol), dimedone 2a (20mmol) and MeCN (5 ml) containing TMSCl (10mmol) was refluxed till the reaction was completed (monitored by TLC). After completion the reaction mixture was cooled to RT, extracted with EtOAc (2x 25ml). The organic layer was washed with water (2x 20ml), dried over Na2SO4 and concentrated to obtain crude product. The crude product was crystallized by ethanol to obtain pure 9-aryl-1,8dioxooctahydroxanthene 5a as white crystalline solid. The representative spectral (1H NMR) data of 1,8-dioxo-octahydroxanthene derivatives 5a-5e are given below. 3,3,6,6-Tetramethyl-9-phenyl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-dione (5a). Mp 201203 0C (Lit.11 mp 202-2040C); 1H NMR (300MHz, CDCl3), d0.99(s, 6H, CMe2); 1.11(s, 6H, CMe2); 2.14-2.23(q, J=15.86Hz, 4H 2xCH2); 2.43 (s, 4H, 2xCH2); 4.68 (s, 1H, CH); 7.04-7.25 (m, 5H, Ar). 9-(4-Chlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-dione (5b). Mp 230-232 0C, (Lit.11mp 228-2300C); 1H NMR (300MHz, CDCl3), d0.99(s, 6H, CMe2); 1.11(s, 6H, CMe2); 2.10-2.23(q, J=16.61Hz, 4H 2xCH2); 2.42 (s, 4H, 2xCH2); 4.63 (s, 1H, CH); 7.14 7.20 (m, 4H, Ar). 9-(2,4-Dichlorophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-dione (5c). Mp 254-255 0C (Lit.11 mp 253-254 0C); 1H NMR (300MHz, CDCl3), d1.03(s, 6H, CMe2); 1.11(s, 6H, CMe2); 2.10-2.22(q, J=16.61Hz, 4H 2xCH2); 2.40 (s, 4H, 2xCH2); 4.85 (s, 1H, CH); 7.13-7.43(m, 3H, Ar). 9-(4-Bromophenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-dione (5d). Mp 240-242 0C; IR (KBr) .max 3442(br), 2932(br), 1660(vs), 1585(s), 1362(s), 1274(m), 1201(m), 1138(w), 1047(m), 694(w), 572, cm-1;1H NMR (300MHz, CDCl3), d0.99(s, 6H, CMe2); 1.11(s, 6H, CMe2); 2.10-2.23(q, J=16.61Hz, 4H 2xCH2); 2.42 (s, 4H, 2xCH2); 4.63 (s, 1H, CH); 7.12(d, J=8.30Hz, 2H, Ar) 7.29(d, J=8.30Hz, 2H, Ar); 13C NMR (300MHz, CDCl3): d 196.3 (2x C=O), 162.4 (2x C=C-O), 143.2 , 131.1, 130.1, 120.2 (6x ArC), 115.2 (2x(C=C), 50.6 (2x CH2), 40.8 (2x CH2), 32.1(2x >C<), 31.5(CH), 29.2, 27.2 (4x CH3); MS (ESI) m/z 429 ([M+H])+. Anal. Calcd for C23 H25 Br O3: C, 64.34; H, 5.87; Found: C, 64.33, H, 5.87. 9-(3-Methoxyphenyl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-2H-xanthene-1,8-dione (5e). Mp160-162 0C; IR (KBr) .max 3442(br), 2932(br), 1660(s), 1585(s), 1362(s), 1274, (sh) 1201(m), 1138(m), 1047(w), 694(w), 572, cm-1; 1H NMR (300MHz, CDCl3), d1.01(s, 6H, CMe2); 1.11(s, 6H, CMe2); 2.12-2.23(q, J=15.86Hz, 4H 2xCH2); 2.43 (s, 4H, 2xCH2); 3.37(s, 3H, OMe); 4.66 (s, 1H, CH); 6.58-7.10(m, 4H, Ar); 13C NMR (300MHz, CDCl3): d 196.2 (2x C=O), 162.2 (2x C=C-O), 159.3, 145.6, 128.8, 120.8, 115.5, 114.3(6x ArC), 111.8 2x C=C), 55.0 (OCH3), 50.7 (2x CH2), 40.8 (2x CH2), 32.1 (2x >C<), 31.7 (CH), 29.1, 27.3(4x CH3); MS (ESI) m/z 381 ([M+H])+. Anal. Calcd for C24 H28 O4: C, 75.76; H, 7.42; Found: C, 75.76, H, 7.41. ISSN 1424-6376 Page 147 ©ARKAT

Page  148 General Papers ARKIVOC 2006 (xvi) 136-148 Acknowledgements We thank Dr. J. S. Yadav, Director, IICT, Hyderabad for constant encouragement and support. References 1. Kidwai, M.; Saxena, S.; Khan, M. K. R.; Thukral, S. S. Eur. J. Med. Chem. 2005, 40, 816. 2. (a) Yarim. M.; Sarac, S.; Kilic, S. F.; Erol, K. Il Farmaco. 2003, 58,17. (b) Yarim, M, Sarac, S.; Ertan, M.; Kilic, S. F.; Erol, K. Arzneim-Forsch. 2002, 52, 27. 3. Hassani, Z.; Islami, M. R.; Kalantari, M. Bio. Org., Med. Chem. Lett. 2006, 16, 4479. 4. (a) Tonkikh, N. N.;.Strakovs, A; Petrova, M. V. Chem. Heterocycl.Compds 2004, 40, 43. (b) Candan, M. M.; Kendi, E.; Yarim, M.; Sarac, S.; Ertan, M. Anal. Sci. 2001, 17, 1023. (c) Sabitha, G.; Reddy, G. S. K.; Reddy, K. B.; Yadav, J. S. Tetrahedran Lett. 2003, 44, 6497. 5. Kantevari S.; Srinivasu, V. N. V.; Biradar, D. O.; Nagarapu L. J. Mol. Catalysis A: Chemical 2006, 266, 109. 6. (a) Dilman, A. D.; Loffe, S. L.; Chem. Rev. 2003, 103, 733. (b) Lee, P. H.; Seomoon, D.; Lee, K.; Heo, Y. J. Org. Chem. 2003, 68, 2510. (c) Wang, L. S.; Hollis, T. K. Org.Lett. 2003, 14, 2543. (d) Liu, Y.; Xu, X.; Zang, Y. Tetrahedron 2004, 60, 4867. e) Sabitha, G.; Reddy, G. S. K.; Reddy, K. B.; Yadav, J. S. Synthesis 2004, 263. (f) Sabitha, G.; Reddy, K. S.; Reddy, G. S K.; Fatima, N. Synlett 2005, 2347. (g) Barga, A. L.; Vargas, F.; Sehnem, J. A.; Barga, R. C. J. Org. Chem. 2005, 70, 9021. (h) Xu, L. W.; Xia, C. G. Synthesis 2004, 2191. 7. Wang, T.; Zhang, Z.; Meanwell, N. A. Tetrahedron Lett. 1999, 40, 6745. 8. Zigeuner, G.; Eisenreich, V.; Weichsel, H.; Adam, W. Monatsh. Chem. 1970, 101, 1731. 9. Kappe, C. O. J. Org. Chem. 1997, 62, 7201. 10. Zhu, Y-l.; Huang, S-l.; Pan, Y-j. Eur. J. Org. Chem., 2005, 2354. 11. Jin, T-S.; Zang, J-S.; Xiao, J-C.; Wang, A-Q.; Li, T-S. Synlett 2004, 866. 12. Lin, H.; Zhao, Q.; Xu, B.; Wang, X. J. Mol. Catalysis A: Chemical, 2007 (In Press) 13. We thank the referees and scientific editor for their valuable suggestions. ISSN 1424-6376 Page 148 ©ARKAT