research article an efficient, clean, and catalyst-free...

Research ArticleAn Efficient Clean and Catalyst-Free Synthesis of FusedPyrimidines Using Sonochemistry

M Mamaghani1 K Tabatabaeian1 R Araghi1 A Fallah2 and R Hossein Nia1

1 Department of Chemistry Faculty of Sciences University of Guilan PO Box 41335-1914 Rasht Iran2Department of Chemistry Faculty of Sciences Islamic Azad University Rasht Branch PO Box 41335-3516 Rasht Iran

Correspondence should be addressed to M Mamaghani mchem41gmailcom

Received 26 August 2014 Accepted 27 October 2014 Published 16 November 2014

Academic Editor Jonathan White

Copyright copy 2014 M Mamaghani et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

In this report synthesis of indenopyrido[23-119889]pyrimidine and pyrimido[45-119887]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3119867)one 13-indanedione or 13-cyclohexadione andarylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65∘C In these reactions fused pyrimidine derivatives weresynthesized with high to excellent yields (82ndash97) and short reaction times (10ndash33min)

1 Introduction

Pyrimidine structural moiety constitutes a major class ofheterocyclic compounds which have various pharmaceuti-cal applications For example they are found to possessantineoplastic [1ndash3] antiviral [4ndash6] antibiotic [7] and anti-inflammatory properties [8] Pyrimidines also exhibit arange of pharmacological activities such as antibacterial [9ndash11] antifungal [12 13] anticancer [14 15] and cardiopro-tective effects [16] Bicyclic and tricyclic fused pyrimidinederivatives have received much attention in connectionwith biologically significant systems such as pyrido[23-d]pyrimidines Pyrido[23-d]pyrimidine structural motif ispresent in pirenperone (tranquilizer) [17] and ramastine(antiallergic) [18] as well as in some antiulcerative andantiasthmatic agents [19] In addition quinolines have phar-macological properties which include wide applications inmedicinal chemistry for example this scaffold structure ispresent in anti-inflammatory agents antimalarial drugs andantihypertensive antiasthmatic antibacterial and tyrosinekinase inhibiting agents [20ndash25]

Moreover the importance of uracil and its annulatedderivatives is well recognized by synthetic [26 27] aswell as biological [28 29] chemists The 6-amino-uracilderivatives represent very important classes of function-alized uracils also 6-amino-uracils find wide applications

as starting materials for the synthesis of a number offused uracils of biological significance for example pyrano-pyrido- pyrazolo- pyrimido- and pyridazinopyrimidines[30 31]

On the other hand ultrasonic reactions have beenincreasingly used as clean green and environmentallybenign routes for the preparation of organic compoundsof synthetic and biological values [32ndash37] A large numberof organic reactions can be carried out in higher yieldshorter reaction time and under milder conditions by usingultrasonic irradiation [38ndash41]

These observations led us to attempt the synthesis ofsome new fused pyrimidine derivatives using 6-amino-alkyltiouracil as startingmaterial under sonochemical condi-tions The present work describes our approach for the syn-thesis of polyfunctional pyrimidines using green chemistry

2 Experimental

21 Chemicals and Apparatus Melting points were mea-sured on an electrothermal 9100 apparatus IR spectra weredetermined on a Shimadzo IR-470 spectrometer 1HNMRand 13CNMR spectra were recorded on a 400MHz BrukerDRX-400 in DMSO-d

6as solvent and TMS as an inter-

nal standard Chemical shifts on 1H and 13C NMR were

Hindawi Publishing CorporationOrganic Chemistry InternationalVolume 2014 Article ID 406869 9 pageshttpdxdoiorg1011552014406869

2 Organic Chemistry International

expressed in ppm downfield from tetramethylsilane Son-ication was performed in Elmasonic S 40H ultrasoniccleaning unit Elemental analyses were carried out on aCarlo-Erba EA1110CNNO-S analyser and agreed with thecalculated values All the chemicals were purchased fromMerck and used without further purification All sol-vents used were dried and distilled according to standardprocedures

22 General Procedure for the Synthesis of (4andashr) A mixtureof equimolar amounts of 6-amino-2-(alkylthio)pyrimidin-4(3H)-one 1 (1mmol) 13-indanedione 2 (1mmol) or 13-cyclohexadione 5 and aldehydes 3 (1mmol) in ethylene glycol(5mL) was placed in a Pyrex-glass open vessel and irradiatedat 65∘C by ultrasonic irradiations (40 kHz) (for conventionalconditions the reaction mixture was heated under refluxconditions) The progress of the reaction was monitoredby TLC (EtOAcpetroleum ether 8 4) After completion ofreaction the mixture was concentrated and cooledThe solidobtained was filtered off and recrystallized from EtOHH

2O

(11) to furnish the desired pure product

23 Spectral Data for the Products

231 5-(4-Chlorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46(5H11H)-dione (4a) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3448 3410 3271 30622932 1680 1653 1585 1541 1502 1452 1350 1271 1078 899742 707 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 260 (s

3H CH3) 482 (s 1H CH) 730ndash725 (m 5H Ar-H) 736

(t 1H J = 740Hz Ar-H) 745 (t 1H J = 740Hz Ar-H)779 (d 1H J = 720Hz Ar-H) 1113 (br s 1H NH) 1260(br s 1H COndashNH) ppm 13C NMR (100MHz DMSO-d

6)

120575 = 133 (Me) 342 (CH) 999 1079 1204 1209 1284 13011308 1312 1324 1336 1366 1375 1448 1535 1558 1615(CONH) 1911 (C=O) ppm Anal Cald for C

21H14ClN3O2S

(40787) C 6184 H 346 N 1030 Found C 6195 H 331N 1043

232 2-(Methylthio)-5-phenyl-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4b) Red Powder Mpgt300∘C IR (KBr) ]max = 3448 3040 2922 2851 1685 16471582 1537 1500 1456 1358 1273 742 702 cmminus1 1HNMR(400MHz DMSO-d

6) 120575 = 260 (s 3H CH

3) 482 (s 1H

CH) 715ndash711 (m 1H Ar-H) 726ndash721 (m 4H Ar-H) 734(t 2H J = 740Hz Ar-H) 744 (t 1H J = 760Hz Ar-H)778 (d 1H J = 720Hz Ar-H) 1107 (br s 1H NH) 1255 (brs 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6) 120575 =

133 (Me) 345 (CH) 1000 1085 1203 1208 1266 12741282 1285 1306 1323 1337 1367 1460 1533 1557 1625(CONH) 1911 (C=O) ppm Anal Cald for C

21H15N3O2S

(37343) C 6754 H 405 N 1125 Found C 6739 H 412N 1112

233 5-(4-Bromophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4c) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3380 3300 3100 30802920 2820 1690 1640 1618 1558 1498 1440 1348 1270 1070

850 800 760 cmminus1 1HNMR (400MHz DMSO-d6) 120575 = 260

(s 3H CH3) 480 (s 1H CH) 721 (d 2H J = 760Hz Ar-H)

726 (d 1H J = 680Hz Ar-H) 735 (t 1H J = 720Hz Ar-H)742 (m 3H Ar-H) 779 (d 1H J = 680Hz Ar-H) 1112(br s 1H NH) 1258 (br s 1H COndashNH) ppm 13CNMR(100MHz DMSO-d

6) 120575 133 (Me) 343 (CH) 999 1078

1197 1204 1209 1296 1305 1308 1313 1324 1336 13661452 1558 1621 (CONH) 1911 (C=O) ppm Anal Cald forC21H14BrN3O2S (45232) C 5576 H 312 N 929 Found

C 5563 H 301 N 938

234 5-(4-Fluorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4d) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3440 3400 3026 29212840 1677 1641 1602 1578 1539 1493 1458 1357 1275 1149843 798 748 709 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 =

260 (s 3H CH3) 483 (s 1H CH) 707ndash701 (m 4H Ar-H)

726 (d 2H J = 640Hz Ar-H) 735 (t 1H J = 740Hz Ar-H)745 (t 1H J = 720Hz Ar-H) 779 (d 1H J = 720Hz Ar-H)1110 (br s 1H NH) 1256 (br s 1H COndashNH) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 133 (Me) 340 (CH) 996 1081

1149 (d 2119869C-F = 210Hz) 1203 1207 1299 (d 3119869C-F =80Hz) 1306 1321 1339 1368 1426 1533 1561 1589 1606(d 1119869C-F = 2400Hz) 1910 (C=O) ppm Anal Cald forC21H14FN3O2S (39142) C 6444 H 361 N 1074 Found

C 6438 H 362 N 1085

235 5-(2-Bromophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4e) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3350 3300 3110 30802920 2820 1690 1645 1618 1558 1498 1440 1347 1270 1070895 845 800 760 710 cmminus1 1HNMR (400MHz DMSO-d6) 120575 = 260 (s 3H CH

3) 524 (s 1H CH) 706 (dt 1H J =

840Hz 22Hz Ar-H) 728ndash721 (m 3HAr-H) 735 (t 1H J =740Hz Ar-H) 748ndash743 (m 2H Ar-H) 780 (d 1H J =720Hz Ar-H) 1111 (br s 1H NH) 1226 (br s 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6) 120575 = 133 (Me)

357 (CH) 1000 1078 1204 1207 1234 1281 1284 13071320 1322 1328 1336 1366 1367 1449 1537 1556 1621(CONH) 1907 (C=O) ppm Anal Cald for C

21H14BrN3O2S

(45232) C 5576 H 312 N 929 Found C 5583 H 308N 945

236 5-(2-Chlorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4f) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3460 3385 3120 30602930 2854 1685 1649 1616 1580 1541 1502 1445 1345 12771078 893 764 cmminus1 1HNMR(400MHzDMSO-d

6)120575=260


721 (t 2H J = 740Hz Ar-H) 729 (d 2H J = 720Hz Ar-H)735 (t 1H J = 720Hz Ar-H) 744 (t 1H J = 720Hz Ar-H)779 (d 1H J = 720Hz Ar-H) 1110 (br s 1H NH) 1249 (brs 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6) 120575 =

133 (Me) 333 (CH) 999 1076 1204 1207 1274 1281 12951307 1319 1322 1329 1336 1366 1431 1537 1559 1621(CONH) 1907 (C=O) ppm Anal Cald for C

21H14ClN3O2S

(40787) C 6184 H 346 N 1030 Found C 6172 H 331N 1018

Organic Chemistry International 3

237 5-(2-Hydroxyphenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4g) OrangPowder Mp gt300∘C IR (KBr) ]max = 3450 3270 30502920 2820 1700 1645 1620 1600 1560 1500 1440 13471280 1180 868 800 760 700 cmminus1 1HNMR (400MHzDMSO-d

6) 120575 = 259 (s 3H CH

3) 498 (s 1H CH) 672ndash669

(m 2H Ar-H) 703ndash70 (m 2H Ar-H) 725 (d 1H J =680Hz Ar-H) 735 (t 1H J = 740Hz Ar-H) 745 (t 1H J =740Hz Ar-H) 779 (d 1H J = 720Hz Ar-H) 958 (br s1H NH) 1112 (s 1H OH) 1273 (br s 1H COndashNH) ppm13CNMR (100MHz DMSO-d

6) 120575 = 133 (Me) 296 (CH)

1000 1079 1175 1200 1202 1208 1279 1300 1306 13231338 1368 1369 1548 1550 1564 1565 1639 (CONH)1911 (C=O) ppm Anal Cald for C

21H15N3O3S (38943)

C 6477 H 388 N 1079 Found C 6470 H 398 N1088

238 5-(24-Dichlorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4h)Red Powder Mp gt300∘C IR (KBr) ]max = 3448 32283066 2940 2854 1683 1649 1580 1539 1506 1460 13521275 1103 1060 858 764 704 cmminus1 1HNMR (400MHzDMSO-d

6) 120575 = 260 (s 3H CH

3) 522 (s 1H CH) 723 (d

1H J = 640Hz Ar-H) 737ndash727 (m 3H Ar-H) 747ndash744(m 2H Ar-H) 780 (d 1H J = 720Hz Ar-H) 1113 (br s 1HNH) 1252 (br s 1H COndashNH) ppm 13CNMR (100MHzDMSO-d

6) 120575 = 133 (Me) 330 (CH) 994 1071 1205 1207

1276 1287 1308 1317 1322 1330 1335 1339 1423 13661538 1560 1620 (CONH) 1907 (C=O) ppm Anal Caldfor C21H13Cl2N3O2S (44232) C 5702 H 296 N 950

Found C 5688 H 283 N 935

239 5-(2-Nitrophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4i) RedPowder Mp gt300∘C IR (KBr) ]max = 3350 3060 29231685 1649 1578 1540 1504 1450 1539 1342 1277 770708 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 260 (s 3H

CH3) 483 (s 1H CH) 705 (t 2H J = 880Hz Ar-H)

729ndash725 (m 3H Ar-H) 735 (t 1H J = 740Hz Ar-H) 745(t 1H J = 740Hz Ar-H) 779 (d 1H J = 720Hz Ar-H)1110 (br s 1H NH) 1257 (br s 1H COndashNH) ppm 13C NMR(100MHz DMSO-d

6) 120575 = 133 (Me) 339 (CH) 970 1082

1150 1152 1204 1209 1263 1299 1300 1308 1324 13361367 1421 1557 1600 1624 (CONH) 1911 (C=O) ppmAnal Cald for C

21H14N4O4S (41843) C 6028 H 337 N

1339 Found C 6010 H 348 N 1351

2310 5-(4-Methoxyphenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4j) RedPowder Mp gt300∘C IR (KBr) ]max = 3211 3040 29202851 1674 1645 1606 1554 1500 1442 1352 1261 1219 1020898 835 766 706 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 =

259 (s 3H CH3) 368 (s 3H OCH

3) 476 (s 1H CH) 679

(d 2H J = 820Hz Ar-H) 714 (d 2H J = 820Hz Ar-H)726 (d 1H J = 720Hz Ar-H) 735 (t 1H J = 720Hz Ar-H)744 (t 1H J = 740Hz Ar-H) 778 (d 1H J = 680Hz Ar-H)1103 (br s 1H NH) 1253 (br s 1H COndashNH) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 133 (Me) 336 (CH) 554 (MeO)


22H17N3O3S (40345) C 6549 H 425 N

1042 Found C 6530 H 435 N 1028

2311 2-(Methylthio)-5-(p-tolyl)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4k) Red PowderMp gt300∘C IR (KBr) ]max = 3490 3227 3059 2940 28541681 1645 1585 1539 1504 1456 1350 1275 897 773 cmminus11HNMR (400MHz DMSO-d

6) 120575 = 221 (s 3H CH

3) 259


712 (d 2H J = 720Hz Ar-H) 725 (d 1H J = 640Hz Ar-H)734 (t 1H J = 720Hz Ar-H) 744 (t 1H J = 720Hz Ar-H)777 (d 1H J = 680Hz Ar-H) 1104 (br s 1H NH) 1254(br s 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6)

120575 = 133 (Me) 210 (Me) 341 (CH) 1002 1087 1202 12081280 1284 1290 1306 1323 1337 1356 1368 1431 15321555 1624 (CONH) 1911 (C=O) ppm Anal Cald forC22H17N3O2S (38745) C 6820 H 442 N 1085 Found

C 6838 H 425 N 1078

2312 5-(34-Dimethoxyphenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4l)Red Powder Mp gt300∘C IR (KBr) ]max = 33893223 3130 3063 2933 2839 1691 1653 1554 15041450 1340 1226 1024 897 798 764 710 cmminus1 1HNMR(400MHz DMSO-d

6) 120575 = 260 (s 3H SCH

3) 367

(s 3H OCH3) 371 (s 3H OCH

3) 479 (s 1H CH)

664 (d 1H J = 840Hz Ar-H) 674 (d 1H J =840Hz Ar-H) 695 (s 1H Ar-H) 727 (d 1H J = 680HzAr-H) 734 (t 1H J = 720Hz Ar-H) 743 (t 1H J = 720HzAr-H) 777 (d 1H J = 720Hz Ar-H) 1101 (br s 1H NH)1254 (br s 1H COndashNH) ppm 13CNMR (100MHz DMSO-d6) 120575 = 133 (Me) 339 (CH) 559 (MeO) 560 (MeO) 100


23H19N3O4S (43348) C 6373 H 442 N

969 Found C 6388 H 433 N 986

2313 5-(24-Dichlorophenyl)-2-(ethylthio)-511-dihydro-3H-indeno[210158401101584056]pyrido[23-d]pyrimidine-46-dione (4m)Red Powder Mp 282ndash284∘C IR (KBr) ]max = 3203 31363059 2966 2926 1649 1607 1550 1502 1450 1350 1190 11011070 858 764 700 cmminus1 1HNMR(400MHzDMSO-d

6)120575=

136 (t 3H J = 71Hz CH3) 322 (q 2H J = 71Hz CH

2) 522

(s 1H CH) 722 (d 1H J = 68Hz Ar-H) 746ndash726 (m 5HAr-H) 780 (d 1H J = 72Hz Ar-H) 1109 (s 1H NH) 1248(br s 1H NHndashC=O) ppm 13CNMR (100MHz DMSO-d

6)

120575 = 150 (Me) 247 (CH2) 330 (CH) 994 1071 1205 1275


Found C 5774 H 323 N 905

2314 5-(4-Chlorophenyl)-2-(ethylthio)-511-dihydro-3H-in-deno[210158401101584056]pyrido[23-d]pyrimidine-46-dione (4n) RedPowder Mp 268ndash270∘C IR (KBr) ]max = 3209 31403063 2876 1649 1545 1504 1452 1350 1188 1146 860 764704 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 136 (t 3H


J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 482 (s 1H

CH) 726 (m 5H Ar-H) 735 (t 1H J = 72Hz Ar-H) 745(t 1H J = 74Hz Ar-H) 779 (d 1H J = 72Hz Ar-H) 1108(s 1H NH) 1256 (br s 1H NHndashC=O) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 151 (Me) 246 (CH

2) 342 (CH)

999 1120 1079 1204 1209 1284 1301 1308 1312 13231335 1366 1448 1558 1911 (C=O) ppm Anal Cald forC22H16ClN3O2S (42190) C 6263 H 382 N 996 Found

C 6238 H 395 N 976

2315 2-(Ethylthio)-5-(2-fluorophenyl)-511-dihydro-3H-inde-no[210158401101584056]pyrido[23-d]pyrimidine-46-dione (4o) RedPowder Mp 257ndash259∘C IR (KBr) ]max = 3221 31323057 2932 1684 1647 1583 1539 1491 1350 1263 1182 760706 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 137 (t 3H

J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 504 (s 1H

CH) 703 (m 2H Ar-H) 718 (m 1H Ar-H) 725 (t 2HAr-H) 734 (t 1H J = 72Hz Ar-H) 744 (t 1H J = 72HzAr-H) 780 (d 1H J = 68Hz Ar-H) 1106 (s 1H NH) 1248(br s 1H NHndashC=O) ppm 13CNMR (100MHz DMSO-d

6)

120575 = 151 (Me) 246 (CH2) 290 (CH) 994 1074 1155 (2J =

220Hz) 1204 (3J = 100Hz) 1208 1246 1284 1285 13071311 1322 1328 1329 1336 1367 1536 1558 (CONH)1603 (1119869C-F = 2450Hz) 1910 (C=O) ppm Anal Cald forC22H16FN3O2S (40544) C 6517 H 398 N 1036 Found

C 6506 H 381 N 1022

2316 5-(4-Bromophenyl)-2-(ethylthio)-511-dihydro-3H-in-deno[210158401101584056]pyrido[23-d]pyrimidine-46-dione (4p) RedPowder Mp 255ndash257∘C IR (KBr) ]max = 3230 28581645 1578 1539 1499 1450 1352 1182 1016 797 708 cmminus11HNMR (400MHz DMSO-d

6) 120575 = 136 (t 3H J = 72Hz

CH3) 323 (q 2H J = 72Hz CH

2) 481 (s 1H CH) 721 (d

2H J = 80Hz Ar-H) 726 (d 1H J = 72Hz Ar-H) 735 (t1H J = 72Hz Ar-H) 744 (m 3H Ar-H) 779 (d 1H J =72Hz Ar-H) 1107 (s 1H NH) 1255 (br s 1H NHndashC=O)ppm 13CNMR (100MHz DMSO-d

6) 120575 = 151 (Me) 246

(CH2) 344 (CH) 997 1078 1197 1204 1209 1305 1307

1313 1323 1336 1366 1452 1558 1618 (CONH) 1910(C=O) ppm Anal Cald for C

22H16BrN3O2S (46635) C

5666 H 346 N 901 Found C 5653 H 327 N 916

2317 2-(Ethylthio)-5-(4-methylthiophenyl)-511-dihydro-3H-indeno[210158401101584056]pyrido[23-d]pyrimidine-46-dione (4q)Red Powder Mp 250ndash252∘C IR (KBr) ]max = 3219 31383057 2964 2922 1645 1551 1499 1450 1354 1184 835 768712 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 136 (t 3H

J = 72Hz CH3) 241 (s 3H CH

3) 322 (q 2H J = 72Hz

CH2) 478 (s 1H CH) 713 (d 2H J = 80Hz Ar-H) 719

(d 2H J = 80Hz Ar-H) 726 (d 1H J = 72Hz Ar-H)734 (t 1H J = 72Hz Ar-H) 744 (t 1H J = 74Hz Ar-H)778 (d 1H J = 72Hz Ar-H) 1103 (s 1H NH) 1253 (br s1H NHndashC=O) ppm 13CNMR (100MHz DMSO-d

6) 120575 =

151 (Me) 154 (Me) 247 (CH2) 341 (CH) 1000 1083

1203 1208 1264 1288 1306 1323 1337 1360 1367 14291538 1540 1555 1556 1911 (C=O) ppm Anal Cald forC23H19N3O2S2(43355) C 6372 H 442 N 969 Found

C 6357 H 459 N 956

2318 2-(Ethylthio)-5-phenyl-511-dihydro-3H-indeno[210158401101584056]pyrido[23-d]pyrimidine-46-dione (4r) RedPowderMp273ndash276∘C IR (KBr) ]max = 3119 3026 2922 2849 17161645 1541 1495 1452 1352 1184 744 710 cmminus1 1HNMR(400MHz DMSO-d

6) 120575 = 136 (t 3H J = 72Hz CH

3) 323

(q 2H J = 72Hz CH2) 482 (s 1H CH) 713 (m 1H Ar-H)

724 (m 5HAr-H) 735 (t 1H J =74HzAr-H) 744 (t 1H J =74Hz Ar-H) 779 (d 1H J = 72Hz Ar-H) 1102 (s 1H NH)1252 (br s 1H NHndashC=O) ppm 13CNMR (100MHz DMSO-d6) 120575 = 151 (Me) 246 (CH

2) 345 (CH) 1085 1203 1209

1266 1282 1285 1307 1323 1336 1366 1459 1556 1625(CONH) 1912 (C=O) ppm Anal Cald for C

22H17N3O2S

(38710) C 6826H 442N 1085 Found C 6808H 455N 1097

2319 2-(Ethylthio)-5-(4-fluorophenyl)-58910-tetrahydro-3H7H-pyrimido[45-b]quinoline-46-dione (6a) WhitePowder Mp 300ndash302∘C IR (KBr) ]max = 3221 3142 30673032 2957 2880 1647 1607 1553 1483 1364 1226 1186 837797 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 131 (t 3H J =

72Hz CH3) 195ndash182 (m 2H CH

2ndashCH2ndashCH2) 229ndash218

(m 2H CH2ndashCH2ndash) 266ndash256 (m 2H CH

2ndashCH2ndashC=O)

313 (q 2H J = 72Hz CH2ndashCH3) 495 (s 1H CH) 701 (t

2H J = 88Hz Ar-H) 722 (dd 2H J = 82 58Hz Ar-H)985 (s 1H NH) 1233 (br s 1H NHndashC=O) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 332 (CH

2ndashC=O) 372 (CH) 984 1109 1150

(2119869CF = 210Hz) 1296 (3119869CF = 80Hz) 1433 (4119869CF = 20Hz)1524 1535 1536 1610 (1119869CF = 2400Hz) 1622 (CONH)1950 (C=O) ppm Anal Cald for C

19H18FN3O2S (37143) C

6144 H 488 N 1131 Found C 6132 H 470 N 1118

2320 2-(Ethylthio)-5-(naphthalen-2-yl)-58910-tetrahydro-3H7H-pyrimido[45-b]quinoline-46-dione (6b) WhitePowder Mp 310ndash312∘C IR (KBr) ]max = 3221 3138 30633028 2953 2874 1647 1607 1554 1479 1450 1366 1186 797752 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 131 (t 3H J =

72Hz CH3) 194ndash185 (2H m CH



2ndashCH2ndashC=O)

315 (q 2H J = 72Hz CH2ndashCH3) 512 (s 1H CH) 743

(3H m Ar-H) 762 (s 1H Ar-H) 784ndash774 (m 3H Ar-H)988 (s 1H NH) 1233 (br s 1H NHndashC=O) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 270 (CH

2ndashC=O) 342 (CH) 983 1110 1257

1258 1262 1277 1272 1279 1282 1322 1332 1446 15351536 1949 (C=O) ppm Anal Cald for C

23H21N3O2S

(40350) C 6846 H 525 N 1041 Found C 6860 H517 N 1055

2321 2-(Ethylthio)-5-(p-tolyl)-58910-tetrahydro-3H7H-pyrimido[45-b]quinoline-46-dione (6c) White PowderMp 292ndash294∘C IR (KBr) ]max = 3225 3142 30672878 1649 1614 1556 1475 1366 1186 794 cmminus1 1HNMR(400MHz DMSO-d

6) 120575 = 131 (t 3H J = 72Hz CH

3ndash

CH2) 192ndash180 (m 2H CH

2ndashCH2ndashCH2) 23ndash21 (m 5H

CH2ndashCH2ndash and CH

3-Ar) 265ndash257 (m 2H CH

2ndashCH2ndash

C=O) 314 (q 2H J = 72Hz CH2ndashCH3) 490 (s 1H CH)

699 (d 2H J = 76Hz Ar-H) 708 (d 2H J = 76Hz Ar-H)


+ ArCHO+HN

N

O

RS

O

O

NH N

NH

O O

SR

Ar

1 2 3

Ethylene glycol

R = Me Et

65

∘C USNH

2

4andashr

Scheme 1 Synthesis of indenopyrido[23-d]pyrimidine (4andashr)

Ethylene glycol+

HN

NEtS

O

+

1

ArCHONH

N

NH

OAr

SEt

OO

O

5 3

NH2

65

∘C US

6andashf

Scheme 2 Synthesis of of pyrimido[45-b]quinoline 6andashf

979 (s 1H NH) 1231 (br s 1H NHndashC=O) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 151 (Me) 210 (Me) 213 (CH

2)

245 (CH2) 268 (CH

2) 269 (CH

2ndashC=O) 333 (CH) 986

1112 1278 1289 1352 1442 1532 1533 1948 (C=O) ppmAnal Cald for C

20H21N3O2S (36746) C 6537 H 576 N

1141 Found C 6521 H 552 N 1125

2322 2-(Ethylthio)-5-(4-methoxyphenyl)-58910-tetrahy-dro-3H7H-pyrimido[45-b]quinoline-46-dione (6d) WhitePowder Mp 288ndash290∘C IR (KBr) ]max = 3225 3140 30673030 2949 1649 1608 1553 1479 1366 1184 1230 1034835 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 131 (t 3H

J = 72Hz CH3) 195ndash181 (m 2H CH

2ndashCH2ndashCH2) 223


2ndashCH2ndashC=O)

313 (q 2H J = 72Hz CH2ndashCH3) 367 (s 3H OCH

3)

489 (s 1H CH) 675 (d 2H J = 84Hz Ar-H) 710 (d2H J = 84Hz Ar-H) 978 (s 1H NH) 1230 (br s 1HNHndashC=O) ppm 13CNMR (100MHz DMSO-d

6) 120575 = 151

(Me) 213 (MeO) 245 (CH2) 269 (CH

2) 328 (CH

2) 372

(CH2ndashC=O) 554 (CH) 988 1113 1137 1288 1395 1531

1532 1579 1620 (CONH) 1948 (C=O) ppm Anal Cald forC22H21N3O2S (38346) C 6264 H 552 N 1096 Found

C 6264 H 558 N 1085

2323 2-(Ethylthio)-5-(5-methylthiophen-2-yl)-58910-tet-rahydro-3H7H-pyrimido[45-b]quinoline-46-dione (6e)White Powder Mp 280ndash282∘C IR (KBr) ]max = 32233138 3067 3030 2951 2872 1649 1607 1553 1479 14481364 1182 798 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 =

132 (t 3H J = 72Hz CH3) 198ndash185 (m 2H CH

2ndashCH2ndash

CH2ndash) 227 (m 2H CH

2ndashCH2ndash) 230 (s 3H CH

3-Ar)

262ndash254 (m 2H CH2ndashCH2ndashC=O) 313 (q 2H J = 72Hz

CH2ndashCH3) 515 (s 1H CH) 648 (s 2H Ar-H) 990 (s 1H

NH) 1241 (br s 1H NHndashC=O) ppm 13CNMR (100MHzDMSO-d

6) 120575 = 151 (Me) 154 (Me) 213 (CH

2) 246 (CH

2)

269 (CH2) 286 (CH

2ndashC=O) 372 (CH) 980 1106 1230

1250 1370 1486 1525 1534 1620 (CONH) 1947 (C=O)

ppm Anal Cald for C18H19N3O2S2(37309) C 5788 H

513 N 1125 Found C 5795 H 520 N 1110

2324 5-(4-Chlorophenyl)-2-(ethylthio)-58910-tetrahydro-3H7H-pyrimido[45-b]quinoline-46-dione (6f) WhitePowder Mp 262ndash265∘C IR (KBr) ]max = 3261 3182 30452941 2822 1647 1553 1500 1454 1342 1188 1063 825 cmminus11HNMR (400MHz DMSO-d

6) 120575 = 131 (t 3H J = 72Hz



CH2ndashCH2ndash) 265ndash255 (m 2H CH

2ndashCH2ndashC=O) 313 (q

2H J = 72Hz CH2ndashCH3) 492 (s 1H CH) 721 (d 2H J =

84Hz Ar-H) 725 (d 2H J = 84Hz Ar-H) 986 (s 1HNH) 1236 (br s 1H NHndashC=O) ppm 13CNMR (100MHzDMSO-d

6) 120575 = 151 (Me) 212 (CH

2) 246 (CH

2) 268

(CH2) 336 (CH

2ndashC=O) 371 (CH) 981 1107 1107 1282

1298 1308 1316 1460 1536 1537 1949 (C=O) ppm AnalCald for C

19H18ClN3O2S (38789) C 5883 H 468 N

1083 Found C 5870 H 447 N 1068

3 Results and Discussion

As part of our continuing efforts on the development ofnew synthetic strategies for the preparation of heterocycliccompounds [42ndash48] herein we wish to report one-pot three-component synthesis of fused pyridopyrimidines undersonochemical conditionswithout the use of catalyst (Schemes1 and 2)

In the initial experiment to optimize the reactionconditions different solvents were screened for thesynthesis of 5-(4-chlorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione 4a asa model reaction The reaction between equimolar amountsof 6-amino-2-(methylthio)pyrimidin-4(3H)-one 1 (preparedby the condensation of thiourea with ethylcyanoacetate insodium ethoxide and followed by alkylation with alkyliodide[49]) 13-indanedione 2 and 4-chlorobenzaldehyde wereexamined in various solvents and different temperatures


Table 1 Effect of various solvents in the synthesis of 4a under conventional conditions and ultrasonic irradiations

Entry Solvent Conventional method Sonochemical methodTime (min) Yield ()a Time (min) Yield ()a

1 Ethylene glycol 180 90b 25 95c

2 AcOH 180 86 29 903 DMF 210 82 29 884 EtOH 220 84 30 885 H2O 240 78 41 836 Acetone 240 70 42 767 CHCl3 270 66 47 708 CH3CN 300 60 50 65aIsolated yieldbReflux temperaturec65∘C

Table 2 Synthesis of indenopyrido[23-119889]pyrimidine 4andashr

Entry Product R Ar Time (min) Yield ()a

1 4a Me 4-ClC6H4 25 952 4b Me C6H5 33 923 4c Me 4-BrC6H4 28 (220)b 95 (91)b

4 4d Me 4-FC6H4 20 (160)b 97 (85)b

5 4e Me 2-BrC6H4 30 (220)b 94 (88)b

6 4f Me 2-ClC6H4 27 (210)b 96 (89)b

7 4g Me 2-OHC6H4 32 (240)b 90 (90)b

8 4h Me 24-Cl2C6H3 20 (160)b 96 (90)b

9 4i Me 2-NO2C6H4 22 (170)b 97 (90)b

10 4g Me 4-OCH3C6H4 35 9011 4k Me 4-CH3C6H4 35 9312 4l Me 34-(OCH3)2C6H3 35 (280)b 90 (85)b

13 4m Et 24-Cl2C6H3 15 (180)b 95 (90)b

14 4n Et 4-ClC6H4 20 (185)b 89 (80)b

15 4o Et 2-FC6H4 18 8616 4p Et 4-BrC6H4 25 8517 4q Et 4-MeSC6H4 22 8518 4r Et C6H5 27 87aIsolated yieldbConventional conditions

(25 50 65 and 80∘C) under sonochemical conditions Theresults of this study are summarized in Table 1 It is evidentfrom the results that ethylene glycol is the most effectivesolvent among the selected solvents giving the highest yield(95) and lower reaction time (25min) under ultrasoundirradiation (entry 1) For comparison the preparation of4a was carried out under conventional heating at refluxconditions which furnished the desired product at loweryield and much higher reaction time (180min) (Table 1entry 1) The results revealed that the reaction inducedby ultrasonic irradiations offered better result than theconventional condition (Figure 1)

Using the optimized reaction conditions various deriva-tives of indenopyrido[23-d]pyrimidines 4andashr (Scheme 1)were prepared in high to excellent yields (85ndash97) and lowerreaction times (Table 2)

NH N

NH

O O

SMe

Cl

4a

Figure 1

Due to remarkable results from the above experimentswe decided to broaden the scope of this protocol for


Table 3 Synthesis of pyrimido[45-b]quinoline 6andashf

Entry Product Ar Time (min) Yield ()a

1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b

4 6d 4-CH3OC6H4 23 875 6e 5-methylthiophen-2-yl 25 826 6f 4-ClC6H4 17 90aIsolated yieldsbConventional conditions

O

O

+ ArCHOKnoevenagel condensation

O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+

Scheme 3 The plausible mechanism of synthesis of fused pyrimidine derivatives 4andashr and 6andashf

the synthesis of quinoline derivatives as another fusedpyrimidine derivative We investigated the reaction between6-amino-2-(ethylthio)pyrimidin-4(3H)-one 1 13-cyclohex-adione 5 and arylaldehydes 3 under the aforementionedoptimized reaction conditions and obtained pyrimido[45-b]quinoline-46-diones 6andashf (Scheme 2) in high yields (82ndash95) and short reaction times (10ndash25min) (Table 3)

The plausible mechanism of this MCRs involves Kno-evenagel condensation between CH-acid (2 or 5) and arylaldehydes (3) resulting in the arylidene intermediate 7followed by Michael addition of enaminone 1 cyclizationand removal of H

2O to form the desired products (4 or 6)

(Scheme 3)

All the synthesized pyridopyrimidine derivativeswere characterized on the basis of elemental and spectral(1HNMR 13CNMR and IR) analyses

4 Conclusion

In summary we have developed a simple green and effi-cient protocol for the synthesis of novel fused derivativesof pyrimidine under ultrasonic irradiations The easy workof the products without the use of catalyst mild reactioncondition high to excellent yields short reaction timesand cleaner reaction profiles are the notable features of this


protocolThemethod is amenable for the iterative generationof combinatorial libraries

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

Theauthors are grateful to the ResearchCouncil of Universityof Guilan and Islamic Azad University Rasht Branch forfinancial support of this work

References

[1] S A Giller R A Zhuk and M I U Lidak ldquoAnalogs ofpyrimidine nucleosides I N

1

-(alpha-furanidyl) derivatives ofnatural pyrimidine bases and their antimetabolitiesrdquo DokladyAkademii nauk SSSR vol 176 no 2 pp 332ndash335 1967

[2] A R Curreri F J Ansfield F A McIver H A Waisman andC Hedelberger ldquoClinical studies with 5-fluorouracilrdquo CancerResearch vol 18 no 4 pp 478ndash484 1958

[3] N K Chaudhary B J Montag and CHeidelberger ldquoStudies onfluorinated pyrimidines III The metabolism of 5-fluorouracil-2-C14 and 5-fluoroorotic-2-C14 acid in vivordquo Cancer researchvol 18 no 3 pp 318ndash328 1958

[4] V Malik P Singh and S Kumar ldquoUnique chlorine effectin regioselective one-pot synthesis of 1-alkyl-allyl-3-(o-chlorobenzyl) uracils anti-HIV activity of selected uracilderivativesrdquo Tetrahedron vol 62 no 25 pp 5944ndash5951 2006

[5] A Holy I Votruba M Masojıdkova et al ldquo6-[2-(Phosphono-methoxy)alkoxy] pyrimidines with antiviral activityrdquo Journal ofMedicinal Chemistry vol 45 no 9 pp 1918ndash1929 2002

[6] P Andres and AMarhold ldquoA new synthesis of 5-trifluorometh-yluracilrdquo Journal of Fluorine Chemistry vol 77 no 1 pp 93ndash951996

[7] J J Reddick S Saha J-M Lee J S Melnick J Perkins and T PBegley ldquoThe mechanism of action of bacimethrin a naturallyoccurring thiamin antimetaboliterdquo Bioorganic and MedicinalChemistry Letters vol 11 no 17 pp 2245ndash2248 2001

[8] BGauthier ldquoOn the thiamineswith an open thiazole ring studyof O S-diacetylthiaminerdquo Annales Pharmaceutiques Francaisesvol 21 pp 655ndash666 1963

[9] E Wyrzykiewicz G Bartkowiak Z Nowakowska and BKedzia ldquoSynthesis and antimicrobial properties of S-substitutedderivatives of 2-thiouracilrdquo Farmaco vol 48 no 7 pp 979ndash9881993

[10] P Sharma N Rane and V K Gurram ldquoSynthesis andQSAR studies of pyrimido[45-d]pyrimidine-25-dione deriva-tives as potential antimicrobial agentsrdquo Bioorganic and Medici-nal Chemistry Letters vol 14 no 16 pp 4185ndash4190 2004

[11] Y M Elkholy and M A Morsy ldquoFacile synthesis of 5 6 7 8-tetrahydropyrimido [4 5-b]-quinoline derivativesrdquo Moleculesvol 11 no 11 pp 890ndash903 2006

[12] B S Holla M Mahalinga M S Karthikeyan P M Akber-ali and N S Shetty ldquoSynthesis of some novel pyrazolo[34-d]pyrimidine derivatives as potential antimicrobial agentsrdquoBioorganic and Medicinal Chemistry vol 14 no 6 pp 2040ndash2047 2006

[13] N Ingarsal G Saravanan P Amutha and S Nagarajan ldquoSyn-thesis in vitro antibacterial and antifungal evaluations of 2-amino-4-(1-naphthyl)-6-arylpyrimidinesrdquo European Journal ofMedicinal Chemistry vol 42 no 4 pp 517ndash520 2007

[14] X L Zhao Y F Zhao S C Guo H S Song D Wangand P Gong ldquoSynthesis and anti-tumor activities of novel[124]triazolo[15-a] pyrimidinesrdquo Molecules vol 12 no 5 pp1136ndash1146 2007

[15] L Cordeu E Cubedo E Bandres et al ldquoBiological profileof new apoptotic agents based on 24-pyrido[23-d]pyrimidinederivativesrdquo Bioorganic and Medicinal Chemistry vol 15 no 4pp 1659ndash1669 2007

[16] N M Khalifa N S Ismail and M M Abdulla ldquoSynthesisand reactions of fused cyanopyrimidine derivatives and relatedglycosides as antianginal and cardio protective agentsrdquoEgyptianPharmaceutical Journal vol 4 pp 277ndash288 2005

[17] R L Smith R J Barrett and E Sanders-Bush ldquoNeuro-chemical and behavioral evidence that quipazine-ketanserindiscrimination is mediated by serotonin 2A receptorrdquo Journalof Pharmacology and Experimental Therapeutics vol 275 no 2pp 1050ndash1057 1995

[18] F Awouters J Vermeire F Smeyers et al ldquoOral antiallergicactivity in ascaris hypersensitive dogs a study of knownantihistamines and of the new compounds ramastine (R 57 959)and levocabastine (R 50 547)rdquo Drug Development Research vol8 no 1ndash4 pp 95ndash102 1986

[19] Y Yanagihara H Kasai T Kawashima and T ShidaldquoImmunopharmacological studies on TBX a new antiallergicdrug (1) Inhibitory effects on passsive cutaneous anaphylaxisin rats and guinea pigsrdquoThe Japanese Journal of Pharmacologyvol 48 no 1 pp 91ndash101 1988

[20] R D Larsen E G Corley A O King et al ldquoPractical route to anew class of LTD4 receptor antagonistsrdquoThe Journal of OrganicChemistry vol 61 no 10 pp 3398ndash3405 1996

[21] Y-L Chen K-C Fang J-Y Sheu S-L Hsu and C-C TzengldquoSynthesis and antibacterial evaluation of certain quinolonederivativesrdquo Journal of Medicinal Chemistry vol 44 no 14 pp2374ndash2377 2001

[22] G RomaMDi Braccio GGrossi FMattioli andMGhia ldquo1 8-Naphthyridines IV 9-Substituted N N -dialkyl-5-(alkylaminoor cycloalkylamino) [124] triazolo [43- a][18]naphthyridine-6-carboxamides new compounds with anti-aggressive andpotent anti-inflammatory activitiesrdquo European Journal ofMedicinal Chemistry vol 35 no 11 pp 1021ndash1035 2000

[23] D Dube M Blouin C Brideau et al ldquoQuinolines as potent 5-lipoxygenase inhibitors synthesis and biological profile of L-746530rdquo Bioorganic amp Medicinal Chemistry Letters vol 8 no10 pp 1255ndash1260 1998

[24] M P Maguire K R Sheets K McVety A P Spada andA Zilberstein ldquoA new series of PDGF receptor tyrosinekinase inhibitors 3-Substituted quinoline derivativesrdquo Journalof Medicinal Chemistry vol 37 no 14 pp 2129ndash2137 1994

[25] O Billker V Lindo M Panico et al ldquoIdentification of xan-thurenic acid as the putative inducer of malaria developmentin the mosquitordquo Nature vol 392 no 6673 pp 289ndash292 1998

[26] T K Bradshaw and D W Hutchinson ldquo5-Substituted pyrim-idine nucleosides and nucleotidesrdquo Chemical Society Reviewsvol 6 no 1 pp 43ndash62 1977

[27] T Sasaki K Minamoto T Suzuki and S Yamashita ldquoSearchfor a simpler synthetic model system for intramolecular 13-dipolar cycloaddition to the 56-double bond of a pyrimidinenucleosiderdquo Tetrahedron vol 36 no 7 pp 865ndash870 1980


[28] R Marumoto and Y Furukawa ldquoKondensierte pyrimidine IIISynthese von Isoxazolo [3 4-d] pyrimidinenrdquo Chemical andPharmaceutical Bulletin vol 25 no 11 pp 2974ndash2982 1977

[29] H Griengl E Wanek W Schwarz W Streicher B Rosenwirthand E De Clercq ldquo21015840-Fluorinated arabinonucleosides of 5-(2-haloalkyl)uracil synthesis and antiviral activityrdquo Journal ofMedicinal Chemistry vol 30 no 7 pp 1199ndash1204 1987

[30] G ShawComprehensive Heterocyclic Chemistry Volume 3 A RKatritzky CW Rees Eds p 57 Pergamon Oxford UK 1984

[31] A Agarwal and P M S Chauhan ldquoSolid supported synthesisof structurally diverse dihydropyrido[23-d] pyrimidines usingmicrowave irradiationrdquo Tetrahedron Letters vol 46 no 8 pp1345ndash1348 2005

[32] G H Mahdavinia S Rostamizadeh A M Amani and ZEmdadi ldquoUltrasound-promoted greener synthesis of aryl-14-H-dibenzo[aj]xanthenes catalyzed by NH

4

H2

PO4

SiO2

inwaterrdquo Ultrasonics Sonochemistry vol 16 no 1 pp 7ndash10 2009

[33] G Cravotto and P Cintas ldquoPower ultrasound in organic synthe-sis moving cavitational chemistry from academia to innovativeand large-scale applicationsrdquo Chemical Society Reviews vol 35no 2 pp 180ndash196 2006

[34] T J Mason and J P Lorimer Applied Sonochemistry The Usesof Power Ultrasound in Chemistry and Processing Wiley-VCH2002

[35] D Mantu C Moldoveanu A Nicolescu C Deleanu and II Mangalagiu ldquoA facile synthesis of pyridazinone derivativesunder ultrasonic irradiationrdquoUltrasonics Sonochemistry vol 16no 4 pp 452ndash454 2009

[36] J T Li Y Yin L Li and M X Sun ldquoA convenient and effi-cient protocol for the synthesis of 5-aryl-13-diphenylpyrazolecatalyzed by hydrochloric acid under ultrasound irradiationrdquoUltrasonics Sonochemistry vol 17 no 1 pp 11ndash13 2010

[37] L Pizzuti P L G Martins B A Ribeiro et al ldquoEfficientsonochemical synthesis of novel 35-diaryl-45-dihydro-1H-pyrazole-1-carboximidamidesrdquo Ultrasonics Sonochemistry vol17 no 1 pp 34ndash37 2010

[38] C-L Ni X-H Song H Yan X-Q Song and R-G ZhongldquoImproved synthesis of diethyl 26-dimethyl-4-aryl-4H-pyran-35-dicarboxylate under ultrasound irradiationrdquo UltrasonicsSonochemistry vol 17 no 2 pp 367ndash369 2010

[39] A Bazgir S Ahadi R Ghahremanzadeh H R Khavasiand PMirzaei ldquoUltrasound-assisted one-pot three-componentsynthesis of spiro[indoline-341015840-pyrazolo[34-b]pyridine]-261015840(11015840H)-diones in waterrdquo Ultrasonics Sonochemistry vol 17 no 2pp 447ndash452 2010

[40] Z-H Zhang J-J Li andT-S Li ldquoUltrasound-assisted synthesisof pyrroles catalyzed by zirconium chloride under solvent-freeconditionsrdquo Ultrasonics Sonochemistry vol 15 no 5 pp 673ndash676 2008

[41] A R Khosropour ldquoUltrasound-promoted greener synthesisof 245-trisubstituted imidazoles catalyzed by Zr(acac)

4

underambient conditionsrdquo Ultrasonics Sonochemistry vol 15 no 5pp 659ndash664 2008

[42] R H Nia M Mamaghani F Shirini and K Tabatabaeian ldquoAconvenient one-pot three-component approach for regioselec-tive synthesis of novel substituted pyrazolo[15-a]pyrimidinesusing Fe+3-montmorillonite as efficient catalystrdquo Journal ofHeterocyclic Chemistry vol 51 no 2 pp 363ndash367 2014

[43] M Mamaghani F Shirini N O Mahmoodi A Azimi-Roshan and A Monfared ldquolsquoon waterrsquo organic synthesis

three-component one-pot synthesis of novel bis(1-(cyclohexylamino)-1-oxoalkyl or aryl) fumaratesrdquo Journalof the Iranian Chemical Society vol 11 no 3 pp 659ndash664 2014

[44] M Mamaghani F Shirini N O Mahmoodi A Azimi-Roshanand H Hashemlou ldquoA green efficient and recyclable Fe+3K10catalyst for the synthesis of bioactive pyrazolo[34-b]pyridin-6(7H)-ones under ldquoon waterrdquo conditionsrdquo Journal of MolecularStructure vol 1051 pp 169ndash176 2013

[45] R Hossein Nia M Mamaghani K Tabatabaeian F Shiriniand M Rassa ldquoAn expeditious regioselective synthesis of novelbioactive indole-substituted chromene derivatives via one-potthree-component reactionrdquo Bioorganic and Medicinal Chem-istry Letters vol 22 no 18 pp 5956ndash5960 2012

[46] M Mamaghani A Loghmanifar and M R Taati ldquoAn efficientone-pot synthesis of new 2-imino-13-thiazolidin-4-ones underultrasonic conditionsrdquo Ultrasonics Sonochemistry vol 18 no 1pp 45ndash48 2011

[47] MNikpassandMMamaghani F Shirini andK TabatabaeianldquoA convenient ultrasound-promoted regioselective synthesis offused polycyclic 4-aryl-3-methyl-47-dihydro-1H-pyrazolo[34-b]pyridinesrdquo Ultrasonics Sonochemistry vol 17 no 2 pp 301ndash305 2010

[48] M Mamaghani N O Mahmoodi F Shirini A Azimi-Roshanand A Monfared ldquoOn water sonochemical multicomponentsynthesis of novel bioactive 111015840-(Aryl)bis(2-(cyclohexylamino)-2-oxoethane-11-diyl) Di(alkanoates and benzoates)rdquo Journal ofChemistry vol 2013 Article ID 125959 8 pages 2013

[49] P Crepaldi B Cacciari M-C Bonache et al ldquo6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidatesfor the antagonism at the P2Y

12

receptorsrdquo Bioorganic ampMedicinal Chemistry vol 17 no 13 pp 4612ndash4621 2009

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


expressed in ppm downfield from tetramethylsilane Son-ication was performed in Elmasonic S 40H ultrasoniccleaning unit Elemental analyses were carried out on aCarlo-Erba EA1110CNNO-S analyser and agreed with thecalculated values All the chemicals were purchased fromMerck and used without further purification All sol-vents used were dried and distilled according to standardprocedures

22 General Procedure for the Synthesis of (4andashr) A mixtureof equimolar amounts of 6-amino-2-(alkylthio)pyrimidin-4(3H)-one 1 (1mmol) 13-indanedione 2 (1mmol) or 13-cyclohexadione 5 and aldehydes 3 (1mmol) in ethylene glycol(5mL) was placed in a Pyrex-glass open vessel and irradiatedat 65∘C by ultrasonic irradiations (40 kHz) (for conventionalconditions the reaction mixture was heated under refluxconditions) The progress of the reaction was monitoredby TLC (EtOAcpetroleum ether 8 4) After completion ofreaction the mixture was concentrated and cooledThe solidobtained was filtered off and recrystallized from EtOHH

2O

(11) to furnish the desired pure product

23 Spectral Data for the Products

231 5-(4-Chlorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46(5H11H)-dione (4a) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3448 3410 3271 30622932 1680 1653 1585 1541 1502 1452 1350 1271 1078 899742 707 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 = 260 (s

3H CH3) 482 (s 1H CH) 730ndash725 (m 5H Ar-H) 736

(t 1H J = 740Hz Ar-H) 745 (t 1H J = 740Hz Ar-H)779 (d 1H J = 720Hz Ar-H) 1113 (br s 1H NH) 1260(br s 1H COndashNH) ppm 13C NMR (100MHz DMSO-d

6)

120575 = 133 (Me) 342 (CH) 999 1079 1204 1209 1284 13011308 1312 1324 1336 1366 1375 1448 1535 1558 1615(CONH) 1911 (C=O) ppm Anal Cald for C

21H14ClN3O2S

(40787) C 6184 H 346 N 1030 Found C 6195 H 331N 1043

232 2-(Methylthio)-5-phenyl-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4b) Red Powder Mpgt300∘C IR (KBr) ]max = 3448 3040 2922 2851 1685 16471582 1537 1500 1456 1358 1273 742 702 cmminus1 1HNMR(400MHz DMSO-d

6) 120575 = 260 (s 3H CH

3) 482 (s 1H

CH) 715ndash711 (m 1H Ar-H) 726ndash721 (m 4H Ar-H) 734(t 2H J = 740Hz Ar-H) 744 (t 1H J = 760Hz Ar-H)778 (d 1H J = 720Hz Ar-H) 1107 (br s 1H NH) 1255 (brs 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6) 120575 =

133 (Me) 345 (CH) 1000 1085 1203 1208 1266 12741282 1285 1306 1323 1337 1367 1460 1533 1557 1625(CONH) 1911 (C=O) ppm Anal Cald for C

21H15N3O2S

(37343) C 6754 H 405 N 1125 Found C 6739 H 412N 1112

233 5-(4-Bromophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4c) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3380 3300 3100 30802920 2820 1690 1640 1618 1558 1498 1440 1348 1270 1070

850 800 760 cmminus1 1HNMR (400MHz DMSO-d6) 120575 = 260


726 (d 1H J = 680Hz Ar-H) 735 (t 1H J = 720Hz Ar-H)742 (m 3H Ar-H) 779 (d 1H J = 680Hz Ar-H) 1112(br s 1H NH) 1258 (br s 1H COndashNH) ppm 13CNMR(100MHz DMSO-d

6) 120575 133 (Me) 343 (CH) 999 1078

1197 1204 1209 1296 1305 1308 1313 1324 1336 13661452 1558 1621 (CONH) 1911 (C=O) ppm Anal Cald forC21H14BrN3O2S (45232) C 5576 H 312 N 929 Found

C 5563 H 301 N 938

234 5-(4-Fluorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4d) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3440 3400 3026 29212840 1677 1641 1602 1578 1539 1493 1458 1357 1275 1149843 798 748 709 cmminus1 1HNMR (400MHz DMSO-d

6) 120575 =

260 (s 3H CH3) 483 (s 1H CH) 707ndash701 (m 4H Ar-H)

726 (d 2H J = 640Hz Ar-H) 735 (t 1H J = 740Hz Ar-H)745 (t 1H J = 720Hz Ar-H) 779 (d 1H J = 720Hz Ar-H)1110 (br s 1H NH) 1256 (br s 1H COndashNH) ppm 13CNMR(100MHz DMSO-d

6) 120575 = 133 (Me) 340 (CH) 996 1081

1149 (d 2119869C-F = 210Hz) 1203 1207 1299 (d 3119869C-F =80Hz) 1306 1321 1339 1368 1426 1533 1561 1589 1606(d 1119869C-F = 2400Hz) 1910 (C=O) ppm Anal Cald forC21H14FN3O2S (39142) C 6444 H 361 N 1074 Found

C 6438 H 362 N 1085

235 5-(2-Bromophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4e) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3350 3300 3110 30802920 2820 1690 1645 1618 1558 1498 1440 1347 1270 1070895 845 800 760 710 cmminus1 1HNMR (400MHz DMSO-d6) 120575 = 260 (s 3H CH

3) 524 (s 1H CH) 706 (dt 1H J =

840Hz 22Hz Ar-H) 728ndash721 (m 3HAr-H) 735 (t 1H J =740Hz Ar-H) 748ndash743 (m 2H Ar-H) 780 (d 1H J =720Hz Ar-H) 1111 (br s 1H NH) 1226 (br s 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6) 120575 = 133 (Me)

357 (CH) 1000 1078 1204 1207 1234 1281 1284 13071320 1322 1328 1336 1366 1367 1449 1537 1556 1621(CONH) 1907 (C=O) ppm Anal Cald for C

21H14BrN3O2S

(45232) C 5576 H 312 N 929 Found C 5583 H 308N 945

236 5-(2-Chlorophenyl)-2-(methylthio)-3H-indeno[561101584021015840]pyrido[23-d]pyrimidine-46 (5H11H)-dione (4f) Red Pow-der Mp gt300∘C IR (KBr) ]max = 3460 3385 3120 30602930 2854 1685 1649 1616 1580 1541 1502 1445 1345 12771078 893 764 cmminus1 1HNMR(400MHzDMSO-d

6)120575=260


721 (t 2H J = 740Hz Ar-H) 729 (d 2H J = 720Hz Ar-H)735 (t 1H J = 720Hz Ar-H) 744 (t 1H J = 720Hz Ar-H)779 (d 1H J = 720Hz Ar-H) 1110 (br s 1H NH) 1249 (brs 1H COndashNH) ppm 13CNMR (100MHz DMSO-d

6) 120575 =

133 (Me) 333 (CH) 999 1076 1204 1207 1274 1281 12951307 1319 1322 1329 1336 1366 1431 1537 1559 1621(CONH) 1907 (C=O) ppm Anal Cald for C

21H14ClN3O2S

(40787) C 6184 H 346 N 1030 Found C 6172 H 331N 1018



6) 120575 = 259 (s 3H CH

3) 498 (s 1H CH) 672ndash669


6) 120575 = 133 (Me) 296 (CH)


21H15N3O3S (38943)

C 6477 H 388 N 1079 Found C 6470 H 398 N1088


6) 120575 = 260 (s 3H CH

3) 522 (s 1H CH) 723 (d


6) 120575 = 133 (Me) 330 (CH) 994 1071 1205 1207


Found C 5688 H 283 N 935


6) 120575 = 260 (s 3H

CH3) 483 (s 1H CH) 705 (t 2H J = 880Hz Ar-H)


6) 120575 = 133 (Me) 339 (CH) 970 1082


21H14N4O4S (41843) C 6028 H 337 N

1339 Found C 6010 H 348 N 1351


6) 120575 =

259 (s 3H CH3) 368 (s 3H OCH

3) 476 (s 1H CH) 679


6) 120575 = 133 (Me) 336 (CH) 554 (MeO)


22H17N3O3S (40345) C 6549 H 425 N

1042 Found C 6530 H 435 N 1028


6) 120575 = 221 (s 3H CH

3) 259



6)


C 6838 H 425 N 1078


6) 120575 = 260 (s 3H SCH

3) 367


3) 479 (s 1H CH)



23H19N3O4S (43348) C 6373 H 442 N

969 Found C 6388 H 433 N 986


6)120575=

136 (t 3H J = 71Hz CH3) 322 (q 2H J = 71Hz CH

2) 522


6)

120575 = 150 (Me) 247 (CH2) 330 (CH) 994 1071 1205 1275


Found C 5774 H 323 N 905


6) 120575 = 136 (t 3H


J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 482 (s 1H


6) 120575 = 151 (Me) 246 (CH

2) 342 (CH)


C 6238 H 395 N 976


6) 120575 = 137 (t 3H

J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 504 (s 1H


6)

120575 = 151 (Me) 246 (CH2) 290 (CH) 994 1074 1155 (2J =


C 6506 H 381 N 1022


6) 120575 = 136 (t 3H J = 72Hz

CH3) 323 (q 2H J = 72Hz CH

2) 481 (s 1H CH) 721 (d


6) 120575 = 151 (Me) 246

(CH2) 344 (CH) 997 1078 1197 1204 1209 1305 1307


22H16BrN3O2S (46635) C

5666 H 346 N 901 Found C 5653 H 327 N 916


6) 120575 = 136 (t 3H

J = 72Hz CH3) 241 (s 3H CH

3) 322 (q 2H J = 72Hz

CH2) 478 (s 1H CH) 713 (d 2H J = 80Hz Ar-H) 719


6) 120575 =

151 (Me) 154 (Me) 247 (CH2) 341 (CH) 1000 1083


C 6357 H 459 N 956


6) 120575 = 136 (t 3H J = 72Hz CH

3) 323



2) 345 (CH) 1085 1203 1209


22H17N3O2S

(38710) C 6826H 442N 1085 Found C 6808H 455N 1097


6) 120575 = 131 (t 3H J =




2ndashCH2ndashC=O)



6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 332 (CH

2ndashC=O) 372 (CH) 984 1109 1150


19H18FN3O2S (37143) C

6144 H 488 N 1131 Found C 6132 H 470 N 1118


6) 120575 = 131 (t 3H J =




2ndashCH2ndashC=O)



6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 270 (CH

2ndashC=O) 342 (CH) 983 1110 1257


23H21N3O2S

(40350) C 6846 H 525 N 1041 Found C 6860 H517 N 1055


6) 120575 = 131 (t 3H J = 72Hz CH

3ndash





2ndashCH2ndash




+ ArCHO+HN

N

O

RS

O

O

NH N

NH

O O

SR

Ar

1 2 3

Ethylene glycol

R = Me Et

65

∘C USNH

2

4andashr


Ethylene glycol+

HN

NEtS

O

+

1

ArCHONH

N

NH

OAr

SEt

OO

O

5 3

NH2

65

∘C US

6andashf



6) 120575 = 151 (Me) 210 (Me) 213 (CH

2)

245 (CH2) 268 (CH

2) 269 (CH

2ndashC=O) 333 (CH) 986


20H21N3O2S (36746) C 6537 H 576 N

1141 Found C 6521 H 552 N 1125


6) 120575 = 131 (t 3H




2ndashCH2ndashC=O)


3)


6) 120575 = 151

(Me) 213 (MeO) 245 (CH2) 269 (CH

2) 328 (CH

2) 372

(CH2ndashC=O) 554 (CH) 988 1113 1137 1288 1395 1531


C 6264 H 558 N 1085


6) 120575 =


2ndashCH2ndash



3-Ar)




6) 120575 = 151 (Me) 154 (Me) 213 (CH

2) 246 (CH

2)

269 (CH2) 286 (CH

2ndashC=O) 372 (CH) 980 1106 1230

1250 1370 1486 1525 1534 1620 (CONH) 1947 (C=O)


513 N 1125 Found C 5795 H 520 N 1110


6) 120575 = 131 (t 3H J = 72Hz







6) 120575 = 151 (Me) 212 (CH

2) 246 (CH

2) 268

(CH2) 336 (CH

2ndashC=O) 371 (CH) 981 1107 1107 1282


19H18ClN3O2S (38789) C 5883 H 468 N

1083 Found C 5870 H 447 N 1068












4 4d Me 4-FC6H4 20 (160)b 97 (85)b

5 4e Me 2-BrC6H4 30 (220)b 94 (88)b

6 4f Me 2-ClC6H4 27 (210)b 96 (89)b

7 4g Me 2-OHC6H4 32 (240)b 90 (90)b

8 4h Me 24-Cl2C6H3 20 (160)b 96 (90)b

9 4i Me 2-NO2C6H4 22 (170)b 97 (90)b


13 4m Et 24-Cl2C6H3 15 (180)b 95 (90)b

14 4n Et 4-ClC6H4 20 (185)b 89 (80)b




NH N

NH

O O

SMe

Cl

4a

Figure 1





1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b


O

O


O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+





(Scheme 3)


4 Conclusion






Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



6) 120575 = 259 (s 3H CH

3) 498 (s 1H CH) 672ndash669


6) 120575 = 133 (Me) 296 (CH)


21H15N3O3S (38943)

C 6477 H 388 N 1079 Found C 6470 H 398 N1088


6) 120575 = 260 (s 3H CH

3) 522 (s 1H CH) 723 (d


6) 120575 = 133 (Me) 330 (CH) 994 1071 1205 1207


Found C 5688 H 283 N 935


6) 120575 = 260 (s 3H

CH3) 483 (s 1H CH) 705 (t 2H J = 880Hz Ar-H)


6) 120575 = 133 (Me) 339 (CH) 970 1082


21H14N4O4S (41843) C 6028 H 337 N

1339 Found C 6010 H 348 N 1351


6) 120575 =

259 (s 3H CH3) 368 (s 3H OCH

3) 476 (s 1H CH) 679


6) 120575 = 133 (Me) 336 (CH) 554 (MeO)


22H17N3O3S (40345) C 6549 H 425 N

1042 Found C 6530 H 435 N 1028


6) 120575 = 221 (s 3H CH

3) 259



6)


C 6838 H 425 N 1078


6) 120575 = 260 (s 3H SCH

3) 367


3) 479 (s 1H CH)



23H19N3O4S (43348) C 6373 H 442 N

969 Found C 6388 H 433 N 986


6)120575=

136 (t 3H J = 71Hz CH3) 322 (q 2H J = 71Hz CH

2) 522


6)

120575 = 150 (Me) 247 (CH2) 330 (CH) 994 1071 1205 1275


Found C 5774 H 323 N 905


6) 120575 = 136 (t 3H


J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 482 (s 1H


6) 120575 = 151 (Me) 246 (CH

2) 342 (CH)


C 6238 H 395 N 976


6) 120575 = 137 (t 3H

J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 504 (s 1H


6)

120575 = 151 (Me) 246 (CH2) 290 (CH) 994 1074 1155 (2J =


C 6506 H 381 N 1022


6) 120575 = 136 (t 3H J = 72Hz

CH3) 323 (q 2H J = 72Hz CH

2) 481 (s 1H CH) 721 (d


6) 120575 = 151 (Me) 246

(CH2) 344 (CH) 997 1078 1197 1204 1209 1305 1307


22H16BrN3O2S (46635) C

5666 H 346 N 901 Found C 5653 H 327 N 916


6) 120575 = 136 (t 3H

J = 72Hz CH3) 241 (s 3H CH

3) 322 (q 2H J = 72Hz

CH2) 478 (s 1H CH) 713 (d 2H J = 80Hz Ar-H) 719


6) 120575 =

151 (Me) 154 (Me) 247 (CH2) 341 (CH) 1000 1083


C 6357 H 459 N 956


6) 120575 = 136 (t 3H J = 72Hz CH

3) 323



2) 345 (CH) 1085 1203 1209


22H17N3O2S

(38710) C 6826H 442N 1085 Found C 6808H 455N 1097


6) 120575 = 131 (t 3H J =




2ndashCH2ndashC=O)



6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 332 (CH

2ndashC=O) 372 (CH) 984 1109 1150


19H18FN3O2S (37143) C

6144 H 488 N 1131 Found C 6132 H 470 N 1118


6) 120575 = 131 (t 3H J =




2ndashCH2ndashC=O)



6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 270 (CH

2ndashC=O) 342 (CH) 983 1110 1257


23H21N3O2S

(40350) C 6846 H 525 N 1041 Found C 6860 H517 N 1055


6) 120575 = 131 (t 3H J = 72Hz CH

3ndash





2ndashCH2ndash




+ ArCHO+HN

N

O

RS

O

O

NH N

NH

O O

SR

Ar

1 2 3

Ethylene glycol

R = Me Et

65

∘C USNH

2

4andashr


Ethylene glycol+

HN

NEtS

O

+

1

ArCHONH

N

NH

OAr

SEt

OO

O

5 3

NH2

65

∘C US

6andashf



6) 120575 = 151 (Me) 210 (Me) 213 (CH

2)

245 (CH2) 268 (CH

2) 269 (CH

2ndashC=O) 333 (CH) 986


20H21N3O2S (36746) C 6537 H 576 N

1141 Found C 6521 H 552 N 1125


6) 120575 = 131 (t 3H




2ndashCH2ndashC=O)


3)


6) 120575 = 151

(Me) 213 (MeO) 245 (CH2) 269 (CH

2) 328 (CH

2) 372

(CH2ndashC=O) 554 (CH) 988 1113 1137 1288 1395 1531


C 6264 H 558 N 1085


6) 120575 =


2ndashCH2ndash



3-Ar)




6) 120575 = 151 (Me) 154 (Me) 213 (CH

2) 246 (CH

2)

269 (CH2) 286 (CH

2ndashC=O) 372 (CH) 980 1106 1230

1250 1370 1486 1525 1534 1620 (CONH) 1947 (C=O)


513 N 1125 Found C 5795 H 520 N 1110


6) 120575 = 131 (t 3H J = 72Hz







6) 120575 = 151 (Me) 212 (CH

2) 246 (CH

2) 268

(CH2) 336 (CH

2ndashC=O) 371 (CH) 981 1107 1107 1282


19H18ClN3O2S (38789) C 5883 H 468 N

1083 Found C 5870 H 447 N 1068












4 4d Me 4-FC6H4 20 (160)b 97 (85)b

5 4e Me 2-BrC6H4 30 (220)b 94 (88)b

6 4f Me 2-ClC6H4 27 (210)b 96 (89)b

7 4g Me 2-OHC6H4 32 (240)b 90 (90)b

8 4h Me 24-Cl2C6H3 20 (160)b 96 (90)b

9 4i Me 2-NO2C6H4 22 (170)b 97 (90)b


13 4m Et 24-Cl2C6H3 15 (180)b 95 (90)b

14 4n Et 4-ClC6H4 20 (185)b 89 (80)b




NH N

NH

O O

SMe

Cl

4a

Figure 1





1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b


O

O


O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+





(Scheme 3)


4 Conclusion






Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 482 (s 1H


6) 120575 = 151 (Me) 246 (CH

2) 342 (CH)


C 6238 H 395 N 976


6) 120575 = 137 (t 3H

J = 72Hz CH3) 323 (q 2H J = 72Hz CH

2) 504 (s 1H


6)

120575 = 151 (Me) 246 (CH2) 290 (CH) 994 1074 1155 (2J =


C 6506 H 381 N 1022


6) 120575 = 136 (t 3H J = 72Hz

CH3) 323 (q 2H J = 72Hz CH

2) 481 (s 1H CH) 721 (d


6) 120575 = 151 (Me) 246

(CH2) 344 (CH) 997 1078 1197 1204 1209 1305 1307


22H16BrN3O2S (46635) C

5666 H 346 N 901 Found C 5653 H 327 N 916


6) 120575 = 136 (t 3H

J = 72Hz CH3) 241 (s 3H CH

3) 322 (q 2H J = 72Hz

CH2) 478 (s 1H CH) 713 (d 2H J = 80Hz Ar-H) 719


6) 120575 =

151 (Me) 154 (Me) 247 (CH2) 341 (CH) 1000 1083


C 6357 H 459 N 956


6) 120575 = 136 (t 3H J = 72Hz CH

3) 323



2) 345 (CH) 1085 1203 1209


22H17N3O2S

(38710) C 6826H 442N 1085 Found C 6808H 455N 1097


6) 120575 = 131 (t 3H J =




2ndashCH2ndashC=O)



6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 332 (CH

2ndashC=O) 372 (CH) 984 1109 1150


19H18FN3O2S (37143) C

6144 H 488 N 1131 Found C 6132 H 470 N 1118


6) 120575 = 131 (t 3H J =




2ndashCH2ndashC=O)



6) 120575 = 151 (Me) 213 (CH

2) 245 (CH

2)

269 (CH2) 270 (CH

2ndashC=O) 342 (CH) 983 1110 1257


23H21N3O2S

(40350) C 6846 H 525 N 1041 Found C 6860 H517 N 1055


6) 120575 = 131 (t 3H J = 72Hz CH

3ndash





2ndashCH2ndash




+ ArCHO+HN

N

O

RS

O

O

NH N

NH

O O

SR

Ar

1 2 3

Ethylene glycol

R = Me Et

65

∘C USNH

2

4andashr


Ethylene glycol+

HN

NEtS

O

+

1

ArCHONH

N

NH

OAr

SEt

OO

O

5 3

NH2

65

∘C US

6andashf



6) 120575 = 151 (Me) 210 (Me) 213 (CH

2)

245 (CH2) 268 (CH

2) 269 (CH

2ndashC=O) 333 (CH) 986


20H21N3O2S (36746) C 6537 H 576 N

1141 Found C 6521 H 552 N 1125


6) 120575 = 131 (t 3H




2ndashCH2ndashC=O)


3)


6) 120575 = 151

(Me) 213 (MeO) 245 (CH2) 269 (CH

2) 328 (CH

2) 372

(CH2ndashC=O) 554 (CH) 988 1113 1137 1288 1395 1531


C 6264 H 558 N 1085


6) 120575 =


2ndashCH2ndash



3-Ar)




6) 120575 = 151 (Me) 154 (Me) 213 (CH

2) 246 (CH

2)

269 (CH2) 286 (CH

2ndashC=O) 372 (CH) 980 1106 1230

1250 1370 1486 1525 1534 1620 (CONH) 1947 (C=O)


513 N 1125 Found C 5795 H 520 N 1110


6) 120575 = 131 (t 3H J = 72Hz







6) 120575 = 151 (Me) 212 (CH

2) 246 (CH

2) 268

(CH2) 336 (CH

2ndashC=O) 371 (CH) 981 1107 1107 1282


19H18ClN3O2S (38789) C 5883 H 468 N

1083 Found C 5870 H 447 N 1068












4 4d Me 4-FC6H4 20 (160)b 97 (85)b

5 4e Me 2-BrC6H4 30 (220)b 94 (88)b

6 4f Me 2-ClC6H4 27 (210)b 96 (89)b

7 4g Me 2-OHC6H4 32 (240)b 90 (90)b

8 4h Me 24-Cl2C6H3 20 (160)b 96 (90)b

9 4i Me 2-NO2C6H4 22 (170)b 97 (90)b


13 4m Et 24-Cl2C6H3 15 (180)b 95 (90)b

14 4n Et 4-ClC6H4 20 (185)b 89 (80)b




NH N

NH

O O

SMe

Cl

4a

Figure 1





1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b


O

O


O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+





(Scheme 3)


4 Conclusion






Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


+ ArCHO+HN

N

O

RS

O

O

NH N

NH

O O

SR

Ar

1 2 3

Ethylene glycol

R = Me Et

65

∘C USNH

2

4andashr


Ethylene glycol+

HN

NEtS

O

+

1

ArCHONH

N

NH

OAr

SEt

OO

O

5 3

NH2

65

∘C US

6andashf



6) 120575 = 151 (Me) 210 (Me) 213 (CH

2)

245 (CH2) 268 (CH

2) 269 (CH

2ndashC=O) 333 (CH) 986


20H21N3O2S (36746) C 6537 H 576 N

1141 Found C 6521 H 552 N 1125


6) 120575 = 131 (t 3H




2ndashCH2ndashC=O)


3)


6) 120575 = 151

(Me) 213 (MeO) 245 (CH2) 269 (CH

2) 328 (CH

2) 372

(CH2ndashC=O) 554 (CH) 988 1113 1137 1288 1395 1531


C 6264 H 558 N 1085


6) 120575 =


2ndashCH2ndash



3-Ar)




6) 120575 = 151 (Me) 154 (Me) 213 (CH

2) 246 (CH

2)

269 (CH2) 286 (CH

2ndashC=O) 372 (CH) 980 1106 1230

1250 1370 1486 1525 1534 1620 (CONH) 1947 (C=O)


513 N 1125 Found C 5795 H 520 N 1110


6) 120575 = 131 (t 3H J = 72Hz







6) 120575 = 151 (Me) 212 (CH

2) 246 (CH

2) 268

(CH2) 336 (CH

2ndashC=O) 371 (CH) 981 1107 1107 1282


19H18ClN3O2S (38789) C 5883 H 468 N

1083 Found C 5870 H 447 N 1068












4 4d Me 4-FC6H4 20 (160)b 97 (85)b

5 4e Me 2-BrC6H4 30 (220)b 94 (88)b

6 4f Me 2-ClC6H4 27 (210)b 96 (89)b

7 4g Me 2-OHC6H4 32 (240)b 90 (90)b

8 4h Me 24-Cl2C6H3 20 (160)b 96 (90)b

9 4i Me 2-NO2C6H4 22 (170)b 97 (90)b


13 4m Et 24-Cl2C6H3 15 (180)b 95 (90)b

14 4n Et 4-ClC6H4 20 (185)b 89 (80)b




NH N

NH

O O

SMe

Cl

4a

Figure 1





1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b


O

O


O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+





(Scheme 3)


4 Conclusion






Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of









4 4d Me 4-FC6H4 20 (160)b 97 (85)b

5 4e Me 2-BrC6H4 30 (220)b 94 (88)b

6 4f Me 2-ClC6H4 27 (210)b 96 (89)b

7 4g Me 2-OHC6H4 32 (240)b 90 (90)b

8 4h Me 24-Cl2C6H3 20 (160)b 96 (90)b

9 4i Me 2-NO2C6H4 22 (170)b 97 (90)b


13 4m Et 24-Cl2C6H3 15 (180)b 95 (90)b

14 4n Et 4-ClC6H4 20 (185)b 89 (80)b




NH N

NH

O O

SMe

Cl

4a

Figure 1





1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b


O

O


O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+





(Scheme 3)


4 Conclusion






Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




1 6a 4-FC6H4 10 (180)b 95 (90)b

2 6b 1-naphtyl 15 (230)b 93 (87)b

3 6c 4-CH3C6H4 20 (270)b 89 (82)b


O

O


O

O

H

Ar

N

NH

O

SCH3

SCH3

SCH3SCH3

SCH3

SCH3

OAr

NH

O

NNO

HH

OAr

NH

O

NNOH

O Ar

NH

O

NNO

HH H

NH

N

NH

OO Ar

HO

NH

N

NH

O OAr

3 17

46

minus

minusH2O

minusH2O

∙∙

∙∙

H2N

+





(Scheme 3)


4 Conclusion






Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of





Acknowledgments


References


1


































4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of







4

H2

PO4

SiO2











4











12











Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of










Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

research article an efficient, clean, and catalyst-free...

Documents