research article (+)-csa catalyzed multicomponent ......research article (+)-csa catalyzed...

Research Article(+)-CSA Catalyzed Multicomponent Synthesis of1-[(13-Thiazol-2-ylamino)methyl]-2-naphthols and TheirRing-Closure Reaction under Ultrasonic Irradiation

Emel Pelit1 and Zuhal Turgut2

1Department of Chemistry Faculty of Art and Sciences Kirklareli University Kayali Campus 39100 Kırklareli Turkey2Department of Chemistry Faculty of Art and Sciences Yildiz Technical University Davutpasa Campus 34210 Istanbul Turkey

Correspondence should be addressed to Emel Pelit epelitkluedutr

Received 12 February 2016 Accepted 29 March 2016

Academic Editor Rajeev Sakhuja

Copyright copy 2016 E Pelit and Z Turgut This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

New 1-[(13-thiazol-2-ylamino)methyl]-2-naphthols were obtained by condensation of 2-aminothiazole aromatic aldehydes and2-naphthol in the presence of (+)-camphor-10-sulfonic acid ((+)-CSA) as an effective catalyst under ultrasound-promotedsolvent-free conditionsThe 1-[(13-thiazol-2-ylamino)methyl]-2-naphthol derivatives were converted in ring-closure reaction withformaldehyde to the corresponding naphthoxazine derivatives

Dedicated to the memory of Professor Yiannis Elemes

1 Introduction

Multicomponent reactions have increasing importance insynthetic organic chemistry because they allow the buildingof several new bonds in a single step [1ndash4] Some of thesignificant advantages of multicomponent reactions overconventional reactions are a high degree of atomic economystructural diversity easier progress of reactions decreasedreaction times low power consumption and lack of wasteproducts [5 6]

The Mannich reaction is one of the most importantcarbon-carbon bond forming reactions in organic chemistryThis reaction is used as a key step in the synthesis of manysynthetically and biologically important nitrogen-contain-ing compounds [7ndash11] A large number of studies on Man-nich-type reactions have been reported under many variedprocesses in the literature [12ndash16] The Mannich reactionhas also been performed to achieve stereoselective synthesisof aminonaphthol derivatives in the last decades Thesestereoselective compounds have exhibited fairly good enan-tioselectivity in asymmetric reactions [17ndash20] There are

some reports on the use of heteroarylamines in Mannich-type reactions and synthesis of 2-amino-13-thiazoles in theliterature [21ndash26]

CSA has been demonstrated to be an efficient nontoxicecofriendly economical andwater soluble catalyst for severalreactions such as synthesis of 120573-amino carbonyl compounds[27] Friedel-Crafts reactions [28 29] Meyer-Schuster reac-tions [30] Friedlander annulations [31] synthesis of 120572-hydroxy and 120572-amino phosphonates [32] synthesis of 134-oxadiazoles [33] synthesis of pseudoglycosides [34] synthe-sis of coumarins [35] synthesis of spirocyclic compounds[36] and rearrangement of 12-dialkynylallyl alcohols [37]and it is widely used in the optical resolution of amines [38]

The development of efficient and environmentallyfriendly chemical processes has an increasing popularityin organic chemistry In this context ultrasound-assistedorganic reactions have become an important research areain recent years [39ndash43] Ultrasound irradiation is able toactivate many organic reactions due to cavitational collapse[44 45] Compared with traditional methods a broad rangeof organic syntheses can be successfully performed in higher

Hindawi Publishing CorporationJournal of ChemistryVolume 2016 Article ID 9315614 9 pageshttpdxdoiorg10115520169315614

2 Journal of Chemistry

yields and selectivity shorter reaction times andmilder reac-tion conditions under ultrasonic irradiation [46ndash48]

13-Oxazine derivatives have shown many biological pro-perties such as analgesic anticonvulsant antitubular antibac-terial antifungal and anticancer activity [49ndash56] Also in thelast decades these compounds have been used in the treat-ment of AIDS and Parkinsonrsquos disease [57 58] Furthermore13-oxazine derivatives can also be used as an intermediate inthe synthesis of N-substituted aminoalcohols [59]Thereforeseveral methods for the synthesis of 13-oxazine derivativeshave been reported [60ndash66]

Here we report on the preparation of 1-[(13-thiazol-2-ylamino)methyl]-2-naphthols catalyzed by (+)-CSA ((+)-camphor-10-sulfonic acid) under ultrasonic irradiation andsolvent-free conditions and then ring-closure reaction ofthese compounds with formaldehyde under ultrasonic irra-diation in THF solvent with short reaction times and goodyields

2 Experimental

21 Materials and Methods NMR spectra were determinedon a Bruker Avance III-500MHz NMR Chemical shifts aregiven in ppm downfield from Me

4Si in DMSO-119889

6or CDCl

3

solution Coupling constants are given in Hz The FTIRspectra were recorded on a Perkin-Elmer FTIR spectrometer(ATR) and absorption frequencies are reported in cmminus1MS spectra were recorded on a Thermo Elemental X SeriesICP-MS Elemental analyses were measured with Flash EA1112 Series apparatus and were in good agreement (plusmn02)with the calculated values Ultrasonication was performedin a Bandelin Sonorex Ultrasonic Bath (Super RK) with afrequency of 35 kHz and a power of 230W The internaldimensions of the ultrasonic cleaner tank were 240 times 140times 100mm with liquid holding capacity of 3 L The reactorwas a 100mL Pyrex round-bottom flask The reaction flaskswere suspended in the center of the bath and the addi-tion or removal of water controlled the temperature of thewater bath Melting points were measured on a Gallenkampmelting-point apparatus Silica gel 60 (Merck) was used forcolumn separation TLC was conducted on standard conver-sion aluminum sheets precoated with a 02mm layer of silicagel All reagentswere commercially available Anhydrous (+)-CSA was purchased from commercial suppliers

22 General Procedure for the Synthesis of 1-[(13-Thiazol-2-ylamino)methyl]-2-naphthols (1andashn) under Ultrasonic Irra-diation A mixture of (+)-CSA (116mg 005mmol) 2-aminothiazole (100mmol) aromatic aldehyde (100mmol)and 2-naphthol (100mmol) was irradiated with ultrasoundof low power (with a frequency of 35 kHz and a nominalpower of 230W) at 50∘C for the period of time indicatedin Table 3 and Scheme 3 The reaction flask was located atthe maximum energy area in the cleaner and the surfaceof the reactants was placed slightly lower than the levelof the water The addition or removal of water controlledthe temperature of the water bath After completion of thereaction as indicated by TLC monitoring the resultant solidwas crystallized from acetone to give products 1andashn

1-[Phenyl(13-thiazol-2-ylamino)methyl]-2-naphthol (1a)White powder mp 197ndash199∘C (Lit [23] 196ndash198∘C) FTIR(ATR cmminus1) 3363 3131 3055 3024 2971 1629 1553 15141439 1338 1264 1248 1157 1055 1029 949 736 1H NMR 120575H(DMSO-119889

6 500MHz) 650 (d J = 600Hz 1H) 710ndash836

(m 13H) 936 (d J = 150Hz 1H) 1222 (br s 1H) 13CNMR 120575C (DMSO-119889

6 125MHz) 5628 10732 12021 12351

12378 12397 12473 12729 12771 12907 12965 1305513600 13980 14396 15032 15537 17106 MSmz (ESI) 333(M+ + 1) 233 215 101 71 57 Anal Calc for C

20H16N2OS C

7226 H 485 N 843 Found C 7213 H 481 N 840

1-[4-Methylphenyl(13-thiazol-2-ylamino)methyl]-2-naphthol(1b Supporting Information Page 2 in SupplementaryMaterialavailable online at httpdxdoiorg10115520169315614)White powder mp 163ndash165∘C FTIR (ATR cmminus1) 33573131 3055 3020 2939 1628 1541 1513 1436 1325 12621246 1155 1051 1020 953 869 805 782 738 1H NMR 120575H(DMSO-119889

6 500MHz) 221 (s 3H) 659 (br s 1H) 698ndash732

(m 9H) 774 (d J = 800Hz 1H) 778 (d 119869 = 850Hz 1H)789 (br s 1H) 834 (br s 1H) 1015 (br s 1H) 13C NMR 120575C(DMSO-119889

6 125MHz) 2052 5343 10662 11290 11848

11926 12230 12608 12843 12854 12862 12919 1321213275 13506 13819 13955 15302 16892 MS mz (ESI)347 (M+ + 1) 247 232 214 189 101 71 57 Anal Calc forC21H18N2OS C 7280 H 524 N 809 Found C 7276 H

521 N 805

1-[4-Bromophenyl(13-thiazol-2-ylamino)methyl]-2-naphthol(1c Supporting Information Page 3) White powder mp173ndash175∘C FTIR (ATR cmminus1) 3377 3113 3060 3020 29661630 1548 1509 1435 1338 1264 1245 1158 1054 1009 946842 805 775 741 1H NMR 120575H (DMSO-119889

6 500MHz) 663

(d J = 350Hz 1H) 700 (d J = 350Hz 1H) 704 (d J =700Hz 1H) 716 (d J = 800Hz 2H) 722 (d J = 850Hz1H) 726 (d J = 750Hz 1H) 735 (d J = 550Hz 1H) 744(d J = 850Hz 2H) 777 (d J = 800Hz 1H) 780 (d J =800Hz 1H) 784 (br s 1H) 838 (d J = 450Hz 1H) 1020(br s 1H) 13C NMR 120575C (DMSO-119889

6 125MHz) 5300 10699

11836 11865 11903 12242 12628 12738 12838 1285312953 13081 13200 13349 13821 14241 15303 16868 MSmz (ESI) 412 (M+ + 1) 312 232 214 189 101 71 57 AnalCalc for C

20H15BrN2OS C 5840 H 368 N 681 Found

C 5825 H 363 N 678

1-[4-Isopropylphenyl(13-thiazol-2-ylamino)methyl]-2-naph-thol (1d Supporting Information Page 4) White powder mp159ndash161∘C FTIR (ATR cmminus1) 3344 3118 3060 3020 29571625 1531 1505 1435 1326 1272 1255 1155 1046 1019 954860 817 782 744 1H NMR (DMSO-119889

6 500MHz) 114 (d

J = 400Hz 6H) 279ndash281 (m 1H) 660 (d J = 350Hz1H) 698ndash735 (m 9H) 776 (dd 119869

1= 1750Hz 119869

2= 750Hz

2H) 797 (d J = 200Hz 1H) 834 (br s 1H) 1013 (br s 1H)13C NMR (DMSO-119889

6 125MHz) 2382 2390 3295 5357

10660 11452 11848 11921 12232 12589 12620 1284612857 12916 13220 13324 13824 13990 14615 1530016888 MS mz (ESI) 375 (M+ + 1) 275 233 215 189 157101 71 57 Anal Calc for C

23H22N2OS C 7376 H 592 N

748 Found C 7372 H 587 N 745

Journal of Chemistry 3

1-[24-Dimethylphenyl(13-thiazol-2-ylamino)methyl]-2-naph-thol (1e Supporting Information Page 5) White powder mp171ndash173∘C FTIR (ATR cmminus1) 3343 3125 3062 3000 29562916 1625 1604 1578 1528 1504 1435 1365 1330 1269 12421156 1083 1043 946 842 816 745 1H NMR (DMSO-119889

6

500MHz) 212 (s 3H) 220 (s 3H) 653 (d J = 350Hz1H) 687ndash690 (m 2H) 693 (d J = 350Hz 2H) 717ndash723(m 3H) 731 (t J = 750Hz 1H) 773 (d J = 900Hz 1H)777 (d J = 750Hz 1H) 802 (d J = 900Hz 1H) 830 (brs 1H) 1008 (br s 1H) 13C NMR (DMSO-119889

6 125MHz)

1897 2042 5295 10620 11769 11842 12221 12575 1273412846 12852 12917 13114 13267 13558 13604 1367013835 15332 16827 MS mz (ESI) 361 (M+ + 1) 318 274260 246 101 71 57 Anal Calc for C

22H20N2OS C 7330

H 559 N 777 Found C 7325 H 560 N 774

1-[(24-Dichlorophenyl)(13-thiazol-2-ylamino)methyl]-2-naph-thol (1f Supporting Information Page 6) White powdermp 164ndash166∘C FTIR (ATR cmminus1) 3336 3122 3072 30272974 1624 1578 1534 1515 1505 1465 1434 1370 1319 12681183 1156 1082 1052 1042 948 883 813 748 1H NMR(DMSO-119889

6 500MHz) 660 (d J = 350Hz 1H) 698 (d J =

350Hz 1H) 701 (d J = 700Hz 1H) 712 (d J = 850Hz 1H)725 (t J = 750Hz 1H) 739ndash741 (m 2H) 747 (d J = 200Hz1H) 766 (d J = 850Hz 1H) 775 (d J = 800Hz 1H) 779(d J = 900Hz 1H) 801 (d J = 650Hz 1H) 843 (br s 1H)994 (br s 1H) 13CNMR (DMSO-119889

6 125MHz) 5257 10681


20H14Cl2N2OS C 5986 H 352 N 698 Found

C 5984 H 350 N 696

1-[(24-Difluorophenyl)(13-thiazol-2-ylamino)methyl]-2-naph-thol (1g) White powder mp 165ndash167∘C FTIR (ATR cmminus1)3313 3126 3069 3055 3024 2970 1620 1607 1548 1515 15001434 1371 1347 1261 1235 1159 1139 1083 1053 966 850 815744 1H NMR (DMSO-119889

6 500MHz) 661 (d J = 350Hz

1H) 698ndash727 (m 6H) 740 (d J = 600Hz 1H) 761 (d J =550Hz 1H) 764ndash806 (m 3H) 838 (br s 1H) 1008 (br s1H) 13C NMR (DMSO-119889

6 125MHz) 4890 10343 10688

11050 11723 11842 12231 12288 12575 12626 1282912853 12952 13020 13215 13828 15325 16798 MS mz(ESI) 369 (M+ + 1) 284 269 256 156 138 101 71 57 AnalCalc for C

20H14F2N2OS C 6520 H 383 N 760 Found

C 6518 H 380 N 758

1-[(3-Phenoxyphenyl)(13-thiazol-2-ylamino)methyl]-2-naph-thol (1h) White powder mp 162ndash164∘C FTIR (ATR cmminus1)3356 3122 3060 3006 2939 1623 1579 1531 1480 1437 13171257 1243 1221 1155 1064 1045 971 866 740 1H NMR(DMSO-119889

6 500MHz) 662 (br s 1H) 678 (d J = 600Hz

1H) 689 (d J = 600Hz 2H) 700 (d J = 950Hz 3H) 708(d J = 950Hz 2H) 724ndash731 (m 6H) 775ndash779 (m 2H)786 (br s 1H) 839 (br s 1H) 1020 (br s 1H) 13C NMR(DMSO-119889

6 125MHz) 5320 10691 11632 11689 11795

11839 11889 12153 12240 12306 12614 12851 1286012945 12962 12986 13205 13344 13818 14538 1530315597 15667 16872 MS mz (ESI) 425 (M+ + 1) 406

362 325 318 274 261 256 202 101 71 57 Anal Calc forC26H20N2O2S C 7356 H 417 N 828 Found C 7353 H

415 N 825

1-[(4-Benzyloxyphenyl)(13-thiazol-2-ylamino)methyl]-2-naph-thol (1i) White powder mp 153ndash155∘C FTIR (ATR cmminus1)3385 3126 3057 3021 2947 2862 1628 1609 1579 1554 15101459 1441 1338 1266 1251 1240 1175 1157 1120 1054 10381027 951 874 810 743 1H NMR (DMSO-119889

6 500MHz) 501

(s 2H) 659 (d J = 350Hz 1H) 689 (d J = 850Hz 2H)698 (d J = 350Hz 2H) 714 (d J = 800Hz 2H) 721 (d J= 900Hz 1H) 724 (d J = 750Hz 1H) 730 (d J = 700Hz1H) 734ndash737 (m 3H) 741 (d J = 700Hz 2H) 774 (d J =900Hz 1H) 778 (d J = 800Hz 1H) 790 (br s 1H) 833(br s 1H) 1015 (br s 1H) 13C NMR (DMSO-119889

6 125MHz)

5325 6909 11427 11491 11845 11916 12118 12231 1247612505 12732 12762 12774 12836 12845 12917 13459137119 13823 13867 13950 15055 15299 15677 16886 MSmz (ESI) 439 (M+ + 1) 420 377 361 339 326 316 299 256247 154 101 71 57 Anal Calc for C

27H22N2O2S C 7395

H 506 N 639 Found C 7393 H 505 N 636

1-[(3-Nitrophenyl)(13-thiazol-2-ylamino)methyl]-2-naphthol(1j) White powder mp 183ndash185∘C (Lit [23] 181ndash183∘C)FTIR (ATR cmminus1) 3387 3124 3054 3020 2927 2852 16281606 1574 1537 1458 1440 1336 1263 1250 1237 1155 11201056 1041 1025 954 876 810 745 1H NMR (DMSO-119889

6

500MHz) 662 (d J = 350Hz 1H) 688ndash778 (m 9H) 787(br s 1H) 800ndash846 (m 3H) 1023 (br s 1H) 13C NMR(DMSO-119889

6 125MHz) 5312 10807 11830 11852 11976

12115 12243 12305 12640 12835 12855 12955 1308113212 13310 13823 13836 14400 15298 16856 MS mz(ESI) 378 (M+ + 1) 360 332 270 201 101 71 57 Anal Calcfor C20H15N3O3S C 6365 H 401 N 1113 Found C 6353

H 403 N 1115

1-[(13-Thiazol-2-ylamino)(thiophen-2-yl)methyl]-2-naphthol(1k Supporting Information Page 7) White powder mp155-156∘C FTIR (ATR cmminus1) 3326 3126 3091 3061 29802908 2869 1629 1550 1514 1436 1372 1340 1266 12471160 1075 1051 945 870 809 744 1H NMR (DMSO-119889

6

500MHz) 663 (d J = 300Hz 1H) 677 (br s 1H) 689 (d J= 300Hz 1H) 702 (d J = 300Hz 1H) 721ndash727 (m 3H) 732(d J = 450Hz 1H) 737 (br s 1H) 777 (d J = 900Hz 1H)780 (d J = 800Hz 1H) 801 (br s 1H) 850 (br s 1H) 1027(br s 1H) 13C NMR (DMSO-119889

6 125MHz) 5081 10706

11840 11851 12242 12403 12444 12611 12653 1285012958 13199 13822 14701 15302 16833 MSmz (ESI) 339(M+ + 1) 318 273 256 239 221 202 101 71 57 Anal Calcfor C18H14N2OS2 C 6388 H 417 N 828 Found C 6385

H 415 N 826

1-[(13-Thiazol-2-ylamino)(thiophen-3-yl)methyl]-2-naphthol(1l) White powder mp 154ndash156∘C FTIR (ATR cmminus1)3328 3122 3055 2975 1624 1549 1513 1434 1362 1338 12481156 1142 1053 949 837 804 741 1H NMR (DMSO-119889

6

500MHz) 660 (d J = 350Hz 1H) 686 (d J = 250Hz1H) 697ndash700 (m 2H) 720ndash726 (m 3H) 735ndash739 (m2H) 773ndash778 (m 2H) 801 (d J = 350Hz 1H) 848 (br s


1H) 1023 (br s 1H) 13C NMR (DMSO-1198896 125MHz) 5129

10668 11855 11881 12051 12233 12587 12704 1284512858 12923 13203 13813 14353 15292 16862 MS mz(ESI) 339 (M+ + 1) 318 273 256 239 221 202 101 71 57Anal Calc for C

18H14N2OS2 C 6388 H 417 N 828

Found C 6386 H 414 N 826

1-[5-Methylfuran-2-yl(13-thiazol-2-ylamino)methyl]-2-naph-thol (1m Supporting Information Page 8) White powdermp 164ndash166∘C FTIR (ATR cmminus1) 3368 3129 3062 30543014 2973 2950 1632 1560 1542 1509 1447 1373 1338 12611240 1215 1175 1154 1103 1053 1020 953 863 817 785 7521H NMR (DMSO-119889

6 500MHz) 214 (s 3H) 596 (d J =

300Hz 1H) 599 (d J = 300Hz 1H) 658 (d J = 350Hz1H) 697ndash698 (m 2H) 718ndash725 (m 2H) 738 (br s 1H)773ndash778 (m 2H) 812 (d J = 800Hz 2H) 843 (br s 1H)1018 (br s 1H) 13C NMR (DMSO-119889

6 125MHz) 1332 4914


19H16N2O2S C 6784 H 479

N 833 Found C 6786 H 477 N 830

1-[5-Bromofuran-2-yl(13-thiazol-2-ylamino)methyl]-2-naph-thol (1n Supporting Information Page 9) White powder mp158ndash160∘C FTIR (ATR cmminus1) 3366 3129 3066 3024 29912980 2915 1632 1580 1542 1508 1448 1373 1337 1271 12581198 1154 1122 1105 1052 1009 921 862 816 787 751 1HNMR (DMSO-119889

6 500MHz) 620 (d J = 300Hz 1H) 646

(d J = 350Hz 1H) 662 (d J = 350Hz 1H) 701 (d J =350Hz 1H) 704 (d J = 650Hz 1H) 721 (d J = 900Hz1H) 727 (t J = 750Hz 1H) 740 (t J = 750Hz 1H) 777(d J = 900Hz 1H) 780 (d J = 800Hz 1H) 808 (d J =850Hz 1H) 847 (d J = 500Hz 1H) 1024 (br s 1H) 13CNMR (DMSO-119889

6 125MHz) 4883 10699 10935 11228

11564 11831 11925 12241 12315 12620 12836 1284512972 13218 13811 15338 15695 16801 MSmz (ESI) 402(M+ + 1) 384 340 302 284 259 255 138 101 71 57 AnalCalc for C

18H13BrN2O2S C 5388 H 327 N 698 Found

C 5385 H 325 N 696

23 General Procedure for the Synthesis of the Naphthox-azines (2andashf) under Ultrasonic Irradiation 1-[(13-Thiazol-2-ylamino)methyl]-2-naphthols 1a 1c 1d 1k 1m and 1n(1mmol) were dissolved in THF (3mL) and 35 aqueousformaldehyde (12mmol) was added The solution was irra-diated with ultrasound of low power (with a frequency of35 kHz and a nominal power of 230W) at 50∘C for 3 hoursThe reaction flask was located at the maximum energy areain the cleaner and the surface of the reactants was placedslightly lower than the level of the water The addition orremoval of water controlled the temperature of the waterbath Solvent was removed and the residue was dried underreduced pressure The crude oil was purified by columnchromatography eluting with EtOAchexane

1-Phenyl-2-(thiazol-2-yl)-23-dihydro-1H-naphtho[12-e][13]ox-azine(2a Supporting Information 0) White powdermp 125-126∘C FTIR (ATR cmminus1) 3126 3106 3077 3057

3025 2944 2922 2898 2850 1623 1599 1508 1483 14661404 1382 1312 1233 1201 1125 1089 1058 1000 969 915816 745 1H NMR (CDCl

3 500MHz) 511 (d J = 1100Hz

1H) 564 (d J = 1100Hz 1H) 667 (d J = 350Hz 1H) 687(s 1H) 713 (d J = 900Hz 1H) 725 (d J = 350Hz 1H)729ndash733 (m 5H) 736ndash738 (m 2H) 744 (d J = 900Hz 1H)773 (d J = 900Hz 1H) 776 (d J = 900Hz 1H) 13C NMR(CDCl

3 125MHz) 5953 7369 10944 11286 11881 12305

12379 12692 12810 12855 12864 12896 12921 1297213189 13963 14090 15169 MS mz (ESI) 345 (M+ + 1)260 232 215 175 102 71 57 Anal Calc for C

21H16N2OS C

7323 H 468 N 813 Found C 7320 H 466 N 810

1-(4-Bromophenyl)-2-(thiazol-2-yl)-23-dihydro-1H-naphtho[12-e][13]oxazine (2b Supporting Information Page 11) Whitepowder mp 101ndash103∘C FTIR (ATR cmminus1) 3119 3062 29522925 2853 1625 1588 1508 1484 1466 1434 1401 1311 12681230 1176 1131 1057 1000 968 917 877 812 773 745 1HNMR (CDCl

3 500MHz) 499 (d J = 1100Hz 1H) 552 (dd

1198691= 1100Hz 119869

2= 200Hz 1H) 662 (d J = 350Hz 1H)

679 (s 1H) 705 (d J = 900Hz 1H) 717 (d J = 850Hz 1H)722ndash733 (m 4H) 736 (d J = 850Hz 2H) 756ndash770 (m3H) 13CNMR (CDCl

3 125MHz) 5869 7381 10967 11880

12284 12351 12394 12708 12864 12924 12995 1306913165 13178 13246 13956 13991 15168 MSmz (ESI) 424(M+ + 1) 339 316 311 293 254 236 102 71 57 Anal Calcfor C

21H15BrN2OS C 5958 H 357 N 662 Found C

5955 H 355 N 660

1-(4-Isopropylphenyl)-2-(thiazol-2-yl)-23-dihydro-1H-naph-tho[12-e][13]oxazine (2c Supporting Information Page 12)White powder mp 115ndash117∘C FTIR (ATR cmminus1) 3113 30913059 3012 2961 2921 2893 2869 1624 1597 1505 1485 14661432 1404 1381 1311 1271 1230 1177 1126 1089 1050 1001973 918 857 812 773 746 1HNMR (CDCl

3 500MHz) 122

(d J = 350Hz 6H) 284ndash292 (m 1H) 513 (d J = 1100Hz1H) 565 (d J = 1100Hz 1H) 666 (d J = 700Hz 1H) 682(s 1H) 712 (d J = 900Hz 1H) 716 (d J = 800Hz 1H)725 (d J = 350Hz 1H) 727 (d J = 800Hz 2H) 731 (d J =800Hz 1H) 734 (d J = 700Hz 1H) 748 (d J = 800Hz1H) 772 (d J = 900Hz 1H) 776 (d J = 800Hz 1H) 13CNMR (CDCl

3 125MHz) 2390 2393 3377 5946 7364

10933 11316 11881 12313 12373 12667 12687 1285112884 12918 12960 13193 13824 13962 14873 15162 MSmz (ESI) 387 (M+ + 1) 318 302 274 256 237 218 202 10271 57 Anal Calc for C

24H22N2OS C 7458 H 574 N 725

Found C 7456 H 576 N 723

2-(Thiazol-2-yl)-1-(thiophen-2-yl)-23-dihydro-1H-naphtho[12-e][13]oxazine (2d) White powder mp 117-118∘C FTIR(ATR cmminus1) 3107 3091 3072 3057 2961 2922 2898 28501623 1598 1505 1485 1467 1405 1376 1361 1312 1230 11691116 1087 1058 1003 967 816 748 706 1H NMR (CDCl

3

500MHz) 533 (d J = 1100Hz 1H) 568 (dd 1198691= 1100Hz

1198692= 200Hz 1H) 669 (d J = 350Hz 1H) 682 (d J =

350Hz 1H) 687 (dd 1198691= 900Hz 119869

2= 350Hz 1H) 702

(s 1H) 710 (d J = 900Hz 1H) 725 (d J = 350Hz 1H)730 (dd 119869

1= 850Hz 119869

2= 150Hz 1H) 732ndash740 (m 2H)

763 (d J = 850Hz 1H) 772 (d J = 900Hz 1H) 775 (d J


N

N

S

S NH2

++

O

H US

OHOH HN

Scheme 1 One-pot three-component Mannich reaction

= 750Hz 1H) 13C NMR (CDCl3 125MHz) 5509 7383

10971 11875 12284 12388 12625 12671 12702 1284112855 12925 12997 13167 13962 14446 15111 MS mz(ESI) 351 (M+ + 1) 323 268 266 238 220 182 101 7157 Anal Calc for C

19H14N2OS2 C 6512 H 403 N 799

Found C 6515 H 405 N 797

1-(5-Methylfuran-2-yl)-2-(thiazol-2-yl)-23-dihydro-1H-naph-tho[12-e][13]oxazine (2e Supporting Information Page 13)White powder mp 126ndash128∘C FTIR (ATR cmminus1) 31113072 3057 3025 2930 2913 2893 2855 1623 1599 15081466 1432 1402 1375 1314 1230 1129 1057 998 969 913 809747 700 1H NMR (CDCl

3 500MHz) 243 (s 3H) 536 (d J

= 1100Hz 1H) 568 (dd 1198691= 1100Hz 119869

2= 150Hz 1H) 651

(dd 1198691= 350Hz 119869

2= 100Hz 1H) 657 (dd 119869

1= 350Hz 119869

2

= 100Hz 1H) 667 (d J = 350Hz 1H) 690 (s 1H) 709 (dJ = 850Hz 1H) 724 (d J = 350Hz 1H) 730ndash741 (m 2H)767 (d J = 850Hz 1H) 771 (d J = 900Hz 1H) 774 (d J =750Hz 1H) 13CNMR (CDCl

3 125MHz) 1545 5535 7372


20H16N2O2S C 6894 H 463 N 804 Found C

6896 H 465 N 802

1-(5-Bromofuran-2-yl)-2-(thiazol-2-yl)-23-dihydro-1H-naph-tho[12-e][13]oxazine (2f ) White powder mp 105ndash107∘CFTIR (ATR cmminus1) 3120 3065 2997 2928 1625 1600 15071467 1434 1352 1314 1230 1202 1164 1122 1058 1000 976950 908 811 782 728 1H NMR (CDCl

3 500MHz) 520 (d

J = 1100Hz 1H) 558 (dd 1198691= 1100Hz 119869

2= 150Hz 1H)

589 (d J = 300Hz 1H) 610 (d J = 300Hz 1H) 657 (d J= 350Hz 1H) 675 (s 1H) 697 (d J = 900Hz 1H) 712 (dJ = 350Hz 1H) 720ndash731 (m 2H) 746 (d J = 850Hz 1H)760 (d J = 900Hz 1H) 763 (d J = 850Hz 1H) 13C NMR(CDCl

3 125MHz) 5361 7413 11014 11226 11400 11877

12228 12277 12301 12401 12716 12865 12928 1302113152 13948 15167 MS mz (ESI) 414 (M+ + 1) 329 306301 283 236 102 71 57 Anal Calc for C

19H13BrN2O2S C

5522 H 317 N 678 Found C 5520 H 315 N 680

3 Results and Discussion

Li and Mao reported that the reaction of 2-aminothiazole 2-naphthol and benzaldehyde under solvent-free conditions at120∘C gave the desired product in 6 h (Lit [23]) We decidedto perform this reaction under ultrasonic irradiation to get a

Table 1 Screening of catalysts for the three-component reaction of2-aminothiazole benzaldehyde and 2-naphthol

Catalyst (mol) Solvent Temperature(∘C)

Time(min)

Yield()a

mdash mdash 25 120 65mdash mdash 50 120 74VB1 (10) mdash 50 60 66Sc(OTf)

3(10) mdash 50 60 70

Bi(OTf)3(10) mdash 50 60 67

Yb(OTf)3(10) mdash 50 60 73

(+)-CSA (10) mdash 50 60 87mdash IL1 50 60 32mdash IL2 50 60 34mdash IL3 50 60 40aIsolated yieldIL1 1-benzyl-3-methylimidazoliumchlorideIL2 1-ethyl-23-dimethylimidazoliumtetrafluoroborateIL3 8-ethyl-18-diazabicyclo[540]-7-undecenium trifluoromethanesulfo-nate

shorter reaction time milder reaction conditions and higheryield

Initially the three-component Mannich reaction of ben-zaldehyde (100mmol) 2-naphthol (100mmol) and 2-amin-othiazole (100mmol) was examined under ultrasonic irra-diation without a catalyst at room temperature (Scheme 1)The reaction was completed in 120 minutes with a yield of65 When the temperature was increased from room tem-perature to 50∘C the yield of product increased In recentyears the field of greener catalysts such as reusable lanthanidetriflates organocatalysts biodegradable reagents and ionicliquids has an increasing importance in synthetic organicchemistry [67ndash70] In order to observe the effect of severalgreener catalysts and ionic liquids such as Bi(OTf)

3

Sc(OTf)3 Yb(OTf)

3 VB1 (thiamine hydrochloride) (+)-CSA

(camphor-10-sulfonic acid) 1-benzyl-3-methylimidazolium-chloride (IL1) 1-ethyl-23-dimethylimidazoliumtetrafluoro-borate (IL2) and 8-ethyl-18-diazabicyclo[540]-7-unde-cenium trifluoromethanesulfonate (IL3) theywere examinedunder ultrasound irradiation (Table 1) at 50∘C As a result(+)-CSA was found to be the most effective catalyst at 50∘Cfor this reaction

Next in order to observe the effect of the amount of (+)-CSA on the reaction we also performed the experiments


USCSA

NH2

++

O

H

OH OH

N

N

HN S

S

Scheme 2

N

N

S

S

NH2

+ +

O

H

OH OH HN

5mol CSA US

50∘CR

R

1andashn

Scheme 3 (+)-CSA catalyzed one-pot three-component Mannich reaction under US conditions

Table 2 Optimization of catalyst loading in the Mannich-typereaction of 2-aminothiazole with benzaldehyde and 2-naphtholusing (+)-CSA (see Scheme 2)

CSA (mol) Temperature (∘C) Time (min) Yield ()a

10 25 60 8110 50 30 8715 50 30 8420 50 30 795 50 30 90aIsolated yield

using different amounts of catalyst (Table 2 and Scheme 2)The best result was obtained by carrying out the reactionusing 5mol of (+)-CSA at 50∘C under solvent-free condi-tions (Table 2 and Scheme 2)

With these optimal reaction conditions we then exam-ined a variety of aromatic and heteroaromatic aldehydes inultrasound-promoted catalytic Mannich-type reactions Asshown in Table 3 and Scheme 3 the one-pot three-com-ponent reactions work well with a variety of aromatic andheteroaromatic aldehydes and the desired compounds wereobtained in good yields However the aryl aldehydes whichcontain electron-withdrawing groups gave the desired pro-ducts in lower yields On the other hand reactions with pyri-dine-2-carbaldehyde and pyridine-4-carbaldehyde did notgive the desired product

The structures of the newly generated compounds havebeen confirmed by Fourier transform-infrared (FTIR) massand NMR techniques The characteristic absorption bandsof OH and NH bands were observed at 3326ndash3385 cmminus1 in

Table 3 (+)-CSA catalyzed one-pot three-component Mannichreaction of 2-naphthol with 2-aminothiazole and aromatic aldehy-des (see Scheme 3)

Product R Time (min) Yield ()a

1a Phenyl 30 901b 4-Methylphenyl 30 761c 4-Bromophenyl 45 701d 4-Isopropylphenyl 30 871e 24-Dimethylphenyl 30 741f 24-Dichlorophenyl 45 721g 24-Difluorophenyl 45 751h 3-Phenoxyphenyl 30 831i 4-Benzyloxyphenyl 30 861j 3-Nitrophenyl 30 681k Thiophen-2-yl 30 751l Thiophen-3-yl 30 701m 5-Methylfuran-2-yl 30 881n 5-Bromofuran-2-yl 30 81aIsolated yield

the FTIR spectra of the 1-[(13-thiazol-2-ylamino)methyl]-2-naphthol derivatives In the 1H NMR spectra NH protonsignals were observed at 829ndash936 ppm The CH protonswhich are next to Ar groups were observed at 596ndash701 ppmand the OH protons appeared in the range 1008ndash1223 ppmThemass spectra of all new compounds showed the expectedmolecular ion peak

13-Oxazine derivatives were prepared by the ring-closurereactions of 1-[(13-thiazol-2-ylamino)methyl]-2-naphthols1a 1c 1d 1k 1m and 1nwith formaldehyde under ultrasoundirradiation at 50∘C (Table 4 and Scheme 4) in THF solvent


N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US

Scheme 4 Synthesis of naphthoxazines under US conditions

Table 4 Synthesis of naphthoxazines (2andashf) (see Scheme 4)


2a Phenyl 120 532b 4-Bromophenyl 120 362c 4-Isopropylphenyl 120 692d Thiophen-2-yl 120 642e 5-Methylfuran-2-yl 120 652f 5-Bromofuran-2-yl 120 57aIsolated yield

The ring-closure reaction of 1a (100mmol) with formalde-hyde (120mmol) without a catalyst under conventionalconditions at room temperature gave the desired product in15 h with 40 yield The best result was obtained by carryingout the reaction at 50∘C under ultrasonic irradiation

In the 1HNMR spectra of 13-oxazine derivatives the CH2

protons which are between N and O atoms appeared in theranges 498ndash537 and 551ndash570 ppm The CH protons whichare near the Ar group were observed at 675ndash702 ppm

4 Conclusions

In conclusion we have described a greener efficient andpractical method for the synthesis of 1-[(13-thiazol-2-ylamino)methyl]-2-naphthols via a three-component one-pot Mannich-type reaction of 2-aminothiazole aromaticaldehydes and 2-naphthol using commercially availableless expensive (+)-camphor-(10)-sulfonic acid ((+)-CSA) asa metal-free catalyst under solvent-free ultrasound irradi-ation The ring-closure reactions of the 1-[(13-thiazol-2-ylamino)methyl]-2-naphthols with formaldehyde gave 13-oxazine derivatives in moderate to good yields The advan-tages of this synthesis are use of ultrasonic irradiation asenergy source nontoxic and economically viable catalystshort reaction times and simplified workup procedure

Competing Interests

The authors declare that there are no competing interestsregarding the publication of this paper

Acknowledgments

This study was financially supported by Kırklareli Universitywith the Project no KLUBAP 015

References

[1] A Domling ldquoRecent developments in isocyanide based multi-component reactions in applied chemistryrdquo Chemical Reviewsvol 106 no 1 pp 17ndash89 2006

[2] J Zhu ldquoRecent developments in the isonitrile-based multicom-ponent synthesis of heterocyclesrdquo European Journal of OrganicChemistry no 7 pp 1133ndash1144 2003

[3] J Zhu and H Bienayme Eds Multicomponent ReactionsWiley-VCH Weinheim Germany 2005

[4] J D Sunderhaus and S FMartin ldquoApplications of multicompo-nent reactions to the synthesis of diverse heterocyclic scaffoldsrdquoChemistrymdashA European Journal vol 15 no 6 pp 1300ndash13082009

[5] A Domling and I Ugi ldquoMulticomponent reactions with iso-cyanidesrdquo Angewandte ChemiemdashInternational Edition vol 39no 18 pp 3169ndash3210 2000

[6] J Zhu Q Wang and M X Wang EdsMulticomponent Reac-tions in Organic Synthesis Wiley-VCH Weinheim Germany2015

[7] L Pu andH-B Yu ldquoCatalytic asymmetric organozinc additionsto carbonyl compoundsrdquo Chemical Reviews vol 101 no 3 pp757ndash824 2001

[8] R Muller H Goesmann and H Waldmann ldquoNN-phthalo-ylamino acids as chiral auxiliaries in asymmetricMannich-typereactionsrdquo Angewandte ChemiemdashInternational Edition vol 38no 1-2 pp 184ndash187 1999

[9] M Arend B Westermann and N Risch ldquoModern variantsof the Mannich reactionrdquo Angewandte ChemiemdashInternationalEdition vol 37 no 8 pp 1044ndash1070 1998

[10] S G Subramaniapillai ldquoMannich reaction a versatile and con-venient approach to bioactive skeletonsrdquo Journal of ChemicalSciences vol 125 no 3 pp 467ndash482 2013

[11] G Roman ldquoMannich bases in medicinal chemistry and drugdesignrdquo European Journal of Medicinal Chemistry vol 89 pp743ndash816 2015

[12] C Chen X Zhu Y Wu et al ldquo5-Sulfosalicylic acid catalyzeddirect Mannich reaction in pure waterrdquo Journal of MolecularCatalysis A Chemical vol 395 no 1 pp 124ndash127 2014

[13] Z Guan J Song Y Xue D-C Yang and Y-H He ldquoEnzyme-catalyzed asymmetric Mannich reaction using acylase fromAspergillus melleusrdquo Journal of Molecular Catalysis B Enzy-matic vol 111 pp 16ndash20 2015

[14] W-J Hao B Jiang S-J Tu et al ldquoA new mild base-catalyzedMannich reaction of hetero-arylamines in water highly effi-cient stereoselective synthesis of 120573-aminoketones undermicrowave heatingrdquo Organic amp Biomolecular Chemistry vol 7no 7 pp 1410ndash1414 2009


[15] U C Rajesh R Kholiya V Satya Pavan and D S Rawat ldquoCata-lyst-free ethylene glycol promoted one-pot three componentsynthesis of 3-amino alkylated indoles via Mannich-type reac-tionrdquo Tetrahedron Letters vol 55 no 18 pp 2977ndash2981 2014

[16] V Kavala C Lin C-W Kuo H Fang and C-F Yao ldquoIodinecatalyzed one-pot synthesis of flavanone and tetrahydropyrim-idine derivatives via Mannich type reactionrdquo Tetrahedron vol68 no 4 pp 1321ndash1329 2012

[17] C Cimarelli G Palmieri and E Volpini ldquoA practical stereos-elective synthesis of secondary and tertiary aminonaphtholschiral ligands for enantioselective catalysts in the addition ofdiethylzinc to benzaldehyderdquo Tetrahedron Asymmetry vol 13no 22 pp 2417ndash2426 2002

[18] C Cimarelli and G Palmieri ldquoSynthesis of enantiopure 2-(Aminoalkyl)phenol derivatives and their application as cata-lysts in stereoselective reactionsrdquoChirality vol 21 no 1 pp 218ndash232 2009

[19] I Szatmari and F Fulop ldquoSyntheses transformations and appli-cations of aminonaphthol derivatives prepared via modifiedMannich reactionsrdquo Tetrahedron vol 69 no 4 pp 1255ndash12782013

[20] E Pelit andZ Turgut ldquoSynthesis of enantiopure aminonaphtholderivatives under conventionalultrasonic technique and theirring-closure reactionrdquo Arabian Journal of Chemistry 2014

[21] A Shaabani A Rahmati and E Farhangi ldquoWater promotedone-pot synthesis of 21015840-aminobenzothiazolomethyl naphtholsand 5-(21015840-aminobenzothiazolomethyl)-6-hydroxyquinolinesrdquoTetrahedron Letters vol 48 no 41 pp 7291ndash7294 2007

[22] A Hosseinian and H R Shaterian ldquoNaHSO4H2O catalyzed

multicomponent synthesis of 1-(Benzothiazolylamino) methyl-2-naphthols under solvent-free conditionsrdquo Phosphorus Sulfurand Silicon and the Related Elements vol 187 no 9 pp 1056ndash1063 2012

[23] Z Li and X Mao ldquoOne-pot three-component solvent-free syn-thesis of 1-[(13-thiazol-2-ylamino)methyl]-2-naphtholsrdquo Hete-rocyclic Communications vol 17 no 5-6 pp 219ndash222 2011

[24] K N Venugopala M Krishnappa S K Nayak et al ldquoSynthesisand antimosquito properties of 26-substituted benzo[d]thia-zole and 24-substituted benzo[d]thiazole analogues againstAnopheles arabiensisrdquo European Journal ofMedicinal Chemistryvol 65 no 1 pp 295ndash303 2013

[25] S Javanshir A Ohanian M M Heravi M R Naimi-Jamaland F F Bamoharram ldquoUltrasound-promoted rapid greenone-pot synthesis of 21015840-aminobenzothiazolomethylnaphtholsvia a multi-component reaction catalyzed by heteropolyacid inaqueous mediardquo Journal of Saudi Chemical Society vol 18 no5 pp 502ndash506 2014

[26] G Chaubet L TMaillard J Martinez andNMasurier ldquoA tan-dem aza-FriedeleCrafts reactionHantzsch cyclization a sim-ple procedure to access polysubstituted 2-amino-13-thiazolesrdquoTetrahedron vol 67 no 26 pp 4897ndash4904 2011

[27] K Kundu and S KNayak ldquo(plusmn)-Camphor-10-sulfonic acid cata-lyzed direct one-pot three-component Mannich type reactionof alkyl (hetero)aryl ketones under solvent-free conditionsapplication to the synthesis of aminochromansrdquo RSC Advancesvol 2 no 2 pp 480ndash486 2012

[28] A Srivastava S Singh and S Samanta ldquo(plusmn)-CSA catalyzedFriedel-Crafts alkylation of indoles with 3-ethoxycarbonyl-3-hydoxyisoindolin-1-one an easy access of 3-ethoxycarbonyl-3-indolylisoindolin-1-ones bearing a quaternary 120572-amino acidmoietyrdquo Tetrahedron Letters vol 54 no 11 pp 1444ndash1448 2013

[29] X Jiang Z Song C Xu Q Yao and A Zhang ldquo(DL)-10-cam-phorsulfonic-acid-catalysed synthesis of diaryl-fused 28-diox-abicyclo[331]nonanes from 2-hydroxychalcones and naphtholderivativesrdquo European Journal of Organic Chemistry vol 2014no 2 pp 418ndash425 2014

[30] D A Engel S S Lopez andG B Dudley ldquoLewis acid-catalyzedMeyer-Schuster reactions methodology for the olefination ofaldehydes and ketonesrdquo Tetrahedron vol 64 no 29 pp 6988ndash6996 2008

[31] N Paul M Murugavel S Muthusubramanian and D SriramldquoCamphorsulfonic acid catalysed facile tandem double Fried-lander annulation protocol for the synthesis of phenoxy linkedbisquinoline derivatives and discovery of antitubercular agentsrdquoBioorganic amp Medicinal Chemistry Letters vol 22 no 4 pp1643ndash1648 2012

[32] P V Shinde A H Kategaonkar B B Shingate and M S Shin-gare ldquoAn organocatalyzed facile and rapid access to 120572-hydroxyand 120572-amino phosphonates under conventionalultrasoundtechniquerdquo Tetrahedron Letters vol 52 no 22 pp 2889ndash28922011

[33] S N R Mule S K Battula G Velespula D R Guda andH B Ballikolla ldquo10-Camphorsulfonic acid ((plusmn)-CSA) catalyzedfacile one-pot synthesis of a new class of 25-disubstituted 134-oxadiazolesrdquo RSC Advances vol 4 no 102 pp 58397ndash584032014

[34] B K Gorityala S Cai J Ma and X-W Liu ldquo(S)-camphor-sulfonic acid catalyzed highly stereoselective synthesis of pseu-doglycosidesrdquo Bioorganic ampMedicinal Chemistry Letters vol 19no 11 pp 3093ndash3095 2009

[35] S S Ali S Nasreen M Farooqui S H Quadri and S SultanldquoFacile synthesis of coumarin under solvent-free conditionrdquoInternational Journal of Research in Pharmaceutical and Bio-medical Sciences vol 2 no 3 pp 1229ndash1231 2011

[36] A Srivastava S MMobin and S Samanta ldquo(plusmn)-CSA catalyzedone-pot synthesis of 67-dihydrospiro[indole-311015840-isoindoline]-2310158404(1H5H)-trione derivatives easy access of spirooxindolesand ibophyllidine-like alkaloidsrdquo Tetrahedron Letters vol 55no 11 pp 1863ndash1867 2014

[37] W-M Dai J Wu K C Fong M Y H Lee and C W LauldquoRegioselective synthesis of acyclic cis-enediynes via an acid-catalyzed rearrangement of 12-dialkynylallyl alcohols Synthe-ses computational calculations and mechanismrdquo Journal ofOrganic Chemistry vol 64 no 14 pp 5062ndash5082 1999

[38] R M Kellogg J W Nieuwenhuijzen K Pouwer et al ldquoDutchresolution separation of enantiomers with families of resolvingagents A status reportrdquo Synthesis no 10 pp 1626ndash1638 2003

[39] MVinatoru E Bartha F Badea and J L Luche ldquoSonochemicaland thermal redox reactions of triphenylmethane and triph-enylmethyl carbinol in nitrobenzenerdquo Ultrasonics Sonochem-istry vol 5 no 1 pp 27ndash31 1998

[40] H Zeng H Li and H Shao ldquoOne-pot three-componentMannich-type reactions using Sulfamic acid catalyst underultrasound irradiationrdquo Ultrasonics Sonochemistry vol 16 no6 pp 758ndash762 2009

[41] J Safari and Z Zarnegar ldquoUltrasound mediation for one-potmulti-component synthesis of amidoalkyl naphthols using newmagnetic nanoparticles modified by ionic liquidsrdquo UltrasonicsSonochemistry vol 21 no 3 pp 1132ndash1139 2014

[42] E Pelit and Z Turgut ldquoThree-component aza-Diels-Alder reac-tions using Yb(OTf)

3catalyst under conventionalultrasonic

techniquesrdquo Ultrasonics Sonochemistry vol 21 no 4 pp 1600ndash1607 2014


[43] C Dong K Sanjay and M AckmezHandbook on Applicationsof Ultrasound Sonochemistry for Sustainability CRC PressTaylor amp Francis Group Boca Raton Fla USA 2012

[44] T J Mason and D Peters ldquoPractical Sonochemistryrdquo in PowerUltrasound Uses and Applications Ellis Horwood New YorkNY USA 2002

[45] T JMason ldquoSonochemistry and the environmentmdashproviding alsquogreenrsquo link between chemistry physics and engineeringrdquoUltra-sonics Sonochemistry vol 14 no 4 pp 476ndash483 2007

[46] J L Luche SyntheticOrganic Sonochemistry PlenumPressNewYork NY USA 1998

[47] J-T Li S-XWang G-F Chen and T-S Li ldquoSome applicationsof ultrasound irradiation in organic synthesisrdquo Current OrganicSynthesis vol 2 no 3 pp 415ndash436 2005

[48] R Gallardo-Macias and K Nakayama ldquoTin(II) compounds ascatalysts for the Kabachnik-fields reaction under solvent-freeconditions facile synthesis of 120572-aminophosphonatesrdquo Synthe-sis no 1 pp 57ndash62 2010

[49] M Adib E Sheibani M Mostofi K Ghanbary and H RBijanzadeh ldquoEfficient highly diastereoselective synthesis of 18a-dihydro-7H-imidazo[21-b][13]oxazinesrdquo Tetrahedron vol 62no 14 pp 3435ndash3438 2006

[50] T Kurz ldquoSynthesis of novel pyrido[23-e][13]oxazinesrdquo Tetra-hedron vol 61 no 12 pp 3091ndash3096 2005

[51] P Zhang E A Terefenko A Fensome J Wrobel R Winnekerand Z Zhang ldquoNovel 6-aryl-14-dihydrobenzo[d] and oxazine-2-thiones as potent selective and orally active nonsteroidalprogesterone receptor agonistsrdquo Bioorganic amp Medicial Chem-istry Letters vol 13 no 7 pp 1313ndash1316 2003

[52] H Van de Poel G Guilaumet and M C Viaud-MassuardldquoSynthesis of 6789-tetrahydropyrido[23-b]indolizine and 34-dihydro-2H-pyrido[210158403101584045]pyrrolo[21-b][13]oxazine deriva-tives as new melatonin receptor ligandsrdquo Tetrahedron Lettersvol 43 no 7 pp 1205ndash1208 2002

[53] S Wang Y Li Y Liu A Lu and Q You ldquoNovel hexacycliccamptothecin derivatives Part 1 Synthesis and cytotoxicity ofcamptothecins with an A-ring fused 13-oxazine ringrdquo Bioor-ganic amp Medicinal Chemistry Letters vol 18 no 14 pp 4095ndash4097 2008

[54] S-H Zhao J Berger R D Clark et al ldquo34-Dihydro-2H-benzo[14]oxazine derivatives as 5-HT6 receptor antagonistsrdquoBioorganic amp Medicinal Chemistry Letters vol 17 no 12 pp3504ndash3507 2007

[55] Y Tabuchi Y Ando H Kanemura et al ldquoPreparation of novel(Z)-4-ylidenebenzo[b]furo[32-d][13]oxazines and their biolo-gical activityrdquo Bioorganic amp Medicinal Chemistry vol 17 no 11pp 3959ndash3967 2009

[56] N Zanatta A M C Squizani L Fantinel et al ldquoSynthesis ofN-substituted 6-trifluoromethyl-13-oxazinanesrdquo Journal of theBrazilian Chemical Society vol 16 no 6 pp 1255ndash1261 2005

[57] J N Joyce S Presgraves L Renish et al ldquoNeuroprotectiveeffects of the novel D

3D2receptor agonist and antiparkin-

son agent S32504 in vitro against 1-methyl-4-phenylpyridi-nium (MPP+) and in vivo against 1-methyl-4-phenyl-1236-tetrahydropyridine (MPTP) a comparison to ropinirolerdquoExperimental Neurology vol 184 no 1 pp 393ndash407 2003

[58] F A J Kerdesky ldquoA novel and efficient method for the conver-sion of a trans-hexahydronaphthoxazine to a cis-isomer usingboron tribromiderdquo Tetrahedron Letters vol 46 no 10 pp 1711ndash1712 2005

[59] C Cimarelli AMazzanti G Palmieri and E Volpini ldquoSolvent-free asymmetric aminoalkylation of electron-rich aromaticcompounds stereoselective synthesis of aminoalkylnaphtholsby crystallization-induced asymmetric transformationrdquo Journalof Organic Chemistry vol 66 no 14 pp 4759ndash4765 2001

[60] M Heydenreich A Koch S Klod I Szatmari F Fulopand E Kleinpeter ldquoSynthesis and conformational analysis ofnaphth[110158402101584056][13]oxazino[32-c][13]benzoxazine and naph-th[110158402101584056][13]oxazino[34-c][13]benzoxazine derivativesrdquoTetrahedron vol 62 no 48 pp 11081ndash11089 2006

[61] R Csutortoki I Szatmari A Koch M Heydenreich E Klein-peter and F Fulop ldquoSynthesis and conformational analysis ofnew naphth[12-e][13]oxazino[34-c]quinazoline derivativesrdquoTetrahedron vol 67 no 44 pp 8564ndash8571 2011

[62] R Csutortoki I Szatmari M Heydenreich et al ldquoNovelpiperidine-fused benzoxazino-and quinazolinonaphthoxa-zinesmdashsynthesis and conformational studyrdquo Tetrahedron vol68 no 31 pp 6284ndash6288 2012

[63] Z Turgut E Pelit and A Koycu ldquoSynthesis of New 13-Disub-stituted-23-dihydro-1H-naphth[12e][13]oxazinesrdquo Moleculesvol 12 no 3 pp 345ndash352 2007

[64] H Cao H-F Jiang C-R Qi W-J Yao and H-J ChenldquoBroslashnsted acid-promoted domino reactions a novel one-potthree-component synthesis of 345-trisubstituted-36-dihydro-2H-13-oxazinesrdquo Tetrahedron Letters vol 50 no 11 pp 1209ndash1214 2009

[65] V D Dhakane S S Gholap U P Deshmukh H V Chavan andB P Bandgar ldquoAn efficient and green method for the synthesisof [13]oxazine derivatives catalyzed by thiamine hydrochloride(VB1) in waterrdquo Comptes Rendus Chimie vol 17 no 5 pp 431ndash436 2014

[66] T Sun Q Cai M Li et al ldquoFacile diastereoselective synthesis ofcis-perfluoroalkylated fused [13]oxazines from aromatic alde-hydes methyl perfluoroalk-2-ynoates and quinolinesrdquo Tetrahe-dron vol 71 no 4 pp 622ndash629 2015

[67] S Fiorito S Genovese V A Taddeo and F Epifano ldquoMicro-wave-assisted synthesis of coumarin-3-carboxylic acids underytterbium triflate catalysisrdquo Tetrahedron Letters vol 56 no 19pp 2434ndash2436 2015

[68] A A Pereira P P de Castro A C de Mello B R V FerreiraM N Eberlin and G W Amarante ldquoBroslashnsted acid catalyzedazlactone ring opening by nucleophilesrdquo Tetrahedron vol 70no 20 pp 3271ndash3275 2014

[69] Y Chen W Shan M Lei and L Hu ldquoThiamine hydrochloride(VB1) as an efficient promoter for the one-pot synthesis of 23-

dihydroquinazolin-4(1H)-onesrdquoTetrahedron Letters vol 53 no44 pp 5923ndash5925 2012

[70] M Vafaeezadeh and H Alinezhad ldquoBroslashnsted acidic ionicliquids green catalysts for essential organic reactionsrdquo Journalof Molecular Liquids vol 218 no 1 pp 95ndash105 2016

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

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International Journal of


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Advances in

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Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


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Applied ChemistryJournal of



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Analytical ChemistryInternational Journal of


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Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


yields and selectivity shorter reaction times andmilder reac-tion conditions under ultrasonic irradiation [46ndash48]

13-Oxazine derivatives have shown many biological pro-perties such as analgesic anticonvulsant antitubular antibac-terial antifungal and anticancer activity [49ndash56] Also in thelast decades these compounds have been used in the treat-ment of AIDS and Parkinsonrsquos disease [57 58] Furthermore13-oxazine derivatives can also be used as an intermediate inthe synthesis of N-substituted aminoalcohols [59]Thereforeseveral methods for the synthesis of 13-oxazine derivativeshave been reported [60ndash66]

Here we report on the preparation of 1-[(13-thiazol-2-ylamino)methyl]-2-naphthols catalyzed by (+)-CSA ((+)-camphor-10-sulfonic acid) under ultrasonic irradiation andsolvent-free conditions and then ring-closure reaction ofthese compounds with formaldehyde under ultrasonic irra-diation in THF solvent with short reaction times and goodyields

2 Experimental

21 Materials and Methods NMR spectra were determinedon a Bruker Avance III-500MHz NMR Chemical shifts aregiven in ppm downfield from Me

4Si in DMSO-119889

6or CDCl

3

solution Coupling constants are given in Hz The FTIRspectra were recorded on a Perkin-Elmer FTIR spectrometer(ATR) and absorption frequencies are reported in cmminus1MS spectra were recorded on a Thermo Elemental X SeriesICP-MS Elemental analyses were measured with Flash EA1112 Series apparatus and were in good agreement (plusmn02)with the calculated values Ultrasonication was performedin a Bandelin Sonorex Ultrasonic Bath (Super RK) with afrequency of 35 kHz and a power of 230W The internaldimensions of the ultrasonic cleaner tank were 240 times 140times 100mm with liquid holding capacity of 3 L The reactorwas a 100mL Pyrex round-bottom flask The reaction flaskswere suspended in the center of the bath and the addi-tion or removal of water controlled the temperature of thewater bath Melting points were measured on a Gallenkampmelting-point apparatus Silica gel 60 (Merck) was used forcolumn separation TLC was conducted on standard conver-sion aluminum sheets precoated with a 02mm layer of silicagel All reagentswere commercially available Anhydrous (+)-CSA was purchased from commercial suppliers

22 General Procedure for the Synthesis of 1-[(13-Thiazol-2-ylamino)methyl]-2-naphthols (1andashn) under Ultrasonic Irra-diation A mixture of (+)-CSA (116mg 005mmol) 2-aminothiazole (100mmol) aromatic aldehyde (100mmol)and 2-naphthol (100mmol) was irradiated with ultrasoundof low power (with a frequency of 35 kHz and a nominalpower of 230W) at 50∘C for the period of time indicatedin Table 3 and Scheme 3 The reaction flask was located atthe maximum energy area in the cleaner and the surfaceof the reactants was placed slightly lower than the levelof the water The addition or removal of water controlledthe temperature of the water bath After completion of thereaction as indicated by TLC monitoring the resultant solidwas crystallized from acetone to give products 1andashn

1-[Phenyl(13-thiazol-2-ylamino)methyl]-2-naphthol (1a)White powder mp 197ndash199∘C (Lit [23] 196ndash198∘C) FTIR(ATR cmminus1) 3363 3131 3055 3024 2971 1629 1553 15141439 1338 1264 1248 1157 1055 1029 949 736 1H NMR 120575H(DMSO-119889

6 500MHz) 650 (d J = 600Hz 1H) 710ndash836

(m 13H) 936 (d J = 150Hz 1H) 1222 (br s 1H) 13CNMR 120575C (DMSO-119889

6 125MHz) 5628 10732 12021 12351

12378 12397 12473 12729 12771 12907 12965 1305513600 13980 14396 15032 15537 17106 MSmz (ESI) 333(M+ + 1) 233 215 101 71 57 Anal Calc for C

20H16N2OS C

7226 H 485 N 843 Found C 7213 H 481 N 840

1-[4-Methylphenyl(13-thiazol-2-ylamino)methyl]-2-naphthol(1b Supporting Information in SupplementaryMaterialavailable online at httpdxdoiorg10115520169315614)White powder mp 163ndash165∘C FTIR (ATR cmminus1) 33573131 3055 3020 2939 1628 1541 1513 1436 1325 12621246 1155 1051 1020 953 869 805 782 738 1H NMR 120575H(DMSO-119889

6 500MHz) 221 (s 3H) 659 (br s 1H) 698ndash732

(m 9H) 774 (d J = 800Hz 1H) 778 (d 119869 = 850Hz 1H)789 (br s 1H) 834 (br s 1H) 1015 (br s 1H) 13C NMR 120575C(DMSO-119889

6 125MHz) 2052 5343 10662 11290 11848

11926 12230 12608 12843 12854 12862 12919 1321213275 13506 13819 13955 15302 16892 MS mz (ESI)347 (M+ + 1) 247 232 214 189 101 71 57 Anal Calc forC21H18N2OS C 7280 H 524 N 809 Found C 7276 H

521 N 805

1-[4-Bromophenyl(13-thiazol-2-ylamino)methyl]-2-naphthol(1c Supporting Information Page 3) White powder mp173ndash175∘C FTIR (ATR cmminus1) 3377 3113 3060 3020 29661630 1548 1509 1435 1338 1264 1245 1158 1054 1009 946842 805 775 741 1H NMR 120575H (DMSO-119889

6 500MHz) 663

(d J = 350Hz 1H) 700 (d J = 350Hz 1H) 704 (d J =700Hz 1H) 716 (d J = 800Hz 2H) 722 (d J = 850Hz1H) 726 (d J = 750Hz 1H) 735 (d J = 550Hz 1H) 744(d J = 850Hz 2H) 777 (d J = 800Hz 1H) 780 (d J =800Hz 1H) 784 (br s 1H) 838 (d J = 450Hz 1H) 1020(br s 1H) 13C NMR 120575C (DMSO-119889

6 125MHz) 5300 10699


20H15BrN2OS C 5840 H 368 N 681 Found

C 5825 H 363 N 678

1-[4-Isopropylphenyl(13-thiazol-2-ylamino)methyl]-2-naph-thol (1d Supporting Information Page 4) White powder mp159ndash161∘C FTIR (ATR cmminus1) 3344 3118 3060 3020 29571625 1531 1505 1435 1326 1272 1255 1155 1046 1019 954860 817 782 744 1H NMR (DMSO-119889

6 500MHz) 114 (d

J = 400Hz 6H) 279ndash281 (m 1H) 660 (d J = 350Hz1H) 698ndash735 (m 9H) 776 (dd 119869

1= 1750Hz 119869

2= 750Hz

2H) 797 (d J = 200Hz 1H) 834 (br s 1H) 1013 (br s 1H)13C NMR (DMSO-119889

6 125MHz) 2382 2390 3295 5357


23H22N2OS C 7376 H 592 N

748 Found C 7372 H 587 N 745



6


6 125MHz)


22H20N2OS C 7330

H 559 N 777 Found C 7325 H 560 N 774


6 500MHz) 660 (d J = 350Hz 1H) 698 (d J =


6 125MHz) 5257 10681


20H14Cl2N2OS C 5986 H 352 N 698 Found

C 5984 H 350 N 696


6 500MHz) 661 (d J = 350Hz


6 125MHz) 4890 10343 10688


20H14F2N2OS C 6520 H 383 N 760 Found

C 6518 H 380 N 758


6 500MHz) 662 (br s 1H) 678 (d J = 600Hz


6 125MHz) 5320 10691 11632 11689 11795

11839 11889 12153 12240 12306 12614 12851 1286012945 12962 12986 13205 13344 13818 14538 1530315597 15667 16872 MS mz (ESI) 425 (M+ + 1) 406


415 N 825


6 500MHz) 501


6 125MHz)


27H22N2O2S C 7395

H 506 N 639 Found C 7393 H 505 N 636


6


6 125MHz) 5312 10807 11830 11852 11976


H 403 N 1115


6


6 125MHz) 5081 10706


H 415 N 826


6





18H14N2OS2 C 6388 H 417 N 828

Found C 6386 H 414 N 826


6 500MHz) 214 (s 3H) 596 (d J =


6 125MHz) 1332 4914


19H16N2O2S C 6784 H 479

N 833 Found C 6786 H 477 N 830


6 500MHz) 620 (d J = 300Hz 1H) 646


6 125MHz) 4883 10699 10935 11228


18H13BrN2O2S C 5388 H 327 N 698 Found

C 5385 H 325 N 696


1-Phenyl-2-(thiazol-2-yl)-23-dihydro-1H-naphtho[12-e][13]ox-azine(2a Supporting Information Page 10) White powdermp 125-126∘C FTIR (ATR cmminus1) 3126 3106 3077 3057

3025 2944 2922 2898 2850 1623 1599 1508 1483 14661404 1382 1312 1233 1201 1125 1089 1058 1000 969 915816 745 1H NMR (CDCl

3 500MHz) 511 (d J = 1100Hz


3 125MHz) 5953 7369 10944 11286 11881 12305


21H16N2OS C

7323 H 468 N 813 Found C 7320 H 466 N 810


3 500MHz) 499 (d J = 1100Hz 1H) 552 (dd

1198691= 1100Hz 119869

2= 200Hz 1H) 662 (d J = 350Hz 1H)


3 125MHz) 5869 7381 10967 11880



5955 H 355 N 660


3 500MHz) 122


3 125MHz) 2390 2393 3377 5946 7364


24H22N2OS C 7458 H 574 N 725

Found C 7456 H 576 N 723


3

500MHz) 533 (d J = 1100Hz 1H) 568 (dd 1198691= 1100Hz

1198692= 200Hz 1H) 669 (d J = 350Hz 1H) 682 (d J =

350Hz 1H) 687 (dd 1198691= 900Hz 119869

2= 350Hz 1H) 702

(s 1H) 710 (d J = 900Hz 1H) 725 (d J = 350Hz 1H)730 (dd 119869

1= 850Hz 119869

2= 150Hz 1H) 732ndash740 (m 2H)

763 (d J = 850Hz 1H) 772 (d J = 900Hz 1H) 775 (d J


N

N

S

S NH2

++

O

H US

OHOH HN


= 750Hz 1H) 13C NMR (CDCl3 125MHz) 5509 7383


19H14N2OS2 C 6512 H 403 N 799

Found C 6515 H 405 N 797


3 500MHz) 243 (s 3H) 536 (d J

= 1100Hz 1H) 568 (dd 1198691= 1100Hz 119869

2= 150Hz 1H) 651

(dd 1198691= 350Hz 119869

2= 100Hz 1H) 657 (dd 119869

1= 350Hz 119869

2


3 125MHz) 1545 5535 7372


20H16N2O2S C 6894 H 463 N 804 Found C

6896 H 465 N 802


3 500MHz) 520 (d

J = 1100Hz 1H) 558 (dd 1198691= 1100Hz 119869

2= 150Hz 1H)


3 125MHz) 5361 7413 11014 11226 11400 11877


19H13BrN2O2S C

5522 H 317 N 678 Found C 5520 H 315 N 680





Time(min)

Yield()a


3(10) mdash 50 60 70

Bi(OTf)3(10) mdash 50 60 67

Yb(OTf)3(10) mdash 50 60 73




3

Sc(OTf)3 Yb(OTf)





USCSA

NH2

++

O

H

OH OH

N

N

HN S

S

Scheme 2

N

N

S

S

NH2

+ +

O

H

OH OH HN

5mol CSA US

50∘CR

R

1andashn




10 25 60 8110 50 30 8715 50 30 8420 50 30 795 50 30 90aIsolated yield










N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US








4 Conclusions


Competing Interests


Acknowledgments


References
























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



6


6 125MHz)


22H20N2OS C 7330

H 559 N 777 Found C 7325 H 560 N 774


6 500MHz) 660 (d J = 350Hz 1H) 698 (d J =


6 125MHz) 5257 10681


20H14Cl2N2OS C 5986 H 352 N 698 Found

C 5984 H 350 N 696


6 500MHz) 661 (d J = 350Hz


6 125MHz) 4890 10343 10688


20H14F2N2OS C 6520 H 383 N 760 Found

C 6518 H 380 N 758


6 500MHz) 662 (br s 1H) 678 (d J = 600Hz


6 125MHz) 5320 10691 11632 11689 11795

11839 11889 12153 12240 12306 12614 12851 1286012945 12962 12986 13205 13344 13818 14538 1530315597 15667 16872 MS mz (ESI) 425 (M+ + 1) 406


415 N 825


6 500MHz) 501


6 125MHz)


27H22N2O2S C 7395

H 506 N 639 Found C 7393 H 505 N 636


6


6 125MHz) 5312 10807 11830 11852 11976


H 403 N 1115


6


6 125MHz) 5081 10706


H 415 N 826


6





18H14N2OS2 C 6388 H 417 N 828

Found C 6386 H 414 N 826


6 500MHz) 214 (s 3H) 596 (d J =


6 125MHz) 1332 4914


19H16N2O2S C 6784 H 479

N 833 Found C 6786 H 477 N 830


6 500MHz) 620 (d J = 300Hz 1H) 646


6 125MHz) 4883 10699 10935 11228


18H13BrN2O2S C 5388 H 327 N 698 Found

C 5385 H 325 N 696



3025 2944 2922 2898 2850 1623 1599 1508 1483 14661404 1382 1312 1233 1201 1125 1089 1058 1000 969 915816 745 1H NMR (CDCl

3 500MHz) 511 (d J = 1100Hz


3 125MHz) 5953 7369 10944 11286 11881 12305


21H16N2OS C

7323 H 468 N 813 Found C 7320 H 466 N 810


3 500MHz) 499 (d J = 1100Hz 1H) 552 (dd

1198691= 1100Hz 119869

2= 200Hz 1H) 662 (d J = 350Hz 1H)


3 125MHz) 5869 7381 10967 11880



5955 H 355 N 660


3 500MHz) 122


3 125MHz) 2390 2393 3377 5946 7364


24H22N2OS C 7458 H 574 N 725

Found C 7456 H 576 N 723


3

500MHz) 533 (d J = 1100Hz 1H) 568 (dd 1198691= 1100Hz

1198692= 200Hz 1H) 669 (d J = 350Hz 1H) 682 (d J =

350Hz 1H) 687 (dd 1198691= 900Hz 119869

2= 350Hz 1H) 702

(s 1H) 710 (d J = 900Hz 1H) 725 (d J = 350Hz 1H)730 (dd 119869

1= 850Hz 119869

2= 150Hz 1H) 732ndash740 (m 2H)

763 (d J = 850Hz 1H) 772 (d J = 900Hz 1H) 775 (d J


N

N

S

S NH2

++

O

H US

OHOH HN


= 750Hz 1H) 13C NMR (CDCl3 125MHz) 5509 7383


19H14N2OS2 C 6512 H 403 N 799

Found C 6515 H 405 N 797


3 500MHz) 243 (s 3H) 536 (d J

= 1100Hz 1H) 568 (dd 1198691= 1100Hz 119869

2= 150Hz 1H) 651

(dd 1198691= 350Hz 119869

2= 100Hz 1H) 657 (dd 119869

1= 350Hz 119869

2


3 125MHz) 1545 5535 7372


20H16N2O2S C 6894 H 463 N 804 Found C

6896 H 465 N 802


3 500MHz) 520 (d

J = 1100Hz 1H) 558 (dd 1198691= 1100Hz 119869

2= 150Hz 1H)


3 125MHz) 5361 7413 11014 11226 11400 11877


19H13BrN2O2S C

5522 H 317 N 678 Found C 5520 H 315 N 680





Time(min)

Yield()a


3(10) mdash 50 60 70

Bi(OTf)3(10) mdash 50 60 67

Yb(OTf)3(10) mdash 50 60 73




3

Sc(OTf)3 Yb(OTf)





USCSA

NH2

++

O

H

OH OH

N

N

HN S

S

Scheme 2

N

N

S

S

NH2

+ +

O

H

OH OH HN

5mol CSA US

50∘CR

R

1andashn




10 25 60 8110 50 30 8715 50 30 8420 50 30 795 50 30 90aIsolated yield










N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US








4 Conclusions


Competing Interests


Acknowledgments


References
























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




18H14N2OS2 C 6388 H 417 N 828

Found C 6386 H 414 N 826


6 500MHz) 214 (s 3H) 596 (d J =


6 125MHz) 1332 4914


19H16N2O2S C 6784 H 479

N 833 Found C 6786 H 477 N 830


6 500MHz) 620 (d J = 300Hz 1H) 646


6 125MHz) 4883 10699 10935 11228


18H13BrN2O2S C 5388 H 327 N 698 Found

C 5385 H 325 N 696



3025 2944 2922 2898 2850 1623 1599 1508 1483 14661404 1382 1312 1233 1201 1125 1089 1058 1000 969 915816 745 1H NMR (CDCl

3 500MHz) 511 (d J = 1100Hz


3 125MHz) 5953 7369 10944 11286 11881 12305


21H16N2OS C

7323 H 468 N 813 Found C 7320 H 466 N 810


3 500MHz) 499 (d J = 1100Hz 1H) 552 (dd

1198691= 1100Hz 119869

2= 200Hz 1H) 662 (d J = 350Hz 1H)


3 125MHz) 5869 7381 10967 11880



5955 H 355 N 660


3 500MHz) 122


3 125MHz) 2390 2393 3377 5946 7364


24H22N2OS C 7458 H 574 N 725

Found C 7456 H 576 N 723


3

500MHz) 533 (d J = 1100Hz 1H) 568 (dd 1198691= 1100Hz

1198692= 200Hz 1H) 669 (d J = 350Hz 1H) 682 (d J =

350Hz 1H) 687 (dd 1198691= 900Hz 119869

2= 350Hz 1H) 702

(s 1H) 710 (d J = 900Hz 1H) 725 (d J = 350Hz 1H)730 (dd 119869

1= 850Hz 119869

2= 150Hz 1H) 732ndash740 (m 2H)

763 (d J = 850Hz 1H) 772 (d J = 900Hz 1H) 775 (d J


N

N

S

S NH2

++

O

H US

OHOH HN


= 750Hz 1H) 13C NMR (CDCl3 125MHz) 5509 7383


19H14N2OS2 C 6512 H 403 N 799

Found C 6515 H 405 N 797


3 500MHz) 243 (s 3H) 536 (d J

= 1100Hz 1H) 568 (dd 1198691= 1100Hz 119869

2= 150Hz 1H) 651

(dd 1198691= 350Hz 119869

2= 100Hz 1H) 657 (dd 119869

1= 350Hz 119869

2


3 125MHz) 1545 5535 7372


20H16N2O2S C 6894 H 463 N 804 Found C

6896 H 465 N 802


3 500MHz) 520 (d

J = 1100Hz 1H) 558 (dd 1198691= 1100Hz 119869

2= 150Hz 1H)


3 125MHz) 5361 7413 11014 11226 11400 11877


19H13BrN2O2S C

5522 H 317 N 678 Found C 5520 H 315 N 680





Time(min)

Yield()a


3(10) mdash 50 60 70

Bi(OTf)3(10) mdash 50 60 67

Yb(OTf)3(10) mdash 50 60 73




3

Sc(OTf)3 Yb(OTf)





USCSA

NH2

++

O

H

OH OH

N

N

HN S

S

Scheme 2

N

N

S

S

NH2

+ +

O

H

OH OH HN

5mol CSA US

50∘CR

R

1andashn




10 25 60 8110 50 30 8715 50 30 8420 50 30 795 50 30 90aIsolated yield










N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US








4 Conclusions


Competing Interests


Acknowledgments


References
























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

N

S

S NH2

++

O

H US

OHOH HN


= 750Hz 1H) 13C NMR (CDCl3 125MHz) 5509 7383


19H14N2OS2 C 6512 H 403 N 799

Found C 6515 H 405 N 797


3 500MHz) 243 (s 3H) 536 (d J

= 1100Hz 1H) 568 (dd 1198691= 1100Hz 119869

2= 150Hz 1H) 651

(dd 1198691= 350Hz 119869

2= 100Hz 1H) 657 (dd 119869

1= 350Hz 119869

2


3 125MHz) 1545 5535 7372


20H16N2O2S C 6894 H 463 N 804 Found C

6896 H 465 N 802


3 500MHz) 520 (d

J = 1100Hz 1H) 558 (dd 1198691= 1100Hz 119869

2= 150Hz 1H)


3 125MHz) 5361 7413 11014 11226 11400 11877


19H13BrN2O2S C

5522 H 317 N 678 Found C 5520 H 315 N 680





Time(min)

Yield()a


3(10) mdash 50 60 70

Bi(OTf)3(10) mdash 50 60 67

Yb(OTf)3(10) mdash 50 60 73




3

Sc(OTf)3 Yb(OTf)





USCSA

NH2

++

O

H

OH OH

N

N

HN S

S

Scheme 2

N

N

S

S

NH2

+ +

O

H

OH OH HN

5mol CSA US

50∘CR

R

1andashn




10 25 60 8110 50 30 8715 50 30 8420 50 30 795 50 30 90aIsolated yield










N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US








4 Conclusions


Competing Interests


Acknowledgments


References
























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


USCSA

NH2

++

O

H

OH OH

N

N

HN S

S

Scheme 2

N

N

S

S

NH2

+ +

O

H

OH OH HN

5mol CSA US

50∘CR

R

1andashn




10 25 60 8110 50 30 8715 50 30 8420 50 30 795 50 30 90aIsolated yield










N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US








4 Conclusions


Competing Interests


Acknowledgments


References
























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

N

+

O

O

H H

OH HN

N

S

50∘C

RR

S

2andashf

THF US








4 Conclusions


Competing Interests


Acknowledgments


References
























































































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 (+)-csa catalyzed multicomponent ......research article (+)-csa catalyzed...

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