synthesis of functionalized fused-ring heterocycles from tautomers of 2-(thiazole, oxazole,...

SYNTHESIS Journal ofSynthetic OrganicChemistry REPRINT

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Thieme

PAPER ▌3453

paperSynthesis of Functionalized Fused-Ring Heterocycles from Tautomers of 2-(Thiazole, Oxazole, Benzothiazole, and Benzoxazole)-1-phenylethenols and 1,3-Diacid Chlorides or N-(Chlorocarbonyl) IsocyanateSynthesis of Functionalized Fused-Ring HeterocyclesHondamuni I. De Silva,* Sabornie Chatterjee, William P. Henry, Charles U. Pittman, Jr.*Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USAFax +1(662)3251618; E-mail: cpittman@chemistry.msstate.edu; E-mail: hicdesilva@gmail.comReceived: 15.08.2012; Accepted after revision: 18.09.2012

Abstract: 2-Methylthiazole, 2,4,5-trimethylthiazole, 2,4,5-trimeth-yloxazole, 2-methylbenzothiazole, and 2-methylbenzoxazole wereeach reacted with benzoyl chloride in acetonitrile–triethylamine togenerate (Z)-2-(heterocyclic)-1-phenylvinyl benzoates. Base hy-drolysis of these vinyl benzoates formed (Z)-2-(heterocyclic)-1-phenylethenols, which exist in both keto and enol tautomeric forms.These tautomers were used as starting materials for fused-ring het-erocycle syntheses. Reactions with 2,2-dialkyl-1,3-diacid chloridesin acetonitrile–triethylamine afforded their corresponding 5,6-ring-fused 8-benzoyl-6,6-dialkyl-6H-thiazolo-, 8-benzoyl-2,3,6,6-tetra-methyl-6H-thiazolo-, 8-benzoyl-2,3,6,6-tetramethyl-6H-oxazolo-,4-benzoyl-2,2-dimethyl-1H-benzo[4,5]thiazolo-, and 4-benzoyl-2,2-dimethyl-1H-benzo[4,5]oxazolo[3,2,-a]pyridinedione deriva-tives. The 5,6,6-tri-ring fused species, 10-benzoyl-7,8-dihydropyra-no[2,3-d]thiazolo[3,2-a]pyridin-5(6H)-one, was formed in thereaction of the tautomers of (Z)-1-phenyl-2-(thiazol-2-yl)ethenolwith cyclobutane-1,1-dicarbonyl dichloride via a ring expansionafter 5,6-ring fusion. Functionalized 5,6-ring-fused 8-benzoyl-6H-thiazolo- and 8-benzoyl-6H-oxazolo[3,2-f]pyrimidine-5,7-diones,and 4-benzoyl-1H-benzo[4,5]thiazolo- and 4-benzoyl-1H-ben-zo[4,5]oxazolo[3,2-c]pyrimidine-1,3(2H)-diones were also synthe-sized by reacting the (Z)-2-(heterocyclic)-1-phenylethenoltautomers with N-chlorocarbonyl isocyanate in THF–triethylamine. Key words: keto-enol tautomers, dielectrophiles, fused-ring het-erocycles, nucleophilic attack, cyclocondensation

Thiazole, oxazole, benzothiazole, and benzoxazole deriv-atives are found in many biologically active compounds.1–4

Therefore, developing synthetic routes to highly function-alized fused-ring systems, containing these four heterocy-cles is a worthwhile goal. We recently reported theconversion of (Z)-2-(heterocyclic)-1-phenylethenols 1a–4a and their keto tautomers 1b–4b with dimethyl acetyl-enedicarboxylate to 5,6- and 5,7-ring-fused heterocycles7–12 (Scheme 1).5 Analogous benzothiazole and benzox-azole tautomers 5a,b and 6a,b subjected to these reactionsproduced only the 5,6-ring-fused products.5

1,3-Diacid chlorides and N-(chlorocarbonyl) isocyanateare useful dielectrophiles that our group used for the syn-theses of highly functionalized fused-ring systems.6–9 Forexample, starting from 2-ethyl-2-thiazoline (13) and 2-ethyl-2-oxazoline (14), Zhou et al. synthesized 5,6-ring-fused heterocycles 17, 18, 21, and 22 using 1,3-diacid

chlorides and N-(chlorocarbonyl) isocyanate in the pres-ence of Et3N in refluxing MeCN (Scheme 2).6,7 These allproceeded via their corresponding cyclic ketene acetal(CKA) intermediates (e.g., 15, 16, 19, and 20).

Scheme 1 Syntheses of 5,6- and 5,7-fused-ring heterocycles5

Scheme 2 Cyclization reactions of 2-ethyl-2-thiazoline (13) and 2-ethyl-2-oxazoline (14) with 1,3-diacid chlorides and N-(chlorocar-bonyl) isocyanate6,7

MeO2CH

CO2MeMeO2C

r.t. or reflux

1a–4a 7–10

1a,b: R1, R2 = H; X = S2a,b: R1 = Me; R2 = H; X = S3a,b: R1, R2 = Me; X = S4a,b: R1, R2 = Me; X =O

1b–4b

OCO2Me

11, 12

R1 R2 R1 R2 R1 R2

11: R1, R2 = Me; X = S12: R1, R2 = Me; X = O

7: R1, R2 = H; X = S8: R1 = Me; R2 = H; X = S9: R1, R2 = Me; X = S10: R1, R2 = Me; X =O

5a,b: X = S6a,b: X = O

O N XO

REt3N, MeCN

reflux

Et3N, MeCN

reflux

13: X = S14: X = O

15: X = S16: X = O

21: X = S22: X = O

17: X = S18: X = O

19: X = S20: X = O

SYNTHESIS 2012, 44, 3453–3464Advanced online publication: 17.10.20120 0 3 9 - 7 8 8 1 1 4 3 7 - 2 1 0 XDOI: 10.1055/s-0032-1316800; Art ID: SS-2012-M0669-OP© Georg Thieme Verlag Stuttgart · New York

Synthesis 2000, No. X, x–xx ISSN 0039-7881 © Thieme Stuttgart · New York

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Synthesis 2000, No. X, x–xx ISSN 0039-7881 © Thieme Stuttgart · New York

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3454 H. I. De Silva et al. PAPER

Synthesis 2012, 44, 3453–3464 © Georg Thieme Verlag Stuttgart · New York

Tricyclic 1,8-naphthyridinetetraones resulted from 2-methylimidazoline tandem reactions with a variety of 1,3-diacid chlorides in the presence of Et3N.8 Furthermore, thereaction of 2-methylimidazole and 2-methylbenzimid-azole with 1,3-diacid chlorides and Et3N in MeCN gener-ated a variety of products, including fused-ringheterocycles.9 Oxazolines,6,7 thiazoline,6,7 imidazolines,8imidazoles,9 and benzimidazoles9 react with both 1,3-di-acid chlorides and N-(chlorocarbonyl) isocyanate via theirCKA intermediates. In contrast, unlike these reactions of diacid chlorides with2-alkylimidazoles and 2-methylbenzimidazoles, cycliza-tions with 2,2-dimethylmalonyl dichloride or 2,2-diethyl-malonyl dichloride did not occur on the aromaticheterocycles, 2,4,5-trimethylthiazole (23), 2,4,5-trimethyl-oxazole (24), or 2-methylbenzothiazole (27) in refluxingMeCN in the presence of Et3N (Scheme 3).7,10 Unreactedstating materials were recovered.7,10

Scheme 3 Unsuccessful fused-ring heterocycles syntheses7,10

Our objective was to react the enol/keto tautomers of (Z)-2-(heterocyclic)-1-phenylethenols, 1a,b and 3a,b–6a,b,with 1,3-diacid chlorides and N-(chlorocarbonyl) isocya-nate to successfully generate fused-ring heterocycles con-taining thiazole, oxazole, benzothiazole, and benzoxazolerings. This might lead to analogues of 25, 26, and 28,which were not achieved more directly via the route inScheme 3. Reactions of these five tautomeric pairs 1a,band 3a,b–6a,b, with 2,2-disubstituted-1,3-diacid chlo-rides (Table 1 and 2) and N-(chlorocarbonyl) isocyanate(Table 3) in the presence of a base were explored and theresults are discussed in this paper.2-Methylthiazole (29), 2,4,5-trimethylthiazole (23),2,4,5-trimethyloxazole (24), 2-methylbenzothiazole (27),and 2-methylbenzoxazole (30) were each reacted withbenzoyl chloride in the presence of Et3N in refluxingMeCN to afford the corresponding (Z)-2-(heterocyclic)-1-phenylvinyl benzoates 31–35 as previously described(Scheme 4).5,10 Base hydrolysis of 31–35 in KOH/anhy-drous MeOH gave the 2-(heterocyclic)-1-phenylethenoltautomers 1a,b and 3a,b–6a,b.5 Each tautomeric pair

1a,b, and 3a,b–6a,b, was then reacted with different 2,2-disubstituted-1,3-diacid chlorides in the presence of Et3Nin refluxing MeCN under various reaction conditions.Sample isolated product yields are summarized in Tables1 and 2.

Scheme 4 Synthesis of 31–35

The tautomers 1a,b reacted with the three dielectrophiles,2,2-dimethylmalonyl dichloride, 2,2-diethylmalonyl di-chloride, and cyclobutane-1,1-dicarbonyl dichloride(Table 1, entries 1–5). Reaction of 1a,b with 2,2-dimeth-ylmalonyl dichloride (1.5 equiv) and Et3N (3.5 equiv) for5 hours at reflux (entry 1) afforded the 5,6-ring-fusedproduct, 8-benzoyl-6,6-dimethyl-6H-thiazolo[3,2-a]pyri-dine-5,7-dione (36), but in only 35% yield. The yield of36 increased from 35 to 65% using 1.7 equivalents of 2,2-dimethylmalonyl dichloride and increasing the reactiontime from 5 to 7 hours (entry 2). Interestingly, the vinylbenzoate ester, (Z)-1-phenyl-2-(thiazol-2-yl)vinyl benzo-ate 31, was also isolated in both reactions (entries 1 and 2).Vinyl ester 31, the original starting material for synthesiz-ing the tautomers 1a,b via hydrolysis with KOH inMeOH,10 must have formed by the self-reaction of the an-ion of 1a with 1b, because 1 is the only source of the ben-zoyl function. A control reaction of 1a,b with Et3N (3.5 equiv) in reflux-ing MeCN, without 2,2-dimethylmalonyl dichloride, wascarried out to investigate how 31 was formed (see Sup-porting Information). A TLC spot for 31 was not observedeven after refluxing for 12 hours. However, 31 appearedon TLC when 1a,b was refluxed with 2,2-dimethylmalo-nyl dichloride (1.5 equiv). Compounds 36 (19%) and 31(16%) were isolated after 8 hours. This suggests that tri-ethylammonium chloride (Et3NH+Cl–) likely catalyzedthe formation of 31. 8-Benzoyl-6,6-diethyl-6H-thiazolo[3,2-a]pyridine-5,7-dione (37) was isolated from 5,6-ring fusion in 52% yieldwhen 1a,b were reacted with 2,2-diethylmalonyl dichlo-ride (1.2 equiv) and Et3N (3.3 equiv) for 5 hours (Table 1,entry 3).

25: X = S26: X = O

23: X = S24: X = O

R = Me, Et

N S N S

EtEt3NMeCN, reflux

Et3NMeCN, reflux

Cl ClEt Et

MeCN, Et3Nreflux

29: X = S; R = H 23: X = S; R = Me 24: X = O; R = Me

31: X = S; R = H 32: X = S; R = Me 33: X = O; R = Me

MeCN, Et3Nreflux

27: X = S30: X = O 34: X = S

35: X = O

1a,b: X = S; R = H 3a,b: X = S; R = Me 4a,b: X = O; R = Me

5a,b: X = S6a,b: X = O

KOHMeOH

PAPER Synthesis of Functionalized Fused-Ring Heterocycles 3455

Reaction of 1a,b with cyclobutane-1,1-dicarbonyl dichlo-ride (1.5 equiv) and Et3N (3.6 equiv) in refluxing MeCNfor 5 hours gave the new 5,6,6-tri-ring-fused product (Fig-ure 1), 10-benzoyl-7,8-dihydropyrano[2,3-d]thiazolo[3,2-a]pyridin-5(6H)-one (40) (Table 1, entries 4 and 5). Theexpected 5,6-ring-fused analogue 43 (Scheme 5) of 36–39was not isolated since it rearranges rapidly to 40 under the

reaction conditions. Adding cyclobutane-1,1-dicarbonyldichloride (1.5 equiv) to a solution of 1a,b and Et3N (3.6equiv) in MeCN at room temperature and then refluxingfor 5 hours gave only 13% of 40 (entry 4). However, 40was isolated in 34% yield using inverse addition (entry 5).Several unidentified fractions in addition to 40 were also

Table 1 Reactions of 1a,b, 2a,b, and 4a,b with 1,3-Diacid Chlorides in MeCN

Entry Tautomeric reagents

1,3-Diacid chloride Equiv 1,3-diacid chloride

Equiv Et3N Reaction time (h)

Isolated products, yield (%)a

36 37 38 39 40 41 42

1b,c1a,bX = SR = H

1.5 3.5 5 35

2b,d1a,bX = SR = H

1.7 3.5 7 65

3b,e1a,bX = SR = H

1.2 3.3 5 52

4b,f1a,bX = SR = H

1.5 3.6 5 13

5f,g1a,bX = SR = H

1.5 3.4 5 34

6b,f3a,bX = SR = Me

1.5 3.6 6 34 10

7g,f3a,bX = SR = Me

1.5 3.5 6 49 5

8b,f4a,bX = OR = Me

1.4 3.4 7 27 18

9g,f4a,bX = OR = Me

1.4 3.5 7 35 –

a Yields (%) were calculated considering the sum of both tautomers as the limiting reagent.b The solution of 1,3-diacid chloride in MeCN was added dropwise to a solution of 1a,b or 3a,b or 4a,b and Et3N in MeCN.c (Z)-1-Phenyl-2-(thiazol-2-yl)vinyl benzoate (31) (Scheme 4) was isolated in 18% yield along with 15% of unreacted 1a,b.d (Z)-1-Phenyl-2-(thiazol-2-yl)vinyl benzoate (31) (Scheme 4) was isolated in 10% yield.e Unreacted 1a,b were isolated in 10% yield.f Unidentifed fractions were isolated.g The solution of 1a,b or 3a,b or 4a,b and Et3N in MeCN was added dropwise to a solution of 1,3-diacid chloride in MeCN (inverse addition).

R1 R1R1 R1 MeCN, reflux

1a, 3a and 4a36–39

1a,b: X = S; R1 = H 3a,b: X = S; R1 = Me4a,b: X = O; R1 = Me

1b, 3b and 4b

41: X = S42: X = O

R2Cl Cl

formed when R' of the diacid chloride isprop-1,3-diyl

36: X = S; R1 = H; R2 = Me37: X = S; R1 = H; R2 = Et38: X = S; R1 = Me; R2 = Me39: X = O; R1 = Me; R2 = Me

isolated with very complex NMR spectra. These were notfurther analyzed. Product 40 is likely formed by the ring-opening of the cy-clobutane ring in the 5,6-ring-fused product 43 by chlo-ride that is present as triethylammonium chloride in thereaction solution (Scheme 5). This generates 44. The dis-placement of chloride in 44 by SN2 attack by the negative-ly charged oxygen gives 40. Formation of a similarproduct by the reaction of 2-methylimidazole with cy-clobutane-1,1-dicarbonyl dichloride was reported byChatterjee et al.9

Scheme 5 A possible route for the formation of 40

Compounds 3a,b, with methyl substituents at both C4 andC5 positions, reacted with 2,2-dimethylmalonyl dichlo-ride (1.5 equiv) in the presence of Et3N (3.6 equiv) inMeCN (Table 1, entry 6) to give 5,6-ring fused product, 8-benzoyl-2,3,6,6-tetramethyl-6H-thiazolo[3,2-a]pyridine-5,7-dione (38) (34%) and bis-vinyl ester 41 (10%). In-verse addition was carried out to minimize the formationof 41 and increase the yield of 38 (entry 7). Product 38formed in an increased yield (49%) carrying out this reac-tion in refluxing MeCN for 6 hours following the inverseaddition. Only 5% of 41 was isolated. The keto-enol tautomers 4a,b were reacted with 2,2-di-methylmalonyl dichloride (1.4 equiv) using room temper-ature addition followed by refluxing in MeCN for 7 hourswith Et3N (3.4 equiv) (Table 1, entry 8). 8-Benzoyl-

2,3,6,6-tetramethyl-6H-oxazolo[3,2-a]pyridine-5,7-di-one (39) (Figure 2) was isolated only in 27% yield (entry8). The bis-vinyl ester 42, was also isolated in 18% yield(entry 8) as a sticky oil. This reaction was repeated usinginverse addition and the yield of 34 increased from 27 to35% upon inverse addition (entry 9).

Figure 2 X-ray crystal structure of 39 (CCDC 894286)11

Reactions of 2-(heterocyclic)-1-phenylethenol tautomerswith 1,3-diacid chlorides were further extended to benzo-thiazole- and benzoxazole-derived tautomers 5a,b and6a,b, respectively (Table 2). The benzothiazole-basedtautomer 5a,b formed both the 5,6-ring-fused 4-benzoyl-2,2-dimethyl-1H-benzo[4,5]thiazolo[3,2-a]pyridine-1,3(2H)-dione (45) and the bis-vinyl ester 46, when refluxed with2,2-dimethylmalonyl dichloride and Et3N (Table 2, en-tries 1 and 2). Compound 45 was isolated in 44% yieldalong with only 7% of 46 after adding 2,2-dimethylmalo-nyl dichloride (1.5 equiv) dropwise to a solution of 5a,band Et3N (3.6 equiv) and holding for 8 hours at reflux (en-try 1). The isolated yield of 45 increased from 44% to 62%using an inverse addition of reagents (entry 2). A trace of46 was seen on TLC.Dropwise addition of 2,2-dimethylmalonyl dichloride(1.5 equiv) into a solution of 6a,b and Et3N (3.6 equiv) inMeCN, and then refluxing for 9 hours (Table 2, entry 3)gave 4-benzoyl-2,2-dimethyl-1H-benzo[4,5]oxazolo[3,2-a]pyridine-1,3(2H)-dione (47) in 31% isolated yield (en-try 2). Using inverse addition (entry 4), 47 was the majorTLC spot and it was isolated in 35% yield. Inverse addi-tion, using 2,2-dimethylmalonyl dichloride (2 equiv) andEt3N (3.5 equiv) (entry 5) produced a 42% yield of 47 af-ter column separation. The bis-vinyl ester analogous to 46was not observed.1,3-Diacid chlorides are hygroscopic and hydrolyze to thecorresponding carboxylic acids if exposed to moisture.These acids could wash out of reaction mixtures duringthe aqueous workup procedures used. While solvents and

43 44 40

glassware were dried prior to use, the small reaction scalesemployed make the reaction yields sensitive to traces ofwater. A postulated mechanism for the formation of 5,6-ring-fu-sion to 36–39, 45, and 47 is discussed employing 38 as anexample (Schemes 6 and 7). Deprotonation of the enolicproton of the tautomer 3a or a proton on the β-carbon oftautomer 3b by Et3N generates the ambident nucleophile48. The electron density in 48 is delocalized over the β-carbon (48a), ring nitrogen (48b), and oxygen (48c)(Scheme 6). Either the β-carbon (48a) or the ring-nitrogen(48b) can initially react with the 1,3-diacid chloride in theprocess forming 38 (Scheme 7). Oxygen, the third nucleo-philic center (48c), can attack the carbonyl carbon of the1,3-diacid chloride during the formation of bis-vinyl ester41.

5,6-Ring-fusion to generate 36–39, 45, and 47 could occurby an initial nucleophilic attack by the β-carbon of 48a onthe 1,3-diacid chloride carbonyl carbon to form the inter-mediate 49. Loss of chloride from 49 gives 50 (Scheme 7).Deprotonation of the acidic hydrogen on the β-carbon of50 by Et3N generates the anionic CKA intermediate 51.An intramolecular nucleophilic attack by the ring nitrogenof 51 on the terminal carbonyl carbon of the side chainforms 52, which loses chloride to give 38. N-(Chlorocarbonyl) isocyanate was also employed as adielectrophile for the synthesis of 5,6-ring-fused com-pounds. The successful synthesis of 53–57 was achievedby reacting each of the five tautomeric pairs, 1a,b and3a,b–6a,b, with 1.4 equivalents of N-(chlorocarbonyl)isocyanate and 2.5 equivalents of Et3N in refluxing THF(Table 3). Products 53–57 were isolated in moderate togood yields.

Table 2 Reactions of the Tautomers 5a,b and 6a,b with 2,2-Dimethylmalonyl Dichloride in MeCN

Entry Tautomeric reagents Reaction time (h) Isolated products, yield (%)a

45 46 47

1b,c 5a,bX = S

8 44 7

2c,d 5a,bX = S

8 62 trace on TLC

3b,c 6a,bX = O

4c,d 6a,bX = O

5c,d 6a,bX = O

a Yields (%) were calculated considering the sum of both tautomers as the limiting reagent.b The solution of 1,3-diacid chloride in MeCN was added dropwise to a solution of 5a,b or 6a,b and Et3N in MeCN.c Neither 5a,b nor 6a,b were observed by TLC in the product mixture.d The solution of 5a,b or 6a,b and Et3N in MeCN was added dropwise to a solution of 1,3-diacid chloride in MeCN.

MeCN, reflux

5a and 6a

5a,b: X = S6a,b: X = O

45: X = S47: X = O

5b and 6b

46: X = S

Scheme 6 Formation of ambident nucleophile 46

Et3NN S

HEt3NH

3a 3b 48

8-Benzoyl-6H-thiazolo[3,2-f]pyrimidine-5,7-dione (53)was generated in 83% isolated yield when 1a,b reactedwith N-(chlorocarbonyl) isocyanate (1.4 equiv) and Et3N(2.5 equiv) for 5 hours in refluxing THF (Table 3, entry 1).8-Benzoyl-2,3-dimethyl-6H-thiazolo[3,2-f]pyrimidine-5,7-dione (54), was isolated similarly in 71% yield from3a,b and N-(chlorocarbonyl) isocyanate (entry 2). Like-wise, 4a,b and N-(chlorocarbonyl) isocyanate affordedthe 5,6-ring-fused product, 8-benzoyl-2,3-dimethyl-6H-oxazolo[3,2-f]pyrimidine-5,7-dione (55) (Figure 3), underthe same conditions in 73% yield (entry 3).

The benzothiazole-derived 5a,b and benzoxazole-derived6a,b tautomers also behaved like the thiazole- and oxa-zole-derived tautomers 1a,b, 2a,b, and 4a,b when re-fluxed for 5 hours in THF with of N-(chlorocarbonyl)isocyanate (1.4 equiv) and Et3N (2.5 equiv) (Table 3, en-tries 4 and 5). Tautomers 5a,b and 6a,b afforded 4-benzo-yl-1H-benzo[4,5]thiazolo[3,2-c]pyrimidine-1,3(2H)-dione(56) (88%) and 4-benzoyl-1H-benzo[4,5]oxazolo[3,2-c]pyrimidine-1,3(2H)-dione (57) (65%), respectively, un-der these conditions.

A plausible mechanism for the formation of 54 (represen-tative of 53–57) is depicted in Scheme 8. The deproton-ation of tautomers 3a,b generates the ambidentnucleophile 48 as previously mentioned in Scheme 6. Ei-ther the β-carbon or the ring nitrogen nucleophilically at-tacks the carbonyl carbon of N-(chlorocarbonyl)isocyanate in the first step. Both routes would eventuallyproduce the 5,6-ring-fused product 54. In Scheme 8, nu-cleophilic attack by the β-carbon of 48a is proposed to oc-cur first. Chloride loss then gives 59. The intermediate 60is formed upon removal of the acidic hydrogen on the β-carbon of 59. The negatively charge nitrogen on the CKAanion 60 promotes an intramolecular nucleophilic attackon the remaining carbonyl carbon. This cyclocondensa-tion to 61 is followed by proton capture to give 54.

Scheme 7 A postulated mechanism for the formation of 38

48a 49 50

515238

––

Table 3 Reactions of the Tautomers 1a,b and 3a,b–6a,b with N-(Chlorocarbonyl) Isocyanate for Five Hours in Refluxing THFa

Entry Substrate Product Isolated yield (%)b

a Mole ratio of tautomers: Et3N/N-chlorocarbonyl isocyanate = 1:2.5:1.4.b Yields (%) were calculated considering the sum of both tautomers as the limiting reagent.

Scheme 8 A plausible mechanism for the formation of 54 from thereaction of the tautomers 3a,b with N-(chlorocarbonyl) isocyanate

In summary, tautomers 1a,b and 3a,b–6a,b react with 2,2-dimethylmalonyl dichloride in the presence of Et3N inMeCN at reflux to afford the 5,6-ring-fused compounds36, 38, 39, 45, and 47. Similarly, 1a,b react with 2,2-di-ethylmalonyl dichloride forming also the 5,6-ring-fusedcompound 37 as expected. However, the reaction of cy-clobutane-1,1-dicarbonyl dichloride with 1a,b producedthe 5,6,6-tri-ring-fused product 40. This is formed by ringexpansion onto the α,β-unsaturated carbonyl oxygen of43, instead of stopping at compound 43. The three bis-vinyl-ester products 41, 42, and 46 were also obtainedwhen two equivalents of tautomers 3a,b, 4a,b, and 5a,bwere reacted with 2,2-dimethylmalonyl dichloride. Theisolated product yields were low to moderate, due to theformation of several by-products via reactions of the am-bident nucleophilic tautomeric anionic intermediates withthe 1,3-diacid chlorides and also due to hydrolysis ofsome acid chloride functions. Optimization of conditionsis expected to improve yields.The tautomers 1a,b and 3a,b–6a,b were reacted with N-(chlorocarbonyl) isocyanate in the presence of Et3N in re-fluxing THF to give good yields of 5,6-ring-fused prod-ucts 53–57.Reactions of tautomeric pairs, 1a,b and 3a,b–6a,b, withdielectrophiles provided a new route for the synthesis ofseveral highly-functionalized fused-ring heterocycles andpresent an alternative to the failed reactions in Scheme 3.Therefore, reactions of these tautomers with other dielec-trophiles such as malonyl dichloride, phthaloyl dichlo-ride, and N-chlorosulfonyl isocyanate are worth exploringin the future.

Chemicals were purchased from commercial suppliers and used asreceived, except that cyclobutane-1,1-dicarbonyl dichloride wassynthesized by treating cyclobutane-1,1-dicarboxylic acid withSOCl2. MeCN and Et3N were distilled from CaH2 under N2. THFwas distilled from Na metal/benzophenone ketyl. The dried MeCNand THF were freshly distilled prior to use. All reactions were car-ried out under N2. Silica gel (230–400 mesh and a pore size 60 Å)purchased from Sorbent Technologies, was used as the stationaryphase for flash chromatography analyses. 1H NMR and 13C NMRspectra were recorded on a Bruker Avance III 300 or 600 spectrom-eters operating at 300 MHz and 600 MHz for proton, and 75 MHzand 150 MHz for carbon. Chemical shifts were reported in parts permillion (ppm) on the δ scale relative to the internal standard TMSfor 1H (δ = 0 ppm) and the center line of the deuterated solvent for13C (CDCl3: δ = 77.0 ppm and DMSO-d6: δ = 39.43 ppm). Standardabbreviations were used to denote the splitting patterns. Couplingconstants, J, were reported in hertz (Hz). High-resolution massspectra were recorded on a Bruker UHPLC-micro-Q/T MS/MSspectrometer in the ESI mode. Melting points were recorded with aMel-Temp apparatus and are uncorrected. IR spectra were recordedon a Nicolet 6700 FT-IR spectrometer. A Bruker AXS Smart 1000diffractometer, upgraded with an APEX II detector and softwarewhich incorporates SHELX components,12 was employed for crys-tal structure determinations at –173 °C. All reactions were carriedout under N2.

(Z)-1-Phenyl-2-(thiazol-2-yl)vinyl Benzoate (31);5 Typical Pro-cedure 1 (TP1)Et3N (1.83 g, 18.1 mmol, 3.6 equiv) was added to a stirred solutionof 2-methylthiazole (29; 0.496 g, 5 mmol, 1 equiv) in MeCN (25mL) at r.t. under N2. Benzoyl chloride (2.13 g, 15 mmol, 3 equiv) inMeCN (20 mL) was added dropwise to this solution at r.t. under N2.This solution was refluxed for 7 h. After cooling to r.t., MeCN wasremoved by rotary evaporation. The residue was dissolved inCH2Cl2 (30 mL), washed with sat. aq NaHCO3 (2 × 30 mL), dried(Na2SO4), and filtered. After removal of CH2Cl2 by rotary evapora-tion, the crude product was purified by column chromatography(silica gel, EtOAc–hexane, 1:3) to give 31 (1.364 g, 89%); yellowsolid; mp 105–106 °C; Rf = 0.39 (EtOAc–hexane, 1:3).IR (neat): 3116, 3069, 3032, 2981, 1732, 1642, 1599, 1448, 1235,1175, 1076, 1058, 1023, 762, 707, 692 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.33 (d, J = 7.48 Hz, 2 H), 7.82 (d,J = 3.0 Hz, 1 H), 7.71 (t, J = 7.40 Hz, 1 H), 7.63–7.55 and 7.37–7.40(m, 8 H), 7.25 (d, J = 3.0 Hz, 1 H).13C NMR (150 MHz, CDCl3): δ = 163.68, 161.42, 150.18, 142.77,134.13, 133.85, 130.57, 129.63, 128.89, 128.85, 128.82, 124.96,119.66, 112.08.

(Z)-2-(4,5-Dimethylthiazol-2-yl)-1-phenylvinyl Benzoate (32)5

Compound 32 was prepared following the TP1 starting from 2,4,5-trimethylthiazole (23; 0.636 g, 5 mmol, 1 equiv), Et3N (1.84 g, 18mmol, 3.6 equiv), and benzoyl chloride (2.13 g, 15 mmol, 3 equiv);yield: 1.11 g (66%); yellow solid; mp 156–158 °C; Rf = 0.50(EtOAc–hexane, 1:3).IR (neat): 3066, 3045, 2951, 2915, 1741, 1655, 1537, 1450, 1432,1227, 1076, 1050, 1023, 885, 767, 694 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.33 (d, J = 7.55 Hz, 2 H), 7.72 (t,J = 7.40 Hz, 1 H), 7.62–7.56 and 7.38–7.35 (m, 7 H), 7.23 (s, 1 H),2.31 (s, 3 H), 2.28 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 163.84, 156.69, 148.75, 148.38,134.03, 134.01, 130.54, 129.29, 129.00, 128.85, 128.79, 127.80,124.73, 112.24, 14.54, 11.35.

(Z)-2-(4,5-Dimethyloxazol-2-yl)-1-phenylvinyl Benzoate (33)5

Compound 33 was prepared following the TP1 starting from 2,4,5-trimethyloxazole (24; 0.585 g, 5 mmol, 1 equiv), Et3N (1.87 g, 18.5mmol, 3.7 equiv), and benzoyl chloride (2.15 g, 15.1 mmol, 3

Et3N..

protontransfer

Et3N..

3a 3b 48 48a

– –

equiv); yield: 1.26 g (79%); sticky oil; Rf = 0.54 (EtOAc–hexane, 0.3).IR (neat): 3062, 2978, 2953, 2923, 2858, 1738, 1633, 1449, 1236,1175, 1082, 1064, 1024, 1000, 760, 705, 689 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.27 (d, J = 7.47 Hz, 2 H), 7.69–7.37 (m, 8 H), 6.83 (s, 1 H), 2.01 (s, 3 H), 1.92 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 164.62, 155.83, 149.71, 143.42,133.82, 133.42, 132.00, 130.16, 129.54, 129.73, 128.69, 128.37,124.86, 103.10, 10.92, 9.59.

(Z)-2-(Benzo[d]thiazol-2-yl)-1-phenylvinyl Benzoate (34)Compound 34 was prepared following the TP1 starting from 2-methylbenzothiazole (27; 1.51 g, 10 mmol, 1 equiv), Et3N (3.71 g,36.7 mmol, 3.7 equiv), and benzoyl chloride (4.26 g, 30 mmol, 3equiv); yield: 1.89 g (53%); yellow solid; mp 146–148 °C; Rf = 0.54(EtOAc–hexane, 1:4).IR (neat): 3061, 2981, 1739, 1641, 1596, 1452, 1445, 1432, 1227,1209, 1175, 1080, 1055, 1023, 1000, 850, 754, 656 cm–1.1H NMR (600 MHz, CDCl3): δ = 8.36 (d, J = 7.80 Hz, 2 H), 7.97 (d,J = 8.19 Hz, 1 H), 7.73 (dd, J = 7.80, 7.61 Hz, 2 H), 7.65 (d, J = 7.65Hz, 2 H), 7.60 (dd, J = 7.65, 7.56 Hz, 2 H), 7.45–7.39 (m, 5 H), 7.31(t, J = 7.56 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 163.71, 161.38, 152.57, 152.48,135.05, 134.20, 133.73, 130.63, 130.05, 128.95, 128.88, 128.80,126.25, 125.32, 125.21, 123.00, 121.29, 112.44.

(Z)-2-(Benzo[d]oxazol-2-yl)-1-phenylvinyl Benzoate (35)Compound 35 was prepared following the TP1 starting from 2-methylbenzoxazole (30; 2.69 g, 20 mmol, 1 equiv), Et3N (7.48 g, 74mmol, 3.7 equiv), and benzoyl chloride (8.51 g, 60.5 mmol, 3equiv); yield: 2.94 g (43%); white crystalline solid; mp 97–98 °C;Rf = 0.58 (EtOAc–hexane, 1:4).IR (neat): 3078, 1731, 1644, 1605, 1540, 1451, 1234, 1181, 1152,1084, 1067, 1027, 946, 848, 790, 746, 701, 687 cm–1.1H NMR (300 MHz, CDCl3): δ = 8.32 (d, J = 7.68 Hz, 2 H), 7.71–7.67, 7.60–7.54, 7.41–7.40, and 7.24–7.18 (m, 11 H), 7.11 (d,J = 8.04 Hz, 1 H) 7.04 (s, 1 H). 13C NMR (150 MHz, CDCl3): δ = 164.47, 159.75, 154.09, 150.06,141.57, 133.67, 133.58, 130.45, 130.41, 129.37, 128.87, 128.56,125.48, 125.19, 124.39, 119.95, and 110.12, 103.22.

(Z)-1-Phenyl-2-(thiazol-2-yl)ethenol (1a) and 1-Phenyl-2-(thia-zol-2-yl)ethanone (1b); Typical Procedure 2 (TP2)Compound 31 (2.144 g, 6.98 mmol, 1 equiv) was dissolved in anhydMeOH (15 mL). KOH (0.788 g, 14.04 mmol, 2 equiv), dissolved inMeOH (10 mL), was added dropwise to this solution and stirred for24 h at r.t. Then, MeOH was removed by rotary evaporation. Theresidue was dissolved in H2O (30 mL), neutralized with aq 1 MH2SO4, and extracted with CH2Cl2 (2 × 25 mL). The combined or-ganic layers were washed with H2O (30 mL), dried (Na2SO4) andfiltered. After removal of CH2Cl2 by rotary evaporation, the crudeproduct was purified by column chromatography (silica gel,EtOAc–hexane, 1:4) to isolate tautomers 1a,b (1.273 g, 90%); darkgreen oil; Rf = 0.48 (EtOAc–hexane, 1:3). 1H and 13C NMR inCDCl3 confirmed that the isolated product consists of the tautomers1a and 1b in a 1:2.0 ratio. IR (neat): 3117, 3084, 3060, 1687, 1622, 1598, 1576, 1494, 1483,1449, 1263, 1210, 1100, 1070, 752, 686, 632 cm–1.1H NMR (600 MHz, CDCl3): δ = 13.18 (br, 1 H), 7.99 (d, J = 7.56Hz, 2 H), 7.74 (d, J = 7.95 Hz, 2 H), 7.70 (d, J = 3.25 Hz, 1 H), 7.61(d, J = 3.32 Hz, 1 H), 7.53 (t, J = 7.37 Hz, 2 H), 7.42 (t, J = 7.70 Hz,2 H), 7.35–7.31 (m, 2 H), 7.26 (d, J = 3.25 Hz, 1 H), 7.00 (d,J = 3.32 Hz, 1 H), 6.28 (s, 1 H), 4.69 (s, 2 H).

13C NMR (150 MHz, CDCl3): δ = 194.46, 168.35, 162.15, 160.64,142.10, 140.11, 135.71, 134.60, 133.71, 129.63, 128.74, 128.52,128.34, 125.42, 120.04, 114.39, 90.99, 42.65.

(Z)-2-(4,5-Dimethylthiazol-2-yl)-1-phenylethenol (3a) and 2-(4,5-Dimethylthiazol-2-yl)-1-phenylethanone (3b) Tautomers 3a/b were prepared following the TP2 starting from 32(0.502 g, 1.50 mmol, 1 equiv) in anhyd MeOH (10 mL) and KOH(0.168 g, 2.99 mmol, 2 equiv) in MeOH (10 mL); yield: 0.308 g(85%); yellow solid; mp 80–81 °C; Rf = 0.44 (EtOAc–hexane, 1:6). In CDCl3, 3a/3b ratio was 1:1.41. IR (neat): 3089, 3055, 3038, 2980, 2918, 1630, 1573, 1555, 1492,1454, 1268, 1146, 1060, 817, 770, 747, 687, 648 cm–1. 1H NMR (300 MHz, CDCl3): δ = 13.52 (br, 1 H), 8.04 (d, J = 7.66Hz, 2 H), 7.79 (d, J = 7.41 Hz, 2 H), 7.58 (t, J = 7.38 Hz, 1 H), 7.48(t, J = 7.57 Hz, 2 H), 7.41–7.35 (m, 3 H), 6.19 (s, 1 H), 4.61 (s, 2 H),2.32, 2.31, 2.30 (s, 12 H). 13C NMR (75 MHz, CDCl3): δ = 194.79, 164.01, 160.45, 157.33,147.50, 145.00, 135.86, 135.10, 133.57, 129.32, 128.69, 128.52,128.33, 127.27, 125.25, 121.56, 90.64, 42.92, 14.52, 14.24, 11.14.

(Z)-2-(4,5-Dimethyloxazol-2-yl)-1-phenylethenol (4a) and 2-(4,5-Dimethyloxazol-2-yl)-1-phenylethanone (4b)Tautomers 4a/b were prepared following the TP2 starting from 33(1.6 g, 5.1 mmol, 1 equiv) in anhyd MeOH (15 mL) and KOH(0.578 g, 10.3 mmol, 2 equiv) in MeOH (10 mL); yield: 0.811 g(74%); dark green oil; Rf = 0.57 (EtOAc–hexane, 1:6). In CDCl3,4a/4b ratio was 1:3.57.IR (neat): 3059, 2980, 2953, 2924, 2882, 1693, 1633, 1598, 1578,1532, 1496, 1449, 1293, 1201, 1066, 1012, 756, 713, 688, 639, 618cm–1.1H NMR (600 MHz, CDCl3): δ = 7.94 (d, J = 7.66 Hz, 2 H), 7.71 (d,J = 7.72 Hz, 2 H), 7.51 (m, 5 H), 7.32 (t, J = 7.56 Hz, 1 H), 5.91 (s,1 H), 4.37 (s, 2 H), 2.17 (s, 3 H), 2.14 (s, 3 H), 2.03 (s, 3 H), 2.02 (s,3 H). The peak for OH was not detected.13C NMR (75 MHz, CDCl3): δ = 193.28, 161.23, 160.92, 155.28,143.98, 140.21, 135.63, 134.42, 133.49, 130.61, 129.41, 128.88,128.57, 128.36, 128.22, 125.08, 84.01, 38.81, 10.88, 10.73, 9.75,9.63.

(Z)-2-(Benzo[d]thiazol-2-yl)-1-phenylethenol (5a) and 2-(Benzo[d]thiazol-2-yl)-1-phenylethanone (5b)Tautomers 5a/b were prepared following the TP2 starting from 34(1.008 g, 2.82 mmol, 1 equiv) in anhyd MeOH (15 mL) and KOH(0.316 g, 5.63 mmol, 2 equiv) in MeOH (10 mL); yield: 0.516 g(73%); yellowish green solid; mp 111–112 °C; Rf = 0.64 (EtOAc–hexane, 1:5). In CDCl3, 5a/5b ratio was 1.63:1. IR (neat): 3057, 2922, 1610, 1596, 1573, 1494, 1473, 1436, 1378,1264, 1249, 1136, 1057, 751, 729, 687, 668 cm–1.1H NMR (600 MHz, CDCl3): δ = 13.91 (br, 1 H), 8.07 (d, J = 7.68Hz, 2 H), 7.99 (d, J = 8.13 Hz, 1 H), 7.85–7.87 (m, 3 H), 7.80 (d,J = 8.10 Hz, 1 H), 7.76 (d, J = 7.93 Hz, 1 H), 7.58 (dd, J = 8.13, 7.91Hz, 1 H), 7.48 (dd, J = 7.68, 7.53 Hz, 2 H), 7.41–7.46 (m, 5 H), 7.36(t, J = 7.53 Hz, 1 H), 7.27 (t, J = 7.53 Hz, 1 H), 6.35 (s, 1 H), 4.81(s, 2 H). 13C NMR (150 MHz, CDCl3): δ = 194.05, 168.07, 165.46 163.44,152.68, 150.38, 135.88, 135.78, 134.74, 133.82, 131.37, 130.28,128.81, 128.64, 128.48, 126.46, 125.96, 125.89, 125.05, 124.11,122.85, 121.51, 121.37, 119.95, 90.83, 43.81.

(Z)-2-(Benzo[d]oxazol-2-yl)-1-phenylethenol (6a) and 2-(Benzo[d]oxazol-2-yl)-1-phenylethanone (6b)Tautomers 6a/b were prepared following the TP2 starting from 35(0.844 g, 2.47 mmol, 1 equiv) in anhyd MeOH (15 mL) and KOH(0.28 g, 5.2 mmol, 2.1 equiv) in MeOH (10 mL); yield: 0.541 g(92%); greenish white solid; mp 87–89 °C; Rf = 0.64 (EtOAc–hexane, 1:5). In CDCl3, 6a/6b ratio was 1.06:1.

IR (neat): 3065, 3032, 3044, 2979, 1625, 1576, 1530, 1453, 1277,1250, 1164, 1064, 850, 792, 743, 762, 702, 685 cm–1. 1H NMR (600 MHz, CDCl3): δ = 12.62 (br, 1 H), 8.05 (d, J = 7.74Hz, 2 H), 7.88 (m, 2 H), 7.72 (m, 1 H), 7.61 (m, 2 H), 7.52–7.45 (m,7 H), 7.34–7.31 (m, 3 H), 7.28 (t, J = 7.66 Hz, 1 H), 6.21 (s, 1 H),4.64 (s, 2 H). 13C NMR (150 MHz, CDCl3): δ = 192.38, 166.19, 165.68, 160.41,151.24, 148.69, 141.26, 139.85, 135.66, 134.03, 133.91, 130.56,128.85, 128.53, 128.53, 125.82, 124.98, 124.61, 124.32, 124.08,119.95, 117.85, 110.61, 110.19, 83.66, 39.56.

8-Benzoyl-6,6-dimethyl-6H-thiazolo[3,2-a]pyridine-5,7-dione (36)2,2-Dimethylmalonyl dichloride (0.779 g, 4.8 mmol, 1.68 equiv) inMeCN (15 mL) was added dropwise over a period of 20 min to astirred solution of the tautomers 1a,b (0.582 g, 2.86 mmol, 1 equiv)and Et3N (1.01 g, 9.98 mmol, 3.5 equiv) in MeCN (30 mL) at r.t. un-der N2. This solution was refluxed for 7 h under N2 and then MeCNwas removed by rotary evaporation. The residue was dissolved inCH2Cl2 (30 mL), washed with 10% aq NaHCO3 (30 mL), followedby H2O (2 × 30 mL), and dried (Na2SO4). After filtration and re-moval of CH2Cl2 by rotary evaporation, the crude product was pu-rified by column chromatography over silica gel (EtOAc–hexane, 1:2). Compound 31 eluted first followed by compound 36.The vinyl benzoate ester 31 (0.045 g, 10%; mp 105–106 °C) and the5,6-ring-fused compound 36 (0.56 g, 65%) were isolated; yellowsolid; mp 213–214 °C; Rf = 0.53 (EtOAc–hexane, 2:3).IR (neat): 3155, 3110, 3095, 2974, 2927, 1741, 1637, 1593, 1568,1523, 1475, 1386, 1331, 1158, 1096, 914, 874, 803, 768, 734, 710,676 cm–1.1H NMR (600 MHz, CDCl3): δ = 7.82 (d, J = 4.60 Hz, 1 H), 7.50 (d,J = 7.65 Hz, 2 H), 7.46 (t, J = 7.39 Hz, 1 H), 7.39 (dd, J = 7.65, 7.39Hz, 2 H), 6.77 (d, J = 4.60 Hz, 1 H), 1.59 (s, 6 H).13C NMR (600 MHz, CDCl3): δ = 191.09, 189.64, 172.70, 167.77,139.96, 130.83, 127.68 (3 C), 122.82, 112.99, 106.63, 53.76, 23.82. HRMS (ESI): m/z ([M + H]+) calcd for C16H14NO3S: 300.0694;found: 300.0692.

8-Benzoyl-6,6-diethyl-6H-thiazolo[3,2-a]pyridine-5,7-dione (37)2,2-Diethylmalonyl dichloride (0.531 g, 2.75 mmol, 1.2 equiv) inMeCN (10 mL) was added dropwise over a period of 20 min to astirred solution of the tautomers 1a,b (0.479 g, 2.36 mmol, 1 equiv)and Et3N (0.815 g, 9.51 mmol, 3.3 equiv) in MeCN (25 mL). Thissolution was refluxed for 5 h. The workup procedure mentionedabove was used for the purification and isolation of products. Thetitle compound 37 was isolated in 52% (0.402 g) along with thestarting tautomers 1a,b in 10% (0.047 g) yield; yellow solid;mp 185–186 °C; Rf = 0.67 (EtOAc–hexane, 2:3).IR (neat): 3161, 3124, 3061, 2962, 2935, 2876, 1729, 1681, 1633,1601, 1475, 1385, 1331, 1204, 1163, 927, 876, 841, 821, 796, 699,676 cm–1.1H NMR (600 MHz, CDCl3): δ = 7.87 (d, J = 4.59 Hz, 1 H), 7.51 (d,J = 7.64 Hz, 2 H), 7.47 (t, J = 7.32 Hz, 1 H), 7.40 (dd, J = 7.64, 7.32Hz, 2 H), 6.77 (d, J = 4.59 Hz, 1 H), 2.13 (qt, Jgem = 15.0 Hz,Jvis = 7.42 Hz, 2 H), 2.01 (qt, Jgem = 15.0 Hz, Jvis = 7.42 Hz, 2 H),0.87 (t, J = 7.42 Hz, 6 H).13C NMR (600 MHz, CDCl3): δ = 191.21, 188.93, 172.16, 168.61,140.21, 130.80, 127.76, 127.63, 122.53, 113.03, 109.06, 32.37 (2C), 9.54 (2 C). HRMS (ESI): m/z ([M + H]+) calcd for C18H18NO3S: 328.1007;found: 328.0992.

10-Benzoyl-7,8-dihydropyrano[2,3-d]thiazolo[3,2-a]pyridin-5(6H)-one (40)Cyclobutane-1,1-dicarbonyl dichloride (0.631 g, 3.49 mmol, 1.5equiv) in MeCN (10 mL) was added dropwise over a period of 15min at r.t. to a stirred solution of the tautomers 1a,b (0.465 g, 2.29mmol, 1 equiv) and Et3N (0.83 g, 8.2 mmol, 3.6 equiv) in MeCN (25mL). This solution was refluxed 5 h. The workup procedure men-tioned above for the purification and isolation of product 36 was fol-lowed. The spot corresponding to the staring tautomers 1a,b wasnot observed on TLC of the products mixture. The title compound40 was isolated in 13% (0.093 g). EtOAc–hexane (1:1) was used asthe eluent for the column chromatography over silica gel. Three oth-er liquid fractions were collected through column in addition to thefraction that corresponds to 40 (eluent: EtOAc–hexane, 1:1). Thesethree fractions were eluted before the product. Fraction 1 (0.217 g)eluted first followed by fraction 2 (0.066 g), and then fraction 3(0.353 g). The 1H NMR spectra of these three fractions were notclear enough to analyze and identify the structures. This reaction was repeated employing an inverse addition by addinga solution of the tautomers 1a,b (0.423 g, 2.08 mmol, 1 equiv) andEt3N (0.71 g, 7.02 mmol, 3.4 equiv) in MeCN (25 mL) to a solutionof cyclobutane-1,1-dicarbonyl dichloride (0.57 g, 3.15 mmol, 1.5equiv) in MeCN (10 mL) dropwise over a period of 20 min at r.t.Then, this solution was refluxed for 5 h. There was no TLC spot de-tected for 1a,b on the TLC. After following the general workup pro-cedure, 40 was isolated; yield: 0.243 g (34%); white crystallinesolid; mp 226–227 °C; Rf = 0.50 (EtOAc–hexane, 3:1). Two otherliquid fractions were also isolated which eluted before the product(eluent: EtOAc–hexane, 1:1). The fraction 1 (0.102 g) was isolatedfirst, followed by fraction 2 (0.207 g). IR (neat): 3149, 3089, 3066, 2979, 2937, 2904, 1645, 1597, 1530,1489, 1333, 1308, 1266, 1183, 1158, 1058, 961, 905, 848, 733, 697cm–1.1H NMR (600 MHz, CDCl3): δ = 8.24 (d, J = 4.48 Hz, 1 H), 7.57 (d,J = 7.69 Hz, 2 H), 7.46 (t, J = 7.29 Hz, 1 H), 7.40 (dd, J = 7.69, 7.29Hz, 2 H), 7.04 (d, J = 4.48 Hz, 1 H), 3.94 (t, J = 5.13 Hz, 2 H), 2.68(t, J = 6.46 Hz, 2 H), 1.95 (tt, J = 5.13, 6.46 Hz, 2 H). 13C NMR (150 MHz, CDCl3): δ = 190.52, 161.37, 159.08, 153.04,141.02, 130.62, 127.90, 127.38, 123.51, 114.00, 104.05, 99.89,66.61, 20.69, 19.67.HRMS (ESI): m/z ([M + H]+) calcd for C17H14NO3S: 312.0694;found: 312.0677.Single crystals of 40 were grown for X-ray crystallography by thevapor diffusion method. Hexane was diffused into a solution ofcompound 40 dissolved in CHCl3.

8-Benzoyl-2,3,6,6-tetramethyl-6H-thiazolo[3,2-a]pyridine-5,7-dione (38) and Bis[(Z)-2-(4,5-dimethylthiazol-2-yl)-1-phenylvi-nyl] 2,2-Dimethylmalonate (41)2-Dimethylmalonyl dichloride (0.53 g, 3.1 mmol, 1.53 equiv) inMeCN (10 mL) was added dropwise over a period of 20 min to astirred solution of the tautomers 3a,b (0.465 g, 2.01 mmol, 1 equiv)and Et3N (0.721 g, 7.13 mmol, 3.55 equiv) in MeCN (25 mL). Thissolution was refluxed for 6 h. After this time, there was no spot onTLC corresponding to the starting material. Three spots with Rf val-ues 0.64, 0.50, and 0.35 (EtOAc–hexane, 1:2) were detected. Theworkup procedure mentioned above in the synthesis of 36 was em-ployed for the purification and isolation of products. EtOAc–hexane(1:2) was used as the eluting solvent for the column chromatogra-phy. The first fraction (Rf = 0.64; EtOAc–hexane, 1:2) was isolatedin 0.099 g. It was unidentified. Product 38 (0.221 g, 34%) elutednext, followed by bis-vinyl ester 41 (0.058 g, 10%). An inverse addition was performed by adding a solution of the tau-tomers 3a,b (0.463 g, 2.0 mmol, 1 equiv) and Et3N (0.712 g, 7.04mmol, 3.52 equiv) in MeCN (25 mL) to a solution of 2,2-dimethyl-malonyl dichloride (0.523 g, 3.03 mmol, 1.51 equiv) in MeCN (10mL) dropwise over a period of 20 min. This solution was refluxed

for 6 h. Three spots were observed (Rf = 0.67, 0.52, 0.36; EtOAc–hexane, 1:2) on TLC and no spot was seen for 3a,b. Compound 38(0.322 g, 49%) was isolated using EtOAc–hexane 1:2 as the elutingsolvent for the column chromatography after the general workupprocedure. The bis-vinyl ester 41 was also isolated in 5% (0.016 g)yield.

38 Yellow crystalline solid; mp 173–174 °C; Rf = 0.50 (EtOAc–hexane, 1:2). IR (neat): 3062, 3022, 2986, 2940, 1741, 1688, 1649, 1589, 1564,1453, 1386, 1372, 1356, 1220, 1184, 1082, 983, 910, 922, 842, 802,768, 735, 708, 634 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.46 (d, J = 7.43 Hz, 2 H), 7.42 (t,J = 7.36 Hz, 1 H), 7.36 (dd, J = 7.43, 7.36 Hz, 2 H), 2.44 (s, 3 H),2.17 (s, 3 H), 1.53 (s, 6 H).13C NMR (150 MHz, CDCl3): δ = 190.81, 188.79, 174.50, 168.24,140.48, 130.89, 130.21, 127.39, 127.35, 118.80, 105.52, 54.70,23.31, 13.93, 10.68.HRMS (ESI): m/z ([M + H]+) calcd for C18H18NO3S: 328.1007;found: 328.0988.

41Pale yellow solid; mp 170–172 °C; Rf = 0.35 (EtOAc–hexane, 1:2). IR (neat): 3057, 2981, 2951, 2922, 2858, 1768, 1745, 1632, 1536,1248, 1129, 1082, 1021, 760, 690 cm–1.1H NMR (600 MHz, CDCl3): δ = 7.54 (d, J = 7.41 Hz, 4 H), 7.26–7.23 (m, 6 H), 7.00 (s, 2 H), 2.34 (s, 6 H), 2.32 (s, 6 H), 1.99 (s, 6 H).13C NMR (150 MHz, CDCl3): δ = 169.58, 156.12, 148.97, 148.32,134.11, 129.26, 128.62, 127.73, 125.23, 111.42, 51.16, 23.63,14.61, 11.29.HRMS (ESI): m/z ([M + H]+) calcd for C31H31N2O4S2: 559.1725;found: 559.1659.

8-Benzoyl-2,3,6,6-tetramethyl-6H-oxazolo[3,2-a]pyridine-5,7-dione (39) and Bis[(Z)-2-(4,5-dimethyloxazol-2-yl)-1-phenylvi-nyl] 2,2-Dimethylmalonate (42)2,2-Dimethylmalonyl dichloride (0.301 g, 1.74 mmol, 1.38 equiv)in MeCN (10 mL) was added dropwise over a period of 20 min to astirred solution of the tautomers 4a,b (0.272, 1.26 mmol, 1 equiv)and Et3N (0.432 g, 4.27 mmol, 3.39 equiv) in MeCN (25 mL). Thissolution was refluxed for 7 h. After this time, the spot correspondingto the starting tautomers 4a,b was not detected by TLC. About fiveto six spots were observed on the TLC analysis of the reaction prod-ucts. The general workup procedure mentioned above was em-ployed for the purification and isolation of products. The separationof each of them was not easy. EtOAc–hexane (1:2) was used as theeluting solvent for the column chromatography. Fractions corre-sponding to all spots were not isolated. Only three fractions werecollected. The 5,6-ring-fused compound 39 was isolated in 27%yield (0.106 g) as the first fraction. The isolated fraction 2 was abrown sticky oil. This compound was identified as the bis-vinyl es-ter 42 (0.059 g, 18%) based on the 1H NMR spectrum. The fraction3 (0.08 g), which eluted last was unidentified.An inverse addition version of this reaction was also performed byadding solution of the tautomers 4a,b (0.47g, 2.2 mmol, 1 equiv)and Et3N (0.781 g, 7.72 mmol, 3.51 equiv) in MeCN (30 mL) to asolution of 2,2-dimethylmalonyl dichloride (0.541 g, 3.14 mmol,1.43 equiv) in MeCN (20 mL) dropwise over a period of 30 min.This solution was then refluxed for 7 h. Several spots were seen onthe TLC of the reaction products as in the previous case. Some ofthese spots were very close. Therefore, separate fractions were notcollected corresponding to all these spots. Different ratios ofEtOAc–hexane (1:3 and then 1:1) were used as the eluting solventfor the column chromatography. Only four fractions were collected.Fraction 1 (0.089 g) followed by fraction 2 (0.045 g) were collectedas the first two fractions. Compound 39 (0.237 g, 35%) was isolated

as the third fraction (fraction 3). Fraction 4 (0.056 g) was collectedas the last fraction and it was also unidentified. The 1H NMR spectraof the isolated unidentified fractions 1, 2, and 4 do not match upwith the spectrum corresponding to bis-vinyl ester 42. 39Yellow crystalline solid; mp 176–178 °C; Rf = 0.36 (EtOAc–hexane, 1:1). IR (neat): 3053, 2997, 2960, 1739, 1715, 1652, 1599, 1586, 1415,1258, 1186, 1014, 986, 914, 821, 803, 770, 749, 712, 691, 651 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.70 (d, J = 7.7 Hz, 2 H), 7.50 (t,J = 7.21 Hz, 1 H), 7.40 (dd, J = 7.70, 7.21 Hz, 2 H), 2.39 (s, 3 H),2.18 (s, 3 H), 1.54 (s, 6 H).13C NMR (150 MHz, CDCl3): δ = 190.95, 190.79, 173.04, 164.25,140.88, 139.29, 132.19, 128.68, 127.97, 117.54, 95.93, 53.63, 9.69,9.49.HRMS (ESI): m/z ([M + H]+) calcd for C18H18NO4: 312.1236;found: 312.1219.Single crystals of 39 were obtained for X-ray crystallography by thevapor diffusion method. Hexane was diffused into a solution ofcompound 39 dissolved in CHCl3.

42Brown sticky oil; Rf = 0.49 (EtOAc–hexane, 1:1). 1H NMR (600 MHz, CDCl3): δ = 7.58 (d, J = 7.60 Hz, 4 H), 7.28–7.23 (m, 6 H), 6.74 (s, 2 H), 2.21 (s, 6 H), 2.08 (s, 6 H), 1.98 (s, 6 H).

4-Benzoyl-2,2-dimethyl-1H-benzo[4,5]thiazolo[3,2-a]pyridine-1,3(2H)-dione (45) and Bis[(Z)-2-(benzo[d]thiazol-2-yl)-1-phenylvinyl] 2,2-Dimethylmalonate (46)2,2-Dimethylmalonyl dichloride (0.293 g, 1.77 mmol, 1.49 equiv)in MeCN (10 mL) was added dropwise over a period of 20 min to astirred solution of the tautomers 5a,b (0.302 g, 1.19 mmol, 1 equiv)and Et3N (0.429 g, 4.24 mmol, 3.56 equiv) in MeCN (25 mL). Thissolution was refluxed for 8 h. After this time, the spot for 5a,b wasnot observed on TLC. The general workup procedure mentioned inthe synthesis of 36 was employed for the purification and isolationof products. EtOAc–hexane (1:3) was used as the eluting solvent forthe column chromatography. Compound 45 (0.182 g, 44%) elutedfirst, followed by compound 46 (0.026 g, 7%). In addition to frac-tions corresponding to 45 and 46, two more fractions have been col-lected, which had complex 1H NMR spectra. These two fractionswere collected before 45 and 46, in the order of fraction 1 (0.061 g)and fraction 2 (0.049 g). An inverse addition reaction was also performed by adding a solu-tion of the tautomers 5a,b (0.507 g, 2.00 mmol, 1 equiv) and Et3N(0.715 g, 7.07 mmol, 3.54 equiv) in MeCN (30 mL) to a solution of2,2-dimethylmalonyl dichloride (0.524 g, 3.04 mmol, 1.52 equiv) inMeCN (15 mL) dropwise over a period of 30 min. This solution wasrefluxed for 8 h and the general workup procedure was followed.EtOAc–hexane (1:3) was used as the eluent for the column chroma-tography. Compound 45 was isolated in 62% yield (0.435 g). Therewere several other spots including a very pale spot for compound46, but these were not isolated.

45White cotton like solid; mp 238–239 °C; Rf = 0.51 (EtOAc–hexane, 1:3).IR (neat): 3126, 3080, 3028, 3000, 2947, 1732, 1657, 1609, 1471,1385, 1356, 1212, 1121, 936, 910, 760, 736, 700, 593 cm–1.1H NMR (600 MHz, CDCl3): δ = 8.61 (d, J = 8.34 Hz, 1 H), 7.68 (d,J = 7.65 Hz, 1 H), 7.52–7.39 (m, 7 H), 1.64 (s, 6 H).13C NMR (150 MHz, CDCl3): δ = 192.05, 190.16, 174.44, 168.27,139.96, 136.09, 131.12, 128.06, 127.78, 127.67, 127.14, 126.80,122.02, 118.02, 107.58, 54.58, 23.80.

HRMS (ESI): m/z ([M + H]+) calcd for C20H16NO3S: 350.0851;found: 350.0819.

46Off-white solid; mp 139–141 °C; Rf = 0.54 (EtOAc–hexane, 1:1).IR (neat): 3059, 2993, 2942, 1760, 1739, 1577, 1253, 1209, 1073,755, 727, 689 cm–1.1H NMR (600 MHz, CDCl3): δ = 8.03 (d, J = 8.09 Hz, 2 H), 7.82 (d,J = 7.91 Hz, 2 H), 7.63 (d, J = 6.94 Hz, 4 H), 7.48 (t, J = 7.56 Hz, 2H), 7.37 (t, J = 7.51 Hz, 2 H), 7.28–7.25 (m, 6 H), 7.17 (s, 2 H), 2.14(s, 6 H).13C NMR (150 MHz, CDCl3): δ = 169.52, 160.72, 153.18, 151.84,134.97, 133.71, 130.07, 128.76, 126.44, 125.68, 125.47, 123.09,121.42, 111.26, 51.44, 23.80.HRMS (ESI): m/z ([M + H]+) calcd for C35H27N2O4S2: 603.1412;found: 603.1339.

4-Benzoyl-2,2-dimethyl-1H-benzo[4,5]oxazolo[3,2-a]pyridine-1,3(2H)-dione (47)2,2-Dimethylmalonyl dichloride (0.373 g, 2.16 mmol, 1.54 equiv)in MeCN (10 mL) was added dropwise over a period of 20 min to astirred solution of the tautomers 6a,b (0.332 g, 1.40 mmol, 1 equiv)and Et3N (0.509 g, 5.03 mmol, 3.59 equiv) in MeCN (25 mL). Thissolution was refluxed for 9 h. After this time, there was no spot onthe TLC analysis corresponding to the starting material. The generalworkup mentioned in the procedure for the synthesis of 36 was em-ployed for the purification and isolation of products. The TLC of theproduct mixture had several spots that were very close. Isolation offractions corresponding to all these spots was not attempted.EtOAc–hexane (1:3) was used as the eluting solvent for columnchromatography. The first collected fraction (brown, oil: 0.076 g)was unidentified. The next fraction collected, corresponding to themajor spot, was 47. This was isolated in 31% yield (0.146 g).Next, an inverse addition reaction was carried out. A solution of thetautomers 6a,b (0.476 g, 2.01 mmol, 1 equiv) and Et3N (0.722 g,7.14 mmol, 3.55 equiv) in MeCN (30 mL) was added dropwise to asolution of 2,2-dimethylmalonyl dichloride (0.526 g, 3.05 mmol,1.52 equiv) in MeCN (15 mL) over a period of 30 min. This solutionwas then refluxed for 9 h. The major spot on the TLC analysis ofthis product mixture corresponded to 47. Compound 47 (0.244 g,35%) was isolated using EtOAc–hexane (1:3) as the eluting solventfor the column chromatography after completing the general work-up procedure. Several other spots, which were not very well sepa-rated, were seen on TLC. Their further separations were notattempted. This reaction was repeated by the inverse addition of 6a,b (0.211 g,0.89 mmol, 1 equiv) and Et3N (0.316 g, 3.12 mmol, 3.55 equiv) toa solution of 2,2-dimethylmalonyl dichloride (0.307 g, 1.78 mmol,2 equiv), followed by refluxing for 9 h. The general workup proce-dure was followed. The 1H NMR of the first fraction isolated(brown oil; 0.034 g) from this reaction was same as that of the firstfraction mentioned above corresponding to the brown oil. The 5,6-ring-fused compound 47 was isolated in 42% yield (0.124 g) aftercolumn separation. White solid; mp 249–250 °C; Rf = 0.38 (EtOAc–hexane, 1:3). IR (neat): 3110, 3095, 3060, 3027, 3001, 2933, 1730, 1644, 1569,1467, 1396, 1352, 1307, 1213, 1159, 11245, 1008, 965, 910, 827,761, 743, 708, 693, 654, 607 cm–1.1H NMR (600 MHz, CDCl3): δ = 8.11 (d, J = 7.94 Hz, 1 H), 7.80 (d,J = 7.79 Hz, 2 H), 7.56 (t, J = 7.36 Hz, 1 H), 7.44 (dd, J = 7.79, 7.36Hz, 2 H), 7.39–7.34 (m, 3 H), 1.64 (s, 6 H).13C NMR (150 MHz, CDCl3): δ = 192.0, 190.07, 172.16 163.38,146.88, 138.38, 132.98, 128.98, 128.29, 126.66, 126.10, 125.90,115.41, 111.10, 97.12, 53.51, 24.42.

HRMS (ESI): m/z ([M + H]+) calcd for C20H16NO4: 334.1079;found: 334.1054.

8-Benzoyl-6H-thiazolo[3,2-f]pyrimidine-5,7-dione (53); Typical Procedure 3 (TP 3)N-Chlorocarbonyl isocyanate (0.335 g, 3.18 mmol, 1.4 equiv) inTHF (15 mL) was added dropwise to a stirred solution of the tauto-mers 1a,b (0.461 g, 2.26 mmol, 1 equiv) and Et3N (0.574 g, 5.67mmol, 2.51 equiv) in THF (20 mL) at r.t. under N2. This solutionwas refluxed (66 °C) for 5 h under N2 and then THF was removedby rotary evaporation. The residue was dissolved in CH2Cl2(50 mL), washed with 10% aq NaHCO3 (30 mL), followed by H2O(2 × 30 mL), and dried (Na2SO4). Filtration, followed by removal ofsolvent rotary evaporation gave the crude product, which was puri-fied by column chromatography over silica gel (EtOAc–hexane, 3:1) to give 53 (0.512 g, 83%); yellow solid; mp 270 °C(dec.); Rf = 0.30 (EtOAc–hexane, 1:1).IR (neat): 3230, 3166, 3106, 1724, 1668, 1580, 1574, 1505, 1404,1336, 1225, 1178, 1093, 938, 868, 801, 776, 758, 654 cm–1.1H NMR (300 MHz, DMSO-d6): δ = 11.77 (br, 1 H), 8.03 (d,J = 3.96 Hz, 1 H), 7.54–7.36 (m, 6 H). 13C NMR (600 MHz, DMSO-d6): δ = 189.73, 163.81, 159.67,145.95, 139.98, 130.40, 127.95, 127.21, 123.58, 114.31, 101.98. HRMS (ESI): m/z ([M]+) calcd for C13H8N2O3S: 272.0256; found:272.0451.

8-Benzoyl-2,3-dimethyl-6H-thiazolo[3,2-f]pyrimidine-5,7-di-one (54)Compound 54 was prepared following the TP3 from the tautomers3a,b (0.307 g, 1.33 mmol, 1 equiv), Et3N (0.336 g, 3.32 mmol, 2.5equiv), and N-chlorocarbonyl isocyanate (0.202 g, 1.92 mmol, 1.44equiv) in THF (25 mL) (eluent for chromatography: EtOAc–hexane, 2:1); yield: 0.283 g (71%); pale white solid; mp 240–241 °C; Rf = 0.36 (EtOAc–hexane, 1:1). IR (neat): 3194, 3117, 3063, 2999, 2936, 2864, 2827, 1752, 1650,1601, 1575, 1489, 1444, 1418, 1324, 1214, 1152, 1062, 993, 931,747, 695, 685, 624 cm–1.1H NMR (600 MHz, DMSO-d6): δ = 11.61 (s, 1 H), 7.49 (d, J = 7.25Hz, 2 H), 7.46 (t, J = 7.28 Hz, 1 H), 7.38 (dd, J = 7.25, 7.28 Hz, 2H), 2.51 (3 H), 2.23 (3 H).13C NMR (600 MHz, DMSO-d6): δ = 189.65, 163.85, 158.97,147.20, 140.26, 131.27, 130.27, 127.89, 127.19, 118.50, 101.58,14.19, 10.57.HRMS (ESI): m/z ([M + H]+) calcd for C15H13N2O3S: 301.0647;found: 301.0651.

8-Benzoyl-2,3-dimethyl-6H-oxazolo[3,2-f]pyrimidine-5,7-di-one (55)Compound 55 was prepared following the TP3 by the reaction ofthe tautomers 4a,b (0.342 g, 1.59 mmol, 1 equiv) and Et3N (0.409g, 4.04 mmol, 2.54 equiv) in THF (15 mL) with N-chlorocarbonylisocyanate (0.236 g, 2.24 mmol, 1.41 equiv) in THF (10 mL) (eluentfor chromatography: EtOAc–hexane, 4:1); Yield: 0.329 g (73%);pale white solid; mp 222–224 °C; Rf = 0.37 (EtOAc–hexane, 3:1).No other spots were detected on the TLC of the crude product mix-ture except the spot for 55. IR (neat): 3101, 2980, 2816, 1750, 1703, 1636, 1600, 1576, 1468,1425, 1350, 1321, 1287, 1249, 1173, 1107, 1045, 1002, 930, 866,747, 694, 668 cm–1. 1H NMR (600 MHz, DMSO-d6): δ = 11.46 (s, 1 H), 7.69 (d, J = 8.08Hz, 2 H), 7.54 (t, J = 7.37 Hz, 1 H), 7.42 (dd, J = 8.08, 7.37 Hz, 2H), 2.35 (s, 3 H), 2.18 (3 H). 13C NMR (600 MHz, DMSO-d6): δ = 188.79, 161.11, 160.26,145.20, 140.62, 139.22, 131.87, 128.59, 127.76, 117.39, 90.97,9.01, 8.98.

HRMS (ESI): m/z ([M + H]+) calcd for C15H13N2O4: 285.0875;found: 285.0830. Single crystals of 55 were obtained for X-ray crystallography by thevapor diffusion method. Hexane was diffused into a solution ofcompound 55 dissolved in acetone. The X-ray crystal structure con-tained a disordered solvent molecule. Therefore, the squeeze com-mand in the Platon software13 was used to squeeze the crystalstructure of 55. The volume that was squeezed is 93 Å3, which re-moved 23 electrons.

4-Benzoyl-1H-benzo[4,5]thiazolo[3,2-c]pyrimidine-1,3(2H)-di-one (56)Compound 56 was prepared following the TP3 by the reaction thetautomers 5a,b (0.321 g, 1.27 mmol, 1 equiv) and Et3N (0.322 g,3.18 mmol, 2.5 equiv) in THF (15 mL) with N-chlorocarbonyl iso-cyanate (0.188 g, 1.78 mmol, 1.4 equiv) in THF (10 mL) (eluent forchromatography: EtOAc–hexane, 4:1); yield: 0.361 g (88%); whitesolid; mp 321 °C (dec.); Rf = 0.37 (EtOAc–hexane, 3:1).IR (neat): 3462, 3181, 3114, 3083, 3068, 3013, 2823, 1744, 1716,1652, 1601, 1490 1410, 1320, 1023, 960, 930, 866, 750, 700, 680,642 cm–1. 1H NMR (600 MHz, DMSO-d6): δ = 11.67 (br s, 1 H), 8.68 (d,J = 8.41 Hz, 1 H), 8.05 (t, J = 7.80 Hz, 1 H), 7.59 (m, 3 H), 7.52 (m,2 H), 7.42 (dd, J = 7.80, 7.00 Hz, 2 H).13C NMR (150 MHz, DMSO-d6): δ = 190.96, 164.30, 159.26,147.61, 139.81, 135.90, 130.87, 127.58, 127.37, 126.84, 126.30,122.89, 117.30, 103.63. HRMS (ESI): m/z ([M + H]+) calcd for C17H11N2O3S: 323.0490;found: 323.0451.

4-Benzoyl-1H-benzo[4,5]oxazolo[3,2-c]pyrimidine-1,3(2H)-di-one (57)Compound 57 was prepared following the TP3 by reacting the tau-tomers 6a,b (0.298 g, 1.26 mmol, 1 equiv) and Et3N (0.32 g, 3.16mmol, 2.51 equiv) in THF (15 mL) with N-chlorocarbonyl isocya-nate (0.187 g, 1.77 mmol, 1.4 equiv) in THF (10 mL) (eluent usedfor chromatography: EtOAc–hexane, 1:1); yield: 0.225 g (65%);white solid; mp 286 °C (dec.); Rf = 0.40 (EtOAc–hexane, 1:1).IR (neat): 3194, 3113, 3075, 1722, 1662, 1634, 1602, 1470, 1434,1297, 1279, 1164, 1106, 1088, 959, 856, 755, 744, 698, 673 cm–1. 1H NMR (600 MHz, DMSO-d6): δ = 11.82 (s, 1 H), 8.03 (d,J = 7.39 Hz, 1 H), 7.87 (d, J = 7.30 Hz, 2 H), 7.65 (d, J = 7.72 Hz,1 H), 7.61 (t, J = 6.88 Hz, 1 H), 7.5–7.41 (m, 4 H). 13C NMR (600 MHz, DMSO-d6): δ = 188.58, 161.60, 159.89,146.69, 145.23, 138.33, 132.72, 128.93, 128.11, 125.98, 125.90,125.64, 114.15, 111.00, 92.23. HRMS (ESI): m/z ([M + H]+) calcd for C17H11N2O4: 307.0719;found: 307.0686.

AcknowledgmentThe authors acknowledge the educational and general funds of Mis-sissippi State University for partial financial support of this work.

Supporting Information for this article is available online athttp://www.thieme-connect.com/ejournals/toc/synthesis. This con-tains the detailed experimental procedures discussed in this articlealong with detailed peak assignments for 1H and 13C NMR spectraand DEPT 135 data.Supporting InformationSupporting Information

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