Reactions of Substituted Oxazoles and Thiazoles with Acid Chlorides: Carbon-Carbon Bond Formation through Cyclic Ketene Acetals

Abstract

Reactions of 2,4,5-trimethyloxazole, 2,4,5-trimethylthiazole, 2-methylthiazole, and 2-ethyl-4,5-dimethylthiazole with different acid chlorides in the presence of different bases were explored. Arylvinyl esters of substituted benzoic acids containing substituted oxazoles or thiazoles were formed when aroyl chlorides were used. Degrees of aroylation were different with different bases. Reactions with alkyl acid chlorides were also explored. Most of these reactions occurred through cyclic ketene acetal intermediates.

Cyclic ketene O,O-, N,O- and -N,S-acetals have been widely used in different cationic polymerizations [¹-¹0] and nucleophilic reactions with various electrophiles. [¹¹-²³] Cyclic ketene acetals are highly nucleophilic due to the presence of two electron-donating heteroatoms at one end of the C=C bond. Resonance delocalization of lone-pair electrons in response to electron demand enhances the exocyclic carbon’s nucleophilicity (Scheme  [¹] ).

Cyclic ketene acetals are readily protonated and then react rapidly with water. [4] [6] [¹³] [¹4] Thus, they are often difficult to isolate and use. Therefore, instead of isolating them before­ use, in situ generation followed by reacting with electrophiles is advantageous. For example, 2-methyl­oxazolines and 2-methylthiazolines were reported to generate different N-acyl-β-keto cyclic ketene N,X-acetals (X = O, S) with excess aroyl and 2,2-dimethylpropanoyl chloride in the presence of a base (Scheme  [²] ). [²4-²6]

These products were reported to form through the in situ formation of N-acyl cyclic ketene acetals (Scheme  [³] ), which further reacted via nucleophilic attack by the exocyclic β-carbon on excess acid chloride.

Recently, reactions of 2-methylimidazoline, 2-methyl-1,4,5,6-tetrahydropyrimidine, and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine were reported to give various cyclic and acyclic products via cyclic ketene N,N′-acetals when treated with aroyl chlorides in the presence of a base. [²7-²9] Also, 2-methylimidazoline, 2-methylimidazole, and 2-methylbenzimidazole formed both polycyclic and acyclic products with diacid chlorides through cyclic ketene acetal intermediates in the presence of a base. [³0] [³¹] Thus, we envisaged that analogous aromatic oxazoles and thiazoles with a 2-methyl group might undergo similar reactions with acid chlorides to those in Scheme  [²] .

Our intent was to react 2,4,5-trimethyloxazole and 2,4,5-trimethylthiazole with excess aroyl chlorides and base to generate the corresponding N-acyl-β-keto cyclic ketene N,X-acetals (X = O, S) 2 (Scheme  [4] ). However, the expected derivatives 2 were not formed, in sharp contrast to what had been previously observed with 2-methyloxazolines and thiazolines [²4] [²5] (Scheme  [²] ). Instead, the

2-(oxazol-2-yl)-1-arylvinyl esters, 3a-f, from 2,4,5- tri­methyloxazole and the corresponding 2-(thiazol-2-yl)-1-arylvinyl esters, 4a-f, from 2,4,5-trimethylthiazole were readily generated (Scheme  [4] ). The reactions of these aromatic oxazole and thiazole derivatives must proceed through five-membered cyclic ketene N,X-acetal (X = O, S) intermediates formed after N-aroylation by deprotonation of the aromatic (6π-electron) N-aroyl-2-methyloxazolium (or thiazolium) chloride salts (Scheme  [5] ). These cyclic ketene N,X-acetals formally contain 7π electrons in their five-membered rings. Thus, the 6π-electron ring cations will lose a portion of their aromaticity upon proton loss (Scheme  [5] ).

2-Methylbenzoxazole and 2-methylbenzothiazole were reported to give 2-(β-aryl-β-aryloxy)vinylbenzoxazoles and 2-(β-aryl-β-aryloxy)vinylbenzothiazoles, respectively, upon reactions with aroyl chlorides in presence of a base. [³²] However, only very few examples were shown; no mechanistic path was proposed and the analogous oxazole and thiazole reactions (Scheme  [4] ) have never been demonstrated. We recently found that 2-methylbenzimidazole does not form cyclic ketene N,N′-acetal intermediates when treated with diethylmalonyl chloride in the presence of a base, whereas 2-methylimidazole readily generates 5,5,5,8-tetraethylimidazo[1,2,3-i,j][1,8]naphthyridine-4,6,7,9-tetraone through cyclic ketene N,N′-acetal intermediate (Scheme  [6] ). [³¹] Thus, the corresponding oxazole and thiazole reactions are of interest versus the behavior of 2-methyl derivatives of benzoxazoles, benzothiazoles, and benzimidazoles.

Reactions of 2,4,5-trimethyloxazole with aroyl chlorides with 3.66 equivalents of base (Table  [¹] , entries 1-16) were performed in acetonitrile, THF, DMF, and DMAC at different temperatures under nitrogen. Reactions in refluxing acetonitrile generated 2-(oxazol-2-yl)-1-arylvinyl esters of aryl carboxylic acids 3a-f in every case in moderate yields.

An X-ray crystal structure confirmed the structure of 3d (Figure  [¹] ). Only the Z-isomers of 3a-f were formed. Aliphatic acid chlorides did not react with substituted oxazoles under these conditions (entries 15,16) and the substituted oxazoles were recovered. The yield of 3a in THF was lower than that in acetonitrile as illustrated by the example in entry 1 versus entry 2 in Table  [¹] . The higher polarity and higher reflux temperature of acetonitrile facilitated the reaction. Reactions were also attempted in the highly polar, high boiling solvents, DMF and DMAC where both diisopropylethylamine (DIPEA) and triethyl­amine were used as bases (Table  [¹] , entries 6-9). None of the reactions in DMA and DMAC gave the arylvinyl ester 3a. Complex mixtures of products were obtained. DMF was reported to react with benzoyl chloride, [³³] [³4] and this might have happened in our work.

Use of a large excess of benzoyl chloride increased the yield of 3a to 68% (e.g., Table  [¹] , entry 3). Substituents on the aroyl chloride did not appear to affect the reaction and similar yields were obtained in all reactions (entries 10-16).

Two suggested mechanisms for this reaction are shown in Scheme  [7] . This route is analogous to that described previously for the conversion of 2-methyloxazolines (and thiazolines) [²4] [²5] into N-acyl-β-keto cyclic ketene N,X-acetals (Scheme  [²] ) up to 1e. If the base deprotonates 1e to the nonaromatic 1f, then 1f could be further converted into 1g.

An interesting feature of this mechanism is the loss of aromaticity­ upon deprotonation of the two 6π-electron oxazolium­ intermediates 1b and 1e to cyclic ketene N,O-acetal, 7π-electron intermediates 1c and 1f, respectively. This feature is not present when either 2-methyloxazolines or 2-methylthiazolines react with aroyl chlorides via cyclic ketene N,X-acetals (X = O, S) intermediates (Scheme  [³] ).

Initial nucleophilic acyl attack by the nitrogen of 2,4,5-trimethyloxazole on an acid chloride’s carbonyl carbon generates zwitterionic intermediate 1a (Scheme  [7] ). Ion pair 1b is formed by the loss of chloride. Proton removal from 1b by Et₃N generates Et₃NH⁺Cl^- and N-acyl cyclic ketene N,O-acetal 1c. Conversion of 1c into intermediate 1d by a second acylation at the β-carbon regenerates aromaticity. Both nitrogen and oxygen in 1c activate the exocyclic double bond of 1c to promote nucleophilic attack on a second acid chloride. The high nucleophilicity of the exocyclic β-carbon promotes the second rapid aroylation, explaining why 1c is not observed, even when a 1:1 substrate to acid chloride is used (Table  [¹] , entry 4). Loss of chloride from 1d forms 1e, which might be deprotonated by triethylamine generating 1f. The further conversion of 1f into 1g, and ultimately the Z-isomers 3a-f, requires the E-isomer of 1f to be available. The Z-isomer is formed with oxazolines and thiazolines (Scheme  [²] ), so it would likely be preferentially formed here also. A low rotational barrier is postulated between the Z- and E-isomers of 1f, made possible by the push-pull electronic structure which reduces [¹8] [²9] [³5] the exocyclic double bond’s order (Scheme  [8] ).

We postulate that deprotonation of 1e to 1f might be slow with oxazoles and thiazoles due to loss of aromaticity in this process. Thus, 1e might react generating 1h by nucleophilic attack of the carbonyl on the, now activated, amide carbonyl carbon of 1e. Intermediate 1h would now rapidly deprotonate to give 1g. This route establishes the new double bond with only the Z-geometry. Ring-opening of 1h between carbon and nitrogen must not occur prior to deprotonation. If this happened, both the E- and Z-isomers could form. This route offers a rational for why 3a-f form with oxazoles and thiazoles, but the same route is not followed by oxazolines or thiazolines. These latter two classes of compounds might deprotonate rapidly from their 1e analogues, because no aromaticity is lost in those cases.

Intramolecular nucleophilic attack of the C-acyl carbonyl oxygen on the N-acyl carbonyl carbon, only possible in the E-isomer, generates zwitterionic aromatic 1g. Further, opening of the six-membered ring in 1g results in the products 3a-f. This is in contrast to 2-methyloxazoline or thiazoline reactions where N to O aroyl transfer does not occur. [²4] [²5] These reactions (Scheme  [²] ) generate N-aroyl-β-keto cyclic ketene acetals where the rotation about the exo-double bond might also have a low barrier. [²4] [²5]

Reactions of 2,4,5-trimethylthiazole with aroyl chlorides under similar conditions produced the corresponding thiazole­-based vinyl esters 4a-f (Scheme  [9] , R^¹ = H, R^² = Me). For example, benzoyl chloride and 1 (X = S) gave benzoic acid 2-(4,5-dimethylthiazol-2-yl)-1-phenylvinyl ester (4a). The X-ray crystal structure of the 3-bromobenzoyl analogue, 4d, is shown in Figure  [²] , confirming that the Z-isomer was formed. All yields in this series were moderate.

2-Ethyl-4,5-dimethylthiazole produced the same type of products 9a,b (Table  [²] , entries 7, 8). The X-ray crystal structure of 9a is shown in Figure  [³] . Thus, an ethyl substituent at the 2-position does not affect the mechanistic pathway. Again, the Z-isomer is exclusively formed for 4a-f and 9a,b (see Scheme  [9] ). Reactions of 2-methylthiazole with aroyl chlorides and base also generated similar Z-isomeric products 10a,b, in higher yields than the corresponding products from 2,4,5-trimethylthiazole.

Just like the case of 2,4,5-trimethyloxazole, reactions of 2,4,5-trimethylthiazole or 2-ethyl-4,5-dimethylthiazole with the alkyl acid chlorides, 2,2-dimethylpropanoyl chloride and acetyl chloride (Table  [²] , entries 12-14) resulted only in the recovery of the reactants (Scheme  [¹0] ). In contrast, 2-methylthiazole reacted with 2,2-dimethylpropanoyl chloride in the presence of a base to form 2,2-dimethylpropionic acid 2,2-dimethyl-1-thiazol-2-ylmethylenepropyl ester (10c) (Scheme  [¹0] ) (Table  [²] , entry 11).

In all of these reactions, triaroylated products were never obtained. In anticipation of obtaining a triaroylated product, a stronger base was used. When 2,4,5-trimethylthia­zole was quantitatively converted into its anion by treatment with n-BuLi in THF and then reacted with aroyl chlorides, triaroylated products were obtained. Treating 2,4,5-trimethylthiazole with n-BuLi followed by benzoyl chloride generated benzoic acid 2-(4,5-dimethylthiazol-2-yl)-3-oxo-1,3-diphenylpropenyl ester (11a) (Table  [³] , entry 1). 4-Chlorobenzoyl chloride gave 11b when reacted with 2,4,5-trimethylthiazole under identical conditions. The mole ratio of aroyl chloride to thiazole did not change the product obtained. Tribenzoylated products were obtained in lower yields at aroyl chloride/thiazole ratios of 2:1 and below without the isolation of mono- or diaroylated products (Table  [³] , entry 2). This observation implies that each succeeding aroylation is faster than the preceding aroylation step.

Table 3 Reactions of 2,4,5-Trimethylthiazole with Aryl and Alkyl Acid Chlorides with n-BuLi in THF

Entry	Substrate	Acid chloride	Substrate/ acid chloride (mol ratio)	Product	Yield (%)
1 2		PhCOCl PhCOCl	1:3 1:2	11a	61 37
3		4-ClC6H4COCl	1:3	11b	63
4		t-BuCOCl	1:3	11c	66
5		PhCOCl	1:3	12	58

Mechanistic studies are planned on this reaction. Finally, triaroylation also occurred using the oxazole analogue, 2,4,5-trimethyloxazole, with n-BuLi followed by adding benzoyl chloride under these conditions (Table  [³] , entry 5) to give 12. In sharp contrast to aroyl chlorides, reacting 2,4,5-trimethylthiazole with n-BuLi followed by 2,2-di­methylpropanoyl chloride generated 1,1-bis-(4,5-dimethylthiazol-2-yl)-2,2-dimethylpropan-1-ol (11c). Thus, nucleophilic attack of the 2,4,5-trimethylthiazole anion on the acid chloride first generated the C-alkylated ketone, with which a second mole of anion reacted to give the Li⁺ salt of the alcohol.

All the aroylation reactions proceed through cyclic ketene acetal intermediates and, unexpectedly, generated highly functionalized 2-(oxazol-2-yl)-1-arylvinyl esters of benzoic acid and substituted benzoic acids and their 2-(thia­zol-2-yl) analogues. Further applications of these reactions are being studied. Similar compounds have been reported to show insecticidal activities. [³6]

Possible cyclization reactions with diacid chlorides were explored based on previously demonstrated cyclization of 2-methyloxazolines and thiazolines. [²6] [²9] [³0] Thus, 2,4,5-trimethylthiazole was reacted with diethylmalonyl chloride and dimethylmalonyl chloride in the presence of a base hoping to obtain the products shown in Scheme  [¹¹] . However, in all cases, the starting materials were recovered. Similar reactions with 2,4,5-trimethyloxazole were also unsuccessful. These cyclizations also did not occur when the 2-methyloxazoles and thiazoles were first quantitatively converted into their anions by n-BuLi and then reacted with these diacid chlorides.

The ^¹H and ^¹³C NMR spectra were recorded on a Bruker Avance III spectrometer operating at 300 MHz for ^¹H and 75 MHz for ^¹³C. Chemical shifts were reported in ppm downfield from TMS. CDCl₃ was used as the solvent for all NMR samples. The FT-IR spectra were recorded as films on KBr plates or on a diamond window. All reactions were performed under N₂. MeCN, THF, and Et₃N were dried by distillation over CaH₂ under N₂. CH₂Cl₂ was predried with CaCl₂ and then distilled from CaH₂ under N₂. DMF was predried with anhyd MgSO₄ and then distilled under reduced pressure. Anhyd N,N-dimethylacetamide (DMAC) and all other chemicals were obtained commercially and used as received. A mixture of dry ice and acetone was used to achieve external bath temperature of -78 ˚C. Melting points were obtained on a Mel-Temp instrument with a heating rate of 5 ˚C/min and are uncorrected.

Benzoic Acid 2-(4,5-Dimethyloxazol-2-yl)-1-phenylvinyl Ester (3a); Typical Procedure

To a solution of 2,4,5-trimethyloxazole [1 (X = O); 0.25 g, 2.1 mmol] in MeCN (15 mL) was added dropwise Et₃N (0.784 g, 7.6 mmol). A solution of benzoyl chloride (0.903 g, 6.3 mmol) in MeCN (15 mL) was added dropwise into the above solution under N₂ at r.t. The reaction mixture was refluxed for 3 h and then the solvent was removed by rotary evaporation. Acetone (3 × 20 mL) was added to the residue to give a solid/liquid mixture. The mixture was filtered and the collected solid was thoroughly washed with acetone (3 × 15mL). The filtrate was concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 5:1 hexane-EtOAc) to give 3a (Table  [¹] ); yield: 366 mg (54%); sticky yellow liquid; R _f  = 0.6 (silica gel, 5:1 hexane-EtOAc).

IR (KBr): 3063, 2923, 1920, 1740, 1634, 1600, 1449, 1313, 1240 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.26 (d, J = 7.1 Hz, OCOC₆H₅ arom ortho, 2 H), 7.62 (m, OCOC₆H₅, 3 H), 7.51 (t, J = 7.7 Hz, C=CC₆H₅ arom ortho, 2 H), 7.35 (m, C=CC₆H₅, 3 H), 6.83 (s, N=CCH=C, 1 H), 1.99 [s, OC(CH ₃)C(CH₃)N, 3 H], 1.89 [s, OC(CH₃)C(CH ₃)N, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 164.52 (OCOC₆H₅), 155.81(N=CCH=C), 149.76 (CH=CC₆H₅), 143.35 [OC(CH₃)C(CH₃)N], 133.85 (CH=CC ₆H₅), 133.33 (OCOC ₆H₅ arom para), 131.97 (OCOC ₆H₅), 130.11 (OCOC ₆H₅ arom ortho), 2 C), 129.47 (arom meta of both C₆H₅ groups, 4 C), 128.63 (OCOC ₆H₅ arom para), 128.31 (OCOC ₆H₅ arom ortho, 2 C), 124.84 [OC(CH₃)C(CH₃)N], 103.05 (N=CCH=C), 10.82 [OC(CH₃)C(CH₃)N], 9.49 [OC(CH₃)C(CH₃)N].

4-Chlorobenzoic Acid 1-(4-Chlorophenyl)-2-(4,5-dimethyl­oxazol-2-yl)vinyl Ester (3b)

Yield: 403 mg (49%); white crystals; mp 123-125 ˚C; R _f  = 0.6 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 3055, 2923, 1738, 1652, 1632, 1592, 1530, 1487, 1400, 1249 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.12 (d, J = 7.6 Hz, OCOC₆H₄Cl (arom ortho, 2 H), 7.46 (d, J = 7.5 Hz, OCOC₆H₄Cl arom meta, 2 H), 7.45 (m, C=CC₆H₄Cl arom ortho, 2 H), 7.28 (d, C=CC₆H₄Cl arom meta, 2 H), 6.68 (s, N=CCH=C, 1 H), 1.93 [s, OC(CH ₃)C(CH₃)N, 3 H], 1.89 [s, OC(CH₃)C(CH ₃)N, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 163.84 (OCOC₆H₄Cl), 155.59 (N=CCH=C), 148.54 (CH=CC₆H₄Cl), 143.81 (OCOC ₆H₄Cl arom para, Cl-bearing), 140.25 [OC(CH₃)C(CH₃)N], 135.71 (CH=CC ₆H₄Cl arom para, Cl-bearing), 132.39 (CH=CC ₆H₄Cl), 131.70 (OCOC ₆H₄Cl arom ortho, 2 C), 129.16 (OCOC ₆H₄Cl, 3 C), 128.96 (CH=CC ₆H₄Cl arom meta 2 C), 127.93 (CH=CC ₆H₄Cl arom ortho, 2 C), 126.22 [OC(CH₃)C(CH₃)N], 103.68 (N=CCH=C), 11.05 [OC(CH₃)C(CH₃)N], 9.89 [OC(CH₃)C(CH₃)N].

2-Methylbenzoic Acid 2-(4,5-Dimethyloxazol-2-yl)-1- o -tolylvinyl Ester (3c)

Yield: 345 mg (47%); brown liquid; R _f  = 0.45 (silica gel, 5:1 hexane-EtOAc).

IR (KBr): 3065, 2925, 2300, 1740, 1636, 1456 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.25 (m, OCOC₆ H ₄Me arom ortho, 1 H), 7.53 (m, OCOC₆ H ₄Me arom para, 1 H), 7.46 (m, OCOC₆ H ₄Me arom meta, 1 H), 7.62 (m, arom ortho and para of C=CC₆ H ₄Me and arom ortho of both phenyl rings, 5 H), 6.34 (s, N=CCH=C, 1 H), 2.59 (s, C=CC₆H₄CH ₃, 3 H), 2.53 (s, OCOC₆H₄CH ₃, 3 H), 2.05 [s, OC(CH ₃)C(CH ₃)N, 6 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 164.78 (OCOC₆H₄Me), 155.83 (N=CCH=C), 151.03 (CH=CC₆H₄Me), 143.40 (OCOC ₆H₄Me arom ortho, Me-bearing), 141.17 [OC(CH₃)C(CH₃)N], 136.29 (CH=CC ₆H₄Me), 135.17 (CH=CC ₆H₄Me arom ortho, Me-bearing), 132.52 (OCOC ₆H₄Me arom para), 131.88 (OCOC ₆H₄Me), 131.66 (OCOC ₆H₄Me arom ortho), 131.40 (CH=CC ₆H₄Me arom meta), 131.02 (OCOC ₆H₄Me arom meta), 129.31 (CH=CC ₆H₄Me arom para), 128.92 (CH=CC ₆H₄Me arom ortho), 128.62 (CH=CC ₆H₄Me arom meta), 125.96 (OCOC ₆H₄Me arom meta), 125.75 [OC(CH₃)C(CH₃)N], 107.80 (N=CCH=C), 21.72 (CH=CC₆H₄ CH₃), 20.95 (OCOC₆H₄ CH₃), 11.09 [OC(CH₃)C(CH₃)N], 9.85 [OC(CH₃)C(CH₃)N].

2-Bromobenzoic Acid 1-(2-Bromophenyl)-2-(4,5-dimethyl­oxazol-2-yl)vinyl Ester (3d) [³7]

Yield: 514 mg (51%); yellow crystals; mp 92-93 ˚C; R _f  = 0.65 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 3067, 2920, 2855, 1910, 1748, 1661, 1632, 1586, 1364 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.30 (dd, J = 7.4 Hz, OCOC₆H₄Br arom ortho, 1 H), 7.70 (dd, J = 7.7 Hz, OCOC₆H₄Br meta, next to Br, 1 H), 7.64 (m, OCOC₆H₄Br arom ortho and para, 2 H), 7.40 (m, C=CC₆H₄Br arom ortho, para, and meta, next to Br, 3 H), 7.23 (m, C=CC₆H₄Br arom meta, 1 H), 6.55 (s, N=CCH=C, 1 H), 2.13 [s, OC(CH ₃)C(CH₃)N, 3 H], 2.07 [s, OC(CH₃)C(CH ₃)N, 3 H].

^¹³C NMR (75 MHz,CDCl₃): δ = 162.80 (OCOC₆H₄Br), 155.07 (N=CCH=C), 148.57 (CH=CC₆H₄Br), 143.73 (CH=CC ₆H₄Br), 135.78 [OC(CH₃)C(CH₃)N], 134.49 (OCOC ₆H₄Br arom para), 133.54 (OCOC ₆H₄Br), 133.13 (OCOC ₆H₄Br arom ortho), 132.48 (OCOC ₆H₄Br arom meta next to Br), 132.24 (CH=CC ₆H₄Br arom meta next to Br), 131.21 (CH=CC ₆H₄Br arom para), 130.65 (CH=CC ₆H₄Br arom ortho), 130.37 (OCOC ₆H₄Br arom meta), 127.41 (OCOC ₆H₄Br arom meta), 127.03 [OC(CH₃)C(CH₃)N], 122.53 (OCOC ₆H₄Br arom ortho, Br-bearing), 121.70 (CH=CC ₆H₄Br arom ortho, Br-bearing), 109.17 (N=CCH=C), 11.04 [OC(CH₃)C(CH₃)N], 9.94 [OC(CH₃)C(CH₃)N].

3-Fluorobenzoic Acid 2-(4,5-Dimethyloxazol-2-yl)-1-(3-fluoro­phenyl)vinyl Ester (3e)

Yield: 399 mg (54%); brown liquid; R _f  = 0.6 (silica gel, 5:1 hexane-EtOAc).

IR (KBr): 3076, 2937, 1733, 1661, 1591, 1455, 1416, 1380, 1273, 1224 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.05 (m, OCOC₆H₄F arom ortho, 1 H), 7.96 (m, OCOC₆H₄F arom ortho, 1 H), 7.51 (m, OCOC₆H₄F arom meta, 1 H), 7.40 (m, arom ortho and meta of C=CC₆H₄F and arom para of OCOC₆H₄F, 3 H), 7.06 (m, C=CC₆H₄F arom para, 1 H), 6.88 (s, N=CCH=C, 1 H), 2.02 [s, OC(CH ₃)C(CH₃)N, 3 H], 1.96 [s, OC(CH₃)C(CH ₃)N, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 164.55 (OCOC₆ H ₄F arom meta, F-bearing), 163.44 (OCOC₆H₄F), 160.81 (CH=CC ₆H₄F arom meta, F-bearing), 155.40 (N=CCH=C), 148.30 (CH=CC₆H₄F), 143.89 [OC(CH₃)C(CH₃)N], 136.06 (CH=CC ₆H₄F), 132.30 (OCOC ₆H₄F), 131.50 (CH=CC ₆H₄F arom meta), 131.40 (OCOC ₆H₄F arom meta), 130.36 (OCOC ₆H₄F arom ortho), 130.13 [OC(CH₃)C(CH₃)N], 126.00 (CH=CC ₆H₄F arom ortho), 120.58 (OCOC ₆H₄F arom para), 117.22 (OCOC ₆H₄F arom ortho), 116.68 (CH=CC ₆H₄F arom para), 111.76 (CH=CC ₆H₄F arom ortho), 104.09 (N=CCH=C), 10.82 [OC(CH₃)C(CH₃)N], 9.63 [OC(CH₃)C(CH₃)N].

4-Nitrobenzoic Acid 2-(4,5-dimethyloxazol-2-yl)-1-(4-nitrophenyl)vinyl Ester (3f)

Yield: 403 mg (47%); yellow solid; mp 207-209 ˚C; R _f  = 0.45 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 3113, 2923, 1733, 1625, 1594, 1522, 1410, 1341, 1245, 1121 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.42 (m, OCOC₆H₄NO₂ arom-H, 4 H), 8.27 (m, C=CC₆H₄NO₂ arom meta, 2 H), 7.75 (m, C=CC₆H₄NO₂ arom ortho, 2 H), 6.95 (s, N=CCH=C, 1 H), 2.03 [s, OC(CH ₃)C(CH₃)N, 3 H], 1.60 [s, OC(CH₃)C(CH ₃)N, 3 H].

^¹³C NMR (75 MHz,CDCl₃): δ = 162.64 (OCOC₆H₄NO₂), 154.76 (OCOC ₆H₄NO₂ arom para), 151.16 (N=CCH=C), 148.07 (CH=CC₆H₄NO₂), 146.70 (CH=CC ₆H₄NO₂ arom para), 144.47 (CH=CC ₆H₄NO₂), 139.67 [OC(CH₃)C(CH₃)N], 134.88 (OCOC ₆H₄NO₂), 133.50 (OCOC ₆H₄NO₂ arom ortho, 2 C), 131.62 (CH=CC ₆H₄NO₂ arom ortho, 2 C), 125.79 [OC(CH₃)C(CH₃)N], 124.42 (OCOC ₆H₄NO₂ arom meta), 123.98 (CH=CC ₆H₄NO₂ arom meta), 106.60 (N=CCH=C), 11.14 (OC(CH₃)C(CH₃)N), 9.76 [OC(CH₃)C(CH₃)N].

Benzoic Acid 2-(4,5-Dimethylthiazol-2-yl)-1-phenylvinyl Ester (4a); Typical Procedure

To a solution of 2,4,5-trimethylthiazole [1 (X = S); 0.25 g, 1.9 mmol] in MeCN (15 mL) was added dropwise Et₃N (0.712 g, 6.9 mmol). A solution of benzoyl chloride (0.817 g, 5.7 mmol) in MeCN (15 mL) was added dropwise to the above solution under N₂ at r.t. The reaction mixture was refluxed for 3 h and then the solvent was removed by rotary evaporation. Acetone (3 × 20 mL) was added to the residue to give a solid/liquid mixture. The mixture was filtered and the collected solid was thoroughly washed with acetone (3 × 15 mL). The filtrate was concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 5:1 hexane-EtOAc) to give 4a; yield: 287 mg (44%); yellow liquid; R _f  = 0.40 (silica gel, 5:1 hexane-EtOAc).

IR (KBr): 3063, 3043, 2949, 2917, 2854, 2479, 1910, 1740, 1699, 1538, 1492, 1314, 1235 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.32 (d, J = 7.8 Hz, OCOC₆H₅ arom ortho, 2 H), 7.69 (m, OCOC₆H₅ arom para, 1 H), 7.57 (m, arom-H, 4 H), 7.35 (m, arom-H, 3 H), 7.30 (s, N=CCH=C, 1 H), 2.31 [s, NC(CH ₃)C(CH₃)S, 3 H], 1.60 [s, NC(CH₃)C(CH ₃)S, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 163.75 (OCOC₆H₅), 156.84 (N=CCH=C), 148.90 [SC(CH₃)C(CH₃)N], 148.20 (CH=CC₆H₅), 133.94 (CH=CC ₆H₅), 130.46 (OCOC ₆H₅ arom para), 129.88 (OCOC ₆H₅), 129.25 (OCOC ₆H₅ arom ortho), 129.00 (OCOC ₆H₅ arom meta), 128.79 (CH=CC ₆H₅ arom meta), 128.18 [NC(CH₃)C(CH₃)S], 127.73 (CH=CC ₆H₅ arom para), 124.74 (CH=CC ₆H₅ arom ortho), 112.01 (N=CCH=C), 14.33 [SC(CH₃)C(CH₃)N], 11.23 [SC(CH₃)C(CH₃)N].

4-Chlorobenzoic Acid 1-(4-Chlorophenyl)-2-(4,5-dimethylthiazol-2-yl)vinyl Ester (4b)

Yield: 378 mg (48%); yellow liquid; R _f  = 0.45 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2921, 1737, 1680, 1590, 1538, 1489, 1426, 1398, 1239, 1223, 1168 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.23 (d, J = 8.5 Hz, OCOC₆H₄Cl arom ortho, 2 H), 7.56 (d, J = 8.5 Hz, OCOC₆H₄Cl arom meta, 2 H), 7.47 (d, J = 8.6 Hz, C=CC₆H₄Cl arom ortho, 2 H), 7.34 (d, J = 8.6 Hz, C=CC₆H₄Cl arom meta, 2 H), 6.68 (s, N=CCH=C, 1 H), 2.30 [s, SC(CH₃)C(CH ₃)N, 3 H], 2.29 [s, SC(CH ₃)C(CH₃)N, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 156.17 (OCOC₆H₄Cl), 148.66 (N=CCH=C), 147.43 [SC(CH₃)C(CH₃)N], 140.78 (CH=CC₆H₄Cl), 135.28 (OCOC ₆H₄Cl arom para, Cl-bearing), 132.47 (CH=CC ₆H₄Cl arom para, Cl-bearing, 2 C), 129.24 (OCOC ₆H₄Cl arom ortho, 2 C), 129.13 (OCOC ₆H₄Cl arom meta, 4 C), 128.16 (OCOC ₆H₄Cl), 127.22 [SC(CH₃)C(CH₃)N], 125.96 (CH=CC ₆H₄Cl arom ortho, 2 C), 112.52 (N=CCH=C), 14.47 [SC(CH₃)C(CH₃)N], 11.34 [SC(CH₃)C(CH₃)N].

2-Methylbenzoic Acid 2-(4,5-Dimethylthiazol-2-yl)- o -tolylvinyl Ester (4c)

Yield: 297 mg (44%); yellow liquid; R _f  = 0.65 (silica gel, 3:1 hexane-EtOAc).

IR (neat): 3001, 2923, 1737, 1651, 1601, 1574, 1543, 1488, 1456, 1380, 1283, 1219, 1164 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.38 (m, OCOC₆ H ₄Me arom ortho, 1 H), 7.50 (m, OCOC₆ H ₄Me arom para and meta, 2 H), 7.37 (m, OCOC₆ H ₄Me arom meta, 1 H), 7.23 (m, CH=CC₆ H ₄Me arom-H, 4 H), 6.75 (s, N=CCH=C, 1 H), 2.58 [s, NC(CH ₃)C(CH₃)S, 3 H], 2.54 (s, OCOC₆H₄CH ₃, 3 H), 2.30 (s, CH=CC₆H₄CH ₃, 3 H), 2.29 [s, NC(CH₃)C(CH ₃)S, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 163.50 (OCOC₆H₄Me), 157.01 (N=CCH=C), 149.89 [SC(CH₃)C(CH₃)N], 147.88 (CH=CC₆H₄Me), 142.29 (OCOC ₆H₄Me arom ortho, Me-bearing), 140.70 (CH=CC ₆H₄Me arom ortho, Me-bearing), 136.09 (CH=CC ₆H₄Me), 135.08 (OCOC ₆H₄Me arom para), 133.05 (OCOC ₆H₄Me), 132.15 (OCOC ₆H₄Me arom ortho), 131.65 (OCOC ₆H₄Me arom meta), 130.89 (CH=CC ₆H₄Me arom meta), 129.00 [SC(CH₃)C(CH₃)N], 128.54 (CH=CC ₆H₄Me arom para), 127.58 (CH=CC ₆H₄Me arom ortho), 127.48 (OCOC ₆H₄Me arom meta), 126.02 (CH=CC ₆H₄Me arom meta), 115.63 (N=CCH=C), 22.11 (OCOC₆H₄ CH₃), 20.87 (CH=CC₆H₄ CH₃),14.38 [SC(CH₃)C(CH₃)N], 11.29 [SC(CH₃)C(CH₃)N].

3-Bromobenzoic Acid 1-(3-Bromophenyl)-2-(4,5-dimethylthiazole-2-yl)vinyl Ester (4d) [³7]

Yield: 406 mg (43%); yellow crystals; mp 133-135 ˚C; R _f  = 0.60 (silica gel, 3:1 hexane-EtOAc).

IR (neat): 3059, 2916, 1957, 1734, 1634, 1590, 1563, 1538, 1473, 1372, 1221, 1113 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.43 (s, OCOC₆H₄Br arom ortho, next to Br, 1 H), 8.25 (s, OCOC₆H₄Br arom ortho, 1 H), 7.83 (m, OCOC₆H₄Br arom para, 1 H), 7.69 (m, CH=CC₆ H ₄Br arom ortho, next to Br, 1 H), 7.48 (m, arom-H, 3 H), 7.25 (m, arom-H and CH=CC₆H₄Br, 2 H), 2.30 [s, NC(CH₃)C(CH₃)S, 6 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 162.50 (OCOC₆H₄Br), 156.08 (N=CCH=C), 148.70 [SC(CH₃)C(CH₃)N], 146.95 (CH=CC₆H₄Br), 137.12 (CH=CC ₆H₄Br), 136.01 (OCOC ₆H₄Br arom para), 133.39 (OCOC ₆H₄Br arom ortho, next to Br), 132.31 (OCOC ₆H₄Br), 130.68 (CH=CC ₆H₄Br arom para), 130.42 (OCOC ₆H₄Br arom meta), 130.39 (CH=CC ₆H₄Br arom meta), 129.07 (CH=CC ₆H₄Br arom ortho, next to Br), 128.49 (OCOC ₆H₄Br arom ortho), 127.76 [SC(CH₃)C(CH₃)N], 123.38 (CH=CC ₆H₄Br aromatic ortho), 123.10 (OCOC ₆H₄Br, Br-bearing), 122.91(CH=CC ₆H₄Br, Br-bearing­), 112.99 (N=CCH=C), 14.36 [SC(CH₃)C(CH₃)N], 11.37 [SC(CH₃)C(CH₃)N].

3-Fluorobenzoic Acid 2-(4,5-Dimethylthiazol-2-yl)-1-(3-fluoro­phenyl)vinyl Ester (4e)

Yield: 337 mg (47%); white crystals; mp 102-103 ˚C; R _f  = 0.6 (silica gel, 5:1 hexane-EtOAc).

IR (KBr): 2976, 1730, 1586, 1538, 1482, 1445, 1333, 1253, 1230 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.11 (m, OCOC₆H₄F arom ortho, 1 H), 7.98 (m, OCOC₆H₄F arom ortho, 1 H), 7.57 (m, OCOC₆H₄F arom meta), 1 H), 7.40 (m, arom ortho and meta of C=CC₆H₄F and arom para of OCOC₆H₄CF, 3 H), 7.23 (m, C=CC₆H₄F arom para, 1 H), 7.05 (s, N=CCH=C, 1 H), 2.30 [s, SC(CH₃)C(CH₃)N, 6 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 164.59 (OCOC₆H₄F), 162.70 (OCOC ₆H₄F arom meta, F-bearing), 161.32 (CH=CC ₆H₄F arom meta, F-bearing), 156.06 (N=CCH=C), 148.67 [SC(CH₃)C(CH₃)N], 147.17 (CH=CC₆H₄F), 136.21 (CH=CC ₆H₄F), 130.77 (OCOC ₆H₄F), 130.59 (OCOC ₆H₄F arom meta), 128.42 (CH=CC ₆H₄F arom meta), 126.27 [SC(CH₃)C(CH₃)N], 126.23 (OCOC ₆H₄F arom ortho), 121.43 (CH=CC ₆H₄F arom ortho), 120.44 (OCOC ₆H₄F arom para), 117.45 (OCOC ₆H₄F arom ortho), 116.10 (CH=CC ₆H₄F arom para), 112.97 (CH=CC ₆H₄F arom ortho), 111.88 (N=CCH=C), 14.35 [SC(CH₃)C(CH₃)N], 11.29 [SC(CH₃)C(CH₃)N].

4-Nitrobenzoic Acid 2-(4,5-Dimethylthiazol-2-yl)-1-(4-nitrophenyl)vinyl Ester (4f)

Yield: 376 mg (46%); yellow solid; mp 218-220 ˚C; R _f  = 0.7 (silica gel, 1:1 hexane-EtOAc).

IR (neat): 3114, 2980, 1741, 1686, 1597, 1526, 1428, 1374, 1311, 1228, 1079 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.49 (m, OCOC₆H₄NO₂ arom-H, 4 H), 8.28 (m, C=CC₆H₄NO₂ arom meta, 2 H), 7.73 (m, C=CC₆H₄NO₂ arom ortho, 2 H), 7.44 (s, N=CCH=C, 1 H), 2.32 [s, SC(CH₃)C(CH ₃)N, 3 H], 1.60 [s, SC(CH ₃)C(CH₃)N, 3 H].

^¹³C NMR (75 MHz,CDCl₃): δ = 163.19 (OCOC₆H₄NO₂), 150.00 (OCOC ₆H₄NO₂ arom para), 149.81 (N=CCH=C), 138.92 (CH=CC₆H₄NO₂), 131.67 (CH=CC ₆H₄NO₂ arom para), 131.26 (CH=CC ₆H₄NO₂), 130.63 [SC(CH₃)C(CH₃)N], 125.41 (OCOC ₆H₄NO₂), 124.27 (OCOC ₆H₄NO₂ arom ortho, 2 C), 124.04 (CH=CC ₆H₄NO₂ arom ortho), 2 C), 123.75 [SC(CH₃)C(CH₃)N], 123.20 (OCOC ₆H₄NO₂ arom meta), 121.99 (CH=CC ₆H₄NO₂ arom meta), 104.55 (N=CCH=C), 11.82 [OC(CH₃)C(CH₃)N], 10.78 [SC(CH₃)C(CH₃)N].

Benzoic Acid 2-(4,5-Dimethylthiazol-2-yl)-1-phenylpropenyl Ester (9a) [³7]

Yield: 312 mg (52%); white crystals; mp 129-131 ˚C; R _f  = 0.65 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 3071, 2920, 1979, 1734, 1682, 1583, 1451, 1323, 1246 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.21 (m, OCOC₆H₅ arom ortho, 2 H), 7.63 (m, OCOC₆H₅ arom para, 1 H), 7.54 (m, arom-H of two aryl groups, 4 H), 7.37 (m, arom-H of two aryl groups, 3 H), 2.38 [d, J = 5.8 Hz, SC(CH₃)C(CH ₃)N, 3 H], 2.30 [d, J = 5.5 Hz, SC(CH ₃)C(CH₃)N, 3 H], 2.26 [d, J = 5.5 Hz, N=CC(CH₃)=C, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 164.34 (OCOC₆H₅), 159.03 (N=CCH=C), 147.53 [SC(CH₃)C(CH₃)N], 145.64 (CH=CC₆H₅), 135.52 (CH=CC ₆H₅), 133.62 (OCOC ₆H₅ arom para), 130.43 (OCOC ₆H₅), 129.60 (OCOC ₆H₅ arom ortho, 2 C), 128.97 (OCOC ₆H₅ arom meta, 2 C), 128.66 (CH=CC ₆H₅ arom meta, 2 C), 128.56 [SC(CH₃)C(CH₃)N], 128.16 (CH=CC ₆H₅ arom para), 127.35 (CH=CC ₆H₅ arom ortho, 2 C), 120.39 [N=CC(CH₃)=C], 14.5 [N=CC(CH₃)=C], 14.68 [SC(CH₃)C(CH₃)N], 11.16 [SC(CH₃)C(CH₃)N].

2-Chlorobenzoic Acid 1-(2-Chlorophenyl)-2-(4,5-dimethylthiazol-2-yl)propenyl Ester (9b)

Yield: 331 mg (46%); white crystals; mp 139-140 ˚C; R _f  = 0.60 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2922, 1750, 1653, 1590, 1544, 1470, 1377, 1271 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.19 (d, J = 7.5 Hz, OCOC₆H₅ arom ortho, 1 H), 7.67 (m, OCOC₆H₅ arom para, 1 H), 7.40 (m, arom-H of two aryl groups, 7 H), 2.31 [d, J = 5.8 Hz, SC(CH₃)C(CH ₃)N, 3 H], 2.29 [d, J = 5.8 Hz, SC(CH₃)C(CH ₃)N, 3 H], 2.16 [N=CC(CH₃)=C, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 152.28 (OCOC₆H₅), 147.81 (N=CCH=C), 142.60 [SC(CH₃)C(CH₃)N], 142.58 (CH=CC₆H₅), 134.97 (OCOC ₆H₄Cl arom ortho, Cl-bearing), 134.05 (CH=CC ₆H₄Cl), 133.68 (OCOC ₆H₄Cl arom para), 133.41 (CH=CC ₆H₄Cl arom ortho, Cl-bearing), 132.92 (OCOC ₆H₄Cl arom ortho), 132.82 (OCOC ₆H₅), 131.45 (CH=CC ₆H₄Cl arom para), 130.27 (OCOC ₆H₅ meta position, next to Cl), 129.72 (CH=CC ₆H₅ meta position, next to Cl), 127.82 [SC(CH₃)C(CH₃)N], 126.71 (CH=CC ₆H₅ arom ortho), 126.68 (OCOC ₆H₄Cl arom meta), 126.53 (CH=CC ₆H₅ arom meta), 122.73 [N=CC(CH₃)=C], 16.81 [N=CC(CH₃)=C], 14.68 [SC(CH₃)C(CH₃)N], 11.20 [SC(CH₃)C(CH₃)N].

Benzoic Acid 1-Phenyl-2-thiazol-2-ylvinyl Ester (10a)

Yield: 579 mg (76%); yellowish white crystals; mp 82-83 ˚C; R _f  = 0.65 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 3062, 1735, 1642, 1598, 1474, 1448, 1226 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.32 (d, J = 7.3 Hz, OCOC₆H₅ arom ortho, 2 H), 7.78 (s, SCHCHN), 7.61 (arom-H and thiazole ring H, 5 H), 7.31 (arom-H), 7.16 (s, N=CCH=C, 1 H).

^¹³C NMR (75 MHz, CDCl₃): δ = 163.35 (OCOC₆H₅), 160.95 (N=CCH=C), 149.76 (CH=CC₆H₅), 142.47 (SCHCHN), 133.87 (CH=CC ₆H₅), 133.42 (OCOC ₆H₅ arom para), 130.13 (OCOC ₆H₅), 129.31 (OCOC ₆H₅ arom ortho, 2 C), 128.56 (arom meta of both rings, 4 C), 128.42 (CH=CC ₆H₅ arom para), 124.56 (CH=CC ₆H₅ arom ortho, 2 C), 119.46 (SCHCHN), 111.72 (N=CCH=C).

2-Methylbenzoic Acid 2-Thiazol-2-yl-1- o -tolylvinyl Ester (10b)

Yield: 518 mg (62%); yellowish liquid; R _f  = 0.60 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2927, 1738, 1653, 1574, 1488, 1381, 1218, 1033 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.39 (d, J = 7.7 Hz, OCOC₆ H ₄Me arom ortho), 7.81(d, J = 3.2 Hz, SCHCHN, 1 H), 7.23 (m, arom-H and thiazole ring H, 8 H), 6.91(s, N=CCH=C, 1 H), 2.65 (s, CH ₃C₆H₄, 6 H).

^¹³C NMR (75 MHz, CDCl₃): δ = 163.23 (OCOC₆H₄Me), 151.12 (N=CCH=C), 142.33 (CH=CC₆H₄Me), 142.21 (SCHCHN), 135.97 (OCOC ₆H₄Me arom ortho, Me-bearing), 134.75 (CH=CC ₆H₄Me), 133.12 (CH=CC ₆H₄Me arom ortho, Me-bearing), 132.11 (OCOC ₆H₄Me arom para), 131.50 (OCOC ₆H₄Me), 130.83 (OCOC ₆H₄Me arom ortho), 129.16 (arom meta of both rings, 2 C), 128.53 (CH=CC ₆H₄Me arom para), 127.27 (CH=CC ₆H₄Me arom ortho), 125.95 (OCOC ₆H₄Me arom meta), 125.90 (CH=CC ₆H₄Me arom meta), 119.51 (SCHCHN), 115.44 (N=CCH=C), 22.00 (CH=CC₆H₄ CH₃), 20.78 (OCOC₆H₄ CH₃).

2,2-Dimethylpropionic Acid 2,2-Dimethyl-1-thiazol-2-ylmethylenepropyl Ester (10c)

Yield: 389 mg (59%); yellowish liquid; R _f  = 0.75 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2970, 1751, 1648, 1479, 1394, 1264, 1091 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 7.71 (s, SCHCHN, 1 H), 7.22 (s, SCHCHN, 1 H), 6.59 (N=CCH=C, 1 H), 1.39 [s, OCOC(CH₃)₃, 9 H], 1.19 [s, CH=CC(CH₃)₃, 9 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 174.83 [OCOC(CH₃)₃], 161.50 [CH=CC(CH₃)₃], 159.35 (N=CCH=C), 142.15 (SCHCHN), 118.05 (SCHCHN), 108.39 (N=CCH=C), 39.24 [OCOC(CH₃)₃], 37.29 [CH=CC(CH₃)₃], 27.73 [OCOC(CH₃)₃], 27.27 [CH=CC(CH₃)₃].

Benzoic Acid 2-(4,5-Dimethylthiazol-2-yl)-3-oxo-1,3-diphenylpropenyl Ester (11a); Typical Procedure

A 2.5 M solution of n-BuLi in hexanes (1.1 mL, 2.7 mmol) was added using a syringe to a solution of 2,4,5-trimethylthiazole [1 (X = S); 0.25g, 1.9 mmol] in THF (20 mL) at -78 ˚C under N₂. The reaction mixture turned yellow. The mixture was stirred at -78 ˚C for 1 h and then benzoyl chloride (0.817 g, 5.7 mmol) was added with a syringe. The mixture was stirred for another 1 h and then warmed gradually to r.t. The mixture was further stirred for another 3 h at r.t. and then the solvent was removed by rotary evaporation. H₂O (20 mL) was added to the residue followed by the extraction with CH₂Cl₂ (3 × 40 mL). The organic layer was washed with 10% aq NaHCO₃ (2 × 20 mL) and H₂O (2 × 20 mL), and dried (Na₂SO₄). The solvent was removed by rotary evaporation and the residue was purified by flash chromatography (silica gel, 5:1 hexane-EtOAc) to give 11a; yield: 520 mg (61%); yellowish liquid; R _f  = 0.45 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2922, 1739, 1678, 1596, 1492, 1322, 1220 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.27 (d, J = 7.5 Hz, OCOC₆H₅ arom ortho, 2 H), 8.07 (d, J = 7.4 Hz, N=CCCOC₆H₅ arom ortho, 2 H), 7.67 (m, OCOC₆H₅ arom para, 1 H), 7.55 (m, OCOC₆H₅ arom meta, 2 H), 7.43 (m, N=CCCOC₆H₅ arom meta and para, 3 H), 7.35 (m, C=CC₆ H ₅ arom ortho, 2 H), 7.16 (C=CC₆ H ₅ arom ortho and para, 3 H), 2.22 [s, NC(CH ₃)C(CH₃)S, 3 H], 2.07 [s, NC(CH₃)C(CH ₃)S, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 193.85 (N=CCCOC₆H₅), 164.39 (OCOC₆H₅), 155.21 (C=CC₆H₅), 148.96 (N=CC=C), 147.75 [SC(CH₃)C(CH₃)N], 136.95 (N=CCCOC ₆H₅), 133.99 (C=CC ₆H₅), 133.94 (N=CCCOC ₆H₅ arom para), 133.31 (OCOC ₆H₅ arom para), 130.51 (OCOC ₆H₅), 129.83 (OCOC ₆H₅ arom ortho, 2 C), 129.63 (N=CCCOC ₆H₅ arom ortho, 2 C), 129.14 (N=CCCOC ₆H₅ arom meta­, 2 C), 128.70 (C=CC ₆H₅ arom meta, 2 C), 128.44 [SC(CH₃)C(CH₃)N], 128.36 (OCOC ₆H₅ arom meta, 2 C), 127.98 (C=CC ₆H₅ arom para), 127.71 (C=CC ₆H₅ arom ortho, 2 C), 125.71 (N=CC=C), 14.42 [SC(CH₃)C(CH₃)N], 11.02 [SC(CH₃)C(CH₃)N].

4-Chlorobenzoic Acid 1,3-Bis(4-chlorophenyl)-2-(4,5-dimethylthiazol-2-yl)-3-oxopropenyl Ester (11b)

Yield: 650 mg (63%); yellow crystals; mp 217-219 ˚C; R _f  = 0.35 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2922, 1733, 1679, 1594, 1487, 1401, 1256 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.20 (d, J = 8.58 Hz, OCOC₆H₄Cl arom ortho, 2 H), 8.99 (d, J = 8.56 Hz, N=CCCOC₆H₄Cl arom ortho, 2 H), 7.54 (d, J = 8.58 Hz, OCOC₆H₄Cl arom meta, 2 H), 7.35 (m, N=CCCOC₆H₄Cl arom meta and C=CC₆ H ₄Cl arom meta, 4 H), 7.17 (d, J = 8.58 Hz, C=CC₆ H ₄Cl arom ortho, 2 H), 2.26 [s, NC(CH ₃)C(CH₃)S, 3 H], 2.08 [s, NC(CH₃)C(CH ₃)S, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 192.39 (N=CCCOC₆H₄Cl), 163.61 (OCOC₆H₄Cl), 154.52 (C=CC₆H₄Cl), 149.36 (N=CC=C), 146.29 [SC(CH₃)C(CH₃)N], 140.82 (N=CCCOC ₆H₄Cl arom para, Cl-bearing), 140.14 (OCOC ₆H₄Cl arom para, Cl-bearing), 136.01 (N=CCCOC ₆H₄Cl), 135.09 (C=CC ₆H₄Cl arom para, Cl-bearing), 132.20 (C=CC ₆H₄Cl), 131.89 (OCOC ₆H₄Cl arom ortho), 2 C), 131.18 (N=CCCOC ₆H₄Cl arom ortho, 2 C), 129.31 (N=CCCOC ₆H₄Cl arom meta, 2 C), 129.22 (OCOC ₆H₄Cl arom meta­), 129.05 (C=CC ₆H₄Cl arom meta, 2 C), 128.90 (OCOC ₆H₄Cl), 128.59 [SC(CH₃)C(CH₃)N], 127.32 (C=CC ₆H₄Cl arom ortho, 2 C), 125.39 (N=CC=C), 14.46 [SC(CH₃)C(CH₃)N], 11.12 [SC(CH₃)C(CH₃)N].

1,1-Bis(4,5-dimethylthiazol-2-yl)-2,2-dimethylpropan-1-ol (11c)

Yield: 221 mg (66%); yellowish white crystals; mp 46-47 ˚C; R _f  = 0.60 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 3316, 2959, 2921, 1558, 1469, 1307, 1259, 1179, 908 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 6.43 (s, OH, 1 H), 3.15 (s, CH₂, 4 H), 2.23 [s, NC(CH ₃)C(CH₃)S, 6 H], 2.16 [s, SC(CH₃)C(CH₃)N, 6 H], 0.99 [s, C(CH₃)₃ 9 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 163.72 (N=CCH₂, 2 C), 146.47 [SC(CH₃)C(CH₃)N, 2 C], 125.32 [SC(CH₃)C(CH₃)N, 2 C], 39.21 (COH), 37.71 (CCH₃), 25.79 (CCH₂, 2 C), 14.27 (CCH₃, 3 C), 10.93 (=CCH₃, 4 C).

Benzoic Acid 2-(4,5-Dimethyloxazol-2-yl)-3-oxo-1,3-diphenylpropenyl Ester (12)

Yield: 522 mg (58%); yellow liquid; R _f  = 0.40 (silica gel, 5:1 hexane-EtOAc).

IR (neat): 2981, 1737, 1675, 1580, 1449, 1357, 1221 cm^-¹.

^¹H NMR (300 MHz, CDCl₃): δ = 8.24 (d, J = 8.26 Hz, OCOC₆H₅ arom ortho, 2 H), 8.12 (d, J = 8.21 Hz, N=CCCOC₆H₅ arom ortho, 2 H), 7.50 (m, arom-H, 8 H), 7.15 (m, arom-H, 3 H), 1.87 [s, NC(CH ₃)C(CH₃)S, 3 H], 1.83 [s, NC(CH₃)C(CH ₃)S, 3 H].

^¹³C NMR (75 MHz, CDCl₃): δ = 192.35 (N=CCCOC₆H₅), 165.21 (OCOC₆H₅), 154.36 (C=CC₆H₅), 149.64 (N=CC=C), 143.64 [OC(CH₃)C(CH₃)N], 136.30 (N=CCCOC ₆H₅), 133.70 (C=CC ₆H₅), 133.58 (N=CCCOC ₆H₅ arom para), 133.53 (OCOC ₆H₅ arom para), 132.31 (OCOC ₆H₅), 130.15 (OCOC ₆H₅ arom ortho, 2 C), 129.93 (N=CCCOC ₆H₅ arom ortho, 2 C), 129.85 (N=CCCOC ₆H₅ arom meta­, 2 C), 129.27 (C=CC ₆H₅ arom meta and OCOC₆H₅ arom meta, 4 C), 128.41 (C=CC ₆H₅ arom para), 128.25 (C=CC ₆H₅ arom ortho, 2 C), 128.06 [OC(CH₃)C(CH₃)N], 118.78 (N=CC=C), 10.88 [OC(CH₃)C(CH₃)N], 9.46 [OC(CH₃)C(CH₃)N].

Acknowledgment

The authors acknowledge the educational and general funds of Mississippi­ State University for partial financial support of this work.

References

• 1 Cao L. Wu Z. Zhu PC. Polym. Prepr.  1999,  39:  406 
  Search in Google Scholar
• 2 Cao L. Wu Z. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1999,  37:  2841 
  CrossrefSearch in Google Scholar
• 3 Cao L. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1999,  37:  2823 
  CrossrefSearch in Google Scholar
• 4 Wu Z. Cao L. Pittman CU. Recent Res. Dev. Polym. Sci.  1998,  2:  467 
  Search in Google Scholar
• 5 Wu Z. Cao L. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1998,  36:  861 
  CrossrefSearch in Google Scholar
• 6 Zhu PC. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1996,  34:  169 
  CrossrefSearch in Google Scholar
• 7 Wu Z. Cao L. Zhu PC. Polym. Prepr.  1997,  38:  121 
  Search in Google Scholar
• 8 Pittman CU. Wu Z. Zhu PC. J. Polym. Sci., Part A: Polym. Chem.  1997,  35:  485 
  CrossrefSearch in Google Scholar
• 9 Zhu PC. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1996,  34:  73 
  CrossrefSearch in Google Scholar
• 10 Liu Y. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1997,  35:  3655 
  CrossrefSearch in Google Scholar
• 11 Gruseck U. Heuschmann M. Tetrahedron Lett.  1987,  28:  6027 
  CrossrefSearch in Google Scholar
• 12 Gruseck U. Heuschmann M. Chem. Ber.  1987,  120:  2065 
  CrossrefSearch in Google Scholar
• 13 Zhou A. Pittman CU. Tetrahedron Lett.  2005,  46:  3801 
  CrossrefSearch in Google Scholar
• 14 Zhu PC. Lin J. Pittman CU. J. Org. Chem.  1995,  60:  5729 
  CrossrefSearch in Google Scholar
• 15 Cao L. Ph.D. Dissertation   Mississippi State University; USA: 1999. 
• 16 Li H. MS Thesis   Mississippi State University; USA: 2005. 
• 17 Ye G. Ph.D. Dissertation   Mississippi State University; USA: 2008. 
• 18 Ye G. Henry WP. Chen C. Zhou A. Pittman CU. Tetrahedron Lett.  2009,  50:  2135 
  CrossrefSearch in Google Scholar
• 19 Zhou A. Cao L. Li H. Liu Z. Pittman CU. Synlett  2006,  201 
  Thieme Connect
• 20 Zhou A. Cao L. Li H. Liu Z. Cho H. Henry WP. Pittman CU. Tetrahedron  2006,  62:  4188 
  CrossrefSearch in Google Scholar
• 21 Diaz-Ortiz AL. Diez-Barra E. de la Hoz A. Prieto P. Moreno A. Langa F. Prange T. Neuman A. J. Org. Chem.  1995,  60:  4160 
  CrossrefSearch in Google Scholar
• 22 Zhou A. Ph.D. Dissertation   Mississippi State University; USA: 2004. 
• 23 Tohda Y. Kawashima T. Ariga M. Akiyama R. Shudoh H. Mori Y. Bull. Chem. Soc. Jpn.  1984,  57:  2329 
  CrossrefSearch in Google Scholar
• 24 Zhou A. Pittman CU. Tetrahedron Lett.  2004,  45:  8899 
  CrossrefSearch in Google Scholar
• 25 Zhou A. Pittman CU. Synthesis  2006,  37 
  Thieme Connect
• 26 Zhou A. Pittman CU. Tetrahedron Lett.  2005,  46:  2045 
  CrossrefSearch in Google Scholar
• 27 Ye G. Chen C. Chatterjee S. Collier WE. Zhou A. Song Y. Beard DJ. Pittman CU. Synthesis  2010,  141 
  Thieme Connect
• 28 Ye G. Chatterjee S. Zhou A. Barker BL. Chen C. Song Y. Pittman CU. Tetrahedron  2010,  66:  2919 
  CrossrefSearch in Google Scholar
• 29 Ye G. Chatterjee S. Zhou A. Barker BL. Chen C. Song Y. Pittman CU. Synthesis  2010,  1209 
  Thieme Connect
• 30 Ye G. Zhou A. Henry WP. Song Y. Chatterjee S. Beard DJ. Pittman CU. J. Org. Chem.  2008,  73:  5170 
  CrossrefSearch in Google Scholar
• 31 Chatterjee S. Ye G. Pittman CU. Tetrahedron Lett.  2010,  51:  1139 
  CrossrefSearch in Google Scholar
• 32 Ciurdaru G. Ciuciu M. J. Prakt. Chem.  1979,  321:  320 
  CrossrefSearch in Google Scholar
• 33 Coppinger GM. J. Am. Chem. Soc.  1954,  76:  1372 
  CrossrefSearch in Google Scholar
• 34 Ruske W. Keilert M. Chem. Ber.  1961,  94:  2695 
  CrossrefSearch in Google Scholar
• 35 Rattananakin P. Pittman CU. Collier WE. Saebo S. Struct. Chem.  2007,  18:  399 
  CrossrefSearch in Google Scholar
• 36 Shibata Y, Aoyagi K, Takahashi H, Iwasa T, and Take T. inventors; PCT. Int. Appl.  WO2000017174.  ; Chem. Abstr. 2000, 132, 251145

CCDC 765577 (3d), 765578 (4d), and 765826 (9a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

References

• 1 Cao L. Wu Z. Zhu PC. Polym. Prepr.  1999,  39:  406 
  Search in Google Scholar
• 2 Cao L. Wu Z. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1999,  37:  2841 
  CrossrefSearch in Google Scholar
• 3 Cao L. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1999,  37:  2823 
  CrossrefSearch in Google Scholar
• 4 Wu Z. Cao L. Pittman CU. Recent Res. Dev. Polym. Sci.  1998,  2:  467 
  Search in Google Scholar
• 5 Wu Z. Cao L. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1998,  36:  861 
  CrossrefSearch in Google Scholar
• 6 Zhu PC. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1996,  34:  169 
  CrossrefSearch in Google Scholar
• 7 Wu Z. Cao L. Zhu PC. Polym. Prepr.  1997,  38:  121 
  Search in Google Scholar
• 8 Pittman CU. Wu Z. Zhu PC. J. Polym. Sci., Part A: Polym. Chem.  1997,  35:  485 
  CrossrefSearch in Google Scholar
• 9 Zhu PC. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1996,  34:  73 
  CrossrefSearch in Google Scholar
• 10 Liu Y. Pittman CU. J. Polym. Sci., Part A: Polym. Chem.  1997,  35:  3655 
  CrossrefSearch in Google Scholar
• 11 Gruseck U. Heuschmann M. Tetrahedron Lett.  1987,  28:  6027 
  CrossrefSearch in Google Scholar
• 12 Gruseck U. Heuschmann M. Chem. Ber.  1987,  120:  2065 
  CrossrefSearch in Google Scholar
• 13 Zhou A. Pittman CU. Tetrahedron Lett.  2005,  46:  3801 
  CrossrefSearch in Google Scholar
• 14 Zhu PC. Lin J. Pittman CU. J. Org. Chem.  1995,  60:  5729 
  CrossrefSearch in Google Scholar
• 15 Cao L. Ph.D. Dissertation   Mississippi State University; USA: 1999. 
• 16 Li H. MS Thesis   Mississippi State University; USA: 2005. 
• 17 Ye G. Ph.D. Dissertation   Mississippi State University; USA: 2008. 
• 18 Ye G. Henry WP. Chen C. Zhou A. Pittman CU. Tetrahedron Lett.  2009,  50:  2135 
  CrossrefSearch in Google Scholar
• 19 Zhou A. Cao L. Li H. Liu Z. Pittman CU. Synlett  2006,  201 
  Thieme Connect
• 20 Zhou A. Cao L. Li H. Liu Z. Cho H. Henry WP. Pittman CU. Tetrahedron  2006,  62:  4188 
  CrossrefSearch in Google Scholar
• 21 Diaz-Ortiz AL. Diez-Barra E. de la Hoz A. Prieto P. Moreno A. Langa F. Prange T. Neuman A. J. Org. Chem.  1995,  60:  4160 
  CrossrefSearch in Google Scholar
• 22 Zhou A. Ph.D. Dissertation   Mississippi State University; USA: 2004. 
• 23 Tohda Y. Kawashima T. Ariga M. Akiyama R. Shudoh H. Mori Y. Bull. Chem. Soc. Jpn.  1984,  57:  2329 
  CrossrefSearch in Google Scholar
• 24 Zhou A. Pittman CU. Tetrahedron Lett.  2004,  45:  8899 
  CrossrefSearch in Google Scholar
• 25 Zhou A. Pittman CU. Synthesis  2006,  37 
  Thieme Connect
• 26 Zhou A. Pittman CU. Tetrahedron Lett.  2005,  46:  2045 
  CrossrefSearch in Google Scholar
• 27 Ye G. Chen C. Chatterjee S. Collier WE. Zhou A. Song Y. Beard DJ. Pittman CU. Synthesis  2010,  141 
  Thieme Connect
• 28 Ye G. Chatterjee S. Zhou A. Barker BL. Chen C. Song Y. Pittman CU. Tetrahedron  2010,  66:  2919 
  CrossrefSearch in Google Scholar
• 29 Ye G. Chatterjee S. Zhou A. Barker BL. Chen C. Song Y. Pittman CU. Synthesis  2010,  1209 
  Thieme Connect
• 30 Ye G. Zhou A. Henry WP. Song Y. Chatterjee S. Beard DJ. Pittman CU. J. Org. Chem.  2008,  73:  5170 
  CrossrefSearch in Google Scholar
• 31 Chatterjee S. Ye G. Pittman CU. Tetrahedron Lett.  2010,  51:  1139 
  CrossrefSearch in Google Scholar
• 32 Ciurdaru G. Ciuciu M. J. Prakt. Chem.  1979,  321:  320 
  CrossrefSearch in Google Scholar
• 33 Coppinger GM. J. Am. Chem. Soc.  1954,  76:  1372 
  CrossrefSearch in Google Scholar
• 34 Ruske W. Keilert M. Chem. Ber.  1961,  94:  2695 
  CrossrefSearch in Google Scholar
• 35 Rattananakin P. Pittman CU. Collier WE. Saebo S. Struct. Chem.  2007,  18:  399 
  CrossrefSearch in Google Scholar
• 36 Shibata Y, Aoyagi K, Takahashi H, Iwasa T, and Take T. inventors; PCT. Int. Appl.  WO2000017174.  ; Chem. Abstr. 2000, 132, 251145

CCDC 765577 (3d), 765578 (4d), and 765826 (9a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.