Abstract
We report here that thioamides can distinguish C–C double bonds and C–C triple bonds chemoselectively when subjected to a reaction with pent-1-en-4-yn-3-ol derivatives in the presence of Ca(OTf)2. This protocol offers a fast, efficient, and high-yielding synthesis of functionalized thiazoles. Interestingly, this reaction offers a time-dependent formation of kinetic and thermodynamic products. The products showed stereoselectivity concerning the alkene geometry. Further, we extended this protocol to synthesize oxazoles from propargyl alcohols and ibuprofen (NSAID) was converted into amide and then subjected to oxazole formation with tert-propargyl alcohols.
Introduction
Thiazoles and oxazoles are important structural moieties, often found in natural products and biologically active or pharmaceutical compounds (Figure 1).1 For example, thiazole natural products, such as the mycothiazole,2 and cystothiazole A3 exhibit a diverse range of biological activities. Additionally, there is increasing interest in these scaffolds for material applications. Thus, the discovery of their significant pharmacological activities and their pivotal role as building blocks/synthetic intermediates have attracted the attention of chemists both in academia and industry, which stimulated the substantial interest in the chemistry and synthesis of thiazoles and of course their bio-isosteres.4 Since the popular Hantzsch thiazole synthesis,5 several catalytic methods have been developed.6,8,9 In recent years, propargyl alcohols are serving as key building blocks for constructing various organic molecules.7 Their utility was also extensively studied for the oxazole synthesis by treating with amides.7,8 However, a limited number of studies were done for thiazole synthesis from sec-propargyl alcohols as well as a couple of reports with tert-propargyl alcohols using silver triflate9a and p-toluenesulfonic acid.9b On the other hand, calcium salts have been identified as sustainable Lewis acid catalysts for various organic reactions due to their large abundance, biodegradability, non-toxic, less expensive, and moisture-stable features.10,11 Over the past 5 years, our group has been actively engaged in utilizing the Ca(II) catalysts for activating propargyl alcohols toward developing various synthetic methodologies.11a–c With this experience, we desired to develop a catalytic, synthetic method for thiazole synthesis by treating propargyl alcohols and thioamides in the presence of a Ca(II) catalyst, thereby extending this to the oxazole synthesis. Further, to advance the synthetic protocol, we wanted to subject the propargyl alcohol bearing a vinyl substitution on the propargylic carbon to reaction with thioamide; this will lead us to investigating the chemoselective cyclization of thioamides with alkene and alkyne (Scheme 1).
Figure 1.
Representative examples of natural and biologically potent thiazoles and oxazoles.
Scheme 1. Possible Ways of Chemoselective Thiazole Formation with the Substrate Having Alkene and Alkyne Groups.
Results and Discussion
As proposed (Scheme 1), we commenced the reaction of compound 1a (prepared using a reported procedure)12 and thiobenzamide 2a with Ca(OTf)2/Bu4NPF6 in 1,2-dichloroethane at rt. Since the reaction showed <5% product formation at rt (entry 1), we heated the reaction mixture in DCE (entry 2). Delightfully, 40% of the product was isolated in 6 h. Continuing beyond 6 h could not increase the product yield. Encouraged by this observation, we planned to screen the reaction conditions to increase the product yield. Accordingly, we have heated the reaction mixture in various solvents, such as acetonitrile, THF, ethanol, hexafluoroisopropanol (HFIP), and toluene (entries 3–7). Thus, we observed that the maximum yield of 3a (85%, entry 7) was obtained in toluene in 40 min. While reproducing this result, it was observed that a positional isomer 3s was initially formed (double bond away from thiazole ring, kinetic product) in 10 min, slowly isomerizing to a more conjugated system 3a (thermodynamically more stable).13 Nevertheless, in both products, the spectral data indicates that the alkyne was involved in the thiazole formation keeping the alkene intact. The chemical shift of the olefinic proton at 6.33 δ ppm in the 1H NMR spectrum indicated the stereoselective olefin (Z) formation of 3a (which was later supported by the single-crystal X-ray data). Continuing the reaction for a long time did not show any increase in the yield of 3a; also, decreasing or increasing the reaction temperature was not fruitful in obtaining a better yield. Surprisingly, the reaction also produced 3a in 60% yield by heating at 120 °C under solvent-free conditions but it took 24 h (entry 9). There was no reaction observed in the absence of a catalyst (entry 10). For other alkaline earth catalysts, Mg (OTf)2 gave a 40% yield in 24 h, and Ca (NTf2)2 gave a complex TLC (entries 11 and 12). The Brønsted acid catalyst (p-TSA) gave 58% product formation (entry 13). Transition-metal catalysts FeCl3, Cu (OTf)2, and Cu (OAc)2 were not found to be suitable under these conditions (entries 14–16). Based on these optimization studies, we realized that entry 7 (Table 1) is the best condition to obtain the maximum yield of 3a.
Table 1. Optimization of Reaction Conditionsa.
| entry | reaction conditions | yield (%)b |
|---|---|---|
| 1 | Ca(OTf)2/Bu4NPF6 (5/5), DCE, rt., 24 h | <5 |
| 2 | Ca(OTf)2/Bu4NPF6 (5/5), DCE, 90 °C, 6 h | 40 |
| 3 | Ca(OTf)2/Bu4NPF6 (5/5), CH3CN, 90 °C, 5 h | 60 |
| 4 | Ca(OTf)2/Bu4NPF6 (5/5), THF, 90 °C, 2 h | 80 |
| 5 | Ca(OTf)2/Bu4NPF6 (5/5), EtOH, 90 °C, 3 h | 40 |
| 6 | Ca(OTf)2/Bu4NPF6 (5/5), HFIP, 80 °C, 4 h | 63 |
| 7c | Ca(OTf)2/Bu4NPF6 (5/5), toluene, 120 °C, 40 min | 85 |
| 8 | Ca(OTf)2/Bu4NPF6 (5/5), toluene, 100 °C, 4 h | 75 |
| 9 | Ca(OTf)2/Bu4NPF6 (5/5), neat, 120 °C, 24 h | 60 |
| 10 | toluene, 120 °C, 24 h | nr |
| 11 | Mg(OTf)2/Bu4NPF6 (5/5), toluene, 120 °C, 24 h | 40 |
| 12 | Ca(NTf2)2/Bu4NPF6 (5/5), toluene, 120 °C, 1 h | $ |
| 13 | p-TSA (5), toluene, 120 °C, 6 h | 58 |
| 14 | FeCl3 (5), toluene, 120 °C, 5 h | $ |
| 15 | Cu(OTf)2 (5), toluene, 120 °C, 24 h | 35 |
| 16 | Cu(OAc)2 (5), toluene, 120 °C, 24 h | <5 |
Reaction conditions: 1a (0.28 mmol), 2a (0.42 mmol), all reactions were monitored up to 24 h; oil bath temperatures mentioned.
Isolated yields.
Optimum condition. $ = complex TLC; nr = no reaction.
Having the optimum reaction conditions in hand, we then planned to check the generality of this protocol (Scheme 2). Initially, we treated propargyl alcohol 1a with para-substituted thiobenzamides bearing trifluoromethyl, methyl, and methoxy groups under standard conditions and witnessed that all of them showed excellent reactivity and furnished the corresponding fully conjugated 4-vinyl thiazoles 3a-3d in good yields. Further, a gram-scale synthesis of 3d (1.14 g) was performed, and its single crystal-X-ray data was obtained to confirm the structure to avoid ambiguity.14 Next, we subjected (E)-1,3,5-triphenylpent-1-en-4-yn-3-ol (1b) and substituted thiobenzamides under the reaction conditions to obtain the more conjugated thiazoles 3e to 3h in good yields. The other substrate (E)-3-(4-chlorophenyl)-1,5-diphenylpent-1-en-4-yn-3-ol (1c) also showed excellent reactivity with thiobenzamide and 4-methyl thiobenzamide to furnish the corresponding fully conjugated thiazoles 3i and 3j. Next, we synthesized thiazole 3k in 81% yield from (E)-1,5-diphenyl-3-(p-tolyl)pent-1-en-4-yn-3-ol (1d) and thiobenzamide 2a under standard conditions. Another fully conjugated thiazole 3l was prepared from (E)-1,5-diphenyl-3-(thiophen-2-yl)pent-1-en-4-yn-3-ol (1e) with thiobenzamide 2a in 80% yield after 2 h. During the synthesis of these thermodynamically more stable products (a trisubstituted olefin in conjugation with thiazoles) 3a to 3l, we observed that in all the cases, another product (a fast forming isomer) was forming, which slowly converts to the compounds mentioned above with time. Therefore, we also wanted to isolate these fast-forming isomers (kinetic products). Accordingly, (E)-3-(4-ethoxyphenyl)-1,5-diphenylpent-1-en-4-yn-3-ol (1f) was subjected to standard reaction conditions with thiobenzamide 2a and isolated the first product 3m in 86% yield after 25 min. The 1H NMR spectrum of 3m indicated that the disubstituted alkene is not in conjugation with thiazole and has a trans geometry. Similarly, (E)-3-(furan-2-yl)-1,5-diphenylpent-1-en-4-yn-3-ol (1g) was also investigated against a variety of thioamides under the reaction conditions and produced the corresponding initial thiazole compounds 3n to 3p in good yields in 40–50 min. The same observation was also made with 1g and 4-(trifluoromethyl) benzothioamide in 40 min; further continuing the reaction up to 70 min produced an inseparable mixture of products 3q and 3r in a 1: 1.25 ratio, which again confirms that with time, 3q is isomerizing to a more conjugated system 3r.15 As 3a was formed from 1a and 2a after 40 min, we repeated this reaction again and stopped the reaction after 10 min to isolate the thiazole 3s in 75% yield. It was also observed that under the standard conditions, 3s was converted to 3a. After developing the reactions of 1 with various thioamides, we tried to extend the same with benzamide; however, compound 1 gave an inseparable mixture of compounds with benzamide under these conditions.
Scheme 2. Substrate Scope of Functionalized Thiazoles 3.
We then investigated the reactivity of tertiary propargyl alcohol 4 in the thiazole formation under standard conditions (Scheme 3). Gratefully, the reaction of 1,1,3-triphenylprop-2-yn-1-ol (4a) gave a nearly quantitative yield of thiazole 5a under standard reaction conditions. When we replaced toluene with water, the reaction gave the same yield but took 24 h. Interestingly, solvent-free conditions provided a similar yield of 5a in 25 min. Albeit the three conditions (heating in toluene, water, and neat) gave comparable yields, the reaction in the water took a long time. Next, we studied that substituted aryl thioamides 2 bearing electron-donating groups gave higher yields than electron-withdrawing groups (though the difference is slight) to furnish thiazoles 5a–5d under standard conditions. Then, we switched to see the scope of various substituted propargyl alcohols having aryl, alicyclic, and aliphatic groups and observed the excellent reactivity and the yields of corresponding thiazoles 5e–5p. It is worth noting that compounds 5a, 5e, 5j, 5 k, 5l, 5 m, 5n, and 5o were also produced in similar yields under solvent-free conditions. Surprisingly, the reaction of 1-(phenylethynyl)cycloheptan-1-ol with benzothiamide did not result in the desired thiazole formation in toluene; instead, the propargyl alcohol underwent a rapid Rupe elimination13 to give the corresponding 1,3-enyne 5q. Nevertheless, we have circumvented this problem by performing the reaction under the solvent-free condition to get the desired thiazole 5r in 81% yield.
Scheme 3. Substrate Scope of tert-Propargyl Alcohols with Thioamides for the Synthesis of Thiazoles.
Unless mentioned, all the reactions were heated in toluene at 120 °C (oil bath temperature); $ = heated at 120 °C under solvent-free conditions.
After the successful demonstration of thiazole synthesis, we were curious to extend this strategy to the oxazole synthesis by treating propargyl alcohols 4 with amide 6 (Scheme 4). Initial attempts under solvent-free conditions gave the oxazole 7a in 85% yield and in aqueous conditions gave poor yields (<10%) even after 24 h. The standard conditions (heating in toluene) provided a nearly quantitative yield of 7a in 30 min. The structure of 7a was further confirmed by obtaining its single-crystal X-ray data.14 With the success of this example, we have studied the scope of both the substituted aryl amides 6 and propargyl alcohols 4 and obtained the desired oxazoles 7b–7o in excellent yields (Scheme 4). It is worth mentioning that the ortho-substituted (methyl) benzamide, when reacted with propargyl alcohol 4a, furnished the corresponding oxazole 7e, which showed the atropisomerism in the 1H NMR spectrum; we have also obtained the crystal structure of 7e.14
Scheme 4. Substrate Scope of tert-Propargyl Alcohols with Amides for the Synthesis of Oxazoles.
Additionally, we have converted ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), to corresponding amide 8 quantitatively by treating with thionyl chloride and aqueous ammonia. Then, the ibuprofen amide 8 was subjected to standard reaction conditions with propargyl alcohol 4a and the corresponding thiazole 9 was obtained in a 65% yield. Similarly, compound 10 was also made in a 69% yield (Scheme 5).
Scheme 5. Amidation of Ibuprofen and Application to Oxazole Synthesis Using Our Protocol.
Next, we subjected thiazole 3d to dioxidation with an excess of m-chloroperbenzoic acid and obtained the corresponding thiazole S, S-dioxide 11 in 81% yield after 12 h (Scheme 6).16 It is important to note that the double bond of 3d did not react with m-CPBA even after 12 h, probably due to the extended conjugation obtained.
Scheme 6. Dioxidation of Thiazole 3d.
The reaction mechanism for this chemo- and stereoselective cyclization reaction is depicted in Scheme 7. Initially, the tautomer of thioamide reacts with activated (with calcium catalyst) propargyl alcohol 1 to form allene (A) by removing water. Then, an intramolecular, regioselective 5-exo dig cyclization of allene produces the thiazole 3. With time, the double bond isomerizes to a highly conjugated (thermodynamically stable) thiazole 3′.
Scheme 7. Proposed Reaction Mechanism.
While synthesizing these thiazoles, we observed the luminescence of all the products under long UV light. Hence, we have selected 10 compounds to study their photophysical properties such as UV–visible and fluorescence characteristics. Four of them were benzhydryl thiazoles (5a, 5d, 5f, 5h), one was cycloheptyl thiazole (5r), one was phenyl alkyl thiazole (5o), two were vinyl thiazoles (3c and 3e), and the last two were furyl allyl thiazoles (3p and 3o). The UV–Visible spectra of these compounds in acetonitrile exhibited the maximum absorption wavelength (λmax) at 252–328 nm, as shown in Table 2 and Figure 2. It should be noted that the λmax covered all of the UV region, i.e., 5d, 5f, 3c, and 3e showed in the UV-A region with wavelengths above 315 nm, 5a, 5o, and 3o showed in the UV-B region at 312, 310, and 314 nm, respectively, and 5h and 5r showed in the UV-C region at 297 and 252 nm, respectively. Thiazoles having extended conjugation on C4, such as furyls (3o, 3p), vinyl (3c, 3e), and benzhydryl (5a, 5o, 5d, 5f), exhibited an enhanced red shift compared to those with alkyl and aromatic substitutions (5h, 5r) due to the diminishment of the energy gap between π → π* interactions. The fluorescence spectra of 5h and 5r showed the emission maxima (λem) at 367 and 355 nm, respectively; the remaining 5a, 5o, 5d, 5f, 3c, 3p, 3e, and 3o emitted at 399–418 nm, which indicates the role of the electron-donating group on the thiazole rings. The absorption peak wavelengths (λabs), calculated molar extinction coefficient (ε), and emission peak wavelengths in acetonitrile are summarized in Table 2. Based on these observations, these compounds may be suitable for appropriate modifications so that they may be useful in the future as fluorescent probes.17
Table 2. Absorbance, Extinction Coefficient (ε), and Emission Wavelengths of Listed Compounds.
| entry | compound | λabs (nm)a | absorbance at λmax | λemm (nm)b | ε (1 × 104 M–1 cm–1) |
|---|---|---|---|---|---|
| 1 | 5a | 317 | 0.33 | 399 | 1.00 |
| 2 | 5o | 310 | 0.34 | 400 | 1.03 |
| 3 | 5d | 319 | 0.36 | 408 | 1.09 |
| 4 | 5f | 318 | 0.65 | 418 | 1.96 |
| 5 | 5h | 297 | 0.41 | 367 | 1.24 |
| 6 | 5r | 252 | 0.33 | 355 | 1.00 |
| 7 | 3c | 328 | 0.42 | 418 | 1.27 |
| 8 | 3p | 273 | 0.96 | 410 | 2.90 |
| 9 | 3e | 273 | 0.43 | 415 | 1.30 |
| 10 | 3o | 320 | 0.40 | 406 | 1.21 |
Figure 2.
Absorbance (a) and fluorescence emission (b) spectra of compounds 5a, 5o, 5d, 5f, 5h, 5r, 3c, 3p, 3e, and 3o in acetonitrile recorded at a concentration of 3.3 × 10–5 M at room temperature (25 °C).
Conclusions
In conclusion, we have described chemo- and stereoselective thiazole synthesis from propargyl alcohols bearing alkene at the propargylic carbon. Interestingly, the reaction showed the formation of time-dependent kinetic and thermodynamic products. The products formed were also stereoselective concerning the geometry of the olefins. This reaction was found to be selective toward alkyne over alkene. We also extended this protocol to the solvent-free synthesis of selected thiazoles with tert-propargyl alcohols, further proving that the reaction conditions were used to make the oxazoles from amides by heating them in toluene. A gram-scale synthesis was demonstrated. A non-steroidal anti-inflammatory drug (NSAID), ibuprofen, was converted into amide and subjected to the corresponding oxazole formation using this protocol. Selective oxidation of 3d to corresponding S,S-dioxide was achieved. Preliminary photophysical properties were also studied. The selective reactivities, fast and high reaction yields, broad substrate scope, use of an alkaline earth catalyst, and atom economy (96.21%) are the other highlights of the work.
Experimental Section
General
Unless otherwise noted, all reagents were used as received from commercial suppliers. Reactions were performed in oven-dried glassware with magnetic stirring. All the reactions were monitored using TLC with aluminum sheets of silica gel 60 F254 from Merck. TLC plates were visualized with UV light (254 nm), iodine treatment, and a p-anisaldehyde stain. Column chromatography was carried out using silica gel 100–200 mesh as the stationary phase. NMR spectra were recorded at 500 and 400 MHz (1H) and at 125 and 100 MHz (13C), respectively, on the Avance Bruker spectrometer. Chemical shifts (δ) are reported in ppm, using the residual solvent peak in CDCl3 (1H: δ = 7.26 and 13C: δ = 77.16 ppm) as an internal standard and coupling constants (J) are given in Hz. HRMS spectra were recorded using ESI-TOF techniques. Melting points were measured with LABINDIA mepa melting apparatus. Single crystal X-ray diffraction data were collected in a Bruker D8-Quest diffractometer. Unless mentioned, all the chemicals were purchased from commercial sources. Propargyl alcohols were prepared using the reported procedures.12,19
General Experimental Procedure (1) for the Synthesis of Thiazole 3
To a mixture of propargyl alcohol 1 (0.28 mmol) and thiobenzamide 2 (0.42 mmol) was added Ca(OTf)2/Bu4NPF6 (5/5 mol %) and heated in toluene at 120 °C. After completion of the reaction (monitored by TLC), the crude product was purified by silica-gel column chromatography (1% EtOAc in petroleum ether) to obtain the corresponding thiazole 3 as a pure product.
General Experimental Procedure (2) for the Synthesis of Thiazole 5
To a mixture of propargyl alcohol 4 (0.35 mmol) and thiobenzamide 2 (0.52 mmol) was added Ca(OTf)2/Bu4NPF6 (5/5 mol %) and heated at 120 °C under neat conditions or heated in toluene (as specified). After completion of the reaction (monitored by TLC), the crude product was purified by silica-gel column chromatography (1% EtOAc in petroleum ether) to obtain the corresponding thiazole 5 as a pure product.
General Experimental Procedure (3) for the Synthesis of Oxazole 7
To a mixture of propargyl alcohol 4 (0.35 mmol) and benzamide 6 (0.52 mmol) was added Ca(OTf)2/Bu4NPF6 (5/5 mol %) and heated at 120 °C in toluene (as specified). After completion of the reaction (monitored by TLC), the crude product was purified by silica-gel column chromatography (1% EtOAc in petroleum ether) to obtain the corresponding thiazole 7 as a pure product.
(E)-2-Phenyl-4-(1-phenyl-3-(p-tolyl)prop-1-en-1-yl)-5-(p-tolyl)thiazole (3a)
Following the general experimental procedure (1), compound 3a was obtained as a white solid (115 mg, 85%); mp: 83–84 °C; 1H NMR (500 MHz, CDCl3): δ 7.93–7.91 (m, 2H), 7.36–7.31 (m, 6H), 7.21–7.18 (m, 2H), 7.14–7.10 (m, 2H), 7.01 (d, J = 7.60 Hz, 2H), 6.91 (d, J = 6.95 Hz, 2H), 6.79 (d, J = 7.85 Hz, 2H), 6.33–6.29 (m, 1H), 3.16 (d, J = 7.20 Hz, 2H), 2.26 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.2, 149.0, 138.1, 137.1, 136.0, 135.5, 135.4, 133.8, 132.0, 130.0, 129.5, 129.1, 129.0, 128.9, 128.6, 128.4, 128.3, 127.3, 126.7, 126.6, 125.4, 35.9, 21.3, 21.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C32H28NS]+: 458.1937; found: 458.1933.; IR (film): νmax 3014, 2918, 2850, 1598, 1492, 813, 755, 716 cm–1.
(E)-4-(1-Phenyl-3-(p-tolyl)prop-1-en-1-yl)-5-(p-tolyl)-2-(4-(trifluoromethyl)phenyl)thiazole (3b)
Following the general experimental procedure (1), compound 3b was obtained as a brown liquid (124 mg, 80%); 1H NMR (500 MHz, CDCl3): δ 8.09 (d, J = 8.10 Hz, 2H), 7.68 (d, J = 8.25 Hz, 2H), 7.40–7.38 (m, 4H), 7.29–7.25 (m, 2H), 7.23–7.20 (m, 1H), 7.09 (d, J = 7.95 Hz, 2H), 6.98 (d, J = 7.80 Hz, 2H), 6.85 (d, J = 7.90 Hz, 2H), 6.40 (t, J = 7.30 Hz, 1H), 3.21 (d, J = 7.35 Hz, 2H), 2.33 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.2, 149.5, 140.1, 138.5, 137.3, 136.9 (2), 135.5, 135.3, 132.2, 129.7, 129.6, 129.2, 129.1, 128.6, 128.5, 128.3, 127.4, 126.7, 126.6, 126.4, 125.9, 124.4, 122.7, 35.9, 21.3, 21.1 ppm; 19F NMR (376 MHz, CDCl3): δ – 62.6 (s); HRMS (ESI-TOF) m/z: [M + H]+calculated for [C33H27F3NS]+: 526.1811; found: 526.1810.
(E)-4-(1-Phenyl-3-(p-tolyl)prop-1-en-1-yl)-2,5-di-p-tolylthiazole (3c)
Following the general experimental procedure (1), compound 3c was obtained as white solid (116 mg, 83%); mp: 167–168 °C; 1H NMR (500 MHz, CDCl3): δ 7.87 (d, J = 7.95 Hz, 2H), 7.41–7.37 (m, 4H), 7.27 (d, J = 7.25 Hz, 2H), 7.24–7.20 (m, 3H), 7.07 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 7.85 Hz, 2H), 6.85 (d, J = 7.80 Hz, 2H), 6.37 (t, J = 7.25 Hz, 1H), 3.22 (d, J = 7.30 Hz, 2H), 2.39 (s, 3H) 2.32 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.4, 148.8, 140.3, 140.2, 137.9, 137.2, 135.6, 135.4, 131.9, 131.2, 129.6, 129.4, 129.0, 128.6, 128.4, 128.2, 127.3, 126.7, 126.5, 35.9, 21.5, 21.3, 21.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C33H30NS]+; 472.2093; Found; 472.2099.
(E)-2-(4-Methoxyphenyl)-4-(1-phenyl-3-(p-tolyl)prop-1-en-1-yl)-5-(p-tolyl)thiazole (3d)
Following the general experimental procedure (1), compound 3d was obtained as yellow solid (123 mg, 85%); mp: 134–135 °C; 1H NMR (500 MHz, CDCl3): δ 7.93–7.91 (m, 2H), 7.41–7.37 (m, 4H), 7.27–7.23 (m, 2H), 7.21–7.18 (m, 1H), 7.06 (d, J = 8.0 Hz, 2H), 6.97–6.93 (m, 4H), 6.85 (d, J = 7.95 Hz, 2H), 6.36 (t, J = 7.30 Hz, 1H), 3.84 (s, 3H), 3.23 (d, J = 7.25 Hz, 2H) 2.31 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.1, 161.2, 148.6, 140.3, 137.9, 137.2, 135.6, 135.4, 135.0, 131.9, 129.4, 129.0, 128.6, 128.4, 128.2, 128.1, 127.3, 126.8, 126.7, 114.3, 55.5, 35.9, 21.3, 21.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C33H30NOS]+: 488.1970; found: 488.2046.; IR (film): νmax 2918, 1686, 1602, 1248, 819, 740 cm–1.
(E)-4-(1,3-Diphenylprop-1-en-1-yl)-2,5-diphenylthiazole (3e)
Following the general experimental procedure (1), compound 3e was obtained as a yellow liquid (104 mg, 75%); 1H NMR (500 MHz, CDCl3): δ 8.01–7.99 (m, 2H), 7.51–7.49 (m, 2H), 7.43–7.40 (m, 5H), 7.28–7.25 (m, 5H), 7.22–7.18 (m, 2H), 7.16–7.10 (m, 3H), 6.96 (d, J = 6.90 Hz, 2H), 6.40 (t, J = 7.30 Hz, 1H), 3.28 (d, J = 7.35 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 165.7, 149.3, 140.2, 135.9, 135.7, 133.7, 131.8, 130.1, 129.6, 129.0, 128.8, 128.7, 128.5, 128.4, 128.1, 127.4, 126.7, 126.6, 126.0, 36.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C30H24NS]+: 430.1624; found; 430.1643.
(E)-4-(1,3-Diphenylprop-1-en-1-yl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)thiazole (3f)
Following the general experimental procedure (1), compound 3f was obtained as a brown liquid (128 mg, 80%); 1H NMR (500 MHz, CDCl3): δ 8.10 (d, J = 8.25 Hz, 2H), 7.69 (d, J = 8.45 Hz, 2H), 7.51–7.49 (m, 2H), 7.29–7.28 (m, 3H), 7.24–7.22 (m, 2H), 7.20–7.17 (m, 2H), 7.15–7.12 (m, 2H), 6.96 (d, J = 7.05 Hz, 2H), 6.42 (t, J = 7.35 Hz, 1H), 3.27 (d, J = 7.35 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 163.7, 149.9, 140.0, 137.2, 136.8, 135.5, 132.0, 131.4, 128.9, 128.7, 128.5, 127.5, 126.7, 127.3, 126.8, 126.7, 126.1, 126.0, 36.4 ppm; 19F NMR (376 MHz, CDCl3): −62.7 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C31H23F3NS]+: 498.1498; found: 498.1499.
(E)-4-(1,3-Diphenylprop-1-en-1-yl)-5-phenyl-2-(p-tolyl)thiazole (3g)
Following the general experimental procedure (1), compound 3g was obtained as a yellow liquid (93 mg, 65%); 1H NMR (500 MHz, CDCl3): δ 7.98–7.96 (m, 2H), 7.89 (d, J = 8.20 Hz, 2H), 7.50–7.48 (m, 2H), 7.41 (d, J = 7.25 Hz, 2H), 7.31–7.28 (m, 3H), 7.27–7.26 (m, 2H), 7.23–7.22 (m, 3H), 7.18–7.14 (m, 2H), 6.97–6.95 (m, 2H), 6.39 (t, J = 7.30 Hz, 1H), 3.28 (d, J = 7.30 Hz, 2H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 185.9, 165.9, 149.2, 145.6, 140.4, 140.2, 135.8, 135.3, 132.9, 131.9, 131.8, 131.2, 129.7 (2), 128.8, 128.7, 128.4 (2), 128.3, 128.0, 127.3, 126.7, 126.6, 126.0, 36.4, 21.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C31H26NS]+: 444.1780; found: 444.1777.
(E)-4-(1,3-Diphenylprop-1-en-1-yl)-2-(4-methoxyphenyl)-5-phenylthiazole (3h)
Following the general experimental procedure (1), compound 3h was obtained as a yellow liquid (126 mg, 85%); 1H NMR (500 MHz, CDCl3): δ 7.94–7.92 (m, 2H), 7.49–7.48 (m, 2H), 7.42–7.40 (m, 2H), 7.28–7.22 (m, 2H), 7.17–7.11 (m, 4H), 6.96–6.94 (m, 5H), 6.39 (t, J = 7.30 Hz, 1H), 3.85 (s, 3H), 3.28 (d, J = 7.30 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 165.6, 161.3, 149.0, 140.2, 135.8, 134.9, 131.9, 131.7, 129.3, 128.8, 128.7, 128.4 (2), 128.3, 128.2, 127.9, 127.3, 126.7, 126.0, 114.3, 55.5, 36.4 ppm; HR-MS (ESI-TOF) m/z: [M + H]+calculated for [C31H26NOS]+: 460.1730; found: 460.1734.
(E)-4-(1-(4-Chlorophenyl)-3-phenylprop-1-en-1-yl)-2,5-diphenylthiazole (3i)
Following the general experimental procedure (1), compound 3i was obtained as a yellow liquid (104 mg, 75%); 1H NMR (500 MHz, CDCl3): δ 8.00–7.98 (m, 2H), 7.46–7.40 (m, 5H), 7.32–7.30 (m, 2H), 7.27–7.25 (m, 3H), 7.23–7.20 (m, 2H), 7.18–7.15 (m, 2H), 7.13–7.11 (m, 1H), 6.97–6.95 (m, 2H), 6.37 (t, J = 7.35 Hz, 1H), 3.28 (d, J = 7.30 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 165.9, 148.8, 139.9, 138.7, 136.1, 134.7, 133.6, 133.1, 132.4, 131.6, 130.2, 129.0, 128.8, 128.7, 128.6, 128.5, 128.3 (2), 127.9, 126.6, 126.1, 36.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C30H23ClNS]+: 464.1234; found: 464.1235; IR (film): νmax 3059, 3026, 2922, 2852, 2188, 1686, 1596, 1490, 760, 692 cm–1.
(E)-4-(1-(4-Chlorophenyl)-3-phenylprop-1-en-1-yl)-5-phenyl-2-(p-tolyl)thiazole (3j)
Following the general experimental procedure (1), compound 3j was obtained as a yellow liquid (112 mg, 83%); 1H NMR (500 MHz, CDCl3): δ 7.88 (d, J = 8.05 Hz, 2H), 7.46–7.44 (m, 2H), 7.33–7.31 (m, 2H), 7.28–7.27 (m, 3H), 7.24–7.21 (m, 4H), 7.18–7.15 (m, 2H), 6.96 (d, J = 7.35 Hz, 2H), 6.37 (t, J = 7.35 Hz, 1H), 3.28 (d, J = 7.30 Hz, 2H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 166.1, 148.6, 140.5, 140.0, 138.7, 135.6, 134.7, 133.1, 132.4, 131.7, 131.0, 130.2, 129.7, 128.8, 128.7, 128.6, 128.5, 128.3, 128.2, 128.0, 126.6, 126.1, 36.4, 21.6 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C31H25ClNS]+: 478.1391; found; 478.1392.
(E)-2,5-Diphenyl-4-(3-phenyl-1-(p-tolyl)prop-1-en-1-yl)thiazole (3k)
Following the general experimental procedure (1), compound 3k was obtained as a colorless liquid (113 mg, 81%); 1H NMR (500 MHz, CDCl3): δ 7.93–7.91 (m, 2H), 7.44–7.41 (m, 2H), 7.36–7.32 (m, 4H), 7.23–7.21 (m, 2H), 7.19–7.16 (m, 3H), 7.09–7.06 (m, 2H), 7.04–6.69 (m, 2H), 6.87 (t, J = 10.65 Hz, 2H), 6.29–6.26 (m, 1H), 3.17 (d, J = 7.25 Hz, 2H), 2.22 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 165.6, 149.5, 140.3, 137.3, 137.1, 135.7, 135.6, 133.8, 131.8, 130.8, 130.1, 129.2, 129.0, 128.8, 128.7, 128.5, 128.4 (2), 128.1, 126.7, 126.5, 126.0, 36.3, 21.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C31H26NS]+: 444.1780; found: 444.1780.
(E)-2,5-Diphenyl-4-(3-phenyl-1-(thiophen-2-yl)prop-1-en-1-yl)thiazole (3l)
Following general experimental procedure (1), compound 3l was obtained as a yellow liquid (111 mg, 80%); 1H NMR (500 MHz, CDCl3): δ 8.02–8.00 (m, 2H), 7.53–7.51 (m, 2H), 7.45–7.42 (m, 3H), 7.31–7.28 (m, 3H), 7.17–7.15 (m, 1H), 7.14–7.09 (m, 3H), 6.94–6.92 (m, 2H), 6.90–6.88 (m, 1H), 6.83–6.82 (m, 1H), 6.35 (t, J = 7.45 Hz, 1H), 3.23 (d, J = 7.40 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 165.8, 148.2, 144.8, 139.8, 136.0, 133.7, 131.6, 130.4, 130.3, 130.2, 129.0, 128.9, 128.7, 128.4 (2), 128.3, 127.5, 126.6, 126.1, 125.2, 124.3, 36.0 ppm; HR-MS (ESI-TOF) m/z: [M + H]+calculated for [C28H22NS2]+: 436.1188; found: 436.1182.
(E)-4-(1-(4-Ethoxyphenyl)-3-phenylallyl)-2,5-diphenylthiazole (3m)
Following the general experimental procedure (1), compound 3m was obtained as a yellow liquid (116 mg, 86%); 1H NMR (500 MHz, CDCl3): δ 7.99–7.98 (m, 2H), 7.46–7.43 (m, 5H), 7.41–7.39 (m, 3H), 7.37 (d, J = 7.45 Hz, 2H), 7.33 (d, J = 8.65 Hz, 2H), 7.26 (t, J = 7.40 Hz, 2H), 7.17 (t, J = 7.3 Hz, 1H), 6.89 (q, J = 15.85 Hz, 1H), 6.84 (d, J = 8.7 Hz, 2H), 6.39 (d, J = 18.95 Hz, 1H), 4.98 (d, J = 8.05 Hz, 1H), 4.00 (q, J = 14.00 Hz, 2H), 1.38 (t, J = 6.95 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 165.8, 157.7, 153.3, 137.5, 135.0, 134.0, 133.1, 131.8, 130.3, 129.9, 129.8, 129.4, 128.9, 128.8, 128.5, 128.3, 127.2, 126.6, 126.5, 114.5, 63.5, 47.9, 15.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C32H28NOS]+: 474.1886; found: 474.1882.
(E)-4-(1-(Furan-2-yl)-3-phenylallyl)-2,5-diphenylthiazole (3n)
Following the general experimental procedure (1), compound 3n was obtained as a yellow liquid (118 mg, 86%); 1H NMR (500 MHz, CDCl3): δ 7.98–7.96 (m, 2H), 7.53–7.51 (m, 2H), 7.46–7.44 (m, 2H), 7.43–7.42 (m, 1H), 7.42–7.40 (m, 2H), 7.40–7.37 (m, 3H), 7.35 (d, J = 0.95 Hz, 1H), 7.29–7.24 (m, 2H), 7.21–7.18 (m, 1H), 6.80 (q, J = 15.85 Hz, 1H), 6.47 (d, J = 16.35 Hz, 1H), 6.33–6.32 (m, 1H), 6.23–6.22 (m, 1H), 5.12 (d, J = 8.05 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 166.1, 155.6, 150.7, 141.7, 137.2, 133.9, 131.6, 131.5, 130.0, 129.8, 129.2, 128.9, 128.5 (2), 127.5, 126.6, 110.5, 106.8, 43.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C28H22NOS]+: 420.1417; found; 420.1415.; IR(film): νmax 2937, 2251, 1599, 1445, 1245, 760, 692 cm–1.
(E)-4-(1-(Furan-2-yl)-3-phenylallyl)-5-phenyl-2-(p-tolyl)thiazole (3o)
Following the general experimental procedure (1), compound 3o was obtained as a colorless liquid (122 mg, 85%); 1H NMR (500 MHz, CDCl3): δ 7.86 (d, J = 8.15 Hz, 2H), 7.52–7.50 (m, 2H), 7.46–7.43 (m, 2H), 7.41–7.39 (m, 2H), 7.37–7.35 (m, 2H), 7.29–7.25 (m, 2H), 7.23–7.18 (m, 3H), 6.80 (q, J = 15.85 Hz, 1H), 6.46 (d, J = 15.85 Hz, 1H), 6.33–6.32 (m, 1H), 6.22 (d, J = 3.2 Hz, 1H), 5.11 (d, J = 8.10 Hz, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 166.3, 155.6, 150.5, 141.6, 140.2, 137.2, 133.4, 131.6, 131.3, 129.8, 129.6, 129.3, 128.9, 128.5, 128.4, 127.5, 126.6, 126.5, 110.5, 106.8, 43.1, 22.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H24NOS]+: 434.1573; found: 434.1572. ; IR (film): νmax 3024, 2919, 2849, 1595, 1499, 1483, 815, 751, 691 cm–1.
(E)-4-(1-(Furan-2-yl)-3-phenylallyl)-2-(4-methoxyphenyl)-5-phenylthiazole (3p)
Following the general experimental procedure (1), compound 3p was obtained as a colorless liquid (132 mg, 88%); 1H NMR (500 MHz, CDCl3): δ 7.91–7.90 (m, 2H), 7.51–7.49 (m, 2H), 7.45–7.42 (m, 2H), 7.40–7.35 (m, 4H), 7.29–7.25 (m, 2H), 7.21–7.18 (m, 1H), 6.94–6.93 (m, 2H), 6.79 (q, J = 15.85 Hz, 1H), 6.46 (d, J = 15.85 Hz, 1H), 6.33–6.32 (m, 1H), 6.22–6.21 (m, 1H), 5.10 (d, J = 8.05 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 166.0, 161.1, 155.6, 150.4, 141.6, 137.2, 132.9, 131.6, 129.8, 129.2, 128.9, 128.5, 128.3, 128.1, 127.5, 126.9, 126.6, 114.2, 110.5, 106.8, 55.5, 43.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H24NO2S]+: 450.1522; found: 450.1527.
(E)-4-(1-(Furan-2-yl)-3-phenylallyl)-5-phenyl-2-(4-(trifluoromethyl)phenyl)thiazole (3q/3r)
Following the general experimental procedure (1), compounds 3q/3r were obtained as an inseparable mixture (1:1.25) and colorless liquid (129 mg, 81%); 1H NMR (500 MHz, CDCl3): δ 8.11–8.06 (m, 4H), 7.70–7.66 (m, 4H), 7.53–7.49 (m, 4H), 7.47–7.41 (m, 3H), 7.40–7.34 (m, 4H), 7.33–7.31 (m, 3H), 7.29–7.26 (m, 3H), 7.22–7.19 (m, 1H), 7.17–7.14 (m, 2H), 7.12–7.09 (m, 1H), 6.94 (d, J = 7.25 Hz, 2H), 6.81–6.76 (m, 1H), 6.54 (t, J = 7.65 Hz, 1H), 6.47 (d, J = 15.85 Hz, 1H), 6.33–6.30 (m, 2H), 6.22–6.21 (m, 1H), 5.99 (d, J = 2.9 Hz, 1H), 5.13 (d, J = 8.00 Hz, 1H), 3.24 (d, J = 7.65 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 164.1, 163.7, 155.4, 153.4, 151.4, 147.3, 142.2, 141.8, 139.8, 137.7, 137.0, 136.9, 136.7, 135.1, 131.9, 131.2, 131.0, 129.8, 129.2, 129.0, 128.8 (2), 128.6 (2), 128.5, 128.4, 127.6, 126.7, 126.6, 126.2, 126.1 (2), 111.5, 110.5, 108.2, 106.8, 43.0, 35.6 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H21F3NOS]+: 488.1290; found: 488.1292.
(E)-2-Phenyl-4-(1-phenyl-3-(p-tolyl)allyl)-5-(p-tolyl)thiazole (3s)
Following the general experimental procedure (1), compound 3s was obtained as a colorless liquid (102 mg, 75%); 1H NMR (500 MHz, CDCl3): δ 8.02–8.00 (m, 2H), 7.47–7.43 (m, 5H), 7.38 (d, J = 8.10 Hz, 2H), 7.35–7.34 (m, 2H), 7.32–7.31 (m, 3H), 7.26–7.22 (m, 2H), 7.11 (t, J = 9.50 Hz, 2H), 6.89 (dd, J = 15.85, 8.2 Hz, 1H), 6.38 (d, J = 16.3 Hz, 1H), 5.04 (d, J = 8.15 Hz, 1H), 2.44 (s, 3H), 2.33 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 165.5, 152.9, 143.3, 138.3, 137.0, 134.7, 134.1, 133.4, 131.7, 130.4, 129.8, 129.7, 129.5, 129.2, 128.9, 128.5, 127.6, 126.5, 126.4, 48.7, 21.4, 21.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C32H28NS]+: 458.1937; found: 458.1940.
4-Benzhydryl-2,5-diphenylthiazole (5a)9a,8m
Following the general experimental procedure (2), compound 5a was obtained as a yellow solid (135 mg, 95%); mp: 153–154 °C; 1H NMR (500 MHz, CDCl3): δ 7.95–7.93 (m, 2H), 7.43–7.41 (m, 4H), 7.41–7.40 (m, 2H), 7.38–7.37 (m, 6H), 7.28 (d, J = 7.40 Hz, 4H), 7.19 (d, J = 7.45 Hz, 2H), 5.56 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 165.5, 152.9, 143.6, 134.1, 134.0, 131.8, 129.9 (2), 129.3, 128.9, 128.4, 128.3, 126.5, 126.4, 50.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C28H22NS]+: 404.1467; found: 404.1472; IR (film): νmax 3058, 1597, 1452, 744, 689 cm–1.
4-Benzhydryl-5-phenyl-2-(p-tolyl)thiazole (5b)
Following the general experimental procedure (2), compound 5b was obtained as a colorless solid (133 mg, 90%); mp: 211–212 °C; 1H NMR (500 MHz, CDCl3): δ 7.82 (d, J = 8.10 Hz, 2H), 7.42–7.41 (m, 4H), 7.40–7.36 (m, 5H), 7.28–7.24 (m, 4H), 7.21–7.17 (m, 4H), 5.55 (s, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.6, 152.7, 143.7, 140.0, 133.5, 132.0, 131.5, 129.9, 129.5, 129.3, 128.8, 128.3, 126.5, 126.4, 50.4, 21.5 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H24NS]+: 418.1624; found: 418.1623.; IR (film): νmax 3024, 1598, 1492, 1450, 745, 695 cm–1.
4-Benzhydryl-2-(4-methoxyphenyl)-5-phenylthiazole (5c)
Following the general experimental procedure (2), compound 5c was obtained as a colorless solid (140 mg, 92%); mp: 232–233 °C; 1H NMR (500 MHz, CDCl3): δ 7.87 (d, J = 8.70 Hz, 2H), 7.42–7.41 (m, 4H), 7.38–7.36 (m, 5H), 7.29–7.24 (m, 4H), 7.20–7.17 (m, 2H), 6.91 (d, J = 8.75 Hz, 2H), 5.54 (s, 1H), 3.83 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 165.4, 161.1, 152.6, 143.7, 133.0, 132.0, 129.9, 129.4, 128.8, 128.3, 128.2, 128.0, 127.2, 126.4, 114.2, 55.5, 50.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H24NOS]+: 434.1573; found: 434.1577.
4-Benzhydryl-5-phenyl-2-(4-(trifluoromethyl)phenyl)thiazole (5d)
Following the general experimental procedure (2), compound 5d was obtained as a pink solid (142 mg, 86%); mp: 199–200 °C; 1H NMR (500 MHz, CDCl3): δ 8.04 (d, J = 8.05 Hz, 2H), 7.65 (d, J = 8.10 Hz, 2H), 7.43 (s, 5H), 7.36 (d, J = 7.60 Hz, 4H), 7.29 (t, J = 7.45 Hz, 4H), 7.24–7.19 (m, 2H), 5.58 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 163.6, 153.6, 143.4, 137.1, 135.3, 131.4, 129.9, 129.3, 129.0, 128.7, 128.4, 126.7, 126.5, 125.9, 50.3 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H21F3NS]+: 472.1341; found: 472.1342.
4-Benzhydryl-2-phenyl-5-(p-tolyl)thiazole (5e)
Following the general experimental procedure (2), compound 5e was obtained as a white solid (127 mg, 90%); mp: 156–157 °C; 1H NMR (500 MHz, CDCl3): δ 7.94–7.92 (m, 2H), 7.41–7.38 (m, 3H), 7.38–7.37 (m, 4H), 7.33–7.31 (m, 2H), 7.29–7.27 (m, 4H), 7.24–7.22 (m, 2H), 7.21–7.17 (m, 2H), 5.55 (s, 1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.2, 152.7, 143.7, 138.4, 134.1, 129.8, 129.6, 129.3, 128.8, 128.3, 126.5, 126.4, 50.3, 21.4 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H24NS]+: 418.1624; found: 418.1626.
5-([1,1′-Biphenyl]-4-yl)-4-benzhydryl-2-phenylthiazole (5f)
Following the general experimental procedure (2), compound 5f was obtained as a brown solid (117 mg, 88%); mp: 184–185 °C; 1H NMR (500 MHz, CDCl3): δ 7.95–7.94 (m, 2H), 7.66–7.62 (m, 4H), 7.51–7.49 (m, 2H), 7.47–7.44 (m, 2H), 7.41–7.40 (m, 2H), 7.40–7.39 (m, 5H), 7.36–7.35 (m, 1H), 7.29 (t, J = 7.40 Hz, 4H), 7.22–7.18 (m, 2H), 5.63 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 165.5, 153.1, 143.6, 141.2, 140.4, 134.0, 133.7, 130.8, 130.2, 129.9, 129.4, 129.0, 128.9, 128.4, 127.7, 127.5, 127.2, 126.5, 126.4, 50.5 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C34H26NS]+; 480.1780; Found; 480.1781.
4-Benzhydryl-5-cyclopropyl-2-phenylthiazole (5g)
Following the general experimental procedure (2), compound 5g was obtained as pale yellow solid (125 mg, 84%); mp: 125–126 °C; 1H NMR (500 MHz, CDCl3): δ 7.84 (s, 2H), 7.40 (s, 4H), 7.36–7.33 (m, 3H), 7.31–7.28 (m, 4H), 7.22–7.19 (m, 2H), 5.77 (s, 1H), 2.00–1.97 (m, 1H), 1.03 (s, 2H), 0.71 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 162.7, 154.7, 143.3, 137.7, 134.3, 129.4, 129.3, 128.7, 128.3, 126.4, 126.3, 50.9, 9.7, 7.6 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C25H22NS]+; 368.1467; Found; 368.1465.; IR (film): νmax 3060, 1597, 1530, 1448, 711, 695 cm–1.
4-Benzhydryl-5-butyl-2-phenylthiazole (5h)
Following the general experimental procedure (2), compound 5h was obtained as yellow sticky compound (115 mg, 80%); 1H NMR (500 MHz, CDCl3): δ 7.85 (d, J = 7.05 Hz, 2H), 7.36–7.33 (m, 4H), 7.32–7.29 (m, 2H), 7.27–7.24 (m, 5H), 7.17 (t, J = 7.45 Hz, 2H), 5.52 (s, 1H), 2.80 (t, J = 7.70 Hz, 2H), 1.60–1.54 (m, 2H), 1.35–1.29 (m, 2H), 0.87 (t, J = 7.65 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 163.5, 152.9, 143.4, 134.8, 134.3, 132.4, 130.1, 129.4, 129.3, 128.7, 128.3, 128.2, 126.3 (2), 50.6, 31.4, 26.3, 22.4, 13.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C26H26NS]+; 384.1780; Found; 384.1777.
4-Benzhydryl-5-pentyl-2-phenylthiazole (5i)
Following the general experimental procedure (2), compound 5i was obtained as pale yellow sticky compound (116 mg, 81%); 1H NMR (500 MHz, CDCl3): δ 7.88–7.85 (m, 2H), 7.37–7.35 (m, 4H), 7.33–7.30 (m, 2H), 7.28–7.25 (m, 5H), 7.19–7.16 (m, 2H), 5.52 (s, 1H), 2.83–2.79 (m, 2H), 1.60 (s, 2H), 1.29–1.28 (m, 4H), 0.84–0.83 (m, 3H); 13C NMR (125 MHz, CDCl3): δ 163.5, 152.9, 143.4, 134.8, 134.3, 129.4, 129.3, 128.7, 128.2, 126.3 (2), 50.5, 31.7, 31.4, 26.5, 22.4, 14.0 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C27H28NS]+; 398.1937; Found; 398.1939.
4-((4-Bromophenyl)(phenyl)methyl)-2,5-diphenylthiazole (5j)
Following the general experimental procedure (2), compound 5j was obtained as pink solid (130 mg, 97%); mp: 113–114 °C; 1H NMR (500 MHz, CDCl3): δ 7.93–7.91 (m, 2H), 7.42 (m, 1H), 7.41–7.40 (m, 4H), 7.40–7.38 (m, 5H), 7.35–7.33 (m, 2H), 7.30–7.27 (m, 2H), 7.24–7.21 (m, 3H), 5.49 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 165.7, 152.3, 143.1, 142.7, 134.2, 133.9, 131.6, 131.4, 131.1, 130.0, 129.8, 129.2, 128.9 (2), 128.5 (2), 126.6, 126.5, 120.4, 49.8 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C28H21BrNS]+; 482.0573; Found; 483.0575.; IR (film): νmax 3021, 1596, 1519, 1442, 759, 734, 687 cm–1.
4-((4-Methoxyphenyl)(phenyl)methyl)-2,5-diphenylthiazole (5k)
Following the general experimental procedure (2), compound 5k was obtained as cream solid (132 mg, 95%); mp: 183–184 °C; 1H NMR (500 MHz, CDCl3): δ 7.94–7.92 (m, 2H), 7.42–7.41 (m, 4H), 7.39–7.37 (m, 3H), 7.36–7.34 (m, 3H), 7.31–7.28 (m, 2H), 7.26–7.22 (m, 2H), 7.19–7.16 (m, 1H), 6.83–6.81 (m, 2H), 5.51 (s, 1H), 3.75 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 165.5, 158.2, 153.3, 144.0, 135.8, 134.1, 133.8, 131.9, 130.3, 129.9, 129.8, 129.2, 128.8, 128.3 (2), 126.5, 126.3, 113.7, 55.3, 49.6 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C29H24NOS]+; 434.1573; Found; 434.1575.; IR (film): νmax 2931, 2833, 1603, 1508, 1456, 740, 689 cm–1.
5-Butyl-4-((4-methoxyphenyl)(phenyl)methyl)-2-phenylthiazole (5l)
Following the general experimental procedure (2), compound 5l was obtained as colorless sticky compound (109 mg, 78%); 1H NMR (500 MHz, CDCl3): δ 7.86–7.84 (m, 2H), 7.34–7.33 (m, 3H), 7.30–7.26 (m, 4H), 7.26–7.23 (m, 2H), 7.17–7.13 (m, 1H), 6.81 (d, J = 8.80 Hz, 2H), 5.47 (s, 1H), 3.70 (s, 3H), 2.80 (t, J = 7.55 Hz, 2H), 1.60–1.54 (m, 2H), 1.37–1.30 (m, 2H), 0.87 (t, J = 7.35 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 163.5, 158.1, 153.2, 143.8, 135.6, 134.5, 134.3, 130.2, 129.3, 129.1, 128.7, 128.2, 126.2, 113.6, 55.2, 49.7, 34.1, 26.2, 22.3, 13.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C27H28NOS]+; 414.1886; Found; 414.1882.
4-(bis(4-Fluorophenyl)methyl)-2,5-diphenylthiazole (5m)
Following the general experimental procedure (2), compound 5m was obtained as white solid (129 mg, 93%); mp: 142–143 °C; 1H NMR (500 MHz, CDCl3): δ 7.93–7.91 (m, 2H), 7.43–7.42 (m, 2H), 7.41–7.40 (m, 3H), 7.39–7.36 (m, 3H), 7.31–7.28 (m, 4H), 6.96 (t, J = 8.75 Hz, 4H), 5.50 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 165.9, 162.8, 160.4, 152.5, 139.2, 134.1, 133.8, 131.6, 130.7, 130.6, 130.0, 129.8, 129.0, 128.6, 126.5, 115.3, 115.1, 48.9 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C28H20F2NS]+; 440.1279; Found; 440.1277.
4-(1-(Benzo[d][1,3]dioxol-4-yl)ethyl)-2,5-diphenylthiazole (5n)
Following the general experimental procedure (2), compound 5n was obtained as yellow solid (133 mg, 92%); mp: 99–100 °C; 1H NMR (500 MHz, CDCl3): δ 8.00–7.98 (m, 2H), 7.46–7.44 (m, 2H), 7.43–7.42 (m, 2H), 7.41–7.40 (m, 3H), 7.40–7.37 (m, 1H), 7.06 (d, J = 1.60 Hz, 1H), 6.82–6.80 (m, 1H), 6.73 (d, J = 8.00 Hz, 1H), 5.92 (d, J = 1.45 Hz, 1H), 5.90 (d, J = 1.45 Hz, 1H), 4.22 (q, J = 14.10 Hz, 1H), 1.67 (d, J = 7.05 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 165.4, 155.6, 147.6, 145.8, 140.0, 134.1, 132.2, 132.0, 129.9, 129.8, 128.9, 128.7, 128.2, 126.5, 120.6, 108.5, 108.1, 100.9, 39.1, 23.5 ppm; HR-MS (ESI-TOF) m/z: [M + H]+calculated for [C24H20NO2S]+; 386.1209; Found; 386.1211.
2,5-Diphenyl-4-(1-phenylethyl)thiazole (5o)
Following the general experimental procedure (2), compound 5o was obtained as cream solid (135 mg, 88%); mp: 209–211 °C; 1H NMR (500 MHz, CDCl3): δ 8.00–7.99 (m, 2H), 7.44–7.43 (m, 3H), 7.41–7.40 (m, 2H), 7.39–7.38 (m, 4H), 7.36–7.35 (m, 1H), 7.29 (t, J = 7.50 Hz, 2H), 7.18 (t, J = 7.35 Hz, 1H), 7.29 (q, J = 14.10 Hz, 1H), 1.72 (d, J = 7.10 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 165.4, 155.6, 145.9, 134.1, 132.3, 132.0, 129.9, 129.8, 128.9, 128.7, 128.5, 128.1, 127.8, 126.5, 126.2, 39.4, 23.2 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C23H20NS]+; 342.1311; Found; 342.1310.
4-(9H-Fluoren-9-yl)-2,5-diphenylthiazole (5p)
Following the general experimental procedure (2), compound 5p was obtained as white solid (140 mg, 98%); mp: 123–124 °C; 1H NMR (500 MHz, CDCl3): δ 7.81–7.80 (m, 2H), 7.75 (d, J = 7.60 Hz, 2H), 7.35–7.34 (m, 4H), 7.34–7.32 (m, 4H), 7.27–7.25 (m, 4H), 7.20 (d, J = 7.45 Hz, 2H), 5.53 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3): δ 166.0, 151.0, 146.4, 141.3, 134.8, 133.7, 131.5, 129.9, 129.7, 128.8, 128.5, 128.2, 127.3, 127.1, 126.6, 125.0, 120.0, 49.1 ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C28H20NS]+; 402.1311; Found; 402.1311.; IR (film): νmax 3051, 1597, 1442, 736, 697 cm–1.
1-(Phenylethynyl)cyclohept-1-ene (5q)
Following general experimental procedure 2, compound 5q was obtained as brown liquid (120 mg, 79%); 1H NMR (500 MHz, CDCl3): δ 7.34–7.32 (m, 2H), 7.22–7.20 (m, 1H), 7.19–7.17 (m, 2H), 6.32 (t, J = 6.70 Hz, 1H), 2.36–2.34 (m, 2H), 2.17–2.14 (m, 2H), 1.71–1.67 (m, 2H), 1.56–1.51 (m, 2H), 1.49–1.44 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 140.4, 131.4, 128.8, 128.3, 127.7, 127.0, 125.4, 124.0, 93.0, 86.9, 34.4, 32.3, 29.4, 26.7, 26.6 ppm; HR-MS (ESI-TOF) m/z: [M + H] + calculated for [C15H17]+; 197.1325; Found; 197.1327.
4-Cycloheptyl-2,5-diphenylthiazole (5r)
Following the general experimental procedure (2), compound 5r was obtained as yellow liquid (125 mg, 81%); 1H NMR (500 MHz, CDCl3): δ 7.52–7.41 (m, 1H), 7.41–7.39 (m, 2H), 7.34–7.32 (m, 1H), 7.30–7.28 (m, 2H), 7.27–7.24 (m, 2H), 7.23–7.18 (m, 1H), 6.39 (t, J = 6.75 Hz, 1H), 2.82–2.69 (m, 1H), 2.43 (t, J = 5.55 Hz, 2H), 2.23 (q, J = 6.40 Hz, 2H), 1.79–1.74 (m, 1H), 1.73–1.71 (m, 1H), 1.67–1.65 (m, 1H), 1.63–1.59 (m, 2H), 1.56–1.52 (m, 1H); 13C NMR (125 MHz, CDCl3): δ 140.3, 131.5, 128.8, 128.3, 127.7, 127.0, 126.8, 126.7, 125.4, 124.0, 34.4, 32.3, 29.4, 26.7 (2) ppm; HRMS (ESI-TOF) m/z: [M + H]+calculated for [C22H24NS]+; 334.1624; Found; 334.1624.
4-Benzhydryl-2,5-diphenyloxazole (7a)(8h)
Following the general experimental procedure (3), compound 7a was obtained as white solid (134 mg, 98%); mp: 174–175 °C; 1H NMR (500 MHz, CDCl3): δ 8.09–8.07 (m, 2H), 7.80–7.79 (m, 1H), 7.62 (d, J = 7.35, 2H), 7.45–7.44 (m, 3H), 7.42–7.41 (m, 5H), 7.37–7.34 (m, 1H), 7.30 (t, J = 7.40, 4H), 7.24–7.20 (m, 2H), 5.64 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 160.1, 146.6, 142.7, 138.5, 132.1, 130.2, 129.3, 128.9, 128.8, 128.7 (2), 128.4 (2), 127.8, 127.4, 126.6, 48.2; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C28H22NO]+: 388.1696; found: 388.1702.
4-Benzhydryl-2-(4-methoxyphenyl)-5-phenyloxazole (7b)
Following the general procedure 3, compound 7b was obtained as white color solid (141 mg, 96%); mp: 185–186 °C; 1H NMR (500 MHz, CDCl3): δ 8.02 (d, J = 8.95 Hz, 2H), 7.62–7.60 (m, 2H), 7.44–7.42 (m, 4H), 7.40–7.33 (m, 3H), 7.31–7.28 (m, 4H), 7.25–7.20 (m, 2H), 6.95–6.93 (m, 2H), 5.63 (s, 1H), 3.85 (s, 3H); 13C NMR (125 MHz, CDCl3): 161.3, 160.1, 146.1, 142.8, 138.2, 129.3, 129.0, 128.9, 128.4, 128.3, 128.1, 126.6, 126.5, 120.7, 114.1, 55.5, 48.2 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C29H24NO2]+: 418.1802; found: 418.1802.
4-Benzhydryl-2-(4-chlorophenyl)-5-phenyloxazole (7c)
Following the general procedure 3, compound 7c was obtained as white solid (133 mg, 90%); mp: 124–125 °C; 1H NMR (500 MHz, CDCl3): δ 8.01 (d, J = 8.50 Hz, 2H), 7.61 (d, J = 7.40 Hz, 2H), 7.46–7.43 (m, 2H), 7.41–7.39 (m, 6H), 7.37–7.35 (m, 1H), 7.30 (t, J = 7.40 Hz, 4H) 7.25–7.21 (m, 2H), 5.63 (s, 1H); 13C NMR (125 MHz, CDCl3):159.2, 146.9, 142.6, 138.6, 136.3, 129.3, 129.0 (2), 128.6, 128.5 (2), 127.9, 126.7 (2), 126.3, 48.2; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C28H21ClNO]+: 422.1306; found: 422.1302.
4-Benzhydryl-5-phenyl-2-(3-(trifluoromethyl)phenyl)oxazole (7d)
Following the general procedure (3), compound 7d was obtained as a white solid (140 mg, 87%); mp: 120–121 °C; 1H NMR (500 MHz, CDCl3): δ 8.31–8.26 (m, 2H), 7.67–7.63 (m, 3H), 7.57–7.54 (m, 1H), 7.48–7.45 (m, 2H), 7.41–7.38 (m, 5H), 7.32 (t, J = 7.35 Hz, 4H), 7.25–7.22 (m, 2H), 5.65 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 158.7, 147.3, 142.4, 138.8, 129.7, 129.3, 129.2, 129.0, 128.7, 128.5, 128.4, 126.8, 126.6, 123.4, 48.2 ppm; 19F NMR (470 CDCl3): δ – 62.7 HRMS (ESI-TOF): m/z [M + H]+ calculated for [C29H21F3NO]+: 456.1570; found: 456.1571.
4-Benzhydryl-5-phenyl-2-(o-tolyl)oxazole (7e)(8h)
Following the general procedure 3, compound 7e was obtained as white solid (131 mg, 93%); mp: 119–120 °C; 1H NMR (500 MHz, CDCl3): δ 8.05–8.04 (m, 1H), 7.64–7.63 (m ,2H), 7.46–7.45 (m, 2H), 7.44–7.43 (m, 4H), 7.37–7.34 (m, 1H), 7.31–7.30 (m, 3H), 7.28–7.24 (m, 4H), 7.22–7.19 (m, 2H), 5.64 (d, J = 1.95 Hz, 1H), 2.70 (d, J = 1.85 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 160.3, 146.0, 142.9, 138.0, 137.8, 131.7, 129.8, 129.3, 129.0, 128.7, 128.4, 128.3, 126.6, 126.5, 125.9, 48.4, 22.3 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C29H24NO]+: 402.1852; found: 402.1856.
4-Benzhydryl-2-(naphthalen-1-yl)-5-phenyloxazole (7f)
Following the general procedure 3, compound 7f was obtained as white solid (134 mg, 87%); mp: 116–117 °C; 1H NMR (500 MHz, CDCl3): δ 9.30 (d, J = 8.50 Hz, 1H), 8.28–8.26 (m, 1H), 7.93 (d, J = 8.15 Hz, 1H), 7.87 (d, J = 8.05 Hz, 1H), 7.69–7.68 (m, 2H), 7.59–7.52 (m, 3H), 7.50–7.48 (m, 4H), 7.47–7.46 (m, 2H), 7.40–7.37 (m, 1H), 7.35–7.32 (m, 4H), 7.25–7.22 (m, 3H), 5.71 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 159.8, 146.3, 142.9, 138.3, 134.1, 131.1, 130.4, 129.3, 129.0, 128.8, 128.5 (2), 128.4, 127.7, 127.5, 126.7, 126.6, 126.3, 125.0, 124.1, 48.5 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C32H25NO]+: 438.1852; found: 438.1850.
4-Benzhydryl-2-phenyl-5-(p-tolyl)oxazole (7g)(8h,8j)
Following the general procedure 3, compound 7g was obtained as pink solid (121 mg, 90%); mp: 140–141 °C; 1H NMR (500 MHz, CDCl3): δ 8.08–8.06 (m, 2H), 7.52–7.50 (m, 2H), 7.44–7.41 (m, 3H), 7.41–7.40 (m, 4H), 7.31–7.28 (m, 4H), 7.26–7.24 (m, 2H), 7.23–7.20 (m, 2H), 5.62 (s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.8, 146.8, 142.8, 138.4, 137.9, 130.1, 129.6, 129.3, 128.7, 128.4, 127.9, 126.6, 126.0, 48.2, 21.5 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C29H24NO]+: 402.1852; found: 402.1855.
5-([1,1′-Biphenyl]-4-yl)-4-benzhydryl-2-phenyloxazole (7h)
Following the general procedure 3, compound 7h was obtained as yellow solid (113 mg, 87%); mp: 123–124 °C; 1H NMR (500 MHz, CDCl3): δ 8.11–8.09 (m, 2H), 7.71–7.67 (m, 4H), 7.63 (d, J = 7.15 Hz, 2H), 7.48–7.46 (m, 2H), 7.44 (s, 3H), 7.43 (s, 4H), 7.37 (t, J = 7.40 Hz, 1H), 7.32 (t, J = 7.50 Hz, 4H), 7.25–7.22 (m, 2H), 5.69 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 160.1, 146.4, 142.7, 141.0, 140.4, 138.7, 130.2, 129.3, 129.0, 128.7, 128.5, 127.8, 127.7, 127.6, 127.1, 126.9, 126.7, 126.6, 48.4 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C34H26NO]+: 464.2009; found: 464.2007.
4-Benzhydryl-5-cyclopropyl-2-phenyloxazole (7i)
Following the general procedure 3, compound 7i was obtained as a white solid (121 mg, 86%); mp: 102–103 °C; 1H NMR (500 MHz, CDCl3): δ 7.94–7.92 (m, 2H), 7.40–7.36 (m, 4H), 7.34 (s, 3H), 7.29 (t, J = 7.40 Hz, 4H), 7.25–7.19 (m, 2H), 5.50 (s, 1H), 1.62–1.60 (m, 1H), 0.92–0.89 (m, 2H), 0.88–0.84 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 158.3, 149.1, 142.7, 137.8, 129.7, 129.2, 128.6, 128.4, 128.0, 126.5, 126.1, 48.3, 6.9, 6.2; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C25H22NO]+: 352.1696; found: 352.1694.
4-(9H-Fluoren-9-yl)-2,5-diphenyloxazole (7j)
Following the general procedure 3, compound 7j was obtained as a white color solid (131 mg, 96%); mp: 201–202 °C; 1H NMR (500 MHz, CDCl3): δ 8.05–8.03 (m, 2H), 7.84–7.80 (m, 3H), 7.55–7.45 (m, 3H), 7.43–7.41 (m, 4H), 7.40–7.38 (m, 2H), 7.32–7.28 (m, 2H), 7.26–7.21 (m, 2H), 5.53 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 160.3, 147.4, 145.0, 141.3, 135.7, 132.2, 130.7, 128.8, 128.5, 128.3, 127.7, 127.5, 127.4, 126.9, 126.7, 126.4, 125.1, 120.2, 46.4; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C28H20NO]+: 386.1539; found: 386.1540.
4-((4-Chlorophenyl)(phenyl)methyl)-2,5-diphenyloxazole (7k)(8f)
Following the general procedure 3, compound 7k was obtained as a yellow solid (125 mg, 94%); mp: 123–124 °C; 1H NMR (500 MHz, CDCl3); δ 8.09–8.07 (m, 2H), 7.61–7.59 (m, 2H), 7.46–7.42 (m, 5H), 7.39–7.37 (m, 3H), 7.34–7.29 (m, 4H), 7.27–7.22 (m, 3H); 5.60 ppm; 13C NMR (125 MHz, CDCl3): 160.2, 146.7, 142.2, 141.2, 137.9, 132.5, 130.7, 130.3, 129.1, 129.0, 128.7, 128.6, 128.5, 127.7, 126.8, 126.6 (2), 47.6; HRMS(ESI-TOF): m/z [M + H]+ calculated for [C28H20ClNO]+: 422.1306; found: 422.1303.
4-((4-Bromophenyl)(phenyl)methyl)-2,5-diphenyloxazole (7l)(8f)
Following the general procedure 3, compound 7l was obtained as a white solid (124 mg, 97%); mp: 134–135 °C; 1H NMR (500 MHz, CDCl3); δ 8.08–8.07 (m, 2H), 7.61–7.59 (m, 2H), 7.46–7.42 (m, 5H), 7.41–7.35 (m, 4H), 7.32–7.29 (m, 3H), 7.27 (m, 1H), 7.25–.22 (m, 2H), 5.58 (s, 1H); 13C NMR (100 MHz, CDCl3): 160.2, 146.7, 142.1, 141.8, 137.8, 131.5, 131.1, 130.3, 129.1, 129.0, 128.7, 128.6, 128.5, 127.7, 126.9, 126.6, 120.6, 47.7 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C28H21BrNO]+: 466.0801; found: 466.0800.
4-((4-Methoxyphenyl)(phenyl)methyl)-2,5-diphenyloxazole (7m)
Following the general procedure 3, compound 7m was obtained as a white solid (121 mg, 91%); mp: 180–181 °C; 1H NMR (500 MHz, CDCl3); δ 8.09–8.08 (m, 2H), 7.62 (d, J = 7.50 Hz, 2H), 7.46–7.40 (m, 5H), 7.39–7.36 (m, 2H), 7.34–7.30 (m, 4H), 7.26–7.20 (m, 2H), 6.85 (d, J = 8.55 Hz, 2H), 5.59 (s, 1H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3): 160.0, 158.3, 146.4, 143.0, 138.7, 134.8, 130.3, 130.2, 129.1, 128.9, 128.7, 128.4, 128.3, 127.8, 126.6, 113.8, 55.3, 47.4; HRMS(ESI-TOF): m/z [M + H]+ calculated for [C29H24NO2]+: 418.1802; found: 418.1801.
4-((3,4-Dichlorophenyl)(phenyl)methyl)-2,5-diphenyloxazole (7n)
Following the general procedure 3, compound 7n was obtained as a white solid (107 mg, 83%); mp: 102–103 °C; 1H NMR (500 MHz, CDCl3): δ 8.09–8.07 (m, 2H), 7.60–7.58 (m, 2H), 7.48–7.47 (m, 1H), 7.46–7.43 (m, 4H), 7.40–7.38 (m, 3H), 7.37–7.31 (m, 3H), 7.27–7.23 (m, 3H), 5.56 (s, 1H); 13C NMR (100 MHz, CDCl3): 160.3, 146.8, 143.0, 141.6, 137.3, 132.3, 131.2, 130.7, 130.4, 130.3, 129.1, 128.8, 128.6, 128.5, 127.6, 127.1, 126.6, 47.4 ppm; HRMS(ESI-TOF): m/z [M + H]+ calculated for [C28H20ClNO]+: 456.0916; found: 456.0917.
4-(bis(4-Fluorophenyl)methyl)-2,5-diphenyloxazole (7o)8f
Following the general procedure 3, compound 7o was obtained as a yellow solid (123 mg, 93%); mp: 140–141 °C; 1H NMR (500 MHz, CDCl3); δ 8.09–8.07 (m, 2H), 7.83–7.81 (m, 3H), 7.59–7.57 (m, 1H), 7.55–7.52 (m, 1H), 7.47 (m, 1H), 7.46–7.45 (m, 2H), 7.44 (m, 2H), 7.35–7.33 (m < 3H), 6.99 (t, J = 8.75 Hz, 3H), 5.60 (s, 1H); 13C NMR (100 MHz, CDCl3): 170.1, 162.9, 160.5, 160.3, 146.6, 138.2, 137.9, 132.9, 132.3, 130.7, 130.6, 130.4, 129.0, 128.8, 128.7, 128.6, 128.5, 127.5, 127.4, 126.6, 126.5, 115.4, 115.2, 46.7 ppm; HRMS (ESI-TOF): m/z [M + H]+ calculated for [C28H20F2NO]+: 424.1507; found: 424.1507.
2-(4-Isobutylphenyl)propenamide (8)
To the stirred thionyl chloride (1.5 equiv), ibuprofen (1 equiv) was added slowly, the reaction mixture was warmed to 50 °C for 1 h and cooled to 10 °C in ice water, 25% aq ammonia (4 mL) was slowly and carefully added, and the solution was stirred for 30 min. The solid precipitated out was collected by filtration, washed with 10% sodium bicarbonate solution and water, dried, and purified by crystallization, and the pure product 8 was obtained as a pink solid (95 mg, 96%). mp: 195–196 °C; 1H NMR (500 MHz, CDCl3): δ 7.26–7.19 (m, 2H), 7.13–7.11 (m, 2H), 5.73 (s, 1H), 5.34 (s, 1H), 3.59–3.55 (m, 1H), 2.45 (d, J = 7.20 Hz, 2H), 1.86–1.82 (m, 1H), 1.51 (d, J = 7.15 Hz, 3H), 0.89 (d, J = 6.60 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ 177.3, 141.0, 138.8, 129.8, 127.4, 46.3, 45.1, 30.3, 22.4, 18.3, ppm; HR-MS (ESI-TOF) m/z: [M + H] + calculated for [C13H20 NO]+: 206.1539; found: 206.1541.
4-Benzhydryl-2-(1-(4-isobutylphenyl)ethyl)-5-phenyloxazole (9)
Following general experimental procedure 3, compound 9 was obtained as a yellow sticky compound (150 mg, 65%); 1H NMR (500 MHz, CDCl3): δ 7.49–7.47 (m, 2H), 7.38–7.34 (m, 6H), 7.31–7.25 (m, 6H),7.23–7.20 (m, 4H), 7.07 (d, J = 7.95 Hz, 2H), 5.56 (s, 1H), 4.28 (q, J = 7.25 Hz, 2H), 2.43 (d, J = 7.20 Hz, 2H), 1.87–1.79 (m, 1H), 1.69 (d, J = 7.25 Hz, 3H), 0.90 (d, J = 3.80 Hz, 3H), 0.88 (d, J = 3.85 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 165.2, 146.4, 142.9, 142.8, 140.3, 139.5, 130.1, 129.9, 129.4, 129.3, 129.2, 128.8, 128.4, 127.2, 126.5, 48.1, 45.1, 39.4, 30.3, 22.5, 20.5 ppm; HR-MS (ESI-TOF) m/z: [M + H] + calculated for [C34H34NO]+: 472.2635; found; 472.2637.
4-(bis(4-Fluorophenyl)methyl)-2-(1-(4-isobutylphenyl)ethyl)-5-phenyloxazole (10)
Following general experimental procedure 3, compound 10 was obtained as a brown sticky compound (170 mg, 69%); 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 7.75 Hz, 2H), 7.37 (t, J = 7.40 Hz, 2H), 7.32–7.27 (m, 5H), 7.22–7.20 (m, 2H), 7.08 (d, J = 8.00 Hz, 2H), 7.00–6.94 (m, 4H), 5.50 (s, 1H), 4.27 (q, J = 7.20 Hz, 2H), 2.43 (d, J = 7.20 Hz, 2H), 1.86–1.79 (m, 1H), 1.69 (d, J = 7.25 Hz, 3H), 0.89 (d, J = 6.60 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 165.4, 162.7, 160.7, 146.4, 140.4, 139.4, 138.5, 138.4 (2), 138.3, 136.3, 130.6 (2), 130.5, 129.4, 128.9, 128.3, 127.1, 126.5, 115.3, 115.2, 46.6, 45.1, 39.4, 30.3, 22.5, 20.4 ppm; HR-MS (ESI-TOF) m/z: [M + H] + calculated for [C34H32F2NO]+: 508.2446; found; 508.2444.
(Z)-2-(4-Methoxyphenyl)-4-(1-phenyl-3-(p-tolyl)prop-1-en-1-yl)-5-(p-tolyl)thiazole 1,1-Dioxide (11)
To a mixture of 3d (1equiv) in DCM was added m-CPBA (5 equiv) and stirred at room temperature for 12 h until complete conversion of 3d monitored by TLC. The resulting solution was quenched with aqueous Na2CO3 and extracted with ethyl acetate thrice. The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo, the crude was purified by column chromatography (100–200 silica gel, 1%, EtOAc in petroleum ether), and the product was obtained as a yellow solid (86 mg, 81%); mp: 122–123 °C; 1H NMR (500 MHz, CDCl3): δ 7.91–7.87 (m, 3H), 7.41–7.37 (m, 4H), 7.28–7.24 (m, 1H), 7.22–7.18 (m, 1H), 7.07 (d, J = 7.95 Hz, 2H), 6.97–6.92 (m, 4H), 6.86–6.83 (m, 3H), 6.37 (t, J = 7.30 Hz, 1H), 3.84 (s, 3H), 3.22 (d, J = 7.30 Hz, 2H), 2.32 (s, 3H), 2.26 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 165.1, 163.0, 161.2, 148.6, 140.2, 137.9, 137.1, 135.5, 135.4, 135.0, 131.9, 129.4, 129.2, 129.0, 128.6, 128.4, 128.1 (2), 127.3, 126.6, 114.3, 113.6, 55.5, 35.9, 21.3, 21.0 ppm; HR-MS (ESI-TOF) m/z: [M + H] + calculated for [C33H30NO3S]+: 520.1941; found: 520.1946.
Acknowledgments
This work is financially supported by the IOE-UOH grant no UoH/IoE/RC1-08. D.S.L. is thankful to RGNF for the fellowship and Rathod Mahesh for the technical support in solving the crystal structures. The authors are thankful to the School of Chemistry, University of Hyderabad, for the facilities.
Supporting Information Available
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.2c05085.
The authors declare no competing financial interest.
Supplementary Material
References
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