Divergent Construction of Pyrazoles via Michael Addition of N-Aryl Hydrazones to 1,2-Diaza-1,3-dienes Serena Mantenuto, Fabio Mantellini, Gianfranco Favi,* and Orazio A. Attanasi Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino Carlo Bo, Via I Maggetti 24, 61029 Urbino (PU), Italy e-mail: gianfranco.favi@uniurb.it SUPPORTING INFORMATION Table of Contents 1. General remarks S2 2. Experimental procedures and spectral data S2 S11 Synthesis of β-azohydrazones 3a k Synthesis of pyrazoles 4a j Synthesis of pyrazoles 5a h S2 S6 S9 3. 1 H and 13 C NMR spectra of all products S12 S36 4. References and notes S37 1
Experimental Section 1. General Remarks. All the commercially available reagents and solvents were used without further purification. N-Aryl hydrazones 1a g were prepared from corresponding hydrazines and aldehydes in EtOH. 1 1,2- Diaza-1,3-dienes 2a e were synthesized as a mixture of E/Z isomers as previously reported. 2,3 Chromatographic purification of compounds was carried out on silica gel (60 200 μm). TLC analysis was performed on pre-loaded (0.25 mm) glass supported silica gel plates (Kieselgel 60); compounds were visualized by exposure to UV light and by dipping the plates in 1% Ce(SO4) 4H2O, % (NH4)6Mo7O24 4H2O in 10% sulphuric acid followed by heating on a hot plate. All 1 H NMR and 13 C NMR spectra were recorded at 400 and 106 MHz, respectively. Proton and carbon spectra were referenced internally to solvent signals, using values of δ = 2.49 ppm for proton (middle peak) and δ = 30 ppm for carbon (middle peak) in DMSO-d6 and δ = 7.26 ppm for proton and δ = 70 ppm for carbon (middle peak) in CDCl3. The following abbreviations are used to describe peak patterns where appropriate: s = singlet, d = doublet, t = triplet q = quartet, m = multiplet and br = broad signal. All coupling constants (J) are given in Hz. FT-IR spectra were obtained as Nujol mulls. Mass spectra were recorded in the EI mode (70eV). Melting points were determined in open capillary tubes and are uncorrected. 2. Experimental procedures and spectral data. General procedure for the NaH-Catalyzed Conjugated Addition of N-Aryl hydrazones 1a g with Diaza-1,3-dienes 2a e; Synthesis of β-azohydrazone Adducts 3a k. N-Aryl hydrazones 1a g (0.8 mmol) in CH3CN (3 ml) was added dropwise to a stirred solution of 1,2-diaza-1,3-dienes 2a e (1.2 mmol) in the presence of a catalytic amount of NaH (10 mol %) in CH3CN (3 ml). Upon completion (10 min h, monitored by TLC), the reaction mixture was concentrated under reduced pressure and purified by column chromatography on silica gel to afford the products 3a k. Important: changing the addition order of the reagents, by adding NaH to the solution of AHs 1 and DDs 2 the reactions gave lower yield. During the course of the reactions, the following work-up, and the long standing, compounds 3a k give a partial isomerization and/or degradation reaction. 2
tert-butyl methoxy-4-oxobut-2-en-2-yl}hydrazinecarboxylate (3a ): N-Michael adduct (hydrazino form) 3a was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) (entries 2 9, Table 1); White solid; mp: 82 86 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1 (s, 9H), 1.80 (s, 3H), 8 (s, 3H), 6.45 (br, 1H), 6.86 6.97 (m, 1H), 7.28 0 (m, 6H), 7.46 (s, 1H), 7.66 (d, J = 8.4 Hz, 1H), 10.27 (s, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 13.2 (q), 28.2 (q), 5 (q), 82.2 (s), 113.9 (d), 120.3 (d), 127.7 (d), 128.6 (d), 129.1 (d), 132.3 (s), 13 (s), 134.9 (s), 147.2 (s), 155.1 (s), 166.2 (s), 168.4 (s); IR (nujol): max = 3194, 1690, 1660 cm -1 ; MS m/z (%): 459 (M + ) (3), 111 (100); anal. calcd. for C23H27ClN4O4 (458.94): C 60.19, H 5.93, N 12.21; found: C 60.30, H 5.80, N 12.13. tert-butyl 2-{3-[2-(4-chlorobenzylidene)-1-phenylhydrazinyl]-4-2-[4-(4-chlorophenyl)-3-(methoxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3a): β- Azohydrazone (C-Michael adduct) 3a was isolated by column chromatography (ethyl acetate/cyclohexane 80:20) in 83% yield (304.7 mg) ( h; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 55:45, *denotes minor diastereoisomer signals): δ = 1.38 (s, 9H), 1.41* (s, 9H), 1.72 (s, 3H), 1.81* (s, 3H), 3.46* (s, 3H), 6 (s, 3H), 4.38 (d, J = 11.2 Hz, 1H), 4.47* (d, J = 10.8 Hz, 1H), 5.36* (d, J = 10.8 Hz, 1H), 5.70 (d, J = 11.2 Hz, 1H), 7.35 7.60 (m, 9H), 1 (s, 1H), 9* (s, 1H). MeO 2 C Me HN CO 2t-Bu N N O N Ph OMe solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 53:47, *denotes minor diastereoisomer signals): δ = 1.38 (s, 9H), 1.40* (s, 9H), 1.72 (s, 3H), 1.83* (s, 3H), 3.45* (s, 3H), 7 (s, 3H), 3.81 (s, 3H), 3.83* (s, 3H), 4.41 (d, J = 10.8 Hz, 1H), 1* (d, J = 10.8 Hz, 1H), 5.43* (d, J = 10.8 Hz, 1H), 5.77 (d, J = 10.8 Hz, 1H), 7.42 7.60 (m, 5H), 7.66* (d, J = 8.4 Hz, 2H), 7.89 (d, J = 8.4 Hz, 2H), 7.95* (d, J = 8.4 Hz, 2H), 9.48 (s, 1H), 9.60* (s, 1H). tert-butyl tert-butyl 2-[4-(4-methoxycarbonylphenyl)-3-(methoxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3b): β- Azohydrazone 3b was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 90% yield (347.4 mg) ( h; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow 2-[4-(2,4-dichlorophenyl)-3-(methoxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3c): β- Azohydrazone 3c was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 90% yield (355.3 mg) (10 min.; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 54:46, *denotes minor diastereoisomer signals): δ = 3
1.38 (s, 9H), 1.39* (s, 9H), 1.72 (s, 3H), 1.87* (s, 3H), 3.49* (s, 3H), 3.62 (s, 3H), 4.47 (d, J = 10.8 Hz, 1H), 5* (d, J = 10.4 Hz, 1H), 5.91 * (d, J = 10.4 Hz, 1H), 6.10 (d, J = 10.8 Hz, 1H), 7.38 7.76 (m, 8H), 9.48 (s, 1H), 9.61* (s, 1H). Ethyl 2-[4-(4-bromophenyl)-3-(ethoxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3d): β- Azohydrazone 3d was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 87% yield (305.4 mg) (10 min.; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 70:30, *denotes minor diastereoisomer signals): δ = 0.94* (t, J = 7.2 Hz, 3H), 4 (t, J = 7.2 Hz, 3H), 6 1.25 (m, 3H), 1.75 (s, 3H), 1.84* (s, 3H), 3.83 4.20 (m, 4H), 4.37 (d, J = 11.2 Hz, 1H), 4.43* (d, J = 10.8 Hz, 1H), 5.34* (d, J = 10.8 Hz, 1H), 5.67 (d, J = 11.2 Hz, 1H), 7.21 7.60 (m, 9H), 9.81 (s, 1H), 9.85* (s, 1H). tert-butyl 2-[4-(3-bromophenyl)-3-(methoxycarbonyl)-4-((E)- phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3e): β- Azohydrazone 3e was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 87% yield (350.4 mg) (10 min.; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 54:46, *denotes minor diastereoisomer signals): δ = 1.38 (s, 9H), 1.42* (s, 9H), 1.74 (s, 3H), 1.82* (s, 3H), 3.47* (s, 3H), 6 (s, 3H), 4.40 (d, J = 11.2 Hz, 1H), 0* (d, J = 10.8 Hz, 1H), 5.35* (d, J = 11.2 Hz, 1H), 5.69 (d, J = 10.8 Hz, 1H), 7.28 (t, J = Hz, 1H), 7.34* (t, J = Hz, 1H), 7.41 7.72 (m, 8H), 4 (s, 1H), 9* (s, 1H). tert-butyl 2-[4-(4-cyanophenyl)-3-(methoxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3f): β- Azohydrazone 3f was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 99% yield (35 mg) ( h; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 51:49, *denotes minor diastereoisomer signals): δ = 1.38 (s, 9H), 1.42* (s, 9H), 1.73 (s, 3H), 1.83* (s, 3H), 3.46* (s, 3H), 8 (s, 3H), 4.44 (d, J = 11.2 Hz, 1H), 0* (d, J = 10.4 Hz, 1H), 5.45* (d, J = 10.4 Hz, 1H), 5.79 (d, J = 11.2 Hz, 1H), 7.45 7.60 (m, 5H), 7.63 (d, J = 8.4 Hz, 2H), 7.72* (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.84* (d, J = 8.4 Hz, 2H), 6 (s, 1H), 9.61* (s, 1H). 4
Cl Me HN CO 2t-Bu N tert-butyl 2-[4-(4-chlorophenyl)-3-(ethoxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3g): β- N O N Ph OEt 3g Azohydrazone 3g was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 100% yield (378.3 mg) (10 min.; TLC check) as a single isomer. Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C): δ = 5 (t, J = 7.2 Hz, 1H), 1.41 (s, 9H), 1 (q, J = 7.2 Hz, 2H), 4.35 (d, J = 11.2 Hz, 1H), 5.68 (d, J = 11.2 Hz, 1H), 7.35 7.60 (m, 9H), 9.49 (s, 1H). Methyl (phenyldiazenyl)pentan-3-ylidene]hydrazinecarboxylate (3h): β- Azohydrazone 3h was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 49% yield (168.9 mg) (10 min.; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 62:38, *denotes minor diastereoisomer signals): δ = 0.66 (t, J = 7.6 Hz, 3H), 0.90* (t, J = 7.6 Hz, 3H), 2.10 2.43 (m, 2H), 3.45* (s, 3H), 6 (s, 3H), 9* (s, 3H), 3.65 (s, 3H), 4.39 (d, J = 10.8 Hz, 1H), 7* (d, J = 10.8 Hz, 1H), 2* (d, J = 10.8 Hz, 1H), 5.75 (d, J = 10.8 Hz, 1H), 7.34 7.60 (m, 9H), 11 (s, 1H). tert-butyl phenylbutan-2-ylidene}hydrazinecarboxylate (3i): β-azohydrazone 3i was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 45% yield (165.2 mg) (20 min.; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 55:45, *denotes minor diastereoisomer signals): δ = 1.34 (s, 9H), 1.40* (s, 9H), 1.71 (s, 3H), 1.80* (s, 3H), 3.43* (s, 3H), 5 (s, 3H), 4.39 (d, J = 11.2 Hz, 1H), 4.48* (d, J = 10.8 Hz, 1H), 5.34* (d, J = 10.8 Hz, 1H), 5.67 (d, J = 11.2 Hz, 1H), 7.25 7.62 (m, 9H), 1 (s, 1H), 9* (s, 1H). tert-butyl 3-[5-(4-chlorophenyl)-4-(methoxycarbonyl)-5-2-{4-[(4-chlorophenyl)diazenyl]-3-(methoxycarbonyl)-4-2-[4-(4-chlorophenyl)-3-(benzyloxycarbonyl)-4- (phenyldiazenyl)butan-2-ylidene]hydrazinecarboxylate (3j): β- Azohydrazone 3j was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 90% yield (385.2 mg) (10 min.; TLC check) as a mixture of inseparable isomers (determined by 1 H NMR). Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C) (dr: 63:37, *denotes minor diastereoisomer signals): δ = 1.35 (s, 9H), 1.38* (s, 9H), 1.72 (s, 3H), 1.82* (s, 3H), 4.46 (d, J = 11.2 Hz, 1H), 2* (d, J = 10.8 Hz, 1H), 4.93* (d, J = 12.8 Hz, 1H), 0* (d, J = 12.8 Hz, 1H), 4 (d, J = 12.8 Hz, 1H), 5.10 (d, J = 12.8 Hz, 1H), 5.38* (d, J = 10.8 Hz, 1H), 5.74 (d, J = 11.2 Hz, 1H), 7.20 5 (m, 14H), 4 (s, 1H), 9.62* (s, 1H). 5
General procedure for the Amberlyst 15(H)-Mediated Cyclization of β-azohydrazone Adducts 3a k to Pyrazoles 4a j. To a magnetically stirred solution of β-azohydrazone adducts 3 ( mmol) in CH2Cl2 (3 ml) was added Amberlyst 15(H) (0.25 g) and the reaction was allowed to stand at room temperature until the complete disappearance of 3a k (2 36 h, monitored by TLC). The solution was filtered, concentrated under reduced pressure and then products 4a j were isolated by chromatography on silica gel column. tert-butyl 3-[5-(4-chlorophenyl)-4-(methoxycarbonyl)-5- (phenyldiazenyl)pentan-3-ylidene]hydrazinecarboxylate (3k): β- Azohydrazone 3k was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 100% yield (378.3 mg) (10 min.; TLC check) as a single isomer. Yellow solid; 1 H NMR (400 MHz, DMSO-d6, 25 C): δ = 0.66 (t, J = 7.6 Hz, 3H), 1.45 (s, 9H), 5 2.23 (m, 2H), 5 (q, J = 7.2 Hz, 2H), 4.37 (d, J = 10.8 Hz, 1H), 5.74 (d, J = 11.2 Hz, 1H), 7.33 9 (m, 9H), 9.67 (s, 1H). Methyl 3-(4-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4a): Pyrazole 4a was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 93% (from 3a) or 65% (from 3l) yield (151.9 mg) (2 h; TLC check). White solid; mp: 94 96 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 7 (s, 3H), 3.78 (s, 3H), 7.35 (d, J = 8.4 Hz, 2H), 7.42 (m, 5H), (d, J = 8.4 Hz, 2H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.8 (q), 51.1 (q), 110.2 (s), 125.8 (d), 127.9 (d), 128.8 (d), 129.3 (d), 130.7 (d), 13 (s), 134.3 (s), 138.6 (s), 145.1 (s), 15 (s), 164.4 (s); IR (nujol): max = 1716 cm -1 ; MS m/z (%): 326 (M + ) (100), 311 (7), 295 (89); anal. calcd. for C18H15ClN2O2 (326.78): C 66.16, H 4.63, N 7; found: C 63, H 4, N 8.46. Methyl 3-[4-(methoxycarbonyl)phenyl]-5-methyl-1-phenyl-1H-pyrazole-4- carboxylate (4b): Pyrazole 4b was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 95% yield (166.4 mg) (12 h; TLC check). Pale yellow solid; mp: 106 108 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 9 (s, 3H), 3.76 (s, 3H), 3.93 (s, 3H), 7.45 (m, 5H), (d, J = 8.4 Hz, 2H), (d, J = 8.4 Hz, 2H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.7 (q), 51.1 (q), 52.1 (q), 11 (s), 125.8 (d), 128.9 (d), 12 (d), 129.3 (d), 129.4 (d), 129.7 (s), 137.7 (s), 138.6 (s), 145.2 (s), 15 (s), 164.4 (s), 16 (s); IR (nujol): max = 1715 cm -1 ; MS m/z (%): 350 (M + ) (100), 335 (7), 319 (70); anal. calcd. for C20H18N2O4 (350.37): C 66, H 5.18, N 0; found: C 68.45, H 5.26, N 7.89. 6
Methyl 3-(2,4-dichlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4c): Pyrazole 4c was isolated by column chromatography (ethyl acetate/cyclohexane 15:85) in 74% yield (133.6 mg) (5 h; TLC check). Yellow oil; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 2.62 (s, 3H), 3.70 (s, 3H), 7.27 (m, 8H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.4 (q), 51.1 (q), 111.9 (s), 125.6 (d), 126.6 (d), 128.7 (d), 12 (d), 129.2 (d), 131.6 (s), 132.1 (d), 134.7 (s), 134.9 (s), 138.4 (s), 144.3 (s), 150.2 (s), 16 (s); IR (nujol): max = 1715 cm -1 ; MS m/z (%): 360 (M + ) (2), 327 (36), 325 (100); anal. calcd. for C18H14Cl2N2O2 (361.22): C 59.85, H 3.91, N 7.76; found: C 59.99, H 3.85, N 7.85. Ethyl 3-(4-bromophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4d): Pyrazole 4d was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 74% yield (14 mg) (12 h; TLC check). White solid; mp: 62 64 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.25 (t, J = 7.2 Hz, 3H), 7 (s, 3H), 4.25 (q, J = 7.2 Hz, 2H), 7.44 (m, 9H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.7 (q), 14.1 (q), 60.1 (t), 110.4 (s), 12 (s), 125.7 (d), 128.8 (d), 129.2 (d), 130.7 (d), 131.1 (d), 13 (s), 138.6 (s), 14 (s), 152.4 (s), 163.9 (s); IR (nujol): max = 1710 cm -1 ; MS m/z (%): 386 (M + +2) (199), 384 (M + ) (100), 341 (50), 339 (55); anal. calcd. for C19H17BrN2O2 (385.25): C 59.23, H 4.45, N 7.27; found: C 59.14, H 4.33, N 7.19. The spectroscopic data of compound 4d are in good agreement with those reported in the literature 4 Methyl 3-(3-bromophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4e): Pyrazole 4e was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 76% yield (141.1 mg) (12 h; TLC check). Yellow oil; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 8 (s, 3H), 3.78 (s, 3H), (m, 1H), 7.44 (m, 7H), 7.84 (m, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.7 (q), 51.1 (q), 110.3 (s), 121.8 (s), 125.8 (d), 126.1 (d), 128.9 (d), 129.2 (d), 129.3 (d), 131.2 (d), 132.3 (d), 135.1 (s), 138.6 (s), 145.2 (s), 15 (s), 164.3 (s); IR (nujol): max = 1716 cm -1 ; MS m/z (%): 372 (M + +2) (58), 370 (M + ) (66), 341 (42), 339 (48), 111 (100); anal. calcd. for C18H15BrN2O2 (371.23): C 58.24, H 7, N 5; found: C 58.38, H 3.96, N 7.46. Methyl 3-(4-cyanophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4f): Pyrazole 4f was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 81% yield (12 mg) (12 h; TLC check). Yellow solid; mp: 132 134 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 8 (s, 3H), 3.79 (s, 3H), 7.44 (m, 5H), 7.69 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H); 13 C NMR (100 MHz, 7
CDCl3, 25 C): δ = 12.8 (q), 51.3 (q), 111.8 (s), 11 (s), 125.8 (d), 129.1 (d), 129.4 (d), 130.1 (d), 13 (d), 137.7 (s), 138.4 (s), 145.4 (s), 151.8 (s), 164.1 (s); IR (nujol): max = 1718 cm -1 ; MS m/z (%): 317 (M + ) (94), 286 (100); anal. calcd. for C19H15N3O2 (317.34): C 71.91, H 4.76, N 13.24; found: C 76, H 4.86, N 13.16. Cl N N Ph O Me 4g OEt Ethyl 3-(4-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4g): Pyrazole 4g was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 95% yield (161.9 mg) (3 h; TLC check). White solid; mp: 90 92 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.24 (t, J = 7.2 Hz, 3H), 8 (s, 3H), 4.25 (q, J = 7.2 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 7.43 (m, 5H), 7.62 (d, J = 8.8 Hz, 2H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.8 (q), 14.1 (q), 60.1 (t), 11 (s), 125.8 (d), 127.8 (d), 128.8 (d), 129.3 (d), 130.8 (d), 131.6 (s), 134.2 (s), 138.6 (s), 14 (s), 152.4 (s), 16 (s); IR (nujol): max = 1714 cm -1 ; MS m/z (%): 340 (M + ) (100), 295 (81); anal. calcd. for C19H17ClN2O2 (340.80): C 66.96, H 3, N 8.22; found: C 66.82, H 5.14, N 8.13. Methyl 3-(4-chlorophenyl)-5-ethyl-1-phenyl-1H-pyrazole-4-carboxylate (4h): Pyrazole 4h was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 100% (from 3h) (170.4 mg) (12 h; TLC check) or 54% yield (from 3k) (9 mg) (2 h; TLC check). Colorless oil; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.21 (t, J = 7.2 Hz, 3H), 2.94 (q, J = 7.2 Hz, 3H), 3.77 (s, 3H), 7.35 (m, 9H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 13.8 (q), 19.3 (t), 51.1 (q), 109.1 (s), 126.2 (d), 127.9 (d), 129.1 (d), 129.3 (d), 130.7 (d), 131.6 (s), 134.2 (s), 138.7 (s), 15 (s), 152.4 (s), 164.2 (s); IR (nujol): max = 1715 cm -1 ; MS m/z (%): 340 (M + ) (100), 309 (65); anal. calcd. for C19H17ClN2O2 (340.80): C 66.96, H 3, N 8.22; found: C 67.13, H 5.14, N 9. Methyl 1-(4-chlorophenyl)-5-methyl-3-phenyl-1H-pyrazole-4-carboxylate (4i): Pyrazole 4i was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 77% yield (125.8 mg) (5 h; TLC check). White solid; mp: 120 122 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 8 (s, 3H), 3.76 (s, 3H), 7.35 (m, 9H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.8 (q), 51.2 (q), 110.6 (s), 12 (d), 127.8 (d), 128.4 (d), 129.3 (d), 129.4 (d), 132.8 (s), 134.6 (s), 137.2 (s), 144.9 (s), 153.8 (s), 164.4 (s); IR (nujol): max = 1714 cm -1 ; MS m/z (%): 326 (M + ) (83), 295 (100); anal. calcd. for C18H15ClN2O2 (326.78): C 66.16, H 4.63, N 7; found: C 61, H 4.74, N 8.49. Benzyl 3-(4-chlorophenyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (4j): Pyrazole 4j was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 91% yield (183.4 mg) (5 h; TLC check). Colorless oil; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 8 (s, 3H), 5.24 (s, 2H), 7.20 (m, 14H); 13 C NMR 8
(100 MHz, CDCl3, 25 C): δ = 12.8 (q), 65.9 (t), 110.2 (s), 125.7 (d), 127.9 (d), 128.1 (d), 128.2 (d), 128.4 (d), 128.8 (d), 129.2 (d), 130.8 (d), 13 (s), 134.2 (s), 135.6 (s), 13 (s), 145.2 (s), 152.6 (s), 163.6 (s); IR (nujol): max = 1696 cm -1 ; MS m/z (%): 402 (M + ) (63), 295 (100); anal. calcd. for C24H19ClN2O2 (402.87): C 75, H 4.75, N 6.95; found: C 71.71, H 4.69, N 6.83. General procedure for the NaH-Mediated Cyclization of β-azohydrazone Adducts 3a k to Pyrazoles 5a h. To a magnetically stirred solution of β-azohydrazone adducts 3a k ( mmol) in CH3CN (3 ml) was added NaH (60% w/w in mineral oil, mmol) and the reaction was allowed to stand at room temperature until the complete disappearance of 3a k (3 36 h, monitored by TLC). The solution was concentrated under reduced pressure and then products 5a h were isolated by chromatography on silica gel column. tert-butyl 2-{1-[3-(4-chlorophenyl)-5-hydroxy-1-phenyl-1H-pyrazol-4- yl]ethylidene}hydrazinecarboxylate (5a): Pyrazole 5a was isolated by column chromatography (ethyl acetate/cyclohexane 10:90) in 46% (from 3a) (98.2 mg) (18 h; TLC check) or 33% (from 3g) (70.4 mg) (12 h; TLC check) or 65% (from 3j) yield (138.7 mg) (3 h; TLC check). Pale yellow solid; mp: 126 128 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.46 (s, 9H), 1.97 (s, 3H), (s, 1H), 7.18 (t, J = 7.6 Hz, 2H), 7.27 (m, 5H), 7.99 (d, J = Hz, 2H), (br, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 15.1 (q), 2 (q), 82.9 (s), 9 (s), 119.7 (d), 12 (d), 128.7 (d), 128.8 (d), 130.6 (d), 132.6 (s), 135.1 (s), 138.6 (s), 149.7 (s), 154.2 (s), 164.6 (s), 16 (s); IR (nujol): max = 3145, 1736 cm -1 ; MS m/z (%): 370 (7), 326 (58), 311 (16), 295 (63), 281 (59), 111 (100); anal. calcd. for C22H23ClN4O3 (426.90): C 61.90, H 5.43, N 13.12; found: C 61.76, H 6, N 14. tert-butyl 2-(1-{5-hydroxy-3-[4-(methoxycarbonyl)phenyl]-1-phenyl- 1H-pyrazol-4-yl}ethylidene)hydrazinecarboxylate (5b): Pyrazole 5b was isolated by column chromatography (ethyl acetate/cyclohexane 30:70) in 75% yield (168.9 mg) (5 h; TLC check). Pale yellow solid; mp: 300 302 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.45 (s, 9H), 1.96 (s, 3H), 3.94 (s, 3H), 7.16 (m, 3H), 7.39 (t, J = 7.6 Hz, 1H), (d, J = Hz, 1H), 7.99 (d, J = 8.4 Hz, 2H), 8.10 (d, J = Hz, 2H), (br, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 15.2 (q), 2 (q), 52.3 (q), 82.9 (s), 9 (s), 119.7 (d), 125.1 (s), 128.7 (d), 129.3 (d), 129.6 (d), 13 (d), 138.6 (s), 138.7 (s), 149.8 (s), 154.2 (s), 164.7 (s), 166.7 (s), 167.3 (s); IR (nujol): max = 3322, 1726 cm -1 ; MS m/z (%): 393 (2), 348 (10), 111 (100); anal. calcd. for C24H26N4O5 (450.49): C 63.99, H 5.82, N 12.44; found: C 63.90, H 5.69, N 12.35. 9
tert-butyl 2-{1-[3-(2,4-dichlorophenyl)-5-hydroxy-1-phenyl-1Hpyrazol-4-yl]ethylidene}hydrazinecarboxylate (5c): Pyrazole 5c was isolated by column chromatography (ethyl acetate/cyclohexane 10:90)in 69% yield (149.9 mg) (12 h; TLC check). White solid; mp: 162 164 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.46 (s, 9H), 1.92 (s, 3H), 5 (s, 1H), 7.18 (t, J = 7.2 Hz, 1H), 7.33 (m, 4H), (d, J = Hz, 1H), 7.99 (d, J = 7.6 Hz, 2H), (br, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 13.6 (q), 2 (q), 8 (s), 9 (s), 119.7 (d), 125.1 (d), 127.4 (d), 128.7 (d), 12 (d), 132.2 (s), 132.4 (d), 135.1 (s), 135.9 (s), 138.6 (s), 14 (s), 154.1 (s), 164.4 (s), 167.1 (s); IR (nujol): max = 3315, 1735 cm -1 ; MS m/z (%): 461 (M + ) (7), 404 (42), 369 (50), 360 (31), 345 (40), 325 (100), 310 (82); anal. calcd. for C22H22Cl2N4O3 (461.34): C 57.28, H 4.81, N 12.14; found: C 57.14, H 4.68, N 12.25. Ethyl 2-{1-[3-(4-bromophenyl)-5-hydroxy-1-phenyl-1H-pyrazol-4- yl]ethylidene}hydrazinecarboxylate (5d): Pyrazole 5d was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 52% yield (115.3 mg) (24 h; TLC check). Brown solid; mp: 144 146 C; 1 H NMR (400 MHz, DMSO-d6, 25 C): δ = 1.21 (t, J = 7.2 Hz, 3H), 1.97 (s, 3H), 2.11 (s, 3H), 4.12 (q, J = 7.2 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H); 13 C NMR (100 MHz, DMSO-d6, 25 C): δ = 14.4 (q), 15.3 (q), 61.6 (t), 9 (s), 11 (d), 122.4 (d), 12 (s), 128.8 (d), 131.3 (d), 131.4 (d), 133.3 (s), 138.8 (s), 14 (s), 15 (s), 164.3 (s), 16 (s); IR (nujol): max = 3378, 1736 cm -1 ; MS m/z (%): 443 (M + ) (13), 341 (12), 306 (9), 207 (42), 111 (100); anal. calcd. for C20H19BrN4O3 (443.29): C 54.19, H 4.32, N 12.64; found: C 55, H 4.20, N 15. tert-butyl 2-{1-[3-(3-bromophenyl)-5-hydroxy-1-phenyl-1H-pyrazol- 4-yl]ethylidene}hydrazinecarboxylate (5e): Pyrazole 5e was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 51% yield (120.2 mg) (36 h; TLC check). White solid; mp: 174 176 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.45 (s, 9H), 1.96 (s, 3H), 7.15 (m, 5H), 6 (d, J = Hz, 1H), 7.66 (s, 1H), 7.99 (d, J = Hz, 2H), 12.33 (br, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 15.2 (q), 2 (q), 82.8 (s), 98.8 (s), 119.7 (d), 12 (s), 125.1 (d), 12 (d), 128.8 (d), 129.9 (d), 13 (d), 132.1 (d), 13 (s), 13 (s), 149.4 (s), 154.2 (s), 16 (s), 167.2 (s); IR (nujol): max = 3148, 1744 cm -1 ; MS m/z (%): 413 (33), 149 (83), 109 (100); anal. calcd. for C22H23BrN4O3 (471.35): C 56, H 4.92, N 11.89; found: C 56.15, H 1, N 11.76. 10
NC N N Ph Me OH N H N CO t-bu (135.7 mg) (4 h; TLC check). Pale yellow solid; mp: 126 128 C; 1 H NMR 5f (400 MHz, CDCl3, 25 C): δ = 1.47 (s, 9H), 0 (s, 3H), 7 (s, 1H), 7.20 (t, J = 7.2 Hz, 1H), 7.40 (t, J = Hz, 2H), 7.62 (d, J = Hz, 2H), 7.72 (d, J = Hz, 2H), 7.98 (d, J = Hz, 2H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 15.4 (q), 28.1 (q), 83.1 (s), 98.8 (s), 112.7 (s), 118.4 (s), 119.7 (d), 125.3 (d), 128.8 (d), 13 (d), 132.2 (d), 138.4 (s), 138.9 (s), 148.8 (s), 154.1 (s), 164.6 (s), 166.9 (s); IR (nujol): max = 3196, 1741 cm -1 ; MS m/z (%): 317 (100), 286 (114.6 mg) (24 h; TLC check). Pale yellow solid; mp: 258 260 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 0.97 (t, J = 7.6 Hz, 2H), 1.47 (s, 9H), 2.34 (q, J = 7.6 Hz, 2H), 6.81 (s, 1H), 7.18 (t, J = 7.6 Hz, 1H), 7.35 (m, 6H), 0 (d, J = Hz, 2H), (br, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 12.3 (q), 20.8 (q), 2 (q), 83.1 (s), 98.4 (s), 119.7 (d), 12 (d), 128.6 (s), 128.7 (d), 130.4 (d), 13 (s), 135.1 (s), 138.7 (s), 14 (s), 15 (s), 165.1 (s), 172.2 (s); IR (nujol): max = 3149, 1745 cm -1 ; MS m/z (%): 340 (10), 311 (5), 149 (66), 111 (100); anal. calcd. for C23H25ClN4O3 (440.92): C 62.65, H 5.71, N 12.71; found: C 69, H 5.83, N 12.85. tert-butyl 2-{1-[3-(4-cyanophenyl)-5-hydroxy-1-phenyl-1H-pyrazol-4- yl]ethylidene}hydrazinecarboxylate (5f): Pyrazole 5f was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 65% yield (83), 272 (19), 149 (55), 111 (74); anal. calcd. for C23H23N5O3 (417.46): C 66.17, H 5, N 16.78; found: C 66.31, H 5.47, N 16.66. tert-butyl 2-{1-[3-(4-chlorophenyl)-5-hydroxy-1-phenyl-1H-pyrazol-4- yl]propylidene}hydrazinecarboxylate (5g): Pyrazole 5g was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 52% yield tert-butyl 2-{1-[1-(4-chlorophenyl)-5-hydroxy-3-phenyl-1H-pyrazol-4- yl]ethylidene}hydrazinecarboxylate (5h): Pyrazole 5h was isolated by column chromatography (ethyl acetate/cyclohexane 20:80) in 76% yield (162.2 mg) (5 h; TLC check). Pale yellow solid; mp: 200 202 C; 1 H NMR (400 MHz, CDCl3, 25 C): δ = 1.41 (s, 9H), 1.87 (s, 3H), 7.21 (d, J = 8.8 Hz, 2H), 7.30 (m, 5H), (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), (br, 1H); 13 C NMR (100 MHz, CDCl3, 25 C): δ = 16.2 (q), 28.1 (q), 84.9 (s), 97.8 (s), 12 (s), 121.4 (d), 128.1 (d), 128.2 (d), 128.9 (d), 129.4 (d), 136.3 (s), 138.7 (s), 151.1 (s), 154.3 (s), 15 (s), 16 (s); IR (nujol): max = 3166, 1748 cm -1 ; MS m/z (%): 326 (52), 311 (71), 297 (22), 295 (46), 281 (42), 149 (57), 129 (80), 127 (89), 111 (100); anal. calcd. for C22H23ClN4O3 (426.90): C 61.90, H 5.43, N 13.12; found: C 63, H 5.34, N 13.26. 11
3. 1 H and 13 C NMR spectra of products. 168.3829 166.2251 15589 147.1878 134.8525 133.4388 132.2661 12537 128.6400 127.6621 120.2463 113.9267 82.1868 77.3120 76.9944 76.6768 51.4616 28.1711 13.1772 12
13-1 1 1 6.81 9.79 3.16 2.28 2.14 0 2 0.72 0.75 2 2.21 14.44 0.95 0.65 6 10.37 3.31 2.74 8 0 3.21 2 3 0.82 0.88 7 12.48 1.93 2.26 1.90 0.97 0.71 1.3812 1.4035 1.7182 1.8258 2.4757 2.4803 2.4849 2.4895 2.4941 3.3229 3.4479 716 3.8125 3.8289 4.4039 4.4313 023 290 5.4205 5.4471 5.7527 5.7801 7.4830 7.4884 7.4971 057 103 138 356 604 684 711 804 853 7.6487 7.6699 7.8877 7.9088 7.9448 7.9659 9.4843 940 N N Ph N Me HN CO 2 Bu O OMe MeO 2 C 3b
14-1 1 1 21.21 3.14 2.40 2.38 0 7 0.82 0.80 3 13.28 1.63 0.89 0.92 0.72 5 2.84 0 0 0.90 1.10 2 3.30 0.75 0.24 0.30 0.76 1.75 1 0.80 0.26 0.9245 0.9419 0.9599 224 398 578 1.1254 1.1428 1.1608 1.1669 1.1845 1.2027 1.7509 1.8414 2.4757 2.4797 2.4840 3.3185 3.9995 172 339 502 639 814 990 4.3662 4.3938 5.3335 5.3605 5.6671 5.6947 7.3683 7.3894 7.4618 7.4813 7.4864 7.4953 028 231 575 630 732 784 9.8126 9.8687
15-1 1 1 7.80 9.85 6 2.34 2.46 0 0.98 0.79 0.78 0 1.17 0.95 12.96 1.91 0.86 0.67 25.75 0 2.86 3.19 2.97 0.94 0.90 0.93 0.88 9.70 2.27 2.29 5.67 0.85 0.89 1.3750 1.4071 1.7284 1.8263 2.4773 2.4816 3.3255 3.4588 706 4.4212 4.4487 121 385 5.4401 5.4664 5.7739 5.8014 7.4755 7.4845 7.4886 7.4955 053 120 358 454 563 657 7.6281 7.6487 7.7155 7.7359 7.7947 7.8155 7.8353 7.8561 256 9.6183
16-1 1 1 6 5 0 2 0.97 0.98 10.33 0.83 6 1.65 2.72 6 8 0 1.63 2.92 0.99 3 4 0 5.36 8.96 1.35 0.6412 0.6601 0.6788 0.8852 0.9041 0.9228 1.3707 2.1460 2.1649 2.1895 2.2083 2.2254 2.4792 2.4833 2.4874 3.3293 3.4525 550 865 3.6547 4.3866 4.4140 538 810 069 342 5.7406 5.7680 7.3516 7.3731 7.3951 7.4080 7.4166 7.4291 7.4618 7.4701 7.4784 7.4910 7.4989 074 196 547 608 658 699 790 1151 2t- 3g
17-1 1 1 9.76 10.15 3.15 2.85 2.84 0 4 0.95 0.99 4 8.97 7 7.90 0.98 0.85 20.38 0 1.73 0 0.40 4.60 7 0.83 12 14.83 0.79 0.39 1.3774 1.4102 1.7219 1.8207 2.4720 2.4764 2.4809 2.4854 2.4898 3.3372 4.4447 4.4657 4.4723 4.4800 159 431 4.9548 4.9937 202 516 931 5.1245 5.3667 5.7322 5.7598 7.2120 7.2170 7.2239 7.2371 7.2507 7.2652 7.2691 7.2894 7.3647 7.3804 7.3861 7.4012 7.4288 7.4504 7.4774 441 9.6263
0.89 8 3.19 2.14 5 3 3 0 2.10 9.24 3.10 1 1 1-18
19-1 1 1 0 2.93 1.91 2 1.96 12.7934 51.1205 76.6821 76.9998 77.3176 110.2268 125.7961 127.9368 128.8309 129.2877 130.7070 13067 134.2765 13958 14723 152.4598 164.3890
20-1 1 1 0 2.98 2.87 4.95 1.86 1.86 12.7407 51.1407 52.1094 76.6821 76.9997 77.3174 11226 125.8175 128.9116 12337 129.3302 129.3760 129.7303 137.6891 13933 145.2188 15075 164.3489 16442
21-1 1 1 0 2.96 0.97 0.94 5.70 12.4257 5949 51.1425 76.6815 76.9995 77.3176 111.8915 12537 126.6123 128.7257 128.9859 129.2021 131.6157 13557 134.6607 134.9188 138.4445 144.2640 150.1460 163.9411
22-1 1 1 4.91 0 1.96 8.85 12.7532 14.1110 29.6351 6630 76.6820 7000 77.3178 110.4421 122.4812 125.7411 128.7555 129.2393 130.7355 13832 13205 13874 144.9499 152.4058 163.8772
23-1 1 1 0 2.94 1.71 3 8 0.82 12.7459 29.6807 51.1313 51.1766 76.6820 76.9997 77.3173 110.3229 121.7560 125.8034 128.1251 128.8799 129.1903 129.3142 131.2311 132.2765 13588 13766 145.1558 15351 164.3016
1.89 1.94 4.92 2.97 0 1 1 1-24
25-1 1 1 7 0 1.98 1.95 4.93 1.90 12.7914 14.1388 60.1021 76.6818 76.9995 77.3173 110.4814 125.7927 127.8327 128.7963 129.2810 130.8144 13646 134.2183 138.6172 144.9755 152.4396 163.9458 4g
26-1 1 1 3.18 8 0 1.98 4.99 1.95 13.7808 19.2802 5534 5910 76.6821 76.9999 77.3177 109.1367 126.1781 127.8966 129.1117 129.3131 130.7069 13783 134.2068 138.6952 150.9538 152.4441 164.1725
27-1 1 1 0 2.99 6 4 1.91 12.7672 51.1096 51.1444 76.6821 76.9997 77.3174 110.6179 126.9722 127.7759 128.3776 129.2592 129.4315 132.8079 13636 137.2193 144.8711 153.8219 164.4390
28-1 1 1 0 3 6.73 6.92 12.8145 65.9218 76.6824 7001 77.3180 110.2450 125.7220 127.8622 12920 128.2159 128.3902 128.7866 129.2424 130.7924 13061 134.1671 135.6143 15661 163.6220
29 1 1 1 1 9.31 8.72 0 2.93 2.10 1.97 6 6.39 6.43 3 1 0.65 1822 2594 76.6820 76.9997 77.3174 82.8894 9411 119.6742 12135 128.6932 128.7370 13965 132.6299 13628 138.6309 149.7125 154.2076 164.6251 167.4693 5a N N Ph OH N H N CO2 t-bu Me Cl
30 1 1 1 1 7.76 2.80 0 1.68 1.90 1.80 1.98 1.87 0.64 15.2383 2475 52.2911 76.6820 76.9998 77.3175 82.9011 98.9796 119.7383 125.1072 128.7494 12442 129.3411 129.6400 130.4596 13471 138.6586 149.8289 154.1869 164.6779 166.6511 167.2893
31 1 1 1 1 9.24 0 1.11 1.14 4.18 4 3 0.91 13.6158 2494 76.6822 76.9997 77.3176 82.9793 9303 119.6962 12576 127.4894 128.7346 12434 132.1623 132.3844 13904 135.8522 13949 14113 154.1187 164.4129 16696
0.26 5 1.83 4.13 1.28 5 10.47 6.63 0 9.60 1 1 1 1 32
33 1 1 1 1 9.28 0 1.10 5.60 1 1 2.14 0.73 15.1583 2497 76.6825 7003 77.3181 82.8325 98.7933 119.7378 122.4796 125.1082 127.9485 128.7545 129.9096 13086 132.1138 13273 13055 149.3454 154.2056 164.4872 167.1808
34 1 1 1 1 9.41 0 4 6 2.18 2.15 2.15 2.15 0.75 15.4343 2691 76.6819 76.9996 77.3174 83.1167 98.8062 112.6521 118.4232 119.7178 125.2939 128.8075 13188 132.1803 138.4884 138.8730 148.7918 154.1200 16909 166.8981 N N Ph OH N H N CO2 t-bu Me NC
35 1 1 1 1 0 9.19 1 0.94 8 6.77 1 0.79 12.3466 20.8132 26.8892 2567 76.6824 7000 77.3177 8627 98.4076 119.6586 124.9718 126.2066 127.9264 128.6340 128.7180 129.3439 130.3935 130.7238 132.9616 13924 138.6519 149.4573 154.4830 16794 172.2386
36 1 1 1 1 9.28 0 2.13 1 1.12 2.13 0.10 16.1669 2795 76.6819 76.9995 77.3169 84.8570 97.7575 12108 121.3597 12971 128.2275 128.4714 128.6970 128.8717 129.2217 129.4166 136.2498 138.7123 151.1252 154.2512 15198 161.4717
4. References. (1) Deng, X.; Mani, N. S. J. Org. Chem. 2008, 2412. (2) Sommer, S. Tetrahedron Lett. 1977, 18, 117. (3) (a) Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S. Synthesis 1984, 671. (b) Attanasi, O. A.; Filippone, P.; Mei, A.; Santeusanio, S. Synthesis 1984, 873. (c) Preti, L.; Attanasi, O. A.; Caselli, E.; Favi, G.; Ori, C.; Davoli, P.; Felluga, F.; Prati, F. Eur. J. Org. Chem. 2010, 4312. (4) (a) Safaei, S.; Mohammadpoor-Baltork, I.; Khosropour, A. R.; Moghadam, M.; Tangestaninejad, S.; Mirkhani, V. Synlett. 2011, 2214. (b) Shen, L.; Cao, S.; Liu, N.; Wu, J.; Zhu, L.; Qian, X. Synlett. 2008, 1341. 37