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DOI: 10.1055/a-1661-5655
Ru-Catalyzed Selective C–H Functionalization of Pyridotriazoles with Acrylates
Abstract
Ruthenium-catalyzed efficient and selective C–H alkenylation of pyridotriazoles with acrylates is described. The combination of metals (Ru and Fe) plays a crucial role in achieving quantitative yields of the desired products. The reaction is proposed to involve the formation of a ruthenium cyclometalated intermediate.
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Transition-metal-catalyzed C–H bond activation has emerged as a new tool in organic synthesis for the functionalization of arenes.[1] In general, selective C–H functionalization is controlled by the directing/functional groups present on the substrates. Therefore, the use of directing groups by transition-metal-catalyzed C–H functionalization has aroused much attention in recent years.[2] Directing groups such as carboxyl,[3] carbonyl,[4] cyano,[5] and hydroxyl[6] are well-known for various transition-metal-catalyzed C–H functionalizations of arenes.
Pyridotriazole is an important scaffold in organic chemistry and plays an important role in several transition-metal-catalyzed denitrogenative transannelation reactions to generate diverse heterocycles.[7] [8] However, to the best of our knowledge, C–H alkenylation reaction using the pyridotriazole as a directing group to form C(sp2)–C(sp2) bonds has never been attempted. In continuation of our works on the transannelation of pyridotriazoles,[8] we herein describe the ruthenium-catalyzed regioselective alkenylation of pyridotriazoles (Scheme [1]).
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Initially, we focused on the optimization of reaction conditions for the selective alkenylation of pyridotriazole 1a with 2a in the presence of [RuCl2(p-cymene)]2 (5 mol%) as the catalyst with 2.0 equiv. of potassium acetate at 140 °C in 1,4-dioxane (1 mL) for 36 h (Table [1]). Under these conditions, a trace amount of product 3a formation was observed (entry 1). With Cu(OAc)2 (0.5 equiv.) as an additive in the absence of base, 20% yield of 3a was obtained (entry 2).
a Conditions: 1a (0.25 mmol), 2a (0.5 mmol), catalyst, additive, base, solvent (1 mL), in an oil bath at 140 ℃ for 24 h.
b Isolated yield.
When the reaction was performed without any catalyst, no product formation was observed (entry 3). When the reaction was performed with 5 mol% [RuCl2(p-cymene)]2, 0.5 equiv. of Cu(OAc)2, and 2.0 equiv. of KOAc, a 42% yield of 3a was obtained after 48 h (entry 4). After screening various solvents (DCE, toluene, DMF, and DMSO) as well as different catalysts (Co, Ni, and Pd) either no reaction or no improvement in yield was observed (entries 5–12). On increasing the amount of additive Cu(OAc)2, to one and two equivalents, the yield of the product was increased to 62% (entries 13 and 14). Performing the reaction with two equivalents of ZnCl2 and FeCl3 as additives 36% and 73% yields of desired product were obtained, respectively (entries 15 and 16). With FeCl3 as additive, the amount of base (KOAc) was decreased to 1.0 equiv., and under these conditions the desired product 3a was obtained in 90% yield (entry 17). On decreasing the base to 0.5 equiv. the yield was reduced to 74% (entry 18). The best yield of 3a was thus obtained under the conditions of entry 17; hence these parameters were set as optimum for further alkenylations of pyridotriazoles with different acrylates (Table [1]).
With this set of optimized conditions, the C–H functionalization of 3-phenyl[1,2,3]triazolo[1,5-a]pyridine (1a) with different acrylates was examined (Scheme [2]).
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Acrylates bearing Me, Et, and Bu groups at the terminal position reacted smoothly with 3-phenyl-[1,2,3]triazolo[1,5-a]pyridine (1a) to afford the corresponding alkenylated products 3a–c in good to excellent yields (72–90%). The reaction of methyl methacrylate also gave the corresponding functionalized product 3d in good yield (87%). Other acrylates such as 2-methoxyethyl acrylate, 2-hydroxyethyl (Z)-but-2-enoate, and 2,2,2-trifluoroethyl acrylate reacted well under the optimized conditions and afforded the corresponding products 3e–g in good to excellent yields (70–90%). Under the same conditions, 3-[(allyloxy)methyl]heptane and acrylonitrile afforded the corresponding products 3h and 3i in 91% and 67% yields, respectively. As is evident from the yields of products 3f–i, effects associated with electron-donating or electron-withdrawing substituents on the acrylate moiety do not affect the efficiency of the transformation.
This transformation is not limited to the 3-phenyl[1,2,3]triazolo[1,5-a]pyridine (1a); indeed, the triazole bearing a chlorine substituent at the 4-position of the phenyl ring 3-(4-chlorophenyl)-[1,2,3]triazolo[1,5-a]pyridine (1b) proved to be amenable to this procedure under the same optimized conditions. Similar reactivities of a range of acrylates were observed with 1b and afford the differently functionalized products 4a–h in good yields ranging from 65–88% (Scheme [3]).
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To gain insight into the reaction mechanism, some control experiments were performed (Scheme [4]). Initially, the reaction was conducted by the addition of the radical scavenger TEMPO under the optimized conditions to establish whether the reaction proceeds via a radical or ionic pathway (Scheme [4a]). Under these conditions, no adduct formation was observed, indicating that the reaction does not proceed through a radical pathway. However, 2-benzoyl pyridine (5) was observed as a side product. To establish possible intermediates, 2-benzylpyridine (6) was reacted with 2a under the standard conditions, but the expected product 3a was not observed (Scheme [4b]). Furthermore, when 2-benzoylpyridine (5) was reacted with 2a under the same conditions, it did not yield 3a (Scheme [4c]). These two reactions (Scheme [4b] and c) suggest that both 5 and 6 are not intermediates in the reaction pathway.
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Based on the control experiments and literature reports,[9] a plausible reaction mechanism is proposed (Scheme [5]). Initially, [RuCl2(p-cymene)]2 in the presence of base (KOAc) generates the active Ru(II) species A, which upon coordination with a nitrogen of the pyridotriazole ring and subsequent ligand-assisted C–H ruthenation via intermediate B gives the ruthenacyclic intermediate C.
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Coordination of the Ru center of C with the addition of the alkene leads to the ruthenacyclic intermediate D that, followed by β-hydride elimination, gives the desired alkenylated products 3/4.
In conclusion, we have developed a ruthenium-catalyzed regioselective C–H alkenylation of pyridotriazoles with a range of acrylates.[10] Different acrylates bearing Me, Et, Bu, trifluoroethyl, 2-methoxyethyl acrylate, 2-hydroxyethyl (Z)-but-2-enoate, 3-((allyloxy)methyl)heptane, and acrylonitrile reacted smoothly and afforded the corresponding products in good yields. Control experiments suggest that the reaction proceeds through an ionic pathway.
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Conflict of Interest
The authors declare no conflict of interest.
Acknowledgment
CSIR-CSMCRI communication No. 184/2021. S. R. is grateful to AcSIR for their PhD enrolment scheme and the ‘Analytical Discipline and Centralized Instrumental Facilities’ for providing instrumentation facilities.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1661-5655.
- Supporting Information
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References and Notes
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10
Experimental SectionAll commercially available chemicals and reagents were used without any further purification unless otherwise indicated. 1H and 13C NMR spectra were recorded at 600, 200, 150, and 125 MHz, respectively. Spectra were recorded in CDCl3 as solvent. Multiplicity is indicated as follows: s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of doublets), and coupling constants (J) are given in Hz. Chemical shifts are reported in ppm relative to TMS as an internal standard. Mass spectra were obtained using electron impact (EI) ionization. Progress of the reactions was monitored by thin-layer chromatography (TLC). All products were purified through column chromatography using silica gel with 100–200 mesh size using ethyl acetate/hexane as eluent unless otherwise stated.General Procedures(A) Synthesis of Triazolopyridine Derivatives 1Hydrazine monohydrate (0.30 mmol) and acetic acid (0.02 mmol) were added to a solution of the requisite 2-acylpyridine (0.20 mmol) in ethanol (1.0 mL) at room temperature. The reaction mixture was heated at reflux for 6 h, and then EtOAc (5.0 mL) and Cu(OAc)2 (0.01 mmol) were added. After stirring at the indicated temperature for the indicated time, the resulting mixture was cooled to room temperature and then diluted with EtOAc (20 mL). The organic phase was washed with water (10 mL) and then dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, followed by purification by column chromatography, the desired triazolopyridine derivatives were isolated.(B) Synthesis of Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3a)To a reaction tube equipped with a magnetic stir bar, 3-phenyl[1,2,3]triazolo[1,5-a]pyridine (1a, 48.8 mg, 0.25 mmol), methyl acrylate (2a, 43.1 mg, 0.5 mmol), [RuCl2(p-cymene)]2 (6.75 mg, 5 mol%), FeCl3 (81.1 mg, 0.5 mmol), and base KOAc (24.5 mg, 0.25 mmol) were added, followed by dry 1,4-dioxane (1 mL). The mixture was heated in a carousel reaction station at 140 °C in a closed tube for 48 h, and progress was monitored by TLC. After completion of reaction, it was allowed to cool to room temperature. Then the mixture was poured into brine (30 mL). The product was extracted with EtOAc (3 × 15 mL) and dried with anhydrous Na2SO4. After filtration and removal of solvent under reduced pressure the residue was purified by column chromatography using silica gel (20% EtOAc/hexane) to afford 3a (62.8 mg, 90% yield).Characterization Data
Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3a)Yield (62.8 mg, 90% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.2 Hz, 1 H), 7.89 (d, J = 16.0 Hz, 1 H), 7.81 (d, J = 7.7 Hz, 1 H), 7.66–7.64 (m, 2 H), 7.53 (t, J = 7.4 Hz, 1 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.31–7.27 (m, 1 H), 7.06 (t, J = 6.8 Hz, 1 H), 6.51 (d, J = 16.0 Hz, 1 H), 3.73 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 167.1, 143.2, 136.6, 133.4, 132.0, 131.2, 130.8, 130.1, 128.7, 127.1, 125.8, 125.5, 119.3, 118.1, 115.5, 51.6. ESI-HRMS: m/z [M + Na]+ calcd for C19H15NONa: 302.0900; found: 302.0898.Ethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3b)Yield (52.8 mg, 72% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.79 (dd, J = 6.9, 2.7 Hz, 1 H), 7.85 (d, J = 16.0 Hz, 1 H), 7.80 (d, J = 7.7 Hz, 1 H), 7.66 (dd, J = 15.4, 8.1 Hz, 2 H), 7.52–7.49 (m, 1 H), 7.47 (t, J = 7.4 Hz, 1 H), 7.28 (d, J = 6.9 Hz, 1 H), 7.03 (t, J = 6.9 Hz, 1 H), 6.49 (d, J = 15.4 Hz, 1 H), 4.19–4.15 (m, 2 H), 1.25 (td, J = 6.9, 1.9 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.6, 143.0, 136.6, 133.4, 132.0, 131.2, 130.8, 130.1, 128.7, 127.1, 125.8, 125.5, 119.8, 118.1, 115.4, 60.4, 14.2. ESI-HRMS: m/z [M + Na]+ calcd for C17H15N3O2Na: 316.1056; found: 316.1056.Butyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3c)Yield (69.1 mg, 86% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.79 (d, J = 7.1 Hz, 1 H), 7.83–7.79 (m, 2 H), 7.67 (d, J = 7.3 Hz, 1 H), 7.63 (d, J = 8.9 Hz, 1 H), 7.53–7.450 (m, 1 H), 7.48 (t, J = 7.5 Hz, 1 H), 7.29–7.26 (m, 1 H), 7.04 (q, J = 7.1 Hz, 1 H), 6.50 (d, J = 15.9 Hz, 1 H), 4.13 (t, J = 6.5 Hz, 2 H), 1.61–1.55 (m, 2 H), 1.34–1.24 (m, 2 H), 0.91–0.86 (m, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.7, 142.9, 142.2, 136.6, 133.4, 132.0, 131.2, 130.9, 130.1, 128.7, 128.1, 127.0, 125.8, 125.5, 120.7, 119.8, 118.1, 115.4, 64.3, 30.6, 19.1, 19.0, 13.7. GC–MS: m/z [M] calcd for C19H19N3O2: 321.1477; found: 321.00.Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)-2-methylacrylate (3d)Yield (63.8 mg, 87% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.76 (d, J = 7.1 Hz, 1 H), 7.71–7.70 (m, 1 H), 7.63 (s, 1 H), 7.55 (d, J = 8.7 Hz, 1 H), 7.50–7.46 (m, 3 H), 7.25–7.22 (m, 1 H), 7.01 (t, J = 6.7 Hz, 1 H), 3.68 (s, 3 H), 2.06 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 167.1, 166.7, 143.7, 143.6, 141.0, 134.8, 133.9, 130.8, 130.7, 130.5, 129.8, 129.2, 129.1, 128.4, 127.9, 124.0, 122.9, 120.4, 112.8, 52.5, 29.8. GC–MS: m/z [M] calcd for C17H15N3O2: 293.1164; found: 293.10.2-Methoxyethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3e)Yield (65.5 mg, 81% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.83 (d, J = 7.0 Hz, 1 H), 7.84 (s, 1 H), 7.82–7.80 (m, 2 H), 7.65 (d, J = 8.5 Hz, 2 H), 7.53 (dd, J = 8.2, 1.8 Hz, 1 H), 7.36–7.32 (m, 1 H), 7.10 (t, J = 6.7 Hz, 1 H), 6.60 (d, J = 15.9 Hz, 1 H), 4.34–4.32 (m, 2 H), 3.65–3.63 (m, 2 H), 3.41 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.4, 142.4, 135.7, 135.1, 135.0, 132.2, 130.3, 129.8, 127.2, 126.3, 125.7, 120.7, 118.0, 115.7, 70.5, 63.8, 59.1. GC–MS: m/z [M] calcd for C18H17N3O3: 323.1270; found: 323.00.2-Hydroxyethyl (E)-3-(2-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}phenyl)but-2-enoate (3f)Yield (56.6 mg, 70% yield, semisolid), eluent 50% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.76 (s, 1 H), 7.76 (d, J = 41.3 Hz, 2 H), 7.60 (s, 1 H), 7.51–7.48 (m, 3 H), 7.26 (s, 2 H), 7.01 (s, 1 H), 4.24 (s, 2 H), 3.78 (s, 2 H), 2.07 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 168.7, 139.2, 137.2, 134.7, 131.8, 130.8, 130.2, 128.8, 128.5, 128.1, 125.6, 118.4, 115.5, 66.6, 61.4, 14.2. GC–MS: m/z [M] calcd for C18H17N3O3: 323.1270; found: 323.00.2,2,2-Trifluoroethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3g)Yield (78.0 mg, 90% yield, semisolid), eluent 10% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.1 Hz, 1 H), 8.02 (d, J = 15.9 Hz, 1 H), 7.83 (d, J = 7.9 Hz, 1 H), 7.69 (d, J = 7.8 Hz, 1 H), 7.65 (d, J = 8.9 Hz, 1 H), 7.55 (t, J = 7.7 Hz, 1 H), 7.49 (d, J = 7.6 Hz, 1 H), 7.31–7.28 (m, 1 H), 7.06 (t, J = 6.8 Hz, 1 H), 6.56 (d, J = 16.0 Hz, 1 H), 4.55 (q, J = 8.2 Hz, 2 H). 13C NMR (150 MHz, CDCl3): δ = 165.0, 164.2, 146.9, 145.8, 136.4, 132.9, 132.1, 131.7, 130.8, 130.3, 129.6, 129.4, 129.1, 128.9, 128.0, 127.4, 126.7, 126.2, 125.7, 125.7, 125.6, 125.5, 124.0, 122.2, 118.5, 118.2, 118.0, 117.4, 115.6, 115.6, 60.7, 60.4, 60.2, 60.0. GC–MS: m/z [M] calcd for C17H12F3N3O2: 347.0882; found: 347.00.(E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylonitrile (3h)Yield (56.0 mg, 91% yield, semisolid), eluent 30% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.82 (d, J = 7.0 Hz, 1 H), 7.77 (d, J = 16.8 Hz, 1 H), 7.72 (d, J = 7.8 Hz, 1 H), 7.69 (d, J = 8.7 Hz, 1 H), 7.64 (d, J = 7.6 Hz, 1 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.36–7.33 (m, 1 H), 7.09 (t, J = 6.9 Hz, 1 H), 5.94 (d, J = 17.0 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 149.3, 136.1, 132.7, 132.0, 131.0, 130.8, 130.6, 130.6, 128.8, 126.5, 126.3, 125.6, 118.1, 117.7, 115.7, 97.5. GC–MS: m/z [M] calcd for C15H10N4: 246.0905; found: 246.20.2-Ethylhexyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3i)Yield (60.6 mg, 67% yield, yellow liquid), eluent 15% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80–8.79 (m, 1 H), 7.78–7.72 (m, 2 H), 7.62 (t, J = 8.7 Hz, 2 H), 7.49 (dd, J = 8.1, 2.3 Hz, 1 H), 7.31–7.29 (m, 1 H), 7.06 (t, J = 6.5 Hz, 1 H), 6.51 (d, J = 16.1 Hz, 1 H), 4.07 (qd, J = 10.9, 5.7 Hz, 2 H), 1.56 (t, J = 6.0 Hz, 1 H), 1.31–1.24 (m, 11 H), 0.88–0.83 (m, 8 H). 13C NMR (150 MHz, CDCl3): δ = 166.6, 141.6, 135.7, 135.1, 134.9, 132.2, 132.1, 130.2, 129.8, 127.1, 126.2, 125.7,
121.1, 118.0, 115.6, 67.1, 38.8, 30.4, 29.0, 23.8, 23.0, 14.1, 11.1. GC–MS: m/z [M] calcd for C23H27N3O2: 377.2103; found: 377.30.Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4a)Yield (65.1 mg, 83% yield, semisolid), eluent 25% ethyl acetate/hexane). 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.0 Hz, 1 H), 7.81–7.76 (m, 2 H), 7.61–7.58 (m, 2 H), 7.49 (d, J = 8.1 Hz, 1 H), 7.32–7.30 (t, J = 6.0 Hz, 1 H), 7.06 (d, J = 6.8 Hz, 1 H), 6.50 (d, J = 16.1 Hz, 1 H), 3.73 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.7, 141.9, 135.5, 135.0, 134.8, 132.0, 130.1, 129.6, 127.1, 126.2, 125.6, 120.5, 117.8, 115.6, 51.8. GC–MS: m/z [M] calcd for C16H12ClN3O2: 313.0618; found: 313.00.Ethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4b)Yield (61.3 mg, 75% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.77 (s, 1 H), 7.84–7.79 (m, 2 H), 7.65 (s, 2 H), 7.50–7.46 (m, 2 H), 7.27 (s, 1 H), 7.02 (s, 1 H), 6.49 (d, J = 15.7 Hz, 1 H), 4.17 (s, 2 H), 1.24 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.8, 143.1, 136.7, 133.6, 132.2, 131.4, 131.0, 130.2, 128.9, 127.2, 125.9, 125.6, 120.0, 118.3, 115.6, 60.5, 14.4. ESI-HRMS: m/z [M + Na]+ calcd for C17H14ClN3O2Na: 350.0667; found: 350.0632.Butyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4c)Yield (76.5 mg, 86% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.1 Hz, 1 H), 7.82 (d, J = 7.8 Hz, 1 H), 7.68 (d, J = 7.3 Hz, 1 H), 7.64 (d, J = 8.9 Hz, 1 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 1 H), 7.30–7.27 (m, 1 H), 7.05 (t, J = 6.8 Hz, 1 H), 6.51 (d, J = 15.9 Hz, 1 H), 4.14 (t, J = 6.5 Hz, 2 H), 1.62–1.58 (m, 2 H), 1.36–1.33 (m, 2 H), 0.92–0.88 (m, 3 H). 13C NMR (150 MHz, CDCl3): δ = 160.0, 159.3, 156.9, 143.9, 138.1, 136.8, 136.2, 130.2, 129.1, 127.6, 122.3, 120.9, 120.5, 114.9, 114.4, 114.3, 113.9, 112.1, 105.4, 55.3, 32.4, 31.2, 30.3. GC–MS: m/z [M] calcd for C19H18ClN3O2: 355.1058; found: 355.10.Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)-2-methylacrylate (4d)Yield (67.2 mg, 82% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.77 (d, J = 7.1 Hz, 1 H), 7.72–7.70 (m, 1 H), 7.64 (s, 1 H), 7.56 (d, J = 8.7 Hz, 1 H), 7.51–7.49 (m, 1 H), 7.48 (d, J = 3.3 Hz, 1 H), 7.25 (t, J = 7.32 Hz, 1 H), 7.02 (t, J = 6.7 Hz, 1 H), 3.69 (s, 3 H), 2.07 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 160.0, 134.8, 131.2, 129.9, 129.0, 128.5, 126.5, 124.8, 124.2, 123.0, 121.7, 121.0, 115.0, 114.3, 109.2, 55.5, 29.7. GCMS: m/z [M] calcd for C17H14ClN3O2: 327.0775; found: 327.05.2-Methoxyethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4e)Yield (69.8 mg, 78% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.79 (d, J = 7.0 Hz, 1 H), 7.80–7.76 (m, 2 H), 7.60 (d, J = 8.5 Hz, 2 H), 7.49 (dd, J = 8.2, 1.8 Hz, 1 H), 7.32–7.28 (m, 1 H), 7.06 (t, J = 6.7 Hz, 1 H), 6.56 (d, J = 15.9 Hz, 1 H), 4.30–4.28 (m, 2 H), 3.61–3.59 (m, 2 H), 3.37 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.2, 142.2, 135.5, 134.9, 134.8, 132.0, 130.2, 129.7, 127.1, 126.2, 125.6, 120.5, 117.8, 115.6, 70.4, 63.7, 59.0. GC–MS: m/z [M] calcd for C18H16ClN3O3: 357.0880; found: 357.10.2-Hydroxyethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)but-2-enoate (4f)Yield (58.1 mg, 65% yield, semisolid), eluent 45% ethyl acetate/hexane). 1H NMR (600 MHz, CDCl3): δ = 8.83 (d, J = 7.1 Hz, 1 H), 7.84–7.80 (m, 2 H), 7.65 (d, J = 8.6 Hz, 2 H), 7.53 (d, J = 8.3 Hz, 1 H), 7.36–7.32 (m, 1 H), 7.10 (t, J = 6.8 Hz, 1 H), 6.60 (d, J = 15.8 Hz, 1 H), 4.33 (t, J = 4.7 Hz, 2 H), 3.65 (t, J = 4.7 Hz, 2 H), 3.41 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 168.7, 139.2, 137.2, 134.6, 131.8, 130.8, 130.2, 128.7, 128.5, 128.1, 125.6, 118.4, 115.5, 66.6, 61.4, 14.2. GC–MS: m/z [M] calcd for C18H16ClN3O3: 357.0880; found: 357.10.2,2,2-Trifluoroethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4g)Yield (84 mg, 88% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.71 (d, J = 7.2 Hz, 1 H), 7.93 (d, J = 16.0 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.57 (d, J = 9.0 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.42 (q, J = 7.8, 7.3 Hz, 1 H), 6.97 (t, J = 6.9 Hz, 1 H), 6.47 (d, J = 16.0 Hz, 1 H), 4.46 (q, J = 8.1 Hz, 2 H). 13C NMR (150 MHz, CDCl3): δ = 167.0, 166.6, 143.6, 143.5, 140.9, 134.7, 133.8, 130.7, 130.6, 130.4, 129.7, 129.1, 129.0, 128.3, 127.8, 123.9, 122.8, 120.3, 112.7, 52.4, 29.7. GC–MS: m/z [M] calcd for C17H11ClF3N3O2: 381.0492; found: 381.30.(E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylonitrile (4h).Yield (60.4 mg, 86% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.24 (d, J = 7.8 Hz, 1 H), 8.02 (d, J = 6.7 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1H ), 7.72 (d, J = 9.2 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 2 H), 7.39 (t, J = 7.5 Hz, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 6.81 (t, J = 6.7 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 149.3, 145.7, 140.1, 128.9, 125.3, 125.2, 124.3, 124.1, 124.0, 122.4, 121.5, 118.2, 111.9. GC–MS: m/z [M] calcd for C15H9ClN4: 280.0516; found: 280.0.Phenyl(pyridin-2-yl)methanone (5)11
Yield (14.0 mg, 31% yield, white solid), mp 42–44 ℃), 5% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.71 (d, J = 4.3 Hz, 1 H), 8.07 (d, J = 7.7 Hz, 2 H), 8.03 (d, J = 7.8 Hz, 1 H), 7.88 (t, J = 7.7 Hz, 1 H), 7.58 (t, J = 7.3 Hz, 1 H), 7.47 (dd, J = 14.2, 6.9 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 193.7, 154.9, 148.4, 136.9, 136.1, 132.7, 130.8, 128.0, 126.0, 124.4.
- 11 Joshi A, Kumar R, Semwal R, Rawat D, Adimurthy S. Green Chem. 2019; 21: 962
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Corresponding Author
Publication History
Received: 23 September 2021
Accepted after revision: 04 October 2021
Accepted Manuscript online:
05 October 2021
Article published online:
13 October 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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10
Experimental SectionAll commercially available chemicals and reagents were used without any further purification unless otherwise indicated. 1H and 13C NMR spectra were recorded at 600, 200, 150, and 125 MHz, respectively. Spectra were recorded in CDCl3 as solvent. Multiplicity is indicated as follows: s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of doublets), and coupling constants (J) are given in Hz. Chemical shifts are reported in ppm relative to TMS as an internal standard. Mass spectra were obtained using electron impact (EI) ionization. Progress of the reactions was monitored by thin-layer chromatography (TLC). All products were purified through column chromatography using silica gel with 100–200 mesh size using ethyl acetate/hexane as eluent unless otherwise stated.General Procedures(A) Synthesis of Triazolopyridine Derivatives 1Hydrazine monohydrate (0.30 mmol) and acetic acid (0.02 mmol) were added to a solution of the requisite 2-acylpyridine (0.20 mmol) in ethanol (1.0 mL) at room temperature. The reaction mixture was heated at reflux for 6 h, and then EtOAc (5.0 mL) and Cu(OAc)2 (0.01 mmol) were added. After stirring at the indicated temperature for the indicated time, the resulting mixture was cooled to room temperature and then diluted with EtOAc (20 mL). The organic phase was washed with water (10 mL) and then dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, followed by purification by column chromatography, the desired triazolopyridine derivatives were isolated.(B) Synthesis of Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3a)To a reaction tube equipped with a magnetic stir bar, 3-phenyl[1,2,3]triazolo[1,5-a]pyridine (1a, 48.8 mg, 0.25 mmol), methyl acrylate (2a, 43.1 mg, 0.5 mmol), [RuCl2(p-cymene)]2 (6.75 mg, 5 mol%), FeCl3 (81.1 mg, 0.5 mmol), and base KOAc (24.5 mg, 0.25 mmol) were added, followed by dry 1,4-dioxane (1 mL). The mixture was heated in a carousel reaction station at 140 °C in a closed tube for 48 h, and progress was monitored by TLC. After completion of reaction, it was allowed to cool to room temperature. Then the mixture was poured into brine (30 mL). The product was extracted with EtOAc (3 × 15 mL) and dried with anhydrous Na2SO4. After filtration and removal of solvent under reduced pressure the residue was purified by column chromatography using silica gel (20% EtOAc/hexane) to afford 3a (62.8 mg, 90% yield).Characterization Data
Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3a)Yield (62.8 mg, 90% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.2 Hz, 1 H), 7.89 (d, J = 16.0 Hz, 1 H), 7.81 (d, J = 7.7 Hz, 1 H), 7.66–7.64 (m, 2 H), 7.53 (t, J = 7.4 Hz, 1 H), 7.49 (d, J = 7.2 Hz, 1 H), 7.31–7.27 (m, 1 H), 7.06 (t, J = 6.8 Hz, 1 H), 6.51 (d, J = 16.0 Hz, 1 H), 3.73 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 167.1, 143.2, 136.6, 133.4, 132.0, 131.2, 130.8, 130.1, 128.7, 127.1, 125.8, 125.5, 119.3, 118.1, 115.5, 51.6. ESI-HRMS: m/z [M + Na]+ calcd for C19H15NONa: 302.0900; found: 302.0898.Ethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3b)Yield (52.8 mg, 72% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.79 (dd, J = 6.9, 2.7 Hz, 1 H), 7.85 (d, J = 16.0 Hz, 1 H), 7.80 (d, J = 7.7 Hz, 1 H), 7.66 (dd, J = 15.4, 8.1 Hz, 2 H), 7.52–7.49 (m, 1 H), 7.47 (t, J = 7.4 Hz, 1 H), 7.28 (d, J = 6.9 Hz, 1 H), 7.03 (t, J = 6.9 Hz, 1 H), 6.49 (d, J = 15.4 Hz, 1 H), 4.19–4.15 (m, 2 H), 1.25 (td, J = 6.9, 1.9 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.6, 143.0, 136.6, 133.4, 132.0, 131.2, 130.8, 130.1, 128.7, 127.1, 125.8, 125.5, 119.8, 118.1, 115.4, 60.4, 14.2. ESI-HRMS: m/z [M + Na]+ calcd for C17H15N3O2Na: 316.1056; found: 316.1056.Butyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3c)Yield (69.1 mg, 86% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.79 (d, J = 7.1 Hz, 1 H), 7.83–7.79 (m, 2 H), 7.67 (d, J = 7.3 Hz, 1 H), 7.63 (d, J = 8.9 Hz, 1 H), 7.53–7.450 (m, 1 H), 7.48 (t, J = 7.5 Hz, 1 H), 7.29–7.26 (m, 1 H), 7.04 (q, J = 7.1 Hz, 1 H), 6.50 (d, J = 15.9 Hz, 1 H), 4.13 (t, J = 6.5 Hz, 2 H), 1.61–1.55 (m, 2 H), 1.34–1.24 (m, 2 H), 0.91–0.86 (m, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.7, 142.9, 142.2, 136.6, 133.4, 132.0, 131.2, 130.9, 130.1, 128.7, 128.1, 127.0, 125.8, 125.5, 120.7, 119.8, 118.1, 115.4, 64.3, 30.6, 19.1, 19.0, 13.7. GC–MS: m/z [M] calcd for C19H19N3O2: 321.1477; found: 321.00.Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)-2-methylacrylate (3d)Yield (63.8 mg, 87% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.76 (d, J = 7.1 Hz, 1 H), 7.71–7.70 (m, 1 H), 7.63 (s, 1 H), 7.55 (d, J = 8.7 Hz, 1 H), 7.50–7.46 (m, 3 H), 7.25–7.22 (m, 1 H), 7.01 (t, J = 6.7 Hz, 1 H), 3.68 (s, 3 H), 2.06 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 167.1, 166.7, 143.7, 143.6, 141.0, 134.8, 133.9, 130.8, 130.7, 130.5, 129.8, 129.2, 129.1, 128.4, 127.9, 124.0, 122.9, 120.4, 112.8, 52.5, 29.8. GC–MS: m/z [M] calcd for C17H15N3O2: 293.1164; found: 293.10.2-Methoxyethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3e)Yield (65.5 mg, 81% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.83 (d, J = 7.0 Hz, 1 H), 7.84 (s, 1 H), 7.82–7.80 (m, 2 H), 7.65 (d, J = 8.5 Hz, 2 H), 7.53 (dd, J = 8.2, 1.8 Hz, 1 H), 7.36–7.32 (m, 1 H), 7.10 (t, J = 6.7 Hz, 1 H), 6.60 (d, J = 15.9 Hz, 1 H), 4.34–4.32 (m, 2 H), 3.65–3.63 (m, 2 H), 3.41 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.4, 142.4, 135.7, 135.1, 135.0, 132.2, 130.3, 129.8, 127.2, 126.3, 125.7, 120.7, 118.0, 115.7, 70.5, 63.8, 59.1. GC–MS: m/z [M] calcd for C18H17N3O3: 323.1270; found: 323.00.2-Hydroxyethyl (E)-3-(2-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}phenyl)but-2-enoate (3f)Yield (56.6 mg, 70% yield, semisolid), eluent 50% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.76 (s, 1 H), 7.76 (d, J = 41.3 Hz, 2 H), 7.60 (s, 1 H), 7.51–7.48 (m, 3 H), 7.26 (s, 2 H), 7.01 (s, 1 H), 4.24 (s, 2 H), 3.78 (s, 2 H), 2.07 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 168.7, 139.2, 137.2, 134.7, 131.8, 130.8, 130.2, 128.8, 128.5, 128.1, 125.6, 118.4, 115.5, 66.6, 61.4, 14.2. GC–MS: m/z [M] calcd for C18H17N3O3: 323.1270; found: 323.00.2,2,2-Trifluoroethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3g)Yield (78.0 mg, 90% yield, semisolid), eluent 10% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.1 Hz, 1 H), 8.02 (d, J = 15.9 Hz, 1 H), 7.83 (d, J = 7.9 Hz, 1 H), 7.69 (d, J = 7.8 Hz, 1 H), 7.65 (d, J = 8.9 Hz, 1 H), 7.55 (t, J = 7.7 Hz, 1 H), 7.49 (d, J = 7.6 Hz, 1 H), 7.31–7.28 (m, 1 H), 7.06 (t, J = 6.8 Hz, 1 H), 6.56 (d, J = 16.0 Hz, 1 H), 4.55 (q, J = 8.2 Hz, 2 H). 13C NMR (150 MHz, CDCl3): δ = 165.0, 164.2, 146.9, 145.8, 136.4, 132.9, 132.1, 131.7, 130.8, 130.3, 129.6, 129.4, 129.1, 128.9, 128.0, 127.4, 126.7, 126.2, 125.7, 125.7, 125.6, 125.5, 124.0, 122.2, 118.5, 118.2, 118.0, 117.4, 115.6, 115.6, 60.7, 60.4, 60.2, 60.0. GC–MS: m/z [M] calcd for C17H12F3N3O2: 347.0882; found: 347.00.(E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylonitrile (3h)Yield (56.0 mg, 91% yield, semisolid), eluent 30% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.82 (d, J = 7.0 Hz, 1 H), 7.77 (d, J = 16.8 Hz, 1 H), 7.72 (d, J = 7.8 Hz, 1 H), 7.69 (d, J = 8.7 Hz, 1 H), 7.64 (d, J = 7.6 Hz, 1 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.36–7.33 (m, 1 H), 7.09 (t, J = 6.9 Hz, 1 H), 5.94 (d, J = 17.0 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 149.3, 136.1, 132.7, 132.0, 131.0, 130.8, 130.6, 130.6, 128.8, 126.5, 126.3, 125.6, 118.1, 117.7, 115.7, 97.5. GC–MS: m/z [M] calcd for C15H10N4: 246.0905; found: 246.20.2-Ethylhexyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}phenyl)acrylate (3i)Yield (60.6 mg, 67% yield, yellow liquid), eluent 15% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80–8.79 (m, 1 H), 7.78–7.72 (m, 2 H), 7.62 (t, J = 8.7 Hz, 2 H), 7.49 (dd, J = 8.1, 2.3 Hz, 1 H), 7.31–7.29 (m, 1 H), 7.06 (t, J = 6.5 Hz, 1 H), 6.51 (d, J = 16.1 Hz, 1 H), 4.07 (qd, J = 10.9, 5.7 Hz, 2 H), 1.56 (t, J = 6.0 Hz, 1 H), 1.31–1.24 (m, 11 H), 0.88–0.83 (m, 8 H). 13C NMR (150 MHz, CDCl3): δ = 166.6, 141.6, 135.7, 135.1, 134.9, 132.2, 132.1, 130.2, 129.8, 127.1, 126.2, 125.7,
121.1, 118.0, 115.6, 67.1, 38.8, 30.4, 29.0, 23.8, 23.0, 14.1, 11.1. GC–MS: m/z [M] calcd for C23H27N3O2: 377.2103; found: 377.30.Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4a)Yield (65.1 mg, 83% yield, semisolid), eluent 25% ethyl acetate/hexane). 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.0 Hz, 1 H), 7.81–7.76 (m, 2 H), 7.61–7.58 (m, 2 H), 7.49 (d, J = 8.1 Hz, 1 H), 7.32–7.30 (t, J = 6.0 Hz, 1 H), 7.06 (d, J = 6.8 Hz, 1 H), 6.50 (d, J = 16.1 Hz, 1 H), 3.73 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.7, 141.9, 135.5, 135.0, 134.8, 132.0, 130.1, 129.6, 127.1, 126.2, 125.6, 120.5, 117.8, 115.6, 51.8. GC–MS: m/z [M] calcd for C16H12ClN3O2: 313.0618; found: 313.00.Ethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4b)Yield (61.3 mg, 75% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.77 (s, 1 H), 7.84–7.79 (m, 2 H), 7.65 (s, 2 H), 7.50–7.46 (m, 2 H), 7.27 (s, 1 H), 7.02 (s, 1 H), 6.49 (d, J = 15.7 Hz, 1 H), 4.17 (s, 2 H), 1.24 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.8, 143.1, 136.7, 133.6, 132.2, 131.4, 131.0, 130.2, 128.9, 127.2, 125.9, 125.6, 120.0, 118.3, 115.6, 60.5, 14.4. ESI-HRMS: m/z [M + Na]+ calcd for C17H14ClN3O2Na: 350.0667; found: 350.0632.Butyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4c)Yield (76.5 mg, 86% yield, semisolid), eluent 20% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.80 (d, J = 7.1 Hz, 1 H), 7.82 (d, J = 7.8 Hz, 1 H), 7.68 (d, J = 7.3 Hz, 1 H), 7.64 (d, J = 8.9 Hz, 1 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 1 H), 7.30–7.27 (m, 1 H), 7.05 (t, J = 6.8 Hz, 1 H), 6.51 (d, J = 15.9 Hz, 1 H), 4.14 (t, J = 6.5 Hz, 2 H), 1.62–1.58 (m, 2 H), 1.36–1.33 (m, 2 H), 0.92–0.88 (m, 3 H). 13C NMR (150 MHz, CDCl3): δ = 160.0, 159.3, 156.9, 143.9, 138.1, 136.8, 136.2, 130.2, 129.1, 127.6, 122.3, 120.9, 120.5, 114.9, 114.4, 114.3, 113.9, 112.1, 105.4, 55.3, 32.4, 31.2, 30.3. GC–MS: m/z [M] calcd for C19H18ClN3O2: 355.1058; found: 355.10.Methyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)-2-methylacrylate (4d)Yield (67.2 mg, 82% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.77 (d, J = 7.1 Hz, 1 H), 7.72–7.70 (m, 1 H), 7.64 (s, 1 H), 7.56 (d, J = 8.7 Hz, 1 H), 7.51–7.49 (m, 1 H), 7.48 (d, J = 3.3 Hz, 1 H), 7.25 (t, J = 7.32 Hz, 1 H), 7.02 (t, J = 6.7 Hz, 1 H), 3.69 (s, 3 H), 2.07 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 160.0, 134.8, 131.2, 129.9, 129.0, 128.5, 126.5, 124.8, 124.2, 123.0, 121.7, 121.0, 115.0, 114.3, 109.2, 55.5, 29.7. GCMS: m/z [M] calcd for C17H14ClN3O2: 327.0775; found: 327.05.2-Methoxyethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4e)Yield (69.8 mg, 78% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.79 (d, J = 7.0 Hz, 1 H), 7.80–7.76 (m, 2 H), 7.60 (d, J = 8.5 Hz, 2 H), 7.49 (dd, J = 8.2, 1.8 Hz, 1 H), 7.32–7.28 (m, 1 H), 7.06 (t, J = 6.7 Hz, 1 H), 6.56 (d, J = 15.9 Hz, 1 H), 4.30–4.28 (m, 2 H), 3.61–3.59 (m, 2 H), 3.37 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 166.2, 142.2, 135.5, 134.9, 134.8, 132.0, 130.2, 129.7, 127.1, 126.2, 125.6, 120.5, 117.8, 115.6, 70.4, 63.7, 59.0. GC–MS: m/z [M] calcd for C18H16ClN3O3: 357.0880; found: 357.10.2-Hydroxyethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)but-2-enoate (4f)Yield (58.1 mg, 65% yield, semisolid), eluent 45% ethyl acetate/hexane). 1H NMR (600 MHz, CDCl3): δ = 8.83 (d, J = 7.1 Hz, 1 H), 7.84–7.80 (m, 2 H), 7.65 (d, J = 8.6 Hz, 2 H), 7.53 (d, J = 8.3 Hz, 1 H), 7.36–7.32 (m, 1 H), 7.10 (t, J = 6.8 Hz, 1 H), 6.60 (d, J = 15.8 Hz, 1 H), 4.33 (t, J = 4.7 Hz, 2 H), 3.65 (t, J = 4.7 Hz, 2 H), 3.41 (s, 3 H). 13C NMR (150 MHz, CDCl3): δ = 168.7, 139.2, 137.2, 134.6, 131.8, 130.8, 130.2, 128.7, 128.5, 128.1, 125.6, 118.4, 115.5, 66.6, 61.4, 14.2. GC–MS: m/z [M] calcd for C18H16ClN3O3: 357.0880; found: 357.10.2,2,2-Trifluoroethyl (E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylate (4g)Yield (84 mg, 88% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.71 (d, J = 7.2 Hz, 1 H), 7.93 (d, J = 16.0 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.57 (d, J = 9.0 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.42 (q, J = 7.8, 7.3 Hz, 1 H), 6.97 (t, J = 6.9 Hz, 1 H), 6.47 (d, J = 16.0 Hz, 1 H), 4.46 (q, J = 8.1 Hz, 2 H). 13C NMR (150 MHz, CDCl3): δ = 167.0, 166.6, 143.6, 143.5, 140.9, 134.7, 133.8, 130.7, 130.6, 130.4, 129.7, 129.1, 129.0, 128.3, 127.8, 123.9, 122.8, 120.3, 112.7, 52.4, 29.7. GC–MS: m/z [M] calcd for C17H11ClF3N3O2: 381.0492; found: 381.30.(E)-3-(2-{[1,2,3]Triazolo[1,5-a]pyridin-3-yl}-5-chlorophenyl)acrylonitrile (4h).Yield (60.4 mg, 86% yield, semisolid), eluent 25% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.24 (d, J = 7.8 Hz, 1 H), 8.02 (d, J = 6.7 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1H ), 7.72 (d, J = 9.2 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 2 H), 7.39 (t, J = 7.5 Hz, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 6.81 (t, J = 6.7 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 149.3, 145.7, 140.1, 128.9, 125.3, 125.2, 124.3, 124.1, 124.0, 122.4, 121.5, 118.2, 111.9. GC–MS: m/z [M] calcd for C15H9ClN4: 280.0516; found: 280.0.Phenyl(pyridin-2-yl)methanone (5)11
Yield (14.0 mg, 31% yield, white solid), mp 42–44 ℃), 5% ethyl acetate/hexane. 1H NMR (600 MHz, CDCl3): δ = 8.71 (d, J = 4.3 Hz, 1 H), 8.07 (d, J = 7.7 Hz, 2 H), 8.03 (d, J = 7.8 Hz, 1 H), 7.88 (t, J = 7.7 Hz, 1 H), 7.58 (t, J = 7.3 Hz, 1 H), 7.47 (dd, J = 14.2, 6.9 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 193.7, 154.9, 148.4, 136.9, 136.1, 132.7, 130.8, 128.0, 126.0, 124.4.
- 11 Joshi A, Kumar R, Semwal R, Rawat D, Adimurthy S. Green Chem. 2019; 21: 962
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