Abstract
Nickel-catalyzed amidation of aryl alkynyl acids using tetraalkylthiuram disulfides as the amine source is described, affording a series of aryl alkynyl amides in good to excellent yields under mild conditions. This general methodology provides an alternative pathway for the synthesis of useful aryl alkynyl amides in an operationally simple manner, which shows its practical synthetic value in organic synthesis. The mechanism of this transformation was explored through control experiments and DFT calculations.
Introduction
Thiuram reagents constitute an important class of compounds that is known to have a wide range of biological activities.1 As low-toxic, easy-to-prepare, and even commercially available organosulfur compounds, thiurams have also been extensively used in organic thiolation reactions2 and thus exhibited its broad applications in modern organic synthesis. As a continuing research interest, our group also selected thiurams as interesting reagents for the development of new synthetic transformations.
Aryl alkynyl amide derivatives are attractive synthetic targets because of their significant biological activities.3 This skeleton and their analogues also act as valuable intermediates in organic synthesis.4 As a consequence, tremendous attention has been focused on the synthesis of aryl alkynyl amides, and a number of methods have been devised. Among the numerous approaches, the coupling reactions between a carbamoyl chloride and a terminal alkyne conducted by 1,4-diazabicyclo[2.2.2]octane (DABCO)5 or Pd/Cu catalysts6 had been commonly used (Scheme 1a). Moreover, N, N-dimethylformamide (DMF) or secondary amines were also proved to be common amidation reagents for their great efficiency on the synthesis of alkynyl amides by reacting with acids7 or aldehydes8 (Scheme 1b). Nevertheless, these documented methods respectively suffer from some drawbacks such as harsh reaction conditions and foul-smelling amines to inhibit the application of these procedures. Meanwhile, by using carbamoylsilane as a source of amine was feasible as well (Scheme 1c).9 Moreover, the synthesis of alkynyl amides through one-pot three-component reactions had also been developed (Scheme 1d). For instance, Bhanage’s group reported a route of highly effective Pd/C-catalyzed oxidative N-dealkylation/carbonylation of various aliphatic as well as cyclic tertiary amines with alkynes.10 Shortly afterward, Lee and co-workers subsequently developed a method for the synthesis of alkynyl amides via the carbonylation of alkynoic acids and C–N activation of tertiary amines.11 Very recently, efficient approaches under metal-free conditions also played a necessary role in the reaction of amidation.12 Despite these advances, to the best of our knowledge, using thiuram reagents as amine sources to synthesize aryl alkynyl amides has not been precedented so far. As a continuation of this research program,13 herein, we present a nickel-catalyzed amidation of aryl alkynyl acids with tetraalkylthiuram to synthesize aryl alkynyl amides (Scheme 1e).
Scheme 1. Procedures for the Synthesis of Aryl Alkynyl Amides.
(a) Traditional procedure, (b) amide formation using amine or formamides as amine sources, (c) amide formation using carbamoylsilane as amine source, (d) one-pot three-component reaction, and (e) tetraalkylthiuram disulfides as amine sources.
Results and Discussion
At the outset of our investigation, phenylpropiolic acid (1a) and tetramethylthiuram disulfide (TMTD, 2a) were chosen as the model substrates to optimize the reaction conditions, and the results were summarized in Table 1. First, the effect of catalysts has been studied. We were delighted to find that the reactions occurred, which afforded the corresponding product 3a (N, N-dimethyl-3-phenylpropiolamide) in acceptable yields (26, 30, and 39%) using CuBr2 (1 equiv), CoBr2 (1 equiv), and NiBr2 (1 equiv) as the catalysts (entries 1–3, Table 1). No desired product was detected when the reaction was carried out in the absence of metal catalysts, which indicated that the metal catalysts were necessary indeed to improve the reaction efficiency (entry 4, Table 1). Consequently, some other nickel salts such as NiCl2, NiF2, and Ni(OAc)2 were further tested in the reaction, and NiCl2 was proven to be superior to other nickel salts that could provide product 3a in 80% yield (entry 5 vs entries 3, 6–7). An investigation of solvents showed that the solvent had an important influence on the reaction. The best yield (85%, entry 13) was given in the solvent of toluene. A substantially decreased reaction efficiency was observed when the reaction was conducted in 1,4-dioxane, THF (tetrahydrofuran), DCE (1,2-dichloorethaan), hexane, and CH3CN (36–69%, entries 8–12). Particularly, the polar solvents such as DMF (N, N-dimethylformamide) and DMSO (dimethyl sulfoxide) showed an even worse performance in this process (trace: 16%, entries 14–15). Next, we evaluated the effect of reaction temperature, and 100 °C was determined as the optimized reaction temperature after a series of screening experiments (90% vs 41–85%, entry 17 vs entries 13, 16, and 18). Lowering the catalyst loading to 20 mol %, the reaction provided a similar yield of product 3a (89% vs 90%, entry 19 vs entry 17). However, a continuous decrease of the catalyst loading caused an unsatisfactory result (76%, entry 20). Therefore, the catalyst loading of 20 mol % was chosen for further optimization. We also briefly screened the reaction time, and 12 h was found to be the best choice (89% vs 79–80%, entry 19 vs entries 21–22). Inert conditions proved to be not critical. When the reaction was run under nitrogen conditions, the product 3a was obtained in a similar yield (84%, entry 23). After surveying a variety of parameters, we found that the optimized reaction conditions were identified as follows: 20 mol % of NiCl2 as the catalyst in toluene at 100 °C under air atmosphere for 12 h (entry 19).
Table 1. Optimization of the Reaction Conditionsa.
| entry | catalyst | solvent | catalyst loadings (equiv.) | temperature (°C) | yields of 3a (%)b |
|---|---|---|---|---|---|
| 1 | CuBr2 | EtOAc | 1 | 120 | 26 |
| 2 | CoBr2 | EtOAc | 1 | 120 | 30 |
| 3 | NiBr2 | EtOAc | 1 | 120 | 39 |
| 4 | EtOAc | 1 | 120 | <5 | |
| 5 | NiCl2 | EtOAc | 1 | 120 | 80 |
| 6 | NiF2 | EtOAc | 1 | 120 | 31 |
| 7 | Ni(OAc)2 | EtOAc | 1 | 120 | 21 |
| 8 | NiCl2 | 1,4-dioxane | 1 | 120 | 43 |
| 9 | NiCl2 | THF | 1 | 120 | 69 |
| 10 | NiCl2 | DCE | 1 | 120 | 58 |
| 11 | NiCl2 | hexane | 1 | 120 | 61 |
| 12 | NiCl2 | CH3CN | 1 | 120 | 36 |
| 13 | NiCl2 | toluene | 1 | 120 | 85 |
| 14 | NiCl2 | DMF | 1 | 120 | 16 |
| 15 | NiCl2 | DMSO | 1 | 120 | trace |
| 16 | NiCl2 | toluene | 1 | 140 | 41 |
| 17 | NiCl2 | toluene | 1 | 100 | 90 |
| 18 | NiCl2 | toluene | 1 | 80 | 77 |
| 19 | NiCl2 | toluene | 0.2 | 100 | 89 |
| 20 | NiCl2 | toluene | 0.1 | 100 | 76 |
| 21c | NiCl2 | toluene | 0.2 | 100 | 80 |
| 22d | NiCl2 | toluene | 0.2 | 100 | 79 |
| 23e | NiCl2 | toluene | 0.2 | 100 | 84 |
Reaction conditions: 1a (0.10 mmol), 2a (0.15 mmol), catalyst (1 equiv), solvent (1.0 mL), 120 °C, 12 h, under air.
Isolated yields.
Run for 18 h.
Run for 6 h.
Under N2.
With the optimal conditions in hand, the cross-coupling reactions of phenylpropiolic acid analogues and tetramethylthiuram disulfide (TMTD, 2a) were first investigated, and the results were summarized in Table 2. Generally, the electron-donating groups (−Me, −OMe, −Et, −OEt, −i-Pr, and −t-Bu) and electron-withdrawing groups (−F, −Cl, −Br, −CF3, and −CHO) were all compatible with this reaction, which afforded the corresponding products in moderate to excellent yields (3a–3a′, 37–95%). Electron-withdrawing groups seemed to be slightly more beneficial to the reaction than electron-donating groups. For example, 3-(p-tolyl)propiolic acid 1b gave the corresponding product 3b in 76% yield, while the bromo, chloro, and fluoro counterparts resulted in 86–93% yields of products 3n–3p. Noteworthily, the bromo-substituted phenylpropiolic acid works well in this transformation, which makes this reaction particularly attractive for further transformation by transition-metal-catalyzed coupling reactions. The position of substituents may not significantly affect the yield of the reaction. ortho-, meta-, and para-Methyl- or methoxyl-substituted substrates worked well and gave the desired products in similar yields (3b vs 3h and 3j, 76% vs 83 and 87%). Interestingly, 3-(4-formylphenyl)propiolic acid 1y was also the suitable substrate to check the reactivity of TMTD, and the desired product 3y was formed in 37% yield. This protocol also exhibited good feasibility with 3-(thiophen-2-yl)propiolic acid 1z and 3-(thiophen-3-yl)propiolic acid 1a′, which provided the products 3z–3a′ in 37–64% yields. To our delight, benzoylformic acid could complete the reaction and afford the product 3b′ in 81% yield (Scheme 2).
Table 2. Amidation of Aryl Alkynyl Acids with TMTDa,b.
Reaction conditions: 1 (0.10 mmol), 2 (0.15 mmol), NiCl2 (20 mol %), toluene (1.0 mL), 100 °C, 12 h, under air.
Isolated yields.
Scheme 2. Amidation of Benzoylformic Acid with TMTD,
Reaction conditions: 1b′ (0.10 mmol), 2a (0.15 mmol), NiCl2 (20 mol%), toluene (1.0 mL), 100 °C, 12 h, under air.
Isolated yields.
We then investigated the substrate scope of tetraalkylthiuram disulfides. As shown in Table 3, N, N, N′, N′-tetraethylthiuram disulfide (TETD, 2b) was initially examined. To our delight, it underwent these transformations smoothly and gave the products 4a–4w in moderate yields (30–76%), respectively. In particular, this protocol was applicable indeed to 3-(thiophen-2-yl)propiolic acid and 3-(thiophen-3-yl)propiolic acid with 2b, even though sharply lower yields were observed in these reactions (4v–4w, 31–46%). N, N, N′, N′-tetrabutylthiuram disulfide (TBTD, 2c) also performed well to give the desired products 4x–4d′ with good yields (51–80%). These results greatly expanded the substrate scope of this reaction. It is worth noting that the longer chain-substituted tetraalkylthiuram disulfides sometimes performed better in these reactions (3z–3a′ vs 4c′–4d′), which indicated that the yields were occasionally modulated by the presence of different alkyl substituents on the tetraalkylthiuram disulfides. The reaction of phenylpropiolic acid with tetraisopropylthiuram disulfide has also been carried out in our lab, and probably because of the larger steric effect of isopropyl group, the tetraisopropylthiuram disulfide is proven to be invalid to this reaction.
Table 3. Amidation of Aryl Alkynyl Acids with N,N,N′,N′-Tetraalkylthiuram Disulfidesa,b.
Reaction conditions: 1 (0.10 mmol), 2 (0.15 mmol), NiCl2 (20 mol %), Toluene (1.0 mL), 100 °C, 12 h, under air.
Isolated yields.
Interestingly, tetramethylthiuram monosulfide (TMTM, 5) is an active substrate to this amidation, and the corresponding product 3a was obtained in 65% yield (Scheme 3a). Bis(pentamethylene)thiuram tetrasulfide (6) could also react with phenylpropiolic acid, which provided the product 7 in 78% yield (Scheme 3b).
Scheme 3. Amidation of Phenylpropiolic Acid with Tetramethylthiuram Monosulfide (a) and Bis(pentamethylene)thiuram Tetrasulfide (b).
To gain a deeply understanding of the reaction mechanism, DFT calculations were utilized. As shown in Scheme 4, TMTD (2a) prefers to dissociate into B, and the reaction Gibbs free energy is 7.30 kcal/mol. This reaction is supported by the investigation of Steudel’s group.14B will combine with NiCl2 spontaneously to form intermediate C, and the Gibbs free energy would decrease to 35.28 kcal/mol. Then, C will form intermediate D via a transition state TS1, and the reaction Gibbs free energy would increase to 43.08 kcal/mol. Subsequently, D will form E via a transition state TS2, and the reaction Gibbs free energy would decrease to 6.85 kcal/mol. E will release CS2 and Cl radical to form F, and the reaction Gibbs free energy would increase to 21.62 kcal/mol. The Ni atom of F will accept the lone pair electrons attached to the carbonyl group of 1a to form G, and the reaction Gibbs free energy would slightly increase to 7.99 kcal/mol. G will form H via a transition state TS3, and the reaction Gibbs free energy would increase to 29.28 kcal/mol. Finally, H will release NiCl2 and OH radical to form the product 3a, and the reaction Gibbs free energy would slightly increase 3.89 to kcal/mol. Notably, the OH radical will combine with B to form A, and the reaction Gibbs free energy would decrease to 42.45 kcal/mol.
Scheme 4. Computational Reaction Mechanism.
In order to further ascertain the mechanism, some control experiments were conducted, and the results were exhibited in Scheme 5. When 2 equiv of radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO), butylated hydroxyl toluene (BHT), or galvinoxyl free radical was added to the reaction of 1a and 2a under the standard conditions, a substantial decrease of the reaction efficiency was observed, illustrating that a radical process may exist in this reaction (Scheme 5a). Particularly, when quencher 1,1-diphenylethylene was added, the sulfur radical was captured to give 8, which also indicated that a radical mechanism might be involved in this reaction (Scheme 5b).
Scheme 5. Radical Quenching Experiment (a) and Radical Capture Experiment (b).
Based on the mechanistic experiments and reported literatures,2c,15 a plausible mechanism is outlined in Scheme 6. The reaction is presumed to involve a sulfur radical A, which is generated by the hemolysis of tetramethylthiuram disulfide under heat conditions, along with the release of by-product H. Sulfur radical A coordinates with NiCl2 to form the intermediate B, which undergoes two steps rearrangement affording the Ni–N species E, CS2, and chloride radical. The following coordination of intermediate E to substrate 1a affords the Ni intermediate F. Then, another rearrangement process occurs to give the intermediate G, Finally, the dissociation of intermediate G produces the product 3a, hydroxyl radical, and the regeneration of NiCl2.
Scheme 6. Plausible Reaction Mechanism.
Conclusions
In summary, we have developed a mild and efficient amidation reaction of aryl alkynyl acids with tetraalkylthiuram disulfides via C–N cross-coupling. These processes gave a series of aryl alkynyl amides in mild conditions. This methodology is versatile and works well with a variety of aryl alkynyl acids and provides a straightforward way for the synthesis of aryl alkynyl amides. Investigation of the synthetic application and biological activities of these products are currently underway in our laboratory.
Experimental Section
General Information
All reactions were carried out under an air atmosphere in a dried tube. All the reagents were obtained commercially and used without further purification. Silica gel was purchased from Qing Dao Hai Yang Chemical Industry Co. Analytical thin-layer chromatography (TLC) was performed on precoated silica gel F254 plates. Compounds were visualized by irradiation with UV light (254 nm).
1H NMR and 13C NMR spectral data were recorded by a BRUKER AVANCE III 400 MHz spectrometer (1H 400 MHz, 13C 100 MHz), using CDCl3 as the solvent with tetramethylsilane (TMS) as the internal standard at room temperature. 1H NMR spectral data are given as chemical shifts in ppm followed by multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet), number of protons, and coupling constants. 13C NMR chemical shifts are expressed in ppm. HRMS data were obtained using an AB SCIEX Triple TOF 5600+ high resolution mass spectrometer (USA). Infrared spectra were recorded with a Thermo Scientific Nicolet 6700 FT-IR spectrometer. The products listed below were determined by 1H and 13C NMR spectra. Melting points were measured on a microscopic apparatus and were uncorrected.
General Procedure for the Preparation of Aryl Alkynyl Acids
Aryl iodide (5 mmol) was added to the reaction tube and dissolved in 6 mL of DMSO, and a propionic acid solution (385 mg, 5.5 mmol dissolved in 6 mL of DMSO) was added dropwise. The reaction was incubated at room temperature for 16–19 h. After the reaction was completed, the reaction was quenched with saturated aqueous sodium bicarbonate, and the aqueous phase was washed twice with ethyl acetate. The aqueous phase was adjusted to pH = 2 with hydrochloric acid and extracted twice with dichloromethane. The organic phase was dried over anhydrous magnesium sulfate. The solvent was evaporated to dryness under reduced pressure, and the product was purified by column chromatography using ethyl acetate/petroleum ether as eluent to give 1b–1a′.
General Procedure for the Reaction of Aryl Alkynyl Acids with Tetraalkylthiuram Disulfides
To a 10 mL tube, aryl alkynyl acids 1 (0.1 mmol) and tetraalkylthiuram disulfides 2 (0.15 mmol), NiCl2 (0.02 mmol), and toluene (1.0 mL) were added under an air atmosphere. The resulting mixture was heated in a 100 °C oil bath with vigorous stirring for 12 h. Then, the reaction mixture was cooled to room temperature, quenched with a sat. NH4Cl solution, and subsequently extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4 and filtered, and the solvent was evaporated under vacuum. The residue was purified by flash chromatography using petroleum ether/ethyl acetate as eluent affording 3 or 4 in 30–95% yields.
N,N-dimethyl-3-phenylpropiolamide (3a)
Purification by column chromatography on silica gel (Rf = 0.37, petroleum ether/ethyl acetate = 3:1) yielded 3a (15.5 mg, 89%) as a pale yellow solid; m. p. 99–101 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.58–7.52 (d, J = 6.7 Hz, 2H), 7.45–7.39 (m, 1H), 7.39–7.33 (m, 2H), 3.29 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.6, 132.3, 130.0, 128.5, 120.6, 90.1, 81.6, 38.4, 34.2; IR(KBr): 2928, 2219, 1622, 1491, 1397, 1278, 1180, 1137, 1065, 996, 765, 729, 692, 572, 531 cm–1; HRMS (ESI) calcd. for C11H11NO: [M + H]+: 174.0919, found: 174.0908.
N,N-dimethyl-3-(p-tolyl)propiolamide (3b)
Purification by column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl acetate = 3:1) yielded 3b (14.2 mg, 76%) as a pale yellow solid; m. p. 79–81 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.48–7.41 (d, J = 8.1 Hz, 2H), 7.20–7.13 (d, J = 7.9 Hz, 2H), 3.29 (s, 3H), 3.03 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.8, 140.5, 132.3, 129.3, 117.5, 90.6, 81.2, 38.4, 34.2, 21.6; IR(KBr): 3423, 2922, 2213, 1620, 1508, 1393, 1269, 1133, 1049, 968, 817, 731, 670, 530, 510 cm–1; HRMS (ESI) calcd. for C12H13NO: [M + H]+: 188.1070, found: 188.1075.
3-(4-Ethylphenyl)-N,N-dimethylpropiolamide (3c)
Purification by column chromatography on silica gel (Rf = 0.34, petroleum ether/ethyl acetate = 3:1) yielded 3c (14.4 mg, 72%) as a pale yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.51–7.43 (d, J = 8.2 Hz, 2H), 7.23–7.16 (d, J = 8.2 Hz, 2H), 3.29 (s, 3H), 3.02 (s, 3H), 2.72–2.62 (q, J = 7.6 Hz, 2H), 1.28–1.19 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.8, 146.7, 132.4, 128.1, 117.7, 90.6, 81.2, 38.4, 34.2, 28.9, 15.2; IR(KBr): 3446, 2965, 2928, 2206, 1631, 1507, 1392, 1271, 1130, 1051, 833, 729 cm–1; HRMS (ESI) calcd. for C13H15NO: [M + H]+: 202.1226, found: 202.1229.
3-(4-Methoxylphenyl)-N,N-dimethylpropiolamide (3d)
Purification by column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl acetate = 3:1) yielded 3d (15.6 mg, 77%) as a pale yellow solid; m. p. 82–84 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.53–7.45 (dt, J = 8.9, 2.7 Hz, 2H), 6.92–6.84 (dt, J = 8.9, 2.7 Hz, 2H, 1H), 3.83 (s, 3H), 3.28 (s, 3H), 3.02 (s, 3H); 13C NMR (100 MHz, CDCl3): 161.0, 154.9, 134.1, 114.2, 112.5, 90.7, 80.9, 55.4, 38.4, 34.2; IR(KBr): 2965, 2925, 2206, 1628, 1509, 1464, 1401, 1297, 1172, 1135, 1024, 837, 723, 671, 546 cm–1; HRMS (ESI) calcd. for C12H13NO2: [M + H]+: 204.1019, found: 204.1023.
3-(4-Ethoxylphenyl)-N,N-dimethylpropiolamide (3e)
Purification by column chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl acetate = 3:1) yielded 3e (11.5 mg, 53%) as a yellow solid; m. p. 75–77 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.52–7.45 (dt, J = 8.8, 2.6 Hz, 2H), 6.90–6.82 (dt, J = 8.8, 2.6 Hz, 2H), 4.10–4.00 (q, J = 7.0 Hz, 2H), 3.28 (s, 3H), 3.02 (s, 3H), 1.47–1.38 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): 160.4, 155.0, 134.1, 114.7, 112.3, 90.8, 80.8, 63.6, 38.4, 34.2, 14.7; IR(KBr): 2978, 2924, 2194, 1626, 1511, 1473, 1396, 1300, 1252, 1181, 1131, 1043, 847, 724, 683, 572 cm–1; HRMS (ESI) calcd. for C13H15NO2: [M + H]+: 218.1176, found: 218.1182.
3-(4-Isopropylphenyl)-N,N-dimethylpropiolamide (3f)
Purification by column chromatography on silica gel (Rf = 0.35, petroleum ether/ethyl acetate = 3:1) yielded 3f (17.9 mg, 83%) as a yellow solid; m. p. 60–62 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.52–7.44 (d, J = 8.3 Hz, 2H), 7.25–7.19 (d, J = 8.2 Hz, 2H), 3.28 (s, 3H), 3.03 (s, 3H), 2.98–2.84 (m, 1H), 1.28–1.21 (d, J = 6.9 Hz, 6H); 13C NMR (100 MHz, CDCl3): 154.8, 151.3, 132.4, 126.7, 117.9, 90.6, 81.1, 38.4, 34.2, 34.2, 23.7; IR(KBr): 2960, 2925, 2211, 1621, 1508, 1392, 1272, 1133, 1054, 843, 834, 729, 567 cm–1; HRMS (ESI) calcd. for C14H17NO: [M + H]+: 216.1383, found: 216.1389.
3-(4-(tert-Butyl)phenyl)-N,N-dimethylpropiolamide (3g)
Purification by column chromatography on silica gel (Rf = 0.42, petroleum ether/ethyl acetate = 3:1) yielded 3g (15.6 mg, 68%) as a pale yellow solid; m. p. 84–86 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.53–7.45 (dt, J = 8.6, 1.9 Hz, 2H), 7.42–7.34 (d, J = 8.6 Hz, 2H), 3.29 (s, 3H), 3.03 (s, 3H), 1.32 (s, 9H); 13C NMR (100 MHz, CDCl3): 154.8, 153.5, 132.2, 125.5, 117.5, 90.6, 81.2, 38.4, 35.0, 34.2, 31.1; IR(KBr): 2968, 2926, 2204, 1624, 1506, 1395, 1267, 1135, 1104, 1058, 834, 730, 642, 568 cm–1; HRMS (ESI) calcd. for C15H19NO: [M + H]+: 230.1539, found: 230.1546.
N,N-Dimethyl-3-(m-tolyl)propiolamide (3h)
Purification by column chromatography on silica gel (Rf = 0.35, petroleum ether/ethyl acetate = 3:1) yielded 3h (15.5 mg, 83%) as a yellow solid; m. p. 52–54 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.39–7.32 (d, J = 8.4 Hz, 2H), 7.29–7.19 (m, 2H), 3.29 (s, 3H), 3.03 (s, 3H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.7, 138.3, 132.8, 130.9, 129.5, 128.4, 120.4, 90.4, 81.3, 38.4, 34.2, 21.2; IR(KBr): 2924, 2218, 1629, 1490, 1395, 1283, 1130, 1065, 796, 729, 691, 582 cm–1; HRMS (ESI) calcd. for C12H13NO: [M + H]+: 188.1070, found: 188.1063.
3-(3-Methoxylphenyl)-N,N-dimethylpropiolamide (3i)
Purification by column chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl acetate = 3:1) yielded 3i (15.8 mg, 78%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.31–7.23 (t, J = 7.8 Hz, 1H), 7.17–7.10 (d, J = 7.6 Hz, 1H), 7.10–7.04 (s, 1H), 7.01–6.93 (dd, J = 8.3, 2.0 Hz, 1H), 3.81 (s, 3H), 3.29 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 159.3, 154.6, 129.6, 124.8, 121.5, 117.0, 116.7, 90.1, 81.3, 55.4, 38.4, 34.2; IR(KBr): 3435, 2919, 2217, 1627, 1454, 1392, 1230, 1258, 1171, 1126, 1046, 869, 728, 685, 575 cm–1; HRMS (ESI) calcd. for C12H13NO2: [M + H]+: 204.1019, found: 204.1017.
N,N-Dimethyl-3-(o-tolyl)propiolamide (3j)
Purification by column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl acetate = 3:1) yielded 3j (16.3 mg, 87%) as a pale yellow solid; m. p. 56–58 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.56–7.49 (d, J = 7.4 Hz, 1H), 7.35–7.26 (td, J = 7.6, 1.2 Hz, 1H), 7.26–7.23 (d, J = 7.6 Hz, 1H), 7.23–7.14 (t, J = 7.6 Hz, 1H), 3.31 (s, 3H), 3.04 (s, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.8, 141.2, 132.9, 130.0, 129.7, 125.8, 120.5, 89.3, 85.4, 38.4, 34.2, 20.8; IR(KBr): 2922, 2202, 1626, 1486, 1396, 1269, 1198, 1136, 1109, 1057, 769, 728, 593, 556 cm–1; HRMS (ESI) calcd. for C12H13NO: [M + H]+: 188.1070, found: 188.1064.
3-(2-Ethylphenyl)-N,N-dimethylpropiolamide (3k)
Purification by column chromatography on silica gel (Rf = 0.42, petroleum ether/ethyl acetate = 3:1) yielded 3k (14.5 mg, 72%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.57–7.50 (d, J = 7.3 Hz, 1H), 7.39–7.31 (t, J = 7.1 Hz, 1H), 7.30–7.23 (d, J = 7.6 Hz, 1H), 7.23–7.15 (t, J = 7.6 Hz, 1H), 3.30 (s, 3H), 3.04 (s, 3H), 2.91–2.75 (q, J = 7.6 Hz, 2H), 1.33–1.19 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.8, 147.3, 133.3, 130.2, 128.1, 125.8, 119.8, 89.1, 85.0, 38.3, 34.2, 27.7, 15.0; IR(KBr): 3436, 2929, 2204, 1631, 1494, 1448, 1393, 1267, 1138, 1112, 1051, 757, 730 cm–1; HRMS (ESI) calcd. for C13H15NO: [M + H]+: 202.1226, found: 202.1223.
3-(2-Methoxylphenyl)-N,N-dimethylpropiolamide (3l)
Purification by column chromatography on silica gel (Rf = 0.34, petroleum ether/ethyl acetate = 3:1) yielded 3l (15.9 mg, 78%) as a yellow solid; m. p. 61–63 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.55–7.48 (dd, J = 7.6, 1.6 Hz, 1H), 7.42–7.33 (td, J = 8.4, 1.7 Hz, 1H), 6.97–6.93 (td, J = 7.6, 0.9 Hz, 1H), 6.93–6.88 (d, J = 8.4 Hz, 1H), 3.88 (s, 3H), 3.33 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 161.1, 154.9, 134.3, 131.6, 120.5, 110.7, 109.9, 86.9, 85.7, 55.8, 38.4, 34.1; IR(KBr): 3005, 2921, 2850, 2209, 1629, 1495, 1437, 1398, 1274, 1142, 1039, 1019, 767, 722, 546 cm–1; HRMS (ESI) calcd. for C12H13NO2: [M + H]+: 204.1019, found: 204.1012.
3-(2-Isopropylphenyl)-N,N-dimethylpropiolamide (3m)
Purification by column chromatography on silica gel (Rf = 0.42, petroleum ether/ethyl acetate = 3:1) yielded 3m (17 mg, 79%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.56–7.49 (dd, J = 7.7, 1.1 Hz, 1H), 7.42–7.34 (td, J = 7.8, 1.3 Hz, 1H), 7.34–7.28 (d, J = 7.0 Hz, 1H), 7.22–7.13 (td, J = 7.5, 1.3 Hz, 1H), 3.55–3.39 (m, 1H), 3.30 (s, 3H), 3.04 (s, 3H), 1.31–1.24 (d, J = 6.9 Hz, 6H); 13C NMR (100 MHz, CDCl3): 154.8, 151.6, 133.3, 130.3, 125.8, 125.1, 119.4, 89.2, 85.3, 38.3, 34.2, 31.7, 23.2; IR(KBr): 3435, 2926, 2202, 1630, 1484, 1446, 1392, 1266, 1133, 1052, 759, 729, 595, 584 cm–1; HRMS (ESI) calcd. for C14H17NO: [M + H]+: 216.1383, found: 216.1381.
3-(4-Bromophenyl)-N,N-dimethylpropiolamide (3n)
Purification by column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl acetate = 3:1) yielded 3n (21.9 mg, 87%) as a pale yellow solid; m. p. 106–108 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.54–7.48 (d, J = 8.5 Hz, 2H), 7.44–7.36 (d, J = 8.5 Hz, 2H), 3.28 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.4, 133.7, 131.9, 124.6, 119.6, 89.0, 82.5, 38.4, 34.2; IR(KBr): 2924, 2214, 1625, 1496, 1392, 1267, 1136, 1069, 1008, 839, 823, 727, 610, 527, 508 cm–1; HRMS (ESI) calcd. for C11H10BrNO: [M + H]+: 252.0019, found: 252.0025.
3-(4-Chlorophenyl)-N,N-dimethylpropiolamide (3o)
Purification by column chromatography on silica gel (Rf = 0.38, petroleum ether/ethyl acetate = 3:1) yielded 3o (17.8 mg, 86%) as a pale yellow solid; m. p. 107–109 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.52–7.44 (d, J = 8.5 Hz, 2H), 7.39–7.31 (d, J = 8.5 Hz, 2H), 3.28 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.4, 136.3, 133.5, 129.0, 119.1, 89.0, 82.4, 38.4, 34.2; IR(KBr): 2922, 2211, 1626, 1587, 1485, 1394, 1268, 1129, 1078, 1011, 819, 728, 630, 528 cm–1; HRMS (ESI) calcd. for C11H10ClNO: [M + H]+: 208.0524, found: 208.0531.
3-(4-Fluorophenyl)-N,N-dimethylpropiolamide (3p)
Purification by column chromatography on silica gel (Rf = 0.39, petroleum ether/ethyl acetate = 3:1) yielded 3p (17.7 mg, 93%) as a pale yellow solid; m. p. 64–66 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.59–7.50 (t, J = 7.1 Hz, 2H), 7.12–7.01 (tt, J = 8.6, 2.7 Hz, 2H), 3.29 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 163.5 (d, J = 250.8 Hz), 154.5, 134.5 (d, J = 8.6 Hz), 116.7 (d, J = 3.5 Hz), 116.0 (d, J = 22.0 Hz), 89.2, 81.4, 38.4, 34.2; IR(KBr): 3420, 2922, 2211, 1626, 1597, 1505, 1393, 1230, 1130, 1092, 970, 838, 728, 670, 527 cm–1; HRMS (ESI) calcd. for C11H10FNO: [M + H]+: 192.0819, found: 192.0821.
N,N-Dimethyl-3-(4-(trifluoromethyl)phenyl)propiolamide (3q)
Purification by column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl acetate = 3:1) yielded 3q (21.5 mg, 89%) as a pale yellow solid; m. p. 95–97 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.69–7.60 (m, 4H), 3.30 (s, 3H), 3.05 (s, 3H); 13C NMR (100 MHz, CDCl3) 154.1, 132.6, 131.6 (q, J = 32.5 Hz), 125.5 (q, J = 3.8 Hz), 124.4 (d, J = 1.2 Hz), 123.6 (q, J = 270.8 Hz), 88.2, 83.3, 38.4, 34.2; IR(KBr): 3056, 2929, 2223, 1628, 1519, 1437, 1396, 1326, 1274, 1132, 1067, 1018, 970, 852, 729, 602, 580 cm–1; HRMS (ESI) calcd. for C12H10F3NO: [M + H]+: 242.0787, found: 242.0781.
3-(3-Bromophenyl)-N,N-dimethylpropiolamide (3r)
Purification by column chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl acetate = 3:1) yielded 3r (18.2 mg, 72%) as a yellow solid; m. p. 42–44 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.72–7.66 (t, J = 1.6 Hz, 1H), 7.58–7.51 (dq, J = 8.1, 1.0 Hz, 1H), 7.51–7.42 (dt, J = 7.8, 1.2 Hz, 1H), 7.29–7.19 (t, J = 7.9 Hz, 1H), 3.29 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.2, 134.9, 133.1, 130.9, 130.0, 122.6, 122.3, 88.3, 82.5, 38.4, 34.2; IR(KBr): 2925, 2222, 1632, 1555, 1472, 1395, 1136, 1073, 787, 728, 679, 577 cm–1; HRMS (ESI) calcd. for C11H10BrNO: [M + H]+: 252.0019, found: 252.0020.
3-(3-Chlorophenyl)-N,N-dimethylpropiolamide (3s)
Purification by column chromatography on silica gel (Rf = 0.43, petroleum ether/ethyl acetate = 3:1) yielded 3s (16.1 mg, 78%) as a yellow solid; m. p. 49–51 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.54–7.50 (t, J = 1.6 Hz, 1H), 7.46–7.42 (d, J = 7.6 Hz, 1H), 7.41–7.36 (d, J = 8.9 Hz, 1H), 7.33–7.26 (t, J = 7.9 Hz, 1H), 3.28 (s, 3H), 3.04 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.2, 134.4, 132.0, 130.5, 130.3, 129.8, 122.3, 88.4, 82.4, 38.4, 34.2; IR(KBr): 2927, 2211, 1635, 1559, 1474, 1318, 1272, 1137, 1059, 886, 860, 791, 730, 682, 576 cm–1; HRMS (ESI) calcd. for C11H10ClNO: [M + H]+: 208.0524, found: 208.0525.
3-(3-Fluorophenyl)-N,N-dimethylpropiolamide (3t)
Purification by column chromatography on silica gel (Rf = 0.40, petroleum ether/ethyl acetate = 3:1) yielded 3t (15.3 mg, 80%) as a pale yellow solid; m. p. 57–59 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.39–7.29 (m, 2H), 7.29–7.20 (m, 1H), 7.19–7.07 (m, 1H), 3.29 (s, 3H), 3.04 (s, 3H); 13C NMR (100 MHz, CDCl3): 162.7 (d, J = 246.0 Hz), 154.2, 130.2 (d, J = 8.5 Hz), 128.2 (d, J = 3.2 Hz), 122.4 (d, J = 9.4 Hz), 119.0 (d, J = 23.2 Hz), 117.4 (d, J = 21.0 Hz), 88.6 (d, J = 3.2 Hz), 82.1, 38.4, 34.2; IR(KBr): 3432, 2925, 2220, 1624, 1579, 1488, 1393, 1285, 1164, 1123, 986, 915, 870, 798, 728, 681, 576, 519 cm–1; HRMS (ESI) calcd. for C11H10FNO: [M + H]+: 192.0819, found: 192.0822.
3-(2-Fluorophenyl)-N,N-dimethylpropiolamide (3u)
Purification by column chromatography on silica gel (Rf = 0.39, petroleum ether/ethyl acetate = 3:1) yielded 3u (16.6 mg, 87%) as a pale yellow solid; m. p. 75–77 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.60–7.52 (td, J = 7.5, 1.7 Hz, 1H), 7.46–7.36 (m, 1H), 7.22–7.07 (m, 2H), 3.31 (s, 3H), 3.04 (s, 3H); 13C NMR (100 MHz, CDCl3): 163.3 (d, J = 252.4 Hz), 154.3, 134.2, 131.9 (d, J = 8.1 Hz), 124.2 (d, J = 3.9 Hz), 115.7 (d, J = 20.4 Hz), 109.4 (d, J = 15.3 Hz), 86.4 (d, J = 3.4 Hz), 83.4, 38.3, 34.2; IR(KBr): 2925, 2217, 1622, 1493, 1397, 1264, 1215, 1139, 1064, 771, 728, 688, 584, 474 cm–1; HRMS (ESI) calcd. for C11H10FNO: [M + H]+: 192.0819, found: 192.0819.
3-(2-Chlorophenyl)-N,N-dimethylpropiolamide (3v)
Purification by column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl acetate = 3:1) yielded 3v (17.8 mg, 86%) as a pale yellow solid; m. p. 55–57 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.66–7.59 (dd, J = 7.6, 1.5 Hz, 1H), 7.46–7.41 (dd, J = 8.0, 0.9 Hz, 1H), 7.39–7.32 (td, J = 7.6, 1.6 Hz, 1H), 7.31–7.23 (td, J = 7.6, 1.2 Hz, 1H), 3.35 (s, 3H), 3.05 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.3, 136.8, 134.5, 131.0, 129.4, 126.7, 120.8, 86.4, 86.2, 38.4, 34.2; IR(KBr): 3066, 2926, 2854, 2207, 1628, 1473, 1395, 1265, 1164, 1138, 1060, 971, 736, 728, 581, 536 cm–1; HRMS (ESI) calcd. for C11H10ClNO: [M + H]+: 208.0524, found: 208.0520.
3-(3-Bromophenyl)-N,N-dimethylpropiolamide (3w)
Purification by column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl acetate = 3:1) yielded 3w (19.5 mg, 77%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.65–7.59 (m, 2H), 7.35–7.30 (td, J = 7.5, 1.2 Hz, 1H), 7.30–7.24 (td, J = 7.5, 1.9 Hz, 1H), 3.37 (s, 3H), 3.05 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.3, 134.7, 132.6, 131.1, 127.3, 126.1, 123.1, 87.9, 85.5, 38.5, 34.3; IR(KBr): 3433, 2925, 2220, 1630, 1464, 1390, 1261, 1135, 1046, 753, 728, 655, 580 cm–1; HRMS (ESI) calcd. for C11H10BrNO: [M + H]+: 252.0019, found: 252.0021.
N,N-Dimethyl-3-(2-(trifluoromethyl)phenyl)propiolamide (3x)
Purification by column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl acetate = 3:1) yielded 3x (22.9 mg, 95%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.80–7.73 (d, J = 7.3 Hz, 1H), 7.73–7.67 (d, J = 7.3 Hz, 1H), 7.61–7.48 (m, 2H), 3.28 (s, 3H), 3.04 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.1, 135.3, 131.9 (q, J = 29.0 Hz), 129.8, 126.0 (q, J = 5.0 Hz), 123.3 (q, J = 271.5 Hz), 118.9 (q, J = 2.0 Hz), 86.4, 85.1, 38.0, 34.3; IR(KBr): 3447, 2929, 2215, 1636, 1494, 1451, 1396, 1318, 1266, 1175, 1134, 1058, 767, 730, 650, 595 cm–1; HRMS (ESI) calcd. for C12H10F3NO: [M + H]+: 242.0787, found: 242.0784.
3-(4-Formylphenyl)-N,N-dimethylpropiolamide (3y)
Purification by column chromatography on silica gel (Rf = 0.31, petroleum ether/ethyl acetate = 3:1) yielded 3y (7.4 mg, 37%) as a yellow solid; m. p. 86–88 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 10.04 (s, 1H), 7.98–7.85 (dd, J = 6.6, 1.8 Hz, 2H), 7.73–7.67 (d, J = 7.4 Hz, 2H), 3.30 (s, 3H), 3.05 (s, 3H); 13C NMR (100 MHz, CDCl3): 191.2, 154.0, 136.6, 132.8, 129.6, 126.6, 88.6, 84.5, 38.4, 34.3; IR(KBr): 3437, 2923, 2212, 1691, 1628, 1601, 1393, 1271, 1207, 1163, 1066, 824, 794, 726, 530 cm–1; HRMS (ESI) calcd. for C12H11NO2: [M + H]+: 202.0863, found: 202.0862.
N,N-Dimethyl-3-(thiophen-3-yl)propiolamide (3z)
Purification by column chromatography on silica gel (Rf = 0.36, petroleum ether/ethyl acetate = 3:1) yielded 3z (11.5 mg, 64%) as a dark yellow solid; m. p. 77–79 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.69–7.64 (dd, J = 3.0, 1.2 Hz, 1H), 7.35–7.29 (dd, J = 5.0, 3.0 Hz, 1H), 7.23–7.17 (dd, J = 5.0, 1.1 Hz, 1H), 3.28 (s, 3H), 3.02 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.7, 132.0, 129.9, 125.9, 119.8, 85.6, 81.5, 38.4, 34.2; IR(KBr): 3081, 2925, 2211, 1620, 1488, 1390, 1262, 1198, 1130, 986, 869, 805, 727, 625, 585 cm–1; HRMS (ESI) calcd. for C9H9NOS: [M + H]+: 180.0478, found: 180.0481.
N,N-Dimethyl-3-(thiophen-2-yl)propiolamide (3a′)
Purification by column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl acetate = 3:1) yielded 3a′ (6.7 mg, 37%) as a dark yellow solid; m. p. 50–52 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.44–7.38 (m, 2H), 7.06–7.02 (dd, J = 4.9, 3.9 Hz, 1H), 3.27 (s, 3H), 3.03 (s, 3H); 13C NMR (100 MHz, CDCl3): 154.5, 135.0, 129.9, 127.4, 120.3, 85.6, 83.9, 38.3, 34.2; IR(KBr): 3429, 2922, 2198, 1623, 1394, 1259, 1198, 1123, 1066, 737, 589 cm–1; HRMS (ESI) calcd. for C9H9NOS: [M + H]+: 180.0478, found: 180.0476.
N,N-Dimethyl-2-oxo-2-phenylacetamide (3b′)
Purification by column chromatography on silica gel (Rf = 0.28, petroleum ether/ethyl acetate = 3:1) yielded 3b′ (14.4 mg, 81%) as a pale yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 8.01–7.92 (m, 2H), 7.71–7.64 (t, J = 7.4 Hz, 1H), 7.58–7.42 (t, J = 7.6 Hz, 2H), 3.33–3.20 (s, 3H), 3.01–2.91 (s, 3H); 13C NMR (100 MHz, CDCl3): 191.8, 167.0, 134.7, 133.1, 129.7, 129.0, 37.1, 34.0; IR(KBr): 3329, 2922, 1670, 1630, 1597, 1450, 1405, 1247, 1146, 994, 882, 726, 683, 643 cm–1; HRMS (EI) calcd. for C10H12NO2: [M]+: 177.0784, found: 177.0783.
N,N-Diethyl-3-phenylpropiolamide (4a)
Purification by column chromatography on silica gel (Rf = 0.33, petroleum ether/ethyl acetate = 3:1) yielded 4a (11.8 mg, 59%) as a pale yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.57–7.50 (d, J = 6.7 Hz, 2H), 7.45–7.39 (m, 1H), 7.39–7.32 (m, 2H), 3.72–3.62 (q, J = 7.1 Hz, 2H), 3.53–3.43 (q, J = 7.1 Hz, 2H), 1.32–1.23 (t, J = 7.2 Hz, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.0, 132.3, 129.9, 128.5, 120.8, 89.0, 82.0, 43.6, 39.3, 14.4, 12.9; IR(KBr): 3438, 2974, 2219, 1624, 1489, 1426, 1380, 1286, 1136, 1072, 921, 733, 689, 531 cm–1; HRMS (ESI) calcd. for C13H15NO: [M + H]+: 202.1226, found: 202.1227.
N,N-Diethyl-3-(p-tolyl)propiolamide (4b)
Purification by column chromatography on silica gel (Rf = 0.35, hexane/ethyl acetate = 6:1) yielded 4b (11.8 mg, 55%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.46–7.40 (d, J = 8.1 Hz, 2H), 7.20–7.13 (d, J = 7.9 Hz, 2H), 3.71–3.61 (q, J = 7.1 Hz, 2H), 3.53–3.43 (q, J = 7.1 Hz, 2H), 2.37 (s, 3H), 1.32–1.23 (t, J = 7.1 Hz, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.2, 140.3, 132.3, 129.3, 117.7, 89.4, 81.5, 43.6, 39.3, 21.6, 14.4, 12.9; IR(KBr): 3434, 2974, 2204, 1626, 1509, 1425, 1289, 1219, 1135, 816, 733, 532 cm–1; HRMS (ESI) calcd. for C14H17NO: [M + H]+: 216.1383, found: 216.1376.
N,N-Diethyl-3-(4-methoxylphenyl)propiolamide (4c)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4c (10.6 mg, 46%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.52–7.44 (dt, J = 9.2, 2.4 Hz, 2H), 6.92–6.85 (dt, J = 9.5, 2.6 Hz, 2H), 3.83 (s, 3H), 3.71–3.61 (q, J = 7.1 Hz, 2H), 3.52–3.42 (q, J = 7.2 Hz, 2H), 1.32–1.23 (t, J = 7.1 Hz, 3H), 1.21–1.11 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 160.9, 154.3, 134.1, 114.2, 112.7, 89.5, 81.2, 55.4, 43.6, 39.3, 14.4, 12.9; IR(KBr): 3447, 2974, 2934, 2203, 1623, 1510, 1426, 1379, 1286, 1251, 1135, 1028, 833, 733, 660, 533 cm–1; HRMS (ESI) calcd. for C14H17NO2: [M + H]+: 232.1332, found: 232.1328.
N,N-Diethyl-3-(4-ethoxyphenyl)propiolamide (4d)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4d (10.1 mg, 41%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.51–7.43 (dt, J = 9.5, 2.7 Hz, 2H), 6.90–6.83 (dt, J = 9.5, 2.6 Hz, 2H), 4.10–3.98 (q, J = 7.0 Hz, 2H), 3.71–3.61 (q, J = 7.1 Hz, 2H), 3.52–3.42 (q, J = 7.2 Hz, 2H), 1.46–1.37 (t, J = 7.0 Hz, 3H), 1.32–1.24 (t, J = 7.1 Hz, 3H), 1.21–1.13 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 160.3, 154.3, 134.1, 114.6, 112.4, 89.6, 81.1, 63.6, 43.6, 39.2, 14.7, 14.4, 12.9; IR(KBr): 3447, 2978, 2933, 2202, 1624, 1509, 1425, 1379, 1205, 1173, 1134, 1042, 922, 828, 732 cm–1; HRMS (ESI) calcd. for C15H19NO2: [M + H]+: 246.1489, found: 246.1496.
N,N-Diethyl-3-(4-isopropylphenyl)propiolamide (4e)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4e (8.8 mg, 36%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.51–7.43 (d, J = 8.2 Hz, 2H), 7.29–7.19 (d, J = 8.1 Hz, 2H), 3.71–3.58 (q, J = 7.1 Hz, 2H), 3.53–3.43 (q, J = 7.1 Hz, 2H), 2.99–2.85 (m, 1H), 1.32–1.27 (d, J = 7.2 Hz, 3H), 1.27–1.21 (d, J = 7.0 Hz, 6H), 1.21–1.15 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.2, 151.2, 132.4, 126.7, 118.0, 89.4, 81.5, 43.6, 39.3, 34.2, 23.7, 14.4, 12.9; IR(KBr): 3436, 2963, 2931, 2205, 1626, 1456, 1380, 1288, 1135, 1054, 833, 734, 563 cm–1; HRMS (ESI) calcd. for C16H21NO: [M + H]+: 244.1696, found: 244.1691.
3-(4-(tert-Butyl)phenyl)-N,N-diethylpropiolamide (4f)
Purification by column chromatography on silica gel (Rf = 0.33, hexane/ethyl acetate = 6:1) yielded 4f (9.3 mg, 36%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.52–7.44 (dd, J = 6.6, 1.8 Hz, 2H), 7.42–7.33 (dd, J = 6.8, 1.9 Hz, 2H), 3.71–3.61 (q, J = 7.1 Hz, 2H), 3.53–3.43 (q, J = 7.2 Hz, 2H), 1.32 (s, 9H), 1.28–1.22 (m, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.2, 153.4, 132.2, 125.5, 117.7, 89.3, 81.5, 43.6, 39.3, 35.0, 31.1, 14.4, 12.9; IR(KBr): 3435, 2969, 2205, 1626, 1425, 1380, 1220, 1173, 1066, 834, 734, 563 cm–1; HRMS (ESI) calcd. for C17H23NO: [M + H]+: 258.1852, found: 258.1849.
N,N-Diethyl-3-(m-tolyl)propiolamide (4g)
Purification by column chromatography on silica gel (Rf = 0.33, hexane/ethyl acetate = 6:1) yielded 4g (6.5 mg, 30%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.38–7.30 (d, J = 6.4 Hz, 2H), 7.30–7.24 (dd, J = 7.6, 2.0 Hz, 1H), 7.24–7.17 (m, 1H), 3.74–3.61 (q, J = 7.2 Hz, 2H), 3.54–3.41 (q, J = 7.1 Hz, 2H), 2.35 (s, 3H), 1.35–1.24 (t, J = 7.1 Hz, 3H), 1.22–1.07 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.1, 138.3, 132.8, 130.8, 129.5, 128.4, 120.6, 89.3, 81.6, 43.6, 39.3, 21.2, 14.4, 12.9; IR(KBr): 3434, 2974, 2212, 1627, 1425, 1331, 1293, 1219, 1132, 1095, 785, 733, 689, 580 cm–1; HRMS (ESI) calcd. for C14H17NO: [M + H]+: 216.1383, found: 216.1379.
N,N-Diethyl-3-(3-methoxylphenyl)propiolamide (4h)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4h (13.4 mg, 58%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.31–7.23 (t, J = 6.4 Hz, 1H), 7.20–7.10 (d, J = 7.6 Hz, 1H), 7.10–7.04 (d, J = 2.4 Hz, 1H), 7.00–6.84 (dd, J = 8.4, 2.6 Hz, 1H), 3.81 (s, 3H), 3.71–3.55 (q, J = 7.1 Hz, 2H), 3.53–3.40 (q, J = 7.2 Hz, 2H), 1.36–1.24 (m, 3H), 1.22–1.12 (d, J = 7.1 Hz, 3H); 13C NMR: 100 MHz, CDCl3 159.4, 154.0, 129.6, 124.8, 121.7, 117.1, 116.5, 88.9, 81.7, 55.4, 43.6, 39.3, 14.4, 12.9; IR(KBr): 3434, 2973, 2933, 2212, 1731, 1626, 1425, 1380, 1259, 1133, 1044, 786, 733, 685 cm–1; HRMS (ESI) calcd. for C14H17NO2: [M + H]+: 232.1332, found: 232.1331.
N,N-Diethyl-3-(o-tolyl)propiolamide (4i)
Purification by column chromatography on silica gel (Rf = 0.34, hexane/ethyl acetate = 6:1) yielded 4i (16.2 mg, 75%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.55–7.49 (dd, J = 7.5, 0.8 Hz, 1H), 7.34–7.26 (td, J = 7.6, 1.3 Hz, 1H), 7.26–7.21 (d, J = 7.6 Hz, 1H), 7.21–7.13 (t, J = 7.6 Hz, 1H), 3.73–3.64 (q, J = 7.2 Hz, 2H), 3.54–3.44 (q, J = 7.2 Hz, 2H), 2.48 (s, 3H), 1.32–1.23 (t, J = 7.1 Hz, 3H), 1.23–1.15 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.1, 141.1, 133.0, 129.9, 129.7, 125.8, 120.6, 88.0, 85.8, 43.6, 39.4, 20.7, 14.5, 12.9; IR(KBr): 3458, 2974, 2204, 1624, 1455, 1422, 1379, 1282, 1220, 1140 ,1074, 948, 826, 758, 593 cm–1; HRMS (ESI) calcd. for C14H17NO: [M + H]+: 216.1383, found: 216.1381.
N,N-Diethyl-3-(2-methoxylphenyl)propiolamide (4j)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4j (14.1 mg, 61%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.54–7.47 (dd, J = 7.6, 1.7 Hz, 1H), 7.42–7.33 (td, J = 7.9, 1.7 Hz, 1H), 6.97–6.91 (td, J = 7.5, 0.9 Hz, 1H), 6.91–6.87 (d, J = 8.4 Hz, 1H), 3.87 (s, 3H), 3.77–3.67 (q, J = 7.1 Hz, 2H), 3.53–3.43 (q, J = 7.1 Hz, 2H), 1.32–1.23 (t, J = 7.1 Hz, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 161.2, 154.3, 134.2, 131.5, 120.5, 110.7, 110.1, 86.1, 85.6, 55.7, 43.6, 39.3, 14.4, 12.9; IR(KBr): 3453, 2973, 2205, 1623, 1491, 1424, 1277, 1139, 1046, 752, 732 cm–1; HRMS (ESI) calcd. for C14H17NO2: [M + H]+: 232.1332, found: 232.1332.
N,N-Diethyl-3-(2-isopropylphenyl)propiolamide (4k)
Purification by column chromatography on silica gel (Rf = 0.33, hexane/ethyl acetate = 6:1) yielded 4k (18.4 mg, 76%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.56–7.49 (dd, J = 7.7, 1.1 Hz, 1H), 7.42–7.34 (td, J = 7.8, 1.3 Hz, 1H), 7.34–7.27 (d, J = 6.8 Hz, 1H), 7.22–7.13 (td, J = 7.5, 1.4 Hz, 1H), 3.73–3.63 (q, J = 7.2 Hz, 2H), 3.54–3.48 (d, J = 7.2 Hz, 2H), 3.48–3.37 (m, 1H), 1.32–1.24 (m, 9H), 1.23–1.15 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.1, 151.5, 133.4, 130.3, 125.8, 125.1, 119.6, 87.9, 85.6, 43.6, 39.4, 31.8, 23.3, 14.5, 12.9; IR(KBr): 3455, 3062, 2968, 2872, 2203, 1625, 1424, 1314, 1220, 1137, 1033, 948, 812, 733, 594 cm–1; HRMS (ESI) calcd. for C16H21NO: [M + H]+: 244.1696, found: 244.1694.
3-(4-Bromophenyl)-N,N-diethylpropiolamide (4l)
Purification by column chromatography on silica gel (Rf = 0.35, hexane/ethyl acetate = 6:1) yielded 4l (10.4 mg, 37%) as a yellow solid; m. p. 81–83 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.55–7.48 (dt, J = 8.8, 2.2 Hz, 2H), 7.48–7.35 (dt, J = 8.8, 2.1 Hz, 2H), 3.70–3.60 (q, J = 7.2 Hz, 2H), 3.53–3.43 (q, J = 7.2 Hz, 2H), 1.32–1.23 (t, J = 7.2 Hz, 3H), 1.22–1.14 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): 153.7, 133.7, 131.9, 124.5, 119.7, 87.8, 82.9, 43.6, 39.4, 14.4, 12.8; IR(KBr): 3432, 2977, 2933, 2208, 1617, 1480, 1431, 1290, 1218, 1139, 1061, 1007, 837, 732, 532 cm–1; HRMS (ESI) calcd. for C13H14BrNO: [M + H]+: 280.0332, found: 280.0334.
3-(4-Chlorophenyl)-N,N-Diethylpropiolamide (4 M)
Purification by column chromatography on silica gel (Rf = 0.34, hexane/ethyl acetate = 6:1) yielded 4 m (9.6 mg, 41%) as a yellow solid; m. p. 56–58 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.52–7.43 (dt, J = 8.8, 2.2 Hz, 2H), 7.38–7.28 (dt, J = 8.8, 2.1 Hz, 2H), 3.70–3.60 (q, J = 7.2 Hz, 2H), 3.53–3.43 (q, J = 7.2 Hz, 2H), 1.32–1.23 (t, J = 7.2 Hz, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) 153.7, 136.2, 133.5, 128.9, 119.2, 87.8, 82.8, 43.6, 39.3, 14.4, 12.9; IR(KBr): 3438, 2981, 2936, 2210, 1615, 1484, 1431, 1317, 1298, 1219, 1141, 1088, 1011, 841, 733, 535 cm–1; HRMS (ESI) calcd. For C13H14ClNO: [M + H]+: 236.0837, found: 236.0834.
3-(4-Fluorophenyl)-N,N-diethylpropiolamide (4n)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4n (8.6 mg, 39%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.53–7.49 (dt, J = 8.9, 2.2 Hz, 2H), 7.10–6.98 (t, J = 8.7 Hz, 2H), 3.70–3.55 (q, J = 7.1 Hz, 2H), 3.53–3.43 (q, J = 7.1 Hz, 2H), 1.33–1.24 (t, J = 7.2 Hz, 3H), 1.23–1.11 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 163.4 (d, J = 250.7 Hz), 153.9, 134.5 (d, J = 8.6 Hz), 116.9 (d, J = 3.0 Hz), 116.0 (d, J = 22.0 Hz), 88.0, 81.8, 43.6, 39.3, 14.4, 12.9; IR(KBr): 3435, 2974, 2221, 1626, 1507, 1427, 1289, 1236, 1136, 1076, 838, 733, 582, 534 cm–1; HRMS (ESI) calcd. for C13H14FNO: [M + H]+: 220.1132, found: 220.1137.
3-(3-Bromophenyl)-N,N-diethylpropiolamide (4o)
Purification by column chromatography on silica gel (Rf = 0.35, hexane/ethyl acetate = 6:1) yielded 4o (9.8 mg, 35%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.69–7.64 (t, J = 1.6 Hz, 1H), 7.58–7.52 (dq, J = 8.1, 1.0 Hz, 1H), 7.52–7.44 (dt, J = 7.8, 1.1 Hz, 1H), 7.29–7.20 (t, J = 7.9 Hz 1H), 3.72–3.60 (q, J = 7.2 Hz, 2H), 3.54–3.43 (q, J = 7.1 Hz, 2H), 1.36–1.23 (t, J = 7.1 Hz, 3H), 1.23–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 153.5, 134.9, 133.0, 130.9, 130.0, 122.8, 122.3, 87.1, 82.9, 43.6, 39.4, 14.5, 12.8; IR(KBr): 3435, 2974, 2211, 1626, 1474, 1426, 1314, 1286, 1137, 1072, 783, 732, 679, 575 cm–1; HRMS (ESI) calcd. for C13H14BrNO: [M + H]+: 280.0332, found: 280.0330.
3-(3-Chlorophenyl)-N,N-diethylpropiolamide (4p)
Purification by column chromatography on silica gel (Rf = 0.33, hexane/ethyl acetate = 6:1) yielded 4p (11.1 mg, 47%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.54–7.47 (t, J = 1.7 Hz, 1H), 7.45–7.41 (dt, J = 7.6, 1.3 Hz, 1H), 7.41–7.36 (dq, J = 8.2, 1.2 Hz, 1H), 7.33–7.28 (t, J = 7.8 Hz, 1H), 3.70–3.60 (q, J = 7.2 Hz, 2H), 3.53–3.43 (q, J = 7.2 Hz, 2H), 1.32–1.23 (t, J = 7.2 Hz, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 153.6, 134.4, 132.0, 130.5, 130.2, 129.8, 122.5, 87.2, 82.8, 43.6, 39.4, 14.4, 12.8; IR(KBr): 3446, 2975, 2212, 1627, 1475, 1427, 1380, 1218, 1139, 1079, 784, 732, 680, 574 cm–1; HRMS (ESI) calcd. for C13H14ClNO: [M + H]+: 236.0837, found: 236.0833.
3-(3-Fluorophenyl)-N,N-diethylpropiolamide (4q)
Purification by column chromatography on silica gel (Rf = 0.34, hexane/ethyl acetate = 6:1) yielded 4q (10.9 mg, 50%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.39–7.28 (m, 2H), 7.28–7.18 (m, 1H), 7.17–7.06 (m, 1H), 3.70–3.60 (q, J = 7.2 Hz, 2H), 3.53–3.43 (q, J = 7.2 Hz, 2H), 1.32–1.23 (t, J = 7.2 Hz, 3H), 1.23–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 162.3 (d, J = 245.9 Hz), 153.6, 130.2 (d, J = 8.6 Hz), 128.2 (d, J = 3.4 Hz), 122.6 (d, J = 9.4 Hz), 119.0 (d, J = 23.2 Hz), 117.3 (d, J = 21.0 Hz), 87.4 (d, J = 3.4 Hz), 82.5, 43.6, 39.4, 14.4, 12.8; IR(KBr): 3426, 2975, 2935, 2216, 1626, 1582, 1426, 1314, 1219, 1175, 1079, 1050, 965, 788, 733, 681, 576 cm–1; HRMS (ESI) calcd. for C13H14FNO: [M + H]+: 220.1132, found: 220.1128.
3-(2-Bromophenyl)-N,N-diethylpropiolamide (4r)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4r (13.4 mg, 48%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.67–7.57 (m, 2H), 7.37–7.29 (td, J = 7.5, 1.2 Hz, 1H), 7.29–7.20 (td, J = 7.4, 1.9 Hz, 1H), 3.82–3.72 (q, J = 7.1 Hz, 2H), 3.54–3.40 (q, J = 7.2 Hz, 2H), 1.33–1.26 (t, J = 7.1 Hz, 3H), 1.22–1.14 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): 153.7, 134.8, 132.6, 131.0, 127.3, 126.0, 123.2, 86.8, 85.8, 43.6, 39.4, 14.6, 12.9; IR(KBr): 3436, 2973, 2211, 1626, 1473, 1380, 1273, 1140, 1048, 755, 732 cm–1; HRMS (ESI) calcd. for C13H14BrNO: [M + H]+: 280.0332, found: 280.0327.
3-(2-Chlorophenyl)-N,N-diethylpropiolamide (4s)
Purification by column chromatography on silica gel (Rf = 0.35, hexane/ethyl acetate = 6:1) yielded 4s (12.2 mg, 52%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.66–7.59 (dd, J = 7.6, 1.6 Hz, 1H), 7.47–7.40 (dd, J = 8.1, 1.1 Hz, 1H), 7.40–7.33 (td, J = 7.5, 1.7 Hz, 1H), 7.33–7.23 (td, J = 7.6, 1.3 Hz, 1H), 3.79–3.69 (q, J = 7.1 Hz, 2H), 3.67–3.44 (q, J = 7.2 Hz, 2H), 1.33–1.24 (q, J = 7.3 Hz, 3H), 1.24–1.15 (q, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): 153.7, 136.8, 134.5, 130.9, 129.4, 126.7, 121.0, 86.5, 85.2, 43.6, 39.4, 14.5, 12.9; IR(KBr): 3434, 2973, 2211, 1624, 1475, 1380, 1259, 1139, 1058, 752, 732 cm–1; HRMS (ESI) calcd. for C13H14ClNO: [M + H]+: 236.0837, found: 236.0838.
3-(2-Fluorophenyl)-N,N-diethylpropiolamide (4t)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4t (11.7 mg, 53%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.60–7.51 (td, J = 7.5, 1.7 Hz, 1H), 7.46–7.35 (m, 1H), 7.20–7.06 (m, 2H), 3.74–3.63 (q, J = 7.2 Hz, 2H), 3.58–3.44 (q, J = 7.1 Hz, 2H), 1.32–1.24 (t, J = 7.1 Hz, 3H), 1.22–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 163.4 (d, J = 252.3 Hz), 153.6, 134.2, 131.8 (d, J = 8.0 Hz), 124.2 (d, J = 3.7 Hz), 115.7 (d, J = 20.4 Hz), 109.6 (d, J = 15.3 Hz), 86.8 (d, J = 3.3 Hz), 82.2, 43.7, 39.4, 14.4, 12.9; IR(KBr): 3437, 2974, 2219, 1628, 1492, 1426, 1365, 1267, 1138, 1072, 836, 758, 733 cm–1; HRMS (ESI) calcd. for C13H14FNO: [M + H]+: 220.1132, found: 220.1135.
N,N-Diethyl-3-(4-formylphenyl)propiolamide (4u)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4u (7.6 mg, 33%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 10.04 (s, 1H), 7.92–7.83 (d, J = 8.3 Hz, 2H), 7.74–7.66 (d, J = 8.2 Hz, 2H), 3.72–3.55 (q, J = 7.2 Hz, 2H), 3.54–3.45 (q, J = 7.2 Hz, 2H), 1.33–1.24 (m, 3H), 1.23–1.16 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 191.2, 153.4, 136.6, 132.8, 129.6, 126.8, 87.5, 84.9, 43.7, 39.4, 14.5, 12.8; IR(KBr): 3430, 2973, 2924, 1703, 1628, 1426, 1283, 1203, 1166, 1066, 828, 732, 608, 532 cm–1; HRMS (ESI) calcd. for C14H15NO2: [M + H]+: 230.1176, found: 230.1176.
N,N-Diethyl-3-(thiophen-3-yl)propiolamide (4v)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4v (9.5 mg, 46%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.69–7.62 (dd, J = 3.0, 1.1 Hz, 1H), 7.35–7.28 (t, J = 4.0 Hz, 1H), 7.22–7.16 (dd, J = 5.0, 1.1 Hz, 1H), 3.70–3.60 (q, J = 7.1 Hz, 2H), 3.52–3.36 (q, J = 7.1 Hz, 2H), 1.31–1.23 (t, J = 7.1 Hz, 3H), 1.22–1.08 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.0, 131.8, 129.9, 125.8, 119.9, 84.4, 81.8, 43.5, 39.2, 14.4, 12.8; IR(KBr): 3434, 2214, 1619, 1427, 1358, 1276, 1130, 1094, 783, 732, 625 cm–1; HRMS (ESI) calcd. for C11H13NOS: [M + H]+: 208.0791, found: 208.0785.
N,N-Diethyl-3-(thiophen-2-yl)propiolamide (4w)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4w (6.4 mg, 31%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.48–7.37 (m, 2H), 7.08–7.00 (dd, J = 5.0, 4.0 Hz, 1H), 3.68–3.59 (q, J = 7.1 Hz, 2H), 3.59–3.40 (q, J = 7.1 Hz, 2H), 1.38–1.26 (d, J = 7.1 Hz, 3H), 1.20–1.14 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): 153.8, 134.8, 129.7, 127.4, 120.5, 86.0, 82.7, 43.5, 39.3, 14.4, 12.9; IR(KBr): 3435, 2973, 2203, 1624, 1412, 1380, 1276, 1066, 1049, 738, 705 cm–1; HRMS (ESI) calcd. for C11H13NOS: [M + H]+: 208.0791, found: 208.0790.
N,N-Dibutyl-3-phenylpropiolamide (4x)
Purification by column chromatography on silica gel (Rf = 0.44, petroleum ether/ethyl acetate = 6:1) yielded 4x (15.0 mg, 58%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.57–7.49 (d, J = 6.6 Hz, 2H), 7.44–7.38 (m, 1H), 7.38–7.31 (m, 2H), 3.64–3.56 (t, J = 7.4 Hz, 2H), 3.45–3.36 (t, J = 7.6 Hz, 2H), 1.70–1.61 (m, 2H), 1.61–1.51 (m, 2H), 1.46–1.37 (m, 2H), 1.37–1.28 (m, 2H), 1.02–0.96 (t, J = 6.4 Hz, 3H), 0.96–0.90 (m, 3H); 13C NMR (100 MHz, CDCl3): 154.4, 132.3, 129.8, 128.5, 120.8, 89.2, 82.2, 48.9, 44.6, 31.0, 29.6, 20.2, 20.0, 13.9, 13.8; IR(KBr): 3436, 2960, 2872, 2213, 1625, 1490, 1422, 1378, 1265, 1138, 1051, 756, 733, 688, 530 cm–1; HRMS (ESI) calcd. for C17H23NO: [M + H]+: 258.1852, found: 258.1853.
N,N-Dibutyl-3-(4-ethoxyphenyl)propiolamide (4y)
Purification by column chromatography on silica gel (Rf = 0.32, hexane/ethyl acetate = 6:1) yielded 4y (16.2 mg, 54%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.50–7.42 (dd, J = 6.9, 1.9 Hz, 2H), 6.90–6.82 (d, J = 8.8 Hz, 2H), 4.10–4.00 (q, J = 7.0 Hz, 2H), 3.63–3.55 (t, J = 7.4 Hz, 2H), 3.44–3.35 (t, J = 7.4 Hz, 2H), 1.72–1.60 (m, 2H), 1.60–1.50 (m, 2H), 1.46–1.41 (d, J = 7.0 Hz, 3H), 1.41–1.30 (m, 4H), 1.02–0.96 (d, J = 7.3 Hz, 3H), 0.96–0.91 (m, 3H); 13C NMR (100 MHz, CDCl3): 160.3, 154.7, 134.0, 114.7, 112.5, 89.8, 81.4, 63.6, 48.9, 44.5, 31.0, 29.6, 20.2, 20.0, 14.7, 13.9; IR(KBr): 2958, 2931, 2872, 2208, 1625, 1509, 1422, 1378, 1250, 1138, 1114, 1043, 837, 732 cm–1; HRMS (ESI) calcd. for C19H27NO2: [M + H]+: 302.2115, found: 302.2113.
N,N-Dibutyl-3-(4-(tert-butyl)phenyl)propiolamide (4z)
Purification by column chromatography on silica gel (Rf = 0.48, hexane/ethyl acetate = 6:1) yielded 4z (17.6 mg, 56%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.51–7.43 (dd, J = 6.6, 1.8 Hz, 2H), 7.42–7.34 (dd, J = 6.7, 1.9 Hz, 2H), 3.67–3.56 (t, J = 7.4 Hz, 2H), 3.44–3.36 (t, J = 7.6 Hz, 2H), 1.71–1.61 (m, 2H), 1.61–1.50 (m, 2H), 1.43–1.38 (m, 2H), 1.38–1.33 (m, 2H), 1.32 (s, 9H), 1.01–0.96 (m, 3H), 0.96–0.90 (m, 3H); 13C NMR (100 MHz, CDCl3): 154.6, 153.4, 132.1, 125.5, 117.8, 89.6, 81.7, 48.9, 44.6, 35.0, 31.1, 31.0, 29.6, 20.2, 20.0, 13.9; IR(KBr): 3435, 2959, 2871, 2211, 1628, 1504, 1421, 1364, 1296, 1208, 1105, 834, 731, 563 cm–1; HRMS (ESI) calcd. for C21H31NO: [M + H]+: 314.2478, found: 314.2481.
N,N-Dibutyl-3-(2-methoxylphenyl)propiolamide (4a′)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4a′ (20.5 mg, 71%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.55–7.48 (dd, J = 7.6, 1.6 Hz, 1H), 7.41–7.33 (td, J = 7.6, 1.6 Hz, 1H), 6.97–6.91 (t, J = 7.5 Hz, 1H), 6.91–6.84 (d, J = 8.4 Hz, 1H), 3.87 (s, 3H), 3.71–3.60 (t, J = 7.5 Hz, 2H), 3.47–3.32 (t, J = 7.6 Hz, 2H), 1.72–1.61 (m, 2H), 1.61–1.50 (m, 2H), 1.46–1.37 (m, 2H), 1.37–1.29 (dt, J = 16.5, 6.8 Hz, 2H), 1.00–0.90 (dt, J = 11.6, 7.3 Hz, 6H); 13C NMR (100 MHz, CDCl3): 161.1, 154.7, 134.4, 131.4, 120.5, 110.6, 110.1, 86.3, 85.9, 55.6, 48.9, 44.5, 31.1, 29.6, 20.2, 20.0, 13.9, 13.9; IR(KBr): 2958, 2930, 2211, 1622, 1595, 1464, 1422, 1376, 1276, 1112, 1046, 1022, 937, 751, 732, 554 cm–1; HRMS (ESI) calcd. for C18H25NO2: [M + H]+: 288.1958, found: 288.1965.
N,N-Dibutyl-3-(4-formylphenyl)propiolamide (4b′)
Purification by column chromatography on silica gel (Rf = 0.31, hexane/ethyl acetate = 6:1) yielded 4b′ (15.7 mg, 55%) as a dark yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 10.04 (s, 1H), 7.93–7.83 (dd, J = 6.6, 1.8 Hz, 2H), 7.71–7.64 (d, J = 8.2 Hz, 2H), 3.67–3.56 (t, J = 7.4 Hz, 2H), 3.46–3.37 (t, J = 7.6 Hz, 2H), 1.71–1.62 (m, 2H), 1.62–1.51 (m, 2H), 1.46–1.38 (m, 2H), 1.38–1.31 (m, 2H), 1.02–0.92 (dt, J = 11.1, 7.3 Hz, 6H); 13C NMR (100 MHz, CDCl3): 191.2, 153.8, 136.5, 132.7, 129.6, 126.9, 87.7, 85.2, 48.9, 44.7, 31.0, 29.5, 20.2, 20.0, 13.9, 13.8; IR(KBr): 3434, 2958, 1702, 1628, 1601, 1423, 1301, 1203, 1166, 1050, 829, 732 cm–1; HRMS (ESI) calcd. for C18H23NO2: [M + H]+: 286.1802, found: 286.1802.
N,N-Dibutyl-3-(thiophen-3-yl)propiolamide (4c′)
Purification by column chromatography on silica gel (Rf = 0.41, hexane/ethyl acetate = 6:1) yielded 4c’ (21.1 mg, 80%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.66–7.61 (dd, J = 3.0, 1.1 Hz, 1H), 7.35–7.28 (dd, J = 5.0, 3.0 Hz, 1H), 7.21–7.15 (dd, J = 5.0, 1.1 Hz, 1H), 3.62–3.54 (t, J = 7.4 Hz, 2H), 3.44–3.35 (t, J = 7.6 Hz, 2H), 1.71–1.60 (m 2H), 1.60–1.50 (m, 2H), 1.46–1.37 (m, 2H), 1.37–1.30 (m, 2H), 1.02–0.96 (d, J = 7.3 Hz, 3H), 0.96–0.91 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.4, 131.8, 129.9, 125.9, 120.0, 84.7, 82.1, 48.8, 44.6, 31.0, 29.6, 20.2, 20.0, 13.9, 13.8; IR(KBr): 3445, 2959, 2872, 2213, 1621, 1519, 1462, 1360, 1293, 1261, 1213, 1134, 1051, 871, 784, 733, 626 cm–1; HRMS (ESI) calcd. for C15H21NOS: [M + H]+: 264.1417, found: 264.1410.
N,N-Dibutyl-3-(thiophen-2-yl)propiolamide (4d′)
Purification by column chromatography on silica gel (Rf = 0.43, hexane/ethyl acetate = 6:1) yielded 4d′ (13.5 mg, 51%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.43–7.36 (t, J = 3.5 Hz, 2H), 7.07–6.98 (t, J = 4.4 Hz, 1H), 3.60–3.52 (t, J = 7.5 Hz, 2H), 3.44–3.31 (t, J = 7.6 Hz, 2H), 1.70–1.60 (m, 2H), 1.60–1.51 (m, 2H), 1.47–1.38 (m, 2H), 1.38–1.30 (m, 2H), 1.03–0.96 (t, J = 7.4 Hz, 3H), 0.96–0.90 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): 154.2, 134.8, 129.7, 127.4, 120.6, 86.2, 82.9, 48.9, 44.6, 31.0, 29.6, 20.2, 20.0, 13.9, 13.8; IR(KBr): 3435, 2959, 2928, 2198, 1623, 1411, 1377, 1292, 1217, 1046, 729, 704 cm–1; HRMS (ESI) calcd. for C15H21NOS: [M + H]+: 264.1417, found: 264.1411.
3-Phenyl-1-(piperidin-1-yl)prop-2-yn-1-one (7)
Purification by column chromatography on silica gel (Rf = 0.42, hexane/ethyl acetate = 3:1) yielded 7 (16.7 mg, 78%) as a pale yellow solid; m. p. 112–114 °C; 1H NMR (400 MHz, CDCl3) ppm: δ 7.61–7.53 (m, 2H), 7.48–7.34 (m, 3H), 3.83–3.77 (t, J = 5.8 Hz, 2H), 3.72–3.46 (t, J = 5.6 Hz, 2H), 1.81–1.55 (m, 6H); 13C NMR (100 MHz, CDCl3): 152.9, 132.3, 129.9, 128.5, 120.8, 90.2, 81.5, 48.2, 42.4, 26.5, 25.4, 24.6; IR(KBr): 2926, 2852, 2202, 1614, 1440, 1274, 1209, 1132, 1020, 850, 761, 692 cm–1; HRMS (EI) calcd. for C14H15NO: [M]+: 213.1148, found: 213.1138.
2,2-Diphenylvinyl Dimethylcarbamodithioate (8)
Purification by column chromatography on silica gel (Rf = 0.35, petroleum ether/EtOAc = 10:1) yielded 8 (6.3 mg, 21%) as a yellow oil; 1H NMR (400 MHz, CDCl3) ppm: δ 7.74 (s, 1H), 7.41–7.33 (m, 6H), 7.32–7.25 (m, 4H), 3.55 (s, 3H), 3.30 (s, 3H); 13C NMR (100 MHz, CDCl3): 194.4, 142.0, 141.1, 139.8, 129.7, 128.4, 128.3, 128.0, 127.8, 127.6, 123.5, 45.4, 41.6 cm–1; HRMS (ESI) calcd. for C17H17NS2: [M + H]+: 300.0875, found: 300.0866.
Acknowledgments
The authors greatly acknowledge financial support by Natural Science Foundation of Henan Province (212300410163), the Education Department of Henan Province (20A210023), Henan Agricultural University (30500567), China Tobacco Henan Industrial Co., Ltd. (2021410001300070, 2021410001300071, and ZW201823), and Hunan Provincial Tobacco Company (HN2020KJ09).
Supporting Information Available
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.2c07353.
Experimental mechanistic studies; 1H and 13C NMR spectra of all compounds (PDF)
The authors declare no competing financial interest.
Supplementary Material
References
- a Enders D.; Rembiak A.; Liebich J. Direct Organocatalytic α-Sulfenylation of Aldehydes and Ketones with Tetramethylthiuram Disulfide. Synthesis 2011, 2, 281–286. [Google Scholar]; b Dong Z.-B.; Liu X.; Bolm C. Copper-Catalyzed C(sp2)-S Coupling Reactions for the Synthesis of Aryl Dithiocarbamates with Thiuram Disulfide Reagents. Org. Lett. 2017, 19, 5916–5919. 10.1021/acs.orglett.7b02911. [DOI] [PubMed] [Google Scholar]
- a Hao S.; Ye X.; Zhao M.; Hu J.; Wang N.; Li J.; Wang F.; Zhang M.; Wu Z. Synthesis of 2-Aryl-2-hydroxyethyl Dithiocarbamates via Regioselective Addition of Tetraalkylthiuram Disulfides to Styrenes under Transition-Metal-Free Conditions. Adv. Synth. Catal. 2020, 362, 5014–5019. 10.1002/adsc.202000729. [DOI] [Google Scholar]; b Cheng C.; Zhao M.; Lai M.; Zhai K.; Shi B.; Wang S.; Luo R.; Zhang L.; Wu Z. Synthesis of Aza-Heteroaromatic Dithiocarbamates via Cross-Coupling Reactions of Aza-Heteroaromatic Bromides with Tetraalkylthiuram Disulfides. Eur. J. Org. Chem. 2019, 2019, 2941–2949. 10.1002/ejoc.201900475. [DOI] [Google Scholar]; c Lai M.; Wu Z.; Li S.; Wei D.; Zhao M. Regioselective Synthesis of Sulfonyl-Containing Benzyl Dithiocarbamates through Copper-Catalyzed Thiosulfonylation of Styrenes. J. Org. Chem. 2019, 84, 11135–11149. 10.1021/acs.joc.9b01829. [DOI] [PubMed] [Google Scholar]; d Wu Z.; Lai M.; Zhang S.; Zhong X.; Song H.; Zhao M. An Efficient Synthesis of Benzyl Dithiocarbamates by BasePromoted Cross-Coupling Reactions of Benzyl Chlorides with Tetraalkylthiuram Disulfides at Room Temperature. Eur. J. Org. Chem. 2018, 2018, 7033–7036. 10.1002/ejoc.201801449. [DOI] [Google Scholar]; e Peng H.-Y.; Dong Z.-B. Transition-Metal-Free C(sp3)-S Coupling in Water: Synthesis of Benzyl Dithiocarbamates Using Thiuram Disulfides as an Organosulfur Source. Eur. J. Org. Chem. 2019, 2019, 949–956. 10.1002/ejoc.201801520. [DOI] [Google Scholar]; f Wu X.; Yan G. Copper-Catalyzed Synthesis of S-Aryl Dithiocarbamates from Tetraalkylthiuram Disulfides and Aryl Iodides in Water. Synlett 2019, 30, 610–614. 10.1055/s-0037-1612086. [DOI] [Google Scholar]; g Kienle M.; Unsinn A.; Knochel P. Synthesis of Dibenzothiophenes and Related Classes of Heterocycles by Using Functionalized Dithiocarbamates. Angew. Chem., Int. Ed. 2010, 49, 4751–4754. 10.1002/anie.201001025. [DOI] [PubMed] [Google Scholar]; h Krasovskiy A.; Gavryushin A.; Knochel P. Highly Stereoselective Access to Sulfur Derivatives Starting from Zinc Organometallics. Synlett 2006, 5, 792–794. [Google Scholar]; i Krasovskiy A.; Gavryushin A.; Knochel P. A General Thiolation of Magnesium Organometallics Using Tetramethylthiuram Disulfide. Synlett 2005, 17, 2691–2693. [Google Scholar]
- a McDonald I.; Mate R.; Zusi F.; Huang D.; Post-Munson D.; Ferrante M.; Gallagher L.; Bertekap R.; Knox R.; Robertson B.; Harden D.; Morgan D.; Lodge N.; Dworetzky S.; Olson R.; Macor J. Discovery of a novel series of quinolone α7 nicotinic acetylcholine receptor agonists. Bioorg. Med. Chem. Lett. 2013, 23, 1684–1688. 10.1016/j.bmcl.2013.01.070. [DOI] [PubMed] [Google Scholar]; b Eibl C.; Munoz L.; Tomassoli I.; Stokes C.; Papke R.; Gundisch D. The 3, 7-diazabicyclo [3.3.1] nonane scaffold for subtype selective nicotinic acetylcholine receptor ligands. Part 2: Carboxamide derivatives with different spacer motifs. Bioorg. Med. Chem. 2013, 21, 7309–7329. 10.1016/j.bmc.2013.09.060. [DOI] [PMC free article] [PubMed] [Google Scholar]
- a Pinto A.; Neuville L.; Retailleau P.; Zhu J. Synthesis of 3-(Diarylmethylenyl)oxindole by a Palladium-Catalyzed Domino Carbopalladation/C–H Activation/C–C Bond-Forming Process. J. Org. Lett. 2006, 8, 4927–4930. 10.1021/ol062022h. [DOI] [PubMed] [Google Scholar]; b Donets P.; Eycken E. Efficient Synthesis of the 3-Benzazepine Framework via Intramolecular Heck Reductive Cyclization. Org. Lett. 2007, 9, 3017–3020. 10.1021/ol071079g. [DOI] [PubMed] [Google Scholar]; c Peng H.; Liu G. Palladium-Catalyzed Tandem Fluorination and Cyclization of Enynes. Org. Lett. 2011, 13, 772–775. 10.1021/ol103039x. [DOI] [PubMed] [Google Scholar]; d Xie X.; Lu X.; Liu Y.; Xu W. Palladium(II)-Catalyzed Synthesis of α-Alkylidene-γ-butyrolactams from N-Allylic 2-Alkynamides. Total Synthesis of (±)-Isocynodine and (±)-Isocynometrine. J. Org. Chem. 2001, 66, 6545–6550. 10.1021/jo001704u. [DOI] [PubMed] [Google Scholar]; e Hay L.; Koenig T.; Ginah F.; Copp J.; Mitchell D. Palladium-Catalyzed Hydroarylation of Propiolamides. A Regioand Stereocontrolled Method for Preparing 3,3-Diarylacrylamides. J. Org. Chem. 1998, 63, 5050–5058. 10.1021/jo980235h. [DOI] [Google Scholar]; f Ryan J.; Stang P. Synthesis of Bicyclic Enediynes from Bis[phenyl[(trifluoromethanesulfonyl)oxy]iodo]acetylene: A Tandem Diels-Alder/Palladium(II)- and Copper(I)-Cocatalyzed Cross-Coupling Approach. J. Org. Chem. 1996, 61, 6162–6165. 10.1021/jo960750k. [DOI] [PubMed] [Google Scholar]
- Zhang J.; Liao Y.; Deng J.; Tang Z.; Xu Y.; Xu L.; Tang R. DABCO-Promoted Decarboxylative Acylation: Synthesis of α-Keto and α,β-Unsaturated Amides or Esters. Asian J. Org. Chem. 2017, 6, 305–312. 10.1002/ajoc.201600591. [DOI] [Google Scholar]
- Hartke K.; Gerber H.; Roesrath U. α, β-acetylenic dithio and thiono esters. Tetrahedron Lett. 1989, 30, 1073–1076. 10.1016/S0040-4039(01)80363-4. [DOI] [Google Scholar]
- a Xie Y.; Song R.; Yang X.; Xiang J.; Li J. Copper-Catalyzed Amidation of Acids Using Formamides as the Amine Source. Eur. J. Org. Chem. 2013, 2013, 5737–5742. 10.1002/ejoc.201300543. [DOI] [Google Scholar]; b Li H.; Pan C.; Cheng Y.; Zhu C. Copper-catalyzed oxidative coupling of carboxylic acids with formamides for the synthesis of α,β-unsaturated amides. Tetrahedron Lett. 2013, 54, 6679–6681. 10.1016/j.tetlet.2013.09.016. [DOI] [Google Scholar]
- Liu Z.; Zhang J.; Chen S.; Shi E.; Xu Y.; Wan X. Cross Coupling of Acyl and Aminyl Radicals: Direct Synthesis of Amides Catalyzed by Bu4NI with TBHP as an Oxidant. Angew. Chem., Int. Ed. 2012, 51, 3231–3235. 10.1002/anie.201108763. [DOI] [PubMed] [Google Scholar]
- Cunico R.; Maity B. Direct Carbamoylation of Alkenyl Halides. Org. Lett. 2003, 5, 4947–4949. 10.1021/ol030110l. [DOI] [PubMed] [Google Scholar]
- Mane R.; Bhanage B. Palladium-Catalyzed Oxidative N-Dealkylation/Carbonylation of Tertiary Amines with Alkynes to α,β-Alkynylamides. J. Org. Chem. 2016, 81, 4974–4980. 10.1021/acs.joc.6b00386. [DOI] [PubMed] [Google Scholar]
- Idris M.; Kim M.; Kim J.; Lee S. Palladium-catalyzed decarboxylative aminocarbonylation with alkynoic acid and tertiary amine for the synthesis of alkynyl amide. Tetrahedron 2019, 75, 4130–4137. 10.1016/j.tet.2019.04.030. [DOI] [Google Scholar]
- a Zha G.; Fang W.; Li Y.; Leng J.; Chen X.; Qin H. SO2F2-Mediated Oxidative Dehydrogenation and Dehydration of Alcohols to Alkynes. J. Am. Chem. Soc. 2018, 140, 17666–17673. 10.1021/jacs.8b10069. [DOI] [PubMed] [Google Scholar]; b Chen W.; Walker J.; Oestreich M. Metal-Free Transfer Hydroiodination of C–C Multiple Bond. J. Am. Chem. Soc. 2019, 141, 1135–1140. 10.1021/jacs.8b12318. [DOI] [PubMed] [Google Scholar]; c Tan W.; Jansch N.; Öhlmann T.; Meyer-Almes F.; Jiang X. Thiocarbonyl Surrogate via Combination of Potassium Sulfide and Chloroform for Dithiocarbamate Construction. Org. Lett. 2019, 21, 7484–7488. 10.1021/acs.orglett.9b02784. [DOI] [PubMed] [Google Scholar]; d Huang S.; Wang M.; Jiang X. Ni-catalyzed C–S bond construction and cleavage. Chem. Soc. Rev. 2019, 51, 8351–8377. [DOI] [PubMed] [Google Scholar]
- a Lai M.; Wu Z.; Wang Y.; Zheng Y.; Zhao M. Selective synthesis of aryl thioamides and aryl-α-ketoamides from α-oxocarboxylic acids and tetraalkylthiuram disulfides: an unexpected chemoselectivity from aryl sulfonyl chlorides. Org. Chem. Front. 2019, 6, 506–511. 10.1039/C8QO01127C. [DOI] [Google Scholar]; b Lai M.; Wu Z.; Su F.; Yu Y.; Jing Y.; Kong J.; Wang Z.; Wang S.; Zhao M. Synthesis of Cinnamides via Amidation Reaction of Cinnamic Acids with Tetraalkylthiuram Disulfides Under Simple Condition. Eur. J. Org. Chem. 2020, 2020, 198–208. 10.1002/ejoc.201901630. [DOI] [Google Scholar]; c Hu J.; Ye X.; Hao S.; Zhao Q.; Zhao M.; Wei Y.; Wu Z.; Wang N.; Ji X. Amidation Reaction of Quinoline-3-carboxylic Acids with Tetraalkylthiuram Disulfides under Simple Conditions: A facile Synthesis of Quinoline-3-carboxamides. Asian J. Org. Chem. 2020, 9, 2191–2195. 10.1002/ajoc.202000462. [DOI] [Google Scholar]; d Wu Z.; Cheng C.; Tang X.; Liu S.; Xi G.; Zhao M.; Liu P. Phosphine-Promoted Amide Bond Formation Reactions from Carboxylic Acids and Tetraalkylthiuram Disulfides. ChemistrySelect 2018, 3, 13038–13041. 10.1002/slct.201803311. [DOI] [Google Scholar]; e Wang L.; Ding S.; Shen H.; Wang Y.; Hao S.; Yin G.; Qiu J.; Lin B.; Wu Z.; Zhao M. Generation of Coumarin-3-Carboxamides From Coumarin-3-Carboxylic Acids and Tetraalkylthiuram Disulfides Catalyzed by Copper Salts. Asian J. Org. Chem. 2021, 10, 2544–2548. 10.1002/ajoc.202100491. [DOI] [Google Scholar]
- Steudel R.; Steudel Y.; Mak A.; Wong M. Homolytic Dissociation of the Vulcanization Accelerator Tetramethylthiuram Disulfide (TMTD) and Structures and Stabilities of the Related Radicals Me2NCSn • (n = 1-4). J. Org. Chem. 2006, 71, 9302–9311. 10.1021/jo061345o. [DOI] [PubMed] [Google Scholar]
- Luo H.; Sun K.; Xie Q.; Li X.; Zhang X.; Luo X. Copper-Mediated Phosphorylation of Arylsilanes with H-Phosphonate Diesters. Asian J. Org. Chem. 2020, 12, 2083–2086. [Google Scholar]
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