Benzotriazole as an Efficient Ligand in Cu-Catalyzed Glaser Reaction

5 days ago - of a base and an oxidant (Scheme 1).2 The Chodkiewicz−. Cadiot coupling method was ... many ways for the last few years.8 Recently, we ...
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Article Cite This: ACS Omega 2019, 4, 2418−2424

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Benzotriazole as an Efficient Ligand in Cu-Catalyzed Glaser Reaction Mala Singh, Anoop S. Singh, Nidhi Mishra, Anand K. Agrahari, and Vinod K. Tiwari* Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India

ACS Omega 2019.4:2418-2424. Downloaded from pubs.acs.org by 109.236.55.38 on 02/04/19. For personal use only.

S Supporting Information *

ABSTRACT: Benzotriazole has been established as an efficient ligand in Cu-catalyzed cross-coupling of terminal alkynes to form 1,3-dialkynes using CuI as the catalyst and K2CO3 as the base at room temperature in an open round-bottom flask. The established protocol has the following notable advantages: simple to handle, easy work-up, mild reaction condition, high substrate scope, requirement of less quantity of ligand and also Cu-catalyst, less expensive, and high reaction yield.

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INTRODUCTION Conjugated 1,3-dialkynes containing molecules are useful in various fields of science as this moiety is found in several biological active natural products, supramolecular, polymer, optical, and electronic materials, as well as they actively participate in a number of organic and inorganic syntheses.1 There are various strategies available for the synthesis of diverse 1,3-dialkynes, where the most important protocol includes Glaser coupling and its modifications in which terminal alkynes are heated with Cu(I) salts in the presence of a base and an oxidant (Scheme 1).2 The Chodkiewicz−

toxic catalysts, low reaction yields, requirement of high reaction temperature, or longer reaction time warrant improved protocols for this type of coupling (Table 1). Advantages associated with benzotriazole, such as high stability, high solubility in most of the organic solvents, and compatibility with the various reaction conditions, make this moiety a suitable auxiliary in organic synthesis.7 Our research group has been exploring the amazing features of this moiety in many ways for the last few years.8 Recently, we have exploited the coordinating property of benzotriazole moiety and have successfully explored it as a ligand in intramolecular C−O coupling reaction.9 In continuation to it, we have presented here 1H-bezotriazole as an efficient ligand for Cu(I)-catalyzed Glaser coupling and isolated the final coupling product in good to excellent yields.

Scheme 1. Comparative Illustration of This Work with Previous Methods

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RESULTS AND DISCUSSION Our synthetic strategy was initiated with Cu-catalyzed reaction of phenyl acetylene 1a taking 20 mol % of 1H-benzotriazole as a ligand in the presence of 10 mol % CuI as catalyst and K2CO3 as a base in traditional Glaser coupling at 120 °C for 12 h and we got almost 85% yield (Scheme 2) after flash column chromatography (SiO2) and compound 2a is well characterized by 1H NMR, 13C NMR, infrared, mass spectrometry, and X-ray crystallography. After achieving favorable promising results, we started the optimizing reaction with compound 1a with respect to the reaction temperature and found that below 50 °C we noticed only a single spot on thin-layer chromatography (TLC) (entries 1−3). Then, we optimized the reaction with respect to the catalyst and found that all Cu(I)-sources give average to good yields but CuI is the best as it converts the starting

Cadiot coupling method was applied to synthesize unsymmetric 1,3-dialkyne via Cu(I)-catalyzed coupling of terminal alkyne and haloalkyne.3 Yu and Jiao nicely utilized Cu(I)catalyzed decarboxylation for the coupling of terminal alkyne and proiolic acid.4 Lei et al. extended the Glaser coupling method for the synthesis of unsymmetric 1,3-dialkyne by using two different terminal alkynes in the presence of NiCl2·6H2O/ CuI with a base and an oxidant.5 Furthermore, Rossi et al. synthesized conjugated 1,3-dialkynes by using palladium salts with CuI.6 Drawbacks related to these methods such as use of © 2019 American Chemical Society

Received: December 5, 2018 Accepted: January 22, 2019 Published: January 31, 2019 2418

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Table 1. Reaction Optimization Study

entrya

catalyst (mol %)

ligand (mol %)

base (equiv)

temp °Cb

solventc

yield (%)d

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

CuI (10) CuI (10) CuI (10) CuBr (10) CuCl (10) CuOAc (10) CuSO4 (10) CuI (5) CuI (2) CuI (1) CuI (0) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2) CuI (2)

BtH (20) BtH (20) BtH (20) BtH (20) BtH (20) BtH (20) BtH (20) BtH (10) BtH (5) BtH (2) BtH (5) BtH (0) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) BtH (5) 5-Cl-BtH (5) HMBt (5) PhCOBt (5) o-OMePhBt (5)

K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (1) K2CO3 (0.5) K2CO3 (0.2) K2CO3 (0) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5) Cs2CO3 (0.5) K3PO4 (0.5) KtOBu (0.5) KOH (0.5) Et3N (0.5) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5) K2CO3 (0.5)

120 50 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25

DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF CHCl3 DCM dioxane CH3CN toluene benzene THF DMF DMF DMF DMF DMF DMF DMF DMF DMF

85 99 99 80 72 75 0 99 99 89 0 trace 99 78 71 trace trace 65 60 39 43 63 80 82 0 60 20 99 10 99 99

Molar ratio: alkyne (1.0 mmol). bTemperature may be vary by 2 °C. cDry solvents. dYields reported after purification by column chromatography (SiO2). a

chemistry and found that it goes equally well with aromatic, heterocyclic, and aliphatic terminal alkynes. We also tested this reaction for glycosylated alkynes but found only 15% yield of the final compound with 5 mol % CuI. It may be due to high crowding around the terminal alkyne part. We also observed that changing the length of the aliphatic terminal alkyne and adding different functional groups on the aromatic ring of alkyne, whether its electron-withdrawing or electron-releasing, do not affect the yield much (Figure 1). To know whether our developed method is good for synthesis of unsymmetrical conjugated 1,3-dialkyne, we set up a reaction between 1.1 equiv phenylacetylene and 1.0 equiv of 1-ethynylcyclohexan-1-ol under the above optimized reaction conditions and isolated 1-(phenylbuta-1,3-diyn-1-yl)cyclohexanol in 70% yield along with 2a, which indicates that our ligand is equally useful for synthesis of unsymmetrical conjugated 1,3-dialkyne. We also generalized this reaction and found that it gives good yields in unsymmetrical mode (Figure 2). For quantity-based generalization of the reaction, we tried this reaction for gram scale and found good yields (98%) of symmetric dialkyne 2a. Similar results were achieved when the reaction was carried out with unsymmetric dialkyne 3a, which

Scheme 2. Prototype Reaction for Synthesis of Symmetric 1,3-Dialkyne

material into the product in almost 100% conversion on TLC with only 2 mol % of loading (entries 3−11). In continuation, we also optimized a suitable base for reaction type and amount of ligand and solvent in which reaction (entries 12−34) and found that entry no. 13, that is, 1.0 equiv of phenylacetylene with 2 mol % of CuI in presence of 5 mol % of 1Hbenzotriazole and 0.5 equiv of K2CO3 in dimethylformamide (DMF) is the most suitable condition for the reaction in open container at 25 °C. Further, we started varying the terminal alkynes to find out the reaction scope in the area of synthetic 2419

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Figure 1. Synthesis of symmetric dialkyne, molar ratios: alkyne (1a−u) (1.0 equiv), K2CO3 (0.5 equiv), CuI (2 mol %), benzotriazole (5 mol %). Yields after flash column chromatography (SiO2).

compared to previously reported methods. Our devised protocol works well at room temperature and also in an open container and gives excellent reaction yields for a variety of aliphatic and aromatic alkynes. Moreover, the ligand was efficiently catalyzed for the synthesis of unsymmetric conjugated dialkynes by Glaser coupling.

suggests that the efficiency of the ligand does not vary by scaling up the reaction quantity (Scheme 3). The plausible mechanism is depicted in Scheme 4, which possibly involves the typical Cu-catalyzed C−C homocoupling steps. According to our postulations, the first step involves the reaction of CuI with 1H-benzotriazole to give intermediate A.10,11 When this intermediate A reacts with terminal alkyne, it activates the sp C−H proton of the alkyne, which further can be easily removed by the use of a base (e.g., K2CO3) and afforded the coordination adduct intermediate B. This intermediate at the last step undergoes C−C bond formation via intermediates C and D to give the respective conjugated 1,3-dialkynes as the final coupling product 2.

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EXPERIMENTAL SECTION General. All solvents and reagents used were of pure grade. TLC was performed on pre-coated aluminum plates and displayed with either an Ultraviolet lamp (λmax = 254 nm) or a specific color reagent (iodine vapor) or by spraying with methanolic H2SO4 solution and subsequent charring by heating at 55 °C (for a carbohydrate derivative only). Solvents were evaporated at a temperature < 50 °C under reduced pressure. Column chromatography was carried out on silica gel (230−400 mesh, Merck) by using distilled n-hexane and ethyl acetate. 1H and 13C NMR were recorded at 500 and 125 MHz, respectively. Chemical shifts were given in ppm downfield from

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CONCLUSIONS In conclusion, we have successfully established 1H-benzotriazole as an efficient ligand for the Glaser coupling of terminal alkynes to produce 1,3-conjugated dialkynes. This method needs a lesser quantity of ligand and Cu-catalysts as 2420

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Figure 2. Synthesis of unsymmetric dialkynes, molar ratios: alkyne (1a−e) (0.5 equiv), K2CO3 (0.5 equiv), CuI (2 mol %), benzotriazole (5 mol %). Yields after flash column chromatography (SiO2).

atmosphere of air. The reaction mixture was vigorously stirred at room temperature for 3−4 h. The progress of reaction was monitored by TLC. After the completion of the reaction, ethyl acetate was added into the reaction mixture and washed with brine. The organic layer was separated, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude mass thus obtained was subjected to purification by flash column chromatography (SiO2) using n-hexane and afforded product 2a (99% yield) as a white solid. 1,4-Diphenylbuta-1,3-diyne (2a).12 White solid, yield 99%; Rf = 0.7 (n-hexane); mp 80−83 °C; MS m/z 203 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.53−7.51 (m, 4H), 7.37−7.33 (m, 6H); 13C NMR (125 MHz, CDCl3): δ 132.3, 129.3, 128.5, 121.9, 81.6, and 74.0 ppm. 1,4-Di-p-tolylbuta-1,3-diyne (2b).13 White solid, yield 99%; Rf = 0.6 (n-hexane); mp 180−182 °C; m/z 231 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.41 (d, J = 8.5 Hz, 4H), 7.13 (d, J = 7.5 Hz, 4H), 2.36 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 139.5, 132.4, 129.3, 118.8, 79.2, and 76.6 ppm. 1,4-Di(cyclohex-1-en-1-yl)buta-1,3-diyne (2c).14 White solid, yield 80%; Rf = 0.5 (n-hexane); mp 60−62 °C; m/z 211 [M + H]; 1H NMR (500 MHz, CDCl3): δ 6.25−6.20 (m, 2H), 2.09−2.06 (m, 8H)), 1.61−1.53 (m, 8H); 13C NMR (125 MHz, CDCl3): δ 138.1, 120.0, 82.7, 71.6, 28.7, 25.9, 22.2, and 21.4 ppm. 1,4-Di-o-tolylbuta-1,3-diyne (2d).15 White solid, yield 99%; Rf = 0.6 (n-hexane); mp 65−68 °C; m/z 231 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.54 (d, J = 7.5 Hz, 2H), 7.30− 7.23 (m, 4H), 7.18 (t, J = 7.5 Hz, 2H), 2.53 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 141.7, 133.0, 129.7, 129.2, 125.8, 121.8, 81.3, 76.9, and 20.8 ppm. Dimethyl-4,4′-(buta-1,3-diyne-1,4-diyl)dibenzoate (2e).16 White solid, yield 99%; Rf = 0.5 (5% ethyl acetate/n-hexane); mp 178−180 °C; m/z 319 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.93 (d, J = 8.5 Hz, 4H), 7.51 (d, J = 8.5 Hz, 4H), 3.85 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 166.3, 132.5, 130.6, 129.6, 126.1, 81.9, 76.3, and 52.4 ppm. 1,4-Bis(2,4,5-trimethylphenyl)buta-1,3-diyne (2f).17 White solid, yield 95%; Rf = 0.5 (3% ethyl acetate/n-hexane); mp 225−228 °C; m/z 287 [M + H]; 1H NMR (500 MHz,

Scheme 3. Gram-Scale Synthesis of Symmetric and Unsymmetric Dialkyne

Scheme 4. Proposed Mechanism for the Synthesis of 1,3Conjugated Dialkynes 2

internal tetra methyl silane (TMS); J values in hertz. Infrared spectra were recorded as Nujol mulls in KBr palettes. Typical Experimental Procedure for the Synthesis of 1,3-Diyne. Phenylacetylene (1.0 mmol), benzotriazole (5.0 mol %), CuI (2.0 mol %), and K2CO3 (0.5 mmol) were taken in a round-bottom flask and dissolved in DMF (1 mL) in an 2421

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CDCl3): δ 7.20 (s, 2H), 6.91 (s, 2H), 2.34 (s, 6H), 2.14 (d, J = 18.0 Hz, 12H); 13C NMR (125 MHz, CDCl3): δ 138.1, 138.1, 133.9, 133.8, 131.0, 131.0, 119.0, 81.2, 76.6, 20.1, 19.8, and 19.1 ppm. 1,4-Bis(3,5-difluorophenyl)buta-1,3-diyne (2g).18 White solid, yield 90%; Rf = 0 (3% ethyl acetate/n-hexane); mp 142−145 °C; m/z 275 [M + H]; 1H NMR (500 MHz, CDCl3): δ 6.93−6.91 (m, 4H), 6.77−6.73 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 163.6, 163.5, 161.7, 161.6, 124.0, 123.9, 123.8, 115.6, 115.5, 115.4, 115.3, 106.1, 105.9, 105.7, 79.9, and 74.9 ppm. 1,4-Bis(2-(trifluoromethyl)phenyl)buta-1,3-diyne (2h).19 White solid, yield 99%; Rf = 0.5 (n-hexane); mp 67−69 °C; m/z 339 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.60 (t, J = 8.5 Hz, 4H), 7.45−7.37 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 135.2, 131.5, 129.2, 126.2, 126.1, 124.4, 119.8, 78.7, and 78.6 ppm. 1,4-Di(thiophen-3-yl)buta-1,3-diyne (2i).15 White solid, yield 91%; Rf = 0.5 (5% ethyl acetate/n-hexane); mp 110− 112 °C; m/z 215 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.51−7.50 (m, 2H), 7.21−7.18 (m, 2H), 7.09−7.08 (m, 2H); 13 C NMR (125 MHz, CDCl3): δ 131.3, 130.2, 125.7, 120.9, 76.6, and 73.6 ppm. 1,4-Bis(4-(tert-butyl)phenyl)buta-1,3-diyne (2j).16 White solid, yield 99%; Rf = 0.4 (n-hexane); mp 182−185 °C; m/z 315 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.48 (d, J = 8.5 Hz, 4H), 7.37 (d, J = 8.5 Hz, 4H), 1.33 (s, 18H); 13C NMR (125 MHz, CDCl3): δ 152.6, 132.3, 125.6, 118.9, 81.6, 73.6, 35.0, and 31.2 ppm. 1,4-Bis(2-methoxyphenyl)buta-1,3-diyne (2k).15 White solid, yield 99%; Rf = 0.5 (5% ethyl acetate/n-hexane); mp 128−130 °C; m/z 263 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.46 (d, J = 7.5 Hz, 2H), 7.32−7.29 (m, 2H), 6.91− 6.81 (m, 4H), 3.88 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 161.4, 134.4, 130.6, 120.5, 111.3, 110.7, 78.7, 78.0, and 55.9 ppm. 1,4-Bis(4-pentylphenyl)buta-1,3-diyne (2l).18 White solid, yield 90%; Rf = 0.3 (n-hexane); mp 66−68 °C; m/z 343 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.43 (d, J = 7.5 Hz, 2H), 7.14 (d, J = 8.0 Hz, 4H), 2.60 (t, J = 7.5 Hz, 4H), 1.62−1.59 (m, 4H), 1.33−1.26 (m, 8H), 0.89 (t, J = 6.5 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 144.5, 132.5, 128.6, 119.1, 81.6, 73.6, 36.0, 31.5, 30.9, 22.6, and 14.1 ppm. 1,4-Bis(4-butylphenyl)buta-1,3-diyne (2m).16 White solid, yield 92%; Rf = 0.5 (n-hexane); mp 78−80 °C; m/z 315 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.41 (d, J = 8.5 Hz, 4H), 7.11 (d, J = 7.5 Hz, 4H), 2.58 (t, J = 8.0 Hz, 4H), 1.58−1.53 (m, 4H), 1.35−1.30 (m, 4H), 0.91 (t, J = 7.5 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 144.5, 132.5, 128.6, 119.1, 81.7, 73.6, 35.8, 33.4, 22.4, and 14.0 ppm. 1,4-Bis(4-methoxy-2-methylphenyl)buta-1,3-diyne (2n).19 White solid, yield 99%; Rf = 0.3 (3% ethyl acetate/n-hexane); mp 66−68 °C; m/z 291 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.42 (d, J = 9.0 Hz, 2H), 6.73 (d, J = 2.5 Hz, 2H), 6.69−6.67 (m, 2H), 3.79 (s, 6H), 2.46 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 160.1, 143.5, 134.4, 115.9, 114.1, 111.5, 80.8, 76.5, 55.3, and 21.1 ppm. Dodeca-5,7-diynedinitrile (2o).13 Oily, yield 91%; Rf = 0.3 (30% ethyl acetate/n-hexane); m/z 185 [M + H]; 1H NMR (500 MHz, CDCl3): δ 2.44−2.37 (m, 8H), 1.84−1.78 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 118.9, 75.3, 66.7, 24.2, 24.1, 18.3, and 16.2 ppm.

Icosa-9,11-diyne-1,20-diol (2p). Oily, yield 90%; Rf = 0.4 (20% ethyl acetate/n-hexane); m/z 307 [M + H]; 1H NMR (500 MHz, CDCl3): δ 3.58 (t, J = 7.0 Hz, 4H), 2.20 (t, J = 6.5 Hz, 4H), 1.52−1.27 (m, 24H); 13C NMR (125 MHz, CDCl3): δ 76.8, 65.3, 62.9, 32.7, 29.2, 29.0, 28.7, 28.3, 25.7, and 19.2 ppm; Anal. Calcd. for C20H34O2: C, 78.38; H, 11.18. Found: C, 78.26; H, 11.29. 1,6-Dicyclohexylhexa-2,4-diyne (2q).13 Oily, yield 40%; Rf = 0.4 (n-hexane); m/z 243 [M + H]; 1H NMR (500 MHz, CDCl3): δ 2.07 (d, J = 6.5 Hz, 4H), 1.73−1.40 (m, 10H), 1.18−1.05 (m, 12H); 13C NMR (125 MHz, CDCl3): δ 76.5, 66.1, 37.3, 32.7, 27.0, 26.2, and 26.1 ppm. 1,4-Di(pyridin-3-yl)buta-1,3-diyne (2r).20 White solid, yield 99%; Rf = 0.6 (2% ethyl acetate/n-hexane); mp 200−202 °C; m/z 205 [M + H]; 1H NMR (500 MHz, CDCl3): δ 8.69 (s, 2H), 8.52−8.51 (m, 2H), 7.75−7.73 (m, 2H), 7.24−7.20 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 153.1, 149.5, 139.4, 123.1, 118.8, 79.2, and 76.6 ppm. 1,1′-(Buta-1,3-diyne-1,4-diyl)dicyclohexanol (2s).17 White solid, yield 95%; Rf = 0.3 (20% ethyl acetate/n-hexane); mp 155−158 °C; m/z 247 [M + H]; 1H NMR (500 MHz, CDCl3): δ 1.92−1.84 (m, 6H), 1.64−1.46 (m, 14H); 13C NMR (125 MHz, CDCl3): δ 83.0, 69.2, 68.4, 39.7, 25.0, and 23.1 ppm. 1,4-Bis(4-methoxyphenyl)buta-1,3-diyne (2t).15 White solid, yield 97%; Rf = 0.5 (5% ethyl acetate/n-hexane); mp 135−138 °C; m/z 263 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 9.5 Hz, 4H), 6.84 (d, J = 8.5 Hz, 4H), 3.80 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 160.3, 134.1, 114.2, 114.0, 81.3, 73.6, and 55.4 ppm. 1,6-Bis((6-(2,2-dimethyl-1, 3-dioxolan -4-yl)-2,2dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)oxy)hexa-2,4diyne (2u). Oily, yield 15%; Rf = 0.4 (30% ethyl acetate/nhexane); 1H NMR (500 MHz, CDCl3): δ 5.16 (s, 2H), 4.79− 4.77 (m, 2H), 4.61 (d, J = 5.5 Hz, 2H), 4.41−4.38 (m, 2H), 4.25 (s, 4H), 4.17−4.09 (m, 2H), 4.05−4.02 (m, 2H), 3.94− 3.93 (m, 2H), 1.46 (d, J = 8.5 Hz, 12H), 1.38 (s, 6H), 1.32 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 112.8, 109.3, 104.9, 85.0, 80.8, 79.4, 74.6, 73.1, 70.4, 66.9, 54.5, 26.9, and 25.9 ppm; HRMS m/z (M + Na) calcd for C30H42O12Na 617.2574; found, 617.2556. 1-(Phenylbuta-1,3-diyn-1-yl)cyclohexanol (3a).21 White solid, yield 70%; Rf = 0.3 (5% ethyl acetate/n-hexane); mp 93−95 °C; m/z 225 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.46 (d, J = 6.5 Hz, 2H), 7.35−7.28 (m, 3H), 1.97−1.95 (m, 2H), 1.73−1.53 (m, 8H); 13C NMR (125 MHz, CDCl3): δ 132.5, 129.2, 128.5, 121.7, 86.3, 78.5, 73.5, 69.4, 69.4, 39.8, 25.1, and 23.2 ppm. (Cyclohex-1-en-1-ylbuta-1,3-diyn-1-yl)benzene (3b).22 Oily, yield 60%; Rf = 0.3 (n-hexane); m/z 207 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.52−7.50 (m, 2H), 7.33−7.28 (m, 3H), 6.31−9.29 (m, 1H), 2.15−2.09 (m, 4H), 1.63−1.56 (m, 4H); 13C NMR (125 MHz, CDCl3): δ 139.0, 132.6, 129.3, 128.5, 121.8, 119.9, 83.9, 81.7, 74.1, 71.9, 28.7, 26.0, 22.4, and 21.4 ppm. 1-((4-(tert-Butyl)phenyl)buta-1,3-diyn-1-yl)cyclohexanol (3c). Oily, yield 68%; Rf = 0.3 (5% ethyl acetate/n-hexane); 1H NMR (500 MHz, CDCl3): δ 7.41 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 3.5 Hz, 2H), 1.97−1.95 (m, 2H), 1.73−1.56 (m, 8H), 1.29 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 152.7, 132.3, 125.5, 128.5, 118.6, 85.8, 78.8, 72.8, 69.4, 69.1, 39.8, 34.9, 31.1, 25.1, and 23.2 ppm; HRMS m/z (M + Na) calcd for C20H24ONa 303.1725; found, 303.1719. 2422

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8-Phenylocta-5,7-diynenitrile (3d).23 Oily, yield 66%; Rf = 0.4 (15% ethyl acetate/n-hexane); m/z 194 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.47 (d, J = 6.5 Hz, 2H), 7.35− 7.28 (m, 3H), 2.55−2.49 (m, 4H), 1.93−1.88 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 132.6, 129.2, 128.5, 121.6, 118.9, 81.3, 75.8, 73.8, 67.0, 24.3, 18.7, and 16.2 ppm. 8-(4-(tert-Butyl)phenyl)octa-5,7-diynenitrile (3e). Oily, yield 65%; Rf = 0.5 (10% ethyl acetate/n-hexane); m/z 251 [M + H]; 1H NMR (500 MHz, CDCl3): δ 7.40 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 2.54−2.49 (m, 4H), 1.93−1.87 (m, 2H), 1.29 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 152.7, 132.4, 125.5, 119.0, 118.5, 80.9, 76.0, 73.2, 67.2, 34.9, 31.1, 24.4, 18.8, and 16.2 ppm; Anal. Calcd. for C18H19N: C, 86.70; H, 7.68; N, 5.62. Found: C, 86.62; H, 7.73; N, 5.65.

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Synthesis to Structure−Property Relationships and Applications. Chem. Rev. 2018, 118, 8474−8597. (2) (a) Glaser, C. Beiträge zur Kenntniss des Acetenylbenzols. Ber. Dtsch. Chem. Ges. 1869, 2, 422−424. (b) Glaser, C. Untersuchungen über einige Derivate der Zimmtsäure. Ann. Chem. Pharm. 1870, 154, 137−171. (c) Kamata, K.; Yamaguchi, S.; Kotani, M.; Yamaguchi, K.; Mizuno, N. Efficient Oxidative Alkyne Homocoupling Catalyzed by a Monomeric Dicopper-Substituted Silicotungstate. Angew. Chem., Int. Ed. 2008, 47, 2407−2410. (d) Eglinton, G.; Galbraith, A. R. Cyclic diynes. Chem. Ind. 1956, 737−738. (e) Hay, A. CommunicationsOxidative Coupling of Acetylenes. J. Org. Chem. 1960, 25, 1275− 1276. (f) Hay, A. S. Oxidative Coupling of Acetylenes. II1. J. Org. Chem. 1962, 27, 3320−3321. (g) Ranu, B.; Banerjee, S. Homocoupling of Terminal Alkynes to 1,4-Disubstituted 1,3-Diynes Promoted by Copper(I) Iodide and a Task Specific Ionic Liquid, [bmim]OH - A Green Procedure. Lett. Org. Chem. 2006, 3, 607−609. (h) Jiang, H.-F.; Tang, J.-Y.; Wang, A.-Z.; Deng, G.-H.; Yang, S.-R. Cu(II)-Promoted Oxidative Homocoupling Reaction of Terminal Alkynes in Supercritical Carbon Dioxide. Synthesis 2006, 1155−1161. (i) Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.; Gayathri, K. U.; Prasad, A. R. Glaser oxidative coupling in ionic liquids: an improved synthesis of conjugated 1,3-diynes. Tetrahedron Lett. 2003, 44, 6493−6496. (j) Nishihara, Y.; Ikegashira, K.; Hirabayashi, K.; Ando, J.-i.; Mori, A.; Hiyama, T. Coupling Reactions of Alkynylsilanes Mediated by a Cu(I) Salt: Novel Syntheses of Conjugate Diynes and Disubstituted Ethynes. J. Org. Chem. 2000, 65, 1780−1787. (k) Siemsen, P.; Livingston, R. C.; Diederich, F. Acetylenic Coupling: A Powerful Tool in Molecular Construction. Angew. Chem., Int. Ed. 2000, 39, 2632− 2657. (l) Zheng, Q.; Hua, R.; Wan, Y. An alternative CuCl− piperidine-catalyzed oxidative homocoupling of terminal alkynes affording 1,3-diynes in air. Appl. Organomet. Chem. 2010, 24, 314− 316. (m) Lampkowski, J. S.; Uthappa, D. M.; Halonski, J. F.; Maza, J. C.; Young, D. D. Application of the Solid-Supported Glaser−Hay Reaction to Natural Product Synthesis. J. Org. Chem. 2016, 81, 12520−12524. (n) Peters, T. B.; Bohling, J. C.; Arif, A. M.; Gladysz, J. A. C8 and C12 sp Carbon Chains That Span Two Platinum Atoms: The First Structurally Characterized 1,3,5,7,9,11-Hexayne. Organometallics 1999, 18, 3261−3263. (o) Zheng, O.; Hua, R.; Wan, Y. An alternative CuCl−piperidine-catalyzed oxidative homocoupling of terminal alkynes affording 1,3-diynes in air. Appl. Organomet. Chem. 2010, 24, 314−316. (p) Jia, X.; Yin, K.; Li, C.; Li, J.; Bian, H. Coppercatalyzed oxidative alkyne homocoupling without palladium, ligands and bases. Green Chem. 2011, 13, 2175−2178. (q) Zhang, S.; Liu, X.; Wang, T. An Efficient Copper-Catalyzed Homocoupling of Terminal Alkynes to Give Symmetrical 1,4-Disubstituted 1,3-Diynes. Adv. Synth. Catal. 2011, 353, 1463−1466. (r) Dar, B. A.; Vyas, D.; Shrivastava, V.; Farooq, S.; Sharma, A.; Sharma, S.; Sharma, P. R.; Sharma, M.; Singh, B. Oxidative homocoupling of terminal alkynes under palladium-, ligand- and base-free conditions using Cu(II)-clay as a heterogeneous catalyst. Compt. Rendus Chem. 2014, 17, 316−323. (s) Niu, X.; Li, C.; Li, J.; Jia, X. Importance of bases on the coppercatalyzed oxidative homocoupling of terminal alkynes to 1,4disubstituted 1,3-diynes. Tetrahedron Lett. 2012, 53, 5559−5561. (3) (a) Wang, L.; Wang, S.; Yu, L.; Li, P.; Meng, L. Copper(I) Iodide Catalyzed Cross-Coupling Reaction of Terminal Alkynes with 1-Bromoalkynes: A Simple Synthesis of Unsymmetrical Buta-1,3diynes. Synthesis 2011, 2011, 1541−1546. (b) Marino, J. P.; Nguyen, H. N. Bulky Trialkylsilyl Acetylenes in the Cadiot-Chodkiewicz CrossCoupling Reaction. J. Org. Chem. 2002, 67, 6841−6844. (c) Chodkiewicz, W. Synthesis of Acetylenic Compounds. Ann. Chim. 1957, 2, 819−869. (d) Chodkiewicz, W.; Cadiot, P. C. R. New synthesis of symmetrical and asymmetrical conjugated polyacetylenes. Hebd. Seances Acad. Sci. 1955, 241, 1055−1057. (4) Yu, M.; Pan, D.; Jia, W.; Chen, W.; Jiao, N. Copper-catalyzed decarboxylative cross-coupling of propiolic acids and terminal alkynes. Tetrahedron Lett. 2010, 51, 1287−1290. (5) Yin, W.; He, C.; Chen, M.; Zhang, H.; Lei, A. Nickel-Catalyzed Oxidative Coupling Reactions of Two Different Terminal Alkynes

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.8b03410. 1 H and 13C NMR spectrum of symmetric dialkyne (2au) and unsymmetric dialkyne (3a-e); and single-crystal X-ray data of compound 2a (PDF) Copies of 1H and 13C NMR spectra for all the synthesized compounds, ortep, and associated X-ray crystallographic data for (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] ORCID

Vinod K. Tiwari: 0000-0001-9244-8889 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank the Science and Engineering Research Board (SERB), New Delhi (grant no. EMR/2016/001123) for the funding and CISC-Banaras Hindu University, Indian Institute of Technology, Delhi, and Indian Institute of Technology (IIT), Kanpur, India, for providing spectroscopic studies of the developed molecules.

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REFERENCES

(1) (a) Shun, A. L. K. S.; Tykwinski, R. R. Synthesis of Naturally Occurring Polyynes. Angew. Chem., Int. Ed. 2006, 45, 1034−1057. (b) Acetylene Chemistry: Chemistry, Biology and Material Science; Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.; Wiley-VCH: Weinheim, 2005. (c) Stefani, H. A.; Guarezemini, A. S.; Cella, R. Homocoupling reactions of alkynes, alkenes and alkyl compounds. Tetrahedron 2010, 66, 7871−7918. (d) Shi, W.; Lei, A. 1,3-Diyne chemistry: synthesis and derivations. Tetrahedron Lett. 2014, 55, 2763−2772. (e) Asiri, A. M.; Hashmi, A. S. K. Gold-catalysed reactions of diynes. Chem. Soc. Rev. 2016, 45, 4471−4503. (f) Kivala, M.; Diederich, F. Conjugation and Optoelectronic Properties of Acetylenic Scaffolds and Charge-Transfer Chromophores. Pure Appl. Chem. 2008, 80, 411−427. (g) Liu, J.; Lam, J. W. Y.; Tang, B. Z. Acetylenic Polymers: Syntheses, Structures, and Functions. Chem. Rev. 2009, 109, 5799−5867. (h) Hu, R.; Tang, B. Z. In Multi-Component and Sequential Reactions in Polymer Synthesis; Theato, P., Ed.; Springer Publishing: Cham: Switzerland, 2015; pp 17−42. (i) Haque, A.; AlBalushi, R. A.; Al-Busaidi, I. J.; Khan, M. S.; Raithby, P. R. Rise of Conjugated Poly-ynes and Poly(Metalla-ynes): From Design Through 2423

DOI: 10.1021/acsomega.8b03410 ACS Omega 2019, 4, 2418−2424

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Article

Using O2 as the Oxidant at Room Temperature: Facile Syntheses of Unsymmetric 1,3-Diynes. Org. Lett. 2009, 11, 709−712. (6) Rossi, R.; Carpita, A.; Bigelli, C. A palladium-promoted route to 3-alkyl-4-(1-alkynyl)-hexa-1,5-dyn-3-enes and/or 1,3-diynes. Tetrahedron Lett. 1985, 26, 523−526. (7) (a) Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Properties and Synthetic Utility of N-Substituted Benzotriazoles. Chem. Rev. 1998, 98, 409−548. (b) Katritzky, A. R.; Rachwal, S. Synthesis of Heterocycles Mediated by Benzotriazole. 1. Monocyclic Systems. Chem. Rev. 2010, 110, 1564−1610. (c) Kale, R. R.; Prasad, V.; Mohapatra, P. P.; Tiwari, V. K. Recent Developments in Benzotriazole Methodology for Construction of Pharmacologically Important Heterocyclic Skeletons. Monatsh. Chem. 2010, 141, 1159− 1182. (d) Wang, X.; Jia, C.; Feng, Y.; Wang, L.; Cui, X. One-Pot Synthesis of N-Alkyl Benzotriazoles via a Brønsted Acid-Catalyzed Three-Component Reaction. Adv. Synth. Catal. 2017, 360, 374−378. (e) Kale, R. R.; Prasad, V.; Hussain, H. A.; Tiwari, V. K. Facile route for N1-aryl benzotriazoles from diazoamino arynes via CuI-mediated intramolecular N-arylation. Tetrahedron Lett. 2010, 51, 5740−5743. (f) Andrzejewska, M. R.; Vuram, P. K.; Pottabathini, N.; Gurram, V.; Relangi, S. S.; Korvinson, K. A.; Doddipalla, R.; Stahl, L.; Neary, M. C.; Pradhan, P.; Sharma, S.; Lakshman, M. K. The Disappearing Director: The Case of Directed N-Arylation via a Removable Hydroxyl Group. Adv. Synth. Catal. 2018, 360, 2503−2510. (g) Wang, K.; Chen, P.; Ji, D.; Zhang, X.; Xu, G.; Sun, J. RhodiumCatalyzed Regioselective N2-Alkylation of Benzotriazoles with Diazo Compounds/Enynones via a Nonclassical Pathway. Angew. Chem., Int. Ed. 2018, 57, 12489−12493. (h) Yin, Z.; Wang, Z.; Wu, X.-F. Silver and Palladium Cocatalyzed Carbonylative Activation of Benzotriazoles to Benzoxazinones under Neutral Conditions. Org. Lett. 2017, 19, 6232−6235. (i) Tanii, S.; Arisawa, M.; Tougo, T.; Yamaguchi, M. Catalytic Method for the Synthesis of C−N-Linked Bi(heteroaryl)s Using Heteroaryl Ethers and N-Benzoyl Heteroarenes. Org. Lett. 2018, 20, 1756−1759. (j) Jian, Y.; Chen, M.; Huang, B.; Jia, W.; Yang, C.; Xia, W. Visible-Light-Induced C(sp2)-P Bond Formation by Denitrogenative Coupling of Benzotriazoles with Phosphites. Org. Lett. 2018, 20, 5370−5374. (8) (a) Singh, A. S.; Agrahari, A. K.; Mishra, N.; Singh, M.; Tiwari, V. K. An Improved N-Acylation of 1H-Benzotriazole Using 2,2′Dipyridyldisulfide and Triphenylphosphine. Synthesis 2018, 51, 470. (b) Singh, A. S.; Kumar, D.; Mishra, N.; Tiwari, V. K. An Unprecedented Synthesis of N-Phenyl Amides via Cleavage of Benzotriazole Ring under Free Radical Condition. ChemistrySelect 2017, 2, 224−229. (c) Singh, A. S.; Kumar, D.; Mishra, N.; Tiwari, V. K. An efficient one-pot synthesis of N,N′-disubstituted ureas and carbamates from N-acylbenzotriazoles. RSC Adv. 2016, 6, 84512− 84522. (d) Singh, A. S.; Mishra, N.; Kumar, D.; Tiwari, V. K. LewisAcid-Mediated Benzotriazole Ring Cleavage (BtRC) Strategy for the Synthesis of 2-Aryl Benzoxazoles from N-Acylbenzotriazoles. ACS Omega 2017, 2, 5044−5051. (e) Kumar, D.; Mishra, A.; Mishra, B. B.; Bhattacharya, S.; Tiwari, V. K. Synthesis of Glycoconjugate Benzothiazoles via Cleavage of Benzotriazole Ring. J. Org. Chem. 2013, 78, 899−909. (f) Mishra, A.; Tiwari, V. K. One-Pot Synthesis of Glycosyl-β-azido Ester via Diazotransfer Reaction toward Access of Glycosyl-β-triazolyl Ester. J. Org. Chem. 2015, 80, 4869−4881. (g) Singh, A. S.; Agrahari, A. K.; Singh, M.; Mishra, N.; Tiwari, V. K. A new methodology for the synthesis of N-acylbenzotriazoles. ARKIVOC 2017, 2017, 80−88. (h) Kumar, D.; Mishra, B. B.; Tiwari, V. K. Synthesis of 2-N/S/C-Substituted Benzothiazoles via Intramolecular Cyclative Cleavage of Benzotriazole Ring. J. Org. Chem. 2013, 79, 251−266. (9) Singh, A. S.; Singh, M.; Mishra, N.; Mishra, S.; Agrahari, A. K.; Tiwari, V. K. N-Acylbenzotriazole as Efficient Ligand in CopperCatalyzed O-Arylation Leading to Diverse Benzoxazoles. ChemistrySelect 2017, 2, 154−159. (10) (a) Verma, A. K.; Singh, J.; Sankar, V. K.; Chaudhary, R.; Chandra, R. Benzotriazole: an excellent ligand for Cu-catalyzed Narylation of imidazoles with aryl and heteroaryl halides. Tetrahedron Lett. 2007, 48, 4207−4210. (b) Battula, S.; Vishwakarma, R. A.;

Ahmed, Q. N. Cu-benzotriazole-catalyzed electrophilic cyclization of N-arylimines: a methodical tandem approach to O-protected4hydroxyquinazolines. RSC Adv. 2014, 4, 38375−38378. (c) Reedijk, J.; Siedle, A. R.; Velapoldi, R. A.; Van Hest, J. A. M. Coordination Compounds of Benzotriazole and Related Ligands. Inorg. Chim. Act. 1983, 74, 109−118. (11) (a) Vilhelmsen, M. H.; Jensen, J.; Tortzen, C. G.; Nielsen, M. B. The Glaser−Hay Reaction: Optimization and Scope Based on 13C NMR Kinetics Experiments. Eur. J. Org. Chem. 2012, 2013, 701−711. (b) Levashov, A. S.; Buryi, D. S.; Goncharova, O. V.; Konshin, V. V.; Dotsenko, V. V.; Andreev, A. A. Tetraalkynylstannanes in the Stille cross coupling reaction: a new effective approach to arylalkynes. New J. Chem. 2017, 41, 2910−2918. (12) Li, X.; Liu, X.; Chen, H.; Wu, W.; Qi, C.; Jiang, H. CopperCatalyzed Aerobic Oxidative Transformation of Ketone-Derived NTosyl Hydrazones: An Entry to Alkynes. Angew. Chem., Int. Ed. 2014, 53, 14485−14489. (13) Chen, Z.; Jiang, H.; Wang, A.; Yang, S. Transition-Metal-Free Homocoupling of 1-Haloalkynes: A Facile Synthesis of Symmetrical 1,3-Diynes. J. Org. Chem. 2010, 75, 6700−6703. (14) Liu, Y.; Gu, N.; Liu, P.; Xie, J.; Ma, X.; Liu, Y.; Dai, B. 3(Diphenylphosphino) propanoic acid: an efficient ligand for the Pd/ Cu-catalyzed homocoupling of terminal alkynes in the presence of oxygen at room temperature. Appl. Organomet. Chem. 2015, 29, 736− 738. (15) Li, X.; Li, D.; Bai, Y.; Zhang, C.; Chang, H.; Gao, W.; Wei, W. Homocoupling reactions of terminal alkynes and arylboronic compounds catalyzed by in situ formed Al(OH) 3 -supported palladium nanoparticles. Tetrahedron 2016, 72, 6996−7002. (16) Sagadevan, A.; Charpe, V. P.; Hwang, K. C. Copper(i) chloride catalysed room temperature Csp−Csp homocoupling of terminal alkynes mediated by visible light. Catal. Sci. Technol. 2016, 6, 7688− 7692. (17) Adimurthy, S.; Malakar, C. C.; Beifuss, U. Influence of Bases and Ligands on the Outcome of the Cu(I)-Catalyzed Oxidative Homocoupling of Terminal Alkynes to 1,4-Disubstituted 1,3-Diynes Using Oxygen as an Oxidant. J. Org. Chem. 2009, 74, 5648−5651. (18) Li, D.; Yin, K.; Li, J.; Jia, X. CuI/iodine-mediated homocoupling reaction of terminal alkynes to 1,3-diynes. Tetrahedron Lett. 2008, 49, 5918−5919. (19) Urgoitia, G.; SanMartin, R.; Herrero, M. T.; Domínguez, E. Efficient copper-free aerobic alkyne homocoupling in polyethylene glycol. Environ. Chem. Lett. 2016, 15, 157−164. (20) Fan, X.; Li, N.; Shen, T.; Cui, X.-M.; Lv, H.; Zhu, H.-B.; Guan, Y.-H. A mild CuI-catalyzed Glaser-type homo-coupling reaction using a,a-dibromo-b-dicarbonyl compounds as oxidants. Tetrahedron 2014, 70, 256−261. (21) Stein, A. L.; Bilheri, F. N.; Zeni, G. Applications of Organo Selenides in the Suzuki, Negishi, Sonogashira and Kumada CrossCoupling Reactions. Chem. Commun. 2015, 51, 15522−15525. (22) Chinta, B. S.; Baire, B. A systematic study on the Cadiot− Chodkiewicz cross coupling reaction for the selective and efficient synthesis of hetero-diynes. RSC Adv. 2016, 6, 54449−54455. (23) Li, X.; Xie, X.; Sun, N.; Liu, Y. Gold-Catalyzed Cadiot− Chodkiewicz-type Cross-Coupling of Terminal Alkynes with Alkynyl Hypervalent Iodine Reagents: Highly Selective Synthesis of Unsymmetrical 1,3-Diynes. Angew. Chem., Int. Ed. 2017, 56, 6994−6998.

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DOI: 10.1021/acsomega.8b03410 ACS Omega 2019, 4, 2418−2424