Benzotriazole as an Efficient Ligand in Cu-Catalyzed Glaser Reaction.

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.

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 ).[2] The Chodkiewicz–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 toxic catalysts, low reaction yields, requirement of high reaction temperature, or longer reaction time warrant improved protocols for this type of coupling (Table ).

Scheme 1

Comparative Illustration of This Work with Previous Methods

Table 1

Reaction Optimization Study

entrya	catalyst (mol %)	ligand (mol %)	base (equiv)	temp °Cb	solventc	yield (%)d
1	CuI (10)	BtH (20)	K2CO3 (1)	120	DMF	85
2	CuI (10)	BtH (20)	K2CO3 (1)	50	DMF	99
3	CuI (10)	BtH (20)	K2CO3 (1)	25	DMF	99
4	CuBr (10)	BtH (20)	K2CO3 (1)	25	DMF	80
5	CuCl (10)	BtH (20)	K2CO3 (1)	25	DMF	72
6	CuOAc (10)	BtH (20)	K2CO3 (1)	25	DMF	75
7	CuSO4 (10)	BtH (20)	K2CO3 (1)	25	DMF	0
8	CuI (5)	BtH (10)	K2CO3 (1)	25	DMF	99
9	CuI (2)	BtH (5)	K2CO3 (1)	25	DMF	99
10	CuI (1)	BtH (2)	K2CO3 (1)	25	DMF	89
11	CuI (0)	BtH (5)	K2CO3 (1)	25	DMF	0
12	CuI (2)	BtH (0)	K2CO3 (1)	25	DMF	trace
13	CuI (2)	BtH (5)	K2CO3(0.5)	25	DMF	99
14	CuI (2)	BtH (5)	K2CO3 (0.2)	25	DMF	78
15	CuI (2)	BtH (5)	K2CO3 (0)	25	DMF	71
16	CuI (2)	BtH (5)	K2CO3 (0.5)	25	CHCl3	trace
17	CuI (2)	BtH (5)	K2CO3 (0.5)	25	DCM	trace
18	CuI (2)	BtH (5)	K2CO3 (0.5)	25	dioxane	65
19	CuI (2)	BtH (5)	K2CO3 (0.5)	25	CH3CN	60
20	CuI (2)	BtH (5)	K2CO3 (0.5)	25	toluene	39
21	CuI (2)	BtH (5)	K2CO3 (0.5)	25	benzene	43
22	CuI (2)	BtH (5)	K2CO3 (0.5)	25	THF	63
23	CuI (2)	BtH (5)	Cs2CO3 (0.5)	25	DMF	80
24	CuI (2)	BtH (5)	K3PO4 (0.5)	25	DMF	82
25	CuI (2)	BtH (5)	KtOBu (0.5)	25	DMF	0
26	CuI (2)	BtH (5)	KOH (0.5)	25	DMF	60
27	CuI (2)	BtH (5)	Et3N (0.5)	25	DMF	20
28	CuI (2)	5-Cl-BtH (5)	K2CO3 (0.5)	25	DMF	99
29	CuI (2)	HMBt (5)	K2CO3 (0.5)	25	DMF	10
30	CuI (2)	PhCOBt (5)	K2CO3 (0.5)	25	DMF	99
31	CuI (2)	o-OMePhBt (5)	K2CO3 (0.5)	25	DMF	99

Molar ratio: alkyne (1.0 mmol).

Temperature may be vary by 2 °C.

Dry solvents.

Yields reported after purification by column chromatography (SiO2).

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.

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 ) after flash column chromatography (SiO2) and compound 2a is well characterized by 1H NMR, 13C NMR, infrared, mass spectrometry, and X-ray crystallography.

Scheme 2

Prototype Reaction for Synthesis of Symmetric 1,3-Dialkyne

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 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 1H-benzotriazole 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 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 ).

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).

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 ).

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).

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 suggests that the efficiency of the ligand does not vary by scaling up the reaction quantity (Scheme ).

Scheme 3

Gram-Scale Synthesis of Symmetric and Unsymmetric Dialkyne

The plausible mechanism is depicted in Scheme , 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.

Scheme 4

Proposed Mechanism for the Synthesis of 1,3-Conjugated Dialkynes 2

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 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.

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 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 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, 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); 13C 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)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)oxy)hexa-2,4-diyne (2u)

Oily, yield 15%; Rf = 0.4 (30% ethyl acetate/n-hexane); 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.

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.