Organic Syntheses Procedure

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Org. Synth. 1998, 75, 146

DOI: 10.15227/orgsyn.075.0146

PREPARATION OF CYANOALKYNES: 3-PHENYL-2-PROPYNENITRILE

[ 2-Propynenitrile, 3-phenyl- ]

Submitted by Fen-Tair Luo, May-Wen Wang, and Ren-Tzong Wang¹ .

Checked by Christopher S. Brook, Wenqing Yao, and Amos B. Smith, III.

1. Procedure

3-Phenyl-2-propynenitrile . A 1-L, two-necked flask, fitted with a 100-mL addition funnel, 2-cm stir bar, and a thermometer, is charged with dimethyl sulfoxide (DMSO) (240 mL), acetonitrile (CH₃CN) (80 mL), and water (4.3 mL, (Note 1)). To this rapidly stirring solution (Note 2) is added cuprous cyanide (CuCN) (43.0 g, 0.48 mol, (Note 3)), sodium iodide (2.4 g, 0.016 mol), and phenylacetylene (17.6 mL, 0.16 mol, (Note 4)). Chlorotrimethylsilane (TMSCl) (60.6 mL, 0.48 mol, (Note 5)) is added to the reaction mixture dropwise over a 2-hr period, via the addition funnel, and the reaction mixture is heated at 50°C (internal temperature) for 72 hr (Note 6). The mixture is cooled to room temperature, 100 mL of water is added, and it is extracted with ether (5 × 200 mL). The combined organic layers are washed with saturated sodium bicarbonate (500 mL), brine (500 mL), dried over magnesium sulfate , and concentrated (Note 7). The crude residue is dissolved in pentane (100 mL), filtered through a silica plug (50 gm), and the precipitate is washed with pentane (2 × 100 mL). The filtrate is concentrated and reduced pressure distillation (Note 8) yields 9.8 g (48% yield) of 3-phenyl-2-propynenitrile (Note 9) as a yellow solid at room temperature.

2. Notes

1. The optimum ratio for DMSO:CH₃CN is 3:1.

2. Cuprous cyanide must be added slowly to the rapidly stirring solution in order to obtain a fine suspension and avoid clumping.

3. Cuprous cyanide was used as purchased from Aldrich Chemical Company, Inc . Trace amounts of copper(II) may cause dimerization of the phenylacetylene.

4. Phenylacetylene (98%) was used as purchased from Aldrich Chemical Company, Inc .

5. Chlorotrimethylsilane (redistilled, 99+%) was used as purchased from Aldrich Chemical Company, Inc . The optimum ratio for NaI:CuCN:phenylacetylene:TMSCl is 0.1:3:1:3.

6. The reaction was monitored by TLC using Whatman K6F 60 Å silica gel TLC plates; R_f = 0.55 (hexane : chloroform = 4 : 1).

7. The checkers found it very important to use low boiling solvents (e.g., ether, pentane) and not to heat the rotary evaporator water bath when removing the solvent. If the bath is heated, a fair amount of the product is observed in the rotary evaporator trap.

8. The product was collected as a dark yellow liquid, bp 140-145°C at 60 mm.

9. The physical properties of 3-phenyl-2-propynenitrile are as follows: mp 37-38°C; ¹H NMR (500 MHz, CDCl₃) δ: 7.41 (t, 2 H, J = 7.2), 7.53 (t, 1 H, J = 7.6), 7.60 (d, 2 H, J = 7.2) ; ¹³C NMR (125 MHz, CDCl₃) δ: 62.9, 82.9, 105.3, 117.4, 128.7, 128.8, 131.8, 133.3, 133.4 ; IR (CHCl₃) cm⁻¹: (C≡N) 2272 ; HRMS calcd for C₉H₅N: 127.0422. Found 127.0417.

Handling and Disposal of Hazardous Chemicals

The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.

These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.

3. Discussion

Cyanoalkynes are important in both synthetic and mechanistic studies.² ³ ⁴ ⁵ ⁶ ⁷ Several synthetic methods have already been developed such as the reaction of metallated acetylides with toxic cyanogen chloride,⁸ ⁹ ¹⁰ pyrolysis of β-ketoalkylidenephosphoranes,¹¹ ¹² dehydration of acetylenic carboxamides,¹³ or the reaction of acetylenic bromides with cuprous cyanide.¹⁴ The drawback to the last three reactions is that they require preparation of precursors: β-ketoalkylidenephosphoranes, acetylenic carboxamides, and acetylenic bromides, respectively. Recently, the reaction of phenylacetylene with CuCN/bis(trimethylsilyl) peroxide to give cyanoalkynes has been described by Ricci, et al.¹⁵ However, the formation of acetylenic dimer in 30% yield severely limits its applicability to the preparation of other cyanoalkynes. This procedure describes the cyanation of terminal acetylenes with cuprous cyanide in the presence of chlorotrimethylsilane, water, and a catalytic amount of sodium iodide in DMSO/CH₃CN to provide a general procedure for preparing cyanoalkynes in fair to good yields as shown in Table I. A wide range of terminal acetylenes bearing various kinds of functional groups can undergo this cyanation reaction. The use of DMSO with CH₃CN as the co-solvent is critically important in this cyanation process. Dimerization can be minimized to less than 4% when the volume ratio of DMSO and CH₃CN is 3 to 1. While increasing the amount of CH₃CN in the reaction can further minimize the dimerization, yield of the desired product is sacrificed. When DMSO is used alone as the solvent, the reaction gave the desired and dimerized products in 11% and 22% yields, respectively. Under the same conditions, the use of other solvent systems such as CH₃CN, THF, THF + HMPA (10%), and benzene led to recovering the starting material after 72 hr at 50°C. The addition of a catalytic amount of sodium iodide (NaI) can facilitate and accelerate the cyanation process.¹⁶ On the other hand, the addition of a stoichiometric amount of NaI in the reaction gave low yields of the desired product along with one unidentified product. In the absence of iodide the desired products were formed in only low yields. For comparison with halide ion as catalyst, various salts were used in the reaction. Most iodide salts such as CuI, ZnI₂, LiI and KI may also be employed as the catalyst in the cyanation reaction to give comparable results, but only low yields of the desired product were obtained when salts such as NaCl or NaBr were used in the reaction. In the absence of either TMSCl or H₂O no cyanation reaction occurred.

TABLE I
CYANOALKYNES VIA IODIDE-CATALYZED CYANATION OF TERMINAL ACETYLENES WITH CUPROUS CYANIDE IN THE PRESENCE OF TMSCI AND H₂O IN DMSO/CH₃CN¹⁷
Entry	R in RC≡CH	Time (hr)	Product^a	Isolated Yield (%)


1	Ph	60	Ph-C≡C-CN	58
2		72		76
3		72		72
4		60		84
5		60		78
6		60		51
7		60		74
8	n-C_5⁻	72	n-C₅-C≡C-CN	56
9	n-C_6⁻	72	n-C₆-C≡C-CN	53

^aAll new compounds have been fully characterized by ¹H and ¹³C NMR, IR or MS spectroscopy.

References and Notes

Institute of Chemistry, Academia Sinica, Nankang, Taipei, Taiwan, ROC.
Ashburn, S. P.; Coates, R. M. J. Org. Chem. 1984, 49, 3127;
Landor, S. R.; Landor, P. D.; Williams, V. E. J. Chem. Soc., Perkin Trans. I 1984, 2677;
Landor, S. R.; Landor, P. D.; Fomum, Z. T.; Mbafor, J. T.; Mpango, G. W. B. Tetrahedron 1984, 40, 2141;
Glass, R. S.; Smith, D. L. J. Org. Chem. 1974, 39, 3712;
Westmijze, H.; Kleijn, H.; Vermeer, P. Tetrahedron Lett. 1979, 3327;
Westmijze, H.; Kleijn, H.; Vermeer, P. Synthesis 1979, 430.
Van der Welle, R. A.; Brandsma, L. Recl. Trav. Chim. Pays-Bas 1973, 92, 667;
Murray, R. E.; Zweifel, G. Synthesis 1980, 150;
Grignard, V.; Perrichon, H. Ann. Chimie 1926, 5, 5.
Gough, S. T. D.; Trippett, S. J. Chem. Soc. 1962, 2333;
Gough, S. T. D.; Trippett, S. J. Chem. Soc. 1964, 543.
Liso, G.; Trapani, G.; Reho, A.; Latrofa, A.; Loidodice, F. J. Chem. Soc., Perkin Trans. I 1983, 567.
Brandsma, L. "Preparative Acetylenic Chemistry", 2nd ed.; Elsevier: New York, 1988; p. 288.
Casarini, A.; Dembech, P.; Reginato, G.; Ricci, A.; Seconi, G. Tetrahedron Lett. 1991, 32, 2169.
The addition of a catalytic amount of NaI has been shown to facilitate the conversion of alcohols into nitriles: Davis, R.; Untch, K. G. J. Org. Chem. 1981, 46, 2985.
Luo, F.-T.; Wang, R.-T. Tetrahedron Lett. 1993, 34, 5911.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

3-Phenyl-2-propynenitrile:
Propiolonitrile, phenyl- (8);
2-Propynenitrile, 3-phenyl- (9); (935-02-4)

Dimethyl sulfoxide:
Methyl sulfoxide (8);
Methane, sulfinylbis- (9); (67-68-5)

Acetonitrile TOXIC (8,9); (75-05-8)

Cuprous cyanide:
Copper cyanide (8,9); (544-92-3)

Phenylacetylene:
Benzene, ethynyl- (8,9); (536-74-3)

Chlorotrimethylsilane:
Silane, chlorotrimethyl- (8,9); (75-77-4)

Notes

References/EndNotes

Article Compounds

Authors