Copper-catalyzed synthesis of alkynyl hydrazones from alkynes and hydrazonyl chlorides

Article abstract of DOI:10.1002/hlca.201300421

A novel ligand-free synthesis of alkynyl hydrazones via coupling reaction of hydrazonyl chlorides and terminal alkynes, catalyzed by CuI led to excellent yields. Copyright

Full text of DOI:10.1002/hlca.201300421

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Helvetica Chimica Acta – Vol. 97 (2014)
Copper-Catalyzed Synthesis of Alkynyl Hydrazones from Alkynes and
Hydrazonyl Chlorides
by Issa Yavari*, Manijeh Nematpour, Sima Yavari, and Fatemeh Sadeghizadeh
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
(phone: þ 98-21-82883465; fax: þ 98-21-82883455; e-mail: yavarisa@modares.ac.ir)
A novel ligand-free synthesis of alkynyl hydrazones via coupling reaction of hydrazonyl chlorides
and terminal alkynes, catalyzed by CuI led to excellent yields.
Introduction. – Alkynyl hydrazones are versatile intermediates, which are used in
heterocyclic synthesis [1][2]. Alkynyl hydrazones are successfully converted to the
corresponding 3-aminoacrylonitriles in the presence of copper catalysts [3]. Despite
the synthetic importance of alkynyl hydrazones, relatively few methods are available
for their synthesis. Alkynyl hydrazones have been prepared from propargyl aldehydes
and hydrazines [4].
Herein, we report a simple and efficient procedure for the synthesis of alkynyl
hydrazones via the Cu-catalyzed coupling reaction of hydrazonyl chlorides [5] and
terminal alkynes (Scheme 1).
Scheme 1
Results and Discussion. – Initially, phenylacetylene (¼ethynylbenzene; 1a) and
(E)-1-[chloro(phenyl)methylidene]-2-phenylhydrazine (¼ N-phenylbenzenecarbohy-
drazonoyl chloride; 2a) were selected as the model substrates. Several catalysts such
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as CuI, CuBr, CuCl, and Cu powder were tested with CuI giving the best results.
Among several solvents screened, (DMF) was the best. When the reaction was
performed in DMF in the presence of 1 equiv. of Et3N at room temperature for 3 h, the
desired product 3a was obtained in 91% yield (Scheme 1). Thus, the optimized reaction
conditions used were 10 mol-% of CuI, 1 mmol of alkyne 1, 1 mmol of Et3N, and
1 mmol of hydrazonyl chloride 2 in DMF at room temperature.
1
Structures of compounds 3a – 3i were assigned by IR, H- and 13C-NMR, and MS
1
data. The H-NMR spectrum of 3a exhibited one singlet for NH (d(H) 8.74), along
with characteristic multiplets for the Ph H-atoms. The 13C-NMR spectrum of 3a
exhibited 15 signals in agreement with the proposed structure. The mass spectrum of 3a
displayed the molecular ion peak at m/z 296. The NMR spectra of products 3b – 3i were
similar to those of 3a, except for the substituents.
A mechanism for the formation of products 3 is proposed in Scheme 2. The yellow
copper acetylide 4, formed from 1 and CuI, undergoes nucleophilic addition reaction
with 2 to afford alkynyl hydrazone 3.
Scheme 2
In conclusion, we have demonstrated that CuI-catalyzed coupling reaction, of
hydrazonyl chlorides with terminal alkynes afford a novel and efficient ligand-free
synthesis of alkynyl hydrazones. The potential diversity of this type of reaction and
available starting materials and catalysts are the main advantages of this methodology.
Experimental Part
General. All chemicals were obtained commercially and used without further purification. M.p.:
Electrothermal-9100 apparatus. IR Spectra: Shimadzu-IR-460 spectrometer; in cmꢀ1. 1H- and 13C-NMR
spectra: Bruker DRX-500 Avance instrument at 500.1 and 125.7 MHz, resp.; d in ppm, J in Hz. MS:
Finnigan-MAT-8430EI-MS mass spectrometer; at 70 eV; in m/z (rel. %). Elemental analyses: Vario EL
III CHNOS elemental analyzer.
General Procedure for the Synthesis of Compounds 3. A mixture of alkyne 1 (1 mmol), CuI
(0.1 mmol), and Et3N (1 mmol) in DMF (3 ml) was slowly added to hydrazonyl chloride 2 (1 mmol), and
stirred at r.t. under N2. After completion of the reaction (ca. 3 h; TLC (AcOEt/hexane 1:7) monitoring),
the mixture was diluted with CH2Cl2 (2 ml) and aq. NH4Cl soln. (3 ml), stirred for 30 min, and the layers
were separated. The aq. layer was extracted with CH2Cl2 (3 ꢁ 3 ml) and the combined org. fractions were
dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash CC (SiO2
(230 – 400 mesh; Merck), hexane/AcOEt 7:1) to give the product.
1-(1,3-Diphenylprop-2-yn-1-ylidene)-2-phenylhydrazine (3a). Yield: 0.27 g (91%). Yellow solid.
M.p. 116 – 1188. IR (KBr): 3332, 2100, 1593, 1506, 1327, 1250, 1157. 1H-NMR: 6.98 (t, J ¼ 7.3, 1 arom. H);
7.24 (d, J ¼ 8.2, 2 arom. H); 7.32 (t, J ¼ 7.3, 2 arom. H); 7.38 (d, J ¼ 7.3, 2 arom. H); 7.44 – 7.47 (m, 4 arom.
H); 7.65 (d, J ¼ 7.3, 2 arom. H); 7.93 (d, J ¼ 8.2, 2 arom. H); 8.74 (s, NH). 13C-NMR: 78.5 (C); 104.1 (C);
113.6 (2 CH); 121.4 (CH); 124.6 (C); 126.7 (2 CH); 126.8 (CH); 128.6 (2 CH); 128.8 (2 CH); 129.4
(2 CH); 129.8 (CH); 131.9 (2 CH); 133.8 (C); 134.5 (C); 143.4 (C). MS: 296 (15, Mþ), 219 (25), 204 (42),

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Helvetica Chimica Acta – Vol. 97 (2014)
195 (32), 101 (100), 92 (70), 77 (54). Anal. calc. for C21H16N2 (296.13): C 85.11, H 5.44, N 9.45; found: C
85.45, H 5.41, N 9.51.
1-[1-(4-Methylphenyl)-3-phenylprop-2-yn-1-ylidene]-2-phenylhydrazine (3b). Yield: 0.27 g (87%).
Yellow solid. M.p. 119 – 1218. IR (KBr): 3738, 2112, 1595, 1507, 1255, 1110. 1H-NMR: 2.44 (s, Me); 6.98 (t,
J ¼ 7.3, 1 arom. H); 7.24 – 7.29 (m, 4 arom. H); 7.35 (t, J ¼ 7.3, 2 arom. H); 7.45 – 7.50 (m, 3 arom. H); 7.68 (t,
J ¼ 7.3, 2 arom. H); 7.94 (d, J ¼ 8.1, 2 arom. H); 8.73 (s, NH). 13C-NMR: 21.3 (Me); 79.1 (C); 103.5 (C);
113.5 (2 CH); 121.0 (CH); 121.7 (C); 125.5 (2 CH); 126.0 (C); 128.7 (2 CH); 128.9 (2 CH); 129.3 (2 CH);
129.6 (CH); 131.9 (2 CH); 133.3 (C); 138.1 (C); 143.8 (C). MS: 310 (10, Mþ), 233 (25), 218 (21), 101
(100), 92 (45), 91 (50), 77 (55). Anal. calc. for C22H18N2 (310.15): C 85.13, H 5.85, N 9.03; found: C 85.51,
H 5.90, N 9.09.
1-[1-(4-Chlorophenyl)-3-phenylprop-2-yn-1-ylidene]-2-phenylhydrazine (3c). Yield: 0.26 g (85%).
Yellow solid. M.p. 120 – 1238. IR (KBr): 3433, 2114, 1577, 1519, 1325, 1254, 1117. 1H-NMR: 6.98 (t, J ¼ 7.3,
1 arom. H); 7.25 (d, J ¼ 7.3, 2 arom. H); 7.34 – 7.42 (m, 5 arom. H); 7.48 (d, J ¼ 7.6, 2 arom. H); 7.65 (d, J ¼
8.1, 2 arom. H); 7.93 (d, J ¼ 8.1, 2 arom. H); 8.75 (s, NH). 13C-NMR: 78.5 (C); 104.1 (C); 113.6 (2 CH);
121.3 (CH); 124.5 (C); 126.7 (2 CH); 127.5 (2 CH); 127.9 (C); 128.7 (2 CH); 129.4 (2 CH); 129.7 (2 CH);
131.9 (CH); 133.8 (C); 134.5 (C); 143.4 (C). MS: 330 (16, Mþ), 253 (42), 238 (50), 111 (35), 101 (100), 92
(30), 77 (65). Anal. calc. for C21H15N2Cl (330.81): C 76.24, H 4.57, N 8.47; found: C 76.71, H 4.62, N 8.85.
1-(1,3-Diphenylprop-2-yn-1-ylidene)-2-(4-nitrophenyl)hydrazine (3d). Yield: 0.31 g (90%). Yellow
solid. M.p. 154 – 1568. IR (KBr): 3535, 2111, 1591, 1499, 1358, 1252. 1H-NMR: 7.00 (t, J ¼ 7.3, 1 arom. H);
7.26 (d, J ¼ 7.3, 2 arom. H); 7.29 (t, J ¼ 7.6, 2 arom. H); 7.41 – 7.49 (m, 5 arom. H); 7.70 (d, J ¼ 8.1, 2 arom.
H); 8.12 (d, J ¼ 8.1, 2 arom. H); 8.79 (s, NH). 13C-NMR: 79.0 (C); 103.8 (C); 113.4 (2 CH); 120.3 (CH);
121.2 (C); 125.7 (2 CH); 127.7 (C); 128.3 (CH); 128.5 (2 CH); 128.8 (2 CH); 129.8 (2 CH); 131.9 (2 CH);
132.5 (C); 135.9 (C); 143.8 (C). MS: 341 (17, Mþ), 264 (26), 240 (22), 137 (31), 101 (100), 91 (57), 77
(40). Anal. calc. for C21H15N3O2 (341.12): C 73.89, H 4.43, N 12.31; found: C 73.56, H 4.47, N 12.38.
1-[1-(4-Methylphenyl)-3-phenylprop-2-yn-1-ylidene]-2-(4-nitrophenyl)hydrazine; (3e). Yield: 0.31 g
1
(86%). Yellow solid. M.p. 131 – 1338. IR (KBr): 3256, 2115, 1592, 1500, 1401, 1257. H-NMR: 2.43 (s,
Me); 6.97 (t, J ¼ 7.3, 1 arom. H); 7.25 – 7.30 (m, 4 arom. H); 7.36 (t, J ¼ 7.3, 2 arom. H); 7.48 (d, J ¼ 7.3, 2
arom. H); 7.68 (d, J ¼ 8.1, 2 arom. H); 7.92 (d, J ¼ 8.1, 2 arom. H); 8.72 (s, NH). 13C-NMR: 21.3 (Me); 79.1
(C); 103.5 (C); 113.5 (2 CH); 120.9 (C); 121.7 (C); 125.5 (2 CH); 126.0 (C); 128.7 (2 CH); 128.8 (2 CH);
129.1 (2 CH); 129.7 (CH); 131.9 (2 CH); 133.2 (C); 138.1 (C); 143.8 (C). MS: 355 (17, Mþ), 264 (38), 233
(26), 137 (62), 101 (100), 91 (70), 77 (67). Anal. calc. for C22H17N3O2 (355.39): C 74.35, H 4.82, N 9.00;
found: C 74.69, H 4.85, N 9.11.
1-[1-(4-Chlorophenyl)-3-phenylprop-2-yn-1-ylidene]-2-(4-nitrophenyl)hydrazine (3f). Yield: 0.31 g
(83%). Yellow solid. M.p. 161 – 1638. IR (KBr): 3431, 2115, 1590, 1507, 1404, 1258. 1H-NMR: 6.96 (t, J ¼
7.3, 1 arom. H); 7.20 – 7.27 (m, 4 arom. H); 7.35 (t, J ¼ 7.6, 2 arom. H); 7.46 (d, J ¼ 7.6, 2 arom. H); 7.67 (d,
J ¼ 8.1, 2 arom. H); 7.93 (d, J ¼ 8.1, 2 arom. H); 8.71 (s, NH). 13C-NMR: 79.1 (C); 103.5 (C); 113.5 (2
CH); 120.9 (CH); 121.7 (C); 125.7 (2 CH); 126.0 (C); 128.3 (2 CH); 128.6 (2 CH); 129.1 (2 CH); 129.6
(C); 131.9 (2 CH); 133.2 (C); 138.2 (C); 143.8 (C). MS: 375 (10, Mþ), 294 (24), 264 (62), 111 (100), 101
(54), 77 (57). Anal. calc. for C21H14ClN3O2 (375.08): C 67.12, H 3.75, N 11.18; found: C 67.39, H 3.79, N
11.14.
1-Phenyl-2-(1-phenylhex-2-yn-1-ylidene)hydrazine (3g). Yield: 0.21 g (79%). Yellow solid. M.p.
101 – 1038. IR (KBr): 3250, 2142, 1576, 1516, 1435, 1367, 1150. 1H-NMR: 1.14 (t, J ¼ 6.2, Me); 1.74 – 1.81
(m, CH2); 2.62 (t, J ¼ 6.8, CH2); 6.93 (t, J ¼ 7.2, 1 arom. H); 7.21 (d, J ¼ 7.2, 2 arom. H); 7.30 – 7.39 (m, 5
arom. H); 7.85 (t, J ¼ 7.2, 2 arom. H); 8.62 (s, NH). 13C-NMR: 13.6 (Me); 21.7 (CH2); 22.1 (CH2); 70.9
(C); 106.1 (C); 113.4 (2 CH); 120.9 (CH); 125.3 (CH); 126.6 (2 CH); 128.7 (2 CH);129.3 (2 CH); 133.6
(C); 134.7 (C); 143.6 (C). MS: 262 (22, Mþ), 219 (16), 195 (32), 92 (100), 77 (42) , 67 (50). Anal. calc. for
C18H18N2 (262.35): C 82.41, H 6.92, N 10.68; found: C, 82.22; H, 6.87; N, 10.92.
1-[1-(4-Chlorophenyl)hex-2-yn-1-ylidene]-2-phenylhydrazine (3h). Yield: 0.22 g (76%). Yellow
solid. M.p. 109 – 1118. IR (KBr): 3430, 2115, 1575, 1525, 1491, 1358, 1160. 1H-NMR: 1.15 (t, J ¼ 6.2, Me);
1.75 – 1.83 (m, CH2); 2.68 (t, J ¼ 6.8, CH2); 6.94 (t, J ¼ 7.6, 1 arom. H); 7.22 (d, J ¼ 7.6, 2 arom. H); 7.33 (t,
J ¼ 7.6, 2 arom. H); 7.44 (d, J ¼ 8.0, 2 arom. H); 7.95 (d, J ¼ 8.0, 2 arom. H); 8.65 (s, NH). 13C-NMR: 13.7
(Me); 21.8 (CH2); 22.1 (CH2); 71.3 (C); 105.7 (C); 113.5 (2 CH); 120.7 (CH); 125.7 (2 CH); 127.5 (C);
128.4 (2 CH); 128.6 (C); 128.9 (2 CH); 136.2 (C); 143.9 (C). MS: 296 (20, Mþ), 253 (12), 219 (33), 111

Helvetica Chimica Acta – Vol. 97 (2014)
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(100), 77 (66), 67 (45), 43 (21). Anal. calc. for C18H17N2Cl (296.11): C 72.84, H 5.77, N 9.44; found: C
72.99, H 5.70, N 9.39.
1-[1-(4-Chlorophenyl)hept-2-yn-1-ylidene]-2-phenylhydrazine (3i). Yield: 0.22 g (72%). Yellow
solid. M.p. 105 – 1078. IR (KBr): 3222, 2119, 1525, 1506, 1468, 1343, 1152. 1H-NMR: 1.17 (t, J ¼ 6.2, Me);
1.26 – 1.36 (m, CH2); 1.76 – 1.84 (m, CH2); 2.65 (t, J ¼ 6.8, CH2); 6.95 (t, J ¼ 7.6, 1 arom. H); 7.24 (d, J ¼ 7.6,
2 arom. H); 7.34 (t, J ¼ 7.6, 2 arom. H); 7.43 (d, J ¼ 8.0, 2 arom. H); 7.98 (d, J ¼ 8.0, 2 arom. H); 8.66 (s,
NH). 13C-NMR: 13.7 (Me); 20.0 (CH2); 21.8 (CH2); 22.2 (CH2); 71.4 (C); 105.7 (C); 113.0 (2 CH); 120.7
(CH); 126.4 (2 CH); 127.2 (C); 128.5 (2 CH); 128.7 (C); 128.9 (2 CH); 136.1 (C); 143.5 (C). MS: 310 (15,
Mþ), 253 (55), 111 (67), 92 (100), 81 (44), 77 (55), 57 (45). Anal. calc. for C19H19N2Cl (310.12): C 73.42,
H 6.16, N 11.41; found: C 73.67, H 6.21, N 11.47.
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Received November 28, 2013