Microwave assisted intramolecular wittig reaction: A facile method for the synthesis of conjugated acetylenes

Article abstract of DOI:10.1081/SCC-120018770

A rapid and efficient synthesis of acetylenic compounds by the microwave assisted intramolecular Wittig reaction of β-oxo-alkylidene-triphenylphosphoranes is reported.

Full text of DOI:10.1081/SCC-120018770

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Microwave Assisted Intramolecular Wittig Reaction:
A Facile Method for the Synthesis of Conjugated
Acetylenes
V. V. V. N. S. Rama Rao a , S. Ravikanth a , G. Venkat Reddy a , D. Maitraie a , R. Yadla a & P.
Shanthan Rao a
a Organic Division II , Indian Institute of Chemical Technology , Hyderabad, India
Published online: 16 Aug 2006.
To cite this article: V. V. V. N. S. Rama Rao , S. Ravikanth , G. Venkat Reddy , D. Maitraie , R. Yadla & P. Shanthan Rao (2003)
Microwave Assisted Intramolecular Wittig Reaction: A Facile Method for the Synthesis of Conjugated Acetylenes, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:9, 1523-1529, DOI:
10.1081/SCC-120018770
To link to this article: http://dx.doi.org/10.1081/SCC-120018770
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 9, pp. 1523–1529, 2003
Microwave Assisted Intramolecular Wittig
Reaction: A Facile Method for the Synthesis of
Conjugated Acetylenes#
V.V.V.N.S.Rama Rao, S.Ravikanth, G.Venkat Reddy,
*
D.Maitraie, R.Yadla, and P.Shanthan Rao
OrganicDivision II, Indian Institute of Chemical
Technology, Hyderabad, India
ABSTRACT
A rapid and efficient synthesis of acetylenic compounds by the micro-
wave assisted intramolecular Wittig reaction of b-oxo-alkylidene-
triphenylphosphoranes is reported.
#IICT Communication No. 020106.
*Correspondence: P. Shanthan Rao, Organic Division II, Indian Institute of
Chemical Technology, Hyderabad 500 007, India; E-mail: psrao@iict.ap.nic.in..
1523
DOI: 10.1081/SCC-120018770
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1524
Rao et al.
Conjugated alkynenitriles and acetylenic carboxylic acid esters are
good substrates for nucleophilic addition reactions and for synthesizing
heterocyclic compounds. Several methods have been reported for prepar-
ing the conjugated alkynenitriles and the acetylenic carboxylic acid esters.
Most of them require introduction of the necessary substituents on a
metal acetylide or creation of the acetylenic bond itself with a suitable
substrate.[1] They involve handling either hazardous chemicals or difficult
reaction conditions to be used as common laboratory methods.
Intramolecular Wittig reaction[2] of b-oxo-alkylidenetriphenylphosphor-
anes 4 offers the most elegant and convenient laboratory synthesis of
conjugated alkynes. In this method, the acetylenic compounds generated
need to be continuously removed from the pyrolyzer as they undergo
polymerization when exposed to drasticconditions for longer periods.
Our investigations involving the fluorinated conjugated alkynenitriles
and acetylenic carboxylic acid esters made us to search for an efficient
and convenient route for their synthesis in the laboratory. In order to
reduce the drawbacks associated with the intramolecular Wittig reaction,
we have investigated the use of microwave irradiation of the b-oxo-alkyl-
idenetriphenylphosphoranes 4 for shorter periods instead of pyrolysis
over 30–45 min. The shorter irradiation times reduced the polymeriza-
tion of acetylenic compounds and resulted in their improved isolated
yield. We wish to describe the synthesis of six conjugated alkyne-
nitriles and three conjugated acetylenic carboxylic acid esters in a two
step process starting from the corresponding acid chlorides 3. The base
promoted acylation of phosphorane 2 with acid chloride 3 in dichloro-
methane provided the b-oxo-alkylidenetriphenylphosphorane 4.
Scheme 1.

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Microwave Assisted Intramolecular Wittig Reaction
1525
The phosphorane 2 is generated in situ[3] from the corresponding
phosphonium salt 1, which was prepared by the addition of triphenyl-
phosphine and RCH2Cl. The oxo-ylids 4a–i on microwave irradia-
tion gave the corresponding acetylenes 6a–i and triphenylphosphine
oxide 7 in high yield. The reaction proceeds via the oxaphosphete
intermediate 5 (Sch. 1).
EXPERIMENTAL
Melting points were determined in open glass capillaries using
Fisher-Johns melting point instrument and were uncorrected. IR spectra
were recorded on FT–IR, Schimadzu Perkin–Elmer 1310 infrared spec-
1
trometer. H and 13C NMR spectra were recorded on Varian Gemini
(200 MHz) instrument in CDCl3 with tetramethylsilane as internal stan-
dard. The mass spectra were measured on a VG micro mass 7070 H mass
spectrometer. Elemental analysis was carried out using Vario EL,
Elementar instrument. Microwave irradiations were carried out using
sealed tube (Aldrich, Ace pressure tube, 10.2 cm, 15 mL) in a domestic
microwave oven (BPL BMO 700T 600 W).
General Procedure for the Synthesis of
b-Oxo-alkylidenetriphenylphosphoranes (4)
Phosphorane 2 (5 mmol), dry dichloromethane (10 mL) and triethyl-
amine (5 mmol) were taken in a two necked round bottom flask, cooled to
10–15ꢀC and a solution of acid chloride 3 in dichloromethane (5 mL) was
added dropwise in about 15 min and the reaction mixture was stirred at
room temperature for about 24 h. The reaction mixture was diluted with
dichloromethane (10 mL) and washed with water (3 ꢁ 20 mL), the organic
layer separated and dried over anhy. sodiumsulphate. The solvent was
removed on rota-vapor and the crude product 4 was purified by recrys-
tallization (1:4 mixture of dichloromethane/hexane).
General Procedure for the Synthesis of
Conjugated Acetylenes (6)
b-Oxo-alkylidenetriphenylphosphorane 4 (45 mmol) was taken in a
sealed tube and subjected to microwave irradiation for 5–7 min.[5]

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1526
Rao et al.
The dark brown reaction mixture was dissolved in dichloromethane
(10 mL) and purified by column chromatography using silicagel
(100–200 mesh). Initial fractions were eluted with pet ether (60–80ꢀC)
afforded the corresponding conjugated alkynes. Later fractions were
eluted with ethyl acetate and pet ether (1:9) afforded the unreacted phos-
phorane 4, followed by triphenylphosphine oxide 7. The yield of the
individual alkynes 6a–i is given in Table 1.
Table 1. Synthesis of conjugated acetylenes.
Starting
S. no material
Time
(min) Product
M.p.
(ꢀC)
Yield
(%)
R
R1
1
2
3
4
5
4a
4b
4c
4d
4e
CN
6
6a
6b
6c
6d
6e
Liquid[2a]
Liquid[2a]
Liquid
Liquid[4]
39
84
81
85
84
92
COOEt
CN
5.5
6
COOEt
CN
5
6
6
4f
COOEt
6
6f
Liquid
82
7
8
4g
4h
CN
CN
7
7
6g
6h
112[2a]
86
80
Liquid[3]
9
4i
CN
6
6i
39[3]
90
a4c–f, 6c, and 6e–f are new compounds. Though compound 6d is reported,[4]
no data is given.
bAll compounds are well characterized by NMR, IR, mass, and elemental analysis.

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Microwave Assisted Intramolecular Wittig Reaction
Spectral Data
1527
4-Fluorobenzoyl-cyanomethylenetriphenylphosphorane (4c): Yield:
93%; m.p. 186ꢀC; IR (KBr): 3056, 2181, 1624, 1569, 1461, 1106 cmꢂ1
;
1H NMR (200 MHz, CDCl3): ꢀ 7.06 (multiplet, 2H, Aromatic), 7.48–7.62
(unresolved, 7H, Aromatic), 7.62–7.63. (Unresolved, 8H, Aromatic), 8.02
(multiplet, 2H, Aromatic); MS (m/z): 423, (Mþ), 278, 145, 126, 95; Anal.
Found: C, 76.58 H, 4.54; N, 3.29. C27H19FNOP requires C, 76.58; H,
4.52; N, 3.30.
4-Fluorobenzoyl-carboethoxymethylenetriphenylphosphorane
(4d):
Yield: 85%; m.p. 104ꢀC; IR (KBr): 2972, 1641, 1599, 1440, 1100 cmꢂ1
;
1H NMR (200 MHz, CDCl3): ꢀ 0.66 (t, 3H, CH3), 3.65 (q, 2H, CH2), 6.9
(multiplet, 2H, Aromatic), 7.4–7.58 (unresolved, 9H, Aromatic), 7.59–7.8
(unresolved, 8H, Aromatic); MS (m/z): 470, 278, 192; Anal. Found: C,
74.04: H, 5.16. C29H24FO3P requires C, 74.03; H, 5.1415.
2,6-Difluorobenzoyl-cyanomethylenetriphenylphosphorane (4e): Yield:
91%; m.p. 226–227ꢀC; IR (KBr): 3056, 2181, 1624, 1343, 1106 cmꢂ1
;
1H NMR (200 MHz, CDCl3): ꢀ 6.9 (multiplet, 2H, Aromatic), 7.25 (mul-
tiplet, 1H, Aromatic), 7.42–7.78 (unresolved, 15H, Aromatic); 13C NMR
(50 MHz, CDCl3): ꢀ 53.1 (C1, JC–P ¼ 122.2 Hz), 182.4 (C2, JC–P ¼ 60 Hz)
120.1 (C3, JC–P ¼ 15 Hz), 121.9 (C4, JC–P ¼ 92.9 Hz), 133.2 (C5, JC–P
¼
10.4 Hz), 128.8 (C6, JC–P ¼ 12.88 Hz), 133 (C7, JC–P ¼ 2.9 Hz), 130.1
1
(C8, d/t, JC–F ¼ 10 Hz, JC–P ¼ 10 Hz), 158.9 (C9, d/d, JC–F ¼ 247.6 Hz,
2
3
3JC–F ¼ 8.1 Hz), 111.1 (C10, d/d, JC–F ¼ 15.9 Hz, JC–F ¼ 8.6 Hz); MS
(m/z): 441 (Mþ), 278, 163, 112; Anal. Found: C, 73.45; H, 4.14; N,
3.17. C27H18F2NOP requires C, 73.46; H, 4.11; N, 3.17.
2,6-Difluorobenzoyl-carboethoxymethylenetriphenylphosphorane (4f ):
Yield: 87%; m.p. 109ꢀC; IR (KBr): 1685, 1589, 1434, 1077 cmꢂ1
;
1H NMR (200 MHz, CDCl3): ꢀ 0.58 (t, 3H, CH3), 3.61 (q, 2H, CH2), 6.8
(multiplet, 1H, Aromatic), 7.38–7.47 (unresolved, 10H, Aromatic), 7.48–
7.66 (unresolved, 5H, Aromatic); MS (m/z): 488 (Mþ), 278, 165, 138; Anal.
Found: C, 701.29; H, 4.75. C29H23F2O3P requires C, 71.30; H, 4.74.
3-(4-Fluorophenyl)propynenitrile (6c): Yield: 92%; liquid; IR
1
(neat): 2925, 2185, 2282 cmꢂ1; H NMR (200 MHz, CDCl3): ꢀ 7.14 (2H,

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1528
Rao et al.
multiplet, Aromatic), 7.65 (2H, m, Aromatic); MS (m/z): 145 (Mþ), 126,
95, 75; Anal. Found: C, 74.49: H, 2.67; N, 9.51. C9H4FN requires C,
74.48; H, 2.77; N, 9.65.
Ethyl 3-(4-fluorophenyl)propiolate (6d): Yield: 84%; liquid; IR (neat):
1
2925, 2210, 1704, 1189 cmꢂ1; H NMR (200 MHz, CDCl3): ꢀ 7.63 (2H,
multiplet, Aromatic), 7.09 (2H, m, Aromatic), 4.3 (2H, q, CH2), 0.9 (3H,
t, CH3); MS (m/z): 192 (Mþ), 147, 120, 99; Anal. Found: C, 74.98; H,
5.19. C11H9FO2 requires C, 74.98; H, 5.14.
3-(2,6-Difluorophenyl)propynenitrile (6e): Yield: 92%; m.p.: 39ꢀC; IR
1
(KBr): 2925, 2367, 2204 cmꢂ1; H NMR (200 MHz, CDCl3): ꢀ 7.4 (1H,
multiplet, Aromatic), 7.9 (2H, m, Aromatic); MS (m/z): 163 (Mþ), 112,
137. Anal. Found: C, 66.27; H, 1.89; N, 8.59. C9H3F2N requires C, 66.26;
H, 1.85; N, 8.58.
Ethyl-3-(2,6-difluorophenyl)propiolate (6f ): Yield: 92%; Liquid; IR
1
(neat): 2988, 2242, 1715, 1198 cmꢂ1; H NMR (200 MHz, CDCl3): ꢀ 7.6
(1H, multiplet, Aromatic), 7.1 (2H, m, Aromatic), 4.3 (2H, q, CH2), 0.9
(3H, t, CH3); MS (m/z): 210 (Mþ), 165, 138, 115; Anal. Found: C, 62.87;
H, 3.88. C11H8F2O2 requires C, 62.86; H, 3.83.
ACKNOWLEDGMENTS
Authors are thankful to Dr. K. V. Raghavan, Director. IICT,
Hyderabad and CSIR, New Delhi for providing financial support.
They are also thankful to Sri S. Narayana Reddy, Scientist-F, IICT for
his interest and encouragement.
REFERENCES
1. (a) Vader Welle, R.A.; Branndsma, L. Recl. Trav. Chim. Pay-Bas
1973, 92, 667; (b) Murray, R.E.; Zeeifel, G. Synthesis 1980, 150; (c)
Grignard, V.; Perichon, H. Ann. Chimie. 1926, 5, 5.
2. (a) Gough, S.T.D.; Trippet, S. J. Chem. Soc. 1962, 2333; (b) Gough,
S.T.D.; Trippet, S. J. Chem. Soc. 1964, 543; (c) Judith, M.; Brittain, R.;
Jones Alan; Sayed Ali Naghi Taheri. Tetrahedron 1992, 48, 7608; (d)
Aitken R. Alan; Seth, S. Synlett 1990, 4, 211; (e) Aitken R. Alan;
Caroline, E.R. Horsburg; McCreadie J. Graeme; Seth Shirley. J.C.S.
Perkin Trans. 1 1994, 13, 1727.
3. Yadla, R.; Jampani Madhusudana Rao. Indian J. Chem. 1988,
27B, 1125.

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Microwave Assisted Intramolecular Wittig Reaction
1529
4. Chisso Corp., Japan. Patent 82120549, 1981; Chem. Abstr. 1981, 97,
181989a.
5. Fifty percent power was used for decomposing phosphoranes 4b, 4d,
4f. For the remaining ylids full microwave power was used.
Received in the UK February 11, 2002

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