Vinyltriphenylphosphonium salt mediated synthesis of 1,4-benzoxazine and coumarin derivatives

Article abstract of DOI:10.1016/S0040-4020(02)00758-5

Protonation of the reactive 1:1 intermediate produced in the reaction between triphenylphosphine and dimethyl acetylenedicarboxylate by 2-aminophenol, 3-aminophenol, 4-aminophenol and 2-amino-3-hydroxypyridine leads to vinyltriphenylphosphonium salts, whi

Full text of DOI:10.1016/S0040-4020(02)00758-5

Tetrahedron 58 (2002) 6895–6899
Vinyltriphenylphosphonium salt mediated synthesis of
1,4-benzoxazine and coumarin derivatives
*
Issa Yavari, Mehdi Adib and Leila Hojabri
Department of Chemistry, University of Tarbiat Modarres, P.O. Box 14115-175, Tehran, Iran
Received 20 December 2001; revised 2 May 2002; accepted 27 June 2002
Abstract—Protonation of the reactive 1:1 intermediate produced in the reaction between triphenylphosphine and dimethyl
acetylenedicarboxylate by 2-aminophenol, 3-aminophenol, 4-aminophenol and 2-amino-3-hydroxypyridine leads to vinyltriphenyl-
phosphonium salts, which undergo Michael addition with the conjugate base of the aminophenol or aminohydroxypyridine to produce highly
functionalized heterocyclic compounds. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
2.1. 2-Aminophenol
Coumarin and its derivatives continue to capture the
attention of synthetic organic chemists, and a large number
of coumarin ring syntheses and application of known
methods to new problems in coumarin chemistry have been
reported.1–7 The coumarin nucleus is incorporated in many
biologically active compounds and natural products.
The reaction of 2-aminophenol with 2 equiv. of DMAD in
the presence of 2 equiv. of triphenylphosphine was carried
out in refluxing toluene. The product was identified as
methyl 2-[2-oxo-2H-1,4-benzoxazine-3(4H )-yliden]acetate
(1) (see Scheme 1).
We have recently described8,9 a new and operationally
convenient approach to the synthesis of coumarin deriva-
tives based on the aromatic electrophilic substitution
reaction between the conjugate base of substituted phenols
and a vinyltriphenylphosphonium salt. As part of our current
studies on the developement of new routes to heterocyclic
and carbocyclic systems, we now report the reaction
between aminophenols and dimethyl acetylenedicarboxyl-
ate (DMAD) in the presence of triphenylphosphine. Thus,
the reaction of DMAD and triphenylphosphine in the
presence of 2-aminophenol, 3-aminophenol, 4-aminophenol
or 2-amino-3-hydroxypyridine leads to functionalized
coumarins, 1,4-oxazines, or iminophosphorane10 deriva-
tives. The reactions of tertiary phosphorus compounds with
DMAD and, on occasion, other acetylenic systems have
been discussed with emphasis upon the synthesis of
phosphorus heterocycles.11
A compound identical with this product has been reported
by Iwanami.12 Proton NMR chemical shifts and melting
point of the compound described in the paper supports its
identity. Complete 1H and 13C NMR shifts for 1 are given in
Section 4.
Compound 1 results from the initial addition of triphenyl-
phosphine to DMAD and subsequent protonation of the
reactive 1:1 adduct by 2-aminophenol. Then the positively
charged ion is attacked by the nitrogen atom of the
conjugate base of the phenol derivative to produce
phosphorane 2. The 2-oxo-2H-1,4-benzoxazine-3(4H )-
ylidene derivative 1 is presumably produced by intra-
molecular lactonization of the unsaturated diester 4, which
is formed by proton-transfer reaction and elimination of
triphenylphosphine (see Scheme 2).
Keywords: aromatic substitution; ring formation; coumarin derivatives;
triphenylphosphine; iminiphosphoranes; 2-oxo-2H-pyrano[2,3-c ]-
pyridines.
*
Corresponding author. Tel.: þ92-21-8006631; fax: þ98-21-8006544;
e-mail: isayavar@yahoo.com
Scheme 1.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00758-5

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I. Yavari et al. / Tetrahedron 58 (2002) 6895–6899
Scheme 2.
well established chemistry of trivalent phosphorus nucleo-
philes, it is reasonable to assume that heterocyclic moiety of
5 results from the initial addition of triphenylphosphine to
the acetylenic ester and subsequent protonation of the
reactive 1:1 adducts, followed by electrophilic attack of the
vinyltriphenylphosphonium cation on the aromatic ring at
the position activated by both activating groups (Scheme 4).
The coumarin moiety is presumably produced by intra-
molecular lactonization of the unsaturated diester 7, which
results from 6 by 1,2-hydrogen shift and elimination of
triphenylphosphine (see Scheme 4). A possibility for
formation of the iminophosphorane moiety is depicted in
Scheme 5. The reaction, presumably proceeds through a
proton shift from nitrogen to the ylidic carbon of 9, which
leads to the 1,4-diionic species 10. This betaine intermediate
can be in equilibrium with the azaphosphetane 11.
Elimination of dimethyl fumarate and dimethyl maleate
from the later produces iminophosphorane derivative 5
(Scheme 5). Observation of of the signals of dimethyl
Scheme 3.
2.2. 3-Aminophenol
The reaction of 3-aminophenol with 2 equiv. of DMAD in
the presence of 2 equiv. of triphenylphosphine was carried
out in refluxing toluene to produce compound 5 (see
Scheme 3). Structure 5 was assigned to the isolated product
on the basis of its elemental analyses and IR, H, 13C, and
1
31P NMR and mass spectral data. No other compound was
obtained from the reaction mixture by column
chromatography.
1
fumarate and dimethyl maleate in the H and 13C NMR
spectra of the crude reaction mixture supports the proposed
mechanism.
Although we have not yet established the mechanism of the
formation of iminophosphorane derivative 5 in an experi-
mental manner, a possible explanation is proposed in
Schemes 4 and 5. 3-Aminophenol potentially has two acidic
protons, which can protonate the 1:1 adduct of triphenyl-
phosphine and acetylenic ester. These processes are
separately shown in Schemes 4 and 5. On the basis of the
2.3. 4-Aminophenol
The reaction of 4-aminophenol with 2 equiv. of DMAD in
the presence of 2 equiv. of triphenylphosphine was carried
out in dichloromethane. A white powder was obtained from
Scheme 4.

I. Yavari et al. / Tetrahedron 58 (2002) 6895–6899
6897
Scheme 5.
Structures 13–16 were assigned to the isolated products
on the basis of their elemental analyses and IR, 1H, 13C, and
31P NMR and mass spectral data. The (E )-configuration of
the carbon–carbon double bond in 15 is based on the
chemical shift of the olefinic proton.13 Formation of
compound 13 may be similar to that outlined in Scheme 2
for 1,4-benzoxazine derivative 1. Compounds 14, 15, and 16
could be obtained by mechanisms similar to those
mentioned in Schemes 2–5.
Scheme 6.
the reaction mixture after 12 h. The product 12 (see Scheme
6) recovered unchanged after refluxing in boiling toluene for
24 h. Compound 12 is only slightly soluble in hot dimethyl
sulfoxide. On the basis of its elemental analyses, IR, and 1H
NMR spectral data we assigned the following structure to
compound 12.
3. Conclusions
We have found that the reaction between triphenyl-
phosphine and dimethyl acetylenedicarboxylate in the
presence of 2-aminophenol, 3-aminophenol, 4-aminophenol
and 2-amino-3-hydroxypyridine leads to vinylphosphonium
salts, which undergo Michael addition with the cojugate
base of the aminophenol or aminohydroxypyridine to
produce highly functionalized heterocyclic systems of
potential synthetic interest. The present method carries the
advantage that, not only is the reaction performed under
neutral conditions, but also the substances can be mixed
without any activation or modification. The unexpected
formation of iminophosphorane derivatives 5 and 16,
requires further investigation of the present method to
establish its utility and scope.
2.4. 2-Amino-3-hydroxypyridine
Under the reaction conditions given for 3-aminophenol, four
products were isolated from the reaction mixture of
2-amino-3-hydroxypyridine with DMAD. These products
were identified as methyl 2-[2-oxo-2H-pyrido[3,2-
b][1,4]oxazin-3(4H )-yliden]acetate (13), methyl 8-amino-
2-oxo-2H-pyrano[2,3-c ]pyridine-4-carboxylate
(14),
dimethyl (E )-2-[8-amino-4-(methoxycarbonyl)-2-oxo-2H-
pyrano[2,3-c ]pyridin-5-yl]-2-butanedioate (15), and methyl
2-oxo-8-[(triphenylphosphoranylidene)amino]-2H-pyr-
ano[2,3-c ]pyridine-4-carboxylate (16) (see Scheme 7).
Scheme 7.

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4. Experimental
4.1.3. Poly(4-aminophenoxytriphenylphosphorane) 12.
White powder, mp 200–2038C (melted and decomposed),
yield 90%. IR (KBr) (nmax, cm21): 3195 (NH), 1710, 1571,
1483, 1427, 1316, 1234, 1099, 826. Anal. Calcd for
(C24H20NOP)n (369.40)n: C, 78.04; H, 5.46; N, 3.79.
Dimethyl acetylenedicarboxylate, triphenylphosphine,
2-aminophenol, 3-aminophenol, 4-aminophenol and
2-amino-3-hydroxypyridine were obtained from Fluka
(Buchs, Switzerland) and were used without further
purification. Melting points were measured on an Electro-
thermal 9100 apparatus. Elemental analyses for C, H and N
were performed using a Heraeus CHN–O-Rapid analyzer.
Mass spectra were recorded on a FINNIGAN-MATT 8430
mass spectrometer operating at an ionization potential of
70 eV. 1H, 13C and 31P NMR spectra were measured (CDCl3
solution) with a Bruker DRX-500 AVANCE spectrometer
at 500.1, 125.8, and 202.5 MHz, respectively. IR spectra
were recorded on a Shimadzu IR-460 spectrometer.
Chromatography columns were prepared from Aldrich
silica gel 70–230 mesh.
1
Found (%): C, 78.1; H, 5.5; N, 3.8. H NMR: d 6.05 (2H,
d, J¼9.0 Hz, 2CH), 6.55 (2H, d, J¼9.0 Hz, 2CH), 7.4–7.7
(15H, m, 3C6H5), 8.51 (1H, br, NH). 31P NMR: d 22.04.
4.1.4. Methyl 2-[2-oxo-2H-pyrido[3,2-b ][1,4]oxazine-
3(4H )-yliden]acetate 13. Pale yellow crystals, mp 117–
1198C (from ethyl acetate), yield 30%. IR (KBr) (nmax
,
cm21): 3185 (NH), 1747, 1668 and 1615 (CvO). MS, m/z
(%): 220 (Mþ, 82), 188 (44), 160 (100), 93 (53), 65 (25).
Anal. Calcd for C10H8N2O4 (220.18): C, 54.55; H, 3.66; N,
12.72. Found (%): C, 54.5; H, 3.6; N, 12.7. 1H NMR: d 3.78
(3H, s, OCH3), 5.97 (1H, s, CH), 6.97 (1H, dd, J¼7.9,
4.8 Hz, CH), 7.38, (1H, d, J¼7.9 Hz, CH), 8.07 (1H, d,
J¼4.8 Hz, CH), 10.76 (1H, br s, NH). 13C NMR: d 51.66
(OCH3), 94.00, 118.29 and 123.95 (3CH), 135.70, 137.33
and 138.04 (3C), 144.74 (CH), 154.98 and 168.99 (2CvO).
4.1. General
To a magnetically stirred solution of triphenylphosphine
(1.05 g, 4 mmol) and 2-aminophenol (0.218 g, 2 mmol) in
toluene (20 mL) was added dropwise a mixture of DMAD
(0.568 g, 4 mmol) in toluene (4 mL) at 258C for 10 min.
The reaction mixture was then allowed to warm up to room
temperature and refluxed for 12 h. The solvent was removed
under reduced pressure and the residue was purified by
column chromatography using hexane–ethyl acetate (2:1)
as eluent. The solvent was removed under reduced pressure
and the product was recrystallized from ethyl acetate or
hexane–ethyl acetate (1:2).
4.1.5. Methyl 8-amino-2-oxo-2H-pyrano[2,3-c ]pyridine-
4-carboxylate 14. Pale orange crystals, mp 2208C (dec)
(from ethyl acetate), yield 25%. IR (KBr) (nmax, cm21):
3450 and 3255 (NH), 1731, 1705 and 1626 (CvO). MS, m/z
(%): 220 (Mþ, 100), 192 (28), 161 (25), 133 (20), 105 (30),
63 (32). Anal. Calcd for C10H8N2O4 (220.18): C, 54.55; H,
1
3.66; N, 12.72. Found (%): C, 54.6; H, 3.7; N, 12.7. H
NMR: d 3.98 (3H, s, OCH3), 6.00 (2H, br, NH2), 7.07 (1H, s,
CH), 7.31 (1H, d, J¼5.5 Hz, CH), 7.90 (1H, d, J¼5.5 Hz,
CH). 13C NMR: d 52.66 (OCH3), 107.85 (CH), 120.29 (C),
123.20 and 123.27 (2CH), 141.65, 142.56 and 149.50 (3C),
158.19 and 163.62 (2CvO).
4.1.1. Methyl 2-[2-oxo-2H-1,4-benzoxazine-3(4H )-
yliden]acetate (1). Pale yellow crystals, mp 167–1688C
(from 2:1 ethyl acetate–hexane) (lit.12 mp 1708C), yield
70%. 1H NMR: d 3.78 (3H, s, OCH3), 5.90 (1H, s, CH), 6.98
(1H, d, J¼7.7 Hz, CH), 7.00 (1H, t, J¼7.5 Hz, CH), 7.11
(1H, t, J¼7.5 Hz, CH), 7.12 (1H, d, J¼7.5 Hz, CH), 10.64
(1H, br s, NH). 13C NMR: d 52.25 (OCH3), 90.64, 114.83,
116.99 and 122.78 (4CH), 124.16 (C), 125.66 (CH), 138.15
and 140.00 (2C), 155.86 and 165.33 (2CvO).
4.1.6. Dimethyl (E )-2-[8-amino-4-(methoxycarbonyl)-2-
oxo-2H-pyrano[2,3-c ]pyridin-5-yl]-2-butanedioate 15.
Yellow crystals, mp 161–1638C (from ethyl acetate),
yield 25%. IR (KBr) (nmax, cm21): 3500 and 3475 (NH),
1726 (CvO). MS, m/z (%): 362 (Mþ, 82), 331 (74), 303
(49), 271 (100), 244 (55), 216 (30), 185 (20), 157 (18), 129
(20), 103 (12), 87 (40), 75 (38), 59 (80). Anal. Calcd for
C16H14N2O8 (362.30): C, 53.04; H, 3.89; N, 7.73. Found
(%): C, 53.1; H, 3.9; N, 7.7. 1H NMR: d 3.80, 3.98 and 3.99
(9H, 3s, 3OCH3), 5.21 (2H, br, NH2), 6.86 (1H, s, CH), 7.18
(1H, s, CH), 7.67 (1H, s, CH). 13C NMR: d 52.12, 52.78 and
53.43 (3OCH3), 109.07 and 119.12 (2CH), 120.87 (C),
124.22 (CH), 137.73, 140.68, 144.04, 146.77 and 147.77
(5C), 157.93, 162.93, 165.54 and 167.91 (4CvO).
4.1.2. Methyl 2-oxo-7-[(triphenylphosphoranylidene)-
amino]-2H-chromene-4-carboxylate 5. Yellow crystals,
mp 161–1638C (from ethyl acetate), yield 90%. IR (KBr)
(nmax, cm21): 1700 (CvO), 1591, 1568, 1489, 1346, 1244,
1122. MS, m/z (%): 479 (Mþ, 100), 402 (10), 277 (7), 262
(15), 183 (80), 108 (25), 51 (12). Anal. Calcd for
C29H22NO4P (479.47): C, 72.65; H, 4.62; N, 2.92. Found
(%): C, 72.7; H, 4.6; N, 2.9. 1H NMR: d 3.92 (3H, s, OCH3),
6.45 (1H, s, CH), 6.53 (1H, d, 4JHH¼2.2 Hz, CH), 6.85 (1H,
4.1.7. Methyl 2-oxo-8-[(triphenylphosphoranylidene)-
amino]-2H-pyrano[2,3-c ]pyridine-4-carboxylate
3
4
dd, JHH¼8.9 Hz, JHH¼2.1 Hz, CH), 7.48 (6H, td,
16.
4
3JHH¼7.7 Hz, JPH¼3 Hz, meta CH), 7.56 (3H, td,
Pale red crystals, mp 204–2068C (from hexane–ethyl
acetate 1:2), yield 10%. IR (KBr) (nmax, cm21): 1714
(CvO), 1570, 1452, 1421, 1350, 1115, 1010. MS, m/z (%):
481 (Mþþ1, 49), 393 (40), 277 (75), 262 (70), 199 (20), 183
(100), 152 (28), 108 (45), 77 (50). Anal. Calcd for
C28H21N2O4P (480.46): C, 70.00; H, 4.41; N, 5.83. Found
(%): C, 70.1; H, 4.4; N, 5.8. 1H NMR: d 3.97 (3H, s, OCH3),
7.07 (1H, s, CH), 7.20 (1H, br d, J¼7.5 Hz, CH), 7.45 (6H,
5
3JHH¼7.7 Hz, JPH¼1.4 Hz, para CH), 7.74 (6H, dd,
3
3JHH¼7.6 Hz, JPH¼12.2 Hz, ortho CH), 7.81 (1H, dd,
4
3JHH¼8.9 Hz, JHH¼0.8 Hz, CH). 13C NMR: d 52.78
3
(OCH3), 106.85 (C), 108.66 (d, JPC¼16.9 Hz, CH),
3
111.32 (CH), 122.41 (d, JPC¼21.8 Hz, CH), 126.53 (d,
3
4JPC¼1.8 Hz, CH), 128.98 (d, JPC¼12.3 Hz, Cm), 129.23
1
4
(d, JPC¼100.2 Hz, Cipso), 132.37 (d, JPC¼2.5 Hz, Cp),
2
3
4
132.57 (d, JPC¼9.7 Hz, Co), 143.14 (C), 156.32 (d,
td, JHH¼7.7 Hz, JPH¼2.8 Hz, meta CH), 7.53 (3H, td,
4
5
2JPC¼2.5 Hz, C–N), 157.58 (d, JPC¼1.2 Hz, C–O),
3JHH¼7.7 Hz, JPH¼1.4 Hz, para CH), 7.71 (1H, br d,
161.83 and 165.27 (2CvO). 31P NMR: d 7.54 (Ph3Pþ–N2).
J¼7.5 Hz, CH), 7.90 (6H, dd, 3JHH¼7.5 Hz, 3JPH¼12.2 Hz,

I. Yavari et al. / Tetrahedron 58 (2002) 6895–6899
6899
ortho CH), 7.81 (1H, dd, 3JHH¼8.9 Hz, 4JHH¼0.8 Hz, CH).
13C NMR: d 53.07 (OCH3), 106.90 (CH), 122.05 (d,
3. Melini, L. Adv. Heterocycl. Chem. 1975, 18, 159.
4. Hepworth, J. D. Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford,
1984; Vol. 3, pp 573–883.
3
4JPC¼4.5 Hz, C), 123.65 (CH), 128.42 (d, JPC¼12.2 Hz,
1
Cm), 129.29 (d, JPC¼101.9 Hz, Cipso), 131.84 (d,
2
4JPC¼2.6 Hz, Cp), 133.22 (d, JPC¼9.9 Hz, Co), 142.87
5. Davis, S. G.; Mobbs, B. E.; Goodwin, C. J. J. Chem. Soc.,
Perkin Trans. 1 1987, 2597.
3
(CH), 143.50 (C), 148.25 (d, JPC¼23.5 Hz, C), 154.08 (d,
2JPC¼6.1 Hz, C), 158.45 and 162.52 (2CvO). 31P NMR: d
6. Hepworth, J. D.; Gabbutt, C. D.; Heron, B. M. Comprehensive
Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 5, pp
301–468.
15.77 (Ph3Pþ–N2).
Acknowledgments
7. Geen, G. R.; Evans, J. M.; Vong, A. K. Comprehensive
Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 5, pp
469–500.
This research was supported by the National Research
Council of the Islamic Republic of Iran (NRCI) as a
National Research project under the grant number 989.
8. Yavari, I.; Hekmat-Shoar, R.; Zonouzi, A. Tetrahedron Lett.
1998, 39, 2391.
9. Yavari, I.; Adib, M.; Hojabri, L. Tetrahedron 2001, 57, 5737.
10. Johnson, A. W. Ylides and Imines of Phosphorus; Wiley: New
York, 1993.
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