Facile One-Pot Synthesis of Photochromic Pyrans

Article abstract of DOI:10.1021/ol035599x

(Equation presented) Photochromic pyrans, including [3H]naphtho[2,1-b] pyrans, [2H]naphtho[1,2-b]pyrans, indeno-fused naphtho[1,2-b]pyrans, and heteroannulated pyrans, were synthesized in excellent yields through a facile one-pot procedure by reaction of propargyl alcohol and naphthol or phenol derivatives in the presence of 5 mol% PPTS and 2 equiv of (MeO)₃CH. Symmetrical and nonsymmetrical bispyrans can also be prepared using the protocol.

Full text of DOI:10.1021/ol035599x

ORGANIC
LETTERS
2003
Vol. 5, No. 22
4153-4154
Facile One-Pot Synthesis of
Photochromic Pyrans
Weili Zhao and Erick M. Carreira*
Laboratorium fu¨r Organische Chemie, ETH-Ho¨nggerberg HCI H335,
CH-8093 Zu¨rich, Switzerland
carreira@org.chem.ethz.ch
Received August 25, 2003
ABSTRACT
Photochromic pyrans, including [3H]naphtho[2,1-b]pyrans, [2H]naphtho[1,2-b]pyrans, indeno-fused naphtho[1,2-b]pyrans, and heteroannulated
pyrans, were synthesized in excellent yields through a facile one-pot procedure by reaction of propargyl alcohol and naphthol or phenol
derivatives in the presence of 5 mol % PPTS and 2 equiv of (MeO)3CH. Symmetrical and nonsymmetrical bispyrans can also be prepared using
the protocol.
Diaryl-benzopyrans and naphthopyrans display highly desir-
able photochromic properties1 and have thus been the subject
of intense investigations aimed at developing novel materials
with useful applications in the marketplace. For convenient
access to designed photochromic compounds based on this
structural motif, it is paramount that reliable, general
synthetic methods be readily available. However, the various
synthetic routes for the synthesis of diaryl-benzopyrans and
naphthopyrans are limited with respect to yield and scope.
Herein we report a synthetic method that leads to improved
access to a wide range of pyrans involving acid-catalyzed
reaction of propargyl alcohols and phenols or naphthols in
the presence of (MeO)3CH as a dehydrating agent.
There are three general approaches to diaryl benzopyrans
or naphthopyrans. The first of these, the Kabbe synthesis,
commences with chromanones and necessitates a multistep
sequence of reactions.2 The second method prescribes the
reaction of aryl Grignard with benzocoumarins, followed by
dehydration.3 The third and most expeditious involves the
Claisen rearrangement of propargyl-aryl ethers prepared in
situ from phenol or naphthol and a diaryl propargyl alcohol
under acidic conditions.4-8 In general, these approaches lack
generality and provide the target photochromic compounds
in poor yield contaminated with byproducts. In this respect,
under the conditions of the condensation reaction of diaryl-
propargyl alcohols with phenols or naphthols, the well-known
Meyer-Schuster rearrangement reaction of the starting
propargyl alcohol is competitive.7b,9 Additionally, under these
conditions, the yield of pyran has been shown to be strongly
dependent on the structure of the phenol or naphthol; thus,
for example, in a report on the synthesis of 32 of heterocyclic
(4) (a) Iwai, I.; Ide, J. Chem. Pharm. Bull. 1963, 11, 1042. (b) Momodam,
J.; Hara, T. U.S. Patent 5808100, 1998.
(5) (a) Tanaka, K.; Aoki, H.; Hosomi, H.; Ohba, S. Org. Lett. 2000, 2,
2133. (b) Moustrou, C.; Rebiere, N.; Samat, A.; Guglielmetti, R.; Yassar,
A. E.; Dubest, R.; Aubard, J. HelV. Chim. Acta 1998, 81, 1293. (c) Heller,
H. G.; Levell, J. R. U.S. Patent 5955520, 1999.
(6) (a) Coelho, P. J.; Carvalho, L. M.; Abrantes, S.; Oliveira-Campos,
A. M. F.; Dubest, R.; Samat, A.; Guglielmetti, R. Tetrahedron 2002, 58,
9505. (b) Coelho, P. J.; Carvalho, L. M.; Rodrigues, S.; Oliveira-Campos,
A. M. F.; Dubest, R.; Aubard, J.; Samat, A.; Guglielmetti, R. Tetrahedron
2002, 58, 925. (c) Oliveira, M. M.; Carvalho, L. M.; Moustrou, C.; Samat,
A.; Guglielmetti, R.; Oliveira-Campos, A. M. F. HelV. Chim. Acta 2001,
84, 1163. (d) Coelho, P. J.; Carvalho, L. M.; Silva, J.; Oliveira-Campos,
A. M. F.; Samat, A.; Guglielmetti, R. HelV. Chim. Acta 2001, 84, 117. (e)
Martin, C. I.; Coelho, P. J.; Carvalho, L. M.; Oliveira-Campos, A. M. F.;
Samat, A.; Guglielmetti, R. HelV. Chim. Acta 2003, 86, 570. (f) Frigoli,
M.; Moustrou, C.; Samat, A.; Guglielmetti, R. WO 01/04233, 2001.
(7) (a) Rickwood, M.; Marsden, S. D.; Hepworth, J. D.; Gabbutt, C. D.
U.S. Patent 5520853, 1996. (b) Harie, G.; Samat, A.; Guglielmetti, R.
Tetrahedron Lett. 1997, 38, 3075. (c) Von Gemert, B. U. S. Patent 5645767,
1997. (d) Knowles, D. B.; Von Gemert, B. U.S. Patent 5464567, 1995.
(8) (a) Pozzo, J. L.; Samat, A.; Guglielmetti, R.; Lokshin, V.; Minkin,
V. Can. J. Chem. 1996, 74, 1649. (b) Kumar, A. U.S. Patent 5411679,
1995.
(1) Gemert B. V. Benzo and Naphthopyrans (Chromenes). In Organic
Photochromic and Thermochromic Compounds; Crano, J. C., Guglielmetti,
R., Eds.; Plenum Press: New York, 1999; Vol. 1, Chapter 3.
(2) (a) Gabbutt, C. D.; Hartley, D. J.; Hepworth, J. D.; Heron, B. M.;
Kanjia, M.; Rahman, M. Tetrahedron 1994, 50, 2507. (b) Kabbe, H.;
Widdig, A. Angew. Chem., Int. Ed. Engl. 1982, 21, 247.
(3) Cottam, J.; Livingstone, R. J. Chem. Soc. 1965, 6646.
(9) Swaninathan, S.; Narayanan, K. V. Chem. ReV. 1971, 71, 429.
10.1021/ol035599x CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/04/2003

Scheme 1
Scheme 2
[3H]-naphtho-[2,1-b]pyran compounds, the yields ranged
from 4 to 40%.4b In recent reports, the use of PPTS as a
catalyst for preparation of sensitive benzopyrans and naph-
thopyrans is documented,5b,6 leading to yields ranging from
9 to 78%.
Our initial studies in this area focused on the use of PPTS
as a catalyst (5%) in the reaction of 1,1-diphenyl-2-propyn-
1-ol and 2-naphthol as model substrates. Under the standard
conditions, the reaction was extremely slow, affording 2%
adduct after 1 week. Interestingly, we observed a dramatic
improvement in the course of the reaction when (MeO)3CH
was used as an additive. Under optimal conditions, treatment
of diarylpropargyl alcohol (1.05-1.1 equiv) and aromatic
phenols or naphthols (1 equiv) in ClCH2CH2Cl with 2 equiv
of (MeO)3CH and 5 mol % PPTS furnished the desired
product in high yields.
As shown in Scheme 2, the experimental protocol is widely
applicable, including both [3H]naphtho[2,1-b]pyrans and
[2H]naphtho[1,2-b]pyrans and indeno-fused naphtho[1,2-b]-
pyrans, as well as heteroannulated pyrans. For comparison
purposes, the yields reported in the literature are included
in parentheses. The yields obtained under the conditions we
describe herein offer considerable improvement over those
previously reported.
The unique advantages of the method can be appreciated
in the preparation of bisnaphthopyran derivatives 7, which
have otherwise been previously obtained in only low
yields.5a,c Under the conditions reported herein, an excellent
yield of 7 was obtained, and analytically pure bisnaphtho-
pyran could be obtained by simple filtration of the cold reac-
tion mixture. Additionally, unsymmetrical bisnaphthopyrans
can be prepared. Thus, in the reaction of the mononaphtho-
pyran 1010 with thienyl propargyl alcohols, 11 and 12 can
be obtained in 87 and 97% yields, respectively.
the presence of 5 mol % PPTS and 2 equiv of (MeO)3CH.
The method permits convenient access to a wide range of
photochromic pyran systems and, importantly, should enable
access of novel, interesting materials that have only been
previously accessed in poor yields with some difficulties.
In conclusion, we have developed a facile one-pot syn-
thesis of photochromic pyran and bispyran compounds by
reaction of propargyl alcohols and naphthol derivatives in
Acknowledgment. We thank the ETH for an internal
research grant (TH-Gesuch).
Supporting Information Available: Characterization
data for compounds 3-12. This material is available free of
charge via the Internet at http://pubs.acs.org.
(10) Compound 10 was prepared in 50% yield by adding slowly a
solution of 1,1-diphenyl-2-propyn-1-ol (1.0 mmol) in 1,2-dichloroethane
(4 mL) into a boiling suspension of 2,6-dihydroxynaphthalene (1.1 mmol),
PPTS (0.05 mmol), and trimethyl orthoformate (2.0 mmol) in 1,2-
dichloroethane (5 mL), followed by 2 h reflux.
OL035599X
4154
Org. Lett., Vol. 5, No. 22, 2003