One-pot synthesis of novel photochromic oxazine compounds

Article abstract of DOI:10.1021/ol2019482

A one-pot domino synthesis of photochromic 2,2-diarylphenanthro-(9,10)-[2H] -[1,4]-oxazines in excellent yield is described starting with acrylic acid derivatives. The reaction mechanism was studied by ReactIR and UV-vis. The cascade sequence of the react

Full text of DOI:10.1021/ol2019482

ORGANIC
LETTERS
2011
Vol. 13, No. 19
5084–5087
One-Pot Synthesis of Novel Photochromic
Oxazine Compounds
Weili Zhao*,†,‡ and Erick M. Carreira*,§
Key Laboratory for Special Functional Materials of the Ministry of Education,
Henan University, Kaifeng, 475004, China, School of Pharmacy, Fudan University,
Shanghai, 201203, China, and Laboratorium fu€r Organische Chemie, ETH-Zu€rich,
CH-8093, Zu€rich, Switzerland
zhaow@henu.edu.cn; carreira@org.chem.ethz.ch
Received July 19, 2011
ABSTRACT
A one-pot domino synthesis of photochromic 2,2-diarylphenanthro-(9,10)-[2H]-[1,4]-oxazines in excellent yield is described starting with acrylic
acid derivatives. The reaction mechanism was studied by ReactIR and UVÀvis. The cascade sequence of the reactions involves five
transformations, namely, acyl azide formation, Curtius rearrangement, arsonium ylide formation, aza-Wittig, and final cyclization to the title
compounds.
Photochromic molecules which undergo reversible color
change upon absorption of light (i.e., sunlight) have led over
the last number of decades to intense investigations in a wide
range of potential applications such as optical switches,
memory storage, imaging devices, as well as ophthalmic
lenses.1 Currently, the largest commercial use of organic
photochromic dyes is in the ophthalmic lens industry in the
design and synthesis of photochromic compounds with
improved properties; these include spiropyrans,2 diaryl
naphthopyrans,3 and spirooxazines.4 It is generally accepted
that diaryl naphthopyrans are more fatigue-resistant than
spiroindolinonaphthopyrans.3,5 Spiroindolinophenanthro-
xazines were reported to have extraordinary stability against
thermal and photochemical degradation.6 In contrast to the
well studied spirooxazine, non-spirooxazine photochormic
compounds have been neglected.7,8 2,2-Diaryl naphtho-
[2H]-[1,4]-oxazine compounds were claimed to have better
fatigue resistance than the structurally closely related
naphthopyrans.7a We have been interested in novel 2,2-
† Henan University.
‡ Fudan University.
§ ETH-Z€urich.
(4) Minkin, V. I. Chem. Rev. 2004, 104, 2751–2776.
(5) Malatesta, V. Photodegradation of Organic Photochromes. In
Organic Photochromic and Thermochromic Compounds; Crano, J. C.,
Guglielmetti, R., Eds.; Plenum Press: New York, 1999; Chapter 2, Vol. 2,
pp 65À166.
(1) (a) Russew, M. M.; Hecht, S. Adv. Mater. 2010, 22, 3282–3287.
(b) Feringa, B. L. Molecular Switches; Wiley-VCH: Weinheim, Germany,
2001. (c) D€urr, H.; Bouas-laurent, H. Photochromism: Molecules and
Systems; Elsevier: Amsterdam, 2003. (d) Crano, J. C.; Guglielmetti, R.
Organic Photochromic and Thermochromic Compounds; Plenum Press:
New York, 1999. (e) McArdle, C. B. Applied Photochromic Polymer
Systems; Chapman and Hall: New York, 1992. (f) Irie, M. Photo-Reactive
Materials for Ultrahigh Density Optical Memory; Elsevier: Amsterdam,
1994. (g) Willner, I. Acc. Chem. Res. 1997, 30, 347–356. (h) Irie, M., Ed.
Special Issue: Photochromism: Memories and Switches. Chem. Rev.
2000, 100, 1683À1890.
(6) Shelepin, N. E.; Metelistsa, A. V.; Vdovenko, A. V.; Palchkov,
V. A.; Knyazhansky, M. I.; Adamova, S. I.; Panina, A. P.; Minkin, V. I.
Mol. Cryst. Liq. Cryst. 1997, 298, 175–180.
(7) (a) Melzig, M.; Zinner, H. U.S. Patent 5,801,243, 1998. (b)
Tennant, G.; Rickwood, M.; Rowe, D.; Pritchard, M. GB 2,338,955, 2000.
(8) Grummt, U. W.; Reichenbacher, M.; Paetzold, R. Tetrahedron
Lett. 1981, 22, 3945–3948.
(9) (a) Zhao, W.; Carreira, E. M. WO 03/042,195, 2003. (b) Zhao, W.;
Carreira, E. M. WO 03/057,679, 2003. For our previous publications on
photochromic compounds, see: (c) Zhao, W.; Carreira, E. M. J. Am. Chem.
Soc. 2002, 124, 1582–1583. (d) Zhao, W.; Carreira, E. M. Chem.;Eur. J.
2007, 13, 2671–2685. (e) Zhao, W.; Carreira, E. M. Org. Lett. 2006, 8,
99–102. (f) Zhao, W.; Carreira, E. M. Org. Lett. 2005, 7, 1609–1612.
(g) Zhao, W.; Carreira, E. M. Org. Lett. 2003, 5, 4153–4154.
(2) (a) Crano, J. C.; Kwak, W. S.; Welch, C. N. In Applied Photo-
chromic Polymer System; McArdle, C. B., Ed.; Chapman and Hall: New
York, 1992; pp 31;79. (b) Mayer, G.; Heckel, A. Angew. Chem., Int. Ed.
2006, 45, 4900–4921.
(3) Gemert, B. V. Benzo and Naphthopyrans (Chromenes). In
Organic Photochromic and Thermochromic Compounds; Crano, J. C.,
Guglielmetti, R., Eds.; Plenum Press: New York, 1999; pp 111À140.
r
10.1021/ol2019482
Published on Web 08/29/2011
2011 American Chemical Society

disubstituted phenanthroxazine (1) with the expectation that
novel oxazines may derive benefits from both spiroindoli-
nophenanthroxazines and 2,2-diaryl-[2H]-naphtho-[1,4]-
oxazine.9 However, the known 2,2-disubstituted [2H]-[1,4]-
oxazine compounds and the methodologies for their
preparation are extremely limited. Hereinwereportaneffi-
cient one-pot synthesis of 2,2-disubstituted phenanthro-(9,10)-
[2H]-[1,4]-oxazine 1.
be prepared directly by Yamada’s protocol from acrylic
acids and diphenylphosphoryl azide (DPPA) in a non-
polar solvent in the presence of a base such as triethy-
lamine or 1,8-bis(dimethylamino)naphthalene (proton
sponge);13,14 however, low yields of isocyanates were
obtained following heating.13 It is known that the
vinylisocyanates polymerize easily even at room tem-
perature.12,15 Additionally, isocyanates are generally
extremely sensitive to acid (polymerization)15 and to
Et3N under heating (isomerization to isocyanurates).13
In the reported attempts at preparation of styryl iso-
cyanate with modified Yamada conditions, no desired
product could be isolated.13
Despite difficulties outlined above, Frøyen’s method is
distinct in that it provides a method for the introduction of
an imine onto a quinone which is sensitive to strongly basic
and nucleophilic conditions.10 An iminoarsenane is believed
to be the key intermediate, which was observed to have low
reactivity toward isocyanates but high reactivity toward
ketones.10 In line with our interest in photoactive com-
pounds, we have explored the development of mild, efficient
methods for the synthesis of oxazines by taking advantage of
the iminoarsenane intermediate. It is known that the sensi-
tivity of iminoarsenanes toward moisture and electrophiles is
attenuated by the presence of electron-withdrawing groups
attached to the nitrogen atom. We speculated that styryl-
conjugated iminoarsenane may provide enough reactivity
toward quinones and decrease sensitivity to moisture, thus
leading to reaction conditions potentially compatible with
isocyanates prepared in situ by Yamada’s protocol. As
discussed below, we have reduced these hypotheses to reality
in the form of a convenient, one-pot procedure to synthesize
photochromic 2,2-diarylphenanthro-(9,10)-[2H]-[1,4]-oxa-
zine (Scheme 2).
The reported method for preparation of 2,2-[bis(p-
dimethylamino)phenyl]phenanthro-(9,10)-[2H]-[1,4]-ox-
azine is limited to the use of functionalized, activated ethyl
amines to undergo reaction with phenanthrene-(9,10)-dione
monooxime.8 R-Halo or hydroxy aromatic acetaldehyde
reacting with o-aminohydroxyaromatic compounds was
also reported to generate 2,2-disubstituted [2H]-[1,4]-
naphthoxazine.7 The yield has been reported to be modest,
and the product is difficult to purify, based on our experi-
ence. 2,2-Disubstituted phenanthro-(9,10)-[2H]-[1,4]-oxa-
zines were previously prepared from isocyanates in
relatively low yields (Scheme 1).10 For example, 2,2-di-
methyl phenanthro-(9,10)-[2H]-[1,4]-oxazine and 2-phenyl
phenanthro-(9,10)-[2H]-[1,4]-oxazine were reported to be
isolated in yields of 38 and 40%, respectively.10
Scheme 1. Previously Reported Synthetic Method for the Pre-
paration of 2-Substituted [2H]-[1,4]-Oxazine10
Scheme 2. One-Pot Synthesis of 2,2-Substituted
Phenanthro-(9,10)-[2H]-[1,4]-oxazine (1)a
The method of Frøyen describes the use of alkenyl
isocyanates;10 however, the fact that these are not readily
available sets a limit to the approach.11 There are various
problems associated with the preparation and isolation of
vinyl isocyanates as well as their precursors, namely,
acryloyl azides. Preparation of acryloyl azides from the
corresponding hydrazides and nitrous acid is frequently
hampered due to competitive cyclization of the unsatu-
rated hydrazides.12 To generate acryloyl azides from vinyl
acid chlorides and sodium azide, the acid chlorides must be
carefully purified to avoid the generation of very explosive
hydrazoic acid. Such reactions may not be entirely reliable
and may be difficult to control. Acryloyl azides could also
a Regents and conditions: DPPA (1.2 equiv), Et3N (5.0 equiv),
triphenylarsine oxide (0.05 equiv), 9,10-phenanthrenequinone (0.7À
0.8 equiv), toluene, 60 °C, over 3 h. The yield reported was based on
9,10-phenanthrenequinone, and the reaction temperature was 80 °C for
compound 1h.
(13) Ninomiya, K.; Shioiri, T.; Yamada, S. Tetrahedron 1974, 30,
2151–2157.
(14) Gilman, J. W.; Otonari, Y. A. Synth. Commun. 1993, 23, 335–
341. The low yield of isocyanates was believed to be due to equilibrium
of phosphoric acid diphenyl ester and triethylammonium phosphate
salt.
(10) Frøyen, P. Phosphorus, Sulfur, Silicon Relat. Elem. 1993, 81, 37–
48.
(11) Smith, P. A. S. Org. React. 1946, 3, 337–449.
(12) Coffman, D. D. U.S. Patent 2,334,476, 1943.
(15) Jones, G. D.; Zomlefer, J.; Hawkins, K. J. Org. Chem. 1944, 9,
500–512.
Org. Lett., Vol. 13, No. 19, 2011
5085

Our procedure commences with 3,3-diaryl acrylic acids
2, which are easily obtained by HornerÀWadsworthÀ
Emmons reaction of aldehydes followed by saponification
of the isolated esters. We have developed a one-pot reac-
tion for the conversion of the acrylic acids to vinyl iso-
cyanates. In the experiment, diphenylphosphoryl azide
(DPPA) was used as an azide source and a catalytic
amount of triphenylarsine oxide (5 mol %) was gener-
ally required to generate aza-ylide. The optimum ratio
was found to be acrylic acid/DPPA/TEA/quinone/
Ph3AsO = 1:1.2:5:0.7:0.05. At least 1 equiv of triethy-
lamine (Et3N) was required; the use of excess Et3N was
found to be beneficial in the overall formation of
oxazine. The best solvent for the reaction was identified
as toluene or benzene. Excellent yields of phenanthroxa-
zine were obtained for diaryl-substituted species, and
the yield is essentially unchanged within the reaction
temperature range from 60 to 100 °C for 2,2-diaryl-
substituted oxazines. The best yield for 2-cyclopropyl-2-
phenylphenanthro-(9,10)-[2H]-[1,4]-oxazine (1g) was
80% when the reaction was performed at 60 °C. How-
ever, 2-methyl-2-phenylphenanthro-(9,10)-[2H]-[1,4]-
oxazine (1h) was obtained in lower yield (39%) when the
reaction was performed at 60 °C. The yield was im-
proved to 62% when the reaction was conducted at
80À100 °C. Under reflux conditions, 54% yield of 1h
was isolated.
to monitor the formation of 1a (see Supporting Informa-
tion for details). The results are shown in Figure 1.
The consumption of DPPA and formation of acyl azide
intermediate can be clearly observed by in situ ReactIR
spectroscopy, and the generation of CO2 is also captured.
The formation of the iminoquinone intermediate and the
generation of compound 1a could be observed by UVÀvis.
On the basis of our observation, we believed the reaction
involves five transformations shown in Scheme 3.
The fast reaction of DPPA and acid in the presence of
base leads to an acyl azide. The acyl azide undergoes
Curtius rearrangement to form an isocyanate. This iso-
cyanate is trapped by Ph3AsO to form the corresponding
arsonium ylide, which undergoes the StaudingerÀMeyerÀ
Hauser (aza-Wittig) reaction with 9,10-phenanthrenequi-
none to generate a quinone imine intermediate that then
cyclizes to the targeted oxazines (1).
Scheme 3. Mechanism of Formation of Oxazine 1
We believe the success of the one-pot reaction is due to a
sequence of efficient transformations in a domino fashion.
Excess triethylamine ensures fast formation of acryloyl
azide. The unstable vinyl isocyanate generated by Curtius
rearrangement is rapidly trapped by triphenylarsine oxide
to generate iminoarsenane, which is in turn stabilized by
virtue of the styryl substitution and consequently has low
sensitivity to moisture. The arsonium ylide has low reac-
tivity toward isocyanates (several orders less reactive than
its phosphonium analogue) and high reactivity toward
ketones (more reactive than the corresponding phospho-
nium analogue).10 It is noteworthy that reaction com-
mences with an acid, and the arsonium ylide formed and
reacted uneventfully in the presence of a large excess of
phosphoric acid diphenyl ester byproduct.
The current one-pot strategy provides a number of
advantages. It provides much higher yield and avoids use
of unstable vinyl isocyanate generated from acrylic acid.
The one-pot method is sensitive neither to moisture nor to
air. The solvent may be employed directly from commer-
cially available sources without further purification. The
one-pot method we developed is also not sensitive to the
order of addition of reagents, and the product is amenable
to convenient purification procedures. Finally, it should
Figure 1. Reaction that results from monitoring the formation
of 2,2-diphenylphenanthro-(9,10)-[2H]-[1,4]-oxazine in toluene:
(a) in situ ReactIR spectra; (b) UVÀvis spectra.
The success of the method piqued our interest in the
reaction mechanism. We employed in situ ReactIR spec-
troscopic techniques and UVÀvis spectrometric methods
5086
Org. Lett., Vol. 13, No. 19, 2011

also be noted that all experimental attempts involving
separate steps were significantly inferior to the one-pot
procedure described herein and led to product formation
in lower yield.
(366 nm) light, the colorless solution of 1f turned blue-
gray, which has a very broad of absorption and relatively
fast fading (t1/2 = 31.5 s in hexane, 16.0 s in dioxane, and
4.9 s in acetonitrile). This is very unusual for photochromic
oxazine compounds which cover the entire visible region.
Further detailed study on the photochromism of these
compounds is currently under investigation and will be
reported in due course.
In conclusion, we have developed a one-pot methodology
for efficient synthesis of novel 2,2-diarylphenanthro-(9,10)-
[2H]-[1,4]-oxazine compounds using triphenylarsine oxide
catalyzed domino reactions starting from an acrylic acid.
The one-pot synthesis procedure is marked by high effi-
ciency and high yield, involving five reagents and accom-
panying transformations.
Acknowledgment. We thank the National Natural
Science Foundation of China (20872026), the Hi-Tech
Research and Development Program of China (863
Plan, 2009AA02Z308), Shanghai Pujiang Talent Plan
Project (09PJ01176), and Sino Swiss Science and Tech-
nology Cooperation (SSSTC, EG 30-032010) for finan-
cial support.
Figure 2. Fading of the colored form of 2-(p-methoxyphenyl)-
2-(p-piperidinophenyl)-phenanthro-(9,10)-[2H]-[1,4]-oxazine in
hexane with 6.57 s/scan.
All of the synthesized oxazine compounds are photo-
chromic, displaying rather interesting features. The co-
lored forms of the 2,2-diarylphenanthro-(9,10)-[2H]-[1,4]-
oxazine compoundsexhibittwo or three absorption bands.
For example, the colored forms of 2-(p-methoxyphenyl)-
2-(p-piperidinophenyl)phenanthro-(9,10)-[2H]-[1,4]-ox-
azine 1f are shown in Figure 2. Upon irradiation with UV
Supporting Information Available. Characterization
data for oxazines as well as the detailed reaction mechan-
istic studies using ReactIR and UVÀvis spectrometers.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Org. Lett., Vol. 13, No. 19, 2011
5087