Synthesis of a highly reactive heterocyclic reactant and its unusual photochemistry; mechanistic and exploratory organic photochemistry

Article abstract of DOI:10.1021/ol048438h

(Chemical Equation Presented) A unique new set of reactions has been observed in heterocyclic photochemistry. 2-Methyl-4,4-diphenyl-3,4- dihydropyrimidin-1(2H)-one has been synthesized and its photochemistry investigated. This compound has been found to l

Full text of DOI:10.1021/ol048438h

ORGANIC
LETTERS
2004
Vol. 6, No. 21
3779-3780
Synthesis of a Highly Reactive
Heterocyclic Reactant and Its Unusual
Photochemistry; Mechanistic and
Exploratory Organic Photochemistry1,2
Howard E. Zimmerman* and Alexei Pushechnikov
Department of Chemistry, UniVersity of Wisconsin-Madison,
Madison, Wisconsin 53706
zimmerman@chem.wisc.edu
Received August 6, 2004
ABSTRACT
A unique new set of reactions has been observed in heterocyclic photochemistry. 2-Methyl-4,4-diphenyl-3,4-dihydropyrimidin-1(2H)-one has
been synthesized and its photochemistry investigated. This compound has been found to lead to a rearranged, dimeric product arising from
a unique bond-scission process.
We recently began a study of heterocyclic analogues of
carbocyclic photochemical reactants. The aim was to deter-
mine whether parallel reactivity was observed, and also the
use of heterocycles promised to provide better substrates for
host-guest chemistry as a consequence of enhanced hydro-
gen bonding.
of the hydroxy heterocycle 3, which then undergoes Michael
addition to highly reactive aza-enone 1.
Hence, our study of the photochemistry of aza-enone 1
was carried out with thorough purging with nitrogen in a
semimicro immersion apparatus and with a copper sulfate
filter. This photolysis (benzene, 10 h) led to a single
The first heterocycle selected was the dihydropyrimidin-
one 1. The precursor sulfone 2 was obtained as outlined in
Scheme 1. Treatment with sodium hydride then afforded the
desired nitrogen enone analogue 1.
Scheme 1. Synthesis of Dihydropyrimidin-one 1
However, this compound proved to be remarkably reactive
toward even weak nucleophiles. For example, with water,
or exposure to the atmosphere, it rapidly formed hydroxy
compound 3 and, additionally, dimeric ether 5.3 This is
depicted in eq 1. The evidence is that there is initial formation
(1) This is publication number 273 of our General Series.
(2) For publication number 272, see: Zimmerman, H. E. The Quantitative
Cavity Concept in Crystal Lattice Organic Photochemistry; Mechanistic
and Exploratory Organic Photochemistry. In CRC Handbook of Photo-
chemistry and Photobiology; Horspool, W., Ed.; CRC, Inc.: Boca Raton,
FL, 2004, Chapter 75.
10.1021/ol048438h CCC: $27.50
© 2004 American Chemical Society
Published on Web 09/17/2004

Scheme 2. Photochemical Mechanism
photoproduct whose structure was established by NMR and
X-ray analyses to be that of compound 6. Note eq 2.
Consideration of the photoproduct structure, together with
the known electrophilic reactivity of aza-enone 1, suggested
that this product arises from two fragments: reactant 1 and
zwitterion 7. Hence, the photochemistry must initially lead
to this zwitterion. Further insight came from unpublished
heterocyclic photochemistry in our hands,4 which suggests
a general tendency for fission of bond 4-5 in heterocycles
of this type.
A further point is that this type of photochemical reactivity
arises as a consequence of stabilization of the valence at C-5
by the adjacent nitrogen lone pair. This has analogy where
C-5 is substituted by other stabilizing substituents.6
Acknowledgment. Support of this research by the
National Science Foundation is gratefully acknowledged with
special appreciation for its support of basic research. Ad-
ditionally, we acknowledge initial efforts by Dr. Vladimir
Tyurin. Finally, we dedicate this paper to Prof. Nikolai
Zefirov on the occasion of his 70th birthday.
Supporting Information Available: Experimental de-
tails, X-ray data, and computational details. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL048438H
The mechanism for formation of 7 is thus suggested in
Scheme 2. The reaction is characteristic of a singlet process.4
Thus, species 7z and 7d are both singlets. However, the
reaction begins on the singlet (i.e., S1) hypersurface. Radia-
tionless decay to S0 seems likely to occur via a conical
intersection or avoided crossing at this point, and this is being
explored computationally.
At this point, our computations5 utilizing CASSCF and
natural orbital analysis suggest that S1 species 7d is best
described as a singlet diradical, while 7z is an S0 zwitterion.
(5) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;
Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.
D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.;
Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick,
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.;
Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi,
I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M.
W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.9; Gaussian,
Inc.: Pittsburgh, PA, 1998.
(6) (a) Zimmerman, H. E.; Solomon, R. D. J. Am. Chem. Soc. 1986,
108, 6276-6289. (b) Note also ref 7.
(7) Canovas, A.; Fonrodona, J.; Bonet, J.-J.; Brianso, M. C.; Brianso, J.
L. HelV. Chim. Acta 1980, 63, 2380-2389.
(3) Compounds 3 and 5 were characterized by NMR and high-resolution
MS. The sulfone 2 was characterized by NMR and elemental analysis.
(4) Studies with Dr. Oleg Mitkin to be published.
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Org. Lett., Vol. 6, No. 21, 2004