A. K. Bose et al. / Tetrahedron Letters 47 (2006) 3213–3215
3215
Acknowledgments
OH
OH
O2N
HOOC
We thank Union Mutual Foundation, Merck Company,
and The Camille and Henry Dreyfus Special Grant Pro-
gram in the Chemical Sciences for financial support. For
useful discussions and encouragement we are grateful to
Dr. F. T. Jones, Dr. Malcolm MacCoss, and Dr. Mark
Cardillo. We are indebted to the reviewer for valuable
suggestions.
2
3
4
OH
2
OH
2
HOOC
O2N
NO
NO
1
References and notes
Scheme 1.
1. (a) Loupy, A. Microwave in Organic Synthesis; Wiley-VCH:
Weinheim, 2002; (b) Kingston, H. M.; Haswell, S. J.
Microwave Enhanced Chemistry; American Chemical Soci-
ety Publications: Washington, 1997; (c) Tierney, J. P.;
Lidstrom, P. Microwave Assisted Organic Chemistry; CRC
Press: Boca Raton, 2005; (d) Kappe, C. Oliver; Stadler, A.
Microwaves in Organic and Medicinal Chemistry; C.H.I.P.S.
Books: Weimar, 2005.
The interrelations shown in Scheme 1 indicate the
sequence of steps leading to the dinitro compound. It is
interesting to note that the first step is the ipso decarb-
oxylation with replacement by a nitro group; nitration
of the phenolic ring is therefore the second step.
2. Bose, A. K.; Ganguly, S. N.; Manhas, M. S.; Srirajan, V.;
Bhattacharya, A.; Rumthao, S.; Sharma, A. Tetrahedron
Lett. 2004, 45, 1179.
The ‘Cold Microwave Chemistry’ approach could thus
allow easy determination of the first step in a reaction
involving two or more steps. These are novel aspects
of microwave enhanced reactions that do not appear
to have been reported before.
3. Experimental procedure: Cold microwave chemistry for the
nitration of 4-hydroxycinnamic acid: 4-Hydroxycinnamic
acid (2 g, 12 mmol) and aqueous nitric acid (20 mL, 10%
strength) in a 100 mL Erlenmeyer flask was cooled to
À30 °C with a liquid nitrogen bath. This frozen reaction
mixture was irradiated in an unmodified domestic micro-
wave oven at 300 W power for 30 s. Immediately after
irradiation, 75 mL of ice cold water was added with stirring.
An orange yellow solid that separated was collected by
filtration. The solid was washed with cold water until the
filtrate was acid free and then dried. It was crystallized from
methanol–ethyl acetate mixture to provide the mono-nitro
product 3 (1.8 g, 11 mmol), mp 204–205 °C, yield 90%. An
analytical sample was prepared by repeated crystallization.
In summary, chemical reactions under microwave irra-
diation may be modified by the starting temperature of
the irradiation experiment. For example, microwave
irradiation of identical reaction mixtures at room
temperature or pre-cooled to À30 °C may give different
products. The cold microwave chemistry product
(obtained by microwave irradiation of a pre-cooled
reagent mixture) may identify the first step in a reaction
that involves two or more steps; this could provide
useful information about reaction mechanisms and thus
supplement traditional studies involving reaction
kinetics. These microwave chemistry experiments can
be conducted in inexpensive domestic microwave (800–
1000 W) ovens.
1
IR (KBr): 3280, 1518, 1320, 976, and 825 cmÀ1. H NMR
(CDCl3, d): 7.58 (d, J = 13.7 Hz, 1H); 7.96 (d, J = 13.7 Hz,
1H); 7.42–8.09 (aromatic protons, 4H); 10.65 (s, chelated,
1H). Anal. Calcd for C8H7NO3: C, 58.18; H, 4.24; N, 8.48.
Found: C, 58.31; H, 4.22; N, 8.44.