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     Microwave-Assisted Reduction of Carbonyl Compounds in Solid State
               Using Sodium Borohydride Supported on Alumina

                   Rajender S. Varma and Rajesh K. Saini

          Tetrahedron Letters, Vol 38, No 25, pp. 4337-4338 (1997)


        Abstract: A manipulatively simple and rapid method for the
        reduction of carbonyl compounds is described that is conducted
        under solventless 'dry' conditions using NaBH4-Alumina and
        microwave irradiation.
 
	Heterogeneous reactions that are facilitated by supported reagents 
on various solid inorganic surfaces have received attention in recent 
years [1]. The advantage of these methods over conventional homogeneous 
reactions is that they provide greater selectivity, enhanced reaction 
rates, cleaner products and manipulative simplicity. Relatively inexpensive 
sodium borohydride, NaBH4, has been extensively used as a reducing agent in 
view of its compatibility with protic solvents and safe nature [2]. NaBH4
impregnated on neutral alumina reduces a wide variety of carbonyl compounds
to the corresponding hydroxy derivatives in solution phase [3]. The solid
state reduction of ketones has also been achieved by mixing with sodium
borohydride and storing the mixture in a dry box for five days [4]. The
major disadvantage in the heterogeneous reaction with NaBH4 is that solvent
reduces the reaction rate while in the solid state reactions time period is
too long (5 days) for it to be of any practical utility. Also, the large
excess of the hydride reagent requirement (tenfold) in the later case is a
serious limitation [4]. Consequently, there is interest in the use of NaBH4
'doped' supports that are efficient and offer operational advantages [5].

	In continuation of our program to develop environmentally benign 
solventless methods using solid supports and microwave activation [6], we
now wish to report a facile reduction of aldehydes and ketones by alumina
supported NaBH4 [7] that proceeds in the solid state using microwaves. The
process in its entirety involves a simple mixing of carbonyl compound with
(10%) NaBH4-Alumina in solid state and irradiating the mixture in an
unmodified household microwave oven for the time specified in the table.
The extraction of the product in dichloromethane affords the corresponding
alcohol in high yields. The reduction of aldehydes is completed within
seconds on admixing with NaBH4 doped alumina (10%) at room temperature but
p-nitrobenzaldehyde requires gentle warming for completion of the reaction
(Entry 3). The useful chemoselective feature of the reaction is apparent
from the reduction of trans-cinnamaldehyde (cinnamaldehyde/NaBH4-alumina,
1:1 mol equiv.); olefinic moiety remains intact and only the aldehyde
functionality is reduced in a facile reaction that takes place at room
temperature. In the case of chalcone (chalcone/NaBH4-alumina, 1:8 mol
equiv.), however, two products are formed in the ratio of 60:40 as shown in
equation below. The additional examples are summarized in the table.

                     NaBH4-Al2O3
trans-PhCH=CH-C-Ph  =============>  trans-Ph-CH=C-CH-Ph + Ph-CH2-CH2-CH-Ph
              \\          MW                      |                  |
               O                                  OH                 OH
                                          60%                40%

	The reduction of acetophenone is representative of the general 
procedure employed: Freshly prepared NaBH4-alumina (7) (1.13 g, 3.0 mmol of 
NaBH4) is thoroughly mixed with neat acetophenone (0.36 g, 3.0 mmol) in a 
test tube and placed in an alumina bath inside the microwave oven and 
irradiated (30 sec) (8). Upon completion of the reaction, monitored on TLC
(hexane:EtOAc, 8:2, v/v), the product is extracted into methylene chloride
(2x15 mL). Removal of solvent under reduced pressure essentially provides
pure sec-phenethyl alcohol in 87% yield. No side product formation is
observed in any of the reactions investigated and no reaction takes place
in the absence of alumina. Further, the recovered alumina can be recycled
by mixing with fresh borohydrlde and reused for subsequent reductions
without any loss in activity. The air used for cooling the magnetron
ventilates the microwave cavity thus preventing hydrogen from reaching
explosive concentrations. Although we did not encounter any accident during
these studies, we recommend extreme caution for reactions on larger scale.

                  ___    O                         ___   OH
                 /   \  //     NaBH4-Al2O3        /   \  |
              R-<  O  >-C-R1  =============>   R-<  O  >-C-R1
                 \___/              MW            \___/

Table: Solid state reduction of carbonyl compounds using NaBH4-Al2O3
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                                    Carbonyl cpd      Time        Percent
Entry   R       R1                 to NaBH4 ratio    sec (a)     Yield (b)
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1       CH3     H                        1:1           RT           90
2       Cl      H                        1:1           RT           93
3       NO2     H                        1:2           40           87
4       H       CH3                      1:1           30           87
5       CH3     CH3                      1:1           90           90
6       H       C6H5                     1:5           120(c)       92
7       H       CH(OH)C6H5               1:8           180          79
8       OCH3    CH(OH)C6H4-p-OCH3        1:5           120          62
             C
9       //\ / \                          1:7           120          85
       |  ||   |
        \\/ \_/
		 
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(a)     RT refers to reactions that are completed on simple mixing of the
        substrates with NaBH4-Al2O3 at room temperature.
(b)     Unoptimized yields of isolated products that exhibited physical and
        spectral properties in accord with the assigned structures.
(c)     In an oil bath at 130°C (temperature attained in MW oven. 2 min),
        the reaction stopped at 40% conversion even after 4 h.

	In conclusion, we have developed a facile and practical method for the
solid state reduction of carbonyl compounds to alcohols using a solventless
system, NaBH4-Al2O3, that is accelerated by microwave irradiation.


					REFERENCES AND NOTES

1.      (a) Balogh, M.; Laszlo, P. Organic Chemistry Using Clays;
            Springer-Verlag: Berlin, 1993.
        (b) Laszlo, P. Preparative Chemistry using Supported Reagents,
            Academic Press, San Diego, California 1987, specially for
            reactions in 'dry' media see p 387.
        (c) McKillop, A.; Young, D.W. Synthesis, 1979, 401, 481.
        (d) Posner, G.H. Angew. Chem. 1978, 90, 527; Angew. Chem. Int.
            Ed. Engl. 1978, 17, 487.
        (e) Kabalka, G.W.; Wadgacnkar, P.P.; Chatla, N. Synth. Commun.
            1990, 20, 293.

2.      Banfi, E.N.; Riva, R. In Reagents for Organic Synthesis, Ed. L.
        Paquette, Wiley, New York, 1995, Vol. 7, pp. 4522-4528.

3.      Santaniello, E.; Ponti, F.; Manzocchi, A. Synthesis 1978, 891.

4.      Toda, F.; Kiyoshige, K.; Yagi, M. Angew. Chem. Int. Ed Engl.
        1989, 28, 320.

5.      Caycho, J.R.; Tellado, F.G.; Armas, P.D.; Tellado, J.J.M.
        Tetrahedron Lett. 1997,38, 277.

6.      (a) Varma, R.S.; Saini, R.K. Tetrahedron Lett. 1997, 38, in press;
        (b) Varma, R.S.; Dahiya, R. Tetrahedron Lett. 1997, 38, 2043;
        (c) Varma, R.S.; Dahiya, R.; Kumar, S. Tetrahedron Lett 1997,
            38, 2039;
        (d) Varma, R.S.; Chatterjee, A.K.; Varma, M. Tetrahedron Lett.
            1993, 34, 3207;
        (e) Varma, R.S.; Chatterjee, A.K.; Varma, M. Tetrahedron Lett.
            1993, 34, 4603;
        (f) Varma, R.S.; Varma, M.; Chatterjee, A.K. J. Chem. Soc.
            Perkin. Trans. 1 1993, 999;
        (g) Varma, R.S.; Lamoure, J.B.; Varma, M. Tetrahedron Lett. 1993,
            34, 3029.

7.      (10%) NaBH4-Alumina, is prepared by thoroughly mixing NaBH4 (5.0 g)
        with neutral alumina (45.0 g) in solid state using a pestle and
        mortar; admixing three components, carbonyl substrate, NaBH4 and
        alumina together is equally efficient.

8.      For a critical evaluation of activation process by microwaves see:
        Raner, K.D.; Strauss, C.R.; Vyskoc, F.; Mokbel, L. J. Org. Chem.
        1993, 58, 950. The temperature of the alumina bath (heat sink)
        inside a Sears Kenmore microwave oven (operating at 2450 MHz)
        equipped with a turntable at full power (900 Watts) found to be
        ~70°C after 30 seconds of irradiation.

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