Microwave Enhanced Deuteriations in the Solid State using Alumina Doped Sodium Borodeuteride

Article abstract of DOI:10.1039/a906977a

A number of deuterated alcohols are rapidly (ca. 1 min) synthesized through the microwave enhanced solid state reduction of the corresponding aldehydes and ketones using alumina doped sodium borodeuteride (NaBD4).

Full text of DOI:10.1039/a906977a

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728 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 728^729y
Microwave Enhanced Deuteriations in the Solid
State using Alumina Doped Sodium
Borodeuteridey
Wouter Th. Erb, John R. Jones* and Shui-Yu Lu
Department of Chemistry, University of Surrey, Guildford, Surrey GU2 5XH, UK
A number of deuteriated alcohols are rapidly (ca. 1 min) synthesised through the microwave enhanced solid state
reduction of the corresponding aldehydes and ketones using alumina doped sodium borodeuteride (NaBD4).
One of the important consequences of the development of
3H NMR spectroscopy1 has been the increased attention
paid to the development of new tritiating reagents,2
especially at carrier free levels. Until recently tritiated com-
pounds at very high speci¢c activity could only be obtained
by hydrogenation or dehalogenation using T2 gas or from
the reduction of functional groups with tritide reagents.
Unfortunately the only reducing agent then available at
close to carrier free levels of radioactivity was sodium
borotritide.3 However, the observation4 that extremely
reactive hydrides can be prepared from alkyl lithium com-
pounds and hydrogen under very mild conditions and near
ambient temperatures has transformed the situation. Tritide
reagents in which the tritium is attached to B, Al, Si, Sn and
Zr are now available, covering a wide range of reactivity.5
In separate investigations6;7 we have shown how
microwaves can greatly increase the attractions of both
hydrogen isotope exchange and hydrogenation reactions
for labelling purposes, initially with deuterium, then tritium.
Here we present our ¢ndings on reductive processes, bene-
¢ting from the recent observation of Varma et al.8;9 that
irradiation of a number of aldehydes and ketones in a
microwave oven in the presence of alumina doped NaBH4
for short periods of time led to rapid reduction (0.5^2 min)
in good yields (62^93%).
the presence of other functional groups and (e) the product
yields were invariably high, the two exceptions refering
to the more volatile products.
Acceleration of reactions through microwave irradiation
coupled to the ability to perform them under solvent-less
conditions are attractive features with considerable
potential, not least in the radiosynthesis area where
reduction of radioactive waste is an important consid-
eration. Consequently these promising deuteriation ¢ndings
can be seen as a precursor for corresponding tritium
reduction processes, using the wider range of tritiated
reducing agents refered to previously.
In the present study seven aldehydes and four ketones
were reduced (Scheme 1).
R1
R1
OH
D
NaBD4/alumina
Microwaves
C
R2
O
R2
1a–10a
1b–10b
O
HO
D
NaBD4/alumina
Microwaves
Me
Me
11a
11b
Scheme 1
1
The NMR spectra [1H of the reactant, H of the product
2
and H (1H decoupled) of the product] showed, see e.g. Fig.
1, that (a) reduction was complete within
1 min of
microwave irradiation; (b) the transformation was not
accompanied by any side product formation so that the
product purity was always > 95%; (c) the degree of
deuterium incorporation was similar to the original enrich-
ment of the NaBD4 reducing agent used (95%); (d) the
reductions were completely selective and not a¡ected by
* To receive any correspondence.
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
Fig. 1 1H NMR spectrum of (a) 8a; (b) 8b and (c) 2H (1H
decoupled) NMR spectrum of compound 8b

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J. CHEM. RESEARCH (S), 1999 729
Table 1 Microwave enhanced deuteriation using alumina doped
NaBD4
(2 cm3). The solvent was removed by rotary evaporation before being
re-dissolved in CHCl3 or CDCl3 prior to NMR analysis. For liquid
carbonyl compounds, thorough mixing was achieved by shaking
the substrate with alumina doped NaBD4 in the glass vial.
Entry
R1
R2
Isolated yield(%)
1
2
3
4
5
6
7
8
9
Ph
H
H
H
H
H
H
H
Me
Me
Me
37
77
37
83
68
85
89
82
68
86
87
trans-PhCHˆCH
4-NO2C6H4
2,4,6-(MeO)3C6H2
PhCH2
1-Naphthyl
2-Naphthyl
Ph
4-NO2C6H4
3-ClC6H4
5-Methyltetralone
Received, 31st August 1999; Accepted, 10th September 1999
Paper E/9/06977A
References
1
E. A. Evans, D. C. Warrell, J. A. Elvidge and J. R. Jones,
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1997, eds. J. R. Heys and D. G. Melillo, Wiley, Chichester,
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10
11
2
Experimental
3
4
C. Than, H. Morimoto, H. Andres and P. G. Williams, J.
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Microwave irradiation was carried out in a Matzui M167 BT
microwave oven (750 W). 1H (300 MHz, CDCl3) NMR and 2H
(46 MHz, CHCl3) NMR spectra are recorded on a Bruker AC300
spectrometer in the customary manner.
Alumina Doped NaBD .ö10% alumina doped NaBD4 was pre-
pared by mixing NaBD44 (0.5 g, 11.9 mmol) and neutral alumina
(4.5 g) using a pestle and mortar under normal atmospheric con-
ditions. The mixture was then transferred to a glass vial and stored
in a silica gel dried dessicator for periods up to a week.
Typical Deuteriation Procedure.öFor solid carbonyl compounds,
the substrate e.g. p-nitroacetophenone (50 mg, 0.3 mmol) was
thoroughly mixed with alumina doped NaBD4 (0.126 g, 0.3 mmol
of NaBD4) using a pestle and mortar. The mixture was transferred
to a loosely capped glass vial and irradiated in the microwave oven
for 1 min at full power (750 W). The sample was allowed to cool
to room temperature. The product was extracted using CHCl3
5
6
7
J. M. Barthez, A. V. Filikov, L. B. Frederiksen, M. L. Huguet,
J. R. Jones and S. Y. Lu, Can. J. Chem., 1998, 76, 726.
M. H. Al-Qahtani, N. Cleator, T. N. Danks, R. Garman, J. R.
Jones, S. Stefaniak, A. D. Morgan and A. J. Simmonds, J.
Chem. Res. (S), 1998, 400.
8
9
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