Chemistry Letters Vol.33, No.7 (2004)
847
centrated in vacuo. The obtained residue was deuterated phos-
phonium salt 2. The reaction was also examined under micro-
wave irradiation. The microwave system is considered to be a
potential substitution for the autoclave of hydrothermal reaction.
As microwave system, we used Discover system from CEM cor-
poration.7,8 In a pressure 10-mL vial which can be sealed by a
septum, a mixture of phosphonium salt (2.0 mmol) and molecu-
lar sieves (4A or 3A, 2–3 pellets in deuterium oxide (3.0 mL)
was placed. The mixture was irradiated with microwave
(100 W) maintaining 180 ꢀC and 1.2 MPa for 15 min. After being
cooled, the mixture was filtered and concentrated in vacuo. The
obtained residue was deuterated phosphonium salt.
The other examples are shown in Table 1. Except the de-
composition cases, the phosphonium salts were recovered quan-
titatively after deuteration. Various additives besides molecular
sieves were examined in reactions using 1b as a substrate. Both
molecular sieves and palladium on activated carbon showed
prominent effect for the acceleration for H–D exchange. From
the economical and practical point of view, we chose molecular
sieves as an additive. The phosphonium salts carrying ethereal
functional groups were decomposed under microwave irradia-
tion. As the irradiation heated an ionic salt directly and drastical-
ly faster than the surrounding deuterium oxide, the salts decom-
posed thermally. On the contrary, traditional heating in
autoclave did not spoil the salts in these cases and performed
H–D exchange reaction. The procedure would not heat the salts
beyond the established reaction temperature.
The role of the molecular sieves is not perfectly clear. Mo-
lecular sieves, however, can be considered to be a weak solid
base. Simple heating of water beyond the boiling point in a
closed pot causes a decrease of pKw.9 This means that the hydro-
thermal water is acidic. An addition of molecular sieves may
change the condition into neutral or weakly basic one. When
the allylic phosphonium salt 1j was treated even with moderate
base like sodium carbonate, it will isomerize into the alkenyl
phosphonium compound.4 In the present method, molecular
sieves did not undergo such isomerization reaction during the
exchange reaction.
sieves and hot water under microwave irradiation. The acidic
protons were exchanged with D atom of deuterium oxide. With-
out molecular sieves, the same condition did not show sufficient
exchange reactions.
As described above, the role of molecular sieves may be
considered to be a solid base. The combination with either hy-
drothermal or normal water will offer a new reaction condition
and site for organic compounds.
This work was supported financially by a Grant-in-Aid for
Scientific Research from The Ministry of Education, Culture,
Sports, Science, and Technology, Japan. The financial support
by Chugai Pharmaceutical Co., Ltd. and Takahashi Industrial
and Economical research foundation are also acknowledged.
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Ph
Ph
CH
MW (180 °C/1.2 MPa), 0.5 h
Ph
CD
3
3
3
3
4a >99% (>99%D)
7
8
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D2O
CH
MW (180 °C/1.2 MPa), 0.5 h
Ph
CH
3
3
3 >99% (3%D)
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Scheme 2. H–D exchange reaction of acetophenone catalyzed
by molecular sieves.
Published on the web (Advance View) June 7, 2004; DOI 10.1246/cl.2004.846