Synthesis with Ultrasonic Waves
Philip Bwdjouk
North Dakota State University, Fargo, ND 58105
The pioneering work on the chemical applications of ultrasound ( I ) was conducted in the 1920's by Richards and
Loomis in their classic survey of the effects of high-frequency sound waves (>280 kHz) on a variety of solutions, solids,
and pure liquids (2). These studies showed that ultrasound
accelerates a broad ranee of transformations such as the
dispersion of mercury, th;: degassing of liquids, the explosion
of nitrogen triiodide, the flocculation of silver chloride, the
depression of the boiling temperatures of liquids, the hydrolvsis of dimethvlsulfate, and the iodine clock reaction.
- In spite of the diversity of the chemical effects of ultrasonic waves discovered by Richards and Loomis, research
since then has been sparse and uneven. For the most part,
the emphases have heen on inorganic reactions, in particular
aqueous solutions, and in nearly all cases the systems were
homogeneous. Also, the sonicators used by the various research erouns were often auite different in confieuration and
delivered differenr frequencies, intensities,and wattages.To
comolirate the matter further. little was known of the roleoi
thesk variables in affecting reaction rates. As a result, there
are few generalizations upon which a new investigator can
rely, and sonochemistry, in particular preparative sonochemistry, must he considered an area that is in its earliest
stages and in need of much further study.
One of the points on which there is general agreement is
that, in order to produce a chemical effect in liquids using
ultrasonic waves, sufficient energy must he imparted to the
liquid to cause cavitation, i.e., the formation and collapse of
bubbles in the solvent medium and the consequent release of
enerw. When ultrasonic waves are oassed through a medium, i i e particles experience oscillati'ons that l e a l t o regions
of compression and rarefaction. The negative pressure in the
rarefaction region gives rise to the formation of bubbles, that
mav he filled with a eas. the vapor of the liauid, or may he
almost empty depenbing on the pressure a n d the forces
holdina the liauid together.
strictly defined, cavitation refers only t o the completely
evacuated bubble or cavitv, a true void, hut, since dissolved
gases are present unless Special steps are taken to remove
themand, since thevapor of the liquid can also penetrate the
cavity, the term cavitation most often encompasses the three
kinds of bubbles.
The collapse of these bubbles, caused by the compression
region of the ultrasonic wave, produces powerful shock
waves that are resoonsible for well-known processes such as
cleaning, dispersion, and the erosion of metals. The energy
output in the reaion of the collapsine
. - bubble is considerable,
with estimatesbf 2-3000°C and pressures in the kiloha;
range for time Deriods in the nanosecond region (3). In summary, the cavitation process generates a transitory highenergy environment. These forces are responsible for the
well-known commercial processes of ultrasonic cleaning, dispersion, and pasteurization as well as the efficiency of ultrasonic drills and the corrosion of ship propeller blades.
Although the early experiments with ultrasound were
- .
' Ullrasonic waves are usually defined as those sound waves with a
frequency of 20 kHz or higher. The human ear Is most sensitive to
z
with upper and lower limits of 0.3
frequencies in the 1-5 k ~ range
and20 kHz, respectively. For general treatments of the theory and
applications of ultrasound see ref. 1.
promising and the commercial applications of ultrasonic
waves have been very successful, little evidence accrued in
the 50 years following Loomis' studies to suggest that sound
would he a form of energy useful to synthetic chemists.
However, there were some indications. In 1938, Porter and
Young described the sonically induced Curtius rearrangement of henzazide,
noting rate enhancements of more than an order of magnitude ( 4 ) . A decade later Mivaeawa r e ~ o r t e dthat the hvdrolysis &acetates, the s a p o n i k k i o n of'fats, and the nitration
of m-xvlene were accelerated simificantlv in the oresence of
high f;equency sound waves (5).In thesame paper i t was
also reported that sake and whiskey mellowed more rapidly
in the presence of ultrasound. Later, Zechmeister (6)showed
that the cleavage of halides of benzene and thiophene by
suspensions of silver nitrate was accelerated by ultrasonic
waves, and Weissler (7) demonstrated that ultrasound promoted the decomposition of acetonitrile to give nitrogen,
hydrogen, and methane.
A verv useful communication anoeared in 1966 in which
~jbberidescriheda convenient
of stable solutions of the dimsvl anion from sodium hvdroxide and dimethylsulfoxide using ultrasonic waves a t room temperature
(8).
Ultrasound eliminated the need for heating and reduced the
extent of decomposition, two distinct advantages over the
conventional preparation.
In recent years, synthetic applications of ultrasound have
attracted widespread attention, and there have been some
notable successes. One of the main reasons for the resureence has been the discovery that the common ultrasonic
iahoratory cleaner is often gobd enough to do the job. T o my
knowledge, Fry (9) was the first to report the use of an
ultrasonic cleaner to accelerate a reacGon, in this case, a
partial reduction of some dihromoketones by mercury.
The report by Luche and coworkers that ultrasonic waves
aid the formation of organolithium and Grignard reagents
and also improve the Barhier reaction spurred much of the
current interest in the synthetic applications of ultrasound
(10)
R-Br
+ Li
,I)
RLi (61-9570)
Ih
where R = Pr, n-Bu, Ph, and
where R = alkyl, aryl, henzyl, allyl, vinyl, and R'&O = ketones and aldehydes.
The ultrasound-promoted Barbier reaction found recent
application by Trost and Coppola (11) as the method of
choice for preparing complex cyclopeutanones. Ultrasound
also proved useful in improving the synthesis of lithio-organocuprates and in preparing aldehydes by the Bouveault formylation (12).
Volume 63 Number 5 May 1986
427
Our entrv into the field of sonochemistrv was sourred hv
our need for high-yield preparations of symmetrical organics
)
lithium wire
and bimetallics. Our first efforts ( 1 3 ~with
were satisfactory hut have since been greatly improved
through the use of lithium dispersion (13b)
2 R,MCl+ Li-
111
>I h
using ultrasound led us to attempt t o generate West's novel
compound, tetramesityldisilene (22).the first example of a
stable species with a silicon-silicon double hond. We prepared this species in one step (23)
MesnSiClz+ Li
R,M-MR, (85-95%)
where R = alkyl, aryl, and M = C, Si, Sn.
Reactions involvina lithium appear t o be ~articularlvgood
candidates for ultras&ic accel&ation. WLhave founhthat
lithium promoted de~rotonations,reductions to anions and
dianions ( l 4 ) ,and reductions of metal halides to active metal powders (15)are enhanced in rate and yield when carried
out in the presence of ultrasonic waves.
Operating under the hypothesis that ultrasonic irradiation would be p .titularly useful for reactionsinvolving metals we extendeu our studies to zinc and soon found three
reactions that were noticeahlv"imnroved
. when conducted in
the presence of ultrasonic waves: the Simmons-Smiti reaction (15).the Reformatskv reaction (16).
. . . and the aeneration
of o-xyl;lene (17).
We felt the Reformatskv reaction was a worthwhile target
because it is the most generally applicable method for converting aldehvdes and ketones to B-hvdroxvesters (18).The
impro;emen<s in yield and reaction time exceeded our expectations.
where RzCO = alkyl and aryl aldehydes and ketones.
Essentially quantitative conversion to the 0-hydroxyester
was effected in a matter of a few minutes (16).The absence
of dehydrated products, a, @-unsaturated esters, as well as
simolified nroduct isolation and nurification are ~ r o h a h l v
the result of running the reaction at, effectively, room temperature. An interesting modification of this reaction, in
which the ketone was replaced by an imine, leading to a very
mild hiah vield svnthesis of 0-lactams has recentlv been
publishid (19).
When zinc and a , a'-dihromo-o-xylene are irradiated with
ultrasonic waves a t room temperature, synthetically useful
quantities of the reactive intermediate, o-xylylene, are generated which can he treated in situ with activated olefins to
give good yields of cycloaddition products (17)
Ultrasound is also very useful in generating carbenes from
diiodomethane and zinc-the Simmons-Smith reaction.
111
where
The disilene (or its precursor formed during the reaction) is
reactive towards lithium, however, and we have found i t very
difficult to obtain consistent results. Most often, hexamesitylcyclotrisilane is isolated in very good yield (24).The cyclotrisilane isvaluable in its own right being oneof only a few
cyclotrisilanes and is, upon photolysis, a useful source of
silylenes and disilenes.
With another highly hindered silane, di-t-hutyldichlorodisilane, lithium reduction a t room temperature in the presence of ultrasonic waves gives high yields of the reactive
divalent species, di-t-hutylsilylene, which was characterized
by its insertion reactions (25)
where R3 = Et3, PhMez.
Preparing compounds that are unstable to these reaction
conditions is a challenge and surely will he a fruitful area of
research. Currently we are investigating flow sonication
methods as an approach to isolating reactive species.
Reduction of binary metal halides leads to finely divided
metal powders that are considerably more reactive than
commercially available powders (26). Ultrasound not only
accelerates the reduction hut also increases the reactivity of
the metal powder produced (14,15,27)
MX,
+ nMI
428
Journal of Chemical Education
-,,,
M* + nLiX
where M = Mg, Ca, B, Al, Si, Ge, Sn, Ge, Sn, Pb, Ti, V, Cr,
Mn, Fe, Co, Ni, Cu, Zn, Nb, Mo,Pd, Ta,Pt, and MI = Li, Na,
K.
The synthesis of a variety of transition metal carbonyls
from some of these sonically activated transition metals and
carbon monoxide has recently been reported (27).
Activation of catalysts prior to a reaction is a fairly common procedure but we have found that if a catalyzed reaction is continuouslv exposed to ultrasonic waves the results
are much bettrr. f o r example, with continuous irradiation.
vallndium-catulvzed hvdrorenations
of oleiins with formic
.
.
k i d are complete in one hour ( 2 8 4
R,C =CR, + HCO,H
We found that cyclopropanation occurs readily with ordinary zinc and the preparation of zinc-copper couples could
be avoided (15). Recently other workers reported similar
observations using mossy zinc (20), and Kitazume and
Ishikawa have shown that the reactions of zinc with perflouroalkyl iodides are also accelerated by ultrasonic waves
(21).
Successes in producing reactive intermediates like o-xylylene and carhene and in preparing himetallics in high yields
Mes~Si=SiMer
+ Pd/C
,I1
R,CH-CHR,
In the absence of ultrasonic waves, the reactions usually
require two or three hours or heating to 80 "C. Using our
procedure, the cyclopropane ring in cyclopropylbenzene was
easily opened to give propylbenzene in >95% yield. Recently
we extended this study by replacing formic acid with a
stream of hydrogen gas huhblina throuah the reaction mixture and fonnd chateven this three-ph&e reaction was significantly accelerated by ultrasonic waves (28b).
Our interest in silicon chemistry quite naturally led to a
study of the hydrosilation reaction, the addition of the Si-H
eroun across an olefin or an acetvlene. This reaction is one of
;he most useful methods of maGing silicon to carbon bonds
and is an important industrial.,process. Typically, homoge-
neous catalysts based on platinum, rhodium, or ruthenium
are used, and while very efficient, they are not recoverable
sures, generally produce greater ultrctsonic acceleration of
chemical reactions than higher temperatures.
(29).
The original patent using platinum as the catalyst calls for
temperatures of 100-300 "C and pressure of 45-115 psi (30).
Our studies show that such rigorous conditions are not required for the hydrosilation reaction with most commercial
sources of platinum on carbon. Usually vigorous stirring a t
slinhtlv elevated temDeratures. 40-80 OC. a t atmos~heric
pressures will give moderate yieids of the pioduct. ~ o k e v e r ,
ultrasound ~ e r m i t the
s reaction to occur at a useful rate a t
30 "C at atmospheric pressure (31)
R:&H
+ -C=CI I + Pt/C
11'
I
r
30 'C, 1-2 h
R.,Si-C-C-H
I
(80-9470)
where
R
= Et, Ph, EtO,
CI.
While i t is early for accurate predictions, one cannot help
but feel that ultrasonic activation or production of catalysts
will he a fruitful area of research. In terms of generating
catalysts via ultrasound, Suslick's discovery that irradiation
of solutions of iron carhonyls produces intermediates that
are very efficient alkene isomerization catalysts must he
regarded as a seminal development (32).
The emphasis of this review has been on recent develo~.
ments in synthetic organic sonochemistry with the focus on
reactions involving metals. Nonmetallic heterogeneous reactions can also be accelerated by ultrasound, hbwever, as in
the preparation of the dimsyl anion (8) and more recently by
Rancher's high yield synthesis of thioamides from amides
and P 4 S 1 0 (33).Regen's facile production of dichlorocarhene
from CHC13 and KOH (34),and our reduction of haloaromatics with LiAlH4 (35).
Little has been offered in terms of a mechanistic framework, however, to explain these observations. This is simply
because this field is a t such an early stage that the necessary
data is not yet available to draw a complete picture. However, some generalizations appear t o he emerging as useful
guidelines: lower-vapor-pressure solvents usually work hetter than higher-vapor-pressure solvents (36),presumably
because the cavitational collapse involves more nearly vacant bubbles and therefore shock waves of higher energy;
and lower temperatures, because they lower the vapor pres-
Acknowledgment
The generous support of the Air Force Office of Scientific
Research through Grant No. 84-0008 is gratefully acknowledged.
Llterature Clted
11) la1 Bmm, B.: Gaodman, J. E. "High Intensity Ultnrsonics-lnduslrial Appliealion%":Van Noatrand: Princeton, 1965. lbl Crseknell, A. P."Ultrasonics"; Wykeham: London, 1980. (el El'piner. I. E."Ultrssound: Physical, Chemical and Biological Effects"; Sinclair, F. L.. Translator: Consultant8 Bureau: New York, 1964.
I21 Richards, W.T.;Loornia, A.L. J , Amer. Chem. Soe. 1927.49,3086.
sehgal. c.: sutherland, R. G.; verrau,
R. E. J . p h y s cham. 1980.84.396.
I41 Porter,C. W.;Young,L. J.Amar Chem.Soc. 1938,60,1497.
I51 Miyagaws, I. J . Soc. Or#. Syn. Chem. 1949,7,167: Chem. Abstr. 1953,d7,4831e.
I61 Zechmeister, L.: Wallcave, L. J. Amer. Chem. Sac. 1955.77.2853.
17) Weissler. A ; Peehl, I.: Anbsr, M.; Science 1965, 1.50, 1238.
(61 Sjdberg, K. TetrahedronLett. 1966,6333.
(91 Fry,A. J.;Hcrr, D. Tetrahedron L d t . 1978.19, 1721.
I101 Luehe, J. L.; Damiano, J. C. J . Amor. Chem. Soc. 1960,102, 7926. The first use of
ulvanaund t o activate Grignard and lithiation reactions was reported by Renaud in
anoften overlooked m m r : Renaud.P. J . Chim. Phw. 1953.50.135 lour thanks toa
ca
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429