Large-scale photochemical reactions of nanocrystalline suspensions: A promising green chemistry method

Article abstract of DOI:10.1021/ol060978m

Photochemical reactions in the solid state can be scaled up from a few milligrams to 10 grams by using colloidal suspensions of a photoactive molecular crystal prepared by the solvent shift method. Pure products are recovered by filtration, and the use of H₂O as a suspension medium makes this method a very attractive one from a green chemistry perspective. Using the photodecarbonylation of dicumyl ketone (DCK) as a test system, we show that reaction efficiencies in colloidal suspensions rival those observed in solution.

Full text of DOI:10.1021/ol060978m

ORGANIC
LETTERS
2006
Vol. 8, No. 12
2615-2617
Large-Scale Photochemical Reactions of
Nanocrystalline Suspensions: A
Promising Green Chemistry Method
Marcel Veerman, Marino J. E. Resendiz, and Miguel A. Garcia-Garibay*
Department of Chemistry and Biochemistry, UniVersity of California,
405 Hilgard AVenue, Los Angeles, California 90095-1569
mgg@chem.ucla.edu
Received April 24, 2006
ABSTRACT
Photochemical reactions in the solid state can be scaled up from a few milligrams to 10 grams by using colloidal suspensions of a photoactive
molecular crystal prepared by the solvent shift method. Pure products are recovered by filtration, and the use of H2O as a suspension medium
makes this method a very attractive one from a green chemistry perspective. Using the photodecarbonylation of dicumyl ketone (DCK) as a
test system, we show that reaction efficiencies in colloidal suspensions rival those observed in solution.
The high selectivity and specificity of photochemical reac-
tions in crystals have been known for many years.1 However,
it is only recently that their potential for synthetic transfor-
mations has been demonstrated in total synthesis.2 While
there has been some recent progress in the prediction and
control of crystallization3 and solid-state reactivity,4,5 it is
now essential to develop a general method that allows large-
scale photochemical reactions to occur in a practical and
energetically efficient manner. Having recently identified the
photodecarbonylation of crystalline ketones6 as a promising
method for the stereospecific synthesis of quaternary ste-
reogenic centers7 (Scheme 1) and recognizing its potential
Scheme 1
(1) (a) Sakamoto, M. Chem. Eur. J. 1997, 3, 684-689. (b) Toda, F.
Acc. Chem. Res. 1995, 28, 480-486. (c) Ramamurthy, V.; Venkatesan, K.
Chem. ReV. 1987, 87, 433-481. (d) Desiraju, G. R. Organic Solid State
Chemistry; Elsevier: Amsterdam, 1987. (e) Scheffer, J. R.; Garcia-Garibay,
M. A.; Nalamasu, O. Org. Photochem. 1987, 8, 249-347.
(2) Ng, D.; Yang, Z.; Garcia-Garibay, M. A. Org. Lett. 2004, 6, 645-
647.
(3) (a) Desiraju, G. R. Curr. Sci. 2001, 81, 1038-1042. (b) Papaef-
stathiou, G. S.; Kipp, A. J.; MacGillivray, L. R. Chem. Commun. 2001,
2462-2463. (c) MacGillivray, L. R.; Reid, J. L.; Ripmeester, J. A. J. Am.
Chem. Soc. 2000, 122, 7817-7818.
(4) Garcia-Garibay, M. A. Acc. Chem. Res. 2003, 36, 491-498.
(5) (a) Campos, L. M.; Garcia-Garibay, M. A. In CRC Handbook of
Organic Photochemistry; Horspool, W. M., Ed.; CRC Press: Boca Raton,
2003. (b) Campos, L. M.; Ng, D.; Yang, Z.; Dang, H.; Martinez, H. L.;
Garcia-Garibay, M. A. J. Org. Chem. 2002, 67, 3749-3754.
in the development of green chemistry strategies,8,9 we
decided to investigate scale-up procedures that may lead to
solid-state photochemical reactions in the multigram to
(6) For the first observation of photodecarbonylation reactions in crystals,
see: Quinkert, G.; Tabata, T.; Hickmann, E. A. J.; Dobrat, W. Angew.
Chem., Int. Ed. Engl. 1971, 10, 199-200.
10.1021/ol060978m CCC: $33.50
© 2006 American Chemical Society
Published on Web 05/17/2006

Scheme 2
kilogram scales. MacGillivray and co-workers have shown
the feasibility of such processes.10
To investigate these expectations, we selected the readily
available dicumyl ketone (DCK) as a test system. We have
recently shown that irradiation of DCK in solution leads to
formation of dicumene (DC) in 60% yield, isopropylbenzene
and R-methylstyrene in ca. 10% yield each, and several other
unidentified products (20%). In contrast, finely powdered
crystals of DCK react in a very clean solid-to-solid reaction
to give DC as the only product in >99% yield (Scheme 2).11
As a starting point, we compared the reaction efficiency
of single crystals (ca. 1 × 1 × 2 mm3) with that of
microcrystals grown as a thin film by fast evaporation of
diethyl ether over a microscope slide.12 Both experiments
gave DC as the only product. However, after 10 h, the single
crystals had reacted to only ca. 5% conversion while the
smaller crystals had reacted to completion. Large single
crystals had turned opaque and tended to splinter, whereas
crystals in the film remained birefringent when analyzed
under cross polarizers.
To scale up the reaction and promote homogeneous
illumination, samples of DCK were mechanically ground
and suspended in an aqueous solution containing an equiva-
lent mass of sodium dodecyl sulfate (SDS), which was added
to reduce surface tension. Microscopic analysis indicated that
particle sizes in these experiments were in the range of ca.
15-55 µm. Samples prepared with 40, 80, 120, and 180 mg
of DCK in 20 mL of water were irradiated with an external
light source while being continuously stirred. The extent of
reaction was monitored by GC every 2 h and the product
recovered by filtration with a cellulose filter (11 µm nominal
retention size). As illustrated in Figure 1, the initial kinetics
of product formation tended to a zero order law for high
particle loadings and are a linear function of irradiation time,
as expected for an optically dense medium where photons
are the limiting reagent. Notably, the reaction proceeded to
Figure 1. Product formation as a function of irradiation time for
microcrystalline samples suspended in 20 mL of H2O containing
SDS. All reactions proceeded to >99% conversion. The percentage
product recovery indicated on the right of each trace varied.
>98% conversion within 10-26 h, and the efficiency of
product recovery increased with particle loading from 69.9%
(at 2 mg/mL) up to 98.1% (at 8 mg/mL) with a relatively
constant amount of loss material of ca. 0.25 mg/mL.
Knowing that nanocrystalline suspensions of diolefin
monomers are able to retain their single crystalline phase
during a photopolymerization reaction,13 and taking advan-
tage of the reprecipitation method,14 we were able to increase
the scale of the reaction by up to 2 orders of magnitude.
Nanocrystalline suspensions were prepared by slowly adding
a saturated DCK solution in acetone into H2O with SDS.
The method is known to provide stable suspensions with a
distribution of particle size from tens of nanometers to
microns.14,15 Suspensions of DCK had a milky-white ap-
pearance characterized by particle sizes with an average in
the 800-1500 nm range, as determined by dynamic light
scattering. FT-IR analysis confirmed formation of the same
polymorph as that obtained by solvent evaporation.11 Sus-
pensions prepared in this manner were ideally suited for
irradiation with an immersion well (Figure 2a). The progress
(7) (a) Ellison, M. E.; Ng, D.; Dang, H.; Garcia-Garibay, M. A. Org.
Lett. 2003, 5, 2531-2534. (b) Yang, Z.; Ng, D.; Garcia-Garibay, M. A. J.
Org. Chem. 2001, 66, 4468-4475.
(8) Mortko, C. J.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 2005, 127,
7994-7995.
(9) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: Oxford, 1998. (b) Poliakoff, M.;
Fitzpatrick, J. M.; Farren, T. R.; Anastas, P. T. Science 2002, 297, 807-
810.
(10) Frisˇcˇicˇ, T.; MacGillivray, L. R. Chem. Commun. 2003, 1306-1307.
(11) Resendiz, M. J. E.; Garcia-Garibay, M. A. Org. Lett. 2005, 7, 371-
374.
(12) All photochemical experiments were carried using a 400 W medium-
pressure Hg-lamp using Pyrex glass as a filter (λ > 290 nm).
Figure 2. Experimental set up used for the photolysis of 2 and 10
g of DCK in H2O.
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Org. Lett., Vol. 8, No. 12, 2006

and to partial sedimentation of particles during the longer
experiment. These problems should be easily solved by using
a closed, evacuated system and a suitable stirrer.
The macroscopic homogeneity of the nanocrystalline
suspensions and their ability to trap all the absorbable
photons emitted by the source suggested an opportunity to
determine the absolute quantum yield of the reaction by
conventional valerophenone actinometry.16 We established
that the quantum yield of reaction of DCK in benzene (Φ
) 0.41 ( 0.04)17 is only twice as large as that in the solid
(Φ ) 0.20 ( 0.02). However, DC is the only product formed
in crystals. In conclusion, the use of nanocrystalline suspen-
sions is a promising strategy to scale-up photochemical
reactions of crystalline solids. Strategies shown here suggest
simple ways to scale these reactions to the multi-kilogram
scale. We believe that reactions in crystals will provide a
practical green chemistry approach for the synthesis of
structurally complex, specialty chemicals. This work provides
a strong incentive to investigate the formation and control
of organic molecular nanocrystals.
Figure 3. Product formation as a function of irradiation time for
samples of 2 and 4 g of DCK suspended in 1.0 L of H2O.
of reactions carried out with suspensions containing 2 and 4
g of DCK in a 1 L well revealed a remarkably efficient
process with reaction velocities of ca. 1 g/h with the 400 W
medium-pressure Hg lamp (Figure 3). Given that suspensions
with greater particle loading were not stable, larger reaction
scales were explored with a flow reactor consisting of a 5 L
vessel and a submersible pump that circulates the suspension
through the immersion well. Shown in Figure 2b, a reaction
of 10 g of DCK in 3.3 L of water (3 g/L) led to 91.2%
conversion in 19 h for an apparent rate of ca. 0.5 g/h. Possible
reasons for the lower efficiency in the latter experiment may
be related to the formation of foam, which ascends to the
upper portion of the vessel trapping some of the reactant,
Acknowledgment. Financial support by NSF Grant Nos.
CHE0242270, CHE0551938, and DMR0307028 is gratefully
acknowledged.
Supporting Information Available: Photochemical pro-
cedures and NMR data for DCK and DC. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL060978M
(16) Carmichael, I.; Hug, G. L. In Handbook of Organic Photochemistry;
Scaiano, J. C., Ed.; CRC Press: Boca Raton, FL, 1989; Vol. I, pp 369-
403.
(17) This value is lower than that reported for diphenylacetone (Φ )
0.70 ( 0.1 to 0.87 ( 0.12): (a) Noh, T.; Step, E.; Turro, N. J. J. Photochem.
Photobiol. A 1993, 72, 133-145. (b) Engel, P. S., J. Am. Chem. Soc. 1970,
92, 6074-6076. (c) Robbins, W. K.; Eastman, R. H. J. Am. Chem. Soc.
1970, 92, 6076-6077. (d) Turro, N. J.; Kraeutler, B.; Anderson, D. R. J.
Am. Chem. Soc. 1979, 101, 7435-7437.
(13) Takahashi, S.; Miura, H.; Kasai, H.; Okada, S.; Oikawa, H.;
Nakanishi, H. J. Am. Chem. Soc. 2002, 124, 10944-10945.
(14) Kasai, H.; Nalwa, H. S.; Oikawa, H.; Okada, S.; Matsuda, H.;
Minami, N.; Kakuta, A.; Ono, K.; Mukoh, A.; Nakanishi, H. Jpn. J. Appl.
Phys. 2 1992, 31, L1132-L1134.
(15) Baba, K.; Kasai, H.; Okada, S.; Oikawa, H.; Nakanishi, H. Opt.
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Org. Lett., Vol. 8, No. 12, 2006
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