Efficient preparation and processing of the 4-methoxybenzyl (PMB) group for phenolic protection using ultrasound

Article abstract of DOI:10.1021/jo800577f

(Chemical Equation Presented) Power ultrasound efficiently facilitates the rapid preparation and reaction of 4-methoxybenzyl chloride (PMB-Cl) 1 in providing protected phenolic ether intermediates for organic synthesis. Using two-phase systems in both the ultrasound-promoted preparation and reactions of PMB-Cl, typical runs produce PMB-protected products within 15 min. When compared with nonsonicated control reactions, the results demonstrate clear advantage in terms of efficiency when the protocol is applied to the mild and selective protection of various multisubstituted phenols including sensitive phenolic aldehydes.

Full text of DOI:10.1021/jo800577f

based protecting groups and can be removed by a wide range
of reagent systems. Introduction of the PMB group is mainly
facilitated with 4-methoxybenzyl chloride (PMB-Cl) 1, a
compound which has safety and stability issues associated with
its handling, shipping and storage.4 Other types of benzylating
reagents can take the form of the corresponding benzylic iodide,
bromide or trichloroacetimidate, depending on the degree of
mildness required by the protection step.5 More recently,
benzylating reagents have taken the form of the corresponding
2-benzyl or 2-(4-methoxybenzyl)pyridinium or -quinolinium
triflates.6 Typically, the preparation of benzylic chlorides such
as PMB-Cl or benzyl chloride can be performed under mild,
nonaqueous conditions by treatment of the corresponding
alcohols with chlorinating reagent systems utilizing thionyl
chloride, N-chlorosuccinimide, triphenylphosphine/isocyanuric
chloride or tertiary halides in ionic liquids.7 In contrast,
conversion of 4-methoxybenzyl alcohol to PMB-Cl 1 may be
facilitated more economically by the employment of hydro-
chloric acid under strictly aqueous conditions or with the use
ofacosolvent.8 Organicreactionprocessesinvolvingliquid-liquid
and solid-liquid systems can be normally facilitated by power
ultrasound.9 Hence, we determined that the two-phase halogena-
tion reaction involving p-anisyl alcohol and aqueous concen-
trated HCl (eq 1) with promotion by ultrasound would be a
good case in point and would rapidly provide 1 at minimal
expense.
Efficient Preparation and Processing of the
4-Methoxybenzyl (PMB) Group for Phenolic
Protection Using Ultrasound† 1
,
Frederick A. Luzzio* and Juan Chen
Department of Chemistry, UniVersity of LouisVille, 2320
South Brook Street, LouisVille, Kentucky 40292
faluzz01@gwise.louisVille.edu
ReceiVed March 13, 2008
Power ultrasound efficiently facilitates the rapid preparation
and reaction of 4-methoxybenzyl chloride (PMB-Cl) 1 in
providing protected phenolic ether intermediates for organic
synthesis. Using two-phase systems in both the ultrasound-
promoted preparation and reactions of PMB-Cl, typical runs
produce PMB-protected products within 15 min. When
compared with nonsonicated control reactions, the results
demonstrate clear advantage in terms of efficiency when the
protocol is applied to the mild and selective protection of
various multisubstituted phenols including sensitive phenolic
aldehydes.
When power ultrasound was applied to a suspension of
reagent-grade concentrated hydrochloric acid and p-anisyl
alcohol for 15 min, the immediate result was the formation of
a top layer of the 4-methoxybenzyl chloride. The product
The 4-methoxybenzyl (PMB or MPM) group has been
extensively used as a protecting group for alcohols, phenols and
various nitrogen moieties in organic synthesis.2 Some time ago
we used the PMB group for the efficient protection of the imide
nitrogen in ribosyl nucleobases,3a and in the protection of the
glutarimide nitrogen in thalidomide analogues.3b However, the
PMB group has since gained in popularity and is now a
“textbook” protecting group as it has been used in applications
too numerous to specifically cite here.3c–e For most applications
overall, such as those in carbohydrate chemistry, the PMB group
is more robust and less expensive than many of the silicon-
(4) Brewer, S. E.; Vickery, T. P.; Bachert, D. C.; Brands, K. M. J.; Emerson,
K. M.; Goodyear, A.; Kumke, K. J.; Lam, T.; Scott, J. P. Org. Process Res.
DeV. 2005, 9, 1009–1012.
(5) (a) Nakajima, N.; Horita, K.; Abe, R.; Yonemitsu, O. Tetrahedron Lett.
1988, 29, 4139–4142. (b) Walkup, R. D.; Kane, R. R.; Boatman, P. D., Jr.;
Cunningham, R. T. Tetrahedron Lett. 1990, 31, 7587–7590. (c) Takaku, H.;
Ueda, S.; Ito, T. Tetrahedron Lett. 1983, 24, 5363–5366.
(6) (a) Poon, K. W. C.; Dudley, G. B. J. Org. Chem. 2006, 71, 3923–3927.
(b) Nwoye, E. O.; Dudley, G. B. Chem. Commun. 2007, 1436–1437. (c) Poon,
K. W. C.; Albiniak, P. A.; Dudley, G. B. Org. Synth. 2007, 84, 295–305.
(7) (a) Chen, G.; Shan, W.; Wu., Y.; Ren, L.; Dong, J.; Ji, Z. Chem. Pharm.
Bull. 2005, 53, 1587–1590. (b) Firouzabadi, H.; Gholinejad, M.; Iranpoor, N.
Can. J. Chem. 2006, 84, 1006–1012. (c) Hiegel, G. A.; Rubino, M. Synth.
Commun. 2002, 32, 2691–2694.
† Dedicated to Professor E. J. Corey on the occasion of his 80th birthday.
(1) Abstracts of papers, 234th National Meeting of the American Chemical
Society, Boston, Massachusetts, August, 2007, American Chemical Society:
Washington, DC, 2007; ORGN 847.
(2) (a) Greene, T.; Wuts, P. ProtectiVe Groups in Organic Synthesis, 3rd
ed.; Wiley: New York, 1999; pp 269-270. (b) Venuti, M. C.; Loe, B. E.; Jones,
G. H.; Young, J. M. J. Med. Chem. 1988, 31, 2132–2136.
(8) (a) Quelet, R.; Allard, J. Bull. Soc. Chim. Fr. 1937, 4, 1468–1472. (b)
Mounetou, E.; Poisson, C.; Monteil, A.; Madelmont, J. C. J. Labelled Cmpd.
Radiopharm. 1998, 41, 181–189.
(9) (a) Luche, J. L. , Ed. Synthetic Organic Sonochemistry; Plenum Press:
New York, 1998; Chapter 9. (b) Mason, T. J.; Lorimer, J. P. Applied
Sonochemistry: The Uses of Power Ultrasound in Chemistry and Processing;
Wiley-VCH Verlag: Weinheim, 2002. For effective applications of power
ultrasound in synthesis involving solid/liquid systems, see: (c) Perez, J. M.;
Wilhelm, E. J.; Sucholeiki, I. Bioorg. Med. Chem. Lett. 2000, 10, 171–174.
(10) (a) Luzzio, F. A. Tetrahedron 2001, 57, 915–945. For an array of
protected phenols, see:(b) Srikrishna, A.; Viswajanani, R.; Sattigeri, J. A.;
Vijaykumar, D. J. Org. Chem. 1995, 60, 5961–5962. (c) Recently, power
ultrasound was employed to protect alcohols as silyl ethers under solvent free
conditions: Mojtahedi, M. M.; Abaee, M. S.; Hamidi, H.; Zolfaghari, A. Ultrason.
Sonochem. 2007, 14, 596–598.
(3) (a) Luzzio, F. A.; Menes, M. E. J. Org. Chem. 1994, 59, 7267–7272. (b)
Luzzio, F. A.; Zacherl, D. P.; Figg, W. D. Tetrahedron Lett. 1999, 40, 2087–
2090. Papers which inspired our application of the PMB group in both nucleoside
and thalidomide synthesis are: (c) Danishefsky, S. J.; DeNinno, S. L.; Chen, S.;
Boisvert, L.; Barbachyn, M. J. Am. Chem. Soc. 1989, 111, 5810–5818. (d)
Akiyama, T.; Kumegawa, M.; Takesue, Y.; Nishimoto, H.; Ozaki, S. Chem.
Lett. 1990, 339–342. (e) Van Aerschot, A.; Jie, L.; Herdewijn, P. Tetrahedron
Lett. 1991, 32, 1905–1908.
10.1021/jo800577f CCC: $40.75
Published on Web 06/13/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 5621–5624 5621

TABLE 1. Ultrasound-Promoted and Silent (Control) Conversions
of Phenols to PMB Ethers
chloride 1 was then easily separated from the aqueous portion
and dried, whereupon 1H NMR analysis demonstrated the
product to be at least 98% pure. The product could then be
used in a subsequent reaction or otherwise Kugelro¨hr-distilled
and then immediately employed in any reaction or protection
step. The distilled 4-methoxybenzyl chloride can also be stored
for up to three weeks over a small amount of anhydrous
powdered potassium carbonate and taken out by syringe as
needed. With an efficient method for preparing PMB-Cl now
in hand we put it to practice in a separate project which initially
involved the rapid preparation of a number of PMB-protected
phenolic aldehydes for use in the Henry reaction.10a Hence, we
were prompted as well to explore the application of power
ultrasound in the protection of the phenolic hydroxyl under
heterogeneous conditions using the freshly prepared PMB
chloride.10b,c Potassium bases such as potassium hydroxide or
potassium carbonate together with a polar aprotic solvent,
typically acetone under reflux, appear to be the reagent systems
or conditions of choice when alkylating phenolic oxygens. Since
acetone is relatively low boiling, we decided to use N,N-
dimethylformamide (DMF) as the reaction medium due to its
similar polarity and significantly higher boiling point, a property
which we found compatible with power ultrasound when
external cooling was not employed. We also employed reagent-
grade anhydrous potassium carbonate to promote the reaction
between the substrate phenol and 1 (eq 2). Applying ultrasound
1 Reactions were run for 15 min with a 300 W Sonics and Materials
Vibra-Cell titanium probe. 2 Yields are for isolated, purified product.
3 The reaction times listed are for full disappearance of starting material
as determined by analytical TLC unless otherwise noted. 4 New
compounds (3e-3i) were characterized by 1H, 13C NMR, IR and
HRMS.
to a suspension of a typical substrate phenol 2a-i and PMB-
Cl (one molar equivalent each) and 2 equiv of potassium
carbonate in anhydrous DMF resulted in complete consumption
of starting material in 15 min (Table 1). Following extractive
workup, concentration and silica gel chromatography, the
products 3a-i were isolated in modest to high yields. For
comparison, nonsonicated (usually termed stirred or “silent”)
reactions were conducted with the same group of substrates
while monitoring their disappearance by thin-layer chromatog-
raphy (Table 1). From comparing the reaction times of both
the sonicated and nonsonicated control experiments, it is clearly
evident that ultrasound offers an expedient in terms of time but
not a great advantage in terms of yield. The efficiency advantage
is apparent when considering the conversion of simple aldehydic
phenols such as 2 h f 3 h (15 min sonicated, 97% versus 17 h
nonsonicated, 97%). But in contrast, ultrasound compromises
the yields in the cases of more activated substrates such as the
allyl phenols 2b and 2g. In one of the experiments involving
2e f 3e, we isolated the phenolic methoxydiphenylmethane
4(∼6%), which presumably occurs through acid-catalyzed ortho
ethers.10b In order to clarify the role of anhydrous potassium
carbonate as either a base in generating phenoxide ion or as a
simple buffering agent, several control reactions were carried
out using deuterium oxide (D2O). Sonication of a suspension
of anhydrous potassium carbonate and m-cresol in DMF in the
presence of D2O resulted in no phenolic deuterium exchange
while the same experiments employing anhydrous potassium
hydroxide instead of K2CO3 resulted in complete deuterium
exchange.11 Hence, these results suggest that potassium carbon-
ate acts as an active buffer which absorbs the generated
hydrogen chloride and that power ultrasound accelerates the
buffering action by formation of a reactive microdispersion of
K2CO3 in DMF. Moreover, when considering that many
protocols require the generation of a preformed phenoxide when
preparing benzylic phenolic ethers, the sonication method in
DMF represents a simpler and more convenient methodology.
For purposes of comparison, benzyl chloride was substituted
for PMB-Cl in the sonicated reaction of substrate 2e with all
conditions remaining the same as in Table 1. As expected the
less reactive benzyl halide cleanly afforded the benzyl analogue
of 3e, 1-(benzyloxy)-3-methoxybenzene, in 51% conversion
after 15 min, thereby suggesting that the sonication avenue may
have potential in providing simple Bn-protected phenolic ethers.
Preliminary experiments with ultrasound-promoted N-protection
(11) Acetone as a solvent, which is less polar (µ, 2.69) and has a lower
dielectric constant (ε, 20.70), gave no deuterium exchange with K2CO3, m-cresol
and ultrasound.
rearrangement of 3e. Not surprisingly, similar rearrangements
were found to occur during the deprotection of PMB phenolic
5622 J. Org. Chem. Vol. 73, No. 14, 2008

with CH2Cl2 (2 × 30 mL), and the combined organic layers were
dried over magnesium sulfate and concentrated. The crude residue
was purified by gravity column chromatography (hexane/ethyl
acetate) on silica gel to afford the PMB phenolic ether products
3a-i.
4-(4-Methoxybenzyloxy)-3-methoxybenzaldehyde (3a): white
solid (mp 105-106 °C, Lit.14 106-107 °C), Rf 0.45 (hexane/ethyl
acetate, 1:1).
of imides with 1 were promising. Treatment of a suspension of
glutarimide, 1 and K2CO3/DMF with ultrasound irradiation
(20min) gave N-PMB glutarimide 5 in 86% recrystallized yield
while the nonsonicated control reaction required 24 h for
complete conversion to 5 (Supporting Information).12 The
growing number of laboratories having access to microwave
equipment as compared to those using power ultrasound
equipment prompted us to conduct experiments with microwaves
for comparison. Admixture of p-anisyl alcohol to concentrated
HCl followed by irradiating the suspension with microwaves
(30min/120 °C) gave 1 in 71% yield after workup and bulb-
to-bulb (Kugelro¨hr) distillation. Furthermore, microwave ir-
radiation efficiently promoted the preparation of the O-PMB
aldehyde 3c (94%) using freshly prepared 1 and phenolic
aldehyde 2c.13
In summary, power ultrasound efficiently facilitates the rapid
conversion of p-anisyl alcohol to PMB-Cl using hydrochloric
acid and thus avoids the use of more expensive chlorinating
reagents and lengthy workup and purification procedures. The
PMB-Cl thus prepared can be stored over potassium carbonate
for extended periods; however, it is best used immediately after
separation from the reaction mixture or after bulb-to-bulb
distillation. In terms of expense, convenience and time the rapid
preparation and use of PMB-Cl far precludes purchase and
storage of the material. Using ultrasound in sequence, the freshly
prepared PMB chloride was used to protect an array of phenolic
hydroxyl groups rapidly and in good yield while again avoiding
prolonged reaction times and low-boiling refluxing solvent
systems. Moreover, the method is an efficient alternative to the
time-consuming preparation and use of the corresponding
phenoxides prior to treatment with 1. The application of the
ultrasound method to the preparation of protected phenolic
aldehydes has been especially useful as these intermediates are
availablequicklyandreactsmoothlyinavarietyofcarbon-carbon
bond-forming transformations.
1-(4-Methoxybenzyloxy)-2-allylbenzene (3b): colorless oil
(Lit.15), Rf 0.50 (hexane/ethyl acetate, 4:1).
4-(4-Methoxybenzyloxy)benzaldehyde (3c): white solid (mp
100-101 °C, Lit.16 101-102 °C), Rf 0.52 (hexane/ethyl acetate,
1:1).
3-(4-Methoxybenzyloxy)-4-methoxybenzaldehyde (3d): white
solid (mp 79-80 °C, Lit.14 80-81 °C), Rf 0.40 (hexane/ethyl
acetate, 1:1).
1-Methoxy-3-(4-methoxybenzyloxy)benzene (3e): white solid
(mp 41-42 °C), Rf 0.35 (hexane/ethyl acetate, 4:1); FTIR (KBr,
cm-1) 3054, 2986, 1604, 1515, 1422, 1264, 1151, 1035, 895, 738,
1
706. H NMR (500 Hz, CDCl3) δ 3.79 (s, 3H), 3.83 (s, 3H), 4.98
(s, 2H), 6.54 (d, 2H), 6.59 (d, 1H), 6.93 (d, 2H), 7.19 (t, 1H), 7.37
(d, 2H); 13C NMR (125 Hz, CDCl3) δ 160.8, 160.1, 159.4, 129.8,
129.2, 129.0, 114.0, 106.9, 106.5, 101.3, 69.8, 55.3, 55.2; HRMS
([M + H]+) calculated for C15H16O3 ([M + Na]+) 245.1172, found
245.1174.
1-(4-Methoxybenzyloxy)-3-methylbenzene (3f): white solid
(mp 60-61 °C), Rf 0.52 (hexane/ethyl acetate, 4:1); FTIR (KBr,
1
cm- ) 3054, 2986, 1612, 1515, 1421, 1265, 737, 706. H NMR
1
(500 Hz, CDCl3) δ 2.38 (s, 3H), 3.86 (s, 3H), 5.01 (s, 2H), 6.82
(d, 2H), 6.86 (d, 1H), 6.96 (d, 2H), 7.21(t, 1H), 7.40 (d, 2H); 13C
NMR (125 Hz, CDCl3) δ 159.4, 158.9, 139.5, 129.2, 121.7, 115.7,
113.9, 111.6, 69.6, 55.2, 21.5; HRMS ([M + H]+) calculated for
C15H16O2 ([M + H]+) 229.1228, found 229.1226.
4-Allyl-2-methoxy-1-(4-methoxybenzyloxy)benzene (3 g): white
solid (mp 85-86 °C), Rf 0.33 (hexane/ethyl acetate, 4:1); FTIR
(KBr, cm-1) 3853, 3735, 3054, 2986, 1516, 1397, 1265, 737, 706.
1H NMR (500 Hz, CDCl3) δ 3.35 (d, 2H), 3.82 (s, 3H), 3.88 (s,
3H), 5.07 (s, 2H), 5.10 (m, 2H), 5.97 (m, 1H), 6.68 (dd, 1H), 6.75
(d, 1H), 6.85 (d, 1H), 6.91 (d, 2H), 7.38 (d, 2H); 13C NMR (125
Hz, CDCl3) δ 159.2, 149.6, 146.5, 137.6, 133.2, 129.3, 128.9, 120.3,
115.6, 114.4, 113.8, 112.4, 70.9, 55.9, 55.2, 39.8; HRMS ([M +
Na]+) calculated for C18H20O3 ([M + Na]+) 307.1309, found
307.1306.
Experimental Section
4-Methoxybenzyl Chloride (PMB-Cl or MPM Chloride
(1). In a 500 mL round-bottom flask was placed p-anisyl alcohol
(20 mL, 22.24 g, 161.12 mmol) followed by concentrated HCl (160
mL). Upon addition of the acid, the heterogeneous mixture then
turned cloudy white. The ultrasound probe (1/4′′ microtip) was
immersed 0.5′′ below the surface, and the instrument was turned
to full power. The reaction mixture then turned homogeneous during
the sonication process. After 15 min, the reaction mixture was
poured into a separatory funnel, and the top chloride layer was
separated and dried over anhydrous calcium chloride. Removal of
the drying agent gave product (19.1 g, 75%) of sufficient purity to
use directly in many of the reactions. Kugelro¨hr distillation
(117-118 °C @ 1 mm)8a gave the product chloride 1 of excellent
purity which can be stabilized by addition of powdered anhydrous
potassium carbonate and stored under nitrogen.
General Procedure for the Preparation of Phenolic PMB
Ethers (3a-i). In a 100 mL round-bottom flask was placed
potassium carbonate (6 mmol, 2 equiv) and the substrate phenol
2a-i (3 mmol, 1 equiv) followed by N,N-dimethylformamide
(6-6.5 mL) and 4-methoxybenzyl chloride 1 (3 mmol, 1 equiv).
The ultrasound probe (1/4′′ microtip) was immersed 0.5′′ below
the surface, and the instrument was turned to full power. After 15
min, the reaction mixture was diluted with distilled H2O (200 mL)
and poured into a separatory funnel. The product was extracted
2-(4-Methoxybenzyloxy)benzaldehyde (3 h): yellow solid (mp
88-89 °C), Rf 0.30 (hexane/ethyl acetate, 4:1); FTIR (KBr, cm-1
)
3853, 3749, 3688, 1684, 1597, 1516, 1456, 1251, 1187, 1026, 828,
1
737,706. H NMR (500 Hz, CDCl3) δ 3.82 (s, 3H), 5.12 (s, 2H),
6.94 (d, 2H), 7.05 (q, 2H), 7.37 (d, 2H), 7.54 (t, 1H), 7.85 (d, 1H),
10.52 (s, 1H); 13C NMR (125 Hz, CDCl3) δ 189.9, 161.1, 159.6,
135.9, 129.1, 128.4, 128.0, 125.2, 120.9, 114.1, 113.1, 70.3, 55.3;
HRMS ([M + Na]+) calculated for C18H20O3 M + Na]+) 265.0840,
found 265.0837.
4-Methoxy-5-(4-methoxybenzyloxy)-2-nitrobenzaldehyde (3i):
yellow solid (mp 109-110 °C), Rf 0.20 (toluene/ethyl acetate, 99:
1); FTIR (KBr, cm-1) 3944, 3757, 3690, 3055, 2986, 2839, 2685,
1689, 1572, 1518, 1422, 1265, 1175, 1060, 895, 737,706. 1H NMR
(500 Hz, CDCl3) δ 3.82 (s, 3H), 4.02 (s, 3H), 5.21 (s, 2H), 6.93
(d, 2H), 7.39 (d, 2H), 7.50 (s, 1H), 7.62 (s, 1H), 10.44 (s, 1H); 13
C
NMR (125 Hz, CDCl3) δ 187.7, 159.9, 152.8, 152.4, 143.8, 129.5,
128.9, 128.5, 127.0, 125.3, 114.2, 111.3, 107.3, 71.2, 56.7, 55.3;
HRMS ([M + Na]+) calculated for C16H15NO6 ([M + Na]+)
340.0796, found 340.0793.
Preparation of 4-Methoxybenzyl Chloride (PMB-Cl or
MPM chloride) (1) by Microwave Irradiation. p-Anisyl alcohol
(14) Plourde, G. L.; Spaetzel, R. R. Molecules 2002, 7, 697–705.
(15) Tasadaque, S.; Shah, A.; Khan, K. M.; Muhammad, H. H.; Anwar, U.;
Fecker, M.; Voelter, W. Tetrahedron 2005, 61, 6652–6656.
(16) Bernard, S.; Paillat, C.; Oddos, T.; Seman, M.; Milcent, R. Eur. J. Med.
Chem. 1995, 30, 471–472.
48.(12) Salanski, P.; Ko, Y. K.; Lee, K. I. MendeleeV Commun. 2006, 16, 46–
(13) We kindly thank a reviewer for suggesting the microwave reactions.
J. Org. Chem. Vol. 73, No. 14, 2008 5623

(1 mL, 1.11 g, 8.05 mmol) was placed in a 10 mL reaction tube
followed by concentrated HCl (2 mL). Upon addition of the acid,
the heterogeneous mixture then turned cloudy white. The tube was
sealed, placed into the microwave apparatus and irradiated (30 min/
120 °C). After irradiation, the reaction mixture was poured into a
separatory funnel, and the top chloride layer was separated and
dried over anhydrous calcium chloride. Removal of the drying agent
and Kugelrohr distillation (as above) gave the product chloride 1
(0.91 g, 71%) of excellent purity which can be stabilized by addition
of powdered anhydrous K2CO3.
Preparation of 4-(4-Methoxybenzyloxy) benzaldehyde (3c)
by Microwave Irradiation. 4-Hydroxybenzaldehyde 2c (0.09 g,
0.74 mmol), potassium carbonate (0.20 g, 1.48 mmol, 2 equiv) and
N,N-dimethylformamide (1 mL) were placed in a 10 mL reaction
tube followed by 4-methoxybenzyl chloride 1 (0.10 mL, 0.74 mmol,
1 equiv). The tube was sealed and placed into the microwave
apparatus and irradiated (30 min/120 °C). After irradiation, the
reaction mixture was diluted with distilled H2O (30 mL) and poured
into a separatory funnel. The product was extracted with CH2Cl2
(3 × 10 mL), and the combined organic layers were dried over
magnesium sulfate and concentrated. The crude residue was purified
by gravity column chromatography on silica gel (hexane/ethylac-
etate, 1:1) to afford the PMB-protected aldehyde product 3c which
gave analytical data identical to those of the product of the
corresponding ultrasound experiment.
Acknowledgment. Support of the Mass Spectrometry Facility
of the University of Louisville CREAM Center by NSF/
EPSCOR Grant EPS-0447479 is gratefully acknowledged. We
thank Prof. G. B. Hammond for the use of his group’s
microwave apparatus.
Supporting Information Available: Experimental proce-
dures for the sonicated and nonsonicated (control) preparation
1
of 5; H and 13C NMR spectra of all new compounds (3e-i).
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO800577F
5624 J. Org. Chem. Vol. 73, No. 14, 2008