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6
Organic Synthesis Using Microwaves and Supported Reagents
Rajender S. Varma
6.1
Introduction
In the electromagnetic radiation region, microwaves (0.3 GHz300 GHz) lie be-
tween radiowave (Rf) and infrared (IR) frequencies with relatively large wavelengths
(1 mm1 m). Microwaves, nonionizing radiation incapable of breaking bonds, are a
form of energy that manifest as heat through their interaction with the medium or
materials wherein they can be reflected (metals), transmitted (good insulators that
will not heat) or absorbed (decreasing the available microwave energy and rapidly
heating the sample). This unconventional microwave (MW) energy source has been
used for heating food materials for almost 50 years [1] and is now being utilized for a
variety of chemical applications including organic synthesis [211] wherein chemical
reactions are accelerated because of selective absorption of MW energy by polar mo-
lecules, nonpolar molecules being inert to the MW dielectric loss [12]. The initial ex-
periments with microwave heating exploited the use of high dielectric solvents such
as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) in a household
kitchen MW oven. The rate enhancements in such reactions are now believed to be
due to rapid superheating of the polar solvents and pressure effects [12]. However, in
these solution-phase reactions, the development of high pressures, and the use of
specialized sealed vessels are some of the limitations, although they have been cir-
cumvented by the introduction of commercial MW instruments with appropriate
temperature and pressure controls.
Heterogeneous reactions facilitated by supported reagents on inorganic oxide sur-
faces have received attention in recent years, both in the laboratory as well as in in-
dustry. Although the first description of the surface-mediated chemical transforma-
tion dates back to 1924 [13], it was not until almost half a century later that the tech-
nique received extensive attention with the appearance of several reviews, books and
account articles [1422].
A related development that had profound impact on heterogeneous reactions is
the use of microwave (MW) irradiation techniques for the acceleration of organic re-
actions. Since the appearance of initial reports on the application of microwaves for
chemical synthesis in polar solvents [11], the approach has blossomed into a useful
6.2
Microwave-accelerated Solvent-free Organic Reactions
6.2.1
ProtectionDeprotection Reactions
OH O
R
OH Clay, RCHO O
O O
O O
HO MW, 10 min, 6066% HO
OH OH
Scheme 6.1 Formation of acetal derivatives of 1-galactono-1,4-lactone.
R1 OH R1 O
KSF or PTSA
C O +
R OH MW, 1030 min R O
Scheme 6.2 Formation of dioxolanes.
184 6 Organic Synthesis Using Microwaves and Supported Reagents
Methanesulphonothioate,
R1 KF-Alumina R1 SMe
CH2 C
R MW R SMe
tained with the microwave method are better than those obtained using conventional
heating in an oil bath [32].
Thioacetals have been prepared using essentially a similar technique [33]. The ac-
tive methylene compounds are adsorbed on KF-alumina, admixed with methanesul-
fonothioate and are irradiated in microwave oven to produce thioacetals in good
yields (Scheme 6.3).
HO
Alumina MW Alumina
MW
CH(OAc)2 CHO
Neutral alumina
Interestingly, acylal formation has been accomplished with acetic anhydride [37]
on K 10 clay (7598 %) as well as deacylation [38].
CH2CH2CO2R NH2CHCO2R
CH2OH
3 min/Neutral, (92%)
(10 min)
OH
10 min/Acidic, (92%)
NH2CH2CO2R
4 min/Neutral, (95%)
(10 min)
Where R= CH2C6H5 and time in parentheses refer to deprotection in oil bath at the same
temperature
R1
Lewis acid R1
N O NH
R2 But MW R2
Scheme 6.7 Deprotection of N-tert-
O butoxycarbonyl group.
OR OR OR
(10 min, 93%) (11 min, 78%)
(10 min, 91%)
O NH2
CH3 N
HN N
RO O N RO N N
O O
OH OH
CH3
CH3
R1 S X R1
Clayfen
C C O
R2 S Y Room Temp. or MW R2
(8798%)
Where R1 = Ph, p-CH3 C6H4, p-NO2C6H4; R2 = H ; XY = (CH2)2
R 1 = R 2 = C 2H5 ; XY = (CH2)2 ; R1 = R2 = Ph ; X = Y = C2H5
R 1 = Ph ; R2 = CH3 ; XY = (CH2)2
R 1R2 = isoflavanolyl , 2-Methylcyclohexyl; XY = (CH 2 )2
R1
R1 Silica-Ammonium persulfate
C O
C NOH
MW, 1-2 min. R2
R2 (59-83%)
has continued with the availability of a wide range of such agents namely, Raney
nickel, pyridinium chlorochromate, pyridinium chlorochromateH2O2, triethylam-
monium chlorochromate, dinitrogen tetroxide, trimethylsilyl chlorochromate,
Dowex-50, dimethyl dioxirane, H2O2 over titanium silicalite-1, zirconium sulfophe-
nyl phosphonate, N-haloamides, and bismuth chloride [47, 48].
The quest for a solvent-free deprotection procedure has led to the use of relatively
benign reagent, ammonium persulfate on silica, for regeneration of carbonyl com-
pounds (Scheme 6.10) [48]. Neat oximes are simply mixed with solid supported re-
agent and the contents are irradiated in a MW oven to regenerate free aldehydes or ke-
tones in a process that is applicable to both, aldoximes and ketoximes. The critical
role of surface needs to be emphasized since the same reagent supported on clay sur-
face delivers predominantly the Beckmann rearrangement products, the amides [49].
R1
R1
Silica-Moist NaIO4
C O
C NOH
MW, 1-2.5 min. R2
R2 (68-93%)
Where R 1 = CH3 ; R2 = Ph, p-Cl C 6H4, p-Br C6H4, p-CH3 C 6H4, p-CH3O
C6H4; p-NH2 C 6H4,
R1 = R2 = Ph; R1 = R2 = Cyclohexyl, tetrahydronaphthyl,
and R 1 = C 2H5 , R2 = n-Butyl
R1 (NH4)2S2O8 - Clay R1
C N NH R C O
R2 MW or ))))) R2
(65-94%)
Where R 1 = C 4H9, Ph, p-Cl C6H4, p-CH3 C 6H4, p-OH C6H4;
R 2 = CH3; C 2H5
and R = CONH2 , Ph
Scheme 6.12 Regeneration of carbonyls from semicarbazone and
phenylhydrazone derivatives.
6.2.1.11 Dethiocarbonylation
Dethiocarbonylation, transformation of thiocarbonyls to carbonyls, has been accom-
plished with several reagents namely, trifluoroacetic anhydride, CuCl/MeOH/
NaOH, tetrabutylammonium hydrogen sulfate/NaOH, clay/ferric nitrate, NOBF4,
bromate and iodide solutions, alkaline hydrogen peroxide, sodium peroxide, thio-
phosgene, trimethyloxonium fluoroborate, tellurium based oxidants, dimethyl selen-
oxide, benzeneseleninic anhydride, benzoyl peroxide and halogen-catalyzed alkox-
ides under phase transfer conditions [55]. However, these methods have certain lim-
itations such as the use of the stoichiometric amounts of the oxidants that are often
inherently toxic or require longer reaction time or involve tedious procedures. In a
process that is accelerated by microwave irradiation,Varma et al. have demonstrated
efficient dethiocarbonylation process under solvent-free conditions using clayfen or
clayan (Schs. 6.13 and 6.14) [55].
S
O
R2
Clayfen or (Clayan) R2
1-1.5 Min
R1
R1 (90-95 %)
O R1 O R1
Clayfen or (Clayan)
1.5-2 Min
R R
S (85-91 %) O
MW
R OMPM R OH
Clayan
R = alkyl, alkenyl, alkynyl, aryl, acetate, ester, benzyl or silyl ether groups
Scheme 6.15 Cleavage of methoxyphenyl methyl (MPM) ethers using clayan.
O
KF-Al2O3 R1
R1 KF-Al2O3 R1
NH X S Ph CH OH
R2 R2 R2
O (8390%)
(7685%)
Where X = N, CH-O-
Scheme 6.16 Cleavage of sulfonates and sulfonamides on a basic KF-alumina surface.
6.2 Microwave-accelerated Solvent-free Organic Reactions 191
6.2.2
Condensation Reactions
A wide variety of MW-assisted aldol [59, 60] and Knoevenagel condensation reactions
have been accomplished using relatively benign reagents such as ammonium acetate
[61], including the Gabriel synthesis of phthalides with potassium acetate [62].
(Ph)3 P=CHCOOEt
Me R Me
N N
MW H
NH + RCHO NH
O N O N
H H
Scheme 6.18 Knoevenagel condensation reaction of creatinine with alde-
hydes.
192 6 Organic Synthesis Using Microwaves and Supported Reagents
CHO R3
R3 Base (Piperidine)
+
CO2Et MW
R1 OH R1 O O
R2 R2
K 10 Clay or EPZG
CH O H2 N CH
N
+
MW, 13 min.
R R
(9097%)
Y Y
O ( )n ( ) n2
Y EPZG or K 10 Clay 2
N H2 O N
( )n
1
+ ( )n
2 MW, 26 min.
OH
N ( )n ( )n
H 1 1
CHO NO2
NH4OAc
+ RCH2NO2
MW, 2.58 min. R
X X (8092%)
Where R = H, X = H, p-OH, m,p-(OMe)2, m-OMe-p-OH, 1-naphthyl, 2-naphthyl
R = Me, X = H, p-OH, p-OMe, m,p-(OMe)2, m-OMe-p-OH
Scheme 6.22 MW-assisted preparation of a,b-unsaturated nitroalkenes.
R1 R1
CHO CaCO3/K 10 Clay CH=N SO2
R R
+
CH(OMe) 3, MW, 30-70 W
H2NSO2 (52 - 91%)
R2 R2
R R
O O O O
R1 NHNH2 R
R
MW
NHCOPh NHCOPh
O N
R1 NH
MW irradiation conditions [80]. More recently, however, Varma and Kocevar's group
have shown that a solvent-free and catalyst-free reaction of hydrazines with carbonyl
compounds is possible upon MW irradiation (Scheme 6.24) [81]. Interestingly, the
general reaction proceeds smoothly even for solid reactants and is completed below
the melting points of the two reactants possibly via the formation of a eutectic. The
reactions have been conducted in household MW oven and the control experiments
are conducted concurrently in separate open beakers; the reactions can be essentially
followed by visual observation when a melt is obtained [82].
An interesting solid-state synthesis of amides has also been reported in a MW
oven that uses potassium tert-butoxide and easily accessible reagents, nonenolizable
esters and amines [83].
The kinetics of the acid-catalyzed esterification reaction of 2,4,6-trimethylbenzoic
acid in i-PrOH under microwave irradiation have been investigated [84]. A simple
and practical technique for MW-assisted synthesis of esters has been reported
wherein the reactions are conducted either on solid mineral supports or by using a
phase transfer catalyst (PTC) in the absence of organic solvents [85]. The esterifica-
tion of enols with acetic anhydride and iodine has also been recorded [86].
The detailed account of condensation reactions as applied to heterocyclic chemis-
try is found in subsequent section (Sect. 6.2.6), Chapt. 8 [87] and for cycloaddition re-
actions in Chapt. 9 [88].
6.2.3
Isomerization and Rearrangement Reactions
Me Me
Me OH Al 3+ Montmorillonite Me O
MW, 15 min Me
HO Me Me
Me
(98-99%)
Scheme 6.25 Pinacolpinacolone rearrangement on Al3+-montmorillonite
K 10 clay.
SC6H5 SC6H5
Cl AgBF4Al2O3
Cl
Cl MW, 10 min
(75%)
Scheme 6.26 MW-assisted ring expansion reaction on alumina.
R1 O
Montmorillonite K 10 clay
C N OH R1 C NH R2
R2 MW, 7-10 min.
Where R1= CH3 or Ph and R 2 = Ph or substituted phenyl
Scheme 6.27 Beckmann rearrangement of oximes on clay.
196 6 Organic Synthesis Using Microwaves and Supported Reagents
6.2.4
Oxidation Reactions Oxidation of Alcohols and Sulfides
Metal-based reagents have been extensively used in organic synthesis. Peracids, per-
oxides, potassium permanganate (KMnO4), manganese dioxide (MnO2), chromium
trioxide (CrO3), potassium dichromate (K2Cr2O7) and potassium chromate (K2CrO4)
are some of the common oxidizing reagents employed for organic functional groups
[94, 95].
The utility of such reagents in the oxidation processes is compromised due to their
inherent toxicity, cumbersome preparation, potential danger in handling of metal
complexes, difficulties encountered in product isolation and waste disposal pro-
blems. Immobilization of metallic reagents on solid supports has circumvented
some of these drawbacks and provided an attractive alternative in organic synthesis
because of the selectivity and associated ease of manipulation. Further, the localiza-
tion of metals on the mineral oxide surfaces reduces the possibility of their leaching
into the environment.
R1 MnO2-Silica R1
CH OH C O
R2 MW, 20-60 sec. R2
(67-96%)
R1 CrO3Wet Al2O3 R1
CH OH C O
R2 MW, 40 sec. R2
(73-90%)
R1 = Ph, p-MeC6H4, p-MeOC 6H4, p-NO2C6H4 ; R2 = H
R1 = Ph ; R2 = Me, Ph, PhCO; R1 = R2 = ,
Scheme 6.29 Oxidation of alcohols by chromium trioxide supported on
premoistened alumina.
R1 Clayfen R1
CH OH C O
R2 MW, < 1 Min. R2
(87-96%)
R1 H2O2-Claycop R1
CH R3 C O
R2 MW R2
(71-85%)
OH O
R2 Oxone Al2O3 or CuSO4Al2O3 R2
R1 MW, 2-3.5 min. R1
O O
(71-96%)
Under these solvent-free conditions, the oxidation of primary alcohols (e. g. benzyl
alcohol) and secondary alcohols (e. g. 1-phenyl-1-propanol) is rather sluggish and
poor and is of little practical utility. Consequently, the process is applicable only to
a-hydroxyketones as exemplified by various examples including a mixed benzylic/ali-
phatic a-hydroxyketone, 2-hydroxypropiophenone that delivers the corresponding
vicinal diketone [106, 107].
O
20% NaIO 4-Silica (3.0 eq.) 20% NaIO 4-Silica (1.7 eq.)
R1-SO2-R2 R 1-S-R2 R1-S-R2
MW, 1-3 min. MW, 0.5-2.5 min.
(72-93%) (76-85%)
[109]. A relatively reduced amount of the active oxidizing agent is employed which is
safer and easier to handle.
Several refractory thiophenes, that are often not reductively removable by conven-
tional refining processes, can be oxidized under these conditions, e. g. benzothio-
phenes are oxidized to the corresponding sulfoxides and sulfones using ultrasonic
and microwave irradiation, respectively, in the presence of NaIO4silica [109]. A note-
worthy feature of the procedure is its applicability to long chain fatty sulfides that
are insoluble in most solvents and are consequently difficult to oxidize.
O
IBD-Alumina
R1SR2 RSR2
MW, 40-60 sec.
(80-90%)
where R1 = R2 = i-Pr, n-Bu, Ph, PhCH2 ; R 1 = Ph ; R2 = Me, PhCH2
R1 = n-C 12H25 ; R1 = Me ; R1 = R2 = , O
Scheme 6.35 Oxidation of sulfides to sulfoxides by alumina-supported
iodobenzene diacetate.
O
O
N R1 KMnO4- Al2O3 R1
N + O
H R2 MW
R2
CHO
Scheme 6.36 Oxidation of enamines with alumina-supported potassium
permanganate.
6.2 Microwave-accelerated Solvent-free Organic Reactions 201
6.2.5
Reduction Reactions
In MW-assisted chemistry reduction reactions were the last to appear on the scene;
the use of ammonium formate and catalytic transfer hydrogenation were initial ex-
amples [23 b].
R1 Me R1 Me
Aluminum alkoxide
O + CHOH CHOH + O
R2 Me MW R2 Me
Scheme 6.37 Solvent-free reduction of carbonyls using aluminum alkoxides.
O OH
NaBH4-Al2O3
R1 C R2 R1 CH R2
MW, 0.52 min
(6293%)
The useful chemoselective feature of the reaction is apparent from the reduction
of trans-cinnamaldehyde (cinnamaldehyde/NaBH4alumina, 1 : 1 mol equivalent);
olefinic moiety remains intact and only the aldehyde functionality is reduced in a fa-
cile reaction.
No side products are formed and the reaction does not proceed in the absence of
alumina. Further, the reaction rate improves in the presence of moisture. The moist-
ure is absorbed by alumina during the recovery of the product. The alumina support
can be recycled and reused for subsequent reduction, repeatedly, by mixing with
fresh borohydride without any loss in activity. In terms of safety, the air used for cool-
ing the magnetron ventilates the microwave cavity, thus preventing any ensuing hy-
drogen from reaching explosive concentrations. The technique has been elegantly
utilized for MW-enhanced solid-state deuteration using sodium borodeuteride im-
pregnated alumina [120]. Further extension of this work in the specific labeling of
molecules has been explored [121] and is discussed elsewhere in this book [122].
Ba(OH)2 . 8H2O
RCHO + (CH2O)n RCH2OH + RCOOH
MW or oil bath
(80-99%) (1-20%)
Scheme 6.40 Solvent-free crossed Cannizzaro reaction using paraformaldehyde.
204 6 Organic Synthesis Using Microwaves and Supported Reagents
6.2.6
Synthesis of Heterocyclic Compounds
6.2.6.1 Flavones
Naturally occurring flavonoids are widely distributed oxygen heterocyclic com-
pounds in plant kingdom, the most abundant being the flavones. Members of this
class display a wide variety of biological activities and have been useful in the treat-
ment of various diseases [135, 136]. Flavones have been prepared by a variety of
methods such as AllanRobinson synthesis, and synthesis from chalcones via an in-
tramolecular Wittig strategy [137]. The commonly followed approach, however, in-
volves the BakerVenkataraman rearrangement, wherein o-hydroxyacetophenone is
benzoylated to form the benzoyl ester followed by the treatment with base (KOH/pyr-
idine) to effect acyl migration, forming a 1,3-diketone [138, 139]. The ensuing dike-
tone is then cyclized under strongly acidic conditions with sulfuric acid and acetic
acid to afford flavone.
A solvent-free synthesis of flavones has been achieved that simply involves the
MW irradiation of o-hydroxydibenzoylmethanes adsorbed on montmorillonite K 10
clay for 11.5 min. A rapid and exclusive formation of cyclized flavones occurs in
good yields (Scheme 6.41) [140]. The intramolecular Michael addition of o-hydroxy-
chalcones on silica gel surface has also been reported [141].
R2
OH R2 O
K 10 Clay
K 10 Clay
C C O + HN R C C N R
MW
H R R
(9598%) Enamines
R4 R4
OH R R3 O R
R3 NH4OAc
+ H
R2 MW, 28 min R2 Ph
CHO Ph
R1 R1
(7388%)
Where R = morpholinyl, piperidinyl or pyrrolidinyl
and R 1 = R3 = R4 = H ; R2 = H, Cl, NO2
Scheme 6.42 One-pot synthesis of 2-substituted isoflav-3-enes from in situ- generated
enamines.
wherein the in situ generated enamine derivatives have been subsequently reacted
with o-hydroxyaldehydes in the same pot (Scheme 6.42) [145].
R1
O R2
OTs N
K 10 clay
+
MW H S
R1
R2
H2N S (88-96%)
Where R1 = H, Me, OMe, Cl and R2 = Cl, OMe
Scheme 6.43 Synthesis of substituted thiazoles from in situ-generated a-tosyloxyketones.
O OTS
H
K 10 clay N
+ HN NH
MW N
S
S
R1
R1 (85-92%)
Where R1 = H, Me, OMe, Cl
Scheme 6.44 Synthesis of bridgehead thiazoles from a-tosyloxyketones.
O O
X
Y
X Y R2 Lawesson's reagent
S
MW, 3-8 min R2
H H
R1 R1
(83-94%)
Where R1 = H, OMe, Br; R2 = Ph, O-alkyl
and X = Y = CH or N
Scheme 6.45 MW-assisted synthesis of S-heterocycle-containing liquid crystalline compounds.
O
TsO
R1 CHO R1 R2
KF-Al2O3
+ MW
OH O
R2 (89-96%) O
R1 R1
H
NH2 N
R2 K 10 clay R2
C W, 12 min. C
(7080%)
O O
R
NH2 N
R CHO R1
N X Microwave N N X
+ Y Clay
H
Y
R1 NC
X= Y= C X= Y= C
X= C, Y= N X= C, Y= N
X= N, Y=C X= N, Y=C
Scheme 6.48 Synthesis of imidazo[1,2-a]annulated N-heterocycles via the Ugi reaction.
A similar strategy has been used for the Biginelli condensation reaction to synthe-
size a set of pyrimidinones (6595 %) in a household MW oven [152]. This MW ap-
proach has been successfully applied to combinatorial synthesis [153]. Yet another
example is the convenient synthesis of pyrroles (6072 %) on silica gel using readily
available enones, amines and nitro compounds [154].
6.2.7
Miscellaneous Reactions
CHO CN
NH2OH.HCl / K 10 clay
MW, 1-1.5 min
R2 R2
R1 R1
Where R1 = H, R2 = H, OCH3, NO2, OH, Br, CH3 (89-95 %)
R1 = R2 = OCH3
Scheme 6.49 Transformation of arylaldehydes to nitriles by hydroxylamine hydrochlorideclay.
6.2 Microwave-accelerated Solvent-free Organic Reactions 209
NO 2
CHO
Clayfen (Clayan)
+
MW or oil bath
(minor)
R R R
Where R = H, Cl, CH3, OCH 3
Scheme 6.50 Preparation b-nitrostyrenes using clay-supported nitrate salts.
H R
PdL2X2 + -
C C + RX + Base C C + BaseH X
Scheme 6.51 Palladium-catalyzed carboncarbon bond forming reactions using microwaves.
210 6 Organic Synthesis Using Microwaves and Supported Reagents
R2
I
Pd-CuI-PPh3
KF-Al 2O3
+ R2 H
MW
R1 R1
D
_ _
NH3+ Cl ND3+Cl ND3+ Cl
_
D2 O D2O
MW
CH3 CH3
D CH3
Scheme 6.53 Deuteration and tritiation reactions using MW irradiation.
6.2 Microwave-accelerated Solvent-free Organic Reactions 211
Me Me Me Me
- + + -
2TCOOH + N(CH2)2N 2TCOO H N(CH2)2N H O2CT
Me Me
Me Me
Scheme 6.54 Hydrogenation reactions using formates.
OH OH
H H OCOR'
Me Lipase
Me Me
+ R'CO2R +
N N
MW R X
+
PF6 - NH4 PF6
X - NH4 BF4 -
BF4
+ +
N N N N N N
R R MW
R
The approach precludes the usage of volatile organic solvents, is relatively much
faster, efficient, and eco-friendly. Significant rate enhancements are reported in the
1,3-dipolar cycloaddition reactions including the use of covalently grafted dipolaro-
philes on the ionic liquids [189].
6.3
Conclusions
Microwave heating, being specific and instantaneous, is unique and has found a
place in the expeditious chemical synthesis domain. Specifically, the solvent-free re-
References 213
actions are convenient to perform and have demonstrated clear advantage over the
conventional heating procedures as summarized in this chapter. Numerous selective
organic functional group transformations have been accomplished more efficiently
and expeditiously using a variety of supported reagents on mineral oxides as cata-
lysts. Although a large body of work has been performed around the world using an
unmodified household microwave oven (multimode applicator), more recent work
does point out the advantages of using commercial systems wherein not only the im-
proved temperature/power control is possible but also the relatively large-scale reac-
tions can be conducted [190, 191] with additional options for a continuous operation.
The engineering and scale-up aspects for the chemical process development have
also been discussed [192].
There are distinct advantages of these solvent-free procedures in instances where
catalytic amounts of reagents or supported agents are used since they provide reduc-
tion or elimination of solvents, thus preventing pollution at source. Although not
delineated completely, the reaction rate enhancements achieved in these methods
may be ascribable to nonthermal effects. The rationalization of microwave effects
and mechanistic considerations are discussed in detail elsewhere in this book [25,
193]. A dramatic increase in the number of publications [23 c], patents [194203],
a growing interest from pharmaceutical industry, with special emphasis on combina-
torial chemistry, and development of newer microwave systems bodes well for micro-
wave-enhanced chemical syntheses.
References
1 C. R. Buffler, Microwave Cooking and 8 R. S. Varma, Pure Appl. Chem. 2001, 73,
Processing. Van Nostrand Reinhold, 193.
New York, 1993, pp. 168. 9 F. Langa, P. de la Cruz, A. de la Hoz,
2 R. S. Varma in: ACS Symposium Series A. Daz-Ortiz, E. Dez-Barra,
No. 767/Green Chemical Syntheses and Contemp. Org. Chem. 1997, 4, 373.
Processes. P. T. Anastas, L. Heine, 10 A. Loupy, A. Petit, J. Hamelin,
T. Williamson, (eds.), American Che- F. Texier-Boullet, P. Jacquault,
mical Society, Washington DC, 2000, D. Math, Synthesis 1998, 1213.
Chapt. 23, pp. 292313. 11 a) R. Gedye, F. Smith, K. Westaway,
3 R. S. Varma in: Green Chemistry: Chal- H. Ali, L. Baldisera, L. Laberge,
lenging Perspectives. P. Tundo, P. T. Ana- J. Rousell, Tetrahedron Lett. 1986, 27,
stas, (eds.), Oxford University Press, 279; b) R. J. Giguere, A. M. Namen,
Oxford, 2000, pp. 221244. B. O. Lpez, A. Arepally, D. E. Ramos,
4 R. S. Varma, Green Chem. 1999, 1, 43. G. Majetich, J. Defauw, Tetrahedron
5 R. S. Varma, Clean Products Proc. 1999, Lett. 1987, 28, 6553.
1, 132. 12 C. Gabriel, S. Gabriel, E. H. Grant,
6 R. S. Varma in: Microwaves: Theory and B. S. J. Halstead, D. M. P. Mingos,
Application in Material Processing IV. Chem. Soc. Rev. 1998, 27, 213.
D. E. Clark,W. H. Sutton, D. A. Le- 13 Using chemical reagents on porous car-
wis, (eds.), American Ceramic Society, riers, Akt.-Ges. Fur Chemiewerte. Brit.
Westerville, Ohio, 1997, pp. 357365. Pat. 1924, 231,901. (Chem. Abstr. 1925,
7 a) R. A. Abramovich, Org. Prep. Proc. 19, 3571).
Int. 1991, 23, 683; b) S. Caddick, Tetra- 14 A. McKillop, K. W. Young, Synthesis
hedron 1995, 51, 10403. 1979, 401 and 481.
214 6 Organic Synthesis Using Microwaves and Supported Reagents