Microwave-assisted selenium dioxide oxidation of camphor derivatives to α-dicarbonyl compounds and oxoimines

Article abstract of DOI:10.1080/00397910500501557

Camphor-derived α-dicarbonyl compounds and 3-oxo-camphorsulfonylimine have been synthesized from the corresponding ketones or sulfonylimine by microwave-assisted oxidation with selenium dioxide. Compared to the classical reaction conditions, good yields were obtained in much shorter reaction times. Additionally, the selenium precipitation is more quantitative, and its removal from the reaction mixture is easier. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500501557

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Microwave‐Assisted Selenium Dioxide
Oxidation of Camphor Derivatives to
α‐Dicarbonyl Compounds and Oxoimines
Sarah Belsey a b , Timothy N. Danks a c & Gabriele Wagner a
a Chemistry Division, SBMS, University of Surrey, Guildford, Surrey, United
Kingdom
b Prior's Field School, Godalming, Surrey, United Kingdom
c Oratory School, Woodcote, Reading, Berkshire, United Kingdom
Version of record first published: 16 Aug 2006.
To cite this article: Sarah Belsey, Timothy N. Danks & Gabriele Wagner (2006): Microwave‐Assisted
Selenium Dioxide Oxidation of Camphor Derivatives to α‐Dicarbonyl Compounds and Oxoimines, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:8,
1019-1024
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Synthetic Communicationsw, 36: 1019–1024, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500501557
Microwave-Assisted Selenium Dioxide
Oxidation of Camphor Derivatives to
a-Dicarbonyl Compounds and Oxoimines
Sarah Belsey
Chemistry Division, SBMS, University of Surrey, Guildford, Surrey,
United Kingdom and Prior’s Field School, Godalming, Surrey,
United Kingdom
Timothy N. Danks
Chemistry Division, SBMS, University of Surrey, Guildford, Surrey,
United Kingdom and Oratory School, Woodcote, Reading, Berkshire,
United Kingdom
Gabriele Wagner
Chemistry Division, SBMS, University of Surrey, Guildford, Surrey,
United Kingdom
Abstract: Camphor-derived a-dicarbonyl compounds and 3-oxo-camphorsulfonylimine
have been synthesized from the corresponding ketones or sulfonylimine by microwave-
assisted oxidation with selenium dioxide. Compared to the classical reaction conditions,
good yields were obtained in much shorter reaction times. Additionally, the selenium
precipitation is more quantitative, and its removal from the reaction mixture is easier.
Keywords: Diketones, microwave irradiation, oxoimines, selenium dioxide
Camphor-derived a-dicarbonyl compounds do not only play an important role
as chiral building blocks or auxiliaries in organic synthesis but have also
Received in the U.K. April 9, 2005
Address correspondence to Gabriele Wagner, Chemistry Division, SBMS, Univer-
sity of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom. Tel.: þ44 (0) 1483
686831; Fax: þ44 (0) 1483 686851; E-mail: g.wagner@surrey.ac.uk
1019

1020
S. Belsey, T. N. Danks, and G. Wagner
received interest in biomolecular sciences in recent years. Thus, 3-oxo-
camphorsulfonic acid was found to act an arginine-specific reagent in the
functional characterization of enzymes.[1] Camphor-derived a-dicarbonyl
compounds have also been proposed as anticancer agents because of their
ability to deactivate prenylating enzymes.[2] Such enzymes modify oncopro-
teins with the effect that cell growth becomes uncontrolled.
Generally, a-dicarbonyl compounds can be synthesized by SeO2
oxidation of a-methylene ketones.[3] Methods of more limited range use
reagents such as CuBr2/KI/DMSO, tBuOCH(NMe2)2/O2/hv, HNO3,
KMnO4, DDQ, or PCC.[4] Alternatively, 1,2-diketones can be prepared by
oxidation of alkynes,[5] vicinal diols,[6] or a-hydroxidations.[7]
SeO2 oxidations are typically performed in refluxing dioxane, ethanol, or
acetic acid, and reactions with easily enolizable substrates are complete within
approximately 4 h.[8] Poorly enolizing substrates such as camphor derivatives,
however, are less prone to SeO2 oxidations. Reaction of camphor takes 15 h, in
acetic anhydride,[9] and camphorsulfonylimine takes 20 h, in acid[10a] and 14
days in dioxane.[10b] The oxidation of camphorsulfonic acid with selenous
acid in dioxane has been reported to be complete within 72 h; reaction of cam-
phorsulfonylnorleucine requires 90 h.[11] The use of microwave irradiation is
anticipated to accelerate these reactions in a similar way to other organic trans-
formations,[12] in particular the microwave-assisted SeO2 oxidation of allylic[13]
and heteroaromatic[14] methyl groups to aldehydes and the dehydrogenation of
4,5-dihydropyridazin-3(2H)-ones with SeO2.[15] In the present work, the effect
of microwave irradiation on the reactions shown in Table 1 was studied. For all
reactions, the optimum reaction time was determined by 1H NMR monitoring.
A 20% excess of SeO2 was used to achieve complete conversion.
Under focused monomode microwave irradiation, camphor, camphorsul-
fonylimine, and camphorsulfonic acid oxidized to the respective 3-oxo
compounds within 75 min at 1508C, with the further advantage of an almost
quantitative precipitation of black selenium, which is easy to remove by fil-
tration. Camphor and camphorsulfonylimine were reacted in ethanol or
acetic acid as solvents without noticeable difference. If camphorsulfonic
acid is oxidized in EtOH at 1508C under microwave irradiation, 3-oxo-cam-
phorsulfonic acid is formed as the major product in 60% yield, together with
two uncharacterized camphor-derived compounds in approx. 10 and 15%.
However, the sulfonic acid catalyzes the condensation of ethanol to diethyl
ether under these conditions,[16] causing an undue rise of pressure in the
reaction vessel to up to 16 bar. To avoid this side reaction, the reaction was
run in water under otherwise the same conditions to provide a similar
product distribution as in ethanol.
When the oxidation of camphor was attempted in water, no reaction
occurred because the camphor sublimed into the cold upper parts of the
tube. Camphorsulfonylimine (1) was oxidized to the 3-oxo compound (2) in
water; however, the reaction is accompanied by hydrolysis to provide the sul-
fonamides (3) and (4) and sulfonic acids (5) and (6) together with a minor

Selenium Dioxide Oxidation of Camphor Derivatives
1021
Table 1. SeO2 oxidation of camphor derivatives
Entry
1
Reaction
Solvent T (8C) Time (min) Yield (%)
HOAc
EtOH
H2O
150
150
150
75
75
75
90
92
0
2
3
HOAc
EtOH
H2O
150
150
150
75
75
75
88
85
29a
EtOH
H2O
150
150
75
75
60b
56b
aOxidation is accompanied by hydrolysis of the sulfonamide (see Scheme 1).
bTwo by-products of unknown structure are formed in approx. 10% and 15%.
quantity of two uncharacterized compounds (7) and (8) (Scheme 1).
Compounds (7) and (8) were also detected in the oxidation of camphorsulfonic
acid. Compounds (2), (3), and (4) were extracted with dichloromethane, and
(4) was isolated by chromatography. Compounds (5) and (6) were identified
in the aqueous phase. Samples irradiated with microwaves for 75 min at a
set temperature of 1508C showed the following composition: (1) 5.7%, (2)
28.5%, (3) 1.5%, (4) 14.3%, (5) 11.7%, (6) 26.6% (7) 4.7%, and (8) 7.0%.
In conclusion, the use of focused monomode microwave irradiation for
the SeO2 oxidation of camphor derivatives to a-dicarbonyl compounds and
oxoimines provides several advantages over traditional thermal heating: (a)
Scheme 1. SeO2 oxidation of camphorsulfonylimine in water.

1022
S. Belsey, T. N. Danks, and G. Wagner
the reactions complete within significantly shorter times, (b) work in sealed
vessels allows use of higher temperatures and moderate pressure, (c) work in
a closed system is also safer because volatile selenium-containing by-
products produced during the reaction are not released into the environment
in an uncontrolled way, as it would be the case in an open reflux system,
and (d) the workup procedure is simplified because the selenium forming
during the reaction precipitates almost quantitatively in its black modification,
which is easy to filter. Thermal reactions, in contrast, often require repeated
reflux–filtration cycles to achieve complete selenium removal.
EXPERIMENTAL
In a typical procedure, a Pyrex cylindrical reaction tube adapted to the
SmithCreatorTM microwave (Personal Chemistry/Biotage) was charged
with the corresponding substrate (5 mmol), SeO2 (6 mmol, 665 mg), 3 ml of
the solvent (see Table 1), and a magnetic stirrer bar. The septum-sealed
tube was irradiated with microwaves at the set temperature, which was
measured by IR detection and maintained constant by modulated irradiation
of 100 W to 15 W. The cooled reaction mixture was subjected to individual
workup procedures. (a) Reactions in EtOH: the black selenium was filtered
off, and the filtrate was evaporated to dryness to produce TLC- and NMR-
pure products whose analytical data correspond to those given in the literature.
(b) Reactions in HOAc: the solvent was evaporated under reduced pressure,
and the solid residue extracted with dichloromethane (3 ꢀ 10 ml). After evap-
oration of the solvent, TLC- and NMR-pure products were obtained. (c)
Reactions in water: the reaction mixture was filtered to remove the black
selenium, and the filtrate was extracted with dichloromethane (3 ꢀ 10 ml).
Organic and aqueous phases were evaporated to dryness in separate flasks,
1
and the residues were analyzed by H and 13CNMR.
7,7-dimethyl-2,3-dioxo-bicyclo[2.2.1]heptane-methanesulfonamide (4):
Method (c), after chromatography of the CH2Cl2 soluble fraction (SiO2,
CH2Cl2/Et2O 9:l). Elemental analysis calculated for C10H15SO4N:
C, 48.96; H, 6.16; N, 5.71; S, 13.07; found: C, 48.19; H, 6.34; N, 5.93;
S, 12.88. CI-MS: (M ¼ 245.30) 246 [M þ H]þ, 228 [M 2 H2O]þ, 164
[M 2 H2O 2 SO2]þ. IR (selected bands), cm2l: 3336 and 3270 s n(NH),
1
1760 and 1775 s n(C55O), 1323 and 1165 s v (SO2). H NMR in CDCl3, d
(ppm): 1.01 (s, 3H, H-9) 1.14 (s, 3H, H-10), 1.75 (m, 1H, H-5 endo), 2.22
(m, 1H, H-6 endo), 2.25 (m, 1H, H-5 exo), 2.44 (m, 1H, H-6 exo), 2.71
(d, 5.0 Hz, 1H, H-4), 3.31 (d, 15.0 Hz, 1H, H-8), 3.67 (d, 15.0 Hz, 1H, H-8),
5.36 (s, br., 2H, NH2). 13C NMR in CDCl3, d (ppm): 18.0 (CH3, C-10),
2.14 (CH3, C-9), 22.3 (CH2, C-5), 26.9 (CH2, C-6), 44.6 (Cq, C-7), 52.9
(CH2, C-8), 57.6 (CH, C-4), 59.6 (Cq, C-1), 200.1, 202.1 (Cq, C-2, C-3).

Selenium Dioxide Oxidation of Camphor Derivatives
1023
7,7-dimethyl-2,3-dioxo-bicyclo[2.2.1]heptane-methanesulfonic acid (6):
Method (c), after crystallization from a minimum amount of H2O.
Elemental analysis calculated for C10H14SO5: C, 48.77; H, 5.73; S, 13.02;
found: C, 49.22; H, 5.96; S, 12.76. CI-MS: (M ¼ 246.28) 247 [M þ H]þ,
165 [M 2 SO3H]þ. IR (selected bands), cm21: 313 1 s n(OH), 1752 and
1771 s n(C55O), 1400, 1191, and 1051 s n(SO3). 1H NMR in CDCl3, d
(ppm): 0.93 (s, 3H, H-9), 1.17 (s, 3H, H-l0), 1.66 (m, 1H, H-5 endo), 1.95
(m, 1H, H-6 endo), 2.24 (m, 1H, H-5 exo), 2.65 (d, 5.2 Hz, 1H, H-4), 2.71
(m, 1H, H-6 exo), 3.00 (d, 14.8 Hz, 1H, H-8), 3.37 (d, 14.8 Hz, 1H, H-8).
13C NMR in CDCl3, d (ppm): 17.9 (CH3, C-10), 21.1 (CH3, C-9), 22.1
(CH2, C-5), 25.1 (CH2, C-6), 44.0 (Cq, C-7), 46.7 (CH2, C-8), 57.7 (CH,
C-4), 59.0 (Cq, C-1), 202.0, 202.1 (Cq, C-2, C-3).
ACKNOWLEDGMENT
The authors are grateful to Personal Chemistry/Biotage for the provision of a
Smith CreatorTM microwave reactor and to the Nuffield Foundation for a
science bursary.
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