III. Oxidation of Carbon-Carbon Double Bonds

III.
Oxidation of Carbon-Carbon Double Bonds
The chapter deals with the direct oxidation of the carbon-carbon double
bond. It is divided into three main sections. The first one includes the oxi-
dation of alkenes under a variety of conditions. The second section reports
on oxidations of enol ethers and of O-silylated enolates. The third section
deals with the oxidation of aromatic double bonds, including ring oxidation
of polynuclear arenes and of aromatic heterocyclic compounds and the oxi-
dation of phenols and aromatic amines.
A. Oxidation of Alkenes
The oxidation of double bonds is usually of minor interest for preparative

purposes, since the reaction leads in several cases to a variety of different
products, among them epoxides, IX-ketols, or cleavage products like ketones
and carboxylic acids. Aldehydes, ketones, and carboxylic acids having the
same number of carbon atoms as the parent alkene may also be formed via
rearrangement. The reaction is further complicated by competitive oxidation
at the allylic positions. The course of the reaction strongly depends upon the
structure of the olefin and the conditions employed: partially aqueous
mediums generally favor oxidative cleavage of the double bond whereas
anhydrous conditions lead to allylic attack or to the formation of partially
oxidized products like epoxides and ketols. Chromic acid oxidation of double
bonds has proved to be useful in some special cases such as the Barbier-
Wieland and Marker degradation of steroids, epoxidation of tetraarylolefins,
and allylic oxidations.
1. Oxidation of Alkenes With Chromium Trioxide

in~Acetic Anhydride or Acetic Acid
While chromic acid in aqueous sulphuric acid usually cleaves the double
bond, the oxidation of substituted olefins in acetic anhydride (chromyl ace-
tate) gives the corresponding epoxide as the main product in yields depending
upon the structure of the olefins. Small amounts of fission materials are
always present:
59
G. Cainelli et al., Chromium Oxidations in Organic Chemistry
© Springer-Verlag Berlin Heidelberg 1984
III. Oxidation of Carbon-Carbon Double Bonds
The yield of epoxide is greatest when one or each of the unsaturated

carbon atoms of the olefin carries no hydrogen atoms. Thus, cyclohexene
gives only a poor yield of epoxide. No epoxides could be isolated from
styrene, pent-2-ene, or oct-I-ene, although the formation of an epoxide
from oct-I-ene may be reasonably inferred from the formation of I-acetoxy-
octan-2-one, when the oxidation is carried out in acetic acid [I]. Table I
presents some of the results obtained.
The formation of stable epoxides from oletins by the action of chromium
trioxide has been achieved in acetic anhydride as well as in acetic acid [5].
For instance, the oxidation oftetraphenylethylene has been reported to afford
the corresponding tetraphenylethylene oxiae. The yield of epoxide is in the
range of 50-70% when the reaction mixture contains no water [5]. Small
amounts of benzophenone and benzopinacol carbonate are also obtained:
57% 70%
~
Ph-C-Ph 11 % 16%
19%
In contrast, an aqueous acetic acid medium will lead to low amounts

of benzpinacolone by rearrangement of the epoxide [5]:
Ph 0 Ph 36-56%
Ph~Ph
Ph 0
\ II
Ph~C-Ph 5-16%
Ph
~
Ph-C-Ph 26-44%
The presence of nitrogroups in the phenyl rings reduces the yield of

epoxide in favor of the cleavage products. Thus, for instance, tetra-p-
nitrophenylethylene upon oxidation with chromic acid in acetic acid gives
60
Table 1. Epoxidation of Tetra- and Trisubstituted Diolefins With Chromic Trioxide

in Acetic Anhydride
Substrate Product Yield % Ref.
d=< ~ 88 2
~
60 2
Br
B~ 64 2
Br
Br
CI
c,~ 30 2
CI
CI
W
o 0
mainly 3
~ ~
o H
53 4
61
Table 1. (continued)
~ ~ 14 4
CI
c~
CI
o H
50 4
CI
Br
Br
~Br
o H
54 4
}P
CI
CI
~ 62 4
CI
CI
49 4
CI
CI
62
rise to a mixture of 28 % of tetra~p-nitrophenyloxirane and 63 % of 4,4'-

dinitrobenzophenone [6]:
°oNo, ~
o'qo)OJ
6b AcOH
o +
02N N02
63%
The oxidation oftetraphenylethylene in acetic anhydride affords a 10-20 %

yield of benzpinacolcarbonate. No benzpinacolcarbonate is formed unless
the reaction mixture contains acetic anhydride (or propionic anhydride).
Carbonate formation predominates (62 % yield) when potassium acetate
Table 2. Cyclic Carbonates From Tetrasubstituted Olefins [5]
Substrate Product Yield %
Br Br
Br
66
Br Br
Br Br
d=b
o 0
gAg
o 0
42
~00 ~ 00
25 -30
~
a a ~
o 0
48
63
is added to the reaction mixture. In th~s way a certain number of carbonates

have been prepared from the corresponding arylethylenes (see Table 2).
1,2-Diphenylacenaphthylene affords 1,8-dibenzoylnaphthalene in ap-
proximately 90 % yield, both in aqueous acetic acid and in the presence of
acetic anhydride. In this case the absence of the corresponding epoxide is
explained by its instability caused by the strain within the five-membered
ring [5]: .
°
Ph Ph
~&5
Cr03'
,AcOH,H20 . ~Qt==DC Cr03. AcOH. Ac2..o +
25-30%
[OOJ
00
or AcOK
Cr03,AcOH
90%
60%
However, when the acenaphthylene was oxidized in the presence of

potassium acetate, cis-l,2-diphenylacenaphthenediol carbonate (25-30 %)
in addition to the dibenzoylderivative was obtained. The oxidation of tetra-
arylethylenes containing electron withdrawing substituents on the rings
gives higher yields of carbonate esters than the analogous oxidation of the
unsubstituted parent compound. Thus, tetrakis(p-bromophenyl)ethylene
yields 33 % of the corresponding carbonate without addition of potassium
acetate and 66 % in the presence of this salt r5].
The oxidation of tetraarylethylenes with chromic acid lacks stereo-
specificity since 1,2-diphenyl-l ,2-(p-chlorophenyl)ethylenes give mixtures
of the two stereoisomeric epoxides and carbonates [7]:
00 bd'
CI
6b db
22%o1a
+ 1: 1 mixture
o
CI
Cr03
o 0 CI
0
AC20,AcOH
• CI CI CI
CI
~O~O~ OO~O{) 53%o1a
~+~
1: 1 mixture
o 0 0 0
CI
64
Only tetraaryl ethylenes appear to give high yields of the corresponding

pinacol carbonates. In fact, no carbonate ester was isolable when tetramethyl-
ethylene was oxidized.
Many steroidal and terpenic cyclic alkenes react with chromic acid
in acetic acid to give epoxides and saturated, lX,jJ-unsaturated, IX-hydroxy
and lX,jJ-epoxyketones which arise from the intermediate epoxides:
I I
-c-c-c-
I I "
H H 0
H H
I I I I I I I
-c-c=c- -c-c-c- -c-c-c-
I I '0'
H H H
I OHO
I "
I I I I I I I I I
-C=C-C-H
I
- -c=c-c=o -C-C-C=O
OH '0'
The primarily formed epoxide may, indeed, undergo rearrangement

to the corresponding ketone or ring cleavage to give a diol or an allylic
alcohol which are further oxidized to the end products. Several examples
have been reported in the literature. Thus, for instance, 3jJ-acetoxy-51X-
cholest-6-ene on treatment with chromic acid in acetic acid gives, together
with acidic material, 3jJ-acetoxycholest-5-en-7-one [8]:
Another example is the oxidation of 3jJ-acetoxylanost-8-ene with chromic

acid in chloroform-acetic acid [9]. The oxidation strongly depends upon the
reaction temperature: after a brief treatment at room temperature the only
compounds present in the reaction mixture are the starting material and the
le -9(11 )-diene. At 50 °e a 74% yield of LJ 9 (11 )-7 -ketone together with 15 % of
the LJ8-7,1l-diketoderivative is obtained. At 60 °e the former product is con-
verted to the latter in good yield. The sequence of chromic acid oxidation
at temperatures below 60 °e, therefore, seems to be the following:
65
Homo and heteroannular steroidal and terpenic dienes seem to follow

the same scheme as above. Ergosterol acetate, for instance, reacts with sodium
dichromate in acetic acid/benzene to give LJ7,22-ergostadiene-3f3-acetoxy-
50:-hydroxy-6-one and the corresponding 50:-hydroxy-60:-acetoxyderivative
[10] :
AcO . l:tJ
HO 0
+
ACOctY
HO OAc
Upon oxidation with chromic acid in aqueous sulphuric acid/acetone

(Jones' reagent) 3f3-acetoxy-50:-cholest-8,14-diene furnishes 3-acetoxy-9-hy-
droxy-15-oxo-50:-cholest-8(14)-ene through an intermediate formation of the
corresponding 140:, 150:-epoxide [11]:
-l W, AcO :
~ 0'"
CSH17@,,,;CSH17J
-
AcO ;
OH;
OH
H H
66
The oxidation of certain complex, olefinic substrates may sometimes take

a course which depends upon peculiar structural and stereochemical features
of the molecule. The favorable relative position of double bond and carboxylic
group in the pentacyclic triterpene oleanolic acid is responsible for the for-
mation of high amounts of a keto lactone from oxidation of the acetate of
oleanolic acid with chromic acid in acetic acid [12]:
•
AcOH
AcO AcO
In other cases the oxidation appears to be less predictable giving rise to

anomalous products. An interesting example is the formation of the so called
"Os-acetate" from chromic acid oxidation of 3f3-acetoxy-olean-ll,13(18)-
diene [13]:
---
Cr03
AcOH
A synthetically useful cleavage of a double bond by means of chromium

trioxide in acetic acid has been devised by Barbier [14] which was first
applied for degradation of bile acid side chains by Wieland [15]. The degra-
dation involves oxidation of the trisubstituted olefin obtained by reaction
of a carboxylic ester with a Grignard reagent (usually phenyl magnesium
bromide or, less frequently, methyl magnesium iodide) followed by dehydra-
tion of the resulting tertiary alcohol:
R'
I
RCHCOOCH3 + C6H5MgBr
R-COOH
~
er03
b AcOH
R-C-R'
o"
a, R'= H b, R'= Alkyl
67
If the starting ester contains a methylene group adjacent to the carboxyl

(R' =H), the Barbier-Wieland degradation procedure affords the next
lower acid. Esters branched in Ct.-position (R' = alkyl or aryl) give rise to the
corresponding ketones.
In some early examples the intermediate carbinol is directly oxidized by
means of chromic acid in boiling acetic acid [15]. Best results have been
obtained, however, by performing the oxidation on the diphenylethylene
intermediate in acetic acid alone or together with co-solvents like chlorinated
hydrocarbons at temperatures ranging from below 15°C to 50 dc. The
method has been extensively used in the bile acid field but has also been applied
for the degradation of straight chain or branched chain fatty acids including
phenyl substituted [16] ones and of olefinic [17 a, b] and acetylenic acids [17 a].
Despite the relative length of the procedure, the overall yields on degradation
of an acid to the next lower homolog may reach 50 % (Table 3).
A modification of the Barbier-Wieland procedure, which allows the
shortening of a carboxylic acid side chain by three atoms at one time, has
been extensively applied in steroid chemistry known there to as the Meystre-
Miescher-Wettstein degradation [22]. The method involves oxidative cleavage
of a conjugated diene obtained by allylic bromination and dehydrobromi-
nation of the Barbier-Wieland diphenylethylene intermediate:
yH3
R-CH-CH2CH2-COOCH3
CH 3
I
R-C=O +
The yields of the oxidative cleavage lie in the order of 70-80 %, whereas
those of the overall degradation are in the range of 30-35 %. It is worth
mentioning that up to 0.7 equiv. of diphenylacrolein per equivalent of methyl
ketone has been isolated.
Double bonds conjugated with a carbonyl group seem to better resist
the cleavage. Thus, for instance, L1 4 • 20 , 23 -3-keto-21-acetoxy-24,24-diphenyl-
cholatriene is converted with chromium trioxide in acetic acid/ethylene
chloride at 0°-25°C into ll-desoxy-corticosterone acetate [23]:
er03
68
Table 3. Barbier-Wieland Degradation of Steroids
Substrate End Product' Overall yield % Ref.
~COO" COOH
HO ~o~ 13 18
~oo"
COOH
AcO ~o~ 20 19
HO'" ct5f9 ; COOH
HO
.#COO",
46 20
ct5f9 "octSD
HO COOH
" ' COOH

9 21
HO'
HO' ~ ct59
.' '
"OH
COOH
HO"
• After one or more Barbier-Wieland degradation steps.

"OH
COOH
41 21
Table 4 presents some examples of oxidation cleavage of steroidal dienes.

Oxidative cleavage of cycloolefins to the corresponding dialdehydes in
satisfactory yields has been achieved by means of chromium trioxide/tri-
fluoroacetic anhydride (chromyl trifluoroacetate) in tetrachloromethane-
acetone at room temperature [26]:
r--'CH
r - CHO ' n=3 33%
(CH2)n II (CH2)n n=4 46%
~CH n=5 68%
"--CHO.
n=6 61 %
69
Table 4. Meystre-Miescher-Wettstein Degradation of Steroids
Substrate End Product Overall yield % Ref.
HO'"
c66 0
COOMe
HO"
~OO
18.5 22
o o~ 64 24
~
#
24
o
r 0
AcO...
25
AcO'"
o~ 25
As by-products the corresponding epoxides and trans diols have been

isolated.
Chromic acid in acetic acid has been successfully used to cleave the double
bond of enol ethers to an ester and a carbonyl compound:
An important example 1S the preparation of LJ16-20-ketosteroids from

sapogenins [27]:
70
erOa
AcOH/H20/AcONa
AcOH
It has been shown, in fact, that steroidal sapogenins are converted with
acetic anhydride at 200°C by cleavage of the ring F, with introduction of a
20,22-double bond, to the corresponding pseudosapogenins or furostadiene
derivatives. Chromic acid oxidation of these compounds in 90 % acetic acid
containing sodium acetate at room temperature for several hours affords
a ketoester acetate which on treatment with boiling acetic acid gives the
J16-20-ketopregnane compound.
2. Oxidation of Alkenes With Chromic Acid

in Aqueous Sulphuric Acid
The main reaction occurring in chromic acid/aqueous sulphuric acid oxi-
dation of olefinic double bonds is oxidative fission. The reaction is, however,
complicated by rearrangements.
Asymmetric disubstituted olefins lead to the formation of an acid with the
same number of carbon atoms as the original olefins. Thus, for instance,
a good yield of 2,3-dimethylbutanoic acid was obtained from the oxidation
of 2,3-dimethylbut-l-ene [28].
erOa
.. ~COOH
This may correlate with the fact that epoxyderivatives of such olefins,
namely 1,2-epoxy-l, I-disubstituted ethylenes, are prone to "i-earrangement
or breakdown in .the oxidation medium and hence cannot be isolated. The
reported isolation in high yields of diphenylacetic acid and benzophenone
from the chromium trioxide-acetic anhydride oxidation of 1, I-diphenyl-
ethylene supports this view [29]:
erOa
acidic condo ~COOH. ~o
71
Another example is the facile conversion, on treatment with aqueous

acid, of 4,4-dimethyl-2-neopentyl-l,2-epoxypentane to 4,4-dimethyl-2-neo-
pentylpentanal. In the presence of chromic acid this may be oxidized to the
corresponding acid. In fact, this acid is the principal product of chromic
acid oxidation of both the epoxide and the corresponding olefin [30a, b]:
o
COOH
CrOa
H2 S04fH20
"t,/-01 ~ al.
\\&'1- ~,/-o'"
--
o
sOD.I CHO
~'/- H30+
The results of oxidation of 1, I-disubstituted ethylenes with chromic acid

in aqueous sulphuric acid are summarized in Table 5.
Table 5. Oxidation of l.1-Disubstituted Olefins With Chromic Acid in Aqueous Sul-

phuric Acid
Substrate Products (yield %) Ref.
}
CI CI CI
~o ~COO" 31
46.5 20
Sr Sr Br Br
\
0 CHO
~C~" 31
Br Br Br Br
50 12.5 24
COOH
0
¢ COOH
31
49.5 38
72
Substrate Products (yield %) Ref.
}
OMe OMe
~o ¢
OMe
31
eOOH
50 48
d= do }COOH 32
eOOH
~ ~o )=0
~ c6 32
eOOH
0
¢ eOOH
32
Trisubstituted and tetra substituted olefins oxidize under aqueous acidic

conditions through normal cleavage and by a similar rearrangement as
above affording ketones and acids with the same number of carbon atoms
as the parent olefins. The course of the reaction seems to depend upon the
concentration of sulphuric acid. Thus, for instance, the oxidation of tetra-
methyl ethylene in a low concentration of sulphuric acid affords mainly
-acetone, the product of normal oxidative cleavage; in aqueous sulphuric
acid of a concentration exceeding 50 % the product contains a considerable
proportion of 3,3-dimethylbutan-2-one resulting from rearrangement [33]
(Table 6):
er03
)=0 +
73
Table 6. Oxidative Cleavage of Olefins by Chromic Acid-Aqueous Sulphuric Acid
Substrate Products Ref.
do <go
~ Q-COOH 4
dY
CI
do
CI
Q-COOH 4
~
4
Q-COOH
CI CI
Br Br
dY
Br Br
CI
0 Q-COOH 4
}?
CI
o . ~o Q-COOH 4
CI CI
~ ~o 0-\ Q-COOH 4
74
~O 2
Br Br
0 )=0 2
Br Br
CI
0 )=0 2
CI CI
d=< dO )=0 )-COOH 2
75
Under similar conditions 2,4-dimethylpent-2-ene gives 2,2,3-trimethyl

butanoic acid together with acetone and isobutyric acid [33]:
~COOH + >=0 + >-COOH
~CHO
Table 7. Oxidation of Tri- and Tetrasubstituted Olefins With Chromic Acid III
Aqueous Sulphuric Acid
)=0 33
-<-eOOH ~eOOH 28
~ \COO" +eOOH JO ~ 34
X 2tCOO" -1- eOOH =>0 34
-)-
~ -1- eOOH 34
-\tOH
76
The 2,2,3-trimethylbutanoic acid may arise by rearrangement of the first

formed epoxide, followed by oxidation [28]. The formation of rearranged acids
and ketones together with the normal fission products has been reported
for the oxidation in aqueous sulphuric acid of a number of tri- and tetra-
substituted olefins (fable 7).
Whether the observed products of oxidative rearrangement could be in all
cases adequately accounted for on the basis of the acid catalyzed opening
of an intermediate epoxide is an open question. Evidence against this view
seems to be provided by observations on some diaryl-2-methylpropenes;
these give rise to epoxides in high yields by reaction with chromic acid in acetic
anhydride, yet they are oxidized by aqueous sulphuric-chromic acid faster
than the epoxide is hydrated by aqueous sulphuric acid of the same strength
[4]. Terminal olefins are relatively unreactive towards the Jones' reagent
(for preparation see p. l33). When the reagent is added to an acetone solution
of a terminal olefin at 20°C a slow non-selective oxidation takes place. Addi-
tion of a catalytic amount of mercuric acetate or mercuric propionate (20 %
mol based on olefin) to the solution results in a rapid conversion of the olefin
to the corresponding methylketone in yields of 80-90 %(fable 8), probably
through the formation of a 2-hydroxyalkylmercury(II) derivative, which is,
in turn, oxidized to the corresponding acid-labile 2-ketoalkylmercury(II)
compound. Protolysis of the carbonmercury bond of this substance affords
the methyl ketone and regenerates the mercury(II) species [35]:
+ H20 ?H [0] ~
R-CH=CH2 + [H90AC] = R-CH-CH 2-HgOAc - R-C-CH 2 -HgOAc
!w
o
R-g-CH3 + [H90AC] +
Similar oxidations of 1,2-disubstituted olefins give fair (20-70 %) yields

of ketones; in the case of unsymmetrically substituted olefins, mixtures of
ketones are produced.
3. Mechanism of Alkenes Oxidation With Chromic Acid
The formulation of a detailed mechanism for chromium(VI) oxidation of
olefins is rather difficult because of the diversity of reactions and the lack
of certain basic information. Thus, since the intermediate valsmce states
[chromium(IV) ap.d (V)] react faster than chromium(VI) and since all in-
formation obtained from kinetic studies refers only to chromium(VI) the
data may account for merely one third of the products formed. The oxidation
of olefins by chromium (VI) is first order in olefin and chromic acid, acid
catalysed and solvent dependent. The rate of the reaction is higher with an
increasing number of alkyl substituents and is primarily determined by their
number rather than by their position on the double bond (Table 9). Thus
cis- and trans-2-butenes and isobutene react at about the same rate [36].
In this respect chromium(VI) oxidation closely resembles olefin reactions
leading to a three membered ring product or intermediate like in epoxidation
77
Table 8. Oxidation of Terminal Olefins by Jones' Reagent Catalyzed by Mercury(II)

[35]
0
~ ~ 82
0
~COOH ~COOH 83
~ >ly 0
86
~ W 0
70
~ (J(' 26
Table 9. Rates of the Chromium(VI) Oxidation of Olefins at

25 °C in 0.002 M Sulphuric Acid in 95 % Acetic Acid [36]
Olefin
CH3CH=CHZ 0,95
C~C~CH=C~ 1.53
CH3 CH z C~ CH = CHz 2.22
(CH3)3 CCH= CHz 2.02
(CH 3)zC=CHz 7.28
(CH3)3CC~C=CHz 10.1
I
CH3
cis-CH3 CH = CHCH3 8.42
trans-CH3 C'H = CHCH3 5.55
(CH3)zC = CHCH3 91.9
(CH3)zC = CHC(CH3)3 32.4
(CH 3 )zC= C(CH3 )z 469
Cyclohexene 72.4
Cyclopentene 93.1
Norbornene 397
C 6 H s CH=CHz 167
(C6 H s )zC=CHz 363
trans-C6 Hs CH = CHC;,Hs 221
78
and halogen addition, and appears to be diametrically different from acid

catalyzed hydration or from oxidation of olefin with thallic ions. In both
of these reactions isobutene is about I03-lCf times more reactive than the
2-butenes and the reaction proceeds through a carbonium ion type inter-
mediate. The conclusion which can be drawn from this comparison is that the
transition state for the oxidation must be symmetrical. The reaction does not
seem to be very sensitive to steric effects. Tert-butylethylene and IX-neopentyl-
IX-methyl ethylene exhibit reactivities characteristic of similar substituted
olefins containing no bulky groups. The most significant rate effect which
can be ascribed to steric hindrance is observed for lX-tert-butyl-f3,f3-dimethyl-
ethylene which reacts almost three times slower than ethylene. The insensitivity
of the chromium (VI) oxidation to steric effects has been taken as an indication
that the formation of a direct chromium to carbon bond in the transition state
is unlikely. A proposal for a scheme of the reaction mechanism has been
made which is consistent with most experimental data including the lack
of stereospecificity in the formation of epoxides and diol carbonates [36, 5]:
R, /R
c-c
R/ '0/ 'R
--
c
R, ~
,
R-C-C-R
R
o
II
C
[0] R 0' '0 R
,I 1/
c-c
R" "R
79
In accord with the proposed mechanism, the addition of acetate ions and
the use of negatively substituted tetraarylethylenes results in higher yields of
carbonates. The high nucleophilicity of the acetate ion, compared with acetic
acid or acetic anhydride, allows for more effective competition of the carbonate
forming pathway. Another possible mechanism for the epoxidation is a
"three center" type addition similar to that pictured in the epoxidation of
olefins with peracids.
4. Oxidation of Alkenes With Chromyl Chloride

The first study of chromyl chloride on the oxidation of olefins was made by
Etard in 1881, who reported [37] of an aldehyde produced from the olefin
camphene by the action of chromyl chloride. The reaction was applied
without great succes§ on several terpenes under formation of complex
mixtures of ketones, aldehydes, and chlorinated compounds which were
usually not identified [38].
The nature of the products resulting from chromyl chloride oxidation
of carbon-carbon double bonds in alkenes, cycloalkenes, and styrenes has
been a subject of great controversy for several years.
It has been reported [39] that excess chromyl chloride (up to a 1 : 2 molar
ratio) oxidizes alkenes to chlor6hydrins in low yields. Thus, cyclohexene
was found to give, among other unidentified materials, trans-2-chlorocyclo-
hexanol (21 %), cis-2-chlorocyclohexanol (14%), and cyclohexanone (6%)
whereas 1-hexene was converted to 2-chloro-1-hexanol (33 %), l-chloro-2-
hexanol (9 %), and 1-chloro-2-hexanone (5 %) together with small amounts
of other carbonyl compounds. However, more recent studies [40] have shown
that when a 1 : 1 molar ratio of chromyl chloride and alkene is used, the major
oxidation products are carbonyl compounds which arise from hydride or
alkyl migration:
hydrolysis
[adduct]
O-SoCZn
The significant difference between these results is probably due to the

vastly different experimental procedures. Many products arise from sub-
sequent reactions, e.g. oxidation, chlorination, double bond cleavage, etc.,
occurring during isolation and during reductive hydrolysis.
In order to obtain high yields of carbonyl products and to minimize
undesiderable secondary reactions (carbon-carbon double bond cleavage,
chlorination, etc.) the initially formed chromyl chloride-alkene adduct is
80
not isolated buthydrolyzed under reducing conditions. Presumably, the reduc-

ing agent (S02 or Zn dust) reduces any Cr(IV), Cr(V), or Cr(VI) species that
might be formed during hydrolysis of the adduct. Zinc dust is the preferred
reducing agent when aldehydes are formed, since sulphur dioxide catalyze the
polymerization of aliphatic aldehydes.
Illustrative Example: 2,4,4- Trimethylpentanal [41]
A solution of 112,2 g (1.00 mole) of2,4,4-trimethyl-l-pentene in 11 of methyl-
ene chloride is cooled to 0-5 °C. A solution of 158 g (1.02 moles) of freshly
distilled chromyl chloride in 200 ml of methylene chloride is added dropwise.
The reaction mixture is then stirred for 15 min. and 184 g of 90-95 %
technical grade zinc dust is added. The mixture is stirred for 5 min., 11 of
ice-water and 100 g of ice are added as rapidly as possible and the mixture
is stirred for an additional 15 minutes. The methylene chloride is removed
and the residue is steam distilled. A yield of 90-100 g (70-78 %) of 2,4,4-
trimethylpentanal is obtained by distillation of the organic phase.
Table 10 shows some of the carbonyl compounds obtained with this
procedure.
If the halogenated solvents are replaced by the relatively polar solvent
acetone, chromyl chloride will react with symmetrical, disubstituted and
trisubstituted olefins to afford oc-chloroketones as the only product [43]:
CI 1
R L---R
acetone ~R2
o
Zinc dust reduction prior to work-up produces the corresponding ketones.

Best results are obtained when the chromyl chloride is added to the acetone
solution at -70 dC'although the yield at higher temperatures (-5°C to
3 0c) is still quite good. The inconvenience of cooling large scale reactions
to -70°C and the insolubility of many substrates in acetone at such tem-
peratures should make this latter choice preferable in certain cases. The
reaction is remarkably clean with trans-disubstituted olefins: only traces
of by-products are formed. On the contrary, cis disubstituted olefins react
more slowly and yields are low (a similar effect was observed in oxidation
of olefins with permanganate in acetic anhydride [44]). With the only tri-
substituted olefine tested, 2-methyl-2-heptene, a chlorohydrin is formed in
addition to the expected chloroketone.
Illustrative Example: oc-Chlorocyclododecanone [43]
A solution of 16.6 g (0.10 mole) of cyclododecene (91 % trans, 7 % cis, 2 %
diene) in 500 ml acetone is cooled to -70°C and then treated dropwise under
stirring with 33.0 g (0.21 mol) of chromyl chloride. The reaction mixture was
stirred at -70°C for 1 h, then allowed to warm to room temperature and
stirred at 25°C for 1 h. The homogeneous red-brown mixture is then slowly
poured into an ice-cold aqueous 0.3 M sodium bisulphite solution. After
30 min. stirring at 0 °C, the green mixture is extracted with ethyl ace-
81
Table 10. Chromyl Chloride Oxidation of Alkenes
80 428
75 428
:>lyCHO
~ 35 428
Jy { >Y
0
50
428
~ 6
2 9~
60
42b
2 3
d=b
o 0
70 42c
tate: hexane (1 : 1). After evaporation of the solvent a greenish yellow oil was
obtained (24 g). The crude oil was distilled to afford 17.1 g (79 %) of IX-chloro-
cyc1ododecanone.
A selection of obtained chloroketones is listed in Table 11.
82
Table 11. Oxidation of Olefins by Chromyl Chloride in Acetone [43]
0 0° 79a , 70 b
W C 90 a ,8l b
C) C:X~I 68 a , 65 b
a
~ 35 a
{
~ CI
CI
35 a
~
a
~
{J0 Y)<
a
54 a
6a
~
(~ cia
45 a
unidentified chlorhydrin 32 a
0 0: 1 38 a
rh rt:r.: 58 a
a b
at 70°C al-5-3°C
83
To obtain ketones the reaction mixture, after addition of chromyl

chloride, was treated with zinc dust in acetic acid at room temperature.
Another modification of the chromyl chloride oxidation procedure
leads to highly preferential formation of a single useful product. When
oxidation is performed in methylene chloride in the presence of acetyl
chloride, vicinal chloroacetates are produced in good yields [45]:
X
RHO
+
Q
Cr
0
,
I , . (2:1), - 78 DC
R1 H CI CI
The reaction is brought about at -78°C using methylene chloride-

acetyl chloride (2: 1) as solvent. Unsymmetrical olefins show a high preference
for the regioisomer in which the chlorine atom is attached to the more
substituted carbon (i.e. formally an anti-Markownikow addition of CI + and
AcO- across the double bond). As shown by the oxidation of (Z)-l-deuterio-
l-decene there is a preference for cis-addition of CI and AcO.
Hydrolysis of the chloroacetates obtained leads, in fact, to an erythro:

threo mixture of 4: 1. Similarly, (E)-cyc1ododecene gave threo-2-chlorocyc10-
dodecyl acetate. However, (Z)- and (E)-5-decene and cyc10hexene give
varying amounts of erythro- ai1d threo-chloroacetates. Presumably the iso-
mers resulting from trans-addition of CIOAc are due to trans opening of
an epoxide intermediate. A number of examples of chloroacetate formation
from simple olefins is presented in Table 12.
Table 12. Oxidation of Olefins With Cr0 2 CI2 /AcCl [45]
Substrate Product • Yield %
~OAe 65
CI
~CI 12
OAe
~OAe 74
CI
~CI 14
OAe
84
Substrate Product Yield 0/0
CI OAe
C4H9) - - l · C4H9 26
H H
~ CI OAe
C4H9';;)---I<: H 52
H C4H9
CI OAe
C4H9')----J<:C4H9 '2
H H
~
CI OAe
C4H9·)----\;."H 52
H C4H9
CI
~OAe
00 55
0 ~~ , 56
a
"_~ 5
CI 5'
OAe
0
a:~e 20
r 40
r
~.
4
~ ~OAe 29
C"H23 -..;::: C"H23
CI
85
5. Mechanism of Alkene Oxidation With Chromyl Chloride

A considerable uncertainty exists about the mechanism of chromyl chloride
oxidation of olefins. Structures I-III have been suggested as possible inter-
mediates for the electrophilic attack of the chromyl species on the double
bond.
R2 R R2
y!
R R2 R
R' R3 ~ R' I I R3 R~R3
Slo+\t) \o~ CI OCrOCI
I
:"~r (I) CrOCI (II)
CI/ 'CI CIs
.~
R2 R R2
R~R3 R' ~
0
) R3
R 0 and lor
R
Vr--TR2
R CI 0
The scheme shows some of the possible pathways. It was initially

supposed that the intermediate II is attacked from the back by the chloride
ion. This was based on the observation that cyclohexene gives trans-chloro-
hydrin after hydrolysis of the intermediate adduct and that terminal olefins
give anti-Markownikow addition of the elements of HOCl. However, this
picture was complicated by later observations [39] that both cis and trans
chlorohydrins are formed from cyclohexene and cyclopentene. It was there-
fore supposed that the cationic intermediate I or an intermediate II with a
considerable contribution of I might be involved [39]. More recently,
however, arguments have arisen against a significant cationic charge develop-
ment in the intermediate wherein the carbon-chlorine bond is formed which
would therefore oppose the possibility of formation of intermediates I or II.
This was based on the observation that oxidation of (E)-tert-butylmethyl-
ethylene with chromyl chloride in acetone gives mainly 3-chloro-4,4-di-
methylpentan-2-one and no detectable products of a Wagner-Meerwein
rearrangement [46].
86
acetone ¥CI
+
~
o
54% 6%
It was established that, when the oxidation was conducted at low tem-
perature in methylene chloride, only three primary products are formed:
epoxide, chlorohydrin, and, in some cases, vicinal dichlorides [46]. More
importantly, the chlorohydrin results from highly stereoselective cis-addition
of the elements of HOCI across the olefin linkage. It was therefore concluded
that epoxide and chlorohydrin, both resulting from cis addition, are the
primary products of these oxidations and that chlorohydrin resulting from
trans addition is a secondary product derived by opening of the epoxide. Epo-
xidation is stereospecific yielding an epoxide with the same geometry as the
starting olefin [46]:
CI OH
:~:,
primary products
:>r-<:,
OH
secondary products
CI
A new mechanism which should explain all these facts, especially cis-
oxychlorination and the cis-dichlorination, occasionally observed as a side
reaction, has been proposed. The initial step consists in the formation of a
chromyl chloride-olefin n-complex. The complex is then suggested to evolve
through two possible pathways A and B, both of which lead to chromium(VI)
organometallic intermediates. In path A the olefin inserts into a chlorine-
chromium bond (cis-chlorometalation) to produce the alkyl chromium inter-
mediate which could give the dichloride by reductive elimination or the
chlorohydrin by migration of the alkyl group from chromium to oxygen.
Both of the processes are supposed to occur with retention of the configu-
ration at the carbon center bound to chromium in order to result in overall
cis-addition [46]
In path B a four centered intermediate is formed via a [2 + 2] interaction
between olefin and an oxogroup of chromium, a process which is essentially
the microreverse of the olefin forming step in the Wittig reaction. The inter-
mediate could then yield either the chlorohydrin or the epoxide precursor
by the appropriate reductive elimination process. Path A and path B may be
competitive processes and the extent of involvement of each may vary with the
nature of the substrate and with reaction conditions. A comparison of
chromyl chloride oxidation with other electrophilic additions to norborn-
adiene has been recently made [47]. The norbornadiene system is known to be
87
o R
"Cr~
CI 0
~
CI"" ~O
+ - CI',II
~I
Cr-I (
o CI R
A/
;
17
~
o CI
~I ~
O~ nCrx R
CI R
/
18 21
CI
/
O~ ncr-OXR
" IY
CI R
very sensitive to the cationic charge development and has been extensively
employed as a probe in the mechanistic studies of electrophilic addition
reactions.
~OH J:y 0H
CI
V-lCI +
50% 37%
The comparison of product distribution in chromyl chloride oxidation

with that in other electrophilic addition reactions leads to the conclusion that
chromyl chloride oxidation of norbornadiene generates a partial carbonium
ion character merely sufficient to give rise to a certain amount of Wagner-
Meerwein rearrangement products, while strong electrophiles (e.g. TsOR
in AcOH and Br2 ) generate more fully developed carbonium ion inter-
mediates. ,
6. Oxidation of Alkenes With Silver Chromate-Iodine

Alkenes react with silver chromate and iodine in dichloromethane at 0 °C
in the presence of pyridine to give high yields of the corresponding oc-iodo-
carbonyl derivatives [48]:
88
The reaction seems to have wide applicability. In general, electron rich

olefins give better results while electron-deficient ones are recovered un-
changed. Table 13 summarizes some of the results obtained.
The oxidation appears to be regioselective since terminal olefins are
converted exclusively to the corresponding oc-iodoketones. Concerning the
mechanism of the reaction it has been proposed that, in analogy to the well-
known Prevost reaction, the oxidation procedes throught the addition to the
Table 13. Oxidation of Olefins With Silver Chromate-Iodine [48]
0 O~ 60
0 o~ 65
~ ~I 74
0
/'[..........]~
6
/ [..........]~I 65
6 0
~I
~ 86
~OAC QrYOAC 82
lfoal
0
(Jfo~ 49
0 0 C( 39
89
double bond of a hypoiodous-chromic acid mixed anhydride generated

in situ from the silver chromate and iodine. The Q(-iodochromate then im-
mediately decomposes to the Q(-iodoketones:
o
\.:}.. H
RCH=CH2 + "
AgO~rOI
o
R-CH- CH2
')
I
R-C)-CH 2 1
I
0- o
I I:;;>
O=Cr=O O=Cr=O
IV
I OAg
OAg
An application of this reaction in the field of prostaglandins has been

reported [49]:
QAe OAe
~ ~
. A92 Cr04f12
CH2 CI2
OR OR
B. Oxidation of Enol-Derivatives
1. Oxidation of Enol-Ethers With Pyridinium Chlorochromate
Generally, the n-system of alkenes is unaffected by pyridinium chloro-

chromate, the only reaction which occasionally may occur is an attack at
allylic positions (see p. 50). In contrast, the more electron rich enol ethers
react with pyridinium chlorochromate at room temperature to give high
yields of esters and lactones [50].
~OR
H °
0-
(OyH
A possible reaction mechanism could involve initial attack upon the

olefin by the reagent to afford an unstable cyclic intermediate which de-
composes by chromium-oxygen bond cleavage and l,2-hydride shift to
result in the carbonyl compound.
90
B. Oxidation of Enol-Derivatives
PCC
..
Some examples of this reaction, which constitutes a first possibility of

direct conversion of enol ethers into lactones are presented in Table 14.
Table 14. Oxidation of Enol Ethers With PCC [50]
95
~ll ~~ 90
o AcO
75
o o
90
o o
85
The reaction has been successfully applied in the carbohydrate field. As an

example, the glucal derivatives (1) and (2) are converted to the corresponding
lactones by pyridinium chlorochromate in methylene chloride at room
temperature at a yield of about 70% [51]:
91
..
C·n
OBz
~
OBZ
..
Bz9 BzO 0
~ 2. OBz 0
The course of the reaction depends on the nature of the protecting

groups of the glucal. Thus, under similar conditions, 3,4,6-tri-O-benzyl-D-
glucal will give a 60 % yield of the corresponding saturated lactone, whereas
3,4,6-tri-O-tert-butyl-dimethylsilyl-D-glucal is converted into a 4: I mixture
of saturated and oc,,B-unsaturated lactones.
2. Oxidation of O-Silylated Enolates With Chromyl Chloride

Chromyl chloride does add, under mild conditions (-78°C in CH2 CIz)
to the double bond of O-silylated enolates to form oc-hydroxyketones in
moderate yields [52]:
OSiMe3' [OSiMe3
R
A.~CH
Cr02CI2
•
R-6-CHOH
I 1
~1 CH2CI2 CI R1
Under the same conditions the reaction does not yield any isolable
products from further oxidation nor any oc-chloroketones due to dIrect
dichlorination of the starting material.
Use of acetone as solvent results in the formation of oc-hydroxyketones
and the starting ketone, only. Concerning the mechanism of this reaction,
which provides an alternative to the use of peracids or osmium tetroxide/
N-methylmorpholine-N-oxide, intermediate formation of a chlorohydrin
and/or epoxide has been suggested.
C. Ring ~xidation of Aromatic Compounds
The behaviour of homocyclic and heterocyclic aromatic systems toward

chromium (VI) is highly structure dependent. While mononuclear aromatic
compounds appear to be very resistant towards chromic acid, polynuclear
aromatic compounds generally result in quinones. The presence of hydroxyl
or amino substituents greatly facilitates the formation of quinones. However,
the oxidation is in this case often complicated by the formation of dime'ric and
polymeric compounds arising from coupling reactions. Alkyl aryl ethers show
some resemblances to those of phenols. By contrast, aromatic heterocycles,
92
C. Ring Oxidation of Aromatic Compounds
Table 15. Oxidation of Silyl Enol Ethers With Chromyl Chloride [52]
(S" (y0H
0
65
OCS~
00H 66
0
&' (YH 76
~hk'
0
LQT-0H 62
~ ' . ~OH
0
67
~OH 82
especially five-membered ones, undergo cleavage of the heterocyclic ring as

the most frequent, reaction observed.
1. Oxidation of Polynnclear Arenes With Chromium(VI)

Under Acidic Conditions
Chromic acid in acidic medium constitutes one of the most versatile reagents
for oxidation of arenes. While alkyl benzenes and polynuclear structures
containing a single aromatic nucleus are relatively resistant to ring oxidation
and lead almost exclusively to attack at the benzylic positions, polynuclear
aromatic arenes readily undergo ring oxidation to yield the corresponding
93
Ill. Oxidation of Carbon-Carbon Double Bonds
quinones in preference to benzylic oxidation. The chemoselectivity of the

oxidation is strongly dependent upon the acidity of the medium. Neutral
conditions (e.g. sodium dichromate in neutral aqueous solution) favor
benzylic attack, acidic conditions ring oxidation. Thus, 2,3-dimethylnaph-
thalene yields high amounts of 2,3-dimethylnaphthoquinone upon oxidation
with chromic acid in glacial acetic acid [53] and 2,3-naphthalenedicarboxylic
acid with sodium dichromate in neutral aqueous solution [54, 55]:
orx
0
()t\ r \.
.... 100%
~ 0
00(
~
Na2~
0c ~O
2So
ro COOH
COOH
93%
In some cases both ring and benzylic oxidations are observed. As an

example, 2-methylanthracene is converted with sodium dichromate in
aqueous sulphuric acid at 90°C to the corresponding anthraquinone-2-
carboxylic acid in quantitative yield [56]:
$COOH
o -100%
Some significant examples are listed in Table 16.

Illustrative Example: Phenanthraquinone [65]
To a suspension of 100 g (0.56 mol) of phenanthrene in 11 water containing
210 g (2.1 mol) of chromic acid, 410 ml of concentrated sulphuric acid are
added under stirring. After addition of sulphuric acid is complete, a mixture
of 210 g (2.12 mol) of chromic acid and 500 ml of water is added carefully.
The resulting mixture is boiled under reflux for 20 minutes. After being
cooled at room temperature, the reaction mixture is poured into an equal
volume of water. The crude precipitate is separated by filtration. Purification
by crystallization from.95 %ethanol affords a 80 %yield of quinone.
Alkyl groups may be eliminated during the oxidation. This is the case
for 9-ethylphenanthrene which is converted into phenanthraquinone [66]:
~
Cr03 inAcOH
94
Table 16. Oxidation of Polycyclic Aromatic Compounds
00 0:) 0
18-22 57,58
oor
0
lV(Y 0
25-40 59
00 660
60
«X
0
00( 60-80 61
00« # 0
31 62
006 0)6 0
not reported 63
00()( «)CreOOH 0
~100 56
~'
4 0
64
oro
0
0:)) 0
65
95
Similarly, 1,2,5-trimethylnaphthalene yields, among other products, the

corresponding ortho-quinones and para-quinones by oxidative elimination
of the I-methyl group [67]:
+ other
products
The chromic acid oxidation of anthracene derivatives has been widely used
in a number of total syntheses of the clinically important anthracycline
antibiotics [68, 69, 70]. The reaction is surprisingly tolerant of a number of
sensitive, functional groups like ketols, acetates, and even boronic esters:
OAc
~
0 0
OAc
····O)BPh
CrD3,AC20
AcOH, 25 DC
20 h
«)¢Qi
o
OAc
····o--kPh
57 Ofo
OAc 0
~ OAc
CrD3, AcOH
25 DC,2h
..
~ o OAc
70 Ofo
2. Oxidation of Phenols and Aromatic Amines With Chromium(VI)

Under Acidic Conditions
The oxidation of phenols and aromatic amines may lead to the formation
of quinones or to dimeric, trimeric, or polymeric coupling compounds. Nearly
any derivative of phenol and aniline can be oxidized to the corresponding
para-quinone by means of chromic acid under acidic conditions. The ease
of oxidation strongly depends upon the nature and position of the ring
substituents. A hydrogen atom in para position decreases the yield whereas a
hydroxyl or amino group greatly increases it.
¢ -0- ¢J
o
X=H,OH,NH2
x o x
Thus, 2,5,6-trimethylphenol upon oxidation with sodium dichromate in

90 % sulphuric acid at 10-20 °C affords the corresponding para-quinones
in 50 %yield [71]. Similarly, ortho-toluidine has been converted to the quinone
in 86 % yield [72]:
96
XX
OH
Xr
0
Na2 Cr04
90 % H2SO4
50%
10 - 20 DC 0
'16 V
0
2 Na2 Cr04
25 % H2SO4
..
10 - 20 DC 86%
0
Many other para-substituted groups, as for instance halogen atoms,

sulphonyl, and methyl groups, will be eliminated or oxidized under appro-
priate conditions and usually a certain amount of the corresponding quinones
may be isolated. As an example, the 2,4,6-tribromo-3-methylphenol on
oxidation with chromium trioxide in 50 %acetic acid gives the corresponding
quinone in 77 %yield [73]:
crOs
in50%
AcOH 77%
Halogen substituents assist the oxidation, thus improving the yield.

Haloquinones have been prepared from the corresponding halogen substi-
tuted phenols. The oxidation is in general carried out with chromic anhydride
in aqueous acetic acid, with yields of about 75 %. Para-substituted amino-
phenols and diamines easily afford para-quinones in high yields upon oxi-
dation with chromic acid-sulphuric acid at 0 °C-I0 0c. Thus, for instance,
3-iodo-4-aminophenol gives almost quantitatively 3-iodobenzoquinone on
treatment with sodium dichromate in sulphuric acid [74]:
~Io 95%
The oxidation of para-hydroquinones to qUl110nes with chromium

trioxide in aqueous acetic acid is also a very easy reaction although its
synthetic utility is limited by the availability of starting material (Table 17).
Illustrative Example: 1,4-Naphthoquinone [89}
A hot solution of 70 g (0.36 mol) of pure 1,4-aminonaphthol hydrochloride
in 2100 ml of water and 100 ml concentrated sulphuric acid is rapidly poured,
at room temperature, into a solution of 74 g (2.4 mol) of potassium di-
chromate in 1 I water. The quinone separates at once as a mass of fine yellow
needles. After recrystallization from ether a yield of 78-81 % of quinone
is obtained.
97
Table 17. Oxidation of Phenols and Aromatic Amines
N
OH 0
)6r 0
50 72
CI*
OH
CI
V
CI
I
0
0
I good 75
.'*"
OH 0
Br
I V
Br I 77 74
Br 0
e,*", OH
CI
C II V
I
0
0
CI
69 76
'*
OH 0
IV 20 77
S03H 0
1*'
OH 0
I II
'V 15 77
S03H 0
A
0
~ 0
30 78
ff N
0
55 79
98
c~
D o
~ . . .-:: 17 80
Y
NH2
V
0
40 81
~ N
0
40 81
¢'a
OH 0
Vel
I I
0
88 82
OH
JtJC
AcNH
0 0H
OH
DO
AcNH:-'" 0
75 83
AcNH AcNH
~OH
AcN D OH
J00
ACNH:-'" 0
78 84
~ 0'
~
72 85
HO 0 o ...-;
0
OH
0
~ NH2
~ 0
86
99
~ NH2
~ I
0
I
87
OH
e'i¢r"' CIVCI I
0
j 89 88
NH2 0
Illustrative Example: 2,6-Dihaloquinones from Sym- Trihalogenated Phenols

[89bJ
To a solution of 1 g of the sym-trihalogenated phenol in a small amount
of glacial acetic acid, a solution of 19 equivalents of chromium trioxide in
an equal weight of water is added at 50°C all at once. After a few seconds
(5-10 sec. in the case of the trichlorophenol, 20 sec. in the other two cases),
the mixture is poured under stirring into 200 ml of water. The crude oxi-
dation product which separated was filtered by suction within one half hour
and dried in a dessiccator over concentrated sulphuric acid for about eighteen
hours. Yields were 45 %, 44 %, and 85 % for chloro-, bromo-, and iodo-
quinones, respectively.
Ortho-quinones are nearly always prepared from the corresponding
catechols [90]. Amines usually are unsatisfactory starting materials. One
of the few preparations in which an amine has proved useful as a starting
material is the oxidation of 2-amino-4,5-dimethylphenol to 4,5-dimethyl-
o-quinone with a chromic acid-sulphuric acid mixture for which a yield
of 45 %was obtained [91]:
~O
AA-o
45%
The oxidation reactions of alkyl aryl ethers show some resemblance to

those of phenols [92]. Many derivatives of anisole having an unsubstituted
para position undergo oxidation upon treatment with chromic acid in an
acidic medium, to give derivatives of para-benzoquinone. During the reaction
an oxygen enters the para-position providing one of the oxygen atoms
100
of the quinoide system, the other being derived from the alkoxy group of the
parent ether. Thus, 2,6-dimethoxytoluene upon oxidation with chromic
acid in aqueous acetic acid affords 2-methoxy-3-methyl-para-benzoquinone
in good yield [93]:
o
Me0L6roMe Cr03
AcOH/H20 •
MeoOO
~
0 ~
Substituted 1,4-dimethoxybenzenes undergo oxidative demethylation to

give benzol-l,4-quinones in good yields. Thus, for instance, di-O-methyl-
latifoline is converted to latifolone [94]:
Meorago~e Meocgo
~ I
MeO
o
0"
o OMe OMe
A number of examples of this kind are presented in Table 18.
Table 18. Oxidation of Alkyl Aryl Ethers With Chromic Acid
Substrate Product Ref.
r!\rOMe
~
95
~OM'
~OMe
V
95
r!\rOMe
~
95
~
LBr o Br
I I 95
MeoMoMe MeO
o
101
Substrate Product Ref.
OMe
MeO ~"
00 Br
~o 96
Br OMe
OEt
000
0
«)OJ 0
97
~ OMe
~ 0
98
~~ ~ 99
Br Br 0
MeOOOOMe M e O WOMe
100
0r00C::: «n:::
0
101
MeO
JQ!OOroMO Br
MeO
@o~ 102
Br Br 0
102
Similarly, I,2-dimethoxy derivatives of certain structures containing

fused rings give the corresponding o-quinones. An interesting example is
the oxidation of brucine to strychnine-I 0, II-quinone in 80 I~ yield with
chromic acid in 5N sulphuric acid at 10°C [103]:
M'OrrW
Meo~~
.
Cr03 in H2S04/H20 O~Nca
O~)
N N 50%
However, 1,4-benzoquinones are always preferentially formed if possible.

As an example, I,2,4-trimethoxy-5-methylbenzene affords exclusively the
4
corresponding para-quinone in almost quantitative yield [104]:
0M ' __ ~OMe
OMe
~o '" 100 %
Phenols and alkyl aryl ethers which bear an alkyl group in para position
to the oxygen function may give, upon oxidation with chromic acid under
acidic conditions, coupling products in addition to quinones. This is exem-
plified by the oxidation of 3-methyl-4,6-di-tert-butylphenol in 50 % acetic
acid/20 % sulphuric acid at 50-55°C using two equivalents of sodium di-
chromate, leading to a good yield of hexaalkyl dihydroxy biphenyl [105]:
OH OH
+~ o
76% 22%
A minor product is the 2-methyl-5-tert-butylquinone arising from oxi-

dative elimination of the tertiary alkyl group in para position.
Steric hindrance of the phenolic hydroxyl group plays an important
role in directing the course of the reaction. In fact, by examining Table 19,
it does appear that for a good yield of hexaalkyl dihydroxydiphenyl from
3,4,6-trialkylphenols, the alkyl group in position 6 must be tertiary. When the
2-position of 3,4,6-trialkylphenols is substituted, the oxidation reaction is
primarily directed to quinone formation by elimination of the C-4 sub-
stituent. There is no evidence that the substituent in position 2 is removed
to permit dimerization. Thus, for instance, the oxidation of 2-chloro-3-
methyl-4,6-di-tert-butylphenol using potassium dichromate and sulphuric
acid in acetic acid solution gives the 2-chloro-3-methyl-6-tert-butyl-para-
quinone without any trace of the corresponding hexaalkyldihydroxy bi-
phenyl derivative.
103
Table 19. Oxidation of 3,4,6-Trisubstituted Phenols With Na2Cr207 in Sulphuric

Acid-Acetic Acid [105]
2 J~
0 76
2 ~~ 76
2 ~~
0 89
2 ; 50
2
CI
fOH CI CI
23
~H M
o h
21
J: o 4("
h Br
24
104
&~
~CI
Xo
°VCI
18
J~ Xo
oJ:( 22
Several other 3,4,6-trisubstituted phenols have been found to behave

similarly. On the other hand, 2,5-dimethyl-4-tert-butylphenol exclusively
gives 2,5-dimethylquinone. The amount of oxidizing agent seems to be critical,
since, when more or less than double quantities are employed a smaller
yield results [105].
Oxidative cOupling may also occur in substituted methoxybenzenes
having a free ortho position. Thus, 2,5-dimethoxytoluene and l-chloro-Z,5-
dimethoxytoluene may be converted by chromic acid in acetic acid-sulphuric
acid to the corresponding dipheno-3,6-quinones in moderate yield [106]:
OMe
~
..
~
Cr03
AcOH/H2S04
OMe OMe 0
OMe
OMe 0
c,~ a~a
Cr03
•
AcOH/H2S04
OMe OMe 0
An interesting example of transannular oxidative coupling of a di-

methoxymetacyc~ophane derivative with Jones' reagent has been reported
to give a 94 % yield of the corresponding bisdienone [107]:
OMe
..
~
Jones
94%
OMe o
105
3. Oxidation of Phenols With Chromyl Chloride

Chromyl chloride reacts with halogen and alkyl substituted phenols to give
brown amorphous solids which, in general, do not show a stoichiometric
composition. The hydrolysis of these solids gives varying yields of quinones,
diphenoquinone, and polymeric compounds. The reaction is performed at
room temperature in carbon tetrachloride using different substrate to oxidant
ratios. AI: 1 ratio is generally used for the oxidation of chlorophenols [108].
It has been showed that substitution of hydrogen by chlorine in the 2 and 6
Table 20. Oxidation of Phenols With Chromyl Chloride
Substrate p-benzoquinone % Other products
o
2 :1
ifo
OH o
lOr 2:1
V o
48
V 1.3 : 1
2: 1
~ 0
36
68
traces
N
0
14
15 Polymeric tars
0
1 :1
2:1
# 27
82 Polymeric tars
A
0
5 :1 49
10 :1 56 Polymeric tars
106
positions leads to a considerable increase in the yield of quinone. Thus,

while 2,6-dichlorophenol and 2,4,6-trichlorophenol give good yields of
2,6-dichloro-p-benzoquinone, and pentachlorophenol gives a yield of chlor-
ani I in excess of70 %, o-chlorophenol gives only a very small yield of2-chloro-
p-benzoquinone and phenol itself gives only traces of para-benzoquinone.
cin ci
o
CI*OH CI
CI 0 CI CIVCI
o
CI
70-80%
The oxidation of mono- and dialkyl substituted monohydric phenols affords

both quinones and products resulting from coupling [109].
Table 20 summarizes some of the most significant results.
Phenols which have the largest groups in ortho-position give the most
stable radicals and the highest yield of quinone. That the yield of quinone
increases will the stability of the radical is exemplified by the results obtained
from the reaction of o-cresol, 2,6-dimethylphenol, and 2,6-tert-butylphenol.
A high oxidant to substrate ratio favors the formation of quinones. This
may be explained in terms of radical stability and side chain attack. For the
unstable radical the greater the excess of oxidant, the more likely the for-
mation of quinone. Concerning the coupling products obtained, 2,6-dialkyl-
phenols afford diphenoquinone where all other substrates afford complex
mixtures of polymeric products.
4. Oxidation of Hydroquinone SHyl Ethers

With Pyridinium Chlorochromate
In many syntheses of naturally occurring quinones it may be convenient

to effect the required synthetic elaboration of the molecule using a protected
form of a hydroquinone which is converted by oxidation to the corresponding
quinone only in a later stage of synthesis. Silyl enol ethers, especially hindered
ones containing the bis-(tert-butyldimethyl) group, are widely used for this
purpose being stable to many reaction conditions. They may be then directly
converted to the qui nones by treatment with 2 equivalents ofpyridinium
.*o
chi oro chromate jn methylene chloride at room temperature in 50-99 %
yield [110]:
OSi::::
·
Rl 2PCC
R
OSiE
Some examples are listed in Table 21.
107
Table 21. Oxidation of Hydroquinones Silyl Ethers to Quinones With PCC [110]
OTMS 0
~OMe (rOMe
I I 65
OTMS 0
OTMS
;Or N
0
93
OTMS 0
V
OTMS 0
~ OTMS 0
62
Ai: o .
OTMS
OTMS
# 91
¢ 0
0
99
OTMS 0
qc,
OTMS
no reaction
OTMS
Ot-BDMS 0
~OMe, (rOMe
I I 50
Ot-BDMS 0
*
Ot-BDMS
N
0
80
Ot-BDMS 0
108
ijM' (y 90
Ot-BDMS o
99
Ot-BDMS
5. Oxidation of Ortho-Allylphenols
With Tetraalkylammonium Dichromate
Synthesis of chrom-3-enes through cyclohydrogenation of 2-(3' ,3'-dialkyl-
allyl)phenols with 2,3-dichloro-5,6-dicyanobenzoquinone has been extensively
studied.
The same oxidation may be performed with tetraalkylammonium di-
chromate in boiling benzene [111]. The reagent is easily obtained by treating
potassium dichromate with Adogen 464 [a commercial mixture of methyl
trialkyl (C8 -C18 ) ammonium chloride] in benzene in a 1:2 ratio. By this
procedure, precocene, an inhibitor of juvenile hormone, was obtained in
83 % yield probably through the intermediate formation of a quinone
methide:
83%
Other example~ of the same kind of reaction are included in Table 22.
6. Oxidation of Some Aromatic Heterocyclic Compounds

With Chromium(VI)
Some aromatic heterocyclic derivatives like furans, benzofurans, indoles,
and pyrazoles undergo cleavage of the heterocyclic ring on treatment with
chromium(VI) reagents under a variety of conditions.
Pyridinium chlorochromate is particularly effective in the oxidation of
the furan ring since it shows an unusual behaviour as a dienophile and oxi-
109
Table 22. Oxidation of o-Allylphenols With Cr2 0i ~ /Adogen 464 [Ill]
H
Me0lO(Jl Meo~
83
MY »)< 78
~ £0< 76
~ ~ 77
do I ~
0.--:: 45
dant. 2,5-Dia1ky1furans, by action of peC in boiling methylene chloride

solution undergo an oxidative ring fissioJ} to lX,p-unsaturated-y-dicarbony1
compounds in high yields [112]:
..
R' R' = Me R2= C 7H15 75 Ofo
R'
~R2
0 '
PCC
O~R2
CH2 CI2 R' = Me R2= C"H23 80 Ofo
0
R' = H R2 = C"H 23 50 Ofo
5-Substituted-2-furylcarbino1s undergo an oxidative rearrangement the

course of which depends on the nature of the substituent in position 5.
If position 5 is substituted with an alkyl group, an oxidative ring enlargement
occurs to give 6-hydroxy-2 H-pyran-3(6 H)ones in high yields [113]. Thus,
5~methyl-2(IX-hydroxyethy1)furan with an excess ofPCC in methylene chloride
110
at room temperature affords 2,6-dimethyl-6-hydroxy'-2 H-pyran-3(6 H)-one

in a yield larger than 90 %.
91 %
~
PCC R= CH3
~R •
in CH2CI2 R= CH2-CH=CH2 90%
OH R
OH
R= n-C 6 H13 94%
Two other examples of this kind of reaction have been reported. In

contrast, 5-bromo-2-furylcarbinols are. converted by the same treatment
into y-hydroxybutenolides [114]:
n
Br/"o.O""y
R
25 DC
FlOHR
o?'-o"'y'
60%
OH OH 65%
It is worth mentioning that the oxidation shows a highly chemoselective

behavior leading only to attack of the aromatic ring leaving the secondary
alcoholic function untouched. When the heteroaromatic nucleus is deactivated
by the presence of a nitrogroup in position 5, the oxidant preferentially will
oxidize the alcoholic function, affording (5-nitro-2-furyl)ketones [115].:
77%
75%
A general mechanism of action of PCC on furan derivatives has been

proposed which involves the preliminary formation of an addition compound
by 1,4-electrophilic attack of chlorochromate anion upon the furan ring:
Subsequently, the decomposition of the unstable key intermediate by

heterolytic cleavage of the Cr-O bond leads to (l(,p-unsaturated y-dicarbonyl
compounds, hydroxypyranones, hydroxybutenolides, and furyl alkyl ketones.
The decomposition strictly depends on the nature of R 1 and R 2 . Furthermore,
the formation of 6-hydroxy-2 H-pyran-3(6 H)ones from 5-alkyl-2-furyl-
carbinols involves a nucleophilic participation of the alcoholic function
of the side chain in heterolysis.
111
2,3-Dialkyl and aryl substituted F-benzofurans oxidize with chromic

trioxide in boiling acetic acid by cleavage of the heterocyclic ring affording
ortho-acyloxy aromatic ketones in 40-80 % yield [116]:
rro-
R2 R2 R1 = Ph, R2 = Ph 61 %
R1
Cr03
AcOH ~lR1 R1 = Ph,
R1 = Me,
R2
R2
=
= Ph
Me 48%
81 %
2-Phenyl(F -benzo )furan, having a substituent in position 2, behave in a

different manner upon oxidation with the same reagent under similar con-
ditions: The (F-benzo)furan ring is cleaved at the C-O bond to give 1-(2-
hydroxy-F -phenyl)-2-phenylethandione in poor yield [116]:
Cr03 ~ JllUJ
AcOH ~nu1f
OH
-v-
4%
Similarly oxidation of 6-methyl-2-phenylbenzofuran with Jones' reagent

affords the same kind of product in a slightly better yield [117].
~O0
fi3~
~ 0 V
Jones
.. 0
/ OH 26%
The oxidation probably starts by hydrogen abstraction at C(3). Treat-

ment of 6-methyl-2-phenylbenzofuran with chromium trioxide in acetic acid
affords, indeed, an unusual dimeric oxidation product, 2,2' -dibenzoyloxy-
4,4' -dimethylbenzyl which could arise by dimerization of the starting material
at C(3) followed by oxidative cleavage at the C-C bond:
/
~~
U
"V' '0'
Cr03
AcOH
28%
Some examples of oxidative cleavage of the heterocyclic ring of indole

derivatives have been reported. Thus, chromium trioxide in acetic acid
112
causes cleavage of the indole 2,3-double bond of some N-phthalimidoacetyl

indoles affording the corresponding 2-phthalimidoacetanilides [118]:
___C_~~3___
•
CI~O
o N' Rl
AcOH ~o
la, R=H
lb,R= COCH 3
tl 2a, Rl
2b, Rl
2c, Rl
=H
= COCH3
= CHO
The oxidation of 1 a (R = H) leads only to the formation of 2 a in 70 %

yield probably due to the intermediate formation of the dicarbonyl derivative
2c from which the formyl is then removed by oxidation or hydrolysis. In
contrast, 1 b gives under similar conditions a mixture of the dicarbonyl
derivative 2b (55 %) and 2a (21 %).
Oxidative cleavage of the indole ring also occurs in oxidation with
chromic acid in acetic acid ofindole-1,2-dicarboximides which have been con-
verted to the corresponding imidazolidintriones [119]:
H)FD
C~3
____~-..
AcOH
(N02 )CI ~
0 0
NJ\
0
60-70°C J-.. )=o 50-79%

o ~
An analogous oxidative cleavage of a heterocyclic nucleus has been

reported for a pyrazolo[2,3,a]quinoline [120]:
C~3
~AcO~H- "
ro60
. 0 QN"
113
On the other hand, 5-methylthionaphthene has been oxidized on the

benzene ring with chromium trioxide in 80 % acetic acid to give 5-methyl-
thionaphthenequinone in 10% yield [121]:
o
CIOa
in80%
AcOH "00 a 10%
References of Chapter III

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36. p. 11Y, A. K., Rocek, J.: J. Am. Chern. Soc. 91,991 (1969)
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40. Freeman, F., McCart, P. D., Yamachika, N. J.: J. Am. Chem. Soc. 92,4621
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41. Freeman, F., DuBois, R. H., McLaughlin, T. G.: Org. Synth. 51, 4 (1971)
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47. Chung, S. K.: Tetrahedron Lett. 1978, 3211
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55. Friedman, L., Fishel, D. L., Schechter, H.: J. Org. Chem. 30, 1453 (1965)
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59. Herzenberg, J., Ruhemann, S.: Chern. Ber. 60, 893 (1927)
60. Smith, L. 1., Webster, 1. M.: J. Am. Chem. Soc. 59, 662 (1937)
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63. Elbs, K.: J. Prakt. Chern. 2, 41, 142 (1890)
64. Schroeter, G.: Chem. Ber. 57, 2014 (1924)
65. Wendland, R., LaLonde, J.: Org. Synth. 34, 76 (1954)
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115
68. Kende, A. S., Curran, P. D., Tsay, Y., Mills, J. E.: Tetrahedron Lett. 1977,
3537
69. Wiseman, J. R., French, N. I., Hallmark, R. K., Chiong, K. G.: ibid. 1978,3765
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71. Smith, L. I., Opie, J. W., Wawzonek, S., Prochard, W. W.: J. Org. Chern. 4,
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72. Schniter, c.: Chern. 20, 2283 (1887)
73. Smith, L. I., Byers, D. J.: J. Am. Chern. Soc. 63, 612 (1941)
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75. Claus, A., Schweitzer, H.: Chern. Ber. 19, 927 (1886)
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88. Van Erp, H.: ibid. 58, 663 (1925)
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91. Willstatter, E., Muller, H.: ibid. 44,2171 (1911)
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107. Boekelheide, V., Phillips, J. B.: J. Am. Chern. Soc. 89, 1695 (1967)
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1979,836
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116
113. Piancatelli, G., Scettri, A., D'Auria, M.: Tetrahedron Lett. 1977, 2199
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(1945)
117

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III. Oxidation of Carbon-Carbon Double Bonds

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III.

Oxidation of Carbon-Carbon Double Bonds

The oxidation of double bonds is usually of minor interest for preparative

1. Oxidation of Alkenes With Chromium Trioxide

The yield of epoxide is greatest when one or each of the unsaturated

In contrast, an aqueous acetic acid medium will lead to low amounts

The presence of nitrogroups in the phenyl rings reduces the yield of

Table 1. Epoxidation of Tetra- and Trisubstituted Diolefins With Chromic Trioxide

Substrate Product Yield % Ref.

Substrate Product Yield % Ref.

rise to a mixture of 28 % of tetra~p-nitrophenyloxirane and 63 % of 4,4'-

The oxidation oftetraphenylethylene in acetic anhydride affords a 10-20 %

Table 2. Cyclic Carbonates From Tetrasubstituted Olefins [5]

Substrate Product Yield %

is added to the reaction mixture. In th~s way a certain number of carbonates

However, when the acenaphthylene was oxidized in the presence of

Only tetraaryl ethylenes appear to give high yields of the corresponding

The primarily formed epoxide may, indeed, undergo rearrangement

Another example is the oxidation of 3jJ-acetoxylanost-8-ene with chromic

Homo and heteroannular steroidal and terpenic dienes seem to follow

Upon oxidation with chromic acid in aqueous sulphuric acid/acetone

The oxidation of certain complex, olefinic substrates may sometimes take

In other cases the oxidation appears to be less predictable giving rise to

A synthetically useful cleavage of a double bond by means of chromium

a, R'= H b, R'= Alkyl

If the starting ester contains a methylene group adjacent to the carboxyl

Table 3. Barbier-Wieland Degradation of Steroids

Substrate End Product' Overall yield % Ref.

HO'" ct5f9 ; COOH

" ' COOH

• After one or more Barbier-Wieland degradation steps.

Table 4 presents some examples of oxidation cleavage of steroidal dienes.

Table 4. Meystre-Miescher-Wettstein Degradation of Steroids

Substrate End Product Overall yield % Ref.

As by-products the corresponding epoxides and trans diols have been

An important example 1S the preparation of LJ16-20-ketosteroids from

2. Oxidation of Alkenes With Chromic Acid

Another example is the facile conversion, on treatment with aqueous

The results of oxidation of 1, I-disubstituted ethylenes with chromic acid

Table 5. Oxidation of l.1-Disubstituted Olefins With Chromic Acid in Aqueous Sul-

Substrate Products (yield %) Ref.

Substrate Products (yield %) Ref.

Trisubstituted and tetra substituted olefins oxidize under aqueous acidic

Table 6. Oxidative Cleavage of Olefins by Chromic Acid-Aqueous Sulphuric Acid

Substrate Products Ref.

Substrate Products Ref.

d=< dO )=0 )-COOH 2

Under similar conditions 2,4-dimethylpent-2-ene gives 2,2,3-trimethyl

~COOH + >=0 + >-COOH

Substrate Products Ref.

X 2tCOO" -1- eOOH =>0 34

The 2,2,3-trimethylbutanoic acid may arise by rearrangement of the first

Similar oxidations of 1,2-disubstituted olefins give fair (20-70 %) yields

Table 8. Oxidation of Terminal Olefins by Jones' Reagent Catalyzed by Mercury(II)

Substrate Product Yield %

Table 9. Rates of the Chromium(VI) Oxidation of Olefins at

and halogen addition, and appears to be diametrically different from acid

4. Oxidation of Alkenes With Chromyl Chloride

The significant difference between these results is probably due to the

not isolated buthydrolyzed under reducing conditions. Presumably, the reduc-

Zinc dust reduction prior to work-up produces the corresponding ketones.

Table 10. Chromyl Chloride Oxidation of Alkenes

Substrate Product Yield % Ref.