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Published on the web February 2, 2013
Molecular Iodine in Aqueous Ammonia: Oxidative Fragmentation of Oxiranes to Nitriles
Ravindra R. Jadhav and Krishnacharya G. Akamanchi*
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology,
Matunga, Mumbai 400019, India
(Received October 27, 2012; CL-121095; E-mail: kg.akamanchi@ictmumbai.edu.in)
I2
Oxiranes undergo oxidative fragmentation, when treated
O
Aqueous ammonia
with iodine in aqueous ammonia, to give nitriles. The reaction
goes via formation of 1,2-amino alcohols as intermediates
followed by C-C bond cleavage. Advantages of the method
are use of off-the-shelf nonexplosive, unlike previously used
potentially explosive o-iodoxybenzoic acid, reagents, mild
reaction conditions, and easy work-up procedure.
CN
R
R
Acetonitrile, 70 °C
6-7 h
R= alkyl, aryl
2
1
Scheme 1. Oxidative C-C fragmentation of oxiranes to
nitriles.
Table 1. Optimization of reagent and reaction conditionsa
Iodine, a readily available, versatile, and mild oxidizing
agent, is a good alternative for toxic heavy metal reagents in
many oxidative transformations, and transformations using it
are of current interest.1 Iodine promotes many transformations,
which include oxidative cyclizations, oxidative rearrangements,
ring expansion and contraction, and C-N bond formation among
others.2 Iodine-aqueous ammonia combination has been used
in oxidative transformation of 1-arylethanols and arylmethyl
halides, giving arylamides3a and arylnitriles3b respectively.
Nitriles formed by the oxidation of primary alcohols and
aldehydes using this reagent system under microwave irradi-
ation, have been converted, in situ, into triazines and tetrazoles,
through [2 + 3] cycloaddition with dicyanamide and sodium
azide respectively.3c
O
I2
CN
Aqueous ammonia
Acetonitrile
2a
1a
Entry
Temperature
Time/h
Yieldb/%, 2a
1
2
rt
70 °C
18
6
10
86
aReactions were carried out on 5 mmol scale using I2
(2.5 equiv) in aqueous ammonia and acetonitrile as
cosolvent. Isolated yields.
a
b
Oxidative fragmentation of double bond and oxiranes is a
significant transformation useful in synthetic organic chemistry.
Oxiranes, showing particular polarity and a strained three-
membered ring system,4 are an important class of organic
compounds5 and are amenable for a variety of useful trans-
formations.6 Literature reports a variety of methods for oxidative
C-C bond fragmentation of oxiranes. Reagents used for
oxidative C-C bond fragmentation of terminal oxiranes are
iodine is not really essential for the oxidative fragmentation
and molecular iodine in aqueous ammonia would be equally
effective. These findings, using off-the-shelf reagents, molecular
iodine and aqueous ammonia, leading to a new, more conven-
ient, and cost effective method for oxidative C-C fragmentation
of oxiranes is reported in this letter (Scheme 1). The present
method is an improved version of our ealier method with respect
to use of nonexplosive molecular iodine over potentially
explosive IBX.
In our preliminary experiments, 1.0 equiv of phenyloxirane
(1a) was treated with 2.5 equiv of I2 in aqueous ammonia, using
acetonitrile as a cosolvent at 70 °C. Oxidative fragmentation
occurred giving benzonitrile (2a) in good yields in 6 h, the same
reaction performed at room temperature was slow, and the
reaction remained incomplete even after stirring for 18 h and
gave 2a in just 10% yields (Table 1, Entries 1and 2).
To explore the generality of the reaction, a variety of
oxiranes including substituted aromatic, heteroaromatic, aliphat-
ic, and alicyclic were transformed into nitriles smoothly via this
protocol, i.e., oxirane was treated with 2.5 equiv of I2 in aqueous
ammonia and acetonitrile as a cosolvent at 70 °C,15 the results
are summarized in Table 2. Aromatic substrates, carrying
electron-withdrawing or -donating groups, reacted equally facile
(Table 2, Entries 2-12). Thiophene- and furan-containing sub-
strates also underwent reaction smoothly (Table 2, Entries 13
and 14). Equally facile reaction was observed with aliphatic
sodium dichromate in aqueous sulfuric acid7 and CAN.8
A
catalytic method, using molecular oxygen and DMSO with
bismuth(III) mandelate as catalyst, is also known leading to
formation of corresponding carboxylic acids and CO2.9 Exten-
sively investigated reagents, for this transformation, are hyper-
valent iodine-based oxidizing agents. Reaction of I,I-bis(tri-
fluoroacetoxy)iodobenzene (BTI) with 2-aryloxiranes brings
about exclusively C-C fragmentation giving benzaldehydes,
whereas with alkyl-substituted oxiranes there was no fragmen-
tation, instead oxidative ring opening occurs leading to
formation of ¡-hydroxy ketones.10 Similarly, other hypervalent
iodine reagents used are, HIO4 or combination of HIO4 and
sodium periodate,11,12 PhIO along with HBF4 in a CH2Cl2-
hexafluoroisopropyl alcohol-H2O system.13 Mechanistically, in
all these cases, formation of vicinal diol is the first step and is
followed by oxidative cleavage.
Recently, we have reported oxidative fragmentation of
oxiranes to nitriles with hypervalent iodine(V) reagents, partic-
ularly o-iodoxybenzoic acid (IBX) in aqueous ammonia.14 In
continuation of our studies, we found that hypervalency of
Chem. Lett. 2013, 42, 162-164
© 2013 The Chemical Society of Japan
Jadhav, Ravindra R.
