Oxidative fragmentation of oxiranes to nitriles with hypervalent iodine(V) reagents in aqueous ammonia

Article abstract of DOI:10.1016/j.tetlet.2011.06.068

Oxiranes undergo oxidative fragmentation when treated with hypervalent iodine(V) reagents particularly o-iodoxybenzoic acid in aqueous ammonia to give nitriles. The reaction goes via the formation of 1, 2-amino alcohols as intermediates followed by C-C bond cleavage.

Full text of DOI:10.1016/j.tetlet.2011.06.068

Tetrahedron Letters 52 (2011) 4533–4536
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Tetrahedron Letters
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Oxidative fragmentation of oxiranes to nitriles with hypervalent iodine(V)
reagents in aqueous ammonia
⇑
Swapnil S. Deshmukh, Sameerana N. Huddar, Ravindra R. Jadhav, Krishnacharya G. Akamanchi
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Oxiranes undergo oxidative fragmentation when treated with hypervalent iodine(V) reagents particularly
o-iodoxybenzoic acid in aqueous ammonia to give nitriles. The reaction goes via the formation of 1, 2-
amino alcohols as intermediates followed by C–C bond cleavage.
Received 4 May 2011
Revised 14 June 2011
Accepted 16 June 2011
Available online 23 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
o-Iodoxybenzoic acid
Aqueous ammonia
Oxiranes
Nitriles
Oxidative fragmentation
Oxidative fragmentation of oxirane is one of the significant
reactions developed in organic chemistry. Oxiranes are easily pre-
pared from olefins1 or carbonyl compounds2 and are important
intermediates in organic synthesis.3 The trend of oxiranes to un-
dergo oxidative ring-opening reactions is well-known.4 Due to
their particular polarity and strained three member ring system,
a large variety of nucleophiles can be employed for ring opening
of these compounds5 and subsequently transformed into a variety
of products.6 One such a transformation is oxidative C–C bond frag-
mentation leading to dicarbonyl compounds including diketones,
aldehydes, carboxylic acids and their combination depending on
the substrate and conditions.7
A major advantage of accessing carbonyl compounds through
oxiranes via diols rather than olefins is to have additional scope
for selective epoxidation of compounds with multiple double
bonds.8 1,2-Amino alcohols that can be readily obtained from oxir-
anes undergo photooxidative fragmentation forming carbonyl
compounds.9 Direct oxidative fragmentation of oxiranes using
domino reactions such as epoxide opening followed by oxidation
is limited. Some examples are the reaction of I,I-bis(trifluoroacet-
oxy) iodobenzene (BTI) with 2-phenyloxirane undergoing
exclusively C–C fragmentation, giving benzaldehyde and formalde-
hyde. Outcome of the reaction is different if oxirane is alkyl substi-
Other hypervalent based oxidizing agents such as periodic
acid10b HIO4 and sodium periodate,11a,11c PhIO along with HBF4
in CH2Cl2-hexafluoroisopropanol (HFIP)-H2O system11b have been
used with terminal oxiranes leading to formation of aldehydes
with one carbon less.
In all these cases formation of vicinal diol is the first step and is
followed by oxidative cleavage.11c Oxidative fragmentations of ter-
minal oxiranes are well reported with other reagents such as so-
dium dichromate12a in aqueous sulfuric acid as well as CAN12b as
stoichiometric reagent. A catalytic oxidation of oxiranes has been
described using molecular oxygen and DMSO with bismuth(III)
mandelate as a catalyst in which terminal oxiranes led to the cor-
responding carboxylic acids and CO2.12c
IBX chemistry is of current interest as indicated by many latest
reviews.13 Recently we have reported a facile transformation of
aldehydes to nitriles14a in almost quantitative yield as well as
oxidative decarboxylation of
a
-amino acids to nitriles14b using
o-iodoxybenzoic acid in aqueous ammonia. In continuation of
O
CN
IBX
aqueous ammonia
tuted and undergoes C–O fragmentation to give
a-hydroxy
Acetonitrile, 70 0
C
ketones.10a
R
R
2a
1a
R= H
⇑
Corresponding author. Tel.: +91 22 33612214; fax: +91 22 33611020.
E-mail address: kgap@rediffmail.com (K.G. Akamanchi).
Scheme 1. Oxidative fragmentation of phenyloxirane to benzonitrile.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.068

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S. S. Deshmukh et al. / Tetrahedron Letters 52 (2011) 4533–4536
Table 1
Table 2 (continued)
Optimization of reagent and reaction conditionsa
Entry Substrate (1)
Product (2)
Yield (%)b
Entry
Reagent combination
Temp
Time (h)
Yieldb (%) 2a
O
CN
1
2
3
4
5
6
IBX/Water
IBX/Water
IBX/aqueous ammonia
IBX/aqueous ammonia
DMP/aqueous ammonia
DMP/aqueous ammonia
rt
70 °C
rt
70 °C
rt
70 °C
12
8
12
4
12
7
NRc
NRc
NRc
90
10
11
86
2j
H3C
NRc
80
1j
H3C
CN
O
a
b
c
Reaction performed on 5 mmol of 1a.
Isolated yields.
NR = no reaction.
85
2k
1k
O
S
O
O
CN
CN
12
13
82
84
2l
Table 2
Oxidative fragmentation of oxiranes to nitrilesa
1l
S
Entry Substrate (1) Product (2)
CN
Yield (%)b
O
O
2m
1m
CN
1
90
14
15
90
76
O
2a
CN
1n
2n
1a
O
CN
O
2o
1o
2
3
4
91
82
85
a
Cl
2b
Reactions were carried out on 5 mmol scale in aqueous ammonia at 70 °C with
IBX. (2.0 equiv) up to 3.5–4 h.
Cl
1b
b
Isolated yields.
O
Cl
Cl
CN
2c
Cl
our investigations with hypervalent iodine reagents in aqueous
ammonia, we reacted phenyloxirane with IBX in aqueous ammonia
at 70 °C and observed oxidative fragmentation forming benzoni-
trile (Scheme 1). In the follow up investigations it was found that
oxiranes undergo nucleophilic ring opening on reaction with
ammonia forming 1,2-amino alcohol as intermediates which sub-
sequently undergo oxidative fragmentation. To the best of our
knowledge, this is the first report on the oxidative fragmentation
of oxiranes (aryl/alkyl) forming nitriles.
In our preliminary experiments, 1.0 equiv of phenyloxirane 1a
was treated with 2.0 equiv of IBX in aqueous ammonia in acetoni-
trile as a co-solvent at 70 °C. As expected benzonitrile, 2a was ob-
tained in excellent yields in 4 h, whereas the reaction did not occur
at room temperature even after 12 h (Table 1).
1c
O
CN
Cl
2d
Cl
F
Cl
O
1d
CN
5
6
83
86
F
2e
1e
O
CN
2f
O2N
It is to be noted that when only water is the solvent, there was
no reaction (Table 1, entries 1 and 2). Another hypervalent iodine
reagent Dess–Martin periodinane (DMP) was also found to be via-
ble for this reaction (Table 1, entry 6).
O2N
1f
O
CN
To explore the generality of the reaction, a variety of substrates
were reacted with optimized reaction conditions15
, that is,
7
85
2.0 equiv of IBX in aqueous ammonia in acetonitrile as a co-solvent
at 70 °C. The results are summarized in Table 2. A variety of oxir-
anes including substituted aromatic, hetero-aromatic and aliphatic
were transformed into nitriles smoothly via this protocol in mod-
erate to good yields. Aromatic substrate carrying electron with-
drawing or donating groups reacted equally facile (Table 2,
entries 2–10). Thiophene and furan rings were stable under the
present reaction conditions (Table 2, entries 12 and 13). Equally
facile reaction was observed with aliphatic oxiranes (Table 2, en-
tries 14 and 15).
2g
NO2
NO2
1g
O
CN
8
9
84
83
2h
CN
MeO
MeO
MeO
MeO
1h
O
Towards understanding the transformation an explanation is gi-
ven in Scheme 2.
2i
OMe
Oxirane on nucleophilc ring opening with ammonia forms 1,
2-amino alcohol which on reaction with IBX undergoes fragmenta-
tion to form aldehyde (A) and aldimine (B) intermediates
1i
OMe

S. S. Deshmukh et al. / Tetrahedron Letters 52 (2011) 4533–4536
4535
NH
O
O
4
HO
O
NH4
OH
I
I
N
O
O
H
O
O
NH2
H
O
O
O
NH3
+
NH2
+
NH
N
4
HO
I
H
O
OH
O
H
O
O
H
N
IBX
NH3
(A)
NH
+
IBX
H
(B)
Scheme 2. Plausible mechanism for the oxidative fragmentation of oxirane to nitrile.
NH2
OH
CN
IBX
IBX
aqueous ammonia
aqueous ammonia
Acetonitrile, 70 0
C
OH
Acetonitrile, 70 0C
NH2
4
3
Scheme 3. Reaction of 1, 2-amino alcohols with IBX/aqueous ammonia.
5. (a) Smith, G. J. Synthesis 1984, 629; (b) Bonini, C.; Righi, G. Synthesis 1994, 225.
6. (a) Antoniotti, S.; Dunach, E. Synthesis 2003, 2753; (b) Surendra, K.;
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for Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004;
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Backvall, J. E.; Ericsson, A. M.; Juntunen, S. K.; Najera, C.; Yus, M. J. Org. Chem.
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Lett. 2008, 49, 2764.
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Zhdankin, V. V. ARKIVOC 2009, 1, 1; (c) Zhdankin, V. V.; Stang, P. J. Chem. Rev.
2008, 108, 5299; (d) Ladziata, U.; Zhdankin, V. V. ARKIVOC 2006, 9, 26.
14. (a) Arote, N. D.; Bhalerao, D. S.; Akamanchi, K. G. Tetrahedron Lett. 2007, 48,
3651; (b) Bellale, E. V.; Huddar, S. N.; Mahajan, U. S.; Akamanchi, K. G. Pure
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respectively. These undergo subsequent oxidations to form ni-
triles.14 This mechanism was supported by carrying out reaction
of 2-amino-2-phenylethanol 3 and 2-amino-1-phenylethanol 4
with IBX in aqueous ammonia at 70 °C, where expected benzoni-
trile was obtained in very high yields and as the sole product
(Scheme 3). It is pertinent to note that reaction carried out in
IBX/water the substrate failed to react pointing to ammonolysis
of oxirane as the first step (Table 1, entries 1 and 2).
This is the first report of oxidative fragmentation of oxiranes by
hypervalent iodine(V) reagents including DMP and IBX in aqueous
ammonia giving nitriles with ammonolysis being the first step.
Further explorations on this transformation are under way.
Acknowledgements
We sincerely thank the University Grants Commission (UGC)
and Council of Scientific and Industrial Research (CSIR) India for
financial support. We are grateful to M/S Omkar Chemicals, Badla-
pur, Thane, India, for generous gift of IBX and DMP.
References and notes
15. General procedure for oxidative fragmentation of oxiranes. To a stirred solution of
IBX (10.0 mmol) in aqueous ammonia (25 mL of a 28–30% solution) was added
oxirane (5.0 mmol) in 5 mL of acetonitrile in one portion. The reaction mixture
was stirred at 70 °C until complete consumption of starting material as
observed on TLC (up to 4 h). After completion of reaction, the reaction mixture
was extracted with chloroform (2 Â 15 mL). The organic layer was washed
with water (2 Â 10 mL); bisulfate solution (15 mL) followed by water (10 mL),
dried over anhydrous sodium sulfate and concentrated under reduced pressure
1. Lane, B. S.; Burgess, K. Chem. Rev. 2003, 103, 2457.
2. (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1962, 84, 867; (b) Corey, E. J.;
Chaykovsky, M. J. Am. Chem. Soc. 1962, 84, 3782.
3. Behrens, C. H.; Ko, S. Y.; Sharpless, K. B.; Walker, F. J. J. Org. Chem. 1985, 50,
5687.
4. Gritter, R. J. In The Chemistry of the Ether Linkage; Patai, S., Ed.; Wiley-
Interscience: New York, 1967. Chapter 9.

4536
S. S. Deshmukh et al. / Tetrahedron Letters 52 (2011) 4533–4536
to give crude product. Pure product was obtained after column
chromatography (silica gel, mesh size 60–120, eluent ethyl acetate/hexane
1.6 Hz).
2-Cyanothiopene (2m). Oil (lit.16a Oil). IR (Neat): 2227 cmÀ1 1H NMR (300 MHz,
.
05:95).
CDCl3): d = 7.98 (1H, dd, J = 5.0 and 3.8 Hz) 7.65(1H, d, J = 3.8 Hz), 7.61 (1H, d,
J = 5.0 Hz).
Spectral data of selected nitriles. 4-Nitrobenzonitrile (2f): solid, mp 140–142 °C
(lit.16a142 °C). IR (KBr): 2230 cmÀ1
J = 8.9 Hz), 7.91 (2H, d, J = 8.9 Hz).
.
1H NMR (300 MHz, CDCl3): d = 8.36 (2H, d,
Phenylacetonitrile (2n). Oil (lit.16b Oil). IR (neat): 2221 cmÀ1
.
1H NMR (60 MHz,
CDCl3): d = 7.61–7.55(5H, m), 3.24 (2H, s).
4-Methoxybenzonitrile (2h): solid, mp 55–56 °C (lit.16a 55À57 °C). IR (neat):
Pentanenitrile (2o). Oil (lit.16b oil). IR (neat): 2245 cmÀ1 1H NMR (300 MHz,
.
2216 cmÀ1
.
1H NMR (300 MHz, CDCl3): d = 7.76 (2H, d, J = 8.9 Hz), 6.91 (2H, d,
CDCl3): d = 1.86 (2H, t), 1.67 (2H, m), 1.32(2H, m), 0.87 (3H, t).
16. (a) Iida, S.; Ohmura, R.; Togo, H. Tetrahedron 2009, 65, 6257; (b) Dictionary of
Organic Compounds, Sixth Ed.; Chapman and Hall electronic Publishing House,
London 1996.
J = 8.9 Hz), 3.83 (3H, s).
2-Cyanofuran (2l). Oil (Lit.16b Oil). IR (Neat): 2229 cmÀ1 1H NMR (60 MHz,
.
CDCl3): d = 8.02 (1H, d, J = 1.6 Hz), 7.16 (1H, d, J = 3.62), 6.71 (1H, dd, J = 3.6 and