Synthesis ofα-azido ketones and esters using recyclable hypervalent iodine reagent

Article abstract of DOI:10.1080/00397910903531888

A simple and mild method for the preparation of αazido ketones and esters using hypervalent iodine reagent, 4,4'-bis-(dichloroiodo)-biphenyl, and sodium azide in 1,4-dioxane is discussed. Advantages of this system are easy workup, recyclable reagent, and

Full text of DOI:10.1080/00397910903531888

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Synthesis of α-Azido Ketones and Esters
Using Recyclable Hypervalent Iodine
Reagent
Vikas N. Telvekar a & Hemlata V. Patile a
a Department of Pharmaceutical Sciences and Technology , Institute
of Chemical Technology, Matunga , Mumbai, India
Published online: 14 Dec 2010.
To cite this article: Vikas N. Telvekar & Hemlata V. Patile (2010) Synthesis of α-Azido Ketones
and Esters Using Recyclable Hypervalent Iodine Reagent, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:1, 131-135, DOI:
10.1080/00397910903531888
To link to this article: http://dx.doi.org/10.1080/00397910903531888
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Synthetic Communications1, 41: 131–135, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903531888
SYNTHESIS OF a-AZIDO KETONES AND ESTERS
USING RECYCLABLE HYPERVALENT IODINE REAGENT
Vikas N. Telvekar and Hemlata V. Patile
Department of Pharmaceutical Sciences and Technology,
Institute of Chemical Technology, Matunga, Mumbai, India
A simple and mild method for the preparation of a-azido ketones and esters using hyper-
valent iodine reagent, 4,40-bis-(dichloroiodo)-biphenyl, and sodium azide in 1,4-dioxane
is discussed. Advantages of this system are easy workup, recyclable reagent, and moderate
to good yields.
Keywords: a-Azido esters; a-azido ketones; 4,40-bis-(dichloroiodo)-biphenyl; recycle; sodium azide
INTRODUCTION
Azido carbonyl compounds are valuable intermediates that have found
extensive use in the synthesis of acyclic and cyclic nitrogen-containing compounds
and natural products.[1,2] There are very few methods known for the preparation
of a-azido ketones and esters. These methods involve oxidative addition of azide
anion to silyl enol ether or nucleophilic substitution reaction of a-halo ketones,
nosyloxy ketones, a-keto triflates, or a-tosyloxy ketones with sodium azide.[3–6]
Iodine and iodine reagent systems have found widespread application in
organic synthesis because of their selectivity and simplicity of use. Our group has
been working extensively on the development of novel methodologies under mild
reaction conditions using various hypervalent iodine reagents.[7,8]
4,40-Bis-(dichloroiodo)-biphenyl is very good reagent for the iodochlorination
of alkenes.[9] Recently, we exploited this reagent for oxidation of primary and
secondary alcohols to the corresponding aldehydes and ketones, respectively.[10]
We observed that this reagent could be used in combination with sodium azide
for the direct preparation of a-azido ketones and esters from their corresponding
ketones and esters. For our initial studies, ethyl phenylacetate was chosen as the
model substrate. A mixture of ethyl phenylacetate, sodium azide, triethylamine,
and 4,40-bis-(dichloroiodo)-biphenyl in 1,4- dioxane was stirred at reflux tempera-
ture. The starting material was consumed within 4 h as indicated by thin-layer
Received September 19, 2009.
Address correspondence to Vikas N. Telvekar, Department of Pharmaceutical Sciences and
Technology, Institute of Chemical Technology, Matunga, Mumbai, India. E-mail: vikastelvekar@
rediffmail.com
131

132
V. N. TELVEKAR AND H. V. PATILE
Scheme 1. Ethyl phenylacetate converted into a-azido using 4,40bis-(dichloroiodo)-biphenyl.
chromatography (TLC) analysis. After workup and purification by silica-gel column
chromatography, a-azido ethyl phenylacetate was isolated in 80% yield.
a-Azidation of ethyl phenylacetate also takes place in the absence of base, but
less yield is isolated after 24 h. Under similar reaction conditions, in the absence of
sodium azide, no a-chloro ethyl phenylacetate was observed.
The reactions were also carried out in the presence of various anhydrous
solvents, and it was noted that 1,4-dioxane, toluene, tetrahydrofuran, N,N-dimethyl-
formamide, and chloroform are suitable solvents for this conversion. Reaction does
not take place at room temperature.
In this reaction, 4,40-bis-(dichloroiodo)-biphenyl has been converted into
4,40-diiodo-biphenyl, which is easily separated by simple filtration during workup
and can be recycled after conversion into 4,40-bis-(dichloroiodo)-biphenyl. Under
similar reaction conditions, dichloroiodobenzene also gives a-azido ketones and
esters. To the best of our knowledge, there is no report on the use of 4,40-bis-
(dichloroiodo)-biphenyl as well as dichloroiodobenzene for a direct azidation
reaction.
RESULTS AND DISCUSSION
Encouraged by these results, we subjected various aromatic and aliphatic
ketones and esters to the reaction conditions, and the results are presented in
Table 1. The results clearly indicate that ester groups are stable to this reaction con-
dition (Table 1, entries 1–7). Similarly, it was found that either electron-deficient or
electron-rich aromatic compounds were suitable for this reaction condition, giving
a-azides in moderate to good yields (Table 1, entries 1– 4). In the case of aromatic
compounds, a slower reaction rate is observed when the chain length increases
(Table 1, entry 6). Longer reaction time is required for a-azidation in esters than
in ketones (Table 1, entries 7–10).
Aliphatic esters and ketones also underwent this transformation smoothly into
a-azido esters and ketones; however, a slower reaction rate was observed than with
the aromatic compounds. Ethyl butyrate (Table 1, entry 11) and 2-pentanone
(Table 1, entry 12) were converted to the corresponding a-azido in good yields. A cyc-
lic ketone like cyclohexanone was also successfully converted into the corresponding
a-azido cyclohexanone (Table 1, entry 13). No reaction was observed in the absence
of an ester or keto group, even after a long reaction time (Table 1, entry 14).
In conclusion, a novel method has been developed for the a-azidation of esters
and ketones using recyclable hypervalent iodine reagent. This method is mild and
gave moderate to good yields of a-azido ketones and esters in both aliphatic and aro-
matic substrates.

a-AZIDO KETONES AND ESTERS
133
Table 1. Conversion of esters and ketones to a-azides using 4,40-bis-(dichloroiodo)-biphenyla
Entry
Substrateb
Product
Time (h)
Yield (%)c
1
4
85
2
3
4
4
4
7
89
85
88
5
6
4
7
85
84
7
8
4
3
80
88
9
3
88
85
10
11
3
9
85
(Continued )

134
V. N. TELVEKAR AND H. V. PATILE
Table 1. Continued
Entry
12
Substrateb
Product
Time (h)
9
Yield (%)c
85
13
14
3
89
—
24
NRd
aReaction conditions: substrate (5.0 mmol), 4,40-bis-(dichloroiodo)-biphenyl (0.55 equiv), triethylamine
(2.1 equiv), and sodium azide (2.1 equiv) in 1,4-dioxon (15 mL), reflux.
bStarting compounds were prepared by standard literature procedures.
cIsolated yields after column chromatography and structures were confirmed by comparison of IR and
1H NMR with those of authentic materials.
dNo reaction.
GENERAL EXPERIMENTAL PROCEDURE
Preparation of a-Azido Ketones and Esters
Sodium azide (2.1 equiv, 10.5 mmol) was added to a stirred solution of
4,40-bis-(dichloroiodo)-biphenyl (0.55 equiv, 2.75 mmol) in 1,4-dioxane (15 mL).
The resultant mixture was stirred for 5 min, and then a solution of ester or ketone
(1.0 equiv, 5 mmol) and triethyl amine (2.1 equiv, 10.5 mmol) in 1,4-dioxane was
added at room temperature. The resultent reaction mixture was stirred at reflux
temperature until the starting material had been completely consumed thin-layer
chromatography (TLC). The reaction mixture was diluted with water (40 mL)
and extracted with ether (2 ꢀ 20 mL). The combined organic layer was washed suc-
cessively with 10% aq. sodium bisulfite solution (2 ꢀ 15 mL), 10% aq. NaHCO3
(2 ꢀ 15 mL), and water (1 ꢀ 20 mL). The organic layer was dried over Na2SO4
and concentrated in vacuo, and the resultant residue was treated with hexane
(25 ml). The precipitate of 4,40-diiodobiphenyl was filtered and washed with hex-
ane. The filtrate was concentrated to obtain the crude product, which was further
purified by silica-gel column chromatography (10% EtOAc–hexane) to afford pure
azides.
Regeneration of Reagent
Isolated 4,40-diiodo-biphenyl from the reaction mixture was recrystallized and
dissolved in chloroform, and excess chlorine was bubbled through the solution
for 1 h at 10–15 ꢁC under stirring. 4,40-Bis-(dichloroiodo)-biphenyl precipitate
was filtered, washed with cold chloroform, and dried [mp. 155 ꢁC (dec.), lit.[11]
mp. 156 ꢁC (dec.)].

a-AZIDO KETONES AND ESTERS
135
ACKNOWLEDGMENT
V. N. T. gratefully acknowledges All India Council for Technical Education
(AICTE), India, for financial support under the Research Promotion Scheme (RPS).
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