A reliable one-pot synthesis of aryl azides from aryl amines using organotin azides as effective and recoverable reagents

Article abstract of DOI:10.1016/j.jorganchem.2016.11.037

A mild and mass-efficient procedure based on the one-pot diazotization-azidodediazoniation of aromatic amines is described. A wide range of aryl azides are obtained in moderate to high yields by using tributyltin azide as an effective and reusable azide source in the presence of p-toluenesulfonic acid at room temperature. The method was also successfully applied employing an insoluble polymer-supported organotin azide.

Full text of DOI:10.1016/j.jorganchem.2016.11.037

Accepted Manuscript
A reliable one-pot synthesis of aryl azides from aryl amines using organotin azides as
effective and recoverable reagents
Leonela Godoy Prieto, Marcos J. Lo Fiego, Alicia B. Chopa, María T. Lockhart
PII:
S0022-328X(16)30550-2
10.1016/j.jorganchem.2016.11.037
JOM 19722
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 19 September 2016
Revised Date: 25 November 2016
Accepted Date: 26 November 2016
Please cite this article as: L.G. Prieto, M.J. Lo Fiego, A.B. Chopa, M.T. Lockhart, A reliable one-pot
synthesis of aryl azides from aryl amines using organotin azides as effective and recoverable reagents,
Journal of Organometallic Chemistry (2016), doi: 10.1016/j.jorganchem.2016.11.037.
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ACCEPTED MANUSCRIPT
NaN3
NH2
N3
RBu2SnN3 RBu2SnOTs
t-BuONO
TsOH
X
X
MeCN
MeCN
0 °C, 30 min
0 °C r.t., 1-2 h
4-NO2
3-Cl
2-Cl
4-OMe 2,4-Br 4-Me
2,4,6-Me 4-COMe
4-Cl
R = Bu (TBSnN3)
or
very good yields
short reaction times
low tin polution
H
2-COOH,4-I 2-COOH
2-COOH,5,6-OMe
2-COOH,5-F
O
Merrifield
resin
4-CN
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A reliable one-pot synthesis of aryl azides from aryl amines using organotin azides as effective
and recoverable reagents
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Leonela Godoy Prieto, Marcos J. Lo Fiego,§ Alicia B. Chopa§§ and María T. Lockhart*
Instituto de Química del Sur, INQUISUR-Departamento de Química, CONICET-Universidad Nacional del
Sur, Av. Alem 1253, B8000CPB, Bahía Blanca, Argentina
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Abstract
A mild and mass-efficient procedure based on the one-pot diazotization-azidodediazoniation of
aromatic amines is described. A wide range of aryl azides are obtained in moderate to high yields
by using tributyltin azide as an effective and reusable azide source in the presence of p-
toluenesulfonic acid at room temperature. The method was also successfully applied employing an
insoluble polymer-supported organotin azide.
Aryl azides; Tributyltin azide; Azidodeamination; Diazotization-azidodediazoniation; Polymer-
supported organotin azide; Recoverable reagent
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1. Introduction
Among organic azides, and due to their relatively high stability, aryl azides have found an
extensive range of applications in diverse fields. In organic chemistry, as valuable intermediates for
the synthesis of aza-derivatives, isocyanates, peptides and heterocycles with a currently increasing
interest within the concept of “Click Chemistry” [1], in biochemistry, acting either as selective
fluorescent probes [2] or photoreactive crosslinking-labeling groups, and also, in materials
chemistry, for the synthesis of conducting polymers [3] or for light-induced activation of polymer
surfaces [4]. Consequently, developments for new reliable and efficient methods for introducing
this key functionality are always welcome.
Although a large and growing number of synthetic approaches towards the preparation of aryl
azides can be found in the literature, the arenediazonium-based azidations are advantageous and
attractive alternatives because they start from inexpensive and broadly available anilines and are
hence usually orthogonal to halide-based reactions. Therefore, several protocols have been
developed with the aim to improve both the efficiency and usefulness of the classical diazotization-
azidodediazoniation route. Among these, neutral conditions [5], neutral and mild conditions with
non-hazardous reagents [6], reusable ionic liquids as solvents [7], water media [8], stable diazonium

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salts intermediates [9], continuous flow processes [10] and polymer-supported diazotizing [11] or
azidating [12] reagents, are a few of the implemented strategies.
Especially attractive is the method proposed by Moses and coworkers [6] for the one-pot
azidation of diverse aromatic amines, using tert-butylnitrite (t-BuONO) in combination with
trimethylsilyl azide (TMSN3), which they also found to be suitable for building triazole linkages by
CuAAC, through a microwave-assisted tandem methodology [13]. It is interesting to note that
TMSN3 plays a key role on the success of the azidation process. Indeed, due to its covalent features,
it allows avoiding the use of large excesses of sodium azide which are needed in non-aqueous
solvents [5]; moreover, because it reacts with the in situ generated diazonium salts, as soon as they
formed, neither excesses of t-BuONO or additives are required. Nevertheless, despite above-
mentioned advantages, the use of TMSN3 has some downsides; it is a highly expensive reagent
which is also both difficult and hazardous to prepare [14] and, due to its extremely high sensitivity
to hydrolysis, decomposes slowly upon storage. In addition, only 36.5% of its molar mass can be
used for the azidation reaction and the volatile trimethylsilyl byproducts are inevitably lost during
solvent evaporation.
Like TMSN3, tributyltin azide (TBSnN3) is also a covalently linked azide that allows reactions in
relatively homopolar solvents; it is less sensitive to hydrolysis, very stable to storage and readily
accessible from the corresponding tributyltin chloride in very good yield [15]. In fact currently,
organotin azides are among the reagents of choice for the last-stage generation of tetrazole linkages
in pharmaceutical synthesis of losartan AT1-receptor antagonist and its analogues [16].
In connection with our continuing effort to explore the synthetic potential of organotin
compounds [17], and given that many of these reagents have become invaluable tools in organic
chemistry, we envisioned that the use of TBSnN3, in place of TMSN3, on Moses’s methodology,
would also achieve the in-situ azidodediazoniation pathway and then, after an appropriate workup,
it could be recovered and recycled from the low volatile and highly stable tributyltin byproducts.
We report here the results obtained from a selection of anilines together with the specific
protocols developed to allow the removal of most of the tin residues from the aryl azide products,
and the recycling of TBSnN3. Moreover, encouraged by the proven effectiveness of TBSnN3 and,
given the growing concern about the toxicity of organotin residues, which makes necessary to
remove them down to ppm levels, we set out to study these reactions employing a polymer-
supported organotin azide. Some selected preliminary results are also reported.
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2. Results and discussion

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We began by applying the standard conditions of Moses’s methodology to the reaction of aniline
(1a). When TBSnN3, instead of TMSN3, was added dropwise to a stirred solution of 1a and t-
BuONO in MeCN at 0 °C, only traces of azidobenzene (2a) were detected together with 1a in
almost quantitative yield (GC-MS), even after 19 h at room temperature. An identical result was
obtained from a reaction conducted at 40 °C, over the same extended time period. In both cases, any
possible side product (benzene, phenol, azobenzene or biphenyl) which are often observed in
diazonium reactions [18], was not detected in the reaction mixtures (Table 1, entries 1 and 2).
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Table 1. Optimization of the reaction conditions
Molecular ratio
-BuONO/TBSnN3/additive) (%)a
Yield
Entry 1a [M] Additive
(1a/t
1b
2b,d
3
0.625
0.625
0.312
0.312
none
none
1.0/1.5/1.2/0.0
1.0/1.5/1.2/0.0
1.0/1.5/1.2/1.2
1.0/1.5/1.8/1.2
1.0/1.5/1.2/1.2
1.0/1.5/1.8/1.2
1.0/2.0/1.2/1.2
1.0/1.2/1.2/1.2
1.0/1.2/1.32/1.2
Tracesc
Tracesc
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.
BF3 OEt2
.
4
BF3 OEt2
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5
0.143 TsOH.H2O
0.143 TsOH.H2O
0.143 TsOH.H2O
0.143 TsOH.H2O
0.143 TsOH.H2O
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9e
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a Determined by GC-MS (0.5 mmol scale) using o-dichlorobenzene (o-DCB)
as internal standard. b By applying Moses´s methodology. c High percentages
of 1a were observed after 19 h of reaction. d Reaction temperature was raise
to 40 °C (oil bath). e By using NaN3 instead of TBSnN3.
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These disappointing results clearly revealed that diazotization step failed and makes it evident
that, in contrast to TBSnN3, its silyl analogue is able to exert some synergistic interaction that
promotes the generation of transient arenediazonium ions and drives the reaction to completion.
Probably, such interactions could be attributed to the stronger oxophilicity of the silicon atom which
result, via a pentacoordinate complex, in an increased of its Lewis acidity and a more nucleophilic
azide group [19].
In order to probe the effectiveness of TBSnN3 in the azidodediazoniation step, we investigated
its reaction with the pre-formed benzenediazonium tetrafluoroborate [20] and, fortunately, a good
yield of 2a (78%) was accomplished within 2 h.

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Based on the above findings, we took into consideration the use of additives, such Brønsted or
Lewis acids, which could promote the in situ generation of the required diazonium salt acting as the
anion source.
Initially, we explored the use of boron trifluoride diethyl etherate (BF3ꢀOEt2) in the stepwise
one-pot procedure from 1a, sketched in Scheme 1.
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Scheme 1. Stepwise one-pot azidodeamination of 1a
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A promising yield of 2a was obtained within 2 h at room temperature when the TBSnN3 (1.2 equiv)
was added to the reaction mixture at 0 °C, than after 1a was treated with t-BuONO (1.5 equiv) in
the presence of BF3ꢀOEt2 (1.2 equiv) during 30 min in MeCN. A slight improvement in yield was
observed by increasing the 1a/TBSnN3 molar ratio (Table 1, entries 3 and 4). Even better results
were achieved employing a Brønsted acid as additive; hence, tested at different reactant molar
ratios, 2a was formed in up to 85% yield in the presence of p-toluenesulfonic acid monohydrate
(Table 1, entries 5-8).
We chose the conditions of the experiment performed at lower molar excess of reagents (Table 1,
entry 8) as optimal to explore the scope of this azidodeamination protocol, with focus on
establishing the appropriate procedures for the removal of tin byproducts as well as for their
recovery and recycling back to TBSnN3. It is worth mentioning that, taking into account the actual
amount of NaN3 consumed for the overall process, we carried out a control experiment by the
reaction of 1a with 1.32 equiv of NaN3 (Table 1, entry 9). The poor yield observed of 2a (24%)
after 2 h at room temperature, can be attributed to the lower solubility of NaN3 in comparison with
TBSnN3 in MeCN.
It should be noted that, in optimized reaction of 1a, the tributyltin ester of p-toluenesulfonic acid
(TBSnOTs) was the only organotin compound detected and identified from crude 119Sn NMR by
comparison with an authentic sample [21]. Therefore, we envisioned that TBSnOTs could be easily

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converted into TBSnN3 by treating with NaN3. In a first attempt, the crude mixture obtained from
the reaction of 1a was subjected to silica gel column chromatography. Although pure 2a was
isolated in good yield from hexane fractions, it was not possible to recover the TBSnOTs, even by
using highly polar eluents and silica gel pre-treated with Et3N 10% v/v. Assuming that this issue
could be due to a strong affinity of the organotin ester with the silanol sites of silica, we decided to
try the conversion of TBSnOTs by adding NaN3 to the reaction mixture upon completion of the
azidodediazoniation. Thus, a stoichiometric amount of NaN3 (with respect to initial TBSnN3) was
added to the MeCN-Et2O solutions coming from quantitative GC-MS analysis and left overnight
under stirring at room temperature. After solid NaOTs was filtered off; the 119Sn NMR spectrum of
filtrate showed only one signal at 111.09 ppm which agreed well with that observed for commercial
TBSnN3. By silica gel column chromatography, the aryl azide 2a was isolated in 77% yield (hexane
fractions) and the TBSnN3 was recovered in 80% yield eluting with ethyl acetate. This protocol was
also successfully applied in the synthesis of aryl azides 2b-g (Scheme 2).
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a
Scheme 2. Scope of the one-pot azidodeamination by TBSnN3

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a Yields of isolated products (2.0 mmol scale), yields in parentheses refers
to those determined by GC-MS using o-DCB as internal standard.
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A more simple procedure was possible for the isolation of azides 2h-j and recovery of TBSnN3.
After conversion of TBSnOTs, these azides were precipitated by dropwise addition of cold hexane
to the previously concentrated resulting filtrates, and the TBSnN3 was then recovered from the
supernatants in near-quantitative yield. Further purification by recrystallization from hexane
afforded the aryl azides 2h-j in an isolated yield range of 72-88%.
Due to their acidic properties, the above-described procedure for the conversion of TBSnOTs to
TBSnN3 must be ruled out for the azidobenzoic acids 2k-n, considering the risks associated with
any possible release of dangerous hydrazoic acid. In this regard, these compounds were precipitated
by gradual addition of an aqueous hydrochloric acid solution; after filtration and washing with
water and hexanes, the organotin by product, as TBSnCl, was almost quantitatively recovered from
the organic/aqueous mixtures by extraction with diethyl ether. Good yields of target azides 2k-n,
ranging from 65% to 77%, were obtained without needing further purification.

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As can be seen from Scheme 2, this method proved to be applicable to various aromatic amines.
In general, no significant correlations were found between electronic and steric effects of
substituents on the aromatic ring and the outcome of reactions. Thus, good isolated yields of aryl
azides 2 were obtained in the presence of both electron-withdrawing and electron-donating groups
with a high tolerance to various common functionalities, owing to the mild conditions employed.
Among them, several aminobenzoic acid derivatives gave good yields of corresponding azides
which did not require purification. Unfortunately, from the reaction of 2-amino-5-chloropyridine
(1o) and 3-aminopyridine (1p), the expected products (2o and 2p) were not obtained. In the first
case, the complete disappearance of the starting amine could not be observed on monitoring of the
diazotization stage by TLC, and not even traces of 2o were detected by GC-MS analysis of the
reaction mixtures. In the second case, despite of the complete consumption of the starting amine,
the reaction failed to give the desired product 2p and N-(3-pyridinyl)acetamide (GC-MS data) was
formed as major product when the temperature was increased to 60 °C in the second stage of the
reaction [22].
It is worth to highlight that, in the evaluation on scope and limitations of the proposed method,
yields and reaction times were taken from at least two independent experiments for each parameter;
by means of the use of recycled TBSnN3 it was possible to accomplish this task consuming
somewhat less than 20% of the amount which would have been stoichiometrically required of the
parent TBSnCl.
Within this concept of recovery and reuse of chemicals, that contributes to improve processes in
terms of both cost reduction and waste minimization, the employment of solid-immobilized
reagents is often one of the most convenient approaches. Indeed, this strategy has been extensively
applied in reactions involving organotins to facilitate the above-mentioned aspects, the workup
procedures, and to minimize the presence of tin at trace level in the products. In such a context, a
helpful and motivating review article, about methodologies developed to limiting or avoiding
contamination by organotin residues in organic synthesis, has been recently published [23].
Taking into consideration that pollution and safety issues related to the toxicity of the organotin
compounds should be circumvented, our findings regarding the efficiency of TBSnN3 as an azide-
transfer reagent led us to explore the employment of a polymer-supported azidostannane on the
previously described method.
In order to establish the feasibility of this approach, we chose the polystyrene resin-bound
dibutyltin chloride 3a, previously described and characterized [24], which appeared to be a suitable
starting material for the syntheses of the corresponding tin azide 3b as depicted in Scheme 3.

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HO
NaH, DMF 0 °C ꢀ r.t., 2 h
i.
, 50 oC, 20 h
NaO
Cl
O
O
SnBu2Cl
SnBu2N3
ii. Bu2SnCl2, Bu2SnH2
AIBN, toluene, 20 oC, 16 h
3a
3b
Merrifield
resin
TBSnN3 (5 equiv)
DMF, r.t., 24 h
2 x
3a
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Scheme 3. Synthesis of the polymer-supported dibutyltin azide 3b
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The supported organotin chloride 3a was prepared in two steps from a Merrifield resin (2.0
mmol Cl/g, 1% DVB), according to previously reported procedures [24], monitoring the progress of
the reactions by gel-phase 13C NMR [25]. For the hydrostannylation step, the disappearance of the
well-defined vinylic carbon signals (117.1 and 135.0 ppm) of the starting allyl ether, was taken as
indicative that this reaction proceeded to completion. Gel-phase 119Sn NMR of the polymer 3a
revealed a single signal at 65.2 ppm. The NMR data were consistent with those previously reported
[24].
Taking into account the high hydrophobicity of the crosslinked polystyrene backbone, which
may disfavour reactions involving ionic species, and that it is necessary to use low to medium polar
solvents for the swelling of microporous resins, we considered that TBSnN3 rather than NaN3, could
be a more suitable reagent to achieve the synthesis of the supported dibutyltin azide 3b from the
chlorostannane 3a. Hence, 3a was swelled in DMF and reacted with a 5-fold excess of TBSnN3,
with respect to its theoretical loading (1.26 mmol Cl/g), at room temperature. After 24 h, the gel-
phase 119Sn NMR spectrum of resulting resin showed a new signal at 25.4 ppm [26]; nonetheless,
the presence of a minor peak at 65.2 ppm revealed incomplete reaction as compared with starting
resin. By repeating subsequently the same process, a complete conversion was confirmed by gel-
phase 119Sn NMR in the limits of this measurement. The azide loading on 3b (0.84 mmol/g) was
determined from elemental analysis indicating a 67 % yield relative to the initial loading of the
Merrifield resin. Afterwards, the excesses of TBSnN3 could be recovered and reused by adding an
equivalent amount of NaN3, based on the experimental loading, to the combined filtrates and
washing solutions resulting of the usual treatments of 3b.
Next, we selected the aryl amines 1-azido-3-chlorobenzene (1c), 4-azidobenzonitrile (1i) and 2-
azido-4-fluorobenzoic acid (1m) to assess if the polymer-supported dibutyltin azide 3b might also
be effective on our azidodeamination protocol (Scheme 4).

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Scheme 4. One-pot azidodeamination of aryl amines 1c, 1i and
1m by polymer-supported dibutyltin azide 3ba
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a
Yields of crude products, yields in parentheses refers to those
b
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determined by GC-MS using o-DCB as internal standard. Residual tin
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content: 47 ppm (ICP). c By using recovered 3b
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By applying the same stepwise procedure 3b was added, instead of TBSnN3, prior dilution with
MeCN (to allow its swelling) and the suspensions were kept under stirring at room temperature for
24 h before vacuum filtration. After the usual treatments, the filtrates obtained from the reactions of
1c and 1i were submitted to quantitative GC-MS analyses. As shown in Scheme 4, very good yields
of the corresponding aryl azides 2c and 2i were observed, only slightly below of those achieved in
solution (Scheme 2). However, there was a major decrease in the crude yields of these products, as
well as in the azidobenzoic acid 2m, after complete removal of solvents. Indeed, this issue should
not be considered as unexpected since it is known that organic azides with an unfavourable (C +
O)/N relationship (≤ 3) are more prone to decomposition in neat form [27]. Although the resulting
losses could be minor, they became more significant on yields because we have worked on a 0.5
mmol scale (less than 90 mg of aryl azides) in this preliminary study. Regardless, it is interesting to
1
highlight that, H and 13C NMR analysis of all crude samples showed fairly pure aryl azides.
Moreover, without further purification, 2c exhibited a very low tin contamination of 47 ppm (ICP)
[28] whereas, in the same compound obtained in solution, it was about 10,000 ppm (1%) after
chromatographic isolation; it should be noted that by a subsequent column chromatography on KF-
silica gel (1:9) [29], its residual tin was reduced to less than 50 ppm, but the yield was dropped from
87% to 70%.
So far, these results showed that the effectiveness of 3b, as azide-transfer reagent, is comparable
to that of its soluble counterpart TBSnN3 in the proposed method. As expected, the use of the resin-
bound tin azide meant a great improvement as regards to isolation of the aryl azides when compared
with those implemented in solution for the same compounds. By a simple filtration and solvent
elimination, the products were obtained with very low levels of residual tin and did not required
further purification.

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Then, we focused on the recyclability of 3b from the polymer-supported dibutyltin sulfonate 3c
recovered by filtration at the end of the reactions (P-SnBu2OTs in Scheme 4) [30]. Bearing in mind
the advantageous good leaving group ability of tosylate ion, the same initial procedure carried out in
the synthesis of 3b (by chloride displacement of 3a with TBSnN3) was applied on the resin 3c
taking into account its theoretical loading (1.04 mmol/g). At the end of the first treatment, a
complete conversion to azide 3b was observed by gel-phase 119Sn NMR analysis and the azide
loading was evaluated to be 0.76 mmol N3/g [31]. The recycled resin was then utilized in the
azidodeamination of 1c and the corresponding azide 2c was obtained in 87% yield (GC‒MS)
showing that no significant loss in reactivity took place (Scheme 4).
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3. Conclusions
We have shown that tributyltin azide is an effective reagent for the synthesis of diverse aryl
azides in good to excellent yields, via diazotization of anilines in a one-pot stepwise procedure
under mild conditions. Beside its easier access and relative stability, one of the main attractiveness
of this covalent azide-transfer reagent lies in that it is readily recoverable from the corresponding
stable and low volatile byproducts. The very good yields of these reactions are appropriate to
perform tandem strategies and, in regards with the concern about tin pollution, also allow to
accomplish further thorough purifications to reduce their tin content at trace levels, if the aryl azides
must be isolated. It is in this connection that we sought to explore the alternative use of an insoluble
polymer-supported organotin azide and encouraging results were obtained, for a selected group of
anilines, in terms of yields, easier workup, low tin pollution of products and recyclability of the
reagent. In addition, all resin-bound organotin reagents are very stable and can be stored at 2-4 °C,
for an extended period of time, without loss of reactivity. Further explorations on the scope of this
approach, as well as on other applications of the supported tin azide, are still ongoing in our
laboratory.
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4. Experimental Section
4.1. General
All the reactions were carried out in open air glassware. Unless otherwise stated, analytical grade
reagents and solvents were purchased and used as received. TBSnN3 was obtained from freshly
distilled TBSnCl as described below. Resin-bound dibutyltin chloride (3a) was prepared according
to the known literature procedure [24] from a Merrifield resin (100-200 mesh, 2 mmol Cl/g, 1%
cross-linked) purchased from Sigma-Aldrich. NMR spectra were recorded at room temperature on a
300 MHz spectrometer operating at 300.1 MHz for 1H, 75.5 MHz for 13C and 111.9 MHz for 119Sn.
13
Chemical shifts (
δ
) are given in ppm referenced to external Me4Sn (119Sn) and Me4Si (1H and C)

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with the residual solvent resonance signal:
δ
H/C 7.27/77.2 for CDCl3 and
δ
H/C 2.54/39.5 for
DMSO-d6. All coupling constants (J values) are quoted in hertz (Hz). Gel-phase 13C NMR (CDCl3)
were recorded with optimized set parameters [25] and gel-phase 119Sn NMR (CDCl3) were
performed as the routine experiments. The acquisition of mass spectra and analytical determinations
were performed using a GC
‒MS instrument (HP5‒MS capillary column, 30 m × 0.25 mm × 0.25
ꢁ
m) equipped with a HP-5972 selective mass detector operating at 70 eV in electron-ionization (EI)
mode. Program: 50 °C for 2 min with increase 10°C/min to 280°C; injection port temperature: 200
ºC. Microanalytical data were obtained using an Exeter Analytical CE-440 CHN/O instrument. The
tin content was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-
AES) analysis at LANAQUI laboratories (CERZOS-CONICET-UNS-Bahía Blanca, Argentina).
CAUTIONS: Because azides are potentially explosive compounds, all azidation reactions and
subsequent workups should be operated carefully and conducted in a fume hood with the sash
positioned as low as possible. For safety instructions on lab-scale synthesis of azido compounds see
ref [1a], pp 5-6.
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4.2. Synthesis of tributyltin azide (TBSnN3)
A round bottom flask was charged with TBSnCl (1.63 g, 1.36 mL, 10 mmol) and NaN3 (0.72 g,
11 mmol). After being stirred for 4 h at room temperature, the reaction mixture was diluted with
Et2O (100 mL) and washed successively with H2O (3 × 50 mL) and brine. The organic layer was
dried over MgSO4 and concentrated under reduced pressure to give 2.96 g (89 % yield) of TBSnN3,
as a colorless liquid, whose NMR spectral data were identical to those of commercial (Sigma-
Aldrich) sample.
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4.3. General procedure for azidodeamination of aryl amines 1
In a 25 mL round bottom flask, a solution of aryl amine 1 (2 mmol) and TsOHꢀH2O (0.456 g, 2.4
mmol) in MeCN (14 mL) was cooled to 0°C in an ice bath and stirred for 15 min. t-BuONO (0.247
g, 0.285 mL, 2.4 mmol) was added dropwise and the solution was kept under stirring for further 15
min at the same temperature. After dropwise addition of TBSnN3 (0.797 g, 0.657 mL, 2.4 mmol)
the reaction mixture was allowed to attain room temperature and stirred for the time indicated in
Scheme 2.
All synthesized aryl azides are known compounds whose physical and spectroscopic properties
are in agreement with those previously reported: 2a, 2e-f, 2h-I, 2k-m [6]; 2c [32], 2d [33], 2g [34],
2j [35]. The characterization data for 2b matched that of an authentic commercial sample (Sigma-
Aldrich, CAS# 3296-05-7).

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4.3.1. General procedure for isolation of aryl azides 2a-j and recovery of TBSnN3
After the above-described procedure, 20 µL of o-DCB (internal standard) was added to the
reaction mixture followed by appropriate dilution with Et2O (to 50 mL) for quantitative GC MS
analysis. Thereafter, NaN3 (0.156 g, 2.4 mmol) was added to the MeCN Et2O resulting solution and
‒
‒
the suspension was left overnight under stirring at room temperature. The precipitated NaOTs was
filtered off under vacuum, rinsed with Et2O (3 × 5 mL) and the filtrate solution was washed
successively with distilled water (5 × 15 mL) and brine. The organic layer was dried over MgSO4,
filtered and concentrated under reduced pressure.
For aryl azides 2a-g, the residue obtained after complete removal of solvent, was subjected to
flash chromatography on silica gel pre-treated with Et3N (10% v/v) giving the corresponding
product in fractions eluted with hexanes. Then, after a fast increasing of eluting power, the TBSnN3
was recovered from AcOEt fractions in around 80 % yield.
Instead, the aryl azides 2h-j were precipitated from the concentrated filtrates by dropwise
addition of cold hexane, and pure products were obtained by recrystallization from the same
solvent. The TBSnN3 was then recovered from the supernatants, in near quantitative yield, after
solvent removal and vacuum drying.
Azidobenzene (2a). Following the general procedures within 2 hours of reaction, 77 % yield of
1
the title compound was obtained as yellow oil ; H NMR (300 MHz, CDCl3)
δ
7.50
‒
7.41, (m, 2H),
140.0,
+ ), 91 [100, (M+·‒ N2)], 64 (61).
1-Azido-2-chlorobenzene (2b). Following the general procedures within 2 hours of reaction, 68
% yield of the title compound was obtained as yellow oil; 1H NMR (300 MHz, CDCl3)
7.29 (dd, J
= 8.0, 1.5 Hz, 1H), 7.25–7.17 (td, J = 8.1, 1.5 Hz, 1H), 7.10 (dd, J = 8.0, 1.5 Hz, 1H), 7.00 (td, J =
7.7, 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
137.3, 130.9, 128.0, 125.8, 125.2, 119.8; MS m/z
(% rel. intensity, ion) 153 (22, M+ ), 125 [100, (M+
-N2)], 90 (69), 63 (48).
1-Azido-3-chlorobenzene (2c). Following the general procedures within 2 hours of reaction, 87
% yield of the title compound was obtained as pale yellow oil; 1H NMR (300 MHz, CDCl3)
7.20
(t, J = 8.0 Hz, 1H), 7.06 (ddd, J = 8.0, 1.9, 1.0 Hz, 1H), 7.03 (d, J = Hz, 1H), 6.96 (t, J = 2.1 Hz,
1H), 6.86 (ddd, J = 8.1, 2.2, 1.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
141.6, 135.6, 130.8, 125.2,
119.5, 117.4; MS m/z (% rel. intensity, ion) 153 (22, M+ ), 125 [100, (M+
- N2)], 90 (69), 63 (48).
7.26 (t, J = 7.4 Hz, 1H), 7.14 (dd, J = 8.6, 1.1 Hz, 2H); 13C NMR (75.5 MHz, CDCl3)
δ
129.7, 124.8, 119.0; MS m/z (% rel. intensity, ion) 119 (25, M
·
δ
δ
·
·
δ
δ
·
·
1-Azido-4-chlorobenzene (2d). Following the general procedures within 1 hour of reaction, 77 %
1
yield of the title compound was obtained as yellow oil; H NMR (300 MHz, CDCl3)
δ
7.20 (d, J =
138.8, 130.3, 129.9, 120.3; MS
- N2)], 90 (69), 63 (48).
8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3)
m/z (% rel. intensity, ion) 153 (22, M+ ), 125 [100, (M+
δ
·
·

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1-Azido-4-nitrobenzene (2e). Following the general procedures within 1 hour of reaction, 40 %
1
yield of the title compound was obtained as orange oil; H NMR (300 MHz, CDCl3)
δ
(ppm) 7.06
(ppm) 147.0, 144.8,
- N2)], 90 (71), 63 (100).
1-Azido-4-methoxybenzene (2f). Following the general procedures within 1 hour of reaction, 68
% yield of the title compound was obtained as yellow oil; 1H NMR (300 MHz, CDCl3)
6.87 (d, J
= 9.1 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H), 3.70 (s, 1H); 13C NMR (75.5 MHz, CDCl3)
157.1, 132.5,
- N2)], 107 (42, p-
(d, J = 9.0 Hz, 2H), 8.18 (d, J = 9.0 Hz, 2H). 13C NMR (75 MHz, CDCl3)
125.7, 119.5. MS m/z (% rel. intensity, ion) 164 (20, M+ ), 136 [56, (M+
δ
·
·
δ
δ
120.1, 115.3, 55.7; MS m/z (% rel. intensity, ion) 149 (20, M+ ), 121 [100, (M+
· ·
An+), 78 (54), 52 (38).
1-Azido-2,4,6-trimethylbenzene (2g). Following the general procedures within 1 hour of reaction,
1
78 % yield of the title compound was obtained as pale brown oil; H NMR (300 MHz, CDCl3)
δ
6.75 (s, 2H), 2.24 (s, 6H), 2.17 (s, 3H); 13C NMR (75 MHz, CDCl3)
20.8, 18.1; MS m/z (% rel. intensity, ion) 161 (18, M+ ), 133 [100, (M+
δ
135.5, 134.5, 132.0, 129.6,
·
·- N2)], 119 (61).
4-Azido-benzonitrile (2h). Following the general procedures within 1 hour of reaction, 75 %
1
yield of the title compound was obtained as orange crystals; H NMR (300 MHz, CDCl3)
δ
(ppm)
144.9, 133.8,
·
), 116 [100, (M+· ‒ N2)], 89 (73), 62
7.64 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2 H); 13C NMR (75 MHz, CDCl3)
119.7, 118.3, 108.3; MS m/z (% rel. intensity, ion) 144 (33, M+
δ
(45).
1-(4-Azidophenyl)ethan-1-one (2i). Following the general procedures within 1 hour of reaction,
1
88 % yield of the title compound was obtained as orange crystals; H NMR (300 MHz, CDCl3)
δ
7.99 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 8.8 Hz, 2H), 2.60 (s, 3H); 13C NMR (75 MHz, CDCl3)
· ·
144.9, 133.9, 130.3, 119.0, 26.4; MS m/z (% rel. intensity, ion) 161 (42, M+ ), 133 [100, (M+
δ
196.5,
- N2)],
90 (54), 63 (63).
1-azido-2,4-dibromobenzene (2j). Following the general procedures within 2 hours of reaction,
72 % yield of the title compound was obtained as yellow solid; 1H NMR (300 MHz, CDCl3)
7.62
(d, J = 2.2 Hz, 1H), 7.38 (dt, J = 10.0, 2.8 Hz, 1H), 6.97 (d, J = 8.6, 1.8 Hz, 1H); 13C NMR (75
MHz, CDCl3) (ppm) 138.2, 136.3, 131.7, 120.6, 117.9; MS m/z (% rel. intensity, ion) 277 (20,
M+ ), 249 [60, (M+
- N2)], 170 (100).
δ
δ
·
·
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4.3.2. General procedure for isolation of azidobenzoic acids 2k-n and recovery of TBSnCl
Once azidodeamination is completed, the reaction mixture was cooled to 0 °C, and 5.4 N
aqueous HCl was added dropwise until no further precipitation is observed. The solid was collected
by vacuum filtration, rinsing it sequentially with distilled water (3 × 10 mL) and cold hexane (3 × 5
mL), providing the title compound in fairly pure form after drying under vacuum. Thereafter, the

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organic layer was separated from the resulting filtrate and the aqueous layer was neutralized and
extracted with Et2O (3 × 10 mL). The combined organic layers were washed with distilled water (3
× 10 mL) and brine, dried over MgSO4 and concentrated under reduced pressure recovering the
TBSnCl in about 95 % yield.
2-Azidobenzoic acid (2k). Following the general procedures within 1 hour of reaction, 72 %
yield of the title compound was obtained as beige solid; 1H NMR (300 MHz, DMSO)
= 7.8, 1.7 Hz, 1H), 7.59 (tt, J = 7.5, 1.7 Hz, 1H), 7.21
7.39 (m, 2H), 3.43 (br s, 1H). 13C NMR (75
MHz, DMSO) 166.5, 138.7, 133.0, 131.1, 124.9, 124.0, 120.9, 39.5.
2-Azido-5-iodobenzoic acid (2l). Following the general procedures within 2 hours of reaction, 65
% yield of the title compound was obtained as brown solid; 1H NMR (300 MHz, CDCl3)
8.38 (d, J
= 2.1 Hz, 1H), 7.87 (dd, J = 8.5 and 2.1 Hz, 1H), 7.02 (d, J = 8.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3) 166.7, 143.1, 141.9, 140.2, 122.6, 121.5, 88.0.
2-Azido-4-fluorobenzoic acid (2m). Following the general procedures within 2 hours of reaction,
77 % yield of the title compound was obtained as white solid; 1H NMR (300 MHz, DMSO)
13.17
(br s, 1H), 7.86 (dd, J = 8.7, 6.4 Hz, 1H), 7.28 (dd, J = 9.9, 2.5 Hz, 1H), 7.11 (td, J = 8.4, 2.5 Hz,
1H); 13C NMR (75 MHz, DMSO)
165.5 (d, JCF = 25.8 Hz), 162.5, 141.5 (d, JCF = 10.2 Hz), 133.6
δ 7.76 (dd, J
‒
δ
δ
δ
δ
δ
(d, JCF = 10.4 Hz), 120.3 (d, JCF = 3.2 Hz), 111.9 (d, JCF = 21.9 Hz), 108.3 (d, JCF = 25.2 Hz).
2-Azido-4,5-dimethoxybenzoic acid (2n). Following the general procedures within 2 hours of
reaction, 71 % yield of the title compound was obtained as grey solid; 1H NMR (300 MHz, CDCl3)
13
δ
7.61 (s, 1H), 7.28 (s, 1H), 6.67 (s, 1H), 3.99 (s, 3H), 3.92 (s, 3H); C NMR (75 MHz, CDCl3)
δ
167.8, 154.2, 146.5, 134.1, 114.7, 112.7, 102.4, 56.5, 56.4.
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4.4. Synthesis of [3-(azidodibutylstannyl)propoxy]methyl Polystyrene (3b)
To a suspension of resin-bound dibutyltin chloride 3a (2.25 g, 2.83 mmol, theoretical loading:
1.26 mmol Cl/g) in DMF (25 mL), TBSnN3 (4.7 g, 14.17 mmol, 5 equiv) was added dropwise and
the mixture was left under gentle stirring 24 h at room temperature. The resin was washed with
DMF (3 × 20 mL) and the same reaction process was repeated once. After vacuum filtration, the
resin was washed successively with DMF, EtOH, DCM and Et2O (3 × 20 mL each) and then dried
under high vacuum (ca. 3 h) to give 3b as a pale yellowish resin (2.03 g, 60 %, 0.84 mmol N3/g,
theoretical loading: 1.25 mmol N3/g); 13C NMR (gel-phase in CDCl3, 75 MHz)
26.9, 25.7, 16.1, 13.8, 10.5; 119Sn NMR (gel-phase in CDCl3, 112 MHz)
25.4; Elemental Analysis
δ 45.3, 40.4, 28.0,
δ
found: C, 61.49; H. 6.48; N 3.54. All combined filtrates and washing solutions were concentrated
and then left overnight under stirring following addition of NaN3 (0.156 g, 2.4 mmol). After the

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usual workup and routine controls, this recovered TBSnN3 (4 g, 12 mmol, 80 %) was used for
another reactions.
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4.4.1 General procedure for azidodeamination of aryl amines 1c, 1i and 1m by using 3b, and its
later recovery
After the above-described diazotization step of aryl amine (0.5 mmol), MeCN (3.5 mL) and
resin 3b (0.5 g, 0.6 mmol, 0.84 mmol N3/g) were added, the suspension was gently stirred for 24 h
at room temperature and the polymeric material was removed by vacuum filtration, washing it
successively with MeCN and Et2O (3 × 5 mL each). Whether it is appropriate, the combined
filtrates and washing solutions were subjected to quantitative GC‒MS analysis and thereafter,
solvent removal and vacuum drying afforded the corresponding pure aryl azide 2. The collected
resin 3c was further washed successively with EtOH, DCM and Et2O (3 × 5 mL each), dried under
high vacuum to constant weight, and stored at 2-4 °C; opportunely, after several experiments, it was
reacted with a 5-fold excess of TBSnN3 in accordance with its theoretical loading (1.04 mmol/g).
After the first reaction process and subsequent workup, applying the same above-described
procedures for its synthesis, 3b was recovered as a yellowish resin (in around 60 % yield) and was
found to contain 0.76 mmol of N3/gr. Elemental Analysis: C, 67.19; H, 6.93; N, 3.19.
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Acknowledgements
We are grateful for financial support provided by CONICET (Consejo Nacional de
Investigaciones Científicas y Técnicas), ANPCyT (Agencia Nacional de Promoción Científica y
Tecnológica), CIC (Comisión de Investigaciones Científicas) and SGCyT-UNS (Secretaría General
de Ciencia y Técnica Universidad Nacional del Sur) from Argentina. CONICET is thanked for a
research fellowship to LGP.
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Supporting Information available
Experimental procedures, characterization data, and copies of gel phase 13C and 119Sn NMR
spectra of resin 3b.
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Authors Information
*Corresponding author, e-mail: lockhart@criba.edu.ar; Fax: (+54)-0291-4595187; Tel: (+54)-0291-
4595101.
§ Member of CONICET
§§ Member of CIC
436
Notes and references

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[1] (a) Organic Azides: Syntheses and Applications, ed. S. Bräse and K. Banert, John Wiley
& Sons, Ltd., Chichester, 2010; (b) D. Intrieri, P. Zardi, A. Caselli and E. Gallo, Chem.
Commun. 50 (2014) 11440-11453.
[2] H. A. Henthorn, M. D. Pluth, J. Am. Chem. Soc. 137 (2015) 15330-15336.
[3] E. W. Meijer, S. Nijhuis, F. C. B. M. Von Vroonhoven, J. Am. Chem. Soc. 110 (1988)
7209-7210.
[4] E J. Park, G. T. Carroll, N. J. Turro, J. T. Koberstein, Soft Matter 5 (2009) 36-50.
[5] J. Das, S. N. Patil, R. Awasthi, C. P. Narasimhulu, S. Trehan, Synthesis (2005) 1801-
1806.
[6] K. Barral, A. D. Moorhouse, J. E. Moses, Organic Lett. 9 (2007) 1809-1811.
[7] (a) A. Hubbard, T. Okazaki, K. K. Laali, J. Org. Chem. 73 (2008) 316-319; (b) A. R.
Hajipour, F. Mohammadsaleh, Org. Prep. Proced. Int. 43 (2011) 451-455.
[8] M. E. Trusova, K. V. Kutonova, V. V. Kurtukov, V. D. Filimonov, P. S. Postnikov,
Resource-Efficient Technologies 2 (2016) 36-42.
[9] A. Zarei, A. R. Hajipour, L. Khazdooz, H. Aghaei, Tetrahedron Lett. 50 (2009) 4443-
4445.
[10] (a) F. Stazi, D. Cancogni, L. Turco, P. Westeruin, S. Bacchi, Tetrahedron Lett. 51 (2010)
5385-5387; (b) C. J. Smith, C. D. Smith, N. Nikbin, S. V. Ley, I. R. Baxendale, Org.
Biomol. Chem. 9 (2011) 1927-1937.
[11] M. A. Karimi Zarchi, R. Ebrahimi, Iran Polym. J. 21 (2012) 591-599.
[12] M. A. Karimini Zarchi, R. Nabaei, J. Appl. Polym. Sci. 124 (2012) 2362-2369.
[13] A. D. Moorhouse, J. E. Moses, Synlett 14 (2008) 2089-2092.
[14] C&EN,
http://cen.acs.org/articles/92/i43/Chemical-Safety-Explosion-hazard-
synthesis.html (accessed May 2016).
[15] H. R. Kricheldorf, E. Leppert, Synthesis (1976) 329-330.
[16] J. Roh, K. Vávrová, A. Hrabálek, Eur. J. Org. Chem. (2012) 6101−6118.
[17] M. J. Lo Fiego, V. B. Dorn, M. A. Badajoz, M. T. Lockhart, A. B. Chopa, RCS Advance
4 (2014) 49079-49085 and references cited herein.
[18] H. Ku and J. R. Barrio, J. Org. Chem. 46 (1981) 5239-5241.
[19] C. Chuit, R. J. P. Corriu, C. Reye, J. C. Young, Chem. Rev. 93 (1993) 1371–1448.
[20] M. P. Doyle, W. J. Bryker, J. Org. Chem. 44 (1979) 1572-1574.
[21] Prepared from bis(tributyltin) oxide and
p-toluenesulfonic acid; P. G. Harrison, R. C.
Philips, J. A. Richards, J. Organomet. Chem. 114 (1976) 47-52.

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[22] Such decomposition reactions of diazonium salts in acetonitrile have been reported; W.
E. Hanby, W.A. Waters, J. Chem. Soc. (1939) 1792-1795.
[23] E. Le Grognec, J.-M. Chrétien, F. Zammattio, J.-P. Quintard, Chem. Rev. 115 (2015)
10207-10260; see also J.-M. Chrétien, J. D. Kilburn, F. Zammattio, E. Le Grognec, J.-P.
Quintard, Tin Chemistry. Fundamentals, Frontiers and Applications, ed. A. G. Davies
,M. Gielen, K. H. Pannell and E. R. T. Tiekink, John Wiley & Sons, Ltd., New York,
2008, ch. 5, pp. 607−621.
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8601−8603.
[25] F. Lorgé, A. Wagner, C. Mioskowski, J. Comb. Chem. 1 (1999) 25-27.
[26] No literature data are available for comparison.
[27] H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int. Ed. 40 (2001) 2004-2021.
[28] From samples digested in nitric acid.
[29] D. C. Harrowven, I. L. Guy, Chem. Commun. (2004) 1968−1969.
[30] The identity of this compound was assumed in according to what it was established in
solution.
[31] The slight decrease in loading of recovered resin, as compared with the fresh one, is
likely to be a consequence of some mechanical degradation of the resin on stirring during
the recovery process.
[32] A. Nocentini, M. Ceruso, F. Carta, C. Supuran, J. Enzyme Inhib. Med. Chem. (2015) 1-
8.
[33] M. Kitamura, S. Kato, M. Yano, N. Tashiro, Y. Shiratake, M. Sando, T. Okauchi, Org.
Biomol. Chem. 12 (2014) 4397-4406.
[34] Y. Li, L.-X. Gao, F.-S. Ham, Chem. Eur. J. 16 (2010) 7969-7972.
[35] H. Jin, Z. D. Huang, C. X. Kuang, X. K. Wang, Chin. Chem. Lett. 22 (2011) 310-313.

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Highlights
•
•
•
One-pot stepwise diazotization-azidodediazoniation of aromatic amines.
Mild and efficient procedure with no risk of release of hydrazoic acid.
Tributyltin azide as hydrolytically stable, easily available and recoverable azide-transfer
reagent.
•
•
A novel and recyclable polymer-supported organotin azide enables down tin residues to
ppm levels in aryl azide products.
Long-term storable reagents.