Microwave-assisted synthesis of substituted fluorophenyl mono- and diazides by SNAr. A fast methodology to prepare photoaffinity labeling and crosslinking reagents

Article abstract of DOI:10.1016/j.jfluchem.2013.10.002

The reaction of sodium azide with perfluorobenzene, containing an electron-withdrawing group, under microwave irradiation results in the fast preparation of p-substituted tetrafluorophenyl monoazides. Having an excess of sodium azide and a strong electron-withdrawing group like NO₂ or CN, fluorophenyl diazides are also produced upon conventional or microwave heating. A synergic effect between the amount of sodium azide and the electron-withdrawing character of the substituents is observed giving different products. A discussion on the products and reaction mechanism is presented.

Full text of DOI:10.1016/j.jfluchem.2013.10.002

Journal of Fluorine Chemistry 156 (2013) 164–169
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Microwave-assisted synthesis of substituted fluorophenyl
mono- and diazides by S Ar. A fast methodology to prepare
N
photoaffinity labeling and crosslinking reagents
1,
Elisa Leyva *, Socorro Leyva, Edgar Moctezuma,
Regina M. Gonz a´ lez-Balderas, Denisse de Loera
Facultad de Ciencias Qu ı´ micas, Universidad Aut o´ noma de San Luis Potos ı´ , Manuel Nava No. 6, 78210 San Luis Potos ı´ , S.L.P., Mexico
A R T I C L E I N F O
A B S T R A C T
Article history:
The reaction of sodium azide with perfluorobenzene, containing an electron-withdrawing group, under
Received 31 May 2013
microwave irradiation results in the fast preparation of p-substituted tetrafluorophenyl monoazides.
Received in revised form 25 September 2013
Accepted 2 October 2013
Available online 11 October 2013
2
Having an excess of sodium azide and a strong electron-withdrawing group like NO or CN, fluorophenyl
diazides are also produced upon conventional or microwave heating. A synergic effect between the
amount of sodium azide and the electron-withdrawing character of the substituents is observed giving
different products. A discussion on the products and reaction mechanism is presented.
ß 2013 Elsevier B.V. All rights reserved.
Keywords:
Fluoroarylazide
Microwave
Photoaffinity labeling
Diazides
1
. Introduction
Aryl azides are high-energy molecules with interesting
The use of aromatic azides for PAL experiments was first
introduced by Bayley and Knowles in 1977 [4]. However, the
photolysis of aryl azides gives a variety of products which yields
are modified by several factors such as temperature, solvent, and
substituents [5]. These reactions are seldom clean with the
production of tars and polymers and have limited the application
of aryl azides in PAL. In a given aryl nitrene, the intermediate
generated upon photolysis of an aryl azide, the presence of
electron-withdrawing substituents is expected to modify its
reactivity. In search of an aryl azide with adequate physicochemi-
cal properties like a facile generation of a highly reactive
intermediate, we investigated the photochemistry of several
fluoro-substituted aryl azides [6]. The experimental observation
that pentafluorophenyl azide undergoes photochemical insertion
with several solvents led to further investigations about the
reactions of this type of azides [7]. It was demonstrated that two
fluorine atoms adjacent to the azide group inhibit ring expansion, a
secondary nitrene reaction, and favor aryl nitrene (C–H and N–H)
insertion reactions [1]. In the case of perfluorophenyl azides, the
presence of another electron-withdrawing group (nitro, carbonyl,
or cyano) in the para-position to the azide group increased C–H
insertion reactions since the electrophilicity of the intermediate
nitrene, generated upon photolysis, was also increased [8].
In recent years, perfluoro aryl azides are applied in the
preparation of bifunctional chelating agents BFCAs utilized in
photochemical properties [1]. Their complex photochemistry
has fascinated theoretical and experimental chemists for many
years. In recent years, they have found many applications in
organic chemistry in the synthesis of heterocyclic compounds [2],
in polymer chemistry as crosslinking agents [3] and in the
biochemical method known as photoaffinity labeling or PAL [4].
In a PAL experiment, a small light-sensitive moiety is appended
to a natural ligand of a biological macromolecule [4]. On
photolysis, the modified ligand must generate a short-lived and
highly reactive intermediate capable of reacting in an indiscrimi-
nating manner with surrounding C–H and N–H bonds present in
the macromolecule to produce an adduct. An aryl carbene was
utilized in the first PAL experiments [4]. However, since this
intermediate is long-lived it can migrate out of the binding site and
reacts predominantly with water. Based on these experimental
results, new reagents for PAL are being synthesized.
*
Corresponding author. Present address: Department of Chemistry, UWO,
Chemistry Building, London, ON N6A5B7, Canada. Tel.: +1 5196912166;
fax: +1 5196613022.
E-mail addresses: eleyvara@uwo.ca, elisa@uaslp.mx (E. Leyva).
1
On sabbatical leave from UASLP, Mexico.
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.10.002

E. Leyva et al. / Journal of Fluorine Chemistry 156 (2013) 164–169
165
PAL [9]. For these latter PAL experiments, an organic compound is
We started by performing the S
N
Ar reaction under conventional
prepared with a photoactive moiety (like an aryl azide) and a
chelating agent (to chelate a transition metal). BFCAs could be
useful reagents in nuclear medicinal chemistry to achieve
attachment of a radiolabeled molecule to antibodies or antibody
fragments which in turn could be attached to specific biological
sites for imaging or cancer therapy [1,9].
The application of microwave irradiation as a non-conventional
energy source for reactions has become a very popular and useful
technique in organic chemistry [10]. In general, the use of this type
of energy leads to enhanced conversion rates, higher yields, easier
work up and cleaner reactions demonstrating the real advantages
of this methodology.
Due to their highly effective and regiospecific reactivity,
fluorophenyl azides have gained an important place in the
interface between organic chemistry, biology, medicinal and
materials science [11]. In the present paper, we report the fast
preparation of several fluorophenyl mono and diazides by reaction
of the corresponding halogenated compounds with sodium azide
under microwave irradiation.
heating (D) and reacted several R-pentafluorobenzene derivatives
1a–e with sodium azide by refluxing in acetone/water for 8 h
(Table 1). Under these previously reported conditions [8], we
obtained the corresponding perfluorophenyl azides 2a–e in good
yields. The reaction of sodium azide with pentafluoroacetophe-
none 1b was investigated under microwave irradiation (MW,
50 W) at 70 8C for 15 min using a mixture of acetone/water as
solvent. The crude product mixture was analyzed by thin layer
chromatography, which indicated that the reaction proceeded very
N
fast. The microwave-assisted S Ar reaction of several pentafluor-
obenzene derivatives 1a–e was performed and the corresponding
aromatic azides 2a–e were obtained in good yields in rather short
times (Table 1).
After performing the preparation of several monoazides by
S
N
Ar, we decided to investigate the effect of an excess of the strong
nucleophile (NaN ) under conventional heating or microwave
irradiation. When a R-pentafluorobenzene derivative, containing a
group like COH or COCH , was reacted with several equivalents of
sodium azide no change in the reaction products was observed
Scheme 1). Even with a large excess of nucleophile only the para-
3
3
(
2
. Results and discussion
substituted fluorophenyl azide was produced.
Performing the reaction of large amounts of sodium azide
Aryl azides are usually prepared by treatment of diazonium
with
(COOCH
a
R-pentafluorobenzene, containing an ester group
3
), results in the production of a mixture of two isomeric
salts with sodium azide [12]. Since this method has some
limitations several alternative procedures have been investigated.
The reaction of p-tosyl azide with several compounds like Grignard
or lithium reagents and aryl amide salts has been reported [13].
The use of this latter transformation has been limited due to the
harsh conditions utilized. The conversion of aromatic amines into
the corresponding azides with triflylazide, a potentially explosive
reagent, has also been reported [14]. Upon refluxing, pentafluor-
obenzene containing an electron-withdrawing group (cyano, nitro,
or carbonyl) undergoes selective aromatic para-substitution with
sodium azide [8]. Recently, the nucleophilic aromatic substitution
of some aryl halides has been performed in ionic liquid solution
using 1-butyl-3-methylimidazolium azide as a nucleophile [15].
However, all of these procedures require long reaction times and
either acidic or basic conditions, which are not compatible with
many functional groups.
ortho- and para-substituted monoazides (Scheme 2). Both
positions in the aromatic compound are actually activated by
the inductive effect of the substituent, but the para-position
must be slightly more activated than the ortho. Interestingly,
two reactions compete under conventional heating or micro-
wave irradiation.
Reacting an equivalent amount of sodium azide with a
pentafluorobenzene derivative containing
a strong electron-
withdrawing group like cyano results in the exclusive formation
of a monoazide product (Table 1). In contrast, utilizing a large
excess of sodium azide (Scheme 3) results in the production of a
mixture of mono and diazide.
Similar results were observed with a pentafluorobenzene
derivative containing a very strong electron-withdrawing group
like NO
2
. A monoazide (Table 1) was obtained with one equivalent
Table 1
Preparation
of
p-substituted
fluorophenyl
azides
2a–e
from
R-fluorobenzene
1a–e.
.
a
b
Product
R
Traditional refluxing
Microwave refluxing
Time/h
Yield %
Time/min
Yield %
2
2
2
2
2
a
b
c
COH
8
8
8
8
8
90
80
80
75
70
15
15
15
15
15
85
85
70
90
90
COCH
3
COOCH
CN
3
d
e
NO
2
Each p-substituted fluorophenyl azide was purified by column chromatography and characterized by UV–vis, IR, NMR and MS.
a
A solution of R-pentafluorobenzene (1 mol) and NaN
3
(1 mol) in acetone (10 mL) and water (3 mL) was refluxed.
b
A solution of R-pentafluorobenzene (1 mol) and NaN
3
(1 mol) in acetone (6 mL) and water (2 mL) was irradiated in a microwave reactor (Discover CEM) at 70 8C (50 W).

1
66
E. Leyva et al. / Journal of Fluorine Chemistry 156 (2013) 164–169
Scheme 1. Reaction of sodium azide with pentafluorobenzaldehyde 1a and pentafluoroacetophenone 1b.
Scheme 2. Reaction of sodium azide with methyl pentafluorobenzoate 1c.
Scheme 3. Reaction of sodium azide with pentafluorobenzonitrile 1d.
amount of sodium azide and a diazide (Scheme 4) was also
produced with a large excess of sodium azide.
halogen atom. It is well known that this
proceeds by an addition-elimination mechanism (Scheme 5)
involving the formation of carbanion with delocalized
N
S Ar reaction
Nucleophilic substitution reactions of aryl halides (S
N
Ar)
a
take place only when an electronic factor makes the carbon
bonded to the halogen susceptible to nucleophilic attack
electrons called a Meisenheimer complex (Fig. 1). This interme-
diate is strongly stabilized due to the presence of fluorine or
other electron-withdrawing group in the several resonance
structures.
[
16]. Therefore, these reactions can occur when strong elec-
tron-withdrawing groups are ortho or para to the leaving
Scheme 4. Reaction of sodium azide with pentafluoronitrobenzene 1e.

E. Leyva et al. / Journal of Fluorine Chemistry 156 (2013) 164–169
167
3 3 2
Scheme 5. Different mechanisms in the reaction of sodium azide with R-pentafluorobenzene (R = COH, COCH , COOCH , CN, NO ).
N 3 3 2
Fig. 1. A free energy diagram for the S Ar reaction of sodium azide with R-pentafluorobenzene (R = COH, COCH , COOCH , CN, NO ).
In the reaction of pentafluoro benzene with a weak electron-
withdrawing substituent (COH, COCH ) only one mechanistic
or conventional heating provide the energy required for both
reactions to occur simultaneously (Fig. 1B). Having a cyano or
nitro substituent in the aromatic ring, the para-position is
actually activated by strong inductive and resonance effects
(Fig. 1C) thus making the first substitution a very fast process
(Scheme 5, Route 1). In this latter reaction, a para-substituted
tetrafluorophenyl azide is produced that contains an ortho-
position strongly activated for a second substitution to take place
(Scheme 5, Route 3).
3
pathway is available (Scheme 5, Route 1). In this case, only the
para-position is sufficiently activated (Fig. 1A) for substitution
under microwave irradiation or conventional heating. Thus the
reaction on ortho-position must require a larger amount of
energy than the one provided. Having an intermediate electron-
withdrawing substituent (COOCH
3
) both mechanisms (Scheme 5,
Route 1 and 2) must be close in energy and microwave irradiation

1
68
E. Leyva et al. / Journal of Fluorine Chemistry 156 (2013) 164–169
3
. Conclusions
4.2.2.2. 4-Azido-2,3,5,6-tetrafluoroacetophenone (2b). Colorless liq-
À1
3
uid [8]; IR (neat, cm ) 2970 (C–H aliphatic) 2127 (–N ), 1642, 1478
In summary, microwave-assisted synthesis of substituted
(C 55 C aromatic), 1707 (C 55 O), 1240, 1196, 1170 (C–F); UV–vis
1
N
fluorophenyl mono- and diazides by S Ar represents a fast
(CH
= 1.77, 3H); F NMR (400 MHz, CDCl
J = 20.74, 13.51, 4.83 Hz, 2F), À152.28(m,J = 20.74, J = 13.51,4.83 Hz,
2F); HRMS calcd for C O was 233.0212, found 233.0210.
3
OH, nm) 268, 209. H NMR (400 MHz, CDCl
3
)
d
(ppm) 2.61 (t, JH–
1
9
methodology to prepare photoaffinity labeling and crosslinking
reagents. A synergic effect between the amount of sodium azide
and the electron-withdrawing character of the substituents is
observed in this reaction. In fact, the type of products obtained
depends on the electron-withdrawing capacity of the substituents
F
3
) d
(ppm) À140.00 (ddd,
7 3 4 3
H F N
4.2.2.3. Methyl 4-azido-2,3,5,6-tetrafluorobenzoate (2c). Colorless
À1
on the fluorophenyl compound. A strong substituent (CN or NO
results in the production of a mixture of mono and diazide. A
medium strength substituent (COOCH ) results in the production
of two mono azides ortho- and para-substituted while a weak
2
)
solid with m.p. 54–55 8C [8]; IR (KBr, cm ) 2960 (C–H aliphatic)
2125 (–N
3
), 1738 (C 55 O), 1624, 1485 (C 55 C aromatic), 1260, 1221,
1
3
1000(C–F);UV–vis(CH OH, nm)264, 207. HNMR(400 MHz, CDCl )
3
3
1
9
d
(ppm) 3.96 (s, 1H); F NMR (400 MHz, CDCl
(ddd, J = 22.80, 13.80, 6.00 Hz, 2F), 161.67 (ddd, J = 22.80, 13.80,
6.00 Hz, 2F); HRMS calcd for C was 249.0161, found
49.0155.
3
)
d
(ppm) À139.45
3
substituent (COH, COCH ) gives exclusively para-substituted
tetrafluorophenyl azide.
8 3 4 3 2
H F N O
2
4
. Experimental
.1. General methods
Caution! Organic azides should be considered explosive. They
4
.2.2.4. 4-Azido-2,3,5,6-tetrafluorobenzonitrile (2d). Pale yellow liq-
À1
4
uid [8], IR (neat, cm ) 2239 (CN), 2121 (–N
3
), 1648, 1475 (C 55 C
OH, nm) 284, 258,
(ppm) À133.37 (ddd, J = 22.71,
15.51, 7.20 Hz, 2F), À149.97 (ddd, J = 22.71, 15.51, 7.20 Hz, 2F);
HRMS calcd for C was 216.0059, found 216.0051.
aromatic), 1266, 1243, 1215 (C–F); UV–vis (CH
3
1
9
3
208. F NMR (400 MHz, CDCl ) d
are thermally and frictionally sensitive and all manipulations
should take place behind a blast shield. They are light sensitive and
all reactions and chromatography procedures should be conducted
under diminished light.
Melting points were measured with a Fisher Johns apparatus.
UV–vis spectra were obtained on a Shimadzu UV-2401 Spectro-
7 4 4
F N
4.2.2.5. 4-Azido-2,3,5,6-tetrafluoronitrobenzene (2e). Pale yellow
À1
liquid [8], IR (neat, cm ) 2121 (–N
3
), 1604, 1511, 1489 (C 55 C
2
), 1129, 1117, 1106 (C–F); UV–vis
aromatic), 1590, 1368 (NO
1
9
photometer. NMR spectra were obtained on a Varian, Mercury
3 3
(CH OH, nm) 275, 253, 208. F NMR (400 MHz, CDCl ) d (ppm)
1
4
00 MHz nuclear magnetic resonance spectrometer. HNMR
À147.05 (ddd, J = 23.50, 15.84, 6.11 Hz, 2F), À150.49 (ddd, J = 23.50,
1
9
spectra were recorded in ppm from tetramethylsilane and
F
6 4 4 2
15.84, 6.11 Hz, 2F); HRMS calcd for C F N O was 235.9957, found
NMR spectra were recorded in ppm from hexafluorobenzene. Mass
spectra analysis was done on a Finnigan MAT 8200 spectrometer.
All the starting compounds were purchased from Aldrich.
Reactions under microwave irradiation were performed in a
CEM microwave reactor, Discover System DU8756.
235.9942.
4.2.2.6. Methyl 2-azido-3,4,5,6-tetrafluorobenzoate (2f). Pale yellow
solid with m.p. 66–68 8C, IR (KBr, cm ) 2970 (C–H aliphatic) 2129
À1
(–N
C–F); UV–vis (CH
(ppm) 3.72 (s, 1H); F NMR (400 MHz, CDCl3)
3
), 1732 (C 55 O) 1644, 1479 (C 55 C aromatic), 1260, 1229, 1216
1
(
3 3
OH, nm) 208, 270. H NMR (400 MHz, CDCl ) d
1
9
4.2. General synthetic methods
d
(ppm) À139.98
(
ddd, J = 18.31, 12.21, 6.10 Hz, 1F), À149.77 (dd, 20.64, 8.72 Hz, 2F),
4
.2.1. Substitution reaction S
A solution of R-pentafluorobenzene (1 mol) and sodium azide
1 or 5 mol) in acetone (10 mL) and water (3 mL) was placed in a
N
Ar under conventional heating (
D
)
À152.28 (dd, J = 20.64, 8.72 Hz, 1F). HRMS calcd for C
8 3 4 3 2
H F N O
was 249.0161, found 249.0155.
(
flask under reflux for 8 h. After cooling, it was poured in an ice/
water mixture and extracted with ether. The organic extract was
4.2.2.7. 2,4-Diazido-3,5,6-trifluorobenzonitrile (3a). Pale yellow liq-
À1
uid; IR (neat, cm ) 2230 (CN), 2116 (N
3
), 1650, 1631, 1475 (C 55 C
OH, nm) 272, 258,
(ppm) À140.31 (d, J = 9.11 Hz,
1F), À148.34 (dd, J = 21.26, 9.11 Hz, 1F), À148.94 (d, J = 21.26).
HRMS calcd for C was 239.0167, found 239.0160.
dried over anhydrous MgSO
4
, filtered and concentrated. Each
aromatic), 1655, 1243, 1211 (C–F); UV–vis (CH
3
1
9
fluorophenyl azide was separated and/or purified by column
chromatography [6].
3
208. F NMR (400 MHz, CDCl ) d
7 3 7
F N
4
.2.2. Substitution reaction S
A solution of R-pentafluorobenzene (1 mol) and sodium azide
1 or 5 mol) in acetone (6 mL) and water (2 mL) was placed in a
N
Ar under microwave irradiation (MW)
4.2.2.8. 2,4-Diazido-3,5,6-trifluoronitrobenzene (3b). Pale yellow
À1
(
liquid; IR (neat, cm ) 2116 (N
3
), 1626, 1579, 1512, 1479 (C 55 C
2
), 1230, 1198, 1157 (C–F); UV–vis
flask equipped with a reflux condenser. The reaction mixture
was irradiated in a microwave oven (at 50 W and 70 8C) for
aromatic), 1599, 1325 (NO
3
(CH OH, nm) 329, 311, 252, 209. F NMR (400 MHz, CDCl ) d
1
9
3
1
5 min. After cooling, it was poured in an ice/water mixture and
extracted with ether. The organic extract was dried over
anhydrous MgSO , filtered and concentrated. Each fluorophenyl
azide was separated and/or purified by column chromatography
6].
(ppm) À133.05 (dd, J = 20.46, 11.05 Hz, 1F), À140.62 (d,
J = 11.05 Hz, 1F), À149.43 (d, J = 20.46 Hz, 1F), HRMS calcd for
4
6 3 7 2
C F N O was 259.0066, found 259.0059.
[
Acknowledgements
4
.2.2.1. 4-Azido-2,3,5,6-tetrafluorobenzaldehyde (2a). Colorless sol-
We would like to acknowledge financial support by CONACyT
(Grant CB-2010-155678). R.M.G.-B. acknowledges financial support
by CONACyT (Scholarship No. 290618) for an internship at UCLA.
À1
id with m.p. 44–45 8C [8]; IR (KBr, cm ) 2917 (C–H aliphatic),
2
860, 2780 (C–H aldehyde), 2116 (–N
3
), 1703 (C 55 O), 1642, 1474
OH, nm) 284,
(C 55 C aromatic), 1263, 1238, 1216 (C–F); UV–vis (CH
3
1
19
References
2
50, 208. H NMR (400 MHz, CDCl
NMR (400 MHz, CDCl
(ppm) À146.34 (dd, J = 20.11, 7.22 Hz, 2F),
À152.40 (dd, J = 20.11, 7.22 Hz, 2F); HRMS calcd for C HF O was
19.0056, found 219.0052.
3
)
d
(ppm) 10.23 (m, 1H);
F
3
) d
[
1] For reviews on aryl azide and aryl nitrene chemistry:
a) E.F.V. Scriven, Azides and Nitrenes: Reactivity and Utility, Academic Press,
New York, 1984;
7
4 3
N
(
2

E. Leyva et al. / Journal of Fluorine Chemistry 156 (2013) 164–169
169
(
b) M.S. Platz, E. Leyva, K. Haider, Selected Topics in the Matrix Photochemistry of
(d) K. Schnapp, R. Poe, E. Leyva, N. Saudararajan, M.S. Platz, Bioconjugate Chem. 4
(1993) 172–177.
[7] (a) E. Leyva, R. Sagredo, Tetrahedron 54 (1998) 7367–7374;
(b) E. Leyva, R. Sagredo, E. Moctezuma, J. Fluorine Chem. 125 (2004)
741–747;
Nitrenes, Carbenes and Excited Triplet States, in: A. Padwa (Ed.), Org. Photochem.,
vol. 11, 1991, pp. 367–429;
(
c) M.S. Platz, Nitrenes, in: R.A. Moss, M.S. Platz, M.S. Jones, Jr. (Eds.), Reactive
Intermediate Chemistry, John Wiley & Sons Inc., New York, 2004;
(
(
d) D. de Loera, E. Leyva, R. Jim e´ nez-Cata n˜ o, Bol. Soc. Qu ı´ m. M e´ x 3 (2009) 93–106;
e) E. Leyva, D. de Loera, S. Leyva, R. Jim e´ nez-Cata n˜ o, Fluorinated aryl nitrene
precursors, in: D.E. Falvey, A.D. Gudmundsdottir (Eds.), Nitrene and Nitrenium
Ions, John Wiley & Sons Inc, New York, 2013.
(c) W.L. Karney, W.T. Borden, J. Am. Chem. Soc. 119 (1997) 3347–3350;
(d) N.P. Gritsan, A.D. Gudmunsdottir, D. Tigelaar, Z. Zhu, W.L. Karney, C.M.
Haddad, M.S. Platz, J. Am. Chem. Soc. 123 (2001) 1951–1962.
[8] (a) F.W. Keana, S.X. Cai, J. Org. Chem. 55 (1990) 3640–3650;
(b) J.F.W. Keana, S.X. Cai, J. Fluorine Chem. 43 (1989) 151–154;
(c) M. Yang, S.X. Cai, J.F.W. Keana, J. Org. Chem. 59 (1994) 5951–5954;
(d) K.A.H. Chehade, H.P. Spielmann, J. Org. Chem. 65 (2000) 4949–4953.
[9] (a) R.S. Pandurangi, S.R. Karra, R.R. Kuntz, W.A. Volkert, Photochem. Photobiol. 65
(1997) 208–221;
[
2] (a) E.F.V. Scriven, K. Turnbull, Chem. Rev. 88 (1988) 297–368;
(
(
b) S. Leyva, V. Castanedo, E. Leyva, J. Fluorine Chem. 121 (2003) 171–175;
c) E. Leyva, D. de Loera, R. Jim e´ nez-Cata n˜ o, Tetrahedron Lett. 51 (2010) 3978–
3
979;
d) E. Leyva, R.-M. Gonz a´ lez-Balderas, D. de Loera, R. Jim e´ nez-Cata n˜ o, Tetrahe-
dron Lett. 53 (2012) 2447–2449;
e) E. Leyva, S. Leyva, R.M. Gonz a´ lez-Balderas, D. de Loera, R. Jim e´ nez-Cata n˜ o,
(
(b) R.S. Pandurangi, K.V. Katti, L. Stilwell, C.L. Barnes, J. Am. Chem. Soc. 20 (1998)
11364–11373;
(
Mendeleev Commun. 23 (2013) 217–218.
3] For examples of aryl mono- and diazides as crosslinking reagents:
(c) R.S. Pandurangi, P. Lusiak, R.R. Kuntz, W.A. Volkert, J. Rogowski, M.S. Platz, J.
Org. Chem. 63 (1998) 9019–9020.
[
[
(
2
(
1
a) M. Yan, M.N. Wybourne, J.F.W. Keana, React. Funct. Polym. 43 (2000) 221–
25;
b) T. Hosoya, A. Inoue, T. Hiramatsu, T. Hikemoto, M. Suzuki, Bioorg. Med. Chem.
7 (2009) 2490–2496;
c) P.J. Crocker, N. Imai, K. Rajagopalan, M.A. Boggess, S. Kwiatkowsky, L.D. Dwyer,
[10] (a) B.L. Hayes, Microwave Synthesis: Chemistry at the Speed of Light, CEM
Publishing, USA, 2002;
(b) J.P. Tierney, P. Lidstr o¨ m, Microwave Assisted Organic Synthesis, Blackwell
Publishing, Oxford, UK, 2005;
(c) A. de la Hoz, A. D ı´ az-Ortiz, A. Moreno, Chem. Soc. Rev. 34 (2005) 164–178.
[11] For a review in new applications of perfluoroarylazides: L.-H. Liu, M. Yang,
Accounts Chem. Res. 43 (2010) 1434–1443.
(
T.C. Vanaman, D.S. Watt, Bioconjugate Chem. 1 (1990) 419–424.
4] For reviews on aryl azides as photoaffinity labels:
(
a) H. Bayley, Photogenerated Reagents in Biochemistry and Molecular Biology,
[12] (a) P.A.S. Smith, J.H. Boyer, J. Am. Chem. Soc. 73 (1951) 2626–2629;
(b) P.A.S. Smith, C.D. Rowe, L.B. Bruner, J. Org. Chem. 34 (1969) 3430–3433;
(c) P.A.S. Smith, G.F. Budde, S.P. Chou, J. Org. Chem. 50 (1985) 2062–2064.
[13] (a) W. Fisher, J.-P. Anselme, J. Am. Chem. Soc. 89 (1967) 5284–5287.
[14] Q. Liu, Y. Tor, Org. Lett. 5 (2003) 2571–2572.
Elsevier, New York, 1983;
(
(
b) S.A. Fleming, Tetrahedron 51 (1995) 12479–12520;
c) E. Leyva, S.Leyva-Ramos,C.Cort e´ s-Garc ı´ a,Rev. Mex. Cienc.Farm. 44(2013) 7–23.
[
5] (a) E. Leyva, M.S. Platz, G. Persy, J. Wirz, J. Am. Chem. Soc. 108 (1986) 3783–3790;
(
(
b) E. Leyva, M.S. Platz, Tetrahedron Lett. 26 (1985) 2147–2150;
c) E. Leyva, M.S. Platz, Tetrahedron Lett. 28 (1987) 11–14.
[15] (a) F. D’Anna, S. Marullo, R. Noto, J. Org. Chem. 73 (2008) 6224–6228;
(b) F. D’Anna, S. Marullo, P. Vitale, R. Noto, Ultrason. Sonochem. 19 (2012) 136–
142.
[
6] (a) E. Leyva, M.J.T. Young, M.S. Platz, J. Am. Chem. Soc. 108 (1986) 8307–8309;
(
(
b) E. Leyva, D. Munoz, M.S. Platz, J. Org. Chem. 54 (1989) 5938–5945;
c) R.Poe,M.J.T.Young,E.Leyva,M.S.Platz,J.Am.Chem.Soc.113(1991)3209–3211;
[16] T.W.G. Solomons, C.B. Fryhle, Organic Chemistry, John Wiley & Sons, Inc., New
York, U.S.A., 2004.