Generation of Iminyl Radicals through Sulfanyl Radical Addition to Vinyl Azides

Article abstract of DOI:10.1021/jo970691q

Benzenethiol and 2-benzo[b]thiophenethiol undergo almost instantaneous reaction with α-azi-dostyrene and 1-azido-trans-stilbene in benzene, at room temperature, to give corresponding β-sulfanylated imines and enamines in virtually quantitative yield. With α-azidostyrene, phenethyl and allyl mercaptan are found to react in a similar fashion, but to rates very much lower. Results are interpreted in terms of radical-chain reactions involving intermediacy of 2-sulfanyliminyl radicals which could result from sulfanyl radical attack at the azide β-carbon followed by nitrogen extrusion by the ensuing radical adduct.

Full text of DOI:10.1021/jo970691q

5
846
J . Org. Chem. 1997, 62, 5846-5848
Gen er a tion of Im in yl Ra d ica ls th r ou gh Su lfa n yl Ra d ica l Ad d ition
to Vin yl Azid es
Pier Carlo Montevecchi,* Maria Luisa Navacchia, and Piero Spagnolo
Dipartimento di Chimica Organica “A. Mangini”, Universit a` di Bologna, Viale Risorgimento 4,
I-40136 Bologna, Italy
Received April 11, 1997X
Benzenethiol and 2-benzo[b]thiophenethiol undergo almost instantaneous reaction with R-azi-
dostyrene and 1-azido-trans-stilbene in benzene, at room temperature, to give corresponding
â-sulfanylated imines and enamines in virtually quantitative yield. With R-azidostyrene, phenethyl
and allyl mercaptan are found to react in a similar fashion, but to rates very much lower. Results
are interpreted in terms of radical-chain reactions involving intermediacy of 2-sulfanyliminyl
radicals which could result from sulfanyl radical attack at the azide â-carbon followed by nitrogen
extrusion by the ensuing radical adduct.
Alkane- and arenethiols are well known to react with
Sch em e 1
alkenes under radical conditions to give 2-sulfanylalkyl
radicals arising from reversible addition of transient
1
sulfanyl radicals to the carbon-carbon double bond. The
radical addition is normally governed by the stability of
the ensuing carbon radical, though steric factors can play
a significant role. We report herein novel radical-chain
reactions of thiols with vinyl azides that form intermedi-
ate iminyl radicals through sulfanyl radical addition at
the â-carbon and disclose unprecedented instances of
H
homolytic substitution of S 2′ type at a vinylic azido
nitrogen. Generation of iminyl radicals is of interest
especially in view of very recent reports of their utility
in synthetic radical chemistry. Iminyl radicals have been
proved to exhibit intramolecular cyclization reactions
Sch em e 2
onto double bonds2 and aromatic rings as well as
-4
2
4
fragmentation reactions to give nitrile products. These
species have been formerly generated by thermolysis or
2
photolysis of various N-substituted imine derivatives,
5
by addition of carbon radicals to nitriles and, very
3
recently, using radical-chain reactions of Bu SnH with
3
4
sulfanylimines , N-benzotriazolylimines, and xanthic
hydrazones.6
Resu lts a n d Discu ssion
Treatment of R-azidostyrene (1) (0.1 M) in dry benzene,
at room temperature, with 1 equiv of benzenethiol (2a )
resulted in immediate evolution of nitrogen which virtu-
ally ceased within ca. 5 min. TLC analysis showed the
absence of the starting azide and apparent formation of
silica gel furnished their hydrolysis product, the â-keto
sulfide 7a , in almost quantitative yield (Scheme 1). The
azide 1 similarly reacted with 2-benzo[b]thiophenethiol
1
a single product, which was shown by H NMR spectros-
copy to be a 80:20 mixture of the sulfanylated enamine
(2b), being rapidly (and quantitatively) converted into the
corresponding 80:20 mixture of tautomers 6b and 5b
which were isolated as keto sulfide 7b upon subsequent
column chromatography (Scheme 1). Analogous reaction
also occurred with phenethyl mercaptan (2c) though it
proceeded much more slowly. In fact, even after 10 days
reaction time column chromatography isolated significant
amounts of unchanged azide (10%) in addition to the
expected sulfide 7c (40%) as the only identifiable product
6
a and its tautomer 5a . Column chromatography on
X
Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) For a recent review on sulfanyl radical additions to alkenes see:
Chatgilialoglu, C.; Guerra, M. Supplement S: The Chemistry of Sulfur-
containing Functional Groups; Patai, S., Rappoport, Z., Eds.; J .
Wiley: Chichester, 1993; Ch. 8.
(2) Atmaran, S.; Forrester, A. E.; Gill, M.; Thomson, R. H. J . Chem.
Soc., Perkin Trans. 1 1981, 1721, and refercences cited therein.
(
(
(
3) Boivin, J .; Fouquet, E.; Zard, S. Z. Tetrahedron 1994, 50, 1745.
4) Kaim, L. E.; Meyer, C. J . Org. Chem. 1996, 61, 1556.
5) Lindsay, D. A.; Lusztyk, J .; Ingold, K. U. J . Am. Chem. Soc. 1984,
(Scheme 1). Similar to the azide 1, under comparable
conditions 1-azido-trans-stilbene (8) was smoothly trans-
formed by benzenethiol 2a into the fairly stable enamine
1
06, 7087. Beckwith, A. L. J .; O’Shea, D. M.; Westwood, S. W. J . Am.
Chem. Soc. 1988, 110, 2565. Curran, D. P.; Seong, C. M. J . Am. Chem.
Soc. 1990, 112, 9401.
1
1, which could be isolated in 75% yield along with minor
amounts (10%) of the derived keto sulfide 12 (Scheme
). Instead, a different behavior was exhibited by â-azi-
dostyrene and 2-azido-3-phenylpropene. These azides in
(6) Callier-Doublanchet, A.-C.; Quiclet-Sire, B.; Zard, S. Z. Tetra-
hedron Lett. 1995, 36, 8791. LeTadic-Biadatti, M.-H.; Callier-Dou-
blanchet, A.-C.; Horner, J . H.; Quiclet-Sire, B.; Zard, S. Z.; Newcomb,
M. J . Org. Chem. 1997, 62, 559.
2
S0022-3263(97)00691-9 CCC: $14.00 © 1997 American Chemical Society

Sulfanyl Radical Addition to Vinyl Azides
J . Org. Chem., Vol. 62, No. 17, 1997 5847
Sch em e 3
only undergo trapping by the thiol H-donor to give the
above isomeric mixture of 5a and 6a .
In the present work we have also examined the
reaction of the azide 1 with allyl mercaptan (2d ) with
the aim to find some evidence for intramolecular cycliza-
tion of the possible radical 4d onto the adjacent sulfanyl
double bond. Unfortunately such a reaction, while prov-
ing to be very much slow, resulted in a complex product
mixture from which only small amounts of the keto
sulfide 7d (7%) could be separated (Scheme 1).
the presence of benzenethiol (2a ) were slowly consumed
over ca. 24 h to give intractable product mixtures.
The above findings suggest that the thiols 2a -c could
add to the vinyl azides 1 and 8 by a radical-chain
mechanism involving intermediate â-sulfanyliminyl radi-
cals 4, 10. These intermediates probably arose from
initial addition of transient sulfanyl radicals (produced
by spontaneous reaction of corresponding thiols with
oxygen) to the â-vinylic carbon followed by â-elimination
of nitrogen from the benzyl radical adducts 3, 9 (Schemes
9
In conclusion, we have shown that addition of sulfanyl
radicals to the â-carbon of vinyl azides can interestingly
lead to transient 2-sulfanyliminyl radicals, provided that
the ensuing radical adducts be properly stabilized by an
adjacent phenyl substituent. We have therefore disclosed
a novel chemical behavior of vinyl azides that enlarges
1
and 2). In principle, the postulated iminyl radicals 4,
0 might have alternately resulted from sulfanyl radical
10
their versatile chemistry and synthetic usefulness.
1
addition to the terminal nitrogen that would form a fairly
resonance-stabilized triazenyl radical (Scheme 3). Azides
are known to undergo homolytic attack at either end of
the azido function.7 However, sulfanyl radical addition
at â-carbon is strongly suggested by the much higher
reactivity of azides 1 and 8 with respect to â-azidostyrene
and 2-azido-3-phenylpropene which would result from a
comparatively higher stability of R-azidobenzyl than
R-azidoalkyl radicals.
The primary intervention of benzenesulfanyl radicals
was substantiated by the finding that the reaction of
benzenethiol (2a ) with R-azidostyrene (1) was inhibited
in carefully degassed benzene solution. Further support
came by reacting benzenethiol (2a ) with the azide 1 in
the presence of phenylacetylene, that is known to smoothly
add the thiol 2a by a free-radical process.8 Usual
treatment of thiol 2a (0.5 equiv) with the azide 1 (1 equiv)
in the presence of increasing amounts of phenylacetylene
Exp er im en ta l Section
Thiols 2a ,c,d were commercially available. Thiol 2b,11
12
12
R-azidostyrene 1, â-azidostyrene, 2-azido-3-phenylpro-
13
13
pene, and 1-azido-trans-stilbene 8 were prepared as de-
scribed in the literature.
Known reaction products as the keto sulfides 7a , 7c,15 and
1
4
6
17
1
21 and phenyl thiobenzoate were identified on the basis of
1
H NMR and MS spectral data. Column chromatography was
performed on Merck silica gel (0.040-0.063 particle size) by
gradual elution with light petroleum (bp 40-70 °C)-diethyl
1
ether. H NMR spectra were recorded at 200 MHz in CDCl
3
solutions using Me
4
Si as internal standard. Mass spectra were
determined by the elctron impact method.
Rea ction of Th iols 2a -d w ith r-Azid ostyr en e (1) a n d
-Azid o-tr a n s-stilben e (8). The appropiate thiol (1 mmol)
1
was added to a solution of azide (1 mmol) in dry benzene (10
mL), and the mixture was stirred at room temperature for the
appropiate time. The solvent was removed, and the residue
1
was normally analyzed by GC-MS and H NMR and was then
chromatographed on silica gel column.
(5, 10, and 20 equiv) led to the formation of the adducts
F r om Ben zen eth iol (2a ) a n d r-Azid ostyr en e (1). Upon
5
a , 6a , and the expected thiol/alkyne Z- and E-styrene
addition of thiol 2a immediate nitrogen evolution occurred.
1
adducts [PhSCHdCHPh]. In agreement with the com-
mon intervention of benzenesulfanyl radicals, the relative
proportions of 5a , 6a to the styrene adducts were found
to decrease roughly linearly with the increasing alkyne
concentration (the ratios of 5a , 6a to the thiol/alkyne
After ca. 5 min H NMR analysis showed the exclusive
presence of a mixture of the enamine 6a and the imine 5a in
1
ca. 80:20 ratio [ H NMR δ (6a ) 4.40 (2H, br s), 5.25 (1H, s),
7
7
.10-7.70 (10H, m); δ (5a ) 4.20 (2H, s), 5.10 (1H, br s), 7.10-
+
.70 (10H, m); MS m/z 227 (M , 70), 226 (30) 104 (100)].
Chromatography gave the keto sulfide 7a (220 mg, 96%). The
reaction was repeated by adding slowly (3 h) with a syringe
pump a solution of thiol 2a (1 mmol) in benzene (5 mL) to the
1
adducts, as determined by H NMR spectroscopy, were
respectively 28:1, 12:1, and 6:1).
1
azide 1 (1 mmol) in benzene (10 mL). H NMR analysis
Sound support to the postulated occurrence of the
iminyl radical 10 was lended by reacting the azide 8 in
the presence of a very low thiol 2a concentration, which
was achieved by adding the thiol (1 equiv) by a syringe
pump over 3 h. Under these circumstances, column
chromatography, besides the compounds 11 and 12 (15%
overall yield), separated benzonitrile (20%), phenyl
thiobenzoate (15%), and trace amounts of benzaldehyde
showed exclusive presence of the above isomeric mixture of
5
a and 6a .
F r om 2-Ben zo[b]th iop h en eth iol (2b) a n d r-Azid osty-
r en e (1). Upon addition of thiol 2b immediate nitrogen
1
evolution occurred. After ca. 5 min H NMR analysis showed
the exclusive presence of the enamine 6b and the imine 5b in
ca. 80:20 ratio [ H NMR δ (6b) 4.50 (2H, br s), 5.30 (1H, s),
1
(
Scheme 2). Evidently, the intermediate 10 could exhibit
(9) The lower reactivity of alkanethiols 2c,d clearly resulted from
their higher S-H bond strength.
competing â-scission to give the benzyl radical 13 that
led to the thiobenzoate and benzaldehyde by further
reaction with oxygen (Scheme 2).
A similar beahvior was instead not displayed by the
iminyl congener 4a under analogous high dilution condi-
tions. Under such conditions also the radical 4a could
(
10) For leading references on vinyl azide chemistry see: Hassner,
A. Acc. Chem. Res. 1971, 4, 9. L’Abb e` , G. Angew. Chem., Int. Ed. Engl.
1975, 14, 775. Hassner, A. In Azides and Nitrenes: Reactivity and
Utility; Scriven, E. F. V., Ed.; Academic Press: London, 1984; ch. 2.
Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297.
(11) Scuetz, R. D.; Fredericks, W. L. J . Chem. Soc. (C) 1970, 2433.
(
12) Hassner, A.; Boerwinkle, F. P.; Levy, A. B. J . Am. Chem. Soc.
970, 92, 4879.
13) Fowler, F. W.; Hassner, A.; Levy, A. B. J . Am. Chem. Soc. 1967,
89, 2077.
(14) Ratts, K. W. J . Org. Chem. 1972, 37, 848.
1
(
(
7) Dang, H.-S.; Roberts, B. P. J . Chem. Soc., Perkin Trans. 1 1996,
493, and references cited therein.
8) Thiol 2a quantitatively reacted with phenylacetylene (10 equiv)
in benzene solution at room temperature over ca. 30 min to give a 90:
0 Z/E mixture of styrene adducts [PhSCHdCHPh]. For a previous
1
(
(15) Kataoka, T.; Tomoto, A.; Shimizu, H.; Hori, M. J . Chem. Soc.,
Perkin Trans. 1 1983, 2913.
(16) Capozzi, G.; Melloni, G.; Modena, G. J . Chem. Soc. (C) 1970,
1
report of radical reactions of thiol 2a with alkynes, including phenyl-
acetylene, see: Benati, L.; Montevecchi, P. C.; Spagnolo, P. J . Chem.
Soc., Perkin Trans. 1 1991, 2103, and references cited therein.-
2621.
(17) Mukaiyama, T.; Katsuyama, H. Bull. Chem. Soc. J pn. 1968,
41, 2703.

5
848 J . Org. Chem., Vol. 62, No. 17, 1997
Montevecchi et al.
7
.10-7.70 (10H, m); δ (5b) 4.20 (2H, s), 7.10-7.70 (10H, m);
C
20
H
17NS: C, 79.17; H, 5.65; N, 4.62; S, 10.57. Found: C, 79.0;
+
MS m/z 283 (M , 30)]. Chromatography gave the keto sulfide
7
m) 7.90 (2H, d, J ) 8 Hz); MS m/z 284 (M , 40), 105 (100).
Anal. Calcd for C16 : C, 67.57; H, 4.25; O, 5.63; S, 22.55.
H, 5.62; N, 4.6; S, 10.38.] Evaporation of the organic filtrate
and chromatography of the residue furnished further enamine
11 (30 mg, 10%) along with the keto sulfide 12 (30 mg, 10%).
The reaction was repeated by adding the thiol 2a in benzene
(5 mL) with a syringe pump over 3 h. Chromatography gave,
in addition to a 1:1 mixture of enamine 11 and ketone 12 (45
mg, 15% overall yield), benzonitrile (20 mg, 20%), benzalde-
hyde (trace amounts, detected by GC-MS analysis), phenyl
thiobenzoate (30 mg, 15%), and unidentifiable material.
Rea ction of Ben zen eth iol (2a ) w ith r-Azid ostyr en e (1)
in th e P r esen ce of P h en yla cetylen e. Following the general
procedure, the thiol 2a (0.5 mmol) was reacted with the azide
1 (1 mmol) in the presence of increasing amounts of phenyl-
1
b (270 mg, 95%). [ H NMR δ 4.30 (2H, s), 7.20-7.70 (8H,
+
H
12OS
2
Found: C, 67.80; H, 4.27; S, 22.6.]
F r om P h en eth yl Mer ca p ta n (2c) a n d r-Azid ostyr en e
(
1). The reaction mixture was stirred for 10 days, after which
time chromatography gave unchanged azide (10%) and the
keto sulfide 7c (90 mg, 40%).
F r om Allyl Mer ca p ta n (2d ) a n d r-Azid ostyr en e (1).
R-Azidostyrene 1 (1 mmol) was allowed to react with thiol 2d
(2 mmol) for 10 days, after which time chromatography gave
1
unchanged azide (60%) and the keto sulfide 7d (7%). [ H NMR
1
(
(
CDCl
1H, d, J ) 9 Hz), 5.20 (1H, d, J ) 16 Hz), 5.80 (1H, m;
) 9 Hz, J ) 16 Hz upon irradiation at δ
.2), 7.40-7.60 (3H, m), 8.0 (2H, d, J ) 8 Hz); MS m/z 192
3
, 200 MHz) δ 3.20 (2H, d, J ) 6 Hz), 3.80 (2H, s), 5.15
acetylene (5, 10, and 20 mmol). H NMR analysis of the re-
spective reaction mixture showed that in each case the tau-
tomers 5a , 6a , and â-(phenylsulfanyl)styrene [PhSCHdCHPh]
(as a ca. 90:10 mixture of the Z- and E-isomers) had formed
collapsing to dd, J
3
(
1
2
8
+
M , 10), 105 (100). A satisfactory analytical sample of this
in relative ratio of 28:1, 12:1, and 6:1, respectively.
compound was not obtained owing to the minute amounts
available.]
Ack n ow led gm en t. This work has been carried out
in the frame of the “Progetto di Finanziamento Trien-
nale Ateneo di Bologna”. We also acknowledge financial
support from the Ministero dell’Universit a` e della
Ricerca Scientifica e Tecnologica (MURST) and CNR
(Rome).
F r om Ben zen eth iol (2a ) a n d 1-Azid o-tr a n s-stilben e (8).
After addition of thiol 2a evident nitrogen evolution occurred
for ca. 30 min, after which time TLC showed the absence of
the starting azide. The solvent was removed, and the crude
was treated with diethyl ether to give a white solid. This was
filtered off and shown to be the enamine 11 (195 mg, 65%):
1
m.p. 104-108 °C. [ H NMR δ 4.7 (2H, br s), 6.4-6.9 (15H,
+
m); MS m/z 303 (M , 100), 193 (40), 104 (45). Anal. Calcd for
J O970691Q