Sc(OTf)3 catalyzed electrophilic amination of arenes: An expeditious synthesis of aryl hydrazides

Article abstract of DOI:10.1246/cl.2002.318

Arenes react smoothly with diethyl azodicarboxylate in the presence of a catalytic amount of scandium triflate in dichloromethane at ambient temperature to afford the corresponding aryl hydrazides in high yields with high regioselectivity.

Full text of DOI:10.1246/cl.2002.318

318
Chemistry Letters 2002
Sc(OTf)3 Catalyzed Electrophilic Amination of Arenes:
An Expeditious Synthesis of Aryl Hydrazides
J. S. Yadav,ꢀ B. V. S. Reddy, G. Veerendhar, R. Srinivasa Rao, and K. Nagaiah
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
(Received October 19, 2001; CL-010988)
Arenes react smoothly with diethyl azodicarboxylate in the
substituted benzenes i.e. phenols reacted rapidly with diethyl
presence of a catalytic amount of scandium triflate in dichloro-
methane at ambient temperature to afford the corresponding aryl
hydrazides in high yields with high regioselectivity.
azodicarboxylate to afford the respective aryl hydrazides in
excellent yields. The activated arenes such as anisole, veratrole,
1,2-methylenedioxybenzene and 1,3,5-trimethoxybenzene also
gave the corresponding aryl hydrazides in high yields in a short
reaction time. In all cases, the reactions proceeded smoothly at
ambient temperature with high regioselectivity. However,
unactivated arenes such as benzene, toluene, naphthalene,
anthracene and xylene took longer reaction time to achieve
Aryl hydrazides are important precursors for the synthesis of
a variety of heterocycles1 such as indoles, pyrazoles, ꢀ-lactams,
quinazolines and many others, which are known to be biologically
active. In addition, they can be easily transformed to aryl amines2
and aryl hydrazines.3 Generally, aryl hydrazides are prepared by
the condensation of aryl lithium or aryl magnesium reagents with
di-t-butyl azodicarboxylate4 and also by the electrophilic
amination of electron rich arenes with bis(2,2,2-trichloroethyl)
Table 1. Sc(OTf)3 catalyzed electrophilic amination of arenes with DEAD
azodicarboxylate under thermal or Lewis acid catalysis.5;6
A
thermal or acid catalyzed electrophilic amination typically
requires high temperature or strongly acidic conditions and the
highly reactive electrophile bis(trichloroethyl) azodicarboxylate
to promote the reaction. However, many of these procedures have
limitations in one way or other thereby restricting their wide
spread applicability. Thus, high acidity, high reaction tempera-
ture, prolonged reaction time, critical handling of catalysts,
unsatisfactory yields, poor regioselectivity and non-catalytic
nature of the reagents are unfavorable factors. Therefore, the
development of new reagents that are more efficient and lead to
convenient procedures and better yields are desirable. Moreover,
no attempt has been made to recycle the catalyst, thereby making
the process more eco-friendly. Metal triflates are unique Lewis
acids that are currently of great research interest.7 Particularly,
scandium salts are attractive because they are quite stable to water
and reusable and in addition they are highly effective for the
activation of nitrogen containing compounds. Therefore, scan-
dium triflate is an efficient catalyst compared to traditional Lewis
acids in several carbon-carbon bond forming reactions and have
found wide applications in organic synthesis.8
In this report, we wish to highlight our results on the
electrophilic amination of arenes with diethyl azodicarboxylate
using catalytic amount of scandium triflate (Scheme 1).
Scheme 1.
The treatment of anisole with diethyl azodicarboxylate (DEAD)
in the presence of 5 mol% Sc(OTf)3 at ambient temperature
resulted in the formation of p-anisyl hydrazide in 90% yield.
Similarly, several arenes reacted smoothly with diethyl azodi-
carboxylate to give the corresponding aryl hydrazides in high
yields.9 The method is clean and highly regioselective. The extent
of electron density and the nature of the substituent on the
aromatic ring show some effect on this conversion. Hydroxy
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
319
yields comparable with those of their electron rich counterparts.
Particularly, benzene and toluene afforded 48% and 53% yields
respectively in the presence of 5 mol% Sc(OTf)3 at their refluxing
temperature for 12 h. Similar yields and selectivity were also
obtained with 5 mol% In(OTf)3 under the same reaction
conditions (Table 2). However, in the absence of catalyst, the
reaction did not yield any product even at reflux temperature. The
lowering of the reaction temperature was detrimental to the
efficiency of this procedure. The scope of scandium triflate
catalyzed electrophilic amination of arenes was investigated with
respect to the activated and unactivated aromatics illustrated in
Table 1. Scandium triflate was found to be the best catalyst for the
amination of activated arenes with DEAD and surprisingly, the
only catalyst effective for the amination of unactivated aromatics,
albeit, requiring longer reaction times (2.5–4.5 h) to achieve
complete conversion. Another advantage of this procedure is that
scandium triflate was recovered from aqueous layer during the
work-up and reused in subsequent reactions with gradual
decrease in activity; for example, the reaction of anisole with
diethyl azodicarboxylate gave the corresponding p-anisyl hy-
drazide in 90%, 85% and 80% yield over three cycles.
In summary, we have demonstrated that Sc(OTf)3 is an
efficient and reusable Lewis acid for the electrophilic amination
of arenes with diethyl azodicarboxylate. In addition to its
efficiency, simplicity, and milder reaction conditions, this method
provides excellent yields of products with high regioselectivity.
This procedure is very useful for acid sensitive molecules where
nitration conditions are unsuitable.
BVS, GVR and RSR thank CSIR New Delhi for the award of
fellowships.
References and Notes
1
2
3
‘‘Encyclopedia of Reagents for Organic Synthesis,’’ ed. by L. A.
Paquette, Wiley (1995), Vol. 6, p 3979.
I. Zaltsgendler, Y. Leblanc, and M. W. Bernstein, Tetrahedron Lett., 34,
2441 (1993).
Table 2. In(OTf)3 catalyzed electrophilic amination of arenes with DEAD
C. Dufresne, Y. Leblanc, C. Berthelette, and C. Mc Cooeye, Synth.
Commun., 27, 3612 (1997).
4
5
J. P. Demers and D. H. Klaubert, Tetrahedron Lett., 28, 4933 (1987).
a) S. H. Schroeter, J. Org. Chem., 34, 4012(1969). b) R. B. Carlinand M.
S. Moores, J. Am. Chem. Soc., 84, 4107 (1962).
6
7
Y. Leblanc and N. Boudreault, J. Org. Chem., 60, 4268 (1995). b) H.
Mitchell and Y. Leblanc, J. Org. Chem., 59, 682 (1994).
S. Kobayashi, Synlett, 1994, 689. b) S. Kobayashi, Eur. J. Org. Chem.,
1999, 15. c) D. Longbottom, Synlett, 1999, 2023. d) S. Kobayashi, J.
Synth. Org. Chem. Jpn., 53, 370(1999).
8
9
J. S. Yadav, B. V. S. Reddy, and T. P. Rao, Tetrahedron Lett., 41, 7943
(2000). b) J. S. Yadav, B. V. S. Reddy, and P. K. Chand, Tetrahedron
Lett., 42, 4057 (2001). c) J. S. Yadav, B. V. S. Reddy, and P. Srihari,
Synlett, 2001, 673.
Experimental Procedure: A mixture of arene (5 mmol), diethyl
azodicarboxylate (5 mmol), scandium triflate or indium triflate
(5 mol%) in dichloromethane (10mL) was stirred at ambient tempera-
ture for an appropriate time (Table 1 and 2). After completion of the
reaction as indicated by TLC, the reaction mixture was diluted with
water and extracted with dichloromethane (2 ꢁ 10 mL). The combined
organic layers were dried over anhydrous Na2SO4, concentrated in
vacuo and purified by column chromatography on silica gel (Merck,
100–200 mesh, ethyl acetate-hexane, 2 : 8) to afford pure aryl
hydrazide. 2b (Table 1): Solid, m.p. 110 ꢂC, 1H NMR (CDCl3) ꢁ:
1.25 (t, 6H, J ¼ 6:8 Hz), 3.80(s, 6H), 4.20(q, 4H, J ¼ 7:0 Hz), 6.70(d,
1H, J ¼ 8:0 Hz), 6.85 (d, 1H, J ¼ 8:0 Hz), 6.94 (s, 1H), 7.20(brs, NH).
13C NMR (CDCl3, proton decoupled) ꢁ: 14.3, 29.5, 55.8, 62.1, 62.7,
109.4, 110.7, 117.3, 134.9, 147.7, 148.7, 155.1, 156.2. IR (KBr)ꢂ: 3345,
3030, 2970, 1740, 1520, 1285, 1038, 790. EIMS: m/z: Mþ, 312, 240,
167, 141, 104, 83, 65, 43. 2n (Table 1): Solid, m.p. 137 ꢂC, 1H NMR
(CDCl3) ꢁ: 1.25 (t, 3H, J ¼ 7:0 Hz), 1.30(t, 3H, J ¼ 7:0 Hz), 4.25 (q,
4H, J ¼ 7:2 Hz), 7.25 (brs, NH), 7.45–7.55 (m, 4H), 7.80–7.90 (m, 2H),
7.95 (d, 1H, J ¼ 8:0 Hz). 13C NMR (CDCl3, proton decoupled) ꢁ: 14.3,
18.3, 22.0, 62.0, 62.9, 121.3, 122.9, 124.6, 125.3, 126.8, 127.9, 128.4,
128.6, 128.8, 130.5, 156.4. IR (KBr)ꢂ: 3350, 3029, 2978, 1720, 1520,
1250, 1070, 795. EIMS: m/z: Mþ, 302, 229, 199, 115, 83, 43. 2o
(Table 1): Solid, m.p. 163 ꢂC, 1H NMR (CDCl3Þ ꢁ: 1.15 (t, 3H,
J ¼ 7:0 Hz), 1.30(t, 3H, J ¼ 7:0 Hz), 2.58 (s, 3H), 4.20(q, 4H,
J ¼ 7:2 Hz), 6.98 (brs, NH), 7.18–7.63 (m, 4H), 7.78–8.0(m, 2H). 13C
NMR (CDCl3, proton decoupled) ꢁ: 14.3, 18.3, 22.0, 62.0, 62.9, 121.3,
122.9, 124.6, 125.3, 126.8, 127.9, 128.4, 128.6, 128.8, 130.5, 156.4. IR
(KBr)ꢂ: 3348, 3027, 2975, 1745, 1525, 1280, 1040, 793 EIMS: m/z:
Mþ, 316, 243, 171, 115, 83, 43.