Tetrahedron Letters
Tetrahedron Letters
Tetrahedron Letters
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
a r t i c l e
i n f o
Article history:
Received 23 June 2015
Revised 27 July 2015
Accepted 31 July 2015
Available online 5 August 2015
Keywords:
Aromatic nitro compounds
Lithium aluminum hydride
Titanium tetrachloride
Aromatic amines
Azobenzenes
a b s t r a c t
A rapid and efficient single-step synthesis of substituted anilines has been developed. The aromatic nitro
compounds were reduced by using reducing systems generated by the action of an excess of LiAlH4 on
TiCl4. Anilines substituted with different functional groups were synthesized in high yields and purity
starting from the corresponding nitro compounds. The developed procedure is applicable to nitroaromatics containing both electron withdrawing and electron donating substituents. Substrates with electron
donor substituents require a larger excess of LiAlH4. The reducing power of the prepared reactant systems
depends on the used molar ratio of LiAlH4 and TiCl4.
2015 Elsevier Ltd. All rights reserved.
Corresponding authors. Tel.: +39 0984 493199 (A. Leggio); tel.: +39 0984
493205; fax: +39 0984 493265 (A. Liguori).
E-mail addresses: [email protected] (A. Leggio), [email protected] (A. Liguori).
http://dx.doi.org/10.1016/j.tetlet.2015.07.089
0040-4039/ 2015 Elsevier Ltd. All rights reserved.
5342
N
N
N
OH
HO
N
N
OH
Entry
R1
R2
R3
Yielda 2
(%)
Yielda 3
(%)
Reaction
time
a
b
c
d
e
f
g
h
i
SO2NEt2
H
H
F
Cl
Br
H
CH3
OCH3
H
SO2NEt2
H
H
H
H
H
H
H
H
H
SO2NEt2
H
H
H
H
H
H
92
89
90
98
91
94
48
45
43
25
28
20
15 min
25 min
25 min
45 min
45 min
45 min
15 h
26 h
29 h
Isolated yield.
R1
R1
R2
R3
NO2
1 g-i
R2
LiAlH 4
TiCl4
R3
NH 2
2 g-i
5343
Entry
R1
R2
R3
Yielda 2 (%)
g
h
i
H
CH3
OCH3
H
H
H
H
H
H
90
88
86
25
30
30
Table 3
Results of reduction of substituted nitrobenzenes with LiAlH4
Entry
R1
R2
R3
Yielda 3 (%)
d
g
h
F
H
CH3
H
H
H
H
H
H
88
89
92
10
15
15
Isolated yield.
Isolated yield.
R1
R2
R3
NO 2
1d, 1g-h
R2
LiAlH 4
R1
R3
N N
R1
R3
R2
3 d, 3g-h
R2
R1
R3
R1
N N
R1
R3
R2
R2
LiAlH4
TiCl 4
R3
NH2
3 d, 3g-h
2 d, 2g-h
Table 4
Results of reduction of substituted azobenzenes with the reducing system LiAlH4/
TiCl4 in molar ratio 10:1
Entry
R1
R2
R3
Yielda 2 (%)
Reaction time
d
g
h
F
H
CH3
H
H
H
H
H
H
98
87
92
5
10
10
Isolated yield.
Supplementary data
Supplementary data (general experimental details, lists of spectral data, copies of 1H and 13C NMR spectra for compounds 2ai,
3d, 3gi, 56) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2015.07.089.
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14. LiAlH4 (5 mmol) was added to a stirred suspension of TiCl4 (1 mmol) in diethyl
ether. The resulting suspension was stirred at room temperature for 15 min.
Then a solution in diethyl ether of the corresponding nitro compound (1a,
1 mmol) was added slowly to the obtained black reducing suspension under
inert nitrogen atmosphere. The reaction was kept stirring at room temperature
and monitored by TLC (diethyl ether/petroleum ether 60:40 v/v). After
complete conversion of the starting material, the reaction mixture was paper
filtered, washed with 1 N aqueous NaOH (3 5 mL) and once with brine
(5 mL). The ethereal layers were dried (Na2SO4) and evaporated to dryness
under reduced pressure conditions to give the corresponding amine 2a in 92%
yield. 4-Amino-N,N-diethylbenzenesulfonamide (2a): 1H NMR (300 MHz, CDCl3)
d: 7.55 (d, J = 9.0 Hz, 2H, Ha, Ha0 ), 6.66 (d, J = 9.0 Hz, 2H, Hb, Hb0 ), 4.15 (sbroad,
2H, NH2), 3.18 (q, J = 6.6 Hz, 4H, NCH2), 1.11 (t, J = 6.6 Hz, 6H, CH3); 13C NMR
(75 MHz, CDCl3) d: 150.2, 129.0, 128.5, 114.0, 42.0, 14.6; GC/MS m/z (% rel.):
228 [M+] (33), 213(40), 156(100), 108(33), 92(35), 65(18); Anal. Calcd for
C10H16N2O2S: C, 52.61; H, 7.06; N, 12.27; S, 14.04; Found: C, 52.70; H, 7.04; N,
11.35; S, 14.05.