A Lewis acid mediated schmidt reaction of benzylic azide: Synthesis of sterically crowded aromatic tertiary amines

Article abstract of DOI:10.1002/ejoc.201100674

An efficient one-pot synthesis of sterically hindered aromatic tertiary amines through Lewis acid induced intermolecular Schmidt reaction of benzylic azides is described. In the presence of EtAlCl₂, benzylic azide underwent a smooth Schmidt reaction to give the corresponding iminium ion, which, upon reduction with NaBH₄ in situ, afforded the tertiary amine. The effects of substituents on the aromatic ring and the steric effects of the alkyl side chain have also been studied.

Full text of DOI:10.1002/ejoc.201100674

FULL PAPER
DOI: 10.1002/ejoc.201100674
A Lewis Acid Mediated Schmidt Reaction of Benzylic Azide: Synthesis of
Sterically Crowded Aromatic Tertiary Amines
Annamalai Murali,[a] Manohar Puppala,[a] Babu Varghese,[a] and Sundarababu Baskaran*[a]
Keywords: Amines / Azides / Cyclization / Fused-ring systems / Lewis acids
An efficient one-pot synthesis of sterically hindered aromatic
tertiary amines through Lewis acid induced intermolecular
Schmidt reaction of benzylic azides is described. In the pres-
ence of EtAlCl2, benzylic azide underwent a smooth Schmidt
reaction to give the corresponding iminium ion, which, upon
reduction with NaBH4 in situ, afforded the tertiary amine.
The effects of substituents on the aromatic ring and the steric
effects of the alkyl side chain have also been studied.
utilized in the synthesis of tertiary amines.[10] Likewise, the
intermolecular Schmidt reaction of benzyl azide with
ketones has also been exploited in the synthesis of α-(N-
arylmethyl)ketones.[11] In addition, the conversion of benzyl
azide into N-methylaniline using the SnCl4/Et3SiH reagent
system has also been reported.[12] However, the direct con-
version of benzylic azide into sterically crowded aromatic
tertiary amines has not been explored. Because of our con-
tinuing interest in the exploration of azides in organic syn-
thesis,[13] we envisaged that hindered aromatic tertiary
amines could be realised through the application of the
Schmidt reaction. Herein, we report an efficient one-pot
method for the direct conversion of benzylic azide into
sterically hindered aromatic tertiary amines through appli-
cation of the Schmidt reaction.
Introduction
Tertiary amines are one of the most important classes of
compounds, with widespread applications in synthetic and
medicinal chemistry. Polysubstituted aromatic amines are
prevalent structural subunits that are present in many
bioactive molecules such as benzodiazepines, phen-
ethylamines and N,N-disubstituted aniline derivatives.[1] Re-
cently, a potent, orally active tertiary amine based non-
steroidal liver X receptor (LXR) agonist has been synthe-
sised and its activity towards LXRα and LXRβ has been
reported.[2] Moreover, aniline derivatives possessing an aryl-
methyl substituent at the 2- or 4-position have been em-
ployed as antioxidants in lubricants and also as synthetic
precursors for heterocyclic compounds.[3] In addition, a
variety of amines play important roles in the agrochemical
and dye industries, as well as in catalysis and polymer chem-
istry.[4] Moreover, sterically hindered amines and their metal
salts are valuable reagents in the regioselective alkylation of
unsymmetrical carbonyl compounds.[5]
Common methods that are employed for the synthesis
of aromatic tertiary amines are transition-metal-catalysed
reductive amination of carbonyl compounds,[6] hydroamin-
ation of olefins,[7] and catalytic and noncatalytic alkylation
or arylation of amines.[8,9] Although these methods are
quite reliable, some of these stepwise alkylation protocols
are often associated with significant drawbacks, in particu-
lar, with respect to the selectivity towards the synthesis of
tertiary amines. Thus, the synthesis of hindered aromatic
tertiary amines is still a challenging endeavour.
Results and Discussion
During the course of our investigation on the Schmidt
reaction of (1-azidoethyl)benzene (1a) with BF3·OEt2, we
observed the formation of tertiary amine 1b in 58% yield
along with a small amount of secondary amine 1c, as
shown in Scheme 1.
The intermolecular Schmidt reaction of a tertiary
alcohol with alkyl azide in the presence of an acid has been
Scheme 1. BF3·OEt2-mediated Schmidt reaction of (1-azidoethyl)-
benzene (1a).
[a] Department of Chemistry,
To improve the efficiency and selectivity of the reaction,
a systematic investigation was carried out with a range of
Lewis and Brønsted acids using (1-azidoethyl)benzene (1a)
as a model substrate; the results obtained are summarised
in Table 1.
Indian Institute of Technology Madras
Chennai 600036, India
Fax: +91-44-22570545
E-mail: sbhaskar@iitm.ac.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100674.
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S. Baskaran et al.
FULL PAPER
Table 1. Reaction of (1-azidoethyl)benzene (1a) with Lewis/ we intended to study the influence of steric and electronic
Brønsted acids.
properties of the substituents on this interesting transfor-
Entry Lewis/Brønsted acid[a] Temp. [°C] Time [h]
Yield [%][b]
mation. Thus, the methodology was tested with a variety of
functionalized benzylic azides; the results are summarised
in Table 2.
Benzylic azide 2a, bearing a p-methoxy group, underwent
smooth reaction to give the corresponding tertiary amine
2b as the only isolable product in 81% yield (Table 2, En-
try 2). The structure of 2b was unambiguously confirmed
by single-crystal X-ray analysis, as shown in Figure 1. Simi-
larly, p-methyl-substituted benzylic azide 3a reacted readily
in the presence of EtAlCl2 to furnish the corresponding ter-
1b
1c
1
2
3
4
5
BF3·OEt2
EtAlCl2
TMSOTf
TiCl4
0
24
2
2
2
2
58
74
56
34
23
16
6
13
54
61
–78
–78
–25
–78
CF3SO3H
[a] In all cases, 1.1 equiv. of Lewis/Brønsted acid was used. [b] Iso-
lated yield.
It is evident from Table 1 that EtAlCl2 efficiently cata- tiary amine 3b in 83% yield (Table 2, Entry 3). Under sim-
lyzes the reaction, providing the tertiary amine in good ilar reaction conditions, p-bromo-substituted benzylic azide
yield. Subsequent to achieving high selectivity and yield, 4a afforded the tertiary and secondary amines 4b and 4c in
Table 2. Lewis acid mediated rearrangement of benzylic azides.
[a] Refers to the combined yield of tertiary and secondary amines. [b] Yield based on recovered starting material. [c] BF3·OEt2 was used
as Lewis acid.
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Sterically Crowded Aromatic Tertiary Amines
a ratio of 5:1, respectively, in 81% yield (Table 2, Entry 4). arrangement with expulsion of N2 and simultaneous mi-
However, benzylic azide 5a, having an electron-withdrawing gration of the phenyl group. The resultant iminium ion 13,
group (NO2) at the para position, resisted any reaction on reduction with NaBH4, would then lead to the forma-
(Table 2, Entry 5). Interestingly, optically active [(R)-1- tion of aromatic tertiary amine 1b. On the other hand, the
azidoethyl]benzene (+)-1a, on exposure to EtAlCl2, fur- Lewis acid complex 11, on Schmidt rearrangement with mi-
nished only racemic tertiary amine (Ϯ)-1b, implying the in- gration of the phenyl group, would result in the formation
volvement of a benzylic carbocation intermediate in the re- of 11b, and ensuing reduction would then furnish the sec-
action (Table 2, Entry 6).
ondary amine 1c.
The proposed mechanism is further supported by the fol-
lowing observations: (i) When benzylic azide 1a was al-
lowed to react with EtAlCl2 in the presence of 1,2-di-
methoxybenzene, compound 14 was isolated in 46% yield
(Scheme 3). This observation further supports the involve-
ment of benzylic carbocation 11a in this reaction
(Scheme 2). (ii) Treatment of benzylic azide 1a with EtAlCl2
followed by hydrolysis with aqueous NaOH afforded sec-
ondary amine 15 in 52% yield (Scheme 4). This observation
signifies the involvement of intermediate iminium ion 13
(Scheme 2).
Figure 1. ORTEP diagram of compound 2b.
Steric effects in this transformation were also studied by
increasing the number of carbon atoms present in the α-
side-chain. Thus, the reaction of (1-azidopropyl)benzene
(6a) under the standard reaction conditions resulted in the
formation of tertiary amine 6b and secondary amine 6c in
a ratio of 6:1, in 80% yield (Table 2, Entry 7). Similarly, (1-
azidobutyl)benzene (7a) afforded the desired tertiary amine
7b and secondary amine 7c (4.6:1) in good yield (Table 2,
Entry 8). It is apparent that the yield of the tertiary amine
decreases with increasing length of the alkyl side-chain. On
the other hand, hindered diphenylmethyl azide (8a) af-
forded secondary amine 8c as the major product, along
with minor amounts of tertiary amine 8b (Table 2, Entry 9).
The cyclic azide 9a, upon exposure to Lewis acid, furnished
the corresponding secondary amine 9c as the only isolable
product (Table 2, Entry 10).
Scheme 3. Reaction of benzylic azide 1a in the presence of 1,2-
dimethoxybenzene.
Scheme 4. Reaction of benzylic azide 1a with EtAlCl2 followed by
hydrolysis.
A tentative mechanism for the formation of the tertiary
amine from benzylic azide is shown in Scheme 2. It is likely
the benzylic azide 1a, in the presence of Lewis acid, leads
to the formation of the benzylic carbocation 11a via Lewis
acid complex 11, which, on intermolecular nucleophilic
Conclusions
A facile, one-pot synthesis of highly hindered aromatic
substitution with another molecule of benzylic azide, would tertiary amines from benzylic azides has been developed
lead to the corresponding aminodiazonium intermediate using the Schmidt reaction as a key step. In general, elec-
12. The intermediate 12 can then undergo Schmidt re- tron-releasing groups favour the formation of tertiary
Scheme 2. Plausible mechanism for the Lewis acid mediated intermolecular Schmidt reaction of benzylic azide.
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(1-Azidoethyl)benzene (1a): Colourless liquid; yield: 3.9 g (94%). IR
amines in high yield, whereas increases in the length of the
alkyl side chain reduces the yield. The present method pro-
vides easy access to synthetically useful sterically hindered
aromatic tertiary amines in good yields.
(neat): ν = 2979, 2085, 1595, 1453, 1242 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 7.43–7.33 (m, 5 H), 4.64 (q, J = 7.2 Hz, 1 H), 1.56 (d,
J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 140.8,
128.7, 128.1, 126.3, 61.0, 21.5 ppm.
N-Ethyl-N-(1-phenylethyl)aniline (1b): Colourless liquid; yield:
103 mg (74%). IR (neat): ν = 3084, 3056, 3024, 2969, 2929, 1595,
˜
Experimental Section
1500, 1447, 1374 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.31–7.19
(m, 7 H), 6.80 (d, J = 8.4 Hz, 2 H), 6.69 (t, J = 8.4 Hz, 1 H), 5.06
(q, J = 7.2 Hz, 1 H), 3.21 (q, J = 7.2 Hz, 2 H), 1.57 (d, J = 7.2 Hz,
3 H), 1.06 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 148.6, 143.2, 129.2, 128.4, 127.1, 126.8, 116.5, 113.7, 56.7, 40.2,
17.7, 14.3 ppm. HRMS (ESI): calcd. for C16H20N [M+ + H]
226.1596; found 226.1596.
General Considerations: All reactions were carried out under nitro-
gen or argon with anhydrous solvents. Solvents for column
chromatography were distilled at atmospheric pressure prior to use.
Reactions were monitored by thin-layer chromatography (TLC)
carried out on 0.25 mm silica gel plates (60F-254) using a UV lamp
to visualize the analytes and iodine and/or KMnO4 solution as
1
developing agents. H and 13C NMR spectra were recorded with a
N-Ethylaniline (1c): Colourless liquid; yield: 9 mg (6%). IR (neat):
Bruker 400 MHz NMR instrument and calibrated using tetrameth-
ylsilane (TMS) as an internal reference. Chemical shifts (δ) are
given in ppm relative to TMS (δ = 0 ppm). Multiplicity is indicated
as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (mul-
tiplet), dd (doublet of doublet), br. s (broad singlet). Coupling con-
stants (J) are reported in Hz. High-resolution mass spectra were
obtained by ESI with a Waters/Micromass Q-TOF mass spectrome-
ter. IR spectra were recorded with a Thermo Nicolet 6700 FTIR
spectrometer. X-ray analysis of compound 2b was recorded with a
Bruker AXS (Kappa Apex2). The structure was solved by direct
methods (SHELXS-97) and refined by full-matrix least-squares
techniques against F2 (SHELXL-97). Optical rotation values were
measured with a Jasco DIP polarimeter at a wavelength of 589 nm.
ν = 3409, 3052, 3023, 2961, 2923, 2853, 1601, 1501, 1450,
˜
1316 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.09 (dt, J = 7.2,
1.2 Hz, 2 H), 6.62 (t, J = 7.2 Hz, 1 H), 6.53 (dd, J = 8.0, 0.8 Hz, 2
H), 3.81 (br. s, 1 H), 3.07 (q, J = 7.2 Hz, 2 H), 1.17 (t, J = 7.2 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.5, 129.2, 117.2,
112.7, 38.5, 14.9 ppm. HRMS (ESI): calcd. for C8H12N [M+ + H]
122.0970; found 122.0966.
(R)-(1-Azidoethyl)benzene [(+)-1a]: Colourless liquid; yield: 330 mg
(77%). [α]2D5 = +15.9 (c = 1.0, CHCl ). IR (neat): ν = 2979, 2085,
˜
3
1595, 1453, 1242 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.43–7.33
(m, 5 H), 4.64 (q, J = 7.2 Hz, 1 H), 1.56 (d, J = 7.2 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 140.8, 128.7, 128.1, 126.3, 61.0,
21.5 ppm.
General Procedure for the Synthesis of Benzylic Azide from the Cor-
responding Alcohol: To a stirred solution of alcohol (1 mmol) in
anhydrous CH2Cl2 (5 mL) at 0 °C, was added triethylamine
(1.5 mmol) followed by methanesulfonyl chloride (1.2 mmol) over
a period of 10 min. After stirring at 0 °C for an additional 15 min,
the mixture was diluted with CH2Cl2 (10 mL), and the organic layer
was washed with water (2ϫ5 mL), brine (5 mL), and dried with
anhydrous Na2SO4. The solvent was removed under reduced pres-
sure to give the corresponding mesylate as a pale-yellow liquid.
The crude mesylate (1 mmol) was re-dissolved in anhydrous DMF
(10 mL), treated with NaN3 (2 mmol), and the resultant mixture
was stirred at room temp. for approximately 3 h. The reaction mix-
ture was poured into ice-cold water (20 mL), extracted with hexane
(2ϫ15 mL), and the combined hexane extracts were washed with
water (2ϫ10 mL), brine (10 mL), and dried with anhydrous
Na2SO4. The hexane solvent was removed under reduced pressure
to give the pure benzylic azide.
1-(1-Azidoethyl)-4-methoxybenzene (2a): Colourless liquid; yield:
1.9 g (96%). IR (neat): ν = 2968, 2088, 1609, 1505, 1463, 1441 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.8 Hz, 2 H), 6.90
(d, J = 8.8 Hz, 2 H), 4.56 (q, J = 6.8 Hz, 1 H), 3.80 (s, 3 H), 1.40
(d, J = 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.4,
132.8, 127.6, 114.0, 60.6, 55.2, 21.4 ppm. MS (ESI): m/z = 135
[M+ – N3].
N-Ethyl-4-methoxy-N-[1-(4-methoxyphenyl)ethyl]aniline
(2b):
Colourless solid; yield: 163 mg (81%). M.p. 61–63 °C. IR (neat): ν
˜
= 2968, 2931, 2832, 1609, 1505, 1463, 1441, 1238, 1175, 1035, 830,
1
811 cm–1. H NMR (400 MHz, CDCl3): δ = 7.23 (d, J = 8.8 Hz, 2
H), 6.85–6.78 (m, 6 H), 4.67 (q, J = 6.8 Hz, 1 H), 3.78 (s, 3 H),
3.75 (s, 3 H), 2.92–3.11 (m, 2 H), 1.40 (d, J = 6.8 Hz, 3 H), 0.961
(t, J = 7.2 Hz 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 158.3,
152.7, 142.9, 135.7, 128.3, 119.1, 114.3, 113.5, 58.9, 55.6, 55.2, 41.4,
18.1, 13.9 ppm. HRMS (ESI): calcd. for C18H24NO2 [M+ + H]
286.1807; found 286.1805.
Representative Procedure for the EtAlCl2-Mediated Intermolecular
Schmidt Reaction of Benzylic Azide: To a stirred solution of benz-
ylic azide (1 mmol) in anhydrous CH2Cl2 (5 mL) at –78 °C, was
added EtAlCl2 (1.8 m in toluene, 1.1 mmol) dropwise. The resultant
mixture was stirred at –78 °C for 45 min and then warmed to room
temperature. After stirring at room temp. for an additional 45 min,
the mixture was cooled to 0 °C and treated with a solution of
NaBH4 (7 mmol) in 15% aqueous NaOH (3 mL). The reaction
mixture was then warmed to room temp. and stirred for an ad-
ditional 45 min. The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (2ϫ10 mL). The combined or-
ganic layer was washed with water (2ϫ5 mL), brine (5 mL), and
dried with anhydrous Na2SO4. The solvent was removed under re-
duced pressure to give the crude compound, which was purified by
column chromatography on silica gel (gradient elution with 0–5%
EtOAc in hexane) to afford the aromatic tertiary amine followed
by the secondary amine.
1-(1-Azidoethyl)-4-methylbenzene (3a): Colourless liquid; yield:
2.3 g (95%). IR (neat): ν = 2970, 2922, 2095, 1611, 1512, 1462,
˜
1
1247 cm–1. H NMR (400 MHz, CDCl3): δ = 7.20 (d, J = 8.4 Hz,
2 H), 7.17 (d, J = 7.6 Hz, 2 H), 4.56 (q, J = 6.8 Hz, 1 H), 2.34 (s,
3 H), 1.50 (d, J = 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 137.8, 137.7, 129.4, 126.3, 60.8, 21.5, 21.1 ppm. MS (ESI): m/z
= 134 [M+ + H – N2].
N-Ethyl-4-methyl-N-(1-p-tolylethyl)aniline (3b): Colourless liquid;
yield: 120 mg (83%). IR (neat): ν = 2970, 2922, 2869, 1618, 1514,
˜
1452, 1372, 1266, 1182, 1117, 802 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.19 (d, J = 7.6 Hz, 2 H), 7.09 (d, J = 7.7 Hz, 2 H),
7.01 (d, J = 8.0 Hz, 2 H), 6.72 (d, J = 8.4 Hz, 2 H), 4.92 (q, J =
6.8 Hz, 1 H), 3.11 (m, 2 H), 2.30 (s, 3 H), 2.24 (s, 3 H), 1.50 (dd,
J = 6.8, 1.2 Hz, 3 H), 1.01 (dt, J = 7.0, 1.6 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 146.4, 140.3, 136.1, 129.6, 128.9,
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Sterically Crowded Aromatic Tertiary Amines
127.0, 125.9, 114.6, 57.1, 40.3, 21.0, 20.2, 17.6, 14.2 ppm. HRMS 7.6 Hz, 1 H), 1.94–1.73 (m, 2 H), 1.54–1.30 (m, 2 H), 0.98 (t, J =
(ESI): calcd. for C18H24N [M+ + H] 254.1909; found 254.1915.
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.9, 128.7,
128.1, 126.9, 66.1, 38.3, 19.5, 13.6 ppm. MS (ESI): m/z = [M+] 175.
1-(1-Azidoethyl)-4-bromobenzene (4a): Colourless liquid; yield:
N-Butyl-N-(1-phenylbutyl)aniline (7b): Colourless liquid; yield:
1.3 g (91%). IR (neat): ν = 2975, 2088, 1487, 1293, 1240, 1072,
˜
1
820 cm–1. H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 8.4 Hz, 2
115 mg (65%). IR (neat): ν = 3088, 3059, 3029, 2956, 2930, 2870,
˜
1596, 1455, 1375, 1283, 1257 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.23–7.12 (m, 7 H), 6.73 (d, J = 8.51 Hz, 2 H), 6.62 (t, J =
7.39 Hz, 1 H), 4.83 (t, J = 7.8 Hz, 1 H), 2.90–2.94 (m, 2 H), 1.93–
1.85 (m, 2 H), 1.38–1.23 (m, 4 H), 1.11 (q, J = 7.2 Hz, 2 H), 0.89
(t, J = 7.2 Hz, 3 H), 0.75 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 149.3, 141.8, 129.1, 128.2, 127.7, 126.8,
116.4, 114.1, 61.9, 45.4, 33.7, 29.9, 20.3, 20.3, 14.2, 13.8 ppm.
HRMS (ESI): calcd. for C20H28N [M+ + H] 282.2222; found
282.2213.
H), 7.20 (d, J = 8.4 Hz, 2 H), 4.58 (q, J = 6.8 Hz, 1 H), 1.50 (d, J
= 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.8,
131.8, 128.0, 121.9, 60.3, 21.5 ppm. MS (ESI): m/z = 198 [M+
–
N2].
4-Bromo-N-[1-(4-bromophenyl)]-N-ethylaniline (4b): Colourless li-
quid; yield: 114 mg (68%). IR (neat): ν = 3084, 3056, 3024, 2969,
˜
2929, 1595, 1447, 1374, 1262, 890 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.43 (d, J = 8.4 Hz, 2 H), 7.27 (d, J = 10.0 Hz, 2 H),
7.14 (d, J = 8.4 Hz, 2 H), 6.63 (d, J = 7.2 Hz, 2 H), 4.90 (q, J =
7.2 Hz, 1 H), 3.17 (q, J = 7.2 Hz, 2 H), 1.54 (d, J = 7.2 Hz, 3 H),
1.06 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
147.3, 141.8, 131.8, 131.5, 128.7, 120.8, 115.7, 108.8, 56.8, 40.5,
17.7, 13.9 ppm. HRMS (ESI): calcd. for C16H18NBr2 [M+ + H]
381.9806; found 381.9799.
N-Butylaniline (7c): Colourless liquid; yield: 26 mg (14%). IR
(neat): ν = 3410, 2957, 1603, 1506, 1320, 747 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 7.18–7.13 (m, 2 H), 6.67 (t, J = 7.2 Hz, 1
H), 6.58 (d, J = 8.0 Hz, 2 H), 3.47 (br. s, 1 H), 3.08 (t, J = 7.2 Hz,
2 H), 1.61–1.54 (m, 2 H), 1.46–1.36 (m, 2 H), 0.94 (t, J = 7.2 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.5, 129.1, 116.9,
112.6, 43.6, 31.6, 20.2, 13.9 ppm. HRMS (ESI): calcd. for C10H16N
[M+ + H] 150.1283; found 150.1282.
4-Bromo-N-ethylaniline (4c): Colourless liquid; yield: 23 mg (13%).
IR (neat): ν = 3084, 3056, 3024, 2969, 2929, 1595, 1447, 1374, 1262,
˜
1210, 680 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.19 (d, J =
9.2 Hz, 2 H), 6.68 (d, J = 9.2 Hz, 2 H), 3.34 (q, J = 7.1 Hz, 2 H),
1.15 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
147.8, 129.2, 115.6, 111.9, 44.3, 12.6 ppm. HRMS (ESI): calcd. for
C8H11NBr [M+ + H] 200.0075; found 200.0078.
Diphenylmethyl Azide (8a): Colourless liquid; yield: 1.9 g (96%).
1
IR (neat): ν = 2975, 2088, 1487, 1293, 1240, 1072 cm–1. H NMR
˜
(400 MHz, CDCl3): δ = 7.42–7.32 (m, 10 H), 5.75 (s, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 139.5, 128.6, 128.0, 127.3,
68.4 ppm. MS (ESI): m/z = 181 [M+ – N2].
1-(1-Azidoethyl)-4-nitrobenzene (5a): Yellow liquid; yield: 960 mg
N-Benzhydryl-N-benzylaniline (8b): Colourless viscous liquid; yield:
(56%). IR (neat): ν = 3084, 3056, 3024, 2093, 1518, 1343,
˜
49 mg (28%). IR (neat): ν = 3084, 3056, 3024, 2969, 2929, 1595,
˜
1
1242 cm–1. H NMR (400 MHz, CDCl3): δ = 8.20 (d, J = 6.8 Hz,
1447, 1374, 1262, 1210, 1179 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.23–7.01 (m, 17 H), 6.77–6.71 (m, 3 H), 6.31 (s, 1 H), 4.59 (s,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.4, 140.6, 139.3,
129.4, 129.3, 129.2, 128.9, 128.7, 128.2, 127.8, 127.4, 127.2, 126.5,
126.0, 117.6, 114.8, 67.4, 52.1 ppm. HRMS (ESI): calcd. for
C26H24N [M+ + H] 350.1909; found 350.1914.
2 H), 7.49 (d, J = 8.8 Hz, 2 H), 4.75 (q, J = 6.8 Hz, 1 H), 1.54 (d,
J = 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.1,
147.4, 127.1, 123.9, 59.9, 21.5 ppm. MS (ESI): m/z = 165 [M+
+
H – N2].
(1-Azidopropyl)benzene (6a): Colourless liquid; yield: 1.1 g (96%).
1
IR (neat): ν = 3080, 3056, 3027, 2960, 2088, 1595, 1499 cm–1. H
˜
N-Benzylaniline (8c): Colourless liquid; yield: 84 mg (45%). IR
NMR (400 MHz, CDCl3): δ = 7.37–7.33 (m, 2 H), 7.31–7.26 (m, 3
H), 4.32 (t, J = 7.2 Hz, 1 H), 1.91–1.71 (m, 2 H), 0.91 (t, J =
7.6 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.7, 128.7,
128.2, 126.9, 67.9, 29.3, 10.8 ppm.
(neat): ν = 3418, 2923, 1601, 1505, 1252 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 7.30–7.14 (m, 5 H), 7.11–7.06 (m, 2 H), 6.65 (t, J =
7.2 Hz, 1 H), 6.56 (d, J = 7.8 Hz, 2 H), 4.31 (s, 2 H), 3.93 (br. s, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.2, 139.5, 129.2,
128.6, 127.5, 127.2, 117.6, 112.9, 48.4 ppm. HRMS (ESI): calcd.
for C13H14N [M+ + H] 184.1126; found 184.1123.
N-(1-Phenylpropyl)-N-propylaniline (6b): Colourless liquid; yield:
120 mg (69%). IR (neat): ν = 3080, 3056, 3027, 2960, 2931, 2873,
˜
1
1595, 1499 cm–1. H NMR (400 MHz, CDCl3): δ = 7.30–7.19 (m,
1-Azido-2,3,4,5-tetrahydronaphthalene (9a): Colourless liquid; yield:
7 H), 6.81 (d, J = 8.2 Hz, 2 H), 6.69 (t, J = 7.2 Hz, 1 H), 4.79 (d,
J = 7.2 Hz, 1 H), 2.98–2.93 (m, 2 H), 2.09–1.94 (m, 2 H), 1.49–
1.33 (m, 2 H), 1.00 (t, J = 7.2 Hz, 3 H), 0.758 (t, J = 7.2 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 149.4, 141.7, 129.9, 128.2,
127.7, 126.9, 116.6, 114.2, 63.9, 47.7, 24.4, 21.0, 11.8, 11.4 ppm.
HRMS (ESI): calcd. for C18H24N [M+ + H] 254.1909; found
254.l911.
800 mg (89%). IR (neat): ν = 3360, 3052, 3014, 2921, 2850, 2098,
˜
1601, 1585, 1475 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.28–7.25
(m, 1 H), 7.23–7.17 (m, 2 H), 7.12–7.10 (m, 1 H), 4.54 (t, J =
4.4 Hz, 1 H), 2.86–2.68 (m, 2 H), 2.03–1.90 (m, 3 H), 1.83–1.75 (m,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.4, 133.8, 129.5,
129.2, 128.2, 126.1, 59.5, 29.2, 28.8, 19.0 ppm.
2,3,4,5-Tetrahydro-1H-benzo[b]azepine (9c): Colourless viscous li-
N-Propylaniline (6c): Colourless liquid; yield: 20 mg (11%). IR
quid; yield: 75 mg (46%). IR (neat): ν = 3360, 3052, 3014, 2921,
˜
(neat): ν = 3410, 2960, 1603, 1507, 1320 cm–1. 1H NMR (400 MHz,
2850, 1601, 1585, 1475 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.01 (d, J = 7.2 Hz, 1 H), 6.94 (dt, J = 7.6, 0.8 Hz, 1 H), 6.73 (dt,
J = 7.2, 0.8 Hz, 1 H), 6.62 (d, J = 8.0 Hz, 1 H), 3.50 (br. s, 1 H),
2.95–2.92 (m, 2 H), 2.68 (dd, J = 5.6, 5.2 Hz, 2 H), 1.73–1.67 (m,
2 H), 1.57–1.52 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
150.4, 133.7, 130.8, 126.6, 120.8, 119.4, 48.9, 36.1, 32.2, 26.9 ppm.
HRMS (ESI): calcd. for C10H14N [M+ + H] 148.1126; found
148.1123.
˜
CDCl3): δ = 7.16 (t, J = 7.6 Hz, 2 H), 6.67 (t, J = 7.2 Hz, 1 H),
6.59 (d, J = 8.4 Hz, 2 H), 3.59 (br. s, 1 H), 3.06 (t, J = 6.8 Hz, 2
H), 1.62 (sext, J = 7.2 Hz, 2 H), 0.98 (t, J = 7.6 Hz, 3 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 148.4, 129.1, 117.0, 112.6, 45.7, 22.6,
11.6 ppm. HRMS (ESI): calcd. for C9H14N [M+ + H] 136.1126;
found 136.1125.
(1-Azidobutyl)benzene (7a): Colourless liquid; yield: 2.8 mg (67%).
1
IR (neat): ν = 3080, 3056, 3027, 2960, 2088, 1595, 1499 cm–1. H
1,2-Dimethoxy-4-(1-phenylethyl)benzene (14): Colourless liquid;
˜
NMR (400 MHz, CDCl3): δ = 7.45–7.33 (m, 5 H), 4.47 (t, J = yield: 150 mg (46%). IR (neat): ν = 3052, 3023, 2998, 2962, 2931,
˜
Eur. J. Org. Chem. 2011, 5297–5302
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5301

S. Baskaran et al.
FULL PAPER
2833, 1591, 1506, 1462, 1416, 1251 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.24–7.12 (m, 4 H), 6.83–6.63 (m, 4 H), 4.05 (q, J =
7.2 Hz, 1 H), 3.81 (s, 3 H), 3.78 (s, 3 H), 1.60 (d, J = 7.2 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 149.0, 147.5, 146.4, 138.9,
128.3, 127.4, 125.9, 120.8, 119.3, 111.4, 55.8, 55.7, 44.3, 22.1 ppm.
HRMS (ESI): calcd. for C16H19O2 [M+ + H] 243.1385; found
243.1380.
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[7]
N-(1-Phenylethyl)aniline (15): Colourless liquid; yield: 32 mg
(52%). IR (neat): ν = 3409, 3052, 3023, 2961, 2923, 2853, 1601,
˜
1501, 1450, 1316, 1257 cm–1. 1H NMR (400 MHz, CDCl3): δ =
7.28–7.12 (m, 4 H), 6.99–6.95 (m, 1 H), 6.97 (t, J = 7.2 Hz, 2 H),
6.53 (t, J = 7.2 Hz, 1 H), 6.38 (d, J = 8.0 Hz, 2 H), 4.39 (q, J =
6.8 Hz, 1 H), 3.90 (br. s, 1 H), 1.44 (d, J = 6.8 Hz, 3 H) ppm. 13C
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C14H16N [M+ + H] 198.1283; found 198.1289.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data, crystal struc-
ture data of compound 2b and NMR spectra of all compounds.
[8]
Acknowledgments
We thank the Department of Science and Technology (DST) and
the Council of Scientific and Industrial Research (CSIR) (New
Delhi) for financial support and DST-FIST (New Delhi) for use of
the NMR facility. A. M. (SRF) thanks IIT-Madras (Chennai), and
P. M. (SRF) thanks CSIR (New Delhi) for fellowships.
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Received: May 12, 2011
Published Online: August 8, 2011
5302
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Eur. J. Org. Chem. 2011, 5297–5302