Metal-free synthesis of secondary arylamines: An aliphatic-to-aromatic transformation

Article abstract of DOI:10.1002/ejoc.201201263

An efficient method for the N-arylation of primary and some secondary amines using 2-halocyclohex-2-enones in an aliphatic-to-aromatic transformation in the presence of a substoichiometric amount of pTsOH has been developed. A series of arylamines have been synthesized from 2-halocyclohex-2-enones by in situ enamine formation followed by aromatization under environmentally friendly conditions using pTsOH. This metal-free, practical, relatively inexpensive protocol is of value in organic synthesis for industrial and academic applications. Copyright

Full text of DOI:10.1002/ejoc.201201263

FULL PAPER
DOI: 10.1002/ejoc.201201263
Metal-Free Synthesis of Secondary Arylamines: An Aliphatic-to-Aromatic
Transformation
M. Teresa Barros,[a] Suvendu S. Dey,[a] and Christopher D. Maycock*[b,c]
Keywords: Synthetic methods / Green chemistry / Metal-free reactions / Amines / Arylation / Enones
An efficient method for the N-arylation of primary and some
phatic-to-aromatic transformation in the presence of a sub-
secondary amines using 2-halocyclohex-2-enones in an ali-
stoichiometric amount of pTsOH has been developed.
ceived particular attention. Aromatic amines can also be
obtained from enamines by using stoichiometric amounts
of SnCl4, SbCl5,[15] and [PdCl2(MeCN)2],[16] as well as with
catalytic amounts of Pd/C.[17] These processes use expensive
and toxic catalysts,[18] hazardous solvents, and produce
waste. Most of these approaches offer limited scope and
structural diversity. Moreover, owing to high demand,
global supplies of precious metals are predicted to reach
critical levels or soon be exhausted.[19] The challenge for
chemists is to find new methods using widely available
metal catalysts, or even metal-free alternatives, to maintain
access to key drugs and other products. It follows that cata-
lytic aromatic C–N bond-forming reactions that are practi-
cal, relatively inexpensive, and feasible for a broad range of
substrates would be valuable in organic synthesis for indus-
trial and academic interests. With this in mind, we have
developed a metal-free, novel, eco-friendly route for the
synthesis of arylamines featuring an aliphatic-to-aromatic
transformation involving 2-halocyclohex-2-en-1-ones and
amines (Scheme 1) in the presence of a substoichiometric
amount of p-toluenesulfonic acid (pTsOH).
Introduction
Arylamines are attractive targets for chemical synthesis
because of their prevalence and wide utility. The N-aryl
moiety[1] widely occurs in many forms in areas such as
pharmaceuticals, agrochemicals, photography, xeroxogra-
phy, pigments, electronic materials, and natural products.
Several commonly occurring DNA lesions are caused by
arylamines, and these have been the target of recent syn-
thetic efforts.[2] Since 1903, the copper-catalyzed Ullmann
reaction[3] has been widely used for N-arylation reactions.[4]
The classic Ullmann reaction normally requires harsh con-
ditions, such as high temperatures (ca. 200 °C), stoichiomet-
ric amounts of copper, and selective halide substrates, which
is problematic for industrial use due to high costs and waste
disposal. Successful methods include the use of catalytic
amounts of copper and arylboronic acids in place of aryl
halides.[5] However, the relative instability of boronic acids
and the tedious purification procedure limit their further
application. Buchwald[6] and Hartwig[7] and their co-
workers have independently established the broad applica-
bility of palladium catalysts for the N-arylation of amines
with aryl halides. Recently, Fe,[8] Ni,[9] Ir,[10] and Rh[11] salts
have also been used for N-aryl coupling reactions. Transi-
tion-metal-free procedures for the N-arylation of amines,
sulfonamides, and carbamates have also been developed.[12]
In the last decade, catalytic amine syntheses such as hydro-
aminations[13] and hydroaminomethylations[14] have re-
Scheme 1. Synthesis of arylamines.
Results and Discussion
[a] REQUIMTE, CQFB, Departamento de Química, Faculdade de
Ciências e Tecnologia, Universidade Nova de Lisboa,
2829-516 Caparica, Portugal
To optimize the reaction conditions, the reaction of 2-
iodocyclohex-2-en-1-one and aniline, to obtain diphenyl-
amine, was carried out under different solvent and catalytic
conditions (Table 1). The best catalyst system was found to
be 20 mol-% pTsOH in solvents such as acetonitrile, meth-
anol, and ethanol. Out of concern for the environment, eth-
anol was chosen as the best medium. Dilution with solvent
led to longer reaction times, whereas in the absence of sol-
vent, some of the product polymerized with a consequent
[b] Instituto de Tecnologia Química e Biologia, Universidade Nova
de Lisboa,
2780-157 Oeiras, Portugal
E-mail: maycock@itqb.unl.pt
Homepage: http://www.itqb.unl.pt/research/chemistry/organic-
synthesis
[c] Departamento de Química e Bioquímica, Faculdade de
Ciências, Universidade de Lisboa,
Campo Grande, 1749-016 Lisboa, Portugal
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201263.
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Metal-Free Synthesis of Secondary Arylamines
reduction of the yield. Changing the halogen on the 2-halo- action (Table 2). In a typical procedure, a mixture of 2-halo-
cyclohex-2-enone had little effect on the outcome of the re- cyclohex-2-en-1-one and amine in dry ethanol (1 m with re-
spect to amine) was heated at 75 °C in the presence of
20 mol-% pTsOH in a screw-capped vessel for the time re-
quired (TLC monitored) to complete the reaction. Concen-
tration of the reaction mixture, dilution with ethyl acetate,
washing with sodium hydrogen carbonate solution, separa-
tion, and evaporation of the organic phase followed by
short flash silica gel chromatography led to the arylamines
in moderate-to-high yields.
Table 1. Optimization of the reaction conditions for the arylation
reaction (PNBA = p-nitrobenzoic acid, BA = benzoic acid).[a]
We then focused our attention on the reactions of dif-
ferent amines with unsubstituted 2-halocyclohex-2-enones
(Table 3). A variety of substituted anilines and aliphatic
Table 3. Library of arylamines synthesized from unsubstituted 2-
halocyclohexenone.[a]
[a]
A mixture of 0.60 mmol of 2-iodocyclohex-2-enone and
0.50 mmol of aniline in 0.5 mL of solvent was studied unless men-
tioned otherwise. [b] Isolated yield.
Table 2. Effect of halide as leaving group in 2-halocyclohex-2-enone
on the arylation reaction.[a]
[a] All reactions were carried out with a mixture of 0.60 mmol of
2-halocyclohexenone and 0.50 mmol of amine in 0.5 mL of EtOH.
[b] Isolated yield. [c] 30 mol-% pTsOH was used. [d] MeOH was
used as solvent. [e] Amine·HCl was used and 1 equiv. K2CO3 was
added. The mixture was stirred at room temp. for 1 h before adding
pTsOH and then heated. Compounds 3, 8, 16, and 19 were synthe-
sized from 2-bromocyclohex-2-enone, 5, 9, 13, and 17 were synthe-
sized from 2-chlorocyclohex-2-enone and the rest were synthesized
from 2-iodocyclohex-2-enone.
[a]
A mixture of 0.6 mmol of 2-halocyclohex-2-enone and
0.50 mmol of aniline in 0.5 mL of EtOH was studied. [b] Isolated
yield.
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M. T. Barros, S. S. Dey, C. D. Maycock
FULL PAPER
amines containing electron-withdrawing and/or -donating 2-halocyclohex-2-enones and amines, highly substituted di-
groups reacted smoothly. However, the synthesis of com- arylamines can be obtained in one step in moderate-to-high
pounds 6, 10, and 11, which contain either a ortho nitro or yields.
para ester group, required 30 mol-% pTsOH to complete the
A straightforward, plausible pathway for the reaction is
reaction. This indicates that the amount of pTsOH used presented in Scheme 2. Michael addition of the reagents is
might have to be changed depending on the nature of the reversible unless cyclization to an aziridine occurs, but that
substituted groups or the basicity of the amines. Cyclohex- requires basic conditions. 1,2-Addition is the predominant
ylamine and cyclic secondary amines such as indoline, pyr- reaction leading to the products and after condensation of
rolidine, and tetrahydoquinoline also underwent spontane- the ketone with the amine to form the imine II in equilib-
ous reaction with 2-halocyclohex-2-enones to afford the rium with enamine III, aromatization occurs through a hy-
corresponding arylamines. Piperidine and acyclic secondary dride shift followed by elimination of HX.
amines were surprisingly inert under the reaction conditions
employed. Methanol could be used as the solvent instead
of ethanol when transesterification became a problem, such
as during the preparation of amines 10 and 11.
The optimized conditions also proved to be efficient for
a wide range of substituted 2-iodocyclohex-2-en-1-ones
(Table 4). It was found that replacement of the methyl
group in enone 26 with the bulkier phenyl group at the
same position, as in 25, resulted in a reduction of the yields
of the corresponding arylamines. Many functional groups
in the starting amine, such as Cl, Br, OMe, COOR, and
NO2, were stable under the reaction conditions. Amide and
ester derivatives of amino acids also reacted accordingly to
form secondary arylamines 14, 15. Thus, by designing the
Scheme 2. Plausible mechanism for the arylation reaction.
Table 4. Library of arylamines synthesized from substituted 2-halo-
cyclohexenone.[a]
Conclusions
We have demonstrated a simple, facile, metal-free synthe-
sis of diaryl- and monoarylamines from simple starting ma-
terials by an aliphatic-to-aromatic transformation using in-
expensive pTsOH. The procedure described herein, which
has distinct advantages over previously applied methods,
such as nonhazardous reaction conditions, shorter reaction
times, high yields, regioselectivity, and the use of inexpen-
sive materials, partially fulfils the philosophy of green
chemistry[20] and the demands for industrial applications.
Experimental Section
General: All chemicals were reagent grade and all reactions were
carried out under argon. All solvents were dried by using standard
procedures. Flash chromatography was performed on Merck Kie-
1
selgel 60 (particle size 0.032–0.063 mm). H and 13C NMR spectra
were obtained with a Bruker 400 and 100 MHz spectrometers using
CDCl3 as solvent unless noted otherwise. Chemical shifts are re-
ported in ppm relative to TMS. IR spectra were obtained with a
Perkin–Elmer 1600 FT-IR spectrophotometer and wavenumbers
are reported in cm–1 (solids as KBr pellets and liquid samples as
neat). Exact masses are measured by ESI-FIA-TOF with a Bruker
MicrOTOF instrument.
Synthesis of the Starting Cyclohex-2-en-1-ones and Corresponding
Iodo Compounds: Ethyl 6-methyl-2-oxocyclohex-2-ene-1-carboxyl-
ate,[21] 5-methylcyclohex-2-en-1-one,[21] 4-methylcyclohex-2-en-1-
one,[21] 4-phenylcyclohex-2-en-1-one,[22] and l-phenylalanine-N-
propargylamide[23] were synthesized following literature pro-
cedures. Iodo compounds a,[24] d,[25] e,[26] f, g,[27] and h were pre-
[a] All reactions were carried out with a mixture of 0.60 mmol of
2-halocyclohexenone and 0.50 mmol of amine in 0.5 mL of EtOH.
[b] Isolated yield. Compounds 20 and 22 were prepared from 2-
iodo-5-methylcyclohex-2-enone and 21, 23, and 24 were prepared
from 2-iodo-3-methylcyclohex-2-enone.
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Metal-Free Synthesis of Secondary Arylamines
pared by the usual iodination procedure[24] with iodine and pyr-
idine in dichloromethane starting from the corresponding cyclohex-
2-en-1-ones (Table 5). 2-Chlorocyclohex-2-en-1-one[28] and 2-bro-
mocyclohex-2-en-1-one[29] were synthesized following literature
procedures.
118.4 (3 C), 61.1, 14.4 ppm. C15H15NO2 (241.29): calcd. C 74.67,
H 6.27, N 5.81; found C 74.65, H 6.28, N 5.78.
2-Bromo-4-methyl-N-phenylaniline (8): Yellow oil (116 mg, 89%).
1
IR: ν
= 3399, 3046, 3025, 2917, 2863, 1596, 1037, 744 cm–1. H
˜
max
NMR: δ = 7.36 (d, J = 1.36 Hz, 1 H), 7.28 (dd, J = 8.1, 7.7 Hz, 2
H), 7.17 (d, J = 8.3 Hz, 1 H), 7.08 (d, J = 7.7 Hz, 2 H), 7.01–6.95
(m, 2 H), 2.27 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
142.4, 138.7, 133.3, 131.3, 129.5 (2 C), 128.8, 121.9, 119.2 (2 C),
116.9, 112.9, 20.3 ppm. C13H12BrN (262.15): calcd. C 59.56, H
4.61, N 5.34; found C 59.36, H 4.58, N 5.52.
Table 5. 2-Halocyclohexenones used for the arylation reactions.
2-Chloro-4-methyl-N-phenylaniline (9): Pale-yellow solid (100 mg,
92%); m.p. 36–40 °C. IR: ν
= 3412, 3399, 3033, 3058, 2923,
˜
max
1569, 1049, 742, 530 cm–1. 1H NMR: δ = 7.29 (t, J = 7.6 Hz, 2 H),
7.19 (d, J = 8.0 Hz, 1 H), 7.18 (s, 1 H), 7.09 (d, J = 7.6 Hz, 2 H),
6.98 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 8.0 Hz, 1 H), 2.27 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 142.3, 137.5, 130.7,
130.1, 129.4 (2 C), 128.1, 122.1, 121.9, 119.1 (2 C), 116.7, 20.3 ppm.
C13H12ClN (217.70): calcd. C 71.72, H 5.56, N 6.43; found C 71.56,
H 5.53, N 6.47.
Methyl 5-Chloro-2-methoxy-4-(phenylamino)benzoate (11): Pale-yel-
low solid (102 mg, 70%); m.p. 105 °C. IR: νmax = 3399, 3004, 2948,
˜
2-Iodo-4-phenylcyclohex-2-enone (f): Yellowish gummy solid. 1H
NMR: δ = 7.77 (d, J = 3.3 Hz, 1 H), 7.37 (t, J = 7.4 Hz, 2 H), 7.31
(t, J = 7.4 Hz, 1 H), 7.21 (d, J = 7.4 Hz, 2 H), 2.28 (m, 1 H), 2.65
(m, 1 H), 2.42 (m, 1 H), 2.13 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 192.0, 161.6, 141.6, 129.1 (2 C), 127.6 (2 C), 104.5,
46.9, 35.9, 32.4 ppm. C12H11IO (298.12): calcd. C 48.35, H 3.72;
found C 48.25, H 3.74.
2834, 1714, 1590, 1403, 1097, 910, 779 cm–1. 1H NMR: δ = 7.95 (s,
1 H), 7.43 (t, J = 7.6 Hz, 2 H), 7.27 (d, J = 7.6 Hz, 2 H), 7.19 (t,
J = 7.6 Hz, 1 H), 6.76 (s, 1 H), 6.47 (br. s, 1 H), 3.88 (s, 3 H), 3.78
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.3, 160.0,
1.45.6, 139.7, 133.5, 129.9 (2 C), 124.8, 122.5 (2 C), 111.3, 110.4,
97.2, 56.2, 51.7 ppm. C15H14ClNO3 (291.73): calcd. C 61.76, H
4.84, N 4.80; found C 61.67, H 4.69, N 5.03.
Ethyl 3-Iodo-6-methyl-2-oxocyclohex-3-enecarboxylate (h): Yellow-
ish liquid (major diastereomer/enol = 1:1.3). 1H NMR: δ = 7.72
(dd, J = 5.6, 2.8 Hz, IH), 7.66 (dd, J = 6.0, 1.9 Hz, 1ϫ1.3 H),
4.35–4.18 (m, 2 H + 2ϫ1.3 H), 3.26 (d, J = 11.6 Hz, 1 H), 2.66
(m, 1 H), 2.37–2.19 (m, 1 H + 1ϫ1.3 H), 2.05 (m, 1ϫ1.3 H), 1.69
(m, 1ϫ1.3 H), 1.36–1.23 (m, 3 H + 3ϫ1.3 H), 1.09 (d, J = 6.4 Hz,
1 H), 1.00 (d, J = 6.4 Hz, 1ϫ1.3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 188.0, 184.5, 158.4, 157.7, 101.4, 97.9, 63.8, 61.3, 60.4,
38.7, 38.1, 36.9, 32.8, 19.3, 19.3, 14.2, 13.9 ppm. C10H13IO3
(308.12): calcd. C 38.98, H 4.25; found C 38.75, H 4.44.
(S)-3-Phenyl-2-(phenylamino)-N-(prop-2-ynyl)propanamide
(14):
Gummy yellow solid (100 mg, 72%). IR: ν = 3394, 3340, 3295,
˜
max
1
3230, 3063, 3031, 1640, 1602, 1504, 1276, 754 cm–1. H NMR: δ =
7.33 (t, J = 7.2 Hz, 2 H), 7.29–7.19 (m, 2 H), 7.16 (t, J = 7.9 Hz,
2 H), 6.94 (br. s, 1 H), 6.79 (t, J = 7.2 Hz, 1 H), 6.53 (d, J = 7.9 Hz,
2 H), 4.14 (m,1 H), 4.02–3.92 (m, 2 H), 3.88 (br. s, 1 H), 3.33 (dd,
J = 14.2, 14.4 Hz, 1 H), 3.06 (dd, J = 14.2, 14.4 Hz, 1 H), 2.17 (t,
J
=
2.4 Hz,
1 H) ppm. HRMS (ESI-FIA-TOF): calcd. for
C18H19N2O [M + H]+ 279.1496; found 279.1492.
3-Methyl-N-octylaniline (20): Colorless oil (96 mg, 88%). IR: ν
˜
max
Representative Experimental Procedure for the Synthesis of Aryl-
= 3410, 3052, 3020, 2957, 2930, 2871, 1604, 1506, 1478, 748,
692 cm–1. 1H NMR: δ = 7.06 (t, J = 7.5 Hz, 1 H), 6.51 (d, J =
7.5 Hz, 1 H), 6.45–6.37 (m, 2 H), 3.09 (t, J = 7.1 Hz, 2 H), 2.27 (s,
3 H), 1.60 (m, 2 H), 1.43–1.20 (m, 10 H), 0.88 (t, J = 7.0 Hz, 3
H) ppm. C15H25N (219.37): calcd. C 82.13, H 11.49, N 6.39; found
C 81.90, H 11.41, N 6.49.
amines:
A
solution of 2-iodocyclohex-2-en-1-one (133 mg,
0.60 mmol), aniline (47 mg, 0.50 mmol), and anhydrous pTsOH
(17 mg, 0.10 mmol) in dry EtOH (0.5 mL) in a sealed 5 mL Teflon®
screw-capped vessel under argon was stirred at 75 °C for 1.5 h. The
reaction mixture was concentrated, diluted with ethyl acetate
(30 mL), and washed with 20% sodium hydrogen carbonate solu-
tion and brine followed by separation and evaporation of the or-
ganic layer to give the crude residue, which was directly subjected
to flash silica gel column chromatography (eluted with hexanes/
ethyl acetate) to afford pure diphenylamine 1 as a grayish white
solid[8a] (74 mg, 87%). 1H NMR: δ = 7.26 (t, J = 7.7 Hz, 2 H), 7.07
(d, J = 7.7 Hz, 2 H), 6.92 (d, J = 7.7 Hz, 1 H), 5.69 (br. s, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 143.2 (2 C), 129.4 (4 C), 121.0
(2 C), 117.8 (4 C) ppm. Data for known arylamines are in accord-
ing with those previously reported.
N-Allyl-3-methylaniline (21): Colorless oil (54 mg, 74%). IR: ν
˜
max
= 3405, 3043, 2919, 2869, 1702, 1671, 1606, 1509, 1492, 769 cm–1.
1H NMR: δ = 7.08 (t, J = 7.6 Hz, 1 H), 6.57 (d, J = 7.6 Hz, 1 H),
6.51–6.48 (m, 2 H), 5.97 (m, 1 H), 5.28 (dd, J = 17.2, 1.4 Hz, 1 H),
5.16 (dd, J = 10.2, 1.4 Hz, 1 H), 3.77 (d, J = 5.5 Hz, 2 H), 2.28 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.3, 139.1, 135.1,
129.1, 119.2, 116.6, 114.4, 110.8, 47.1, 21.6 ppm. C10H13N (147.22):
calcd. C 81.59, H 8.90, N 9.51; found C 81.25, H 8.81, N 9.30.
3-Methoxy-N-(m-tolyl)aniline (23): Colorless oil (86 mg, 81%). IR:
Characterization Data for the New Arylamines
ν
˜
max = 3033, 3000, 2954, 2836, 1598, 1490, 1155 cm–1. 1H NMR: δ
Ethyl 3-(Phenylamino)benzoate (3): Colorless oil (112 mg, 94%). = 7.18–7.12 (m, 2 H), 6.90 (m, 2 H), 6.76 (d, J = 7.5 Hz, 1 H),
1
IR: ν
= 3374, 3045, 2981, 1704, 1594 cm–1. H NMR: δ = 7.65 6.66–6.62 (m, 2 H), 6.47 (m, 1 H), 5.66 (br. s, 1 H), 3.81 (s, 3 H),
˜
max
(s, 1 H), 7.50 (d, J = 7.6 Hz, 1 H), 7.25–7.16 (m, 4 H), 7.01 (d, J
= 7.6 Hz, 2 H), 6.90 (t, J = 7.6 Hz, 3 H), 4.28 (q, J = 7.1 Hz, 2 H),
1.30 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
168.9, 143.6, 142.4, 131.9, 129.6 (2 C), 129.3, 121.9, 121.8, 121.5,
2.34 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.7, 144.7,
142.8, 139.3, 130.1, 129.2, 122.2, 119.1, 115.5, 110.3, 106.1, 103.4,
55.2, 21.6 ppm. HRMS (ESI-FIA-TOF): calcd for C14H16NO [M
+ H]+ 214.1229; found 214.1226.
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M. T. Barros, S. S. Dey, C. D. Maycock
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9018; Angew. Chem. Int. Ed. 2007, 46, 8862–8865; c) A. Correa,
C. Bolm, Adv. Synth. Catal. 2008, 350, 391–394; d) A. Correa,
S. Elmore, C. Bolm, Chem. Eur. J. 2008, 14, 3527–3529; for
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1-(Biphenyl-4-yl)-1,2,3,4-tetrahydroquinoline (25): Pale-yellow solid
(91 mg, 64%); m.p. 86–90 °C. IR: ν
= 3056, 3031, 2927, 2852,
˜
max
2362, 2343, 1596, 1519, 1261, 763 cm–1. 1H NMR: δ = 7.59 (d, J =
7.5 Hz, 2 H), 7.56 (d, J = 8.4 Hz, 2 H), 7.43 (t, J = 7.5 Hz, 2 H),
7.32 (t, J = 7.5 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 2 H), 7.06 (d, J =
7.4 Hz, 1 H), 6.97 (dd, J = 7.8, 7.2 Hz, 1 H), 6.88 (d, J = 7.8 Hz,
1 H), 6.73 (dd, J = 7.4, 7.2 Hz, 1 H), 3.67 (t, J = 5.7 Hz, 2 H), 2.85
(t, J = 5.7 Hz, 2 H), 2.06 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 147.7, 144.1, 140.8, 136.0, 129.4, 128.8 (2 C), 127.9 (2
C), 126.9, 126.8 (2 C), 126.4, 125.2, 124.2 (2 C), 118.8, 116.4, 50.7,
27.7, 22.8 ppm. HRMS (ESI-FIA-TOF): calcd for C21H20N [M +
H]+ 286.1594; found 286.1590.
[2]
[3]
[4]
3-Chloro-N-(p-tolyl)aniline (28): Colorless oil (98 mg, 90%). IR:
ν
˜
max = 3409, 3381, 3023, 3038, 2921, 1548, 1047, 746, 552 cm–1. 1H
NMR: δ = 7.14–7.10 (m, 3 H), 7.0 (d, J = 8.2 Hz, 2 H), 6.95 (m,
1 H), 6.83–6.79 (m, 2 H), 5.61 (br. s, 1 H), 2.32 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 145.6, 139.1, 134.9, 132.2, 130.3,
130.0 (2 C), 120.1 (2 C), 119.8, 115.8, 114.3, 20.7 ppm. C13H12ClN
(217.70): calcd. C 71.72, H 5.56, N 6.43; found C 71.68, H 5.46, N
6.39.
N-(2-Chloro-4-methylphenyl)biphenyl-4-amine (30): Pale-yellow so-
lid (107 mg, 73%); m.p. 79–82 °C. IR: ν
= 3407, 3056, 2919,
˜
max
[5]
[6]
2856, 1606, 1523, 1409, 840, 740 cm–1. H NMR: δ = 7.56 (d, J =
7.4 Hz, 2 H), 7.52 (d, J = 8.5 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 2 H),
7.29 (t, J = 7.4 Hz, 1 H), 7.25 (d, J = 8.3 Hz, 1 H), 7.20 (s, 1 H),
7.15 (d, J = 8.5 Hz, 2 H), 6.96 (d, J = 8.3 Hz, 1 H), 6.01 (br. s, 1
H), 2.28 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.8,
140.8, 137.2, 134.7, 131.1, 130.2, 128.8 (2 C), 128.1, 128.0 (2 C),
126.8, 126.6 (2 C), 122.4, 119.0 (2 C), 117.1, 20.4 ppm. C19H16ClN
(293.80): calcd. C 77.68, H 5.49, N 4.77; found C 77.49, H 5.46, N
4.68.
1
Ethyl 2-Methyl-6-(phenethylamino)benzoate (31): Colorless oil
(109 mg, 77%). IR: ν
= 3360, 3027, 2977, 2933, 1677, 1587,
˜
[7]
[8]
max
1465, 1245 cm–1. 1H NMR: δ = 7.31 (t, J = 7.5 Hz, 2 H), 7.25–7.20
(m, 3 H), 7.16 (t, J = 7.6 Hz, 1 H), 6.56 (d, J = 7.6 Hz, 1 H), 6.48
(d, J = 7.6 Hz, 1 H), 4.31 (q, J = 7.1 Hz, 2 H), 3.39 (t, J = 7.3 Hz,
2 H), 2.94 (t, J = 7.3 Hz, 2 H), 2.42 (s, 3 H), 1.34 (t, J = 7.11 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.6, 149.4, 140.2,
139.4, 132.2, 128.8 (2 C), 128.5 (2 C), 126.4, 119.1, 13.9, 109.1,
60.5, 44.9, 35.5, 23.2, 14.3 ppm. C18H21NO2 (283.37): calcd. C
76.29, H 7.47, N 4.94; found C 76.36, H 7.24, N 5.20.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of all N-arylamines and compounds
f and h and other details.
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Acknowledgments
This work has been supported by the Portuguese Fundação para a
Ciência e a Tecnologia (FCT) (grant numbers PEst-OE/EQB/
LA0004/2011 and PEst-C/EQB/LA0006/2011). S. S. D. is grateful
to the FCT for grants (BPD/66763/2009). The National NMR Net-
work was supported by Programa Operacional Ciência e Inovação
2010 (POCI 2010) (grant number REDE/1517/RMN/2005) and
FCT.
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Received: September 21, 2012
Published Online: December 10, 2012
Eur. J. Org. Chem. 2013, 742–747
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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