Design and synthesis of two aromatic amines with dendritic structure

Article abstract of DOI:10.1002/cjoc.201090071

The design and synthesis of two aromatic amines with dendritic structures, i.e. 3,4,5-tribenzyloxyaniline (3,4,5-G₁-NH₂) and 2,5-dibenzyloxyaniline (2,5-G₁-NH₂), were conducted. A coupling reaction of three or two equivalents of benzyl bromide to one equivalent of methyl hydroxybenzoate generated methyl 3,4,5-tribenzyloxybenzoate (3,4,5-G₁-COOCH₃), methyl 2,5-dibenzyloxybenzoate (2,5-G₁-COOCH₃) and 2,6-dibenzyloxybenzoate (2,6-G₁-COOCH₃) in high yields. All G₁-COOCH₃ derivatives were studied by X-ray analysis. The results show that these dendrons have sufficient volume to be used as the fine ligands for certain catalysts. The amide intermediates (benzamide, G₁-CONH₂) were obtained by reaction between ammonia and G₁-COOCH₃. Interestingly, 2,6-dibenzyloxybenzamide (2,6-G₁-CONH₂) can not be prepared in the same condition, which may be due to the overlarge steric block. Sodium hypochlorite was an effective oxidant to generate methyl carbamates G₁-NHCO₂CH₃.

Full text of DOI:10.1002/cjoc.201090071

FULL PAPER
Design and Synthesis of Two Aromatic Amines
with Dendritic Structure
Luo, Zhenghong*(罗正鸿)
Cheng, Hua(程华)
Xu, Wei(徐伟)
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen
University, Xiamen, Fujian 361005, China
The design and synthesis of two aromatic amines with dendritic structures, i.e. 3,4,5-tribenzyloxyaniline
(3,4,5-G1-NH2) and 2,5-dibenzyloxyaniline (2,5-G1-NH2), were conducted. A coupling reaction of three or two
equivalents of benzyl bromide to one equivalent of methyl hydroxybenzoate generated methyl 3,4,5-tribenzyloxy-
benzoate (3,4,5-G1-COOCH3), methyl 2,5-dibenzyloxybenzoate (2,5-G1-COOCH3) and 2,6-dibenzyloxybenzoate
(2,6-G1-COOCH3) in high yields. All G1-COOCH3 derivatives were studied by X-ray analysis. The results show
that these dendrons have sufficient volume to be used as the fine ligands for certain catalysts. The amide intermedi-
ates (benzamide, G1-CONH2) were obtained by reaction between ammonia and G1-COOCH3. Interestingly,
2,6-dibenzyloxybenzamide (2,6-G1-CONH2) can not be prepared in the same condition, which may be due to the
overlarge steric block. Sodium hypochlorite was an effective oxidant to generate methyl carbamates G1-
NHCO2CH3.
Keywords aromatic amine, dendritic structure, Hofmann rearrangement
Introduction
Experimental
Aromatic amines are important synthetic intermedi-
ates that play a central role in many areas such as poly-
mer and medicine,1-4 which can be produced by the re-
duction of the corresponding nitro aromatic with a met-
allo hydride reagent or by catalytic hydrogenation.5 The
selective reduction of aromatic nitro groups in the pres-
ence of sensitive functional groups, e.g. carbonyl, cyano,
chloro and alkenic groups, with hydrogen is usually dif-
ficult, because these sensitive functionalities are re-
duced faster with hydrogen than the nitro group.6 Fur-
thermore, the above reduction in the presence of sensi-
tive functional groups produces sub-pollution along
with the need for rigorous reaction conditions.6 Com-
paratively, Senanayake et al. found that the conversion
of aliphatic amides into amines with various oxidants
was an effective alternative to the above mentioned
method.7
In this paper, we reported the mild synthesis via
Hofmann rearrangement and characterization of such
aromatic amines with dendritic structures. These amines
have potential values in many fields owing to their
structural features, such as self-assembled supramole-
cular dendrimers,8-10 novel catalyst capping metal
nanoparticles,11 and side-chains in polymers.12 Two
types of aromatic amines with dendritic structures, i.e.,
3,4,5-tribenzyloxyaniline (3,4,5-G1-NH2) and 2,5-dibenz-
yloxyaniline (2,5-G1-NH2), were described in this paper.
All experiments were carried out under an atmos-
phere of nitrogen. The solvent N,N-dimethylformamide
was dried on molecular sieves of 4 Å. Elemental analy-
ses (C, H, N) were performed on a VarioEL III elemen-
tal analyzer. Mass spectra were recorded by a Finnigan
MAT LCQTM mass spectrometer equipped with an elec-
trospray ionization source. NMR spectra were recorded
on a Bruker Avance DPX 400 MHz instrument with
deuterated chloroform (CDCl3) as solvent and tetrame-
thylsilane (TMS) as an internal reference.
Methyl 3,4,5-trihydroxybenzoate was purchased
from Acros Organics Co., methyl 2,5-dihydroxybenzoate
from Aldrich Chemical Co. and methyl 2,6-dihydroxy-
benzoate from Tokyo Chemical Industry Co. All other
chemicals were obtained commercially and used as re-
ceived unless stated otherwise.
General procedure for the synthesis of G1-COOCH3
Methyl 3,4,5-tribenzyloxybenzoate (3,4,5-G1-COO-
CH3) was prepared according to the reference.13 Methyl
3,4,5-trihydroxybenzoate (0.01 mol) and dried potas-
sium carbonate (0.04 mol) were sequentially added into
a 150 mL three-neck bottle. As N,N-dimethylforma-
mide (40 mL) was added into the bottle, sequent benzyl
bromide (0.034 mol) was added dropwise into the solu-
tion above. After being stirred at 50 ℃ for 24 h, the
resultant mixture was allowed to be cooled in ice water.
*
E-mail: luozh@xmu.edu.cn; Tel.: 0086-0592-2187190; Fax: 0086-0592-2187231
Received September 13, 2009; revised October 20, 2009; accepted October 28, 2009.
Project supported by the National Natural Science Foundation of China (No. 20406016) and State Key Laboratory of Physical Chemistry of Solid
Surface (Xiamen University).
Chin. J. Chem. 2010, 28, 303— 308
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303

Luo, Cheng & Xu
FULL PAPER
After removal of the solvent, the residue was chroma-
tographed on silica gel with ethyl acetate/petroleum
ether solution as the eluent to obtain white powder in
which was then cooled to room temperature. The solu-
tion was then extracted with dichloromethane (50
mL×3). The filtrate was concentrated, washed with
water, and dried in vacuum to generate 2,5-dibenzyloxy-
benzamide (2,5-G1-CONH2) as white powder (1.15 g,
1
91% yield. H NMR (CDCl3, 400 MHz) δ: 7.40—7.25
(m, 17H, ArH), 5.14 (s, 4H, ArCH2Om), 5.11 (s, 2H,
ArCH2Op), 3.89 (s, 3H, CO2Me); 13C NMR (CDCl3, 75
MHz) δ: 166.3, 152.2, 142.0, 137.1, 136.3, 128.2, 127.8,
127.7, 127.6, 127.2, 124.9, 108.7, 74.8, 70.9, 51.9; IR
(KBr) ν: 3030, 2946, 2876, 2000—1700, 1750—1725,
1
95.5%); H NMR (CDCl3, 400 MHz) δ: 7.89 (d, J＝8
Hz, 1H, ArH), 7.84 (br, 1H, NH), 7.45—7.30 (m, 10H,
ArH), 7.10 (br, 1H, ArH), 7.01 (d, J＝8 Hz, 1H, ArH),
5.69 (br, 1H, NH), 5.14 (s, 2H, ArCH2O), 5.08 (s, 2H,
ArCH2O); 13C NMR (CDCl3, 75 MHz) δ: 166.6, 153.2,
151.6, 136.9, 135.8, 129.0, 128.7, 128.6, 128.0, 127.9,
127.6, 121.8, 121.0, 117.0, 114.5, 72.0, 70.6; IR (KBr) ν:
3340, 3325, 2876, 2000—1700, 1770－—1710, 1600,
－1
1714, 1600, 1587, 1499, ＋1376, 1300—1200, 1109 cm ;
MS (70 eV) m/z: 454 (M ). Anal. calcd for C29H26O5: C
76.63, H 5.77; found C 76.46, H 5.94.
The preparation procedures of methyl 2,5-dibenzyl-
oxybenzoate (2,5-G1-COOCH3) and methyl 2,6-diben-
zyloxybenzoate (2,6-G1-COOCH3) were similar to that
of 3,4,5-G1-COOCH3. Finally, 2,5-G1-COOCH3 was
1
1587, 1499, 1376, 1300—1200, 1109 cm ; MS (70 eV)
m/z: 333 (M＋). Anal. calcd for C21H19NO3: C 75.68, H
5.71, N 4.20; found C 75.82, H 5.32, N 4.15.
1
obtained as white powders in 87% yield. H NMR
General procedure for the synthesis and purification
of G1-NH2
(CDCl3, 400 MHz,) δ: 7.37—6.93 (m, 13H, ArH), 5.11
(s, 2H, ArCH2Oo), 5.03 (s, 2H, ArCH2Om), 3.90 (s, 3H,
CO2Me); 13C NMR (CDCl3, 75 MHz) δ: 166.6, 152.6,
137.0, 136.8, 128.6, 128.5, 128.1, 127.8, 127.6, 127.0,
121.6, 120.4, 117.2, 116.4, 71.9,70.7, 52.1; IR (KBr) ν:
3030, 2946, 2876, 2000—1700, 1750—1725,－ 1714,
A solution of NaOH (20 mmol) in MeOH (150 mL)
was cooled approximately to 4 ℃. 7 mL of 9% NaOCl
(Chlorox) plus carboxamide 3,4,5-G1-CONH2 (2.0
mmol) was added into this magnetically stirred mixture,
with the former being added drop-wise. The mixture
was allowed to be warmed to room temperature and
then stirred intensively for 30 min to produce the inter-
mediate carbamate 3,4,5-G1-NHCO2CH3. A solution of
NaOH (40 mmol) in MeOH (10 mL) and water (2 mL)
was added, and the whole mixture was heated under
reflux for 4 d. The obtained solution was cooled to room
temperature and then the solvent was evaporated in
vacuum to separate out the precipitate. The precipitate
was removed by filtration, the filtrate concentrated, and
the separated solid collected by filtration and washed
with water to give amine 3,4,5-G1-NH2 as pale yellow
powder (0.62 g, 75.3%); 1H NMR (CDCl3, 400 MHz) δ:
7.42—7.27 (m, 15H, ArH), 6.99 (s, 2H, ArH), 5.05 (s,
4H, ArCH2Om), 4.96 (s, 2H, ArCH2Op), 3.48 (br, 2H,
NH); 13C NMR (CDCl3, 75 MHz) δ: 153.5, 142.7, 138.2,
137.3, 128.7, 128.5, 128.5, 128.1, 128.1, 127.8, 127.7,
127.4, 95.6, 75.5, 71.1; IR (KBr) ν: 3350, 3300, 2870,
2000—1700, 1600, 1587, 1499, 1376, 1300—1200,
1
1600, 1587, 1499, 1376, 1300—1200, 1109 cm ; MS
(70 eV) m/z: 348 (M＋). Anal. calcd for C22H20O4: C
75.84, H 5.79; found C 75.40, H 5.89. 2,6-G1-COOCH3
1
was obtained as white powders in 82% yield. H NMR
(CDCl3, 400 MHz) δ: 7.38—7.29 (m, 10H, Ph), 7.20 (t,
J＝8 Hz, 1H, ArH), 6.59 (d, J＝8 Hz, 2H, ArH), 5.12 (s,
4H, ArCH2O), 3.89 (s, 3H, CO2Me); 13C NMR (CDCl3,
75 MHz) δ: 166.9, 156.5, 136.8, 131.0, 128.5, 127.8,
126.9, 114.3, 105.9, 70.5, 52.3; IR (KBr) ν: 3030, 2946,
2876, 2000—1700, 1750—1725, －1714, 1600, 1587,
1
1499, 1376, 1300—1200, 1109 cm ; MS (70 eV) m/z:
348 (M＋). Anal. calcd for C22H20O4: C 75.84, H 5.79;
found C 75.66, H 5.95.
General procedure for the synthesis of G1-CONH2
A stirred solution of 3,4,5-G1-CO2CH3 (3.06 mmol)
in ethanol (200 mL) was heated approximately to 100
℃. Ammonia gas was bubbled through the mixture for
30 h, which was then cooled to room temperature over-
night. The separated solid was collected by filtration and
washed with water to generate 3,4,5-tribenzyloxybenz-
amide (3,4,5-G1-CONH2) as white needles (1.10 g,
76.4%); 1H NMR (CDCL3, 400 MHz) δ: 7.33—7.23 (m,
15H, ArH), 7.10 (s, 2H, ArH), 5.84 (br, 1H, NH), 5.63
(br, 1H, NH), 5.13 (s, 4H, ArCH2Om), 5.07 (s, 2H,
ArCH2Op); 13C NMR (CDCl3, 75 MHz) δ: 168.8, 152.8,
141.8, 137.4, 136.6, 128.6, 128.5, 128.2, 128.1, 128.0,
127.5, 107.4, 75.2, 71.5; IR (KBr) ν: 3340, 3325, 2876,
2000—1700, 1770—1－710, 1600, 1587, 1499, 1376,
＋
－1
1109 cm ; MS (70 eV) m/z: 411 (M ). Anal. calcd for
C27H25NO3: C 78.83, H 6.08, N 3.41; found C 78.93, H
6.54, N 3.67.
2,5-G1-NH2 was prepared from 2,5-G1-CONH2 (3
mmol), similarly to 3,4,5-G1-CONH2. A pale yellow
solid (0.79 g, 86%) was obtained. 1H NMR (CDCl3, 400
MHz) δ: 7.43—7.28 (m, 10H, ArH), 6.76 (d, J＝8 Hz,
1H, ArH), 6.42 (d, J＝8 Hz, 1H, ArH), 6.30 (br, 1H,
ArH), 5.01 (s, 2H, ArCH2O), 4.98 (s, 2H, ArCH2O),
3.84 (br, 2H, NH); 13C NMR (CDCl3, 75 MHz) δ: 154.0,
141.2, 137.7, 137.5, 137.4, 128.6, 128.5, 128.0, 127.8,
127.6, 127.4, 113.3, 103.3, 103.1, 71.3, 70.4; IR (KBr) ν:
3350, 3300, 2870, 2000—1700, 1600, 1587, 1499, 13＋76,
＋
1
1300—1200, 1109 cm ; MS (70 eV) m/z: 439 (M ).
Anal. calcd for C28H25NO4: C 76.54, H 5.69, N 3.19;
found C 76.44, H 5.63, N 3.25.
－1
1300—1200, 1109 cm ; MS (70 eV) m/z: 305 (M ).
A stirred solution of 2,5-G1-CO2CH3 (3.62 mmol) in
ethanol (100 mL) was heated approximately to 80 ℃.
Ammonia gas was bubbled through the mixture for 4 h,
Anal. calcd for C20H19NO2: C 78.69, H 6.23, N 4.59;
found C 78.54, H 6.75, N 4.69.
304
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Chin. J. Chem. 2010, 28, 303— 308

Synthesis of Two Aromatic Amines with Dendritic Structure
X-ray crystallography
this paper have been deposited with the Cambridge
Crystallographic Data Centre (CCDC 632789-632791).
Copies of the data can be obtained, free of charge, on
application to the Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, U.K. (Fax: 0044-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).
Data collection: SMART (Bruker, 2001); cell re-
finement: SAINT (Bruker, 2001); data reduction:
SAINT; program used to solve structure: SHELXS97
(Sheldrick, 1997); program used to refine structure:
SHELXL97 (Sheldrick, 1997); molecular graphics:
ORETP-3 (Farrugia, 1997) and PLATON (Spek, 2003);
software used to prepare material for publication:
SHELXL97.
Data were collected at 298 K on a Bruker Smart
CCD X-ray diffractometer, fitted with Mo Kα radiation
(0.71073 Å). The structure was solved by direct meth-
ods. Anisotropic displacement parameters were applied
to all non-hydrogen atoms in full-matrix least-squares
refinements based on F2. The hydrogen atoms were set
in calculated positions and refined as riding atoms with
a common fixed isotropic thermal parameter. All crys-
tals of 3,4,5-G1-COOCH3, 2,5-G1-COOCH3 and 2,6-G1-
COOCH3 suitable for structural determination by using
XRD were grown in a mixed ethyl acetate/petroleum
ether (V∶V＝1∶2) solution. Crystallographic and re-
finement parameters are given in Table 1. Supplemen-
tary crystallographic data for the structures reported in
Table 1 X-ray crystal data for 3,4,5-G1-COOCH3, 2,6-G1-COOCH3 and 2,5-G1-COOCH3
3,4,5-G1-COOCH3
632789
2,6-G1-COOCH3
632790
2,5-G1-COOCH3
632791
CCDC number
Formula
C29H26O5
454.50
C22H20O4
348.38
C22H20O4
348.38
Formula weight
Crystal color
Crystal system
Crystal size/mm3
Space group
Radiation type
Wavelength/Å
a/Å
Colorless
Monoclinic
0.45× 0.30× 0.30
P21/n
Colorless
Triclinic
Colorless
Monoclinic
0.45× 0.38× 0.28
P21/c
0.40× 0.18× 0.13
P-1
Mo Kα
Mo Kα
Mo Kα
0.71073
0.71073
0.71073
11.005(2)
16.612(3)
13.350(2)
90
8.859(3)
21.083(5)
10.724(2)
7.8762(17)
90
b/Å
14.280(6)
15.827(6)
64.208(7)
81.443(7)
88.815(8)
1780.4(12)
4
c/Å
α/(°)
β/(°)
104.956(3)
90
93.595(4)
90
γ/(°)
Volume/Å3
2357.8(7)
4
1777.2(7)
4
Z
θ range for data collection/(°)
2.20— 26.29
1.280
2.07— 26.00
1.300
2.71— 28.32
1.302
－
3
D
calc/(Mg•m )
Absorption coefficient/mm－
0.087
0.087
0.089
1
F(000)
960
736
736
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
22192
9167
8613
4141 [R(int)＝ 0.0247]
4140/0/307
1.278
6197 [R(int)＝ 0.0299]
6197/0/469
1.063
3109 [R(int)＝ 0.0194]
3109/0/236
1.044
R1＝ 0.0492
wR2＝ 0.1580
R1＝ 0.0573
wR2＝ 0.1637
0.193
R1＝ 0.0730
wR2＝ 0.1733
R1＝ 0.0950
wR2＝ 0.1868
0.191
R1＝ 0.0510
wR2＝ 0.1609
R1＝ 0.0587
wR2＝ 0.1750
0.348
Final R indices [I＞ 2σ(I0)]
R indices (all data)
－
3
∆ρmax/(e•Å )
－
3
∆ρmin/(e•Å )
－
0.206
－
0.199
－ 0.287
Chin. J. Chem. 2010, 28, 303— 308
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Luo, Cheng & Xu
FULL PAPER
Results and discussion
Preparation of G1-COOCH3
The convergent dendrimer synthesis described by
Hawker and Fréchet is based on the reaction of two
equivalents of benzylic bromide and one equivalent of
the 3,5-dihydroxybenzyl alcohol monomer.14 The first
generation benzylic alcohol can also be easily prepared
in large amounts through a coupling reaction of two
equivalents of benzyl bromide to one equivalent of
methyl 3,5-dihydroxybenzoate. 3,4,5-G1-COOCH3, 2,5-
G1-COOCH3 and 2,6-G1-COOCH3 were prepared
(Scheme 1) successfully according to the paper.13 In
practice, the reaction is also Williamson reaction.13
Scheme 1 Preparation equation of G1-COOCH3
Figure 1 A view of the molecule of 3,4,5-G1-COOCH3, with
the atom-labeling scheme. Displacement ellipsoids are drawn at
the 50% probability level and H atoms are deleted.
Structure of G1-COOCH3
The molecular structures of the dendrons are shown
in Figures 1—3. The two planes of the substitutional
m-phenyl rings are oriented essentially orthogonally to
that of the central phenyl ring (ca. 84.6° and 108°, re-
spectively), and the angle is ca. 23° between the plane
of the substitutional p-phenyl ring and the plane of the
central phenyl ring (3,4,5-G1-COOCH3 is depicted in
Figure 1). Similarly, the planes of the substitutional
phenyl rings which are parallel with each other are ap-
proximately perpendicular (ca. 80.1°) to that of the cen-
tral phenyl ring (2,5-G1-COOCH3 is depicted in Figure
2). There are two different molecular structures in the
asymmetric unit of 2,6-G1-COOCH3, which are shown
in Figure 3. It shows that the plane of one substitutional
o-phenyl ring is approximately on the same plane with
the plane of the central phenyl ring (ca. 2.5°), between
which and the plane of the other substitutional o-phenyl
ring the angle is ca. 70.8° in molecular structure a.
Compared with molecular structure a, one substitutional
o-phenyl ring in molecular structure b is approximately
orthogonal to that of the central phenyl ring (ca. 93°),
between which and the other substitutional plane the
angle is ca. 52.8°.
Figure 2 A view of the molecule of 2,5-G1-COOCH3, with the
atom-labeling scheme. Displacement ellipsoids are drawn at the
50% probability level and H atoms are deleted.
From above, we know that these dendrons have very
great volumes, due to their dendritic structure features.
These bulky dendrons can be used as the fine ligands for
certain catalysts, such as Brookhart’s catalysts.15
Figure 3 Two views of the molecule of 2,6-G1-COOCH3, with
the atom-labeling scheme. Displacement ellipsoids are drawn at
the 50% probability level and H atoms are deleted.
306
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Chin. J. Chem. 2010, 28, 303— 308

Synthesis of Two Aromatic Amines with Dendritic Structure
Transformation process of COOMe to NH2
extraction with dichloromethane. The yield of
2,5-G1-CONH2 was higher than 95% of the theoretical
quantity. Moreover, only 4 h were needed to accomplish
the task.
An interesting thing was that the 2,6-G1-CONH2
could not be prepared in the same condition, which may
be due to the larger steric bulk described above.
Classical methods for the transformation of COOMe
to NH2 include the Hofmann16 and Curtius17 rearrange-
ment. We have concentrated on the former, and the nec-
essary amide intermediates G1-CONH2 were prepared
by reaction with ammonia. Many variations on the
original bromine/aqueous sodium hydroxide rearrange-
ment conditions have been reported. Of particular inter-
est is a method which used sodium hypochlorite in
methanol under mild conditions. In the present research,
this method worked well to give methyl carbamates
G1-NHCOOCH3, which were hydrolyzed in alkali to
liberate the amines G1-NH2; the procedure was opti-
mized so that the isolation step of the carbamates was
unnecessary.
Hofmann rearrangement
The classical method for this transformation in-
volves the use of an alkaline solution of bromine, which
is, however, unsatisfactory and unreliable.19 Numerous
modifications of this rearrangement have been reported
using a variety of oxidants and bases, such as iodine(III)
reagents [PhI(OCOCF3)2,20 PhI-HCO2H, PhI(OTs)OH
and PhI(OAc)2], lead tetraacetate,21 (NBS)-Hg(OAc)2,22
NBS-NaOMe,23 and NBS-DBU.24 Herein, we choose
sodium hypochlorite (NaOCl) as oxidant (Scheme 2),
because it is an inexpensive, convenient and safe alter-
native to the current employed oxidants.25
Ammonolysis
The present process involves a facile method to ex-
tremely pure G1-CONH2. To achieve this, powder G1-
COOCH3 is dissolved in glycol and treated with gaseous
ammonia in 80—100 ℃.
Eq. 1 takes place at as low as 1.01×105 Pa NH3
pressure. Depending on the different reaction time, the
specific conversions of 3,4,5-G1-CONH2 ranged from
47.2% to 76.4% (Figure 4). It was shown that the con-
version increased as the reaction time increased over the
period of 0—24 h, and, a moderate constant conversion
was kept from 24 to 48 h. The reaction rate and the se-
lectivity depended decisively on the use of glycol,
which acts in two ways: while catalyzing the am-
monolysis, it also serves as a very specific solvent in
which the starting benzoates as well as the intermediates
are soluble but the final product 3,4,5-G1-CONH2 is
insoluble.18 The 3,4,5-G1-CONH2 formed is extremely
pure and easy to be isolated by filtration.
Scheme 2 Preparation equation of G1-NH2
When NaOCl was added to a cold solution of car-
boxamide 3,4,5-G1-CONH2 in methanolic NaOH, the
solution became pale yellow gradually. The reaction
was checked after about 0.5 h thin-layer chromatogra-
phy (TLC), which revealed the complete disappearance
of the starting amide. Work up of the reaction afforded
methyl carbamate 3,4,5-G1-NHCO2CH3, which was
hydrolyzed in alkali to liberate the amines
3,4,5-G1-NH2.
Our best results were obtained by the addition of
NaOCl (9 equiv.) in one portion to a chilled (4 ℃),
stirred solution of the 3,4,5-G1-CONH2 (1 equiv.) and
NaOH (6 equiv.) in methanol. Upon dissolution of the
NaOCl, the reaction was stirred for 15 min, followed by
removal of the ice-water bath and warming to room
temperature. Completion of the reaction was evidenced
by TLC, and then another mixed solution (NaOH/
MeOH/H2O) was added to the former solution, which
was refluxed for 4 d, then concentrated, filtrated to af-
ford amine 3,4,5-G1-NH2 in 75.3% isolated yield.
2,5-G1-CONH2 was similarly converted to the corre-
sponding amine 2,5-G1-NH2 in better yield (86%).
The above reaction probably follows a path similar
to the classic Hofmann rearrangement. Under the highly
basic reaction conditions, OCl－ is the predominant
Figure 4 Dependence of 3,4,5-G1-CONH2 conversion on reac-
tion time.
Other than 3,4,5-G1-CONH2, 2,5-G1-CONH2 is
soluble in glycol. So we obtained 2,5-G1-CONH2 by
Chin. J. Chem. 2010, 28, 303— 308
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Luo, Cheng & Xu
FULL PAPER
form of chlorine, which reacts with the amide to form
N-chloroamide to undergo a rearrangement to the iso-
cyanate. In the presence of methanol, the isocyanate
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Two aromatic amines with dendritic structures were
successfully synthesised. The X-ray study of G1-
COOCH3 shows that the three dendrons have large but
proper volumes as the fine ligands of Brookhart's cata-
lyst. The amides prepared by ammonolysis of G1-
COOCH3 in high yields have been readily converted to
the corresponding amines using sodium hypochlorite as
the oxidant. Further studies are in progress in our group.
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Chin. J. Chem. 2010, 28, 303— 308