First synthesis of ring-B C60-substituted derivatives of N,N-(tetrachlorophthaloyl)dehydroabietylamine

Article abstract of DOI:10.1016/j.tet.2012.10.071

A new route to ring-B C₆₀-substituted derivatives of N,N-(tetrachlorophthaloyl) dehydroabietylamine from dehydroabietylamine was reported. This advance was used to achieve the first synthesis of methanofullerene derivatives 14-17 and dehydroabietylamine derivatives 2-13. NMR spectroscopy unambiguously proved that the methanofullerene derivatives were C₁ symmetric structures with a 6,6-junction.

Full text of DOI:10.1016/j.tet.2012.10.071

Tetrahedron 69 (2013) 43e49
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
First synthesis of ring-B C60-substituted derivatives
of N,N-(tetrachlorophthaloyl)dehydroabietylamine
,
,
a
a
Zhi Zhou a b, Zhong-Xiang Lin a , Dan Liang , Jun-Qiang Hu
*
a College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, Jiangsu Province, PR China
b College of Chemistry and Materials Engineering, Kaili University, Kaili 556011, Guizhou Province, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2012
Received in revised form 14 October 2012
Accepted 23 October 2012
Available online 1 November 2012
A new route to ring-B C60-substituted derivatives of N,N-(tetrachlorophthaloyl) dehydroabietylamine from
dehydroabietylamine was reported. This advance was used to achieve the first synthesis of methanofullerene
derivatives 14e17 and dehydroabietylamine derivatives 2e13. NMR spectroscopy unambiguously proved
that the methanofullerene derivatives were C1 symmetric structures with a 6,6-junction.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Dehydroabietylamine
C60
Synthesis
Methanofullerene
C1 symmetric
1. Introduction
binding to an a-D
-mannose specific lectin (Con A). Li et al.19 pre-
pared steroid-C60 adduct, results of a preliminary assay show that it
can inhibit the reconstituted SR Ca2þ-ATPase in soybean phospho-
lipid liposomes and affect the survival of human lung adenocarci-
noma cancer A549 cells.
Dehydroabietylamine (Fig. 1), which possesses an aromatic
diterpene structure with three rings and three chiral carbon atoms,
is the main component of, and can be easily separated from, dis-
proportionated rosin amine. Dehydroabietylamine and its de-
rivatives have been utilised widely because of their biological
activities, such as antimicrobial and surface activating activities and
the separation of racemic mixtures.20e22
Since the discovery of C60, various fullerene derivatives have
been developed and their applications in the fields of material and
biomedical sciences have been studied extensively. One of the most
exciting fields of fullerene chemistry is related to their biological
activity.1e4 C60 derivatives exhibit a range of interesting biological
activities, including inhibiting HIV-1 protease,5e9 inducing DNA
photocleavage10e12 and scavenging free radicals.13,14 Among these
fullerene derivatives C60 hybrids containing bioactive groups have
received considerable attention in recent years. Many bioactive
molecules, such as amino acids, peptides, nucleotide, sugars and
steroids have been linked to C60. Hu et al.15,16 synthesized
b-alanine
16
and cystine C60 derivatives and discovered their protective effect on
hydrogen peroxide-induced apoptosis in rat pheochromocytoma
cells. Toniolo et al.5 obtained a C60-peptide derivative, which ex-
hibits remarkable chemotactic potency, comparable to that of the
parent pentapeptide, and biological activity of inhibiting HIV-1
protease. Sofou et al.17 synthesized proline-rich C60-peptide de-
rivative, which was found to be biologically active against sera from
MCTD and SLE patients. Kato et al.18 synthesized mannosyl [60]
fullerenols and found that they decrease the activity for both ag-
gregating erythrocytes and binding to RCA120 and increase the
12
11
17
1
C
2
14
A
B
3
19
7
6
18
H2N
Fig. 1. Dehydroabietylamine.
These results prompted us to search for new adducts of dehy-
droabietylaminewithC60 todevelopnewrosinaminederivativeswith
potential biological activity. In this paper, we report the synthesis of
ring-B C60-substituted derivatives of N,N-(tetrachlorophthaloyl)
dehydroabietylamine from dehydroabietylamine in 10 reaction steps.
* Corresponding author. Tel./fax: þ86 25 85427065; e-mail addresses:
zhou86zhi@163.com (Z. Zhou), linzhongxiang36@gmail.com (Z.-X. Lin).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.071

44
Z. Zhou et al. / Tetrahedron 69 (2013) 43e49
2. Results and discussion
converted to 12-methoxy derivative 10 in 89% yield by refluxing
with CH3I and K2CO3 in dry acetone. Subsequently, the reactions of
7, 8 and 10 with p-tosylhydrazide yielded the corresponding p-
tosylhydrazones 11, 12 and 13. We tried using EtOH as the solvent in
this reaction, as described in the literature.31 However, large
amounts of the starting solid material always remained, even after
The general procedure for the synthesis of ring-B substituted
derivatives of N,N-(tetrachlorophthaloyl)dehydroabietylamine 14,
15, 16 and 17 is shown in Scheme 1. Dehydroabietylamine, the
starting material, was prepared as described in the literature.23
O
R
(a)
(c)
X
(d)
O
O
O
N
N
H2N
N
Cl
Cl
O
Cl
Cl
O
Cl
Cl
O
2
1
3
Cl
Cl
Cl
Cl
Cl
Cl
4 R = AcO, X = H
5 R = H, X = NO2
(b)
6 R = NO2, X = H
R
R
R
(e)
(h)
(i)
NNHTs
O
O
O
O
N
N
N
Cl
Cl
Cl
Cl
O
O
Cl
Cl
O
Cl
Cl
Cl
Cl
Cl
Cl
14 R = NO2; 15 R = OMe
16 R = AcO; 17 R = OH
(j)
11 R = NO2
12 R = AcO; 13 R = OMe
7 R = NO2
8 R = AcO; 9 R = OH; 10 R = OMe
(g)
(f)
Scheme 1. Reagents, conditions and yields: (a) TCPA, acetic acid, N2,130 ꢀC, 2.5 h, 73%; (b) claycop, Ac2O, CH2Cl2, 25 ꢀC, 2 h, 65% (6:5¼3:2); (c) AcCl, AlCl3, CS2, N2, reflux, 5 h, 77%; (d) 65%
m-CPBA(2 equiv), PTSA(cat., 0.083 equiv), CH2Cl2, rt, 48 h, 71%; (e)65% t-BuOOH (8equiv), CrO3 (0.05 equiv), pyridine (0.1equiv), CH2Cl2, rt, 25 h, 38% for 7, 66% for 8; (f) concd HCl, CHCl3/
MeOH (1:2), N2, reflux,1.5 h, 79%; (g) CH3I, K2CO3, dryacetone, N2, reflux, 5 h, 89%; (h) TsNHNH2 (1.68 equiv), PTSA (cat., 0.09 equiv), benzene/EtOH (4:1), N2, reflux, 8 h, 82% for 11, 77% for
12 and 85% for 13; (i) NaOMe, pyridine, 20 min, rt; then C60 in chlorobenzene, N2, 70 ꢀC, 24 h, 37% for 14, 40% for 15, 33% for 16; (j) concd HCl, CS2/MeOH(1:1), N2, reflux, 4 h, 91%.
Dehydroabietylamine reacted with tetrachlorophthalic anhy-
dride (TCPA, an amino protecting group) to give imide 2 in 73%
yield. Imide 2 was transformed into 3 in 77% yield by FriedeleCrafts
acetylation, followed by BaeyereVilliger oxidation with m-chlor-
operbenzoic acid (m-CPBA) to generate 4.
Imide 2 was mononitrated with clay-supported copper(II) nitrate
(claycop)24 in CH2Cl2 to give a mixture (3:2) of 12-nitro-N,N-(tet-
rachlorophthaloyl)dehydroabietylamine 6 and 14-nitro-N,N-(tetra-
chlorophthaloyl)dehydroabietylamine 5 in 65% yield. The product
ratio of 6 to 5 was determined by 1H NMR. As the chromatographic
properties of the two nitro-compounds 6 and 5 were very similar,
the mixture was C-7 benzylic oxidated without separation and then
purified by column chromatography to produce 7.
The conventional methods for C-7 benzylic oxidations involve the
use of very large excesses of chromium(VI) reagents, such as CrO3 and
Na2CrO4, in a mixed solvent of Ac2O/AcOH,25e29 which led to con-
siderable amounts of toxic effluents and afforded low yields (ap-
proximately 10e15%) in the C-7 benzylic oxidations of compounds 4
and 6 because of their poor solubility in Ac2O/AcOH. When 4 and 6
were treated with an excess of t-BuOOH (8 equiv) as an oxidant and
CrO3/pyridine mixture as a catalyst in CH2Cl2,30 the yields of com-
pounds 7 and 8 increased significantly (38% for 7, 66% for 8).
Ketoester 8 was hydrolysed by concd HCl in a mixed solvent of
CHCl3/CH3OH (1:2) to afford ketophenol 9, which was then
extending the reaction times. To address the poor yields, the con-
ditions were modified: a mixed benzene/ethanol (4:1) solvent was
used to improve the solubility of the starting material and p-tol-
uenesulphonic acid (PTSA) was added as a catalyst, giving p-
tosylhydrazones 11, 12 and 13 in good yields (82% for 11, 77% for 12
and 85% for 13).
Ring-B C60-substituted derivatives 14, 15 and 16 were prepared
by the following procedure.32 First, p-tosylhydrazones 11, 12 and 13
were reacted with NaOMe in anhydrous pyridine for 20 min at
room temperature. A solution of C60 in chlorobenzene was then
added, and the mixture was stirred for 24 h at 70 ꢀC. A mixture of
the monoadduct, higher adducts and unreacted C60 was obtained
and then purified by column chromatography to give the pure
monoadducts 14,15 and 16. Compound 16 was hydrolysed by concd
HCl in a mixed solvent of CS2/CH3OH (1:1) to afford 17.
In the reaction of C60 with p-tosylhydrazones, p-tosylhydrazones
were first base-induced decomposed to afford diazo compounds, af-
ter which two mechanisms in the thermal reaction of C60 with diazo
compounds are conceivable: (1) initial thermal decomposition of the
diazo compounds to form carbenes followed by their concerted ad-
dition to the double 6,6 bond of fullerene and (2) initial 1,3-dipolar
cycloaddition of diazo compounds to fullerene to form the cyclic
pyrazoline intermediate followed by nitrogen elimination from the
pyrazoline intermediate. Carbene additions produce only 6,6-closed

Z. Zhou et al. / Tetrahedron 69 (2013) 43e49
45
isomers33 (methanofullerenes), whereas the latter pathway can af-
ford a mixture of 5,6-open (fulleroid) and 6,6-closed isomers34e36
(the ratio depending on the structure of the diazo compound and
the reaction conditions). In most cases, 5,6-open isomers can be
rearranged into the more thermodynamically stable 6,6-closed iso-
mers by heating or photochemical isomerisation. In our experiment,
no traces of the 5,6-open isomer were found and the only isolated
product was the 6,6-closed isomer, even at a lower reaction temper-
ature (40 ꢀC) or in a shorter reaction time (3 h). Meanwhile the pyr-
azoline intermediate was never detected in the reaction products
(Table 1). Thus, the carbene mechanism is realised in this reaction.
II, 100e200 mesh). Chemical reactions were monitored by thin-
layer chromatography using precoated silica gel GF254 plates.
Melting points were determined on a XT-6 melting point apparatus
and were uncorrected. NMR spectra were recorded on a Bruker
AVANCE AV-500 or Bruker AVANCE AV-300 spectrometer with
resonance frequencies of 300 or 500 MHz for 1H NMR and 75 or
126 MHz for 13C NMR, respectively. The chemical shifts were
reported in
d (parts per million, TMS) and coupling constants in
Hertz. Infrared spectra were recorded as KBr pellets on a Nicolet
360 FT-IR spectrometer, and UVevis spectra were recorded on
a Shimadzu UV-2550 UVevis spectrometer. ESI mass spectra were
obtained on an Agilent 1100 Capillary LC/Micromass Q-TOF
micromass spectrometer. Matrix-assisted laser desorption ionisa-
tion time-of-flight (MALDI-TOF) mass spectra were obtained using
Table 1
Conditionsa and yield of 16
Run
Temp (ꢀC)
Time (h)
Yield of 16 (%)
a Bruker Daltonics Autoflex III mass spectrometer with a-cyano-4-
1
2
3
4
5
6
7
8
9
25
40
40
60
60
60
70
70
70
24
9
24
3
9
24
3
0 (0)b
hydroxycinnamic acid (CHCA) as a matrix in negative-ion reflector
mode. Microanalytical data were obtained on an Elementar Vario
EL III elemental analyser.
5 (89)b
19 (70)b
16 (75)b
31 (71)b
38 (62)b
15 (72)b
30 (56)b
33 (49)b
4.2. N,N-(Tetrachlorophthaloyl)dehydroabietylamine (2)
9
24
A mixture of tetrachlorophthalic anhydride (5 g, 17.5 mmol),
dehydroabietylamine (5 g, 17.5 mmol) and glacial acetic acid
(60 mL) was stirred at 130 ꢀC under nitrogen. After 2.5 h, the re-
action mixture was cooled to room temperature and then poured
into ice water (250 mL). The resulting precipitate was collected by
filtration, washed with distilled water and ethanol and then dried
in vacuo to give the crude product (8.35 g), which was purified by
column chromatography on silica gel (petroleum ether/toluene,
2:1) to yield 2 as a white solid (7.11 g, 73%), mp 220e221 ꢀC. IR (KBr)
nmax/cmꢁ1 2934, 2860, 1776, 1714, 1630, 1498, 1430, 1392, 1369,
1338, 1297, 1200, 1091, 1069, 879, 820, 736, 556, 476; 1H NMR
a
p-Tosylhydrazone, 2 equiv to C60; NaOMe, 2.08 equiv to C60; chlorobenzene.
b
Based on converted C60
.
The 13C NMR spectra of methanofullerenes 14,15,16 and 17, due to
the overlapping, exhibit only 44, 42, 44 and 46 resonance signals for
C60-sp2 carbons, respectively (out of a maximum of 58 sp2-carbon
resonances). The two peaks at d 77e86 ppm(83.77, 77.45 for 14, 85.09,
78.15 for 15, 84.62, 77.67 for 16 and 85.04, 78.05 for 17) were assigned
to the sp3-hybridisedbridgeheadcarbons onthecyclopropylmoiety.37
This pattern is unambiguously diagnostic for a C1 symmetric structure
with a 6,6-junction.37,38 The resonance signals at
d
17e56,
d 106e137
(500 MHz, CDCl3)
d
7.13 (d, J¼7.9 Hz, 1H, H-11), 6.96 (dd, J¼8.2,
164 ppm (C]O), together with the 1H NMR re-
1.5 Hz, 1H, H-12), 6.91 (s, 1H, H-14), 3.68 (d, J¼13.7 Hz, 1H, H-18),
3.55 (d, J¼13.7 Hz, 1H, H-18), 2.98e2.96 (m, 2H, H-7), 2.81 (septet,
and approximately
d
sults, indicated the presence of an N,N-(tetrachlorophthaloyl)dehy-
droabietylamine moiety. In the IR spectra, the two sharp peaks at
1719e1776 cmꢁ1 (1774,1719 for 14,1775,1719 for 15,1758,1719 for 16
and 1776, 1719 for 17) were attributed to the asymmetric and sym-
metric stretching vibration of the imide carbonyl (C]O) and the ab-
sorption peak at approximately 525 cmꢁ1 (525 for 14, 524 for 15, 525
for 16 and 526 for 17) was attributed to the fullerene skeleton. In the
UVevis spectra, the characteristic absorptions for the methanofuller-
enes were observed at approximately 430and 700 nm.32,39 Finally, the
structures of 14,15,16 and 17 as monoadducts were supported by the
matrix-assisted laser desorption/ionisation time-of-flight mass spec-
tra (MALDI-TOF MS), which display the expected peaks at m/z 1316.2,
1301.5, 1329.2 and 1287.2, respectively.
J¼6.9 Hz, 1H, H-15), 2.26 (br d, J¼12.5 Hz, 1H, H-1
b), 2.22e2.18 (m,
1H, H-6b), 1.86e1.79 (m, 1H, H-6a), 1.75e1.62 (m, 2H, H-2), 1.49 (dd,
J¼13.4, 1.2 Hz, 1H, H-5), 1.44e1.28 (m, 3H, H-1
a, H-3), 1.23 (s, 3H, H-
20), 1.21 (d, J¼7.0 Hz, 6H, H-16, H-17), 1.05 (s, 3H, H-19); 13C NMR
(126 MHz, CDCl3)
d 164.50 (2C]O, imide), 147.09 (C-9), 145.69 (C-
13), 140.07 (2C, ꢁN(CO)2C6Cl4), 134.86 (C-8), 129.58 (2C,
ꢁN(CO)2C6Cl4), 127.52 (2C, ꢁN(CO)2C6Cl4), 127.05 (C-14), 123.82 (C-
11), 123.78 (C-12), 49.89 (C-18), 45.39 (C-5), 39.53 (C-4), 38.09 (C-
1), 37.61 (C-10), 37.21 (C-3), 33.44 (C-15), 30.07(C-7), 25.81 (C-20),
23.96 (C-17), 23.94 (C-16), 19.45 (C-6), 19.06 (C-19),18.45 (C-2); TOF
MS (ESꢁ) m/z 524.3 ([M(35Cl4)ꢁ27]ꢁ), 526.2 ([M(35Cl3 37Cl)ꢁ27]ꢁ),
528.2 ([M(35Cl2 37Cl2)ꢁ27]ꢁ). Anal. Calcd for C28H29Cl4NO2 (553.3):
C, 60.78; H, 5.28; N, 2.53. Found: C, 60.37; H, 5.35; N, 2.48.
3. Conclusion
4.3. 12-Acetyl-N,N(tetrachlorophthaloyl)dehydroabietyl-
amine (3)
In conclusion, the first synthesis of ring-B 6,6-closed-C60-at-
tached derivatives of N,N-(tetrachlorophthaloyl) dehydroabietyl-
amine has been achieved from dehydroabietylamine, and the
assigned structures of these compounds were confirmed based on
the spectral data. Studies of the biological activities of these
dehydroabietylamine derivatives and methanofullerene derivatives
are currently underway in our laboratory.
AlCl3 (3.62 g, 27.1 mmol) and acetyl chloride (1.92 mL,
27.1 mmol) were added to a solution of compound 2 (5 g, 9.0 mmol)
in CS2 (60 mL). The mixture was stirred and heated at reflux for 5 h
under nitrogen. The reaction mixture was cooled to room tem-
perature and then poured into a mixture of crushed ice (70 g) and
concd HCl (20 mL), allowed to stir for 10 min, and extracted with
CH2Cl2 (2ꢂ30 mL). The combined organic extracts were washed
with saturated solutions of NaHCO3 (2ꢂ40 mL) and brine
(2ꢂ40 mL), dried over anhydrous MgSO4, and filtered. After the
evaporation of the solvent under reduced pressure, the residue was
purified by column chromatography on silica gel (cyclohexane/
chloroform, 1:10) to yield 3 as a white solid (4.14 g, 77%), mp
230e231 ꢀC. IR (KBr) nmax/cmꢁ1 2926, 2858, 1778, 1716, 1681, 1552,
1431, 1394, 1369, 1344, 1262, 1198, 1092, 974, 885, 736, 560, 481; 1H
4. Experimental
4.1. General
All chemicals and solvents were obtained from commercial
sources and used as received or dried according to standard pro-
cedures. Column chromatography was performed on silica gel (ZCX

46
Z. Zhou et al. / Tetrahedron 69 (2013) 43e49
NMR (300 MHz, CDCl3)
d
7.37 (s, 1H, H-11), 7.09 (s, 1H, H-14), 3.70
clay-supported copper(II) nitrate (claycop) as a light-blue powder
(58 g).24
(d, J¼13.7 Hz, 1H, H-18), 3.57 (d, J¼13.7 Hz, 1H, H-18), 3.47 (septet,
J¼7.0 Hz, 1H, H-15), 3.05e2.95 (m, 2H, H-7), 2.53 (s, 3H, eCOCH3),
Compound 2 (5.54 g, 10.0 mmol) was added to a suspension of
claycop (4.80 g) in a mixture of CH2Cl2 (30 mL) and acetic anhydride
(15 mL) at 25 ꢀC. The reaction mixture was stirred at 25 ꢀC for 2 h
and then filtered. The filter cake was washed with CH2Cl2 (100 mL).
The combined organic portions were washed with water, dried over
anhydrous Na2SO4, and filtered. After the removal of the solvent
under reduced pressure, the residue was separated by column
chromatography on silica gel (petroleum ether/toluene, 1:1) to give
a mixture of 6 and 5 (3:2, 3.87 g, 65%).
2.29 (br d, J¼12.8 Hz, 1H, H-1
b), 2.27e2.22 (m, 1H, H-6b), 1.90e1.79
(m, 1H, H-6
a
), 1.79e1.66 (m, 2H, H-2), 1.54 (d, J¼13.5 Hz, 1H, H-5),
1.41e1.30 (m, 3H, H-1
a
, H-3), 1.25 (s, 3H, H-20), 1.23 (d, J¼6.7 Hz,
3H, H-17), 1.20 (d, J¼6.7 Hz, 3H, H-16), 1.08 (s, 3H, H-19); 13C NMR
(75 MHz, CDCl3)
d 203.19 (eCOCH3), 164.51 (2C]O, imide), 146.67
(C-9), 144.89 (C-12), 140.12 (2C, eN(CO)2C6Cl4), 138.90 (C-13),
136.29 (C-8), 129.60 (2C, eN(CO)2C6Cl4), 127.47 (2C, eN(CO)2C6Cl4),
127.12 (C-14), 123.96 (C-11), 49.75 (C-18), 45.23 (C-5), 39.48 (C-4),
37.97 (C-1), 37.54 (C-10), 37.03 (C-3), 30.45 (C-15), 30.03 (C-7),
28.68 (eCOCH3), 25.79 (C-20), 24.18 (C-17), 24.03 (C-16), 19.21 (C-
6), 19.05 (C-19), 18.31 (C-2); TOF MS (ESþ) m/z 594.1 ([M(35Cl4)þ
H]þ), 596.1 ([M(35Cl3 37Cl)þH]þ), 598.1 ([M(35Cl2 37Cl2)þH]þ), 600.1
([M(35Cl37Cl3)þH]þ). Anal. Calcd for C30H31Cl4NO3 (595.4): C, 60.52;
H, 5.25; N, 2.35. Found: C, 60.15; H, 5.29; N, 2.30.
4.6. Preparation of compounds 7 and 8
To a suspension of CrO3 (45 mg, 0.45 mmol, 0.05 equiv) in
CH2Cl2 (90 mL) were added 65% t-BuOOH (11.6 mL, 72.3 mmol,
8 equiv) and pyridine (0.073 mL, 0.904 mmol, 0.1 equiv). The
mixture was stirred for 3 min at room temperature. Next, com-
pound 4 or a mixture of compounds 6 and 5 (9.035 mmol) was
added. After 25 h of stirring at room temperature, the reaction
mixture was concentrated to approximately 15 mL in vacuo at 30 ꢀC
and then poured into methanol (60 mL). The precipitate formed
was collected by filtration and washed with methanol to give the
crude product, which was purified by column chromatography on
silica gel to afford compound 8 or 7.
4.4. 12-Acetoxy-N,N-(tetrachlorophthaloyl)dehydroabietyl-
amine (4)
Under vigorous stirring at 0 ꢀC, 65% m-chloroperbenzoic acid
(4.46 g, 16.8 mmol, 2 equiv) and p-toluenesulphonic acid hydrate
(120.1 mg, 0.697 mmol, 0.083 equiv) were carefully added to a -
solution of 3 (5 g, 8.4 mmol) in CH2Cl2 (60 mL). The mixture was
stirred at room temperature for 48 h and then filtered. The filter
cake was washed with CH2Cl2 (20 mL). The filtrate was evaporated
under reduced pressure, and the solid residue was dissolved in ethyl
acetate (100 mL). The resulting solution was washed successively
with saturated solutions of Na2S2O3 (2ꢂ30 mL), NaHCO3 (2ꢂ30 mL)
and brine (2ꢂ30 mL), dried over anhydrous MgSO4 and filtered.
After the removal of the solvent under reduced pressure, the residue
was purified by column chromatography on silica gel (chloroform)
to afford 4 as a white solid (3.64 g, 71%), mp 220e221 ꢀC. IR (KBr)
nmax/cmꢁ1 2933, 2866,1757,1712,1496,1433,1395,1369,1343,1206,
1163, 1091, 1040, 1014, 908, 883, 785, 735, 676, 622, 579, 502, 469;
4.6.1. 12-Nitro-7-oxo-N,N-(tetrachlorophthaloyl)dehydroabietyl-
amine (7). The crude product was purified by column chromatog-
raphy on silica gel (toluene) to afford 7 as a white solid (2.11 g, 38%),
mp 168e170 ꢀC. IR (KBr) nmax/cmꢁ1 2966, 2932, 2870, 1780, 1722,
1691, 1611, 1526, 1461, 1434, 1368, 1340, 1294, 1251, 1196, 1093, 888,
815, 738, 628, 580, 499; 1H NMR (500 MHz, CDCl3)
d 8.12 (s, 1H, H-
11), 7.55 (s, 1H, H-14), 3.59 (d, J¼14.0 Hz, 1H, H-18), 3.55 (d,
J¼14.0 Hz, 1H, H-18), 3.30e3.22 (m, 1H, H-15), 3.19 (dd, J¼18.3,
3.7 Hz, 1H, H-6
J¼12.5 Hz, 1H, H-1
(m, 2H, H-2), 1.59e1.50 (m, 2H, H-1
1.32 (d, J¼7.0 Hz, 3H, H-17), 1.31 (s, 3H, H-20), 1.28 (d, J¼7.0 Hz, 3H,
H-16), 1.14 (s, 3H, H-19); 13C NMR (126 MHz, CDCl3)
196.85 (C]O,
b
), 2.79 (dd, J¼18.3, 14.0 Hz, 1H, H-6
a), 2.28 (br d,
), 1.96 (dd, J¼14.0, 3.7 Hz, 1H, H-5), 1.79e1.69
b
1H NMR (500 MHz, CDCl3)
d
6.95 (s, 1H, H-14), 6.77 (s, 1H, H-11),
a
, H-3), 1.43e1.34 (m, 1H, H-3),
3.70 (d, J¼13.7 Hz, 1H, H-18), 3.50 (d, J¼13.7 Hz, 1H, H-18),
2.99e2.92 (m, 2H, H-7), 2.89 (septet, J¼6.9 Hz,1H, H-15), 2.28 (s, 3H,
d
CH3COOe), 2.25e2.17 (m,1H, H-6
b
), 2.13 (br d, J¼12.2 Hz,1H, H-1
b),
C-7), 164.44 (2C]O, imide), 153.94 (C-12), 152.94 (C-9), 140.32 (C-
8), 140.02 (2C, eN(CO)2C6Cl4), 133.13 (C-13), 129.79 (2C,
eN(CO)2C6Cl4), 127.43 (C-14), 127.38 (2C, eN(CO)2C6Cl4), 118.87 (C-
11), 49.24 (C-18), 44.76 (C-5), 39.21 (C-4), 38.11 (C-10), 37.12 (C-1),
36.61 (C-3), 36.25 (C-6), 28.47 (C-15), 24.10 (C-20), 23.49 (C-17),
23.34 (C-16), 18.86 (C-19), 17.75 (C-2); TOF MS (ESþ) m/z 611.1
([M(35Cl4)þH]þ), 613.1 ([M(35Cl337Cl)þH]þ), 615.1 ([M(35Cl2 37Cl2)þ
H]þ), 617.1 ([M(35Cl37Cl3)þH]þ), 619.1 ([M(37Cl4)þH]þ). Anal. Calcd
for C28H26Cl4N2O5 (612.3): C, 54.92; H, 4.28; N, 4.57. Found: C,
54.28; H, 4.24; N, 4.44.
1.86e1.75 (m, 1H, H-6
0.9 Hz,1H, H-5), 1.39e1.25 (m, 3H, H-1
(d, J¼6.7 Hz, 3H, H-17), 1.15 (d, J¼6.7 Hz, 3H, H-16), 1.04 (s, 3H, H-
19); 13C NMR (75 MHz, CDCl3)
170.00 (CH3COOe), 164.52 (2C]O,
a
), 1.70e1.60 (m, 2H, H-2), 1.50 (dd, J¼13.4,
a, H-3), 1.22 (s, 3H, H-20),1.18
d
imide), 148.21 (C-12), 146.00 (C-9), 140.06 (2C, eN(CO)2C6Cl4),
136.84 (C-13), 133.03 (C-8), 129.58 (2C, eN(CO)2C6Cl4), 127.48 (2C,
eN(CO)2C6Cl4), 127.12 (C-14), 117.47 (C-11), 49.59 (C-18), 44.54 (C-
5), 39.49 (C-4), 37.93 (C-1), 37.54 (C-10), 37.10 (C-3), 29.43 (C-7),
27.11 (C-15), 25.71 (C-20), 23.01 (C-17), 22.92 (C-16), 20.93
(CH3COOe), 19.32 (C-6), 19.08 (C-19), 18.29 (C-2); TOF MS (ESþ) m/z
627.2 ([Mþ(35Cl4)þH2O]), 629.2 ([Mþ(35Cl337Cl)þH2O]), 631.2
([Mþ(35Cl237Cl2)þH2O]), 633.2 ([Mþ(35Cl37Cl3)þH2O]). Anal. Calcd
for C30H31Cl4NO4 (611.4): C, 58.94; H, 5.11; N, 2.29. Found: C, 58.42;
H, 4.98; N, 2.20.
4.6.2. 12-Acetoxy-7-oxo-N,N-(tetrachlorophthaloyl)dehydroabietyl-
amine (8). The crude product was purified by column chromatog-
raphy on silica gel (chloroform/acetone, 20:0.3) to afford 8 as
a white solid (3.70 g, 66%), mp 160e162 ꢀC. IR (KBr) nmax/cmꢁ1
2962, 2927, 2871, 1756, 1716, 1680, 1608, 1562, 1433, 1404, 1374,
1335, 1299, 1267, 1201, 1165, 1120, 1093, 1039, 1016, 932, 909, 865,
4.5. 12-Nitro-N,N-(tetrachlorophthaloyl)dehydroabietyl-
amine (6) and 14-nitro-N,N-(tetrachlorophthaloyl)dehy-
droabietylamine (5)
786, 759, 630, 587, 502; 1H NMR (500 MHz, CDCl3)
14), 6.95 (s, 1H, H-11), 3.58 (s, 2H, H-18), 3.15 (dd, J¼18.2, 3.5 Hz, 1H,
H-6
), 3.00 (septet, J¼6.7 Hz, 1H, H-15), 2.75 (dd, J¼18.2, 13.9 Hz,
1H, H-6 ),
), 2.34 (s, 3H, CH3COOe), 2.21 (br d, J¼12.8 Hz, 1H, H-1
1.99 (dd, J¼13.9, 3.5 Hz, 1H, H-5), 1.75e1.68 (m, 2H, H-2), 1.58e1.50
(m, 2H, H-1 , H-3), 1.43e1.35 (m, 1H, H-3), 1.29 (s, 3H, H-20), 1.25
(d, J¼7.0 Hz, 3H, H-17), 1.21 (d, J¼6.7 Hz, 3H, H-16), 1.14 (s, 3H, H-
19); 13C NMR (75 MHz, CDCl3)
197.52 (C]O, C-7), 169.19
d 8.01 (s, 1H, H-
b
Montmorillonite clay (K10, 30 g) was added to a solution of
copper(II) nitrate trihydrate (28 g) in acetone (375 mL) with vig-
orous stirring. The resulting suspension was placed on a rotary
evaporator, and the solvent was removed under reduced pressure
on a water bath at 50 ꢀC. After 30 min, the dry solid crust adhering
to the walls of the flask was flaked off and coarsely crushed with
a spatula. Evaporation continued for another 30 min to produce
a
b
a
d
(CH3COOe), 164.42 (2C]O, imide), 154.47 (C-12), 152.51 (C-9),
140.15 (2C, eN(CO)2C6Cl4), 138.59 (C-8), 129.69 (2C, eN(CO)2C6Cl4),

Z. Zhou et al. / Tetrahedron 69 (2013) 43e49
47
129.02 (C-13), 127.44 (2C, eN(CO)2C6Cl4), 126.72 (C-14), 117.43 (C-
11), 49.26 (C-18), 44.60 (C-5), 39.19 (C-4), 37.87 (C-10), 37.10 (C-1),
36.78 (C-3), 36.20 (C-6), 27.30 (C-15), 24.12 (C-20), 22.77 (C-17),
22.69 (C-16), 20.94 (CH3COOe), 18.85 (C-19), 17.85 (C-2); TOF MS
(ESþ) m/z 624.1 ([M(35Cl4)þH]þ), 626.1 ([M(35Cl337Cl)þH]þ), 628.1
([M(35Cl2 37Cl2)þH]þ), 630.1 ([M(35Cl37Cl3)þH]þ), 632.1 ([M(37Cl4)þ
H]þ). Anal. Calcd for C30H29Cl4NO5 (625.4): C, 57.62; H, 4.67; N, 2.24.
Found: C, 57.34; H, 4.66; N, 2.06.
135.48 (C-8), 129.67 (2C, eN(CO)2C6Cl4), 127.44 (2C, eN(CO)2C6Cl4),
125.90 (C-14), 123.99 (C-13), 104.11(C-11), 55.41 (CH3Oe), 49.85
(C-18), 45.84 (C-5), 39.20 (C-4), 38.27 (C-10), 37.32 (C-1), 36.84 (C-
3), 36.14 (C-6), 26.56 (C-15), 23.99 (C-20), 22.50 (C-17), 22.33 (C-
16), 18.70 (C-19), 17.99 (C-2); TOF MS (ESþ) m/z 596.1 ([M(35Cl4)þ
H]þ), 598.1 ([M(35Cl3 37Cl)þH]þ), 600.1 ([M(35Cl2 37Cl2)þH]þ), 602.1
([M(35Cl37Cl3)þH]þ), 604.1 ([M(37Cl4)þH]þ). Anal. Calcd for
C29H29Cl4NO4 (597.4): C, 58.31; H, 4.89; N, 2.34. Found: C, 57.26; H,
4.95; N, 2.28.
4.7. 12-Hydroxy-7-oxo-N,N-(tetrachlorophthaloyl)dehy-
droabietylamine (9)
4.9. Preparation of compounds 11e13
Concd HCl (10 mL) was added to a solution of compound 8 (5 g,
8.0 mmol) in a mixture of CHCl3 (30 mL) and MeOH (60 mL). The
reaction mixture was stirred and heated at reflux for 1.5 h under
nitrogen, concentrated to approximately 40 mL in vacuo at 35 ꢀC and
cooled. The resulting precipitate was collected by filtration, washed
with absolute methanol (10 mL), and dried in vacuo. The crude
product was purified by column chromatography on silica gel
(chloroform/ethyl acetate, 20:1) to give 9 as a white solid (3.70 g,
79%), mp 292e294 ꢀC. IR (KBr) nmax/cmꢁ1 3414, 2936, 2867, 1778,
1718,1652,1596,1571,1501,1459,1434,1371,1342,1302,1269,1199,
1175,1094,1041, 977, 915, 890, 869, 739, 662, 632, 574, 534, 497, 428;
Compound 7, 8 or 10 (5.29 mmol) was dissolved in a mixture of
benzene (120 mL) and ethanol (30 mL). Next, p-toluenesulphonyl
hydrazide (1.65 g, 8.86 mmol, 1.68 equiv) and p-toluenesulphonic
acid (82 mg, 0.48 mmol, 0.09 equiv) were added successively. The
reaction mixture was stirred and refluxed for 8 h under nitrogen,
concentrated to approximately 60 mL under reduced pressure and
cooled in an ice bath. The resulting precipitate was collected by
filtration and washed with ethanol to give the crude product, which
was purified by column chromatography on silica gel to afford 11,12
or 13.
1H NMR (500 MHz, CDCl3/DMSO-d6)
H-11), 3.52 (d, J¼14.1 Hz,1H, H-18), 3.30 (d, J¼14.1 Hz,1H, H-18), 3.13
(septet, J¼7.0 Hz, 1H, H-15), 2.95 (dd, J¼17.8, 3.4 Hz, 1H, H-6 ), 2.57
(dd, J¼17.8, 13.8 Hz, 1H, H-6 ), 2.05 (br d, J¼12.0 Hz, 1H, H-1 ), 1.92
(dd, J¼13.7, 3.4 Hz, 1H, H-5), 1.71e1.57 (m, 2H, H-2), 1.50e1.30 (m,
d
7.66 (s, 1H, H-14), 6.75 (s, 1H,
4.9.1. 12-Nitro-N,N(tetrachlorophthaloyl)dehydroabietylamine p-to-
sylhydrazone (11). The crude product was purified by column
chromatography on silica gel (toluene/ethyl acetate, 20:0.4) to af-
b
b
a
ford 11 as a white solid (3.40 g, 82%), mp 220e221 ꢀC. IR (KBr) nmax
/
cmꢁ1 3258, 2931, 2859, 1779, 1719, 1627, 1597, 1559, 1519, 1454,
1434, 1393, 1367, 1341, 1298, 1201, 1165, 1091, 1039, 930, 814, 738,
3H, H-1
a
, H-3), 1.17 (s, 3H, H-20),1.16 (d, J¼6.9 Hz, 3H, H-17), 1.13 (d,
J¼6.9 Hz, 3H, H-16), 1.05 (s, 3H, H-19); 13C NMR (126 MHz, CDCl3/
711, 673, 578, 548, 500, 468; 1H NMR (500 MHz, CDCl3)
d 8.26 (s,1H,
DMSO-d6)
d
196.06 (C]O, C-7),163.48 (2C]O, imide),159.66 (C-12),
NH), 8.01 (d, J¼8.4 Hz, 2H, o-HArSO2e), 7.97 (s, 1H, H-14), 7.48 (s,
1H, H-11), 7.36 (d, J¼8.2 Hz, 2H, m-HArSO2e), 3.63 (d, J¼14.1 Hz,1H,
H-18), 3.49 (d, J¼14.1 Hz, 1H, H-18), 3.34 (septet, J¼6.8 Hz, 1H, H-
154.76 (C-9), 138.94 (2C, eN(CO)2C6Cl4), 132.54 (C-8), 128.50 (2C,
eN(CO)2C6Cl4), 126.81 (2C, eN(CO)2C6Cl4), 125.23 (C-14), 122.17 (C-
13), 108.49 (C-11), 48.77 (C-18), 44.52 (C-5), 38.24 (C-4), 36.93 (C-
10), 36.28 (C-1), 35.93 (C-3), 35.22 (C-6), 25.72 (C-15), 23.15 (C-
20), 21.65 (C-17), 21.49 (C-16),17.93 (C-19),17.15 (C-2); TOF MS (ESþ)
m/z 582.1 ([M(35Cl4)þH]þ), 584.1 ([M(35Cl337Cl)þH]þ), 586.1
([M(35Cl2 37Cl2)þH]þ), 588.1 ([M(35Cl37Cl3)þH]þ), 590.1 ([M(37Cl4)þ
H]þ). Anal. Calcd for C28H27Cl4NO4 (583.3): C, 57.65; H, 4.67; N, 2.40.
Found: C, 57.35; H, 4.62; N, 2.18.
15), 3.22 (dd, J¼17.5, 4.1 Hz,1H, H-6
(dd, J¼17.1, 13.4 Hz, 1H, H-6
1.73e1.64 (m, 2H, H-2), 1.60e1.54 (m, 2H, H-1
b
), 2.45 (s, 3H, CH3ArSO2e), 2.41
),
, H-3), 1.45 (dd,
a
), 2.19 (br d, J¼12.5 Hz, 1H, H-1
b
a
J¼13.4, 4.1 Hz, 1H, H-5), 1.44e1.36 (m, 1H, H-3), 1.31 (d, J¼6.8 Hz,
3H, H-17), 1.23 (d, J¼7.0 Hz, 3H, H-16), 1.16 (s, 3H, H-20), 1.11 (s, 3H,
H-19); 13C NMR (126 MHz, CDCl3)
d 164.50 (2C]O, imide), 150.80
(C-12), 150.23 (C]N), 149.52 (C-9), 144.34 (p-ArSO2e), 140.32 (2C,
eN(CO)2C6Cl4),139.82 (C-8),135.34 (p-ArCH3),133.88 (C-13),129.74
(2C, eN(CO)2C6Cl4), 129.57 (2C, m-ArSO2e), 128.47 (2C, o-ArSO2e),
127.27 (2C, eN(CO)2C6Cl4), 124.64 (C-14), 118.79 (C-11), 48.99 (C-
18), 42.38 (C-5), 39.43 (C-4), 37.27 (C-10), 37.07 (C-1), 37.01 (C-3),
28.28 (C-15), 23.52 (C-20), 23.47 (C-6), 23.42 (C-16, C-17), 21.63
(CH3ArSO2e), 19.12 (C-19), 17.78 (C-2); TOF MS (ESþ) m/z 779.2
([M(35Cl4)þH]þ), 781.1 ([M(35Cl337Cl)þH]þ), 783.1([M(35Cl2 37Cl2)þ
H]þ), 785.2 ([M(35Cl37Cl3)þH]þ). Anal. Calcd for C35H34Cl4N4O6S
(780.5): C, 53.86; H, 4.39; N, 7.18. Found: C, 53.52; H, 4.29; N, 7.02.
4.8. 12-Methoxy-7-oxo-N,N-(tetrachlorophthaloyl)dehy-
droabietylamine (10)
A mixture of compound 9 (2 g, 3.43 mmol), CH3I (2.44 g,
17.15 mmol), K2CO3 (0.95 g, 6.86 mmol) and dry acetone (40 mL)
was stirred and heated at reflux for 5 h under nitrogen. After
evaporation of the solvent under reduced pressure, water (50 mL)
was added and extracted with CH2Cl2 (3ꢂ40 mL). The combined
organic extracts were washed with water (40 mL) and brine
(40 mL), dried over anhydrous MgSO4 and filtered. After the re-
moval of the solvent under reduced pressure, the residue was
column chromatographed on silica gel (chloroform/acetone,
20:0.3) to afford 10 as a white solid (1.82 g, 89%), mp 156e158 ꢀC. IR
(KBr) nmax/cmꢁ1 2932, 2866, 1779, 1722, 1671, 1599, 1561, 1494,
1460, 1436, 1370, 1338, 1274, 1255, 1196, 1172, 1124, 1093, 1068,
1043, 961, 917, 889, 850, 803, 738, 658, 629, 562, 496, 449; 1H NMR
4.9.2. 12-Acetoxy-N,N-(tetrachlorophthaloyl)dehydroabietylamine
p-tosylhydrazone (12). The crude product was purified by column
chromatography on silica gel (toluene/ethyl acetate, 20:1.2) to af-
ford 12 as a white solid (3.22 g, 77%), mp 180e181 ꢀC. IR (KBr) nmax
/
cmꢁ1 3235, 2927, 2868, 1759, 1719, 1622, 1599, 1490, 1433, 1371,
1333, 1297, 1201, 1163, 1122, 1085, 1034, 910, 809, 737, 665, 574, 549,
500, 470; 1H NMR (500 MHz, CDCl3)
d
8.03 (d, J¼8.2 Hz, 2H,
(500 MHz, CDCl3)
d
7.93 (s, 1H, H-14), 6.74 (s, 1H, H-11), 3.90 (s, 3H,
o-HArSO2e), 7.96 (s, 1H, NH), 7.85 (s, 1H, H-14), 7.35 (d, J¼7.9 Hz,
CH3Oe), 3.68 (d, J¼13.7 Hz, 1H, H-18), 3.51 (d, J¼13.5 Hz, 1H, H-18),
2H, m-HArSO2e), 6.76 (s, 1H, H-11), 3.67 (d, J¼14.0 Hz, 1H, H-18),
3.26 (septet, J¼7.0 Hz, 1H, H-15), 3.01 (dd, J¼17.9, 3.5 Hz, 1H, H-6
b
b
),
),
3.45 (d, J¼14.0 Hz,1H, H-18), 3.23 (dd, J¼17.2, 4.1 Hz,1H, H-6
b), 2.92
2.74 (dd, J¼17.9, 13.9 Hz, 1H, H-6 ), 2.31 (br d, J¼12.2 Hz, 1H, H-1
a
(septet, 6.9 Hz, 1H, H-15), 2.45 (s, 3H, CH3ArSO2e), 2.38 (dd, J¼17.4,
13.5 Hz, 1H, H-6
), 2.30 (s, 3H, CH3COOe), 2.10 (br d, J¼13.1 Hz, 1H,
H-1 ), 1.72e1.61 (m, 3H, H-2, H-1
2.02 (dd, J¼13.9, 3.5 Hz, 1H, H-5), 1.78e1.71 (m, 2H, H-2), 1.62e1.50
(m, 2H, H-1 , H-3), 1.48e1.38 (m, 1H, H-3), 1.31 (s, 3H, H-20), 1.24
(d, J¼7.0 Hz, 3H, H-17), 1.21 (d, J¼7.0 Hz, 3H, H-16), 1.13 (s, 3H, H-
19); 13C NMR (75 MHz, CDCl3)
197.22 (C]O, C-7), 164.38 (2C]O,
imide), 161.68 (C-12), 155.74 (C-9), 140.16 (2C, eN(CO)2C6Cl4),
a
a
b
a
), 1.57 (br d, J¼13.7 Hz, 1H, H-3),
1.49 (dd, J¼13.4, 4.0 Hz, 1H, H-5), 1.43e1.36 (m, 1H, H-3), 1.24 (d,
d
J¼7.0 Hz, 3H, H-17), 1.17 (d, J¼7.0 Hz, 3H, H-16), 1.15 (s, 3H, H-20),
1.11 (s, 3H, H-19); 13C NMR (75 MHz, CDCl3)
d 169.61 (CH3COOe),

48
Z. Zhou et al. / Tetrahedron 69 (2013) 43e49
164.51 (2C]O, imide), 152.95 (C-12), 150.11 (C]N), 149.63 (C-9),
143.95 (p-ArSO2e), 140.13 (2C, eN(CO)2C6Cl4), 137.68 (C-8), 135.53
(p-ArCH3), 129.66 (2C, eN(CO)2C6Cl4), 129.42 (2C, m-ArSO2e),
128.45 (2C, o-ArSO2e), 128.05 (C-13), 127.36 (2C, eN(CO)2C6Cl4),
124.08 (C-14), 116.71 (C-11), 48.94 (C-18), 41.92 (C-5), 39.46 (C-4),
37.20 (C-10), 37.07 (C-1, C-3), 27.29 (C-15), 23.64 (C-20), 23.56 (C-6),
22.83 (C-17), 22.63 (C-16), 21.58 (CH3ArSO2e), 20.92 (CH3COOe),
19.17 (C-19), 17.92 (C-2); TOF MS (ESþ) m/z 792.2 ([M(35Cl4)þH]þ),
794.2 ([M(35Cl337Cl)þH]þ), 796.2 ([M(35Cl2 37Cl2)þH]þ), 798.2
([M(35Cl37Cl3)þH]þ), 780.2 ([M(37Cl4)þH]þ). Anal. Calcd for
C37H37Cl4N3O6S (793.6): C, 56.00; H, 4.70; N, 5.29. Found: C, 55.60;
H, 4.76; N, 5.07.
J¼6.7 Hz, 3H, H-16); 13C NMR (126 MHz, CDCl3)
d 164.59 (2C]O,
imide), 151.89 (C-12), 149.44, 149.20 (C-9), 148.50, 147.04, 146.61,
145.66, 145.63, 145.40, 145.36, 144.97, 144.92, 144.90, 144.85,
144.82, 144.78, 144.75, 144.48, 144.45, 144.03, 143.97, 143.92,
143.75, 143.39, 143.30, 143.24, 143.17, 143.14, 143.06, 143.00, 142.90,
142.28, 142.17, 142.14, 142.11, 141.79, 141.41, 141.24, 141.21, 140.99,
140.48 (2C, eN(CO)2C6Cl4), 140.45, 139.50 (C-13), 138.61, 138.40,
138.22, 137.92, 137.75, 129.84 (2C, eN(CO)2C6Cl4 and C-8), 127.46
(2C, eN(CO)2C6Cl4 and C-14), 119.22 (C-11), 83.77 (C60-sp3), 77.45
(C60-sp3), 49.98 (C-18), 47.97 (C-5), 43.42 (C-7), 40.87 (C-4), 39.23
(C-1), 39.08 (C-10), 37.28 (C-3), 28.83 (C-15), 27.99 (C-6), 23.88
(C-17), 23.61 (C-16), 22.13 (C-20), 19.20 (C-19), 17.94 (C-2); MALDI-
TOF MS (matrix: CHCA, reflectron negative) m/z 1314.2
([M(35Cl4)]ꢁ), 1316.2 ([M(35Cl337Cl)]ꢁ), 1318.2 ([M(35Cl237Cl2)]ꢁ),
1320.2 ([M(35Cl37Cl3)]ꢁ). Anal. Calcd for C88H26Cl4N2O4 (1316.97): C,
80.26; H, 1.99; N, 2.13. Found: C, 79.88; H, 2.05; N, 1.98.
4.9.3. 12-Methoxy-N,N-(tetrachlorophthaloyl)dehydroabietylamine
p-tosylhydrazone (13). The crude product was purified by column
chromatography on silica gel (chloroform/ethyl acetate, 20:0.4) to
afford 13 as a white solid (3.45 g, 85%), mp 182e184 ꢀC. IR (KBr) nmax
/
cmꢁ1 3227, 2927, 2864, 1779, 1720, 1654, 1594, 1496, 1458, 1436,
1379, 1330, 1276, 1240, 1194, 1164, 1087, 1042, 954, 913, 848, 809,
4.10.2. Ring-B [6,6]-closed-C60-adduct of 12-methoxy-N,N-(tetra-
chlorophthaloyl)dehydroabietylamine (15). The residue was puri-
fied by column chromatography on silica gel, pre-eluted with CS2
to remove unreacted C60 (85.9 mg) and then with CS2/CHCl3
(10:0.5) to give 15 as a dark-brown solid (217.3 mg, 40%; or 57%
based on converted C60). IR (KBr) nmax/cmꢁ1 3426, 2922, 2853,
1775, 1719, 1623, 1563, 1545, 1494, 1460, 1425, 1367, 1325, 1263,
1047, 893, 737, 672, 553, 524, 474; UVevis (CHCl3) lmax (nm):
738, 698, 662, 623, 548, 501, 475; 1H NMR (300 MHz, CDCl3)
d 8.02
(d, J¼8.3 Hz, 2H, o-HArSO2e), 7.91 (s,1H, NH), 7.80 (s,1H, H-14), 7.32
(d, J¼8.1 Hz, 2H, m-HArSO2e), 6.60 (s,1H, H-11), 3.79 (s, 3H, CH3Oe),
3.62 (d, J¼14.0 Hz,1H, H-18), 3.50 (d, J¼14.0 Hz,1H, H-18), 3.27e3.11
(m, 2H, H-6
13.1 Hz,1H, H-6
b
, H-15), 2.42 (s, 3H, CH3ArSO2e), 2.40 (dd, J¼16.7,
a
), 2.20 (br d, J¼12.3 Hz,1H, H-1
b),1.78e1.64 (m, 2H,
H-2), 1.62e1.35 (m, 4H, H-1
a
, H-5, H-3), 1.22 (d, J¼6.9 Hz, 3H, H-17),
697.00, 492.50, 436.50; 1H NMR (500 MHz, CDCl3)
14), 7.01 (s, 1H, H-11), 3.93 (s, 3H, CH3Oe), 3.89 (d, J¼13.5 Hz, 1H,
H-18), 3.63 (dd, J¼14.1, 10.5 Hz, 1H, H-6 ), 3.59 (d, J¼13.7 Hz, 1H,
H-18), 3.43e3.35 (m, 2H, H-6
, H-15), 2.38 (br d, J¼10.1 Hz, 1H, H-
),
d 8.38 (s, 1H, H-
1.18 (d, J¼6.8 Hz, 3H, H-16), 1.14 (s, 3H, H-20), 1.12 (s, 3H, H-19); 13C
NMR (75 MHz, CDCl3)
d
164.44 (2C]O, imide),158.89 (C-12),154.26
b
(C-9), 150.64 (C]N), 143.80 (p-ArSO2e), 140.13 (2C, eN(CO)2C6Cl4),
135.53 (p-ArCH3), 134.91 (C-8), 129.61 (2C, eN(CO)2C6Cl4), 129.32
(2C, m-ArSO2e), 128.55 (2C, o-ArSO2e), 127.29 (2C, eN(CO)2C6Cl4),
123.46 (C-13), 122.18 (C-8), 103.98 (C-11), 55.25 (CH3Oe), 49.37 (C-
18), 43.09 (C-5), 39.45 (C-4), 37.43 (C-10), 37.24 (C-1), 37.16 (C-3),
26.52 (C-15), 23.62 (C-20, C-6), 22.44 (C-17), 22.40 (C-16), 21.56
(CH3ArSO2e), 19.03 (C-19), 18.02 (C-2); TOF MS (ESþ) m/z 764.2
([M(35Cl4)þH]þ), 766.2 ([M(35Cl337Cl)þH]þ), 768.2 ([M(35Cl2 37Cl2)þ
H]þ), 770.2 ([M(35Cl37Cl3)þH]þ), 772.2 ([M(37Cl4)þH]þ). Anal. Calcd
for C36H37Cl4N3O5S (765.6): C, 56.48; H, 4.87; N, 5.49. Found: C,
55.69; H, 4.92; N, 5.23.
a
1
b
), 2.01 (t, J¼9.5 Hz, 1H, H-5), 1.92e1.78 (m, 6H, H-20, H-2, H-1
a
1.62e1.49 (m, 2H, H-3), 1.31 (s, 3H, H-19), 1.25 (d, J¼6.7 Hz, 3H, H-
17), 1.24 (d, J¼6.7 Hz, 3H, H-16); 13C NMR (126 MHz, CDCl3)
d
164.52 (2C]O, imide), 156.08 (C-12), 151.44 (C-9), 150.77, 150.00,
148.21, 147.79, 146.03, 145.98, 145.28, 145.26, 145.21, 145.04, 145.01,
144.96, 144.89, 144.80, 144.78, 144.68, 144.65, 144.19, 144.17,
143.98, 143.88, 143.68, 143.26, 143.19, 143.16, 143.04, 142.84,
142.78, 142.23, 142.21, 142.15, 142.06, 141.90, 141.41, 141.12, 141.04,
140.84, 140.34 (2C, eN(CO)2C6Cl4), 140.22, 138.64, 138.51, 137.82,
137.78, 132.88 (C-13), 129.74 (2C, eN(CO)2C6Cl4), 127.52 (2C,
eN(CO)2C6Cl4), 126.28 (C-14), 124.00 (C-8), 106.31 (C-11), 85.09
(C60-sp3), 78.15 (C60-sp3), 55.42 (CH3Oe), 50.53 (C-18), 48.70 (C-5),
44.56 (C-7), 40.90 (C-4), 39.31 (C-10), 39.15 (C-1), 37.54 (C-3),
28.42 (C-6), 26.61 (C-15), 23.08 (C-17), 22.91 (C-16), 22.43 (C-20),
18.91 (C-19), 18.20 (C-2); MALDI-TOF MS (matrix: CHCA, reflectron
negative) m/z 1299.5 ([M(35Cl4)]ꢁ), 1301.5 ([M(35Cl337Cl)]ꢁ), 1303.6
([M(35Cl237Cl2)]ꢁ), 1305.5 ([M(35Cl37Cl3)]ꢁ). Anal. Calcd for
C89H29Cl4NO3 (1302.00): C, 82.10; H, 2.25; N,1.08. Found: C, 81.56; H,
2.22; N, 1.08.
4.10. Preparation of compounds 14 and 15
Compound 11 or 13 (0.834 mmol) was dissolved in dry pyridine
(10 mL) in a dried three-necked flask under nitrogen flow. Next,
NaOMe (46.9 mg, 0.867 mmol) was added and the mixture was
stirred for 20 min at room temperature. A solution of C60 (300 mg,
0.417 mmol) in dry chlorobenzene (80 mL) was added, and the
mixture was stirred at 70 ꢀC for 24 h. The reaction mixture was
cooled to room temperature, and the solvent was removed in
vacuo. The residue was purified by column chromatography on
silica gel to give the product 14 or 15.
4.11. Ring-B [6,6]-closed-C60-adduct of 12-acetoxy-N,N-(tetra-
chlorophthaloyl)dehydroabietylamine (16)
4.10.1. Ring-B [6,6]-closed-C60-adduct of 12-nitro-N,N-(tetrachlo-
rophthaloyl)dehydroabietylamine (14). The residue was purified by
column chromatography on silica gel, pre-eluted with CS2 to
remove unreacted C60 (91.4 mg) and then with CS2/CHCl3 (3:1) to
give 14 as a dark-brown solid (200.9 mg, 37%; or 53% based on
converted C60). IR (KBr) nmax/cmꢁ1 3445, 2922, 2856, 1774, 1719,
1647, 1558, 1514, 1459, 1427, 1365, 1336, 1286, 1189, 1069, 895, 738,
555, 525, 471; UVevis (CHCl3) lmax (nm): 693.00, 494.00, 433.50;
Compound 12 (2.205 g, 2.778 mmol) was dissolved in dry pyri-
dine (33 mL) in a dried three-necked flask under nitrogen flow. Next,
NaOMe (156.2 mg, 2.888 mmol) was added and the mixture was
stirred for 20 min at room temperature. A solution of C60 (1 g,
1.389 mmol) in dry chlorobenzene (260 mL) was added, and the
mixture was stirred at 70 ꢀC for 24 h. The reaction mixture was
cooled to room temperature, and the solvent was removed in vacuo.
The residue was purified by column chromatography on silica gel,
pre-eluted with CS2 to remove unreacted C60 (329.3 mg) and then
with CS2/CHCl3 (10:1) to give 16 as a dark-brown solid (602.8 mg,
33%; or 49% based on converted C60). IR (KBr) nmax/cmꢁ1 3426, 2921,
2853,1758, 1719, 1632, 1460, 1425, 1365, 1324, 1196, 1163, 1080, 906,
737, 557, 525, 478; UVevis (CHCl3) lmax (nm): 697.00, 494.50,
1H NMR (500 MHz, CDCl3)
3.82 (d, J¼13.9 Hz, 1H, H-18), 3.68e3.63 (m, 2H, H-18, H-6
3.57e3.51 (m, 2H, H-6 ), 1.92
, H-15), 2.39 (br d, J¼12.4 Hz, 1H, H-1
(dd, J¼10.5, 9.0 Hz, 1H, H-5), 1.89e1.78 (m, 5H, H-20, H-2),
1.78e1.70 (m, 1H, H-1
), 1.64 (br d, J¼13.1 Hz, 1H, H-3), 1.50e1.42
(m, 1H, H-3), 1.36 (d, J¼6.7 Hz, 3H, H-17), 1.34 (s, 3H, H-19), 1.33 (d,
d
8.65 (s, 1H, H-14), 7.84 (s, 1H, H-11),
),
b
a
b
a
437.00; 1H NMR (500 MHz, CDCl3)
d 8.47 (s, 1H, H-14), 7.11 (s, 1H, H-

Z. Zhou et al. / Tetrahedron 69 (2013) 43e49
49
11), 3.80 (d, J¼13.6 Hz, 1H, H-18), 3.66 (d, J¼13.6 Hz, 1H, H-18), 3.62
(dd, J¼14.0, 10.4 Hz, 1H, H-6 ), 3.50 (dd, J¼14.0, 8.7 Hz, 1H, H-6 ),
3.09 (septet, J¼6.7 Hz, 1H, H-15), 2.37 (s, 3H, CH3COOe), 2.28 (br d,
J¼11.9 Hz,1H, H-1 ),1.99 (t, J¼9.6 Hz,1H, H-5),1.88e1.79 (m, 5H, H-
20, H-2), 1.78e1.70 (m, 1H, H-1
), 1.60 (br d, J¼13.4 Hz, 1H, H-
1291.2 ([M(35Cl37Cl3)]ꢁ). Anal. Calcd for C88H27Cl4NO3 (1287.97): C,
82.06; H, 2.11; N, 1.09. Found: C, 81.88; H, 2.16; N, 1.10.
b
a
b
Acknowledgements
a
3),1.52e1.45 (m, 1H, H-3), 1.31 (s, 3H, H-19), 1.25 (d, J¼7.0 Hz, 3H, H-
The authors acknowledge financial support from the National
Natural Science Foundation of China (No. 30871989).
17), 1.24 (d, J¼7.0 Hz, 3H, H-16); 13C NMR (126 MHz, CDCl3)
d 169.68
(CH3COOe), 164.59 (2C]O, imide), 151.66 (C-12), 150.39, 149.83 (C-
9), 147.89, 147.43, 145.91, 145.33, 145.30, 145.26, 145.24, 145.15,
145.01,144.94,144.92,144.89,144.80,144.69,144.28,144.25,144.00,
143.95, 143.90, 143.70, 143.28, 143.21, 143.19, 143.10, 143.07, 143.05,
143.01, 142.87, 142.80, 142.25, 142.20, 142.14, 142.08, 141.84, 141.33,
141.21, 141.06, 140.86, 140.33 (2C, eN(CO)2C6Cl4), 140.24, 138.63,
138.47, 137.97, 137.83, 136.36 (C-13), 130.13 (C-8), 129.77 (2C,
eN(CO)2C6Cl4), 127.58 (2C, eN(CO)2C6Cl4), 126.70 (C-14), 117.77 (C-
11), 84.62 (C60-sp3), 77.67 (C60-sp3), 50.13 (C-18), 47.75 (C-5), 44.20
(C-7), 40.89 (C-4), 39.21 (C-10), 38.88 (C-1), 37.48 (C-3), 28.16 (C-6),
27.49 (C-15), 23.37 (C-17), 23.05 (C-16), 22.39 (C-20), 21.07
(CH3COOe), 19.09 (C-19), 18.09 (C-2); MALDI-TOF MS (matrix:
CHCA, reflectron negative) m/z 1327.2 ([M(35Cl4)]ꢁ), 1329.2
([M(35Cl337Cl)]ꢁ), 1331.2 ([M(35Cl2 37Cl2)]ꢁ), 1333.2 ([M(35Cl37Cl3)]ꢁ).
Anal. Calcd for C90H29Cl4NO4 (1330.01): C, 81.27; H, 2.20; N, 1.05.
Found: C, 81.35; H, 2.27; N, 1.02.
References and notes
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Methanol (50 mL) and concd HCl (20 mL) were added to a solu-
tion of compound 16 (300 mg, 0.226 mmol) in CS2 (50 mL). The
mixture was stirred and refluxed for 4 h under nitrogen. After the
removal of the solvent under reduced pressure, the residue was
transferred to a centrifuge tube as a suspension in methanol (40 mL).
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decanted. The dark-brown powder was washed with methanol
(2ꢂ40 mL) using the centrifuge method and dried in vacuo at 60 ꢀC
to give 17 (265.7 mg, 91%). IR (KBr) nmax/cmꢁ13437, 2921, 2853,1776,
1719, 1632, 1450, 1425, 1369, 1338, 1284, 1165, 1043, 738, 554, 526,
473; UVevis (CHCl3) lmax (nm): 696.00, 504.50, 431.00; 1H NMR
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(500 MHz, CDCl3)
J¼13.7 Hz, 1H, H-18), 3.62 (dd, J¼14.2, 10.4 Hz, 1H, H-6
J¼13.7 Hz,1H, H-18), 3.40 (dd, J¼14.0, 8.8 Hz,1H, H-6 ), 3.26 (septet,
J¼6.8 Hz,1H, H-15), 2.30 (br d, J¼12.4 Hz,1H, H-1 ),1.99 (dd, J¼10.2,
9.1 Hz, 1H, H-5), 1.86e1.71 (m, 6H, H-20, H-2, H-1 ), 1.60e1.49 (m,
d
8.37 (s, 1H, H-14), 6.92 (s, 1H, H-11), 3.88 (d,
b
), 3.59 (d,
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a
b
a
2H, H-3), 1.30 (s, 3H, H-19), 1.29 (d, J¼6.9 Hz, 3H, H-17), 1.28 (d,
J¼6.9 Hz, 3H, H-16); 13C NMR (126 MHz, CDCl3)
d 164.53 (2C]O,
imide), 152.15 (C-12), 151.79 (C-9), 150.71, 149.94, 148.15, 147.71,
145.99, 145.95, 145.31, 145.27, 145.22, 145.19, 145.02, 144.98, 144.94,
144.89,144.81,144.79,144.68,144.66,144.22,144.18,144.00,143.96,
143.89, 143.68, 143.27, 143.20, 143.16, 143.05, 143.02, 142.84, 142.79,
142.23, 142.21, 142.15, 142.13, 142.07, 141.90, 141.39, 141.15, 141.06,
140.84, 140.34 (2C, eN(CO)2C6Cl4), 140.21, 138.58, 138.45, 137.82,
137.78, 130.12 (C-13), 129.75 (2C, eN(CO)2C6Cl4), 127.51
(2C, eN(CO)2C6Cl4), 126.58 (C-14), 124.49 (C-8), 111.36 (C-11), 85.04
(C60-sp3), 78.05 (C60-sp3), 50.46 (C-18), 48.54 (C-5), 44.42 (C-7),
40.88 (C-4), 39.28 (C-10), 38.75 (C-1), 37.53 (C-3), 28.37 (C-6), 26.98
(C-15), 22.98(C-17), 22.81(C-16), 22.36 (C-20),18.93 (C-19),18.16 (C-
2); MALDI-TOF MS (matrix: CHCA, reflectron negative) m/z 1285.2
([M(35Cl4)]ꢁ), 1287.2 ([M(35Cl337Cl)]ꢁ), 1289.2 ([M(35Cl237Cl2)]ꢁ),
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