Bifunctionalisation of 1,4-naphthoquinone by the oxidative addition of an alkylamine and iodine

Article abstract of DOI:10.3184/174751912X13547276507240

Novel 2-iodo-3-(alkylamino) naphthalene-1,4-diones are formed in 33-70% yield by the reaction of alkylamine and 1, 4-naphthoquinone in the presence of iodine.

Full text of DOI:10.3184/174751912X13547276507240

34 RESEARCH PAPER
JANUARY, 34–37
JOURNAL OF CHEMICAL RESEARCH 2013
Bifunctionalisation of 1,4-naphthoquinone by the oxidative addition of an
alkylamine and iodine
Huan-Ming Huang, Yu-Jin Li*, Yin-Ping Dai, Wu-Bin Yu, Qin Ye and Jian-Rong Gao
State Key Laboratory Breeding Base of Green Chemistry-SynthesisTechnology, Zhejiang University ofTechnology, Hangzhou 310032,
P. R. China
Novel 2-iodo-3-(alkylamino) naphthalene-1,4-diones are formed in 33–70% yield by the reaction of alkylamine and 1,
4-naphthoquinone in the presence of iodine.
Keywords: 2-iodo-3-(alkylamino) naphthalene-1,4-dione, alkylamine, 1, 4-naphthoquinone, iodine
Some natural products which contain alkylamino derivatives
of naphthoquinones show a wide biological activity as potent
antitumour,1–3 antimalarial4,5 and antibacterial6–9 agents. This
biological activity has made the synthesis of these compounds
attractive. Two major synthetic strategies have been developed:
one which involves the nucleophilic displacement of the
halo-quinone,4,5,10 while the other involves a direct 1,4-addition
of amines to the quinones. Unfortunately, many of these proce-
dures have disadvantages involving strongly acidic conditions
side-reactions, low yields and complex methodology.
Recently, the metal (ion)-free catalysis of organic reaction
has received increasing attention.11–17 The use of molecular
iodine has become popular because of its high tolerance to air
and moisture, low-cost, ready availability, and high catalytic
activity.18–23 For instance, Karimi24 reported a mild and highly
efficient method for the silylation of alcohols using hexameth-
yldisilazane catalysed by iodine under nearly neutral reaction
conditions. Wang25 reported a new decarboxylative cyclisation
to construct pyridines derivatives by a-amino acids and
aldehyde under molecular iodine conditions. Recently, the
preparation of 1,2-diaryldiketones by oxidative cleavage of
1,3-diaryldiketones catalysed by iodine has been reported.26
A one-pot synthesis of flavanone and highly substituted
pyrimidine derivatives via multi component Mannich reaction
catalysed by iodine has also been reported.27
Liu has recently disclosed an iodine-promoted protocol for
the synthesis of 2-amino-1,4-naphthoquinones under ultra-
sonic irradiation at room temperature.28 Unexpectedly when
we tried to repeat the reaction of 1,4-naphthoquinone and a
primary amine in the presence of iodine, the unpublished prod-
uct of iodine addition was obtained (Scheme 1). In this paper,
the synthesis of 2-iodo-3-(alkylamino)naphthalene-1,4- dione
is now reported. As new compounds, besides their potential
bioactivity, they can become very useful intermediates for the
further preparation of derivatives of 2-amino-1,4-naphthoqui-
none.29
Our initial investigations were focused on the preparation of
2-(benzylamino)naphthalene-1,4-dione (4a) from the reaction
of 1,4-naphthoquinone (1a) and benzylamine (2a). The unex-
pected iodine addition product 2-iodo-3-(benzylamino)-
naphthalene-1,4-dione (3a) was obtained in 15% together
with 2-(benzylamino)naphthalene-1,4-dione (4a) in 27.7%
(Table 1, entry 1). To explore this reaction, the conditions were
optimised to improve the yield of 3a. As shown in Table 1, the
solvent of this reaction was studied with 1,4-naphthoquinone
and benzylamine as the model reaction, the yield of 3a and
total yield were both increased with CHCl3 as the solvent
(Table 1, entry 3).
In order to further improve the reaction efficiency and selec-
tivity, the effect of temperature was examined. The selectivity
for the formation of 3a has obviously improved at 0 °C (entries
3,5 and 6), and the corresponding product 3a was obtained in
31.4% and 4a in 38.5% (entry 6).
Under these conditions, the yield of 3a was improved with
increase of iodine. Finally, the yield of 3a and 4a was obtained
in 51.3% and 32.2% at 0 °C in CHCl3 with the ratio of 1a:2a:
I2 as 1:1.2:2. Although 1,4-naphthoquinone was consumed
under optimised condition, the reaction time was extended but
the yield of product 3a was not increased and the ratio of 3a to
4a was not changed (entry 12).
As shown in Table 2, the iodine addition products 3 were
obtained in moderate to good yield in the reaction of 1,4-naph-
thoquinone and different primary amines in CHCl3 as solvent
and starting material molar ratios of 1:2:I2 (1:1.2:2) at 0 °C
(Scheme 2). The total yield of 3 and 4 was in 70–86%. The
selectivity for the formation of 3 was good when the carbon
number of amines were no more than four without steric
hindrance, the ratio of 3 and 4 was above three (entries 2, 3, 4,
5 and 9). As the steric hindrance of the benzylamine and the
long-chain amine increased, the selectivity for 3 decreased and
the yield of 3 and 4 was about equivalent (entries 1, 7 and 8).
In contrast, the product of iodine addition was not obtained
in the reaction of phenylamine and 1,4-naphthoquinone under
the same conditions. The product of iodination of the aniline
ring 2-(4-iodophenylamino)naphthalene-1,4-diol (5) was obtained
instead in 24.6% yield. 2- Phenylamino-1,4-naphthoquinone
(6) was also obtained in 34.2% yield. The structure of 5 was
confirmed by 1H NMR in CDCl3 and D2O.
The following experiments were carried out to understand
the reaction and from our experimental results, a possible
mechanism was proposed (Scheme 4). Product 4a was obtained
in 72.6% yield from the reaction between 1a and benzylamine
2a. Product 3a was obtained in 64.6% yield when 4a as treated
with 2 equiv. iodine, thus demonstrating the intermediacy of
4a in the reaction pathway. When the reaction was prolonged
or used more than 2 equiv. iodine, a greater yield of product 3a
Scheme 1
* Correspondent. Email: lyjzjut@zjut.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2013 35
Table 1 Optimisation of the reaction conditions
Table 2 Reaction between 1,4- naphthoquinone and different
primary amines
Entry a 1a:2a:I2
Solvent T/°C
Yield/% b of
Ratio of
3a:4a
3a:4a
Entry
R
Product 3
Product 4 3/4 Total
yield
1
2
1:1.2:1
1:1.2:1
1:1.2:1
1:1.2:1
1:1.2:1
1:1.2:1
1:1.2:1
1:1.2:1
1:1.2:0.1
1:1.2:1.2
1:1.2:2
1:1.2:2
CH2Cl2
Toluene
CHCl3
C2H5OH
Et2O
Water
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
r.t.
r.t.
14.9/27.7
19.5/28.4
21.4/38.5
15.0/49.5
15.7/37.4
18.7/19.7
12.2/49.5
31.4/38.5
7.4/51.7
0.54
0.68
0.56
0.30
0.42
0.95
0.25
0.81
0.14
1.03
1.59
1.59
3
Yield/%
4
Yield/%
1
2
PhCH2-
CH3-
3a
3b
3c
3d
3e
3f
51.3
56.4
68.7
70.4
67.8
32.8
43.9
47.9
55.0
49.4
4a
4b
4c
4d
4e
4f
32.2
19.5
18.2
15.5
17.3
38.9
30.2
44.0
19.2
21.4
1.6
2.9
3.8
4.5
3.9
0.8
1.5
1.1
2.9
2.3
83.5
75.9
86.9
85.9
85.1
71.7
74.1
87.9
74.2
70.8
3
r.t.
4
r.t.
3
C2H5-
5
r.t.
4
C3H7-
C4H9-
C6H13-
C10H21-
C12H25-
6
r.t.
5
7
60 °C
0 °C
0 °C
0 °C
0 °C
0 °C
6
8
7
3g
3h
4g
4h
4i
9
8
10
11
12c
36.6/35.4
51.3/32.2
52.0/32.7
9
(CH3O)2CHCH2- 3i
HOCH2CH2- 3j
10
4j
a Stirred for 18h. b Isolated yield based on 1a. c Stirred for 36 h.
was not obtained. The iodo compound, 2-iodonaphthalene-
1,4-dione 7 was not obtained with naphthoquinone and iodine.
In terms of our experimental results, a possible sequence
for the formation of the iodinated product 3 is proposed
in which iodinated product 3 was formed by iodination of
intermediate 4.
In summary, we have synthesised a series of 2-iodo-3-
(alkylamino)-naphthalene-1,4-diones by a useful, convenient,
and cost-effective route. These novel compounds have poten-
tial biological activity and their applications to the synthesis of
more complex and interesting products are underway in our
laboratory.
Our experimental results and the work of Liu28 and Wang30,
leads to the sequence shown in Scheme 5. The alkylamine
attacks the 1,4-naphthoquinone activated by molecular iodine
to give the initial addition product II. The intermediate II
and its tautomer III are oxidised to quinones resulting in 4,
The oxidation process can involve the oxygen in air 31 and the
iodine in reaction system. Two possible reaction pathways
leading to 3 are depicted in Scheme 5: One is the iodination
of 2-amino-1,4-naphthoquinone 4 to give the product 3 whilst
the other is the iodination of the hydroquinone III to give the
intermediate VI which is then oxidised to the final product 3.
Experimental
The reagents were obtained from commercial sources. CH2Cl2, CHCl3
and toluene were dried with Na or CaH2. The 1H and 13C NMR spectra
were recorded at 500 and 125 MHz, respectively, in CDCl3 with a
Bruker AM 500 spectrometer. The GC-MS was Agilent (GC6890-
MS5973).
General procedure
A mixture of 1,4-naphthoquinone (0.158 g, 1.0 mmol) and the amine
(1.2 mmol) in CHCl3 (5 mL) was added to I2 (2 equiv.) at 0 °C and
stirred until the starting material was consumed, as determined by
Scheme 2
Scheme 3
Scheme 4

36 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 5
GC-MS and TLC. The reaction mixture was poured into saturated
aqueous sodium thiosulfate (8 mL) and was extracted with CHCl3
(3 × 10 mL). The combined extracts were dried over MgSO4. The
solvent was removed under vacuum, and the mixed crude products 3
and 4 were separated by chromatography on silica gel and eluted with
CH2Cl2–petroleum ether (1:3).
134.65 (1C), 132.32 (1C), 131.71 (1C), 131.33 (1C), 129.86 (1C),
127.45 (1C), 126.93 (1C), 77.25 (1C), 45.59 (1C), 32.69 (1C), 19.73
(1C), 13.67 (1C); GC-MS (m/z): 355.8 (M+1), 354.9 (M, 100%),
228.2, 186.2, 130.1, 102.0.76.0, 50.0; HRMS (ESI-TOF) m/z Calcd
for C14H15INO2 [M+H]+ 356.0142, found 356.0149.
2-Iodo-3-(hexylamino)naphthalene-1,4-dione (3f): Yield 32.8%
1
2-Iodo-3-(benzylamino)naphthalene-1,4-dione (3a): Yield 51.3%
(125.7 mg). Red solid: m.p. 87–88 °C; H NMR (CDCl3): δ (ppm)
1
(199.5 mg). Red solid: m.p. 99–100 °C; H NMR (CDCl3): δ (ppm)
8.16 (dd, J1 = 1.0 Hz, J2 = 8.0 Hz 1H), 8.05 (dd, J1 = 1.5 Hz, J2 =
7.5 Hz 1H), 7.70 (dt, J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 7.64 (dt, J1 =
1.5 Hz, J2 = 8.0 Hz 1H), 6.05 (brs, 1H), 3.90 (q, J = 6.5 Hz, 2H),
1.74–1.69 (m, 2H), 1.47–1.41 (m, 2H), 1.37–1.34 (m, 4H), 1.47–1.41
(m, 2H), 0.92 (t, J = 7.5 Hz, 3H). 13C NMR (CDCl3): δ (ppm) 179.21
(1C), 177.27 (1C), 150.83 (1C), 134.75 (1C), 132.63 (1C), 131.99
(1C), 131.34 (1C), 129.89 (1C), 127.53 (1C), 127.12 (1C), 77.25 (1C),
45.79 (1C), 31.39 (1C), 30.74 (1C), 26.09 (1C), 22.68 (1C), 13.79
(1C). GC-MS (m/z): 383.0 (M+1, 100%), 312.1, 256.4, 186.3, 185.3,
129.3, 76.2, 41.2. HRMS (ESI-TOF) m/z Calcd for C16H19INO2
[M+H]+ 384.0455, found 384.0459.
8.14 (dd, J1 = 1.0 Hz, J2 = 8.0 Hz 1H), 8.02 (dd, J1 = 2.0 Hz, J2 =
7.5 Hz 1H), 7.69 (dt, J1 = 1.5 Hz, J2 = 7.5 Hz 1H), 7.63 (dt, J1 =
2.0 Hz, J2 = 8.0 Hz 1H), 7.42–7.33 (m, 5H),6.21 (brs, 1H), 5.10 (d,
J = 5.5 Hz, 2H); 13C NMR (CDCl3): δ (ppm) 178.99 (1C), 177.38
(1C), 150.71 (1C), 137.64 (1C), 134.63 (1C), 132.46 (1C), 130.98
(1C), 130.13 (1C), 129.24 (1C), 128.09 (1C), 127.70 (2C), 127.44
(2C), 126.99 (1C), 77.30 (1C), 50.05 (1C); GC-MS (m/z): 387.9
(M-1), 386.9 (100%), 262.2, 204.2, 176.2, 157.0, 129.1, 50.0; HRMS
(ESI-TOF) m/z. Calcd for C17H13INO2 [M+H]+ 389.9985, found
389.9983.
2-Iodo-3-(methylamino)naphthalene-1,4-dione (3b):29 Yield 56.4%
(176.6 mg). Red solid: m.p. 185–186 °C (lit.29 186–187 °C); 1H NMR
(CDCl3): δ (ppm) 8.15 (d, J = 7.0 Hz 1H), 8.04 (d, J = 7.5 Hz, 1H),
7.70 (t, J = 7.5 Hz 1H), 7.64 (t, J = 7.0 Hz 1H), 6.13 (brs, 1H), 3.47 (d,
J = 6.0 Hz, 3H); GC-MS (m/z): 313.7 (M+1), 312.7 (M, 100%), 186.0,
158.0, 131.1, 105.0, 89.0.
2-Iodo-3-(ethylamino)naphthalene-1,4-dione (3c): Yield 68.7%
(224.7 mg). Red solid: m.p. 130–131 °C; 1H NMR (CDCl3): δ (ppm)
8.15 (d, J = 8.0 Hz, 1H), 8.04 (d=d, J = 7.5 Hz 1H), 7.70 (dt, J1 =
1.5 Hz, J2 = 7.5 Hz 1H), 7.64 (dt, J1 = 1.5 Hz, J2 = 7.5 Hz 1H), 5.98
(brs, 1H), 3.99–3.93 (m, 2H) 1.37 (t, J = 7.0 Hz, 3H); 13C NMR
(CDCl3): δ (ppm) 179.29 (1C), 177.47 (1C), 150.72 (1C), 134.67
(1C), 132.35 (1C), 131.30 (1C), 129.92 (1C), 127.47 (1C), 126.95
(1C), 77.25 (1C), 40.97 (1C), 15.99 (1C); GC-MS (m/z):327.8 (M+1),
326.8 (M, 100%), 312.1, 200.2, 172.2, 155.1, 144.2, 89.2; HRMS
(ESI-TOF) m/z Calcd for C12H11INO2 [M+H]+ 327.9829, found
327.9835.
2-Iodo-3-(propylamino)naphthalene-1,4-dione (3d): Yield 70.4%
(240.2 mg). Red solid: m.p. 123–124 °C; 1H NMR (CDCl3): δ (ppm)
8.16 (dd, J1 = 1.5 Hz, J2 = 8.0 Hz 1H), 8.05 (dd, J1 = 1.0 Hz, J2 =
7.5 Hz 1H), 7.70 (dt, J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 7.64 (dt, J1 = 1.5
Hz, J2 = 7.5 Hz 1H), 6.07 (brs, 1H), 5.87 (q, J = 7.5 Hz, 2H), 1.79–
1.71 (m, 2H), 1.05 (t, J = 7.5 Hz, 3H); 13C NMR (CDCl3): δ (ppm)
179.28 (1C), 178.20 (1C), 150.85 (1C), 134.75 (1C), 132.61 (1C),
130.99 (1C), 129.46 (1C), 127.55 (1C), 126.70 (1C), 77.23 (1C),
45.80 (1C), 23.97 (1C), 10.84 (1C); GC-MS (m/z): 341.8 (M+1),
341.0 (M, 100%), 312.1, 214.2, 185.2, 130.2, 102.2, 41.2; HRMS
(ESI-TOF) m/z Calcd for C13H13INO2 [M+H]+ 341.9985, found
341.9990.
2-Iodo-3-(decylamino)naphthalene-1,4-dione (3g): Yield 43.9%
1
(192.9 mg). Red solid: m.p. 85–86 °C; H NMR (CDCl3): δ (ppm)
8.16 (dd, J1 = 1.0 Hz, J2 = 8.0 Hz 1H), 8.05 (dd, J1 = 1.0 Hz, J2 =
7.5 Hz 1H), 7.70 (dt, J1 = 1.5 Hz, J2 = 8.0 Hz 1H), 7.64 (dt, J1 =
1.5 Hz, J2 = 7.5 Hz 1H), 6.06 (brs, 1H), 3.90 (q, J = 6.5 Hz, 2H),
1.74–1.68 (m, 2H), 1.46–1.28 (m, 2H), 1.37–1.34 (m, 2H), 1.47–1.41
(m, 14H), 0.89 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3): δ (ppm) 179.33
(1C), 178.71 (1C), 151.12 (1C), 134.64 (1C), 133.97 (1C), 132.31
(1C), 131.92 (1C), 131.46 (1C), 127.46 (1C), 77.23 (1C), 45.99 (1C),
31.90 (1C), 31.74 (1C), 29.51 (1C), 29.29 (1C), 29.26 (1C), 29.22
(1C), 26.60 (1C), 22.60 (1C), 14.17 (1C); GC-MS (m/z): 438.9 (M),
312.1 (100%), 186.2, 174.2, 130.1, 102.2, 77.2, 41.2; HRMS
(ESI-TOF) m/z Calcd for C20H27INO2 [M+H]+ 440.1081, found
440.1078.
2-Iodo-3-(dodecylamino)naphthalene-1,4-dione (3h): Yield 47.9%
1
(223.9 mg). Red solid: m.p. 95–96 °C; H NMR (CDCl3): δ (ppm)
8.15 (dd, J1 = 0.5 Hz, J2 = 7.5 Hz 1H), 8.04 (dd, J1 = 1.0 Hz, J2 =
7.5 Hz 1H), 7.69 (dt, J1 = 1.0 Hz, J2 = 7.0 Hz 1H), 7.63 (dt, J1 =
1.0 Hz, J2 = 7.5 Hz 1H), 6.05 (brs, 1H), 3.90 (q, J = 6.5 Hz, 2H),
1.73–1.67 (m, 2H), 1.45–1.26 (m, 18H), 0.88 (t, J = 6.5 Hz, 3H); 13
C
NMR (CDCl3): δ (ppm) 179.44 (1C), 178.99 (1C), 151.47 (1C),
134.95 (1C), 132.42 (1C), 131.56 (1C), 130.72 (1C), 127.30 (1C),
126.94 (1C), 77.23 (1C), 61.04 (1C), 45.98 (1C), 31.92 (1C), 30.74
(1C), 29.63 (1C), 29.56 (1C), 29.50 (1C), 29.36 (1C), 29.26 (1C),
26.64 (1C), 22.71 (1C), 14.14 (1C); GC-MS (m/z): 468.1 (M+1),
467.1 (M, 100%), 340.2, 312.1, 300.2, 186.2, 55.2, 41.2; HRMS (ESI-
TOF) m/z Calcd for C22H31INO2 [M+H]+ 468.1394, found 468.1381.
2-Iodo-3-(2,2-dimethoxyethylamino)naphthalene-1,4-dione (3i):
1
Yield 55.0% (212.9 mg). Yellow solid: m.p. 87–88 °C; H NMR
(CDCl3): δ (ppm) 8.11 (dd, J1 = 1.5 Hz, J2 = 8.0 Hz 1H), 8.01 (dd,
J1 = 1.5 Hz, J2 = 8.0 Hz 1H), 7.69 (dt, J1 = 1.5 Hz, J2 = 7.5 Hz 1H),
7.63 (dt, J1 = 2.0 Hz, J2 = 8.0 Hz 1H), 6.17 (brs, 1H), 4.58 (t, J =
5.5 Hz, 1H), 4.02 (t, J = 5.5 Hz, 2H), 3.47 (s, 6H); 13C NMR (CDCl3):
δ (ppm) 179.11 (1C), 177.52 (1C), 151.32 (1C), 134.69 (1C), 132.63
(1C), 131.26 (1C), 130.26 (1C), 127.49 (1C), 127.07 (1C), 102.67
(1C), 77.47 (1C), 54.87 (2C), 47.10 (1C);GC-MS (m/z): 387.8 (M),
2-Iodo-3-(butylamino)naphthalene-1,4-dione (3e): Yield 67.8%
(240.8 mg). Red solid: m.p. 119–120 °C; 1H NMR (CDCl3): δ (ppm)
8.16 (dd, J1 = 1.5 Hz, J2 = 8.0 Hz 1H), 8.04 (dd, J1 = 1.5 Hz, J2 =
8.0 Hz 1H), 7.70 (dt, J1 = 1.5 Hz, J2 = 7.5 Hz 1H), 7.64 (dt, J1 =
1.5 Hz, J2 = 7.5 Hz 1H), 6.05 (brs, 1H), 3.91 (q, J = 6.5 Hz, 2H),
1.74–1.68 (m, 2H), 1.51–1.44 (m, 2H), 1.00 (t, J = 7.5 Hz, 3H); 13C
NMR (CDCl3): δ (ppm) 179.20 (1C), 177.45 (1C), 150.70 (1C),

JOURNAL OF CHEMICAL RESEARCH 2013 37
355.8, 326.9, 75.0 (100%), 47.0; HRMS (ESI-TOF) m/z Calcd for
C14H15INO2 [M+H]+ 388.0040, found 388.0049.
δ (ppm) 8.15 (dd, J1 = 1.0 Hz, J2 = 9.0 Hz 2H), 7.80–7.77 (m, 1H),
7.71–7.68 (m, 1H), 7.58 (brs, 1H), 7.46–7.43 (m, 2H), 7.31–7.22 (m,
3H), 6.44 (s, 1H).
2-Iodo-3-(2-hydroxyethylamino)naphthalene-1,4-dione (3j): Yield
1
49.4% (169.5 mg). Red solid: m.p. 54–55 °C; H NMR (CDCl3):
δ (ppm) 8.15 (dd, J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 8.05 (dd, J1 = 1.0 Hz,
J2 = 7.0 Hz 1H), 7.70 (dt, J1 = 1.5 Hz, J2 = 7.0 Hz 1H), 7.65 (dt,
J1 = 1.5 Hz, J2 = 7.0 Hz 1H), 6.37 (brs, 1H), 4.11–4.08 (m, 2H), 3.96–
3.94 (m, 2H), 1.75 (s, 1H); 13C NMR (CDCl3): δ (ppm) 183.22 (1C),
181.97 (1C), 148.38 (1C), 134.64 (1C), 133.54 (1C), 132.14 (1C),
126.32 (1C), 126.20 (1C), 101.15 (1C), 60.07 (1C), 44.22 (1C);
GC-MS (m/z): 342.0 (M), 327.0 (100%), 299.2, 285.1, 206.2.
2-(Benzylamino)-1,4-naphthoquinone (4a):28 Yield 32.2% (84.7 mg).
Red soild: m.p. 156–157 °C (lit.28 m.p. 158–159 °C); 1H NMR
(CDCl3): δ (ppm) 8.12–8.07 (m, 2H), 7.43 (t, J = 6.0 Hz, 1H), 7.68 (t,
J = 6.0 Hz, 1H), 7.39–7.28 (m, 5H), 6.23 (s, 1H), 5.82 (s, 2H), 5.11 (d,
J = 6.0 Hz, 2H); GC-MS (m/z): 263.0 (M), 262.0 (M-1, 100%), 158.0,
130.0, 102.0, 76.0, 50.0.
We gratefully acknowledge the financial support from the
Natural Science Foundation of China (21176223) and the
National Natural Science Foundation of Zhejiang (Y407306).
Received 13 September 2012; accepted 14 November 2012
Paper 1201545 doi: 10.3184/174751912X13547276507240
Published online: 15 January 2013
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2-(Methylamino)-1,4-naphthoquinone (4b):32 Yield 19.5% (36.5 mg).
1
Red needle crystal: m.p. 221–222 °C (lit.33 m.p. 220–230 °C); H
NMR (CDCl3): δ (ppm) 7.70–8.20 (m, 4H), 5.94 (s, 1H), 5.70 (s, 1H),
2.93 (d, 2H);GC-MS (m/z): 187.2 (M, 100%), 146.2, 130.3, 105.2,
89.2, 76.2, 50.1
4
5
6
7
8
9
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2-(Ethylamino)-1,4-naphthoquinone (4c):33 Yield 18.2% (36.6 mg).
Yellow needle crystal: m.p. 139–140 °C (lit.33 141.4 °C); GC-MS
(m/z): 201.0 (M, 100%), 199.1, 186.0, 158.0, 130.1, 102.0, 76.0,
50.0.
2-(Propylamino)-1,4-naphthoquinone (4d):34 Yield 15.5% (33.4 mg).
Yellow needle crystal: m.p. 115–116 °C (lit.34 114–116 °C); 1H NMR
(CDCl3): δ (ppm) 7.20–8.10 (m, 4H), 5.93 (s, 1H), 5.75 (s, 1H), 3.15–
3.19 (m, 2H), 1.71–1.76 (m, 2H), 1.04 (t, J = 7.5 H); GC-MS (m/z):
215.8 (m, 100%), 214.9, 186.0, 131.0, 101.0, 76.0, 50.0.
J. Zhang, N. Redman, A.P. Litke, J. Zeng, J. Zhan, K.Y. Chan and C.-W.T.
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2-(Butylamino)-1,4-naphthoquinone (4e):28 Yield 17.3% (39.7 mg).
Yellow needle crystal: m.p. 117–118 °C (lit.28 115–117 °C); 1H NMR
(CDCl3): δ (ppm) 8.12 (dd, J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 8.06 (dd,
J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 7.76–7.73 (m, 1H), 7.64–7.61 (m, 1H),
5.90 (brs, 1H), 5.75 (s, 1H), 3.20 (q, J = 6.0 Hz, 2H), 1.73–1.67 (m,
2H), 0.99 (t, J = 7.5 Hz, 3H); GC-MS (m/z): 230.0 (M+1), 229.0 (M),
201.0, 186.0 (100%), 146.0, 131.0, 76.0, 41.0.
14 P.A. Chase, G.C. Welch, T. Jurca and D.W. Stephan, Angew. Chem., Int.
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15 P. Spies, S. Schwendemann, S. Lange, G. Kehr, R. Froehlich and G. Erker,
Angew. Chem., Int. Ed., 2008, 47, 7543.
2-(Hexylamino)-1,4-naphthoquinone (4f):35 Yield 38.9% (100.1 mg).
Red needle crystal: m.p. 116–117 °C; 1H NMR (CDCl3): δ (ppm) 8.12
(dd, J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 8.06 (dd, J1 = 1.0 Hz, J2 = 7.5 Hz
1H), 7.75–7.72 (m, 1H), 7.64–7.61 (m, 1H), 5.90 (brs, 1H), 5.74 (s,
1H), 3.19 (q, J = 6.0 Hz, 2H), 1.72–1.67 (m, 2H), 1.43–1.40 (m, 2H),
1.35–1.32 (m, 4H), 0.92 (t, J = 4.5 Hz, 3H); GC-MS (m/z): 257.2,
228.2, 186.3, 146.2, 131.2, 103.2, 76.1, 41.2.
16 Y. Kita, K. Morimoto, M. Ito, C. Ogawa, A. Goto and T. Dohi, J. Am.
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18 N. Deka, D.J. Kalita, R. Borah and J.C. Sarma, J. Org. Chem., 1997, 62,
1563.
19 H. Firouzabadi, N. Iranpoor and H. Hazarkhani, J. Org. Chem., 2001, 66,
7527.
20 B.P. Bandgar and K.A. Shaikh, Tetrahedron Lett., 2003, 44, 1959.
21 B.K. Banik, M. Fernandez and C. Alvarez, Tetrahedron Lett., 2005, 46,
2479.
22 S. Ko, M.N.V. Sastry, C. Lin and C.F. Yao, Tetrahedron Lett., 2005, 46,
5771.
23 R. Varala, S. Nuvula and S.R. Adapa, J. Org. Chem., 2006, 71, 8283.
24 B. Karimi and B. Golshani, J. Org. Chem., 2000, 65, 7228.
25 Q. Wang, C. Wan, Y. Gu, J. Zhang, L. Gao and Z. Wang, Green Chem.,
2011, 13, 578.
26 Y. Yuan and H. Zhu, Eur. J. Org. Chem., 2012, 2012, 329.
27 V. Kavala, C. Lin, C.-W. Kuo, H. Fang and C.-F. Yao, Tetrahedron, 2012,
68, 1321.
28 B. Liu and S.-J. Ji, Synth. Commun., 2008, 38, 1201.
29 M.Yamashita, K. Ueda, K. Sakaguchi and A. Iida, Tetrahedron Lett., 2011,
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30 C.H. Jiang and S.Z. Wang, Synlett, 2009, 7, 1099.
31 H. Miyamura, M. Shiramisu, R. Matsubara and S. Kobayashi, Chem. Lett.
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2-(Decylamino)-1,4-naphthoquinone (4g):35 Yield 30.2% (94.7
mg). Red needle crystal: m.p. 130–131 °C; GC-MS (m/z): 313.0,
242.1, 228.2, 186.2, 174.1, 146.0, 41.1.
2-(Dodecylamino)-1,4-naphthoquinone (4h):35 Yield 44.0%
(150.3 mg). Red needle crystal: m.p. 145–146 °C; 1H NMR (CDCl3):
δ (ppm) 8.15 (dd, J1 = 0.5 Hz, J2 = 7.5 Hz 1H), 8.04 (dd, J1 = 1.0 Hz,
J2 = 7.5 Hz 1H), 7.69 (dt, J1 = 1.0 Hz, J2 = 7.0 Hz 1H), 7.63 (dt,
J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 6.05 (brs, 1H), 5.85 (s, 1H), 3.90 (q,
J = 6.5 Hz, 2H), 1.73–1.67 (m, 2H), 1.45–1.26 (m, 18H), 0.88 (t,
J = 6.5 Hz, 3H); GC-MS (m/z): 342.1, 341.1, 242.2, 228.2, 186.2,
174.2, 146.0, 41.0.
2-(2,2-Dimethoxyethylamino)-1,4-naphthoquinone (4i): Yield 19.2%
(50.2 mg).Yellow needle crystal: m.p. 110–112 °C; 1H NMR (CDCl3):
δ (ppm) 8.11 (dd, J1 = 1.5 Hz, J2 = 8.0 Hz 1H), 8.01 (dd, J1 = 1.5 Hz,
J2 = 8.0 Hz 1H), 7.69 (dt, J1 = 1.5 Hz, J2 = 7.5 Hz 1H), 7.63 (dt,
J1 = 2.0 Hz, J2 = 8.0 Hz 1H), 6.06 (brs, 1H), 5.77 (s, 1H), 4.60 (t,
J = 5.5 Hz, 1H), 3.44 (s, 6H), 3.31 (t, J = 5.0 Hz, 2H); GC-MS (m/z):
262.0, 260.8, 230.0, 201.0, 198.0, 75.0, 47.0.
32 C. Valente, R. Moreira, R.C. Guedes, J. Iley, M. Jaffar and K.T. Douglas,
2-(2-Hydroxyethylamino)-1,4-naphthoquinone (4j):36 Yield 21.4%
(46.5mg).Yellow needle crystal: m.p. 158–159 °C (lit.37 186–187 °C);
1H NMR (CDCl3): δ (ppm) 8.11 (dd, J1 = 1.0 Hz, J2 = 7.5 Hz 1H), 8.05
(dd, J1 = 1.0 Hz, J2 = 7.0 Hz 1H), 7.70 (dt, J1 = 1.5 Hz, J2 = 7.0 Hz 1H),
7.65 (dt, J1 = 1.5 Hz, J2 = 7.0 Hz 1H), 6.23 (brs, 1H), 5.79 (s, 1H),
3.95–3.94 (m, 2H), 3.40–3.37 (m, 2H), 1.86 (s, 1H).
Bioorg. Med. Chem., 2007, 15, 5340–5350.
33 U. Lohmann and K. Hartke, Arch. Pharm., 1984, 317, 313–323.
34 J.S. Yadav, B.V.S. Reddy, T. Swamy and K.S. Shankar, Monatsh. Chem.,
2008, 139, 1317–1320.
35 M.Y. Fosso, K.Y. Chan, R. Gregory and C.-W.T. Chang, ACS Comb. Sci.,
2012, 14, 231–235.
36 S. Cao, B.T. Murphy, C. Foster, J.S. Lazo and D.G.I. Kingston, Bioorg.
Med. Chem., 2009, 17, 2276–2281.
37 L.F. Fieser, E. Berliner, F.J. Bondhus, F.C. Chang, W.G. Dauben,
M.G. Ettlinger, G. Fawaz, M. Fields, C.Heidelberger, H. Heymann,
W.R. Vaughan, A.G. Wilson, E. Wilson, M. Wu, M.T. Leffler, K.E. Hamlin,
E.J. Matson, E.E. Moore, M.B. Moore, H.E. Zaugg, J. Am. Chem. Soc.,
1948, 70, 3174.
2-(4-Iodophenylamino)naphthalene-1,4-diol (5): Yield 24.6%
1
(92.8mg). Red solid; H NMR (CDCl3): δ (ppm) 7.68–8.15 (m, 4H,
ArH), 7.52 (s, 1H, NH), 7.42–7.42 (d, 2H, J = 0 Hz,ArH), 7.05–7.07
(d, 2H, J = 8.5 Hz, ArH), 6.41 (s, H, CH).
2-(Phenylamino)-1,4-naphthoquinone (6):34 Yield 34.2% (85.9mg).
Red solid: m.p. 184–185 °C (lit.34 m.p. 187–189 °C); 1H NMR (CDCl3):

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