Double functionalization of 2-amino-2′-hydroxy-1,1′-biaryls: Synthesis of 4-nitro-dibenzofurans and benzofuro-indoles

Article abstract of DOI:10.1039/c5ra07328f

Several substituted 2′-amino-biphenyl-2-ols were synthesized. The mild and TM-free double functionalization: nitration and cycloetherification of 2′-amino-biphenyl-2-ols have been achieved for the synthesis of functionalized 4-nitro-dibenzofurans utilizing NaNO₂ in TFA and water. Interestingly, nitration of phenol ring was observed along with the dibenzofuran ring formation in the one-pot synthesis. The position of the nitro group in several dibenzofurans is also established by X-ray crystal structure studies. Further functionalization of the obtained 4-nitro-dibenzofurans has been carried into 3-nitro-terphenyl-2-ol, novel benzofuro-indoles, and amino-dibenzofurans. The mechanistic understanding on double functionalization of 2′-amino-biphenyl-2-ols suggests that reaction proceeds by a combination of nitration of the phenol ring followed by Sandmeyer reaction for dibenzofuran ring formation.

Full text of DOI:10.1039/c5ra07328f

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Page 1 of 42
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Double Functionalization of 2-Amino-2′-hydroxy-1,1′-biaryls:
Synthesis of 4-Nitro-dibenzofurans and Benzofuro-indoles
Amit Kumar, Moh Sattar, Ajay Verma, Ankit Dara, Sangit Kumar*
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal,
Indore By-pass Road, Bhauri, Bhopal, Madhya Pradesh, India-462 066
E-mail: sangitkumar@iiserb.ac.in
ABSTRACT: Several substituted 2'-amino-biphenyl-2-ols were synthesized. The mild and TM-
free double functionalization; nitration and cycloetherification (see Scheme) of 2'-amino-
biphenyl-2-ols have been achieved for the synthesis of functionalized 4-nitro-dibenzofurans
utilizing NaNO2 in TFA and water. Interestingly, nitration of phenol ring was observed along
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with the dibenzofuran ring formation in one pot. Position of nitro group in several dibenzofurans
is also established by X-ray crystal structure studies. Further functionalization of the obtained 4-
nitro-dibenzofurans has been carried into 3-nitro-terphenyl-2-ol, novel benzofuro-indoles, and
amino-dibenzofurans. The mechanistic understanding on double functionalization of 2'-amino-
biphenyl-2-ols suggests that reaction proceeds by a combination of nitration of phenol ring
followed by Sandmeyer reaction for dibenzofuran ring formation.
Introduction
The development of new, mild and efficient methods for the synthesis of heterocycles is a
separate area of research in organic synthesis. Heterocycles, particularly dibenzofuran scaffold
present in natural products; kehokorins A-C, rhodomyrtoxin B, vialinin B, vanillic acid possess
cytotoxic, anti-inflammatory, antibacterial and inhibitor of TNF-α production activities (Figure
1).1 Also dibenzofurans served as the ligands in catalysis, precursors in natural product synthesis,
two photon caging group, and used in material science due to their optical and electronic
properties.2
Figure 1. Biologically active dibenzofurans
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Various methods have been reported for the synthesis of substituted dibenzofurans (Scheme 1, eq
1).3-10 Most of the methods depend on transition metal-catalysts, particularly; Pd used in C-H
arylation of 1-halo-2-phenoxybenzene, oxidative C-O cyclization of 2-arylphenol,
dehydrogenative cyclization of biphenyl ether, and decarbonylative intramolecular C-H arylation
of 2-aryloxybenzoic acids.3-6,8
Scheme 1. Synthesis and nitration of dibenzofurans
TM-free approaches such as flash vacuum pyrolysis, super acid Nafion-catalyzed ring closure of
2,2’-dihydroxybiphenyls, and use of NaH in HMPT for the conversion of 2-nitrobiphenyl into
dibenzofurans have also been studied.9 Apart from the only one example of dibenzofuran
reported by Kürti et al. using sodium nitrite reagent for the cyclization of 2'-amino-3'-bromo-
o
[1,1'-biphenyl]-2-ol at 70 C,10 there is no report which uses mild conditions and could tolerate
sensitive functional groups which are essential for post-modifications.
During our study on the transformation of 2'-aminobiphenyl-2-ol into dibenzofuran, nitration in
phenol ring was also observed. Two steps in one pot reduce the waste and cost, avoid isolation of
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intermediates, and create new avenues for further transformations. Further, nitro group has wide
scope in organic synthesis and chemical industry as there are various methods for derivatization
of the nitro group such as conversion into indole, and carbazol and as leaving group in biaryl
cross coupling.11
Nitro-dibenzofurans have been prepared by the electrophilic aromatic substitution in
dibenzofurans utilizing nitrating agents which afforded a mixture of 2- and 3-NO2 substituted
dibenzofurans (eq 2).12 Poor chemo and regioselectivity observed in the nitration of
dibenzofurans. Keumi et al. has achieved regioselective 2- and 3-nitration in dibenzofuran.12d
Nonetheless, synthesis of 4-NO2 substituted dibenzofuran has not been reported till date by direct
nitration and noticed to be difficult. Recently, pre-functionalized dibenzofuran-4-boronic acid
has been used in the preparation of 4-nitrodibenzofurans.13
TM-free approach has attracted considerable interest for C-C and C-X (X = N, O, S, Se) bond
formation and has been explored by us and others in recent time.9e,14,15 Herein we report
regioselective nitration and etherification of 2'-amino-biphenyl-2-ols for the synthesis of 4-nitro-
dibenzofurans (eq 3). Further, synthesis of novel benzofuro-indoles, 3-nitro-terphenyl-2-ol, and
amino-dibenzofurans has also been accomplished from synthesized nitrodibenzofurans.
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Results and Discussion
Table 1. Optimization of reaction conditions a
entry
MNO2
solvent
yield 2a b
ND
78
3a c
ND
trace
ND
53
1
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO3
AgNO2
tBuNO2
NaNO2
H2O
2
CF3COOH
CF3COOH: H2O
CH3COOH: H2O
H2SO4: H2O
HCl (35%)
3
92
4
trace
10
5
54
6
trace
ND
77
68
7
CF3COOH: H2O
CF3COOH: H2O
CF3COOH: H2O
CF3COOH: H2O
ND
trace
46
8
9
10
10d
40
ND
a Reaction were carried out using 1.0 mmol of 2'-amino-biphenyl-2-ol 1a, 3 mmol of nitrite salt
in TFA/H2O (1.5 mL, 15:1 v/v). b 1H NMR yield (mesitylene as internal standard).c Isolated
yield. d Reaction was carried in presence of TEMPO (3 mmol). ND = Not detected
For the optimization, 2'-aminobiphenyl-2-ol 1a was used as a model substrate in the presence of
various nitrate salts in different acids (eq 4, Table 1). First various solvents were screened using
readily available NaNO2 salt to obtain high yield of 4-nitrodibenzofuran 2a. As expected,
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reaction in water alone failed to provide 2a (Table 1 entry 1). When reaction performed in neat
TFA, 2a was obtained in 78% yield (Table 1 entry 2). A 15:1 ratio (v/v) of TFA and water led to
further improvement in the yield (92%) of the desired product 2a (Table 1, entry 3). Water and
other acids combinations were also screened, however, observed to be less effective (entries 4-6,
Table 1). Combination of H2SO4: water or HCl (35%) yielded un-nitrated dibenzofuran as a
t
major product (entries 5-6, Table 1). Next, various nitrite and nitrate salts, BuNO2, AgNO2 and
NaNO3 were studied in the nitro-cycloetherification reaction. Nonetheless, none of the nitrite
found superior to the NaNO2 (entries 7-9, Table 1).
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Table 2. Synthesis of 4-nitrodibenzofurans
entry
substrate a
4-nitrodibenzofurana
1
2
3
1b R = H (84)
1c R = CH3 (87)
1d R = tert-Bu (86)
2b R = H (12), 2b’ (61)b
2c R = CH3 (74)
2d R = tert-Bu (77)
4
5
1e X = F (87)
1f X = Br (89)
2e X = F (74)
2f X = Br (72)
6
1g (79)
2g (49)
7
8
9
1h R = CH3 (91)
1i R = Benz (82)
1j R = CF3 (79)
2h R = CH3 (79)
2i R = Benz (56)
2j R = CF3 (79)
10
11
1k X = H (83)
1l X = Br (67)
2k X = H (65)
2l X = Br (56)
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a
Isolated yield. Aminobiaryl-ols 1b-1l were obtained by the reduction of respective
nitrobiaryl-ols (see experimental section for details). b 2-Nitro-dibenzofuran was also isolated.
The scope of substrate was explored next under the optimized reaction conditions (Tables 2 and
3). 2'-Amino-biphenyl-2-ols 1a-1t were obtained by the reduction of respective 2'-nitro-
biphenyl-2-ols in 67-97% yields. Unsubstituted 2'-amino-biphenyl-2-ol 1b afforded 4-
nitrodibenzofuran 2b as a minor regioisomer (12% yield) along with 2-nitrodibenzofuran 2b′ as
major (61%) Table 2, entry 1. Next, electron donating methyl and tert-butyl 1c and 1d and
withdrawing F, Br and CN 1e-1g substrates were subjected for nitro-cycloetherification reaction.
The outcome of the double functionalization reaction is unaffected by the electronic nature of the
substituents as minor change in the yields (49-77%) of 2c-2g was observed.
Similarly, substrates 1h-1j with OCH3, OCH2Ph and OCF3 functionalities afforded the
corresponding 4-nitrodibenzofurans 2h-2j in 79, 56 and 79% yields respectively (entries 7-9,
Table 2). 4-Phenyl substituted phenol ring substrates 1k and 1l gave the corresponding product
2k and 2l with 65 and 56% yield, respectively. Functionalities such as CN, Cl, Br and OCF3 are
useful for further transformation, however, difficult to preserve under harsh reaction conditions.
Here dibenzofurans 2a 2f, 2g, 2j, and 2l with Cl, Br, and CN functionalities along with a newly
introduced nitro group have been obtained in one pot in good yields.
Next, the effect of substitution on the aniline ring was studied under optimized reaction condition
(Table 3). 2’-Amino-biaryl-2-ols 1m-1o with un-substituted aniline ring underwent double nitro
and etherification reaction successfully lead to 2m-2o in 69-79% yields (entries 1-3, Table 3).
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Table 3. Synthesis of 4-nitrodibenzofurans
entry
substrate
4-nitrodibenzofurana
1
1m (84)
2m (69)
2
3
4
5
6
7
1n (82)
1o (82)
1p (80)
1q (67)
1r (69)
1s (69)
2n (76)
2o (79)
2p (69)
2q (62)
2r (68)
2s (18), 2s’ (45)b
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8
1t (69)
2t (20), 2t’ (50)b
a Isolated yield, b 2-Nitro-dibenzofuran was also isolated
Figure 2. Crystal structures of 2a & 2d (for crystal structure studies of 1p, 2e, and 2o, see
SI pages S118-S158)
Interestingly, nitration on the aniline ring was not observed despite the presence of electron
t
withdrawing Cl or donating Bu and OCH3 substituent in the phenolic ring. Next, electron
donating OCH3 and tBu and electron withdrawing F substituents in the aniline ring furnished the
corresponding 4-nitrodibenzofurans 2p, 2q, and 2r with 69, 62, and 68% yields, respectively
(entries 4-6, Table 3). We also studied the nitration reaction of unsubstituted phenol ring of 2'-
amino -[1,1'-biphenyl]-2-ols (entries 7, 8, Table 3). As noticed above (entry 1, Table 2), 2-nitro-
dibenzofurans 2s’ and 2t’ were obtained as major product whereas 4-nitrodibenzofurans 2s and
2t were minor.
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In several 4-nitrodibenzofurans 2a, 2d, 2e, and 2o, position of NO2 group is also confirmed by
X-ray single crystal study (Figure 2). Worthy to note that nitration occurred in a highly
regioselective manner as it is unaffected by the electronic or steric nature of substituent in both
of the aromatic rings in 2’-amino-biaryl-2-ol substrates 1a-1t.
The feasibility of further transformation has been explored of synthesized 4-nitrodibenzofurans
2a, 2d, 2e, 2k, 2l, and 2n (Schemes 2 and 3). Reaction of 2n with PhMgBr led to carbon-carbon
bond formation by the cleavage of ether ring, which resulted novel terphenyl-2-ol 4n in 43%
yield. Next, 4-nitrodibenzofurans 2e, 2k and 2n were converted into benzofuro-indoles.
Heterocycles containing benzofuran and indole cores could be important in medicinal chemistry.
For this transformation, nitrodibenzofurans were treated with 3 equiv. of vinyl magnesium
bromide. This resulted in novel 1H-benzofuro[3,2-g]indoles 5e, 5k and 5n in 43-65% yields
(Scheme 2).
Scheme 2. Synthesis of terphenylol and benzofuro-indoles
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Next, nitro group in 2a, 2d, 2e, and 2l was selectively reduced into amine using Fe-powder in
ethanol with a catalytic amount of HCl at 80 oC (Scheme 3).
Scheme 3. Reduction of the nitro group in dibenzofurans
Barry and co-workers have studied anti tuberculosis activity of aminodibenzofurans in which
chloride para to ether linkage showed a positive effect on the activity.16 Here, fluoro-, chloro-,
and 4-bromo-phenylsubstituted aminodibenzofurans 6a, 6d, 6e and 6l were obtained in 82-89%
yields.
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Mechanism
Scheme 4. Nitration in dibenzofuran, phenol, anisole and in the presence of TEMPO
For mechanistic understanding, dibenzofuran 3a was subjected under the identical reaction
conditions which provided a mixture of nitro-dibenzofurans 7 and 8 in 7:3 ratio (Scheme 4).
Similarly, unsubstituted dibenzofuran gave a mixture of 3 and 2-nitro dibenzofurans 9 and 10 in
8:2 ratio. Phenol and anisol were then subjected for nitration. Indeed, phenol and anisol also
converted into ortho/ para-nitrophenol and nitroanisol respectively. Next, addition of a radical
quencher TEMPO to the reaction mixture provided nearly the same yields of nitrodibenzofurans
7 and 8 which preclude the possibility of radical pathway. Moreover, nitration in anisole could
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not be achieved if proceeds by radical pathway.17 However, anisole provided quantitative
nitrated anisole under optimized reaction conditions.
Because reactivity of positions in dibenzofuran is in the order of 3 >> 2 > 1 > 4, same as in the
order of their electron density, towards electrophilic substitution of nitration.12c-e And also
unsubstituted dibenzofuran gave 3-nitrodibenzofuran 9 as a major product under our conditions.
Therefore, selective nitration of phenol ring over aniline ring may not be rationalized by
electrophilic substitution in dibenzofuran.
Scheme 5. Proposed mechanism for double functionalization
The tentative mechanism is depicted in Scheme 5 and would involve a combination of nitration
in phenol and Sandmeyer reaction for the formation of dibenzofuran ring. 2'-Amino-biphenyl-2-
ol would transform into diazotonium salt I by the reaction with NaNO2 in aqueous solution of
+
+
CF3CO2H. Excess of NaNO2 with CF3CO2H also generates NO2 . Attack of NO2 , ortho to –OH
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+
in II would lead to intermediate III. Deprotonation then give IV, nucleophilic attack at C-N2 ,
followed by N2 and H+ elimination would furnish 4-nitro-dibenzofuran.
Nitration noticed to be highly regioselective with regards to phenol ring and nitration in the
aniline ring of 2'-amino-biphenyl-2-ols was not observed either at ortho (Tables 1 and 2) or para
to NH2 (entries 1-3, Table 2). This could be due to facile formation of diazonium salt over
+
+
generation of NO2 . The N2 shall make aniline ring electron deficient, disfavoring the
+
electrophilic attack of NO2 .
Summary
To sum up, we have developed a nitration and cyclic-etherification reaction in 2'-amino-
biphenyl-2-ols for the synthesis of 4-nitrodibenzofurans under TM-free reaction conditions in
one pot. The nitration reaction noticed to be highly regioselective with regards to phenolic ring.
Synthesized nitro-dibenzofuran further transformed into 3-nitro-terphenyl-2-ol, benzofuro-
indoles, and amino-dibenzofurans, which demonstrates further utility of 4-nitrodibenzofurans.
The developed methodology could be useful for the synthesis of highly substituted
dibenzofurans. Since, reaction provides selective nitration of phenol ring over aniline under mild
conditions. Further, efforts are being made to accomplish selective nitration in biaryls under TM-
free mild reaction conditions.
General Experimental Details
All NMR experiments were carried out on 400 MHz and 700 MHz spectrometer and NMR
1
chemical shifts are reported in ppm referenced to the solvent peaks of CDCl3, (7.24 ppm for H
and 77.16 (± 0.06) ppm for 13C, respectively), DMSO-d6 (3.31 ppm for H2O, 2.47 ppm for
DMSO, 39.9 for carbon). High resolution mass analysis is performed on quadruple-time of flight
(Q-TOF) mass spectrometer equipped with an ESI and APCI source (+ve/-ve). NaNO2, DMSO,
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phenols, and potassium tert-butoxide (98% purity) used as purchased. Silica gel (100-200 mesh
size) was used for column chromatography. TLC analysis of reaction mixtures was performed
using Merck silica gel (60 F254) plates. Nitro-biaryl-ols substrates of 1a–1h, 1k-1n, 1p and 3a are
known.9e
General Procedure for the Synthesis of Nitro-biaryl-ols (substrates for 1)9e
To a single neck flask, 4-chlorophenol (385 mg, 3.0 mmol) and 1-bromo-4-methyl-2-
nitrobenzene (540 mg, 2.5 mmol) were added in DMSO (7 mL) and resulted reaction mixture
was stirred for 5 min at room temperature under inert atmosphare. After this, KOtBu (673 mg,
6.0 mmol) was added portion wise. Progress of reaction was monitored by TLC. After
completion of the reaction (5 h), the mixture was poured into 10 % aqueous solution of HCl, and
extracted four times with 50 mL of ethyl acetate. The combined organic layer was dried over
Na2SO4, and filtered. The solvent was removed under vacuo and the residue was purified by
column chromatography (silica gel, eluent: hexane/ ethyl acetate). The product was obtained as
yellow solid with 89.5% yield. Rest of the nitro-biaryl-ols were obtained by following the similar
procedure.9e
5-(Benzyloxy)-4'-methyl-2'-nitro-[1,1'-biphenyl]-2-ol (substrate for 1i). Rf = 0.5 (ethyl
1
acetate: hexane 1:9), viscous liquid, yield 0.52 g (62%), H NMR (400 MHz, CDCl3)  7.77 (s,
1H), 7.44-7.39 (m, 4H), 7.38-7.32 (m, 2H), 7.28 (d, J = 7.9Hz, 1H), 6.83 (m, 2H), 7.73(d, J =
7.9Hz, 1H), 5.01 (s, 2H), 4.87 (brs, 1H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3)  153.1,
149.4, 146.7, 139.2, 137.0, 133.7, 132.4, 129.4, 128.6, 128.0, 127.6, 125.9, 124.6, 116.5, 116.4,
115.8, 70.8, 20.9. HRMS (ESI) m/z calcd for C20H17NO4 [M] 335.1158, found 335.1165.
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4'-Methyl-2'-nitro-5-(trifluoromethoxy)-[1,1'-biphenyl]-2-ol (substrate for 1j) Rf = 0.5
1
(ethyl acetate: hexane 2:8), viscous liquid, yield 0.61 g (79%), H NMR (400 MHz, CDCl3) 
7.81 (s, 1H), 7.48 (d, J = 7.1Hz, 1H), 7.28 (d, J = 7.8HZ, 1H), 7.09 (d, J = 3.3Hz, 2H), 6.80-
6.77 (m, 1H), 5.33 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3)  151.1, 149.1, 142.8(q, J
= 2.2), 139.9, 134.0, 132.3, 128.3, 126.3, 124.8, 122.8, 122.3, 121.8, 119.3, 116.4, 116.2, 20.9.
HRMS (ESI) m/z calcd for C14H10F3NO4 [M] + Na 336.0454, found 336.0452.
4-Bromo-4''-methyl-2''-nitro-[1,1':3',1''-terphenyl]-4'-ol (substrate for 1l) Rf = 0.4 (ethyl
1
acetate: hexane 2:8), yellow solid, yield 0.56 g (59%), H NMR (400 MHz, CDCl3)  7.80 (s,
1H), 7.51(m, 2H), 7.47(d, J = 7.8 Hz, 1H), 7.43-7.38 (m, 4H), 7.34(d, J = 7.8 Hz, 1H), 6.88 (d, J
13
= 8.2 Hz, 1H), 5.30 (s, 1H), 2.47(s, 3H); C NMR (100 MHz, CDCl3)  152.4, 149.4, 139.4,
139.3, 133.8, 133.2, 132.5, 131.8, 129.3, 128.4, 128.3, 128.1, 125.6, 124.7, 121.1, 116.2, 21.0.
HRMS (ESI) m/z calcd for C19H14BrNO3 [M] + Na 406.0049, found 406.0060.
5-Methoxy-2'-nitro-[1,1'-biphenyl]-2-ol (substrate for 1o). Rf = 0.4 (ethyl acetate: hexane
1
1:9), yellow solid, yield 0.44 g (72%), H NMR (400 MHz, CDCl3)  7.95 (dd, J = 8.1, 1.0 Hz,
1H), 7.64 (td, J = 7.6, 1.2 Hz, 1H), 7.49 (td, J = 7.6, 1.2 Hz, 1H), 7.42 (dd, J = 7.6, 1.2 Hz, 1H),
13
6.82-6.74 (m, 3H), 4.91 (brs, 1H), 3.77 (s, 3H); C NMR (100 MHz, CDCl3)  153.9, 149.6,
146.3, 132.9, 132.6, 132.5, 128.6, 125.9, 124.2, 116.6, 115.3, 114.9, 55.8. HRMS (ESI) m/z calcd
for C12H11NO4 [M] + Na 268.0580, found 268.0571.
4'-(tert-Butyl)-5-chloro-2'-nitro-[1,1'-biphenyl]-2-ol (substrate for 1q). Rf = 0.5 (ethyl
1
acetate: hexane 1:9), yellow solid, yield 0.50 g (65%), H NMR (400 MHz, CDCl3)  7.98 (d, J
= 2.0 Hz, 1H), 7.67 (dd, J = 8.1, 2.0 Hz, 1H), 7.32 (d, 8.0 Hz, 1H), 7.21-7.18 (m, 2H), 6.77-6.75
(m, 1H), 5.31 (brs, 1H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3)  153.1, 151.3, 149.2, 132.2,
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130.3, 129.6, 129.3, 128.3, 126.8, 125.9, 121.4, 116.9, 35.0, 31.0. HRMS (ESI) m/z calcd for
C16H16ClNO3 [M] -H 304.0711, found 304.0730.
5-Chloro-4'-fluoro-2'-nitro-[1,1'-biphenyl]-2-ol (substrate for 1r) Rf = 0.5 (ethyl acetate:
hexane 1:9), yellow viscous liquid, yield 0.45 g (67%), 1H NMR (400 MHz, CDCl3)  7.72 (td, J
= 8.1, 1.5 Hz, 1H), 7.39 (dd, J = 6.5, 1.5 Hz, 2H), 7.22-7.20 (m, 2H), 6.75-6.72 (m, 1H), 5.24
13
(brs, 1H); C NMR (100 MHz, CDCl3)  162.9, 160.4, 151.0, 134.1(d, J = 7.8 Hz), 129.6 (d, J
= 11.1 Hz), 129.5, 127.6 (d, J = 4.1 Hz), 126.1, 125.9, 120.5, 120.3, 116.8, 116.7, 112.4, 112.1.
HRMS (ESI) m/z calcd for C12H7ClFNO3 [M] -H 266.0015, found 266.0044.
General Procedure for the reduction of –NO2 into –NH2
In a 25 mL round-bottom flask equipped with a stir bar, 5-chloro-4'-methyl-2'-nitro-[1,1'-
biphenyl]-2-ol (263 mg, 1.0 mmol) was added in 10 mL of ethanol/ water (4:1). After that, iron
powder (280 mg, 5 mmol) and HCl (0.1 mL) was added. The reaction mixture was heated under
reflux for 3 hours and then cooled to room temperature. Reaction mixture was diluted with ethyl
acetate, filtered through celite, dried over sodium sulfate and the solvent removed in vacuo. The
concentrated reaction mixture was purified by column chromatography (hexane/ethyl acetate,
90/10). Yield 209 mg (90%). Compounds 1b to 1r were obtained by following the same
procedure.
2'-Amino-5-chloro-4'-methyl-[1,1'-biphenyl]-2-ol (1a). Rf = 0.4 (ethyl acetate: hexane 1:9),
1
white solid, yield 209 mg (90%), H NMR (400 MHz, CDCl3)  7.26-7.20 (m, 2H), 7.10(d, J =
8.0 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 6.69 (s, 1H), 4.65 (brs, 2H), 2.32
13
(s, 3H); C NMR (100 MHz, CDCl3)  152.5, 141.2, 139.5, 131.5, 130.5, 129.0, 127.8, 125.7,
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122.6, 122.4, 119.6, 118.3, 21.1. HRMS (ESI) m/z calcd for C13H12ClNO [M] + H 234.0680,
found 234.0671.
2'-Amino-4'-methyl-[1,1'-biphenyl]-2-ol (1b). Rf = 0.5 (ethyl acetate: hexane 1:9), white solid,
yield 167 mg (84%), 1H NMR (400 MHz, CDCl3)  7.29-6.99 (m, 2H), 7.13 (dd, J = 7.7, 2.6 Hz,
13
1H), 7.04-6.99 (m, 2H), 6.80 (d, J = 7.7 Hz, 1H), 6.69 (s, 1H), 4,66 (brs, 2H), 2.34 (s, 3H); C
NMR (100 MHz, CDCl3)  153.7, 141.6, 139.0, 131.7, 131.1, 129.3, 126.1, 123.2, 121.9, 121.1,
118.0, 117.9, 21.1. HRMS (ESI) m/z calcd for C13H13NO [M] + H 200.1070, found 200.1068.
2'-Amino-4',5-dimethyl-[1,1'-biphenyl]-2-ol (1c). Rf = 0.4 (ethyl acetate: hexane 1:9), white
1
solid, yield 185 mg (87%), H NMR (400 MHz, CDCl3)  7.13-7.08 (m, 3H), 6.93 (d, J = 8.6
Hz, 1H), 6.78 (d, J = 7.7 Hz, 1H), 6.67 (s, 1H), 4.50 (brs, 2H), 2.32 (s, 6H); 13C NMR (100
MHz, CDCl3)  151.4, 141.6, 138.9, 131.6, 131.4, 130.2, 129.8, 125.8, 123.3, 121.8, 117.8,
117.7, 21.1, 20.5. HRMS (ESI) m/z calcd for C14H15NO [M] + H 214.1226, found 214.1248.
2'-Amino-5-(tert-butyl)-4'-methyl-[1,1'-biphenyl]-2-ol (1d). Rf = 0.4 (ethyl acetate: hexane
1:9), white solid, brown viscous liquid, yield 220 mg (86%), 1H NMR (400 MHz, CDCl3)  7.32
(dd, J = 8.4, 2.5 Hz, 1H), 7.28 (d, J = 2.3 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H), 6.96 (d, J =8.4 Hz,
13
1H), 6.80 (d, J = 7.7 Hz, 1H), 6.69 (s, 1H), 4.31(brs, 2H), 2.33(s, 3H), 1.32(s, 9H); C NMR
(100 MHz, CDCl3)  151.3, 143.8, 141.7, 138.9, 131.7, 127.9, 126.2, 125.3, 123.8, 121.8, 117.8,
117.4, 34.2, 31.6, 21.1. HRMS (ESI) m/z calcd for C17H21NO [M] + H 256.1696, found
256.1686.
2'-Amino-5-fluoro-4'-methyl-[1,1'-biphenyl]-2-ol (1e). Rf = 0.4 (ethyl acetate: hexane 1:9),
brown solid, yield 189 mg (87%), 1H NMR (400 MHz, CDCl3)  7.11 (d, J = 7.8 Hz, 1H), 7.00-
6.95 (m, 3H), 6.81 (d, J = 7.8 Hz, 1H), 6.69 (s, 1H), 4.50 (brs, 2H), 2.33 (s, 3H); 13C NMR (100
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MHz, CDCl3)  158.4, 156.0, 149.8, 141.2, 131.5, 127.3(d, J = 7.7Hz), 122.3, 119.2(d, J =
8.3Hz), 118.3, 117.0, 116.7, 115.8, 115.5, 21.1. HRMS (ESI) m/z calcd for C13H12FNO [M] + H
218.0976, found 218.1002.
2'-Amino-5-bromo-4'-methyl-[1,1'-biphenyl]-2-ol (1f). Rf = 0.4 (ethyl acetate: hexane 1:9),
1
brown solid, yield 250 mg (89%), H NMR (400 MHz, CDCl3)  7.41 (d, J = 2.4 Hz, 1H), 7.36
(dd, J = 8.6, 2.5 Hz, 1H), 7.10 (d, J = 7.8 Hz, 1H), 6.90 (d, J = 8.6 Hz, 1H), 6.80 (d, J = 7.6 Hz,
1H), 6.69 (s, 1H), 4.45 (brs, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3)  153.0, 141.2,
139.6, 133.4, 131.9, 131.6, 128.4, 122.5, 122.4, 120.0, 118.3, 112.9, 21.1. HRMS (ESI) m/z calcd
for C13H12BrNO [M] + H 278.0175, found 278.0201.
2'-Amino-6-hydroxy-4'-methyl-[1,1'-biphenyl]-3-carbonitrile (1g). Rf = 0.5 (ethyl acetate:
hexane 3:7), white solid, yield 177 mg (79%), 1H NMR (400 MHz, CDCl3)  7.61 (d, J = 1.9 Hz,
1H), 7.54 (dd, J = 8.3, 2.2 Hz, 1H), 7.08 (m, 2H), 6.84 (d, J = 7.6 Hz, 1H), 6.74 (s, 1H), 4.13
(brs, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3)  157.9, 140.8, 140.1, 135.5, 133.0, 131.7,
127.6, 123.0, 122.2, 119.4, 119.3, 118.9, 104.4, 21.1. HRMS (ESI) m/z calcd for C14H12N2O [M]
+ H 225.1022, found 225.1004.
2'-Amino-5-methoxy-4'-methyl-[1,1'-biphenyl]-2-ol (1h). Rf = 0.4 (ethyl acetate: hexane
1.5:8.5), viscous liquid, yield 208 mg (91%), 1H NMR (400 MHz, CDCl3)  7.13 (d, J = 7.7 Hz,
1H), 6.95 (d, J = 8.6 Hz, 1H), 6.85 (dd, J = 8.6, 3.0 Hz, 1H), 6,83 (d, J = 3.0 Hz, 1H), 6.79 (d, J
13
= 7.7 Hz, 1H), 6.68 (s, 1H), 3.78 (s, 3H), 2.16 (s, 3H); C NMR (100 MHz, CDCl3)  153.8,
147.6, 141.5, 139.1, 131.4, 126.8,123.4, 121.9, 118.8, 117.9, 115.7, 115.0, 55.8, 21.1.HRMS
(ESI) m/z calcd for C14H15NO2 [M] + H 230.1176, found 230.1198.
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2'-Amino-5-(benzyloxy)-4'-methyl-[1,1'-biphenyl]-2-ol (1i). Rf = 0.4 (ethyl acetate: hexane
1:9), brown viscous liquid, yield 250 mg (82%), 1H NMR (400 MHz, CDCl3)  7.43 (d, J = 7.2
Hz, 2H), 7.38 (t, J = 7.0 Hz, 2H), 7.33-7.30 (m, 1H), 7.11 (d, J = 7.8 Hz, 1H), 6.95-6.94 (m,
2H), 6.92 (s, 1H), 6.79 (d, J = 7.2Hz, 1H), 6.68 (s, 1H), 5.04 (s, 2H), 4.28 (brs, 2H), 2.33(s, 3H);
13C NMR (100 MHz, CDCl3)  153.0, 147.9, 141.5, 139.1, 137.3, 131.5, 128.6, 127.9, 127.6,
126.8, 123.4, 122.0, 118.9, 117.9, 116.9, 116.1, 70.7, 21.1. HRMS (ESI) m/z calcd for
C20H19NO2 [M] + H 306.1489, found 306.1511.
2'-Amino-4'-methyl-5-(trifluoromethoxy)-[1,1'-biphenyl]-2-ol (1j). Rf = 0.5 (ethyl acetate:
hexane 2:8), white solid, yield 225 mg (79%), 1H NMR (400 MHz, CDCl3)  7.17-7.10 (m, 3H),
7.01 (d, J = 8.8 Hz, 1H), 6.83 (d, J = 7.6 Hz, 1H), 6.71 (s, 1H), 3.83 (brs, 2H), 2.34 (s, 3H); 13C
NMR (100 MHz, CDCl3)  152.5, 142.8, 141.1(q), 139.7, 131.6, 127.3, 123.6, 122.5, 122.0,
121.9, 119.4, 119.1, 118.4, 21.1. HRMS (ESI) m/z calcd for C14H12NO2F3 [M] - H 282.0736,
found 282.0762.
2''-Amino-4''-methyl-[1,1':3',1''-terphenyl]-4'-ol (1k). Rf = 0.4 (ethyl acetate: hexane 2:8),
1
white solid, yield 225 mg (83%), H NMR (400 MHz, CDCl3)  7.57 (d, J = 7.4 Hz, 2H), 7.54-
7.52 (m, 2H), 7.41 (t, J = 7.7 Hz, 2H), 7.30 (t, J = 7.3 Hz, 1H), 7.19 (d, J = 7.7 Hz, 1H), 7.11-
7.09 (m, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.71 (s, 1H), 4.17 (brs, 2H), 2.34 (s, 3H); 13C NMR (100
MHz, CDCl3)  153.4, 141.6, 140.7, 139.2, 134.2, 131.7, 129.8, 128.8, 128.5, 127.9, 126.8,
126.4, 123.3, 122.1, 118.4, 118.0, 21.2. HRMS (ESI) m/z calcd for C19H17NO [M] + H 276.1383,
found 276.1407.
2''-Amino-4-bromo-4''-methyl-[1,1':3',1''-terphenyl]-4'-ol (1l). Rf = 0.5 (ethyl acetate: hexane
1
2:8), white solid, yield 237 mg (67%), H NMR (400 MHz, CDCl3)  7.52 (dd, J = 6.8, 1.8 Hz,
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2H), 7.49-7.47 (m, 2H), 7.43 (m, 2H), 7.17 (d, J = 7.6 Hz, 1H), 7.10-7.08 (m, 1H), 6.82 (d, J =
7.6 Hz, 1H), 6.72 (s, 1H), 3.86 (brs, 2H), 2.34(s, 3H); 13C NMR (100 MHz, CDCl3)  153.7,
141.5, 139.7, 139.3, 132.9, 131.8, 131.7, 129.6, 128.3, 127.7, 126.6, 123.1, 122.2, 120.9, 118.6,
118.1, 21.1. HRMS (ESI) m/z calcd for C19H16BrNO [M] + H 354.0488, found 354.0510.
2'-Amino-5-chloro-[1,1'-biphenyl]-2-ol (1m). Rf = 0.4 (ethyl acetate: hexane 1:9), white solid,
yield 184 mg (84%), 1H NMR (400 MHz, CDCl3)  7.29 (d, J = 2.5 Hz, 1H), 7.27-7.24 (m, 1H),
13
7.23-7.21 (m, 2H), 7.00-6.95 (m, 2H), 6.87 (d, J = 7.9 Hz, 1H), 4.10 (brs, 2H); C NMR (100
MHz, CDCl3)  152.4, 141.4, 131.7, 130.6, 129.4, 129.2, 127.8, 125.8, 125.4, 121.4, 119.7,
117.6. HRMS (ESI) m/z calcd for C12H10ClNO [M] + H 220.0524, found 220.0546.
2'-Amino-5-(tert-butyl)-[1,1'-biphenyl]-2-ol (1n). Rf = 0.5 (ethyl acetate: hexane 2:8), white
solid, yield 198 mg (82%), 1H NMR (400 MHz, CDCl3)  7.37 (dd, J = 8.4, 2.5 Hz, 1H), 7.34 (d,
J = 2.4 Hz, 1H), 7.30-7.25 (m, 2H), 7.03-6.99 (m, 2H), 6.90 (dd, J = 7.8, 0.8 Hz, 1H), 1.37 (s,
9H); 13C NMR (100 MHz, CDCl3)  151.3, 143.8, 141.9, 131.8, 128.8, 127.9, 126.6, 126.4,
125.4, 120.9, 117.5, 117.1, 34.2, 31.6. HRMS (ESI) m/z calcd for C16H19NO [M] - H 240.1383,
found 240.1400.
2'-Amino-5-methoxy-[1,1'-biphenyl]-2-ol (1o). Rf = 0.5 (ethyl acetate: hexane 2:8), white solid,
1
yield 176 mg (82%), H NMR (400 MHz, CDCl3)  7.25-7.20 (m, 2H), 6.98-6.95 (m, 2H), 6.87
(d, J = 3.0 Hz, 1H), 6.86-6.83 (m, 2H), 4.79 (s, 2H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) 
153.9, 147.6, 141.8, 131.6, 129.0, 126.9, 126.3, 121.0, 118.9, 117.3, 115.7, 115.2, 55.8. HRMS
(ESI) m/z calcd for C13H13NO2 [M] + H 216.1019, found 216.1041.
2'-Amino-5-chloro-4'-methoxy-[1,1'-biphenyl]-2-ol (1p). Rf = 0.5 (ethyl acetate: hexane 2:8),
white solid, yield 199 mg (80%), 1H NMR (400 MHz, CDCl3)  7.23-7.19 (m, 2H), 7.10 (d, J =
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8.4 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.53 (dd, J = 8.4, 2.6 Hz, 1H), 6.40 (d, J = 2.6 Hz, 1H),
13
3.80 (s, 3H), 3.74 (brs, 2H); C NMR (100 MHz, CDCl3)  160.8, 152.4, 143.0, 132.6, 130.6,
128.9, 127.4, 125.6, 119.2, 117.3, 106.8, 102.9, 55.3. HRMS (ESI) m/z calcd for C13H12ClNO2
[M] + H 250.0629, found 250.0659.
2'-Amino-4'-(tert-butyl)-5-chloro-[1,1'-biphenyl]-2-ol (1q). Rf = 0.5 (ethyl acetate: hexane
1
1:9), white solid, yield 185 mg (67%), H NMR (400 MHz, CDCl3)  7.29 (d, J = 2.6 Hz, 1H),
7.23 (dd, J = 8.6, 2.6 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 8.0, 1.8 Hz, 1H), 6.96 (d, J
= 8.6 Hz, 1H), 6.89 (d, J = 1.8 Hz, 1H), 3.76 (brs, 2H), 1.32 (s, 9H); 13C NMR (100 MHz,
CDCl3)  152.8, 152.6, 140.8, 131.4, 130.5, 128.9, 127.8, 125.6, 122.9, 119.7, 118.9, 114.9, 34.6,
31.2. HRMS (ESI) m/z calcd for C16H18ClNO [M] - H 274.0993, found 274.1022.
2'-Amino-5-chloro-4'-fluoro-[1,1'-biphenyl]-2-ol (1r). Rf = 0.5 (ethyl acetate: hexane 1:9),
1
white solid, yield 163 mg (69%), H NMR (400 MHz, CDCl3)  7.26-7.21 (m, 2H), 7.13 (m,
1H), 6.94 (d, J = 8.5 Hz, 1H), 6.65 (td, J = 8.4, 2.5 Hz, 1H), 6.57 (dd, J = 10.0, 2.5 Hz, 1H),
13
6.51 (brs, 1H), 3.83 (brs, 2H), C NMR (100 MHz, CDCl3)  164.9, 162.4, 152.2, 143.8(d, J =
10.7 Hz), 133.1(d, J = 9.8 Hz), 130.6, 129.5, 126.4, 125.9, 119.6(d, J = 2.8 Hz), 119.1, 107.7,
107.5, 103.9, 103.6. HRMS (ESI) m/z calcd for C12H9ClFNO [M] - H 236.0273, found 236.0298.
2'-Amino-4'-methoxy-[1,1'-biphenyl]-2-ol (1s). Rf = 0.4 (ethyl acetate: hexane 1:9), white
solid, yield 150 mg (70%), 1H NMR (400 MHz, CDCl3)  7.29-7.24 (m, 2H), 7.12 (d, J = 8.5 Hz,
1H), 7.03-6.97 (m, 2H), 6.52 (dd, J = 8.5, 2.5 Hz, 1H), 6.40 (d, J = 2.5 Hz, 1H), 3.80 (s, 3H), 13C
NMR (100 MHz, CDCl3)  160.5, 153.6, 143.4, 132.7, 131.2, 129.2, 125.6, 121.1, 117.9, 117.5,
106.3, 102.5, 55.3. HRMS (ESI) m/z calcd for C13H3NO2 [M] - H 214.0868, found 214.0872
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2'-Amino-[1,1'-biphenyl]-2-ol (1t)18. Rf = 0.5 (ethyl acetate: hexane 1:9), white solid, yield 141
1
mg (76%), H NMR (400 MHz, CDCl3)  7.32-7.29 (m, 2H), 7.25-7.21 (m, 2H), 7.05-7.02 (m,
2H), 7.00-6.95 (m, 1H), 6.86 (d, J = 8.1 Hz, 1H), 4.65 (brs, 2H), 13C NMR (125 MHz, CDCl3) 
153.7, 141.8, 131.8, 131.2, 129.5, 129.0, 126.1, 126.0, 121.2, 121.0, 118.1, 117.2.
General procedure for the synthesis of 4-nitro-dibenzofuran
In a 5 mL round-bottom flask equipped with a stir bar, NaNO2 (104 mg, 1.5 mmol), 1a (117 mg,
o
0.5 mmol) were added in 2 mL of CF3COOH/H2O (15:1) at 0 C under nitrogen atmosphare.
o
Then, reaction temperature was increased to 50 C. Progress of reaction was monitored by TLC.
After completion of the reaction (15 min.), the mixture was poured into water, and extracted four
times with 15 mL of ethyl acetate. The combined organic layers were dried over Na2SO4 and
filtered. The solvent was removed in vacuum and the residue was purified by column
chromatography (silica gel, eluent: hexane/ethyl acetate) to afford the product 2a with 92%
yield.
2-Chloro-7-methyl-4-nitrodibenzo[b,d]furan (2a). Rf = 0.5 (ethyl acetate: hexane 0.5:9.5),
white solid, yield 120 mg (92%), 1H NMR (400 MHz, CDCl3)  8.4 (d, J = 2.0 Hz, 1H), 8.06 (d,
J = 2.0 Hz, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.47 (s, 1H), 7.23 (d, J = 7.8 Hz, 1H), 2,54 (s, 3H);
13C NMR (100 MHz, CDCl3)  157.8, 147.1, 140.8, 133.7, 129.8, 128.0, 126.1, 125.7, 122.0,
120.5, 118.9, 112.7, 22.1. HRMS (ESI) m/z calcd for C13H8ClNO3 [M] + Na 284.0085, found
284.0089.
3-Methyl-6-nitrodibenzo[b,d]furan (2b). Rf = 0.6 (ethyl acetate: hexane 1:9), white solid,
1
yield 14 mg (12%), H NMR (400 MHz, CDCl3)  8.73 (d, J = 2.3 Hz, 1H), 8.30 (dd, J = 9.0,
2.3 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.54 (d, J = 9.0 Hz, 1H), 7.37 (s, 1H), 7.22 (d, J = 7.8Hz,
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1H), 2.53 (s, 3H); 13C NMR (100 MHz, CDCl3)  159.2, 157.9, 143.7, 139.8, 125.2, 125.1,
122.4, 120.7, 120.4, 116.6, 112.4, 111.7, 22.0. HRMS (APCI) m/z calcd for C13H9NO3 [M] - H
226.0499, found 226.0524.
7-Methyl-2-nitrodibenzo[b,d]furan (2b'). Rf = 0.5 (ethyl acetate: hexane 1:9), white solid,
1
yield 69 mg (61%), H NMR (400 MHz, CDCl3)  8.26 (dd, J= 8.3, 0.8 Hz, 1H), 8.21 (dd, J
=7.6, 0.8 Hz, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.57 (s, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.29-7.27 (m,
1H), 2.59 (s, 3H). 13C NMR (100 MHz, CDCl3)  157.4, 148.6, 139.8, 134.1, 128.6, 126.5, 125.4,
122.5, 122.4, 120.3, 119.8, 112.7, 22.1. HRMS (APCI) m/z calcd for C13H9NO3 [M] - H
226.0499, found 226.0524.
2,7-Dimethyl-4-nitrodibenzo[b,d]furan (2c). Rf = 0.5 (ethyl acetate: hexane 1:9), white solid,
yield 89 mg (74%), 1H NMR (400 MHz, CDCl3)  7.99 (s, 1H), 7.93 (s, 1H), 7.76 (d, J = 7.8 Hz,
1H), 7.47 (s, 1H), 7.20 (d, J = 7.8 Hz, 1H), 2.54 (s, 3H), 2.52 (s, 3H); 13C NMR (100 MHz,
CDCl3)  157.5, 147.0, 139.5, 133.4, 132.8, 128.4, 126.9, 125.2, 122.8, 120.2, 119.8, 112.6, 22.1,
21.0. HRMS (ESI) m/z calcd for C14H11NO3 [M] + H 242.0812, found 242.0805.
2-(tert-Butyl)-7-methyl-4-nitrodibenzo[b,d]furan (2d). Rf = 0.4 (hexane), white solid, yield
109 mg (77%), 1H NMR (400 MHz, CDCl3)  8.26 (d, J = 1.8 Hz, 1H), 8.19 (d, J = 1.8 Hz, 1H),
13
7.84 (d, J = 7.9 Hz, 1H), 7.51 (s, 1H), 7.23 (d, J = 7.9 Hz, 1H), 2.54 (s, 3H), 1.45 (s, 9H); C
NMR (100 MHz, CDCl3)  157.6, 146.9, 146.7, 139.5, 13.4, 128.2, 125.2, 123.5, 120.2, 120.1,
119.8, 112.7, 35.1, 31.6, 22.1. HRMS (ESI) m/z calcd for C17H17NO3 [M] + Na 306.1101, found
306.1092.
2-Fluoro-7-methyl-4-nitrodibenzo[b,d]furan (2e). Rf = 0.5 (ethyl acetate: hexane 0.5:9.5),
1
white solid, yield 91 mg (74%), H NMR (400 MHz, CDCl3)  7.92 (dd, J = 8.8, 2.5 Hz, 1H),
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7.85 (dd, J = 7.3, 2.5 Hz, 1H), 7.78 (d, J =8.1 Hz, 1H), 7.250 (s, 1H), 7.24 (d, J = 7.3 Hz, 1H),
13
2.54 (s, 3H); C NMR (100 MHz, CDCl3)  158.5, 158.1, 156.1, 145.0, 140.8, 129.5(d, J =9.5
Hz), 125.5, 120.5, 119.4(d, J = 3.4 Hz), 113.4, 113.1, 112.8, 109.7, 109.5, 22.1. HRMS (ESI)
m/z calcd for C13H8FNO3 [M] 245.0483, found 245.0472.
2-Bromo-7-methyl-4-nitrodibenzo[b,d]furan (2f). Rf = 0.5 (ethyl acetate: hexane 0.5:9.5),
1
white solid, yield 110 mg (72%), H NMR (400 MHz, CDCl3)  8.30 (d, J = 1.8 Hz, 1H), 8.23
(d, J = 1.8 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 1.49 (s, 1H), 7.24 (d, J =8.2 Hz, 1H), 2.54 (s, 3H);
13C NMR (100 MHz, CDCl3)  157.7, 147.5, 140.8, 134.0, 130.3, 129.1, 125.8, 124.8, 120.5,
118.7, 114.7, 112.8, 22.1. HRMS (ESI) m/z calcd for C13H8BrNO3 [M] + Na 327.9580, found
327.9568.
7-Methyl-4-nitrodibenzo[b,d]furan-2-carbonitrile (2g).. Rf = 0.5 (ethyl acetate: hexane 2:8),
brown solid, yield 62 mg (49%), 1H NMR (400 MHz, CDCl3)  8.50 (d, J =1.6Hz, 1H), 8.44 (d,
J = 1.6Hz, 1H), 7.88 (d, J = 8.0HZ, 1H), 7.59 (s, 1H), 7.33 (d, J = 8.0Hz, 1H), 2.58 (s, 3H); 13C
NMR (175 MHz, CDCl3) 158.1, 150.4, 141.9, 134.0, 130.0, 129.5, 126.5, 125.9, 120.8, 118.4,
117.1, 113.0, 106.9, 22.3. HRMS (APCI) m/z calcd for C14H8N2O3 [M] 252.0529, found
252.0553.
2-Methoxy-7-methyl-4-nitrodibenzo[b,d]furan (2h). Rf = 0.5 (ethyl acetate: hexane 0.5:9.5),
1
white solid, yield 101 mg (79%), H NMR (400 MHz, CDCl3)  7.76 (d, J = 7.8 Hz, 1H), 7.33
(d, J = 2.5 Hz, 1H), 7.65 (d, J = 2.5 Hz, 1H), 7.46 (s, 1H), 7.19 (d, J = 7.8 Hz, 1H), 3.94 (s, 3H),
2.52 (s, 3H); 13C NMR (100 MHz, CDCl3)  157.9, 155.1, 143.6, 139.9, 133.5, 129.1, 125.1,
120.3, 119.9, 112.7, 112.1, 107.8, 56.5, 22.1. HRMS (APCI) m/z calcd for C14H11NO4 [M] + H
258.0761, found 258.0785.
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2-(Benzyloxy)-7-methyl-4-nitrodibenzo[b,d]furan (2i). Rf = 0.5 (ethyl acetate: hexane 1:9),
1
white solid, yield 93 mg (56%), H NMR (400 MHz, CDCl3)  7.85 (d, J = 2.5 Hz, 1H), 7.78-
7.75 (m, 2H), 7.47 (m, 3H), 7.41 (m, 2H), 7.35 (m 1H), 7.21 (d, J = 8.0 Hz, 1H), 5.20 (s, 2H),
2.53(s, 3H); 13C NMR (100 MHz, CDCl3)  157.9, 154.1, 143.8, 140.0, 135.9, 133.5, 129.2,
128.8, 128.4, 127.6, 125, 120.4, 119.9, 113.3, 112.7, 108.9, 71.4, 22.1. HRMS (APCI) m/z calcd
for C20H15NO4 [M] - H 332.0917, found 332.0945.
7-Methyl-4-nitro-2-(trifluoromethoxy)dibenzo[b,d]furan (2j). Rf = 0.5 (ethyl acetate: hexane
1
1:9), white solid, yield 122 mg (79%), H NMR (400 MHz, CDCl3)  8.10 (d, J = 1.2 Hz, 1H),
8.03 (d, J = 1.2 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.54 (s, 1H), 7.25 (d, J = 7.9 Hz, 1H), 2.56 (s,
3H); 13C NMR (175 MHz, CDCl3)  158.2, 146.8, 143.5(q, J = 2.3 Hz), 141.1, 133.5, 129.7,
125.8, 121.8, 120.6, 119.3, 119.2, 115.6, 112.9, 22.1. HRMS (APCI) m/z calcd for C14H8F3NO4
[M] 311.0400, found 311.0398.
7-Methyl-4-nitro-2-phenyldibenzo[b,d]furan (2k). Rf = 0.5 (ethyl acetate: hexane 1:9), white
solid, yield 98 mg (65%), 1H NMR (400 MHz, CDCl3)  8.4 (d, J = 1.6 Hz, 1H), 8.32 (d, J =1.6
Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.67 (d, J = 7.2 Hz, 2H), 7.52 (t, J = 7.8 Hz, 3H), 7.42 (tt, J =
13
7.3, 1.5 Hz, 1H), 7.26-7.24 (m, 1H), 2.54 (s, 3H); C NMR (100 MHz, CDCl3)  157.8, 148.0,
140.0, 138.9, 136.7, 134.0, 129.2, 129.1, 128.2, 127.3, 125.4, 124.7, 121.2, 120.4, 119.9, 112.8,
22.1. HRMS (ESI) m/z calcd for C19H13NO3 [M] + H 304.o968, found 304.0951.
2-(4-Bromophenyl)-7-methyl-4-nitrodibenzo[b,d]furan (2l). Rf = 0.5 (ethyl acetate: hexane
1:9), light yellow solid, yield 106 mg (56%), 1H NMR (400 MHz, CDCl3)  8.42 (d, J = 1.5 Hz,
1H), 8.34 (d, J = 1.5 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.58 (d, J = 8.2
13
Hz, 3H), 7.30 (d, J = 8.2 Hz, 1H), 2.59 (s, 3H), C NMR (175 MHz, CDCl3)  157.8, 148.1,
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140.2, 137.9, 135.5, 134.0, 132.2, 129.3, 128.9, 125.6, 124.5, 122.6, 121.0, 120.4, 119.8, 112.8,
22.1. HRMS (APCI) m/z calcd for C19H12BrNO3 [M] + H 382.0073, found 382.0064.
2-Chloro-4-nitrodibenzo[b,d]furan (2m). Rf = 0.5 (ethyl acetate: hexane 1:9), white solid,
yield 85 mg (69%), 1H NMR (400 MHz, CDCl3)  8.23 (d, J = 2.0 Hz, 1H), 8.17 (d, J = 2.0 Hz,
1H), 7.94 (d, J = 7.7 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.59 (td, J = 8.4, 1.2 Hz, 1H), 7.44 (t, J
= 7.7 Hz, 1H); 13C NMR (100 MHz, CDCl3)  157.4, 147.1, 134.0, 129.7(2C), 128.2, 126.3,
124.4, 122.7, 121.5, 121.1, 112.7. HRMS (ESI) m/z calcd for C12H6ClNO3 [M] + H 248.0114,
found 248.0117.
2-(tert-Butyl)-4-nitrodibenzo[b,d]furan (2n). Rf = 0.5 (hexane), white solid, yield 102 mg
(76%), 1H NMR (400 MHz, CDCl3)  8.31 (d, J = 1.9 Hz, 1H), 8.24 (d, J = 1.9 Hz, 1H), 7.98(d,
J = 7.6 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.53 (td, J = 8.3, 1.3 Hz, 1H), 7.41(td, J = 7.8, 1.3 Hz,
1H), 1.46 (s, 9H); 13C NMR (100 MHz, CDCl3)  157.2, 146.9, 146.8, 133.5, 128.6, 128.1,
123.9, 123.8, 122.7, 120.7, 120.4, 112.5, 35.1, 31.6. HRMS (ESI) m/z calcd for C16H15NO3 [M]
+ H 270.1125, found 270.1118.
2-Methoxy-4-nitrodibenzo[b,d]furan (2o). Rf = 0.5 (hexane), white solid, yield 96 mg (79%),
1H NMR (400 MHz, CDCl3)  7.92 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 2.4 Hz, 1H), 7.72 (d, J =
2.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 7.39 (t, 7.4 Hz, 1H), 3.96 (s, 3H),
13
1.24 (grease); C NMR (100 MHz, CDCl3)  157.5, 155.2, 143.6, 133.6, 129.0, 128.9, 123.7,
122.5, 120.9, 112.5, 112.4, 108.6, 56.5. HRMS (ESI) m/z calcd for C13H9NO4 [M] + H 244.0604,
found 244.0589.
2-Chloro-7-methoxy-4-nitrodibenzo[b,d]furan (2p). Rf = 0.5 (ethyl acetate: hexane 1:9), white
1
solid, yield 96 mg (69%), H NMR (400 MHz, CDCl3)  8.09 (d, J = 2.1 Hz, 1H), 8.01 (d, J =
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2.1 Hz, 1H), 7.74 (d, J = 8.6 Hz, 1H), 7.18 (d, J = 2.1 Hz, 1H), 6.97 (dd, J = 8.6, 2.1 Hz, 1H),
3,86 (s, 3H); 13C NMR (175 MHz, CDCl3)  161.8, 159.0, 147.2, 133.6, 129.9, 128.3, 12.6,
121.5, 121.1, 114.4, 113.4, 96.8, 55.9. HRMS (APCI) m/z calcd for C13H8ClNO4 [M] 277.0136,
found 277.0165.
7-(tert-Butyl)-2-chloro-4-nitrodibenzo[b,d]furan (2q). Rf = 0.5 (ethyl acetate: hexane 1:9),
white solid, yield 94 mg (62%), 1H NMR (400 MHz, CDCl3)  8.17 (d, J = 2.0 Hz, 1H), 8.12 (d,
J = 2.0, 1.0 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.75 (d, J = 1.4 Hz, 1H), 7.50 (dd, J = 8.3, 1.4
13
Hz, 1H), 1.41 (s, 9H); C NMR (175 MHz, CDCl3)  157.9, 154.5, 147.3, 133.7, 129.8, 128.0,
126.2, 122.2, 122.1, 120.4, 118.7, 109.5, 35.6, 31.5. HRMS (ESI) m/z calcd for C16H14ClNO3
[M] + H 304.0740, found 304.0756.
2-Chloro-7-fluoro-4-nitrodibenzo[b,d]furan (2r). Rf = 0.5 (ethyl acetate: hexane 1:9), white
1
solid, yield 92 mg (68%), H NMR (400 MHz, CDCl3)  8.23 (d, J = 2.0 Hz, 1H), 8.15 (d, J =
2.0 Hz, 1H), 7.92-7.88 (m, 1H), 7.45 (dd, J = 8.4, 2.1 Hz, 1H), 7.21 (td, J = 8.9, 2.1 Hz, 1H); 13C
NMR (100 MHz, CDCl3)  164.8, 162.3, 157.8(d, J = 13.6Hz), 147.6(d, J = 2.0Hz), 133.8,
129.0, 128.7, 126.2, 122.4, 121.9(d, J = 10.4Hz), 117.9(d, J = 2.2Hz), 113.0, 112.8, 100.9,
100.7. HRMS (APCI) m/z calcd for C12H5ClFNO3 [M] 264.9937, found 264.9960.
3-Methoxy-6-nitrodibenzo[b,d]furan (2s). Rf = 0.45 (ethyl acetate: hexane 0.5:9.5), yellow
1
solid, yield 22 mg (18%), H NMR (400 MHz, CDCl3)  8.16 (dd, J = 8.3, 1.0 Hz, 1H), 8.11
(dd, J = 8.3, 1.0 Hz, 1H), 7.82 (d, J = 8.6 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 8.23 (d, J = 2.0 Hz,
13
1H), 7.01(dd, J = 8.6, 2.1 Hz, 1H), 3.91 (s, 3H); C NMR (100 MHz, CDCl3)  161.2, 158.4,
148.7, 133.9, 128.6, 125.9, 122.7, 121.5, 121.2, 115.2, 112.9, 96.8, 55.9. HRMS (ESI) m/z calcd
for C13H9NO4 [M] + Na 266.0424, found 266.0423
29