Acid-catalyzed cascade rearrangement of 4-acetoxy-9-furylnaphtho[2,3-b] furans

Article abstract of DOI:10.1007/s00706-013-1075-7

Acid-catalyzed recyclization of 4-acetoxy-9-furylnaphtho[2,3-b]furans efficiently produced naphtho[1,2-b:3,4-b']difurans. On the other hand, 4-aminonaphtho[2,3-b]furans failed to undergo the analogous recyclization into benzo[g]furo[2,3-e]indoles. The dif

Full text of DOI:10.1007/s00706-013-1075-7

Monatsh Chem (2013) 144:1711–1723
DOI 10.1007/s00706-013-1075-7
ORIGINAL PAPER
Acid-catalyzed cascade rearrangement of 4-acetoxy-9-
furylnaphtho[2,3-b]furans
Alexander V. Fin’ko
Vladimir T. Abaev
•
Valery O. Babikov
•
•
Arkady S. Pilipenko
Igor V. Trushkov Alexander V. Butin
•
•
Received: 21 May 2013 / Accepted: 5 August 2013 / Published online: 24 September 2013
Ó Springer-Verlag Wien 2013
Abstract Acid-catalyzed recyclization of 4-acetoxy-9-
furylnaphtho[2,3-b]furans efficiently produced naphtho[1,2-
b:3,4-b’]difurans. On the other hand, 4-aminonaphtho[2,3-
b]furans failed to undergo the analogous recyclization into
benzo[g]furo[2,3-e]indoles. The difference in behavior of
these two types of substrates was explained by employing
density functional theory calculations.
Introduction
The isomeric naphthofuran core omnipresent in various
natural and synthetic biologically active compounds is an
increasingly attractive target for synthetic and medicinal
chemists [1–10]. Naphthodifurans have been studied less,
but they have potential pharmaceutical utility. For many
years the single reported example of naphtho[1,2-b:3,4-
b’]difuran 1 was tetraphenyl derivative 2 synthesized by
condensation of benzoin with 1,3-dihydroxynaphthalene
Keywords Heterocycles ꢀ Protonation ꢀ Recyclization ꢀ
Reaction mechanisms ꢀ Density functional theory
(Scheme 1a) [11]. We recently reported the acid-catalyzed
transformation of 4-acetoxy-9-furylnaphtho[2,3-b]furans 3
into naphthodifurans 4 (Scheme 1b) [12]. This reaction
represents a simple approach to an array of functionalized
naphthodifurans 4, which can be further modified to access
a large diversity of naphtho[1,2-b:3,4-b’]difurans 1. This
simple idea inspired us to study this transformation in
detail aiming for extension of the reaction applicability and
elucidation of the mechanism of reaction. Herein we pro-
vide a full account of this investigation.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-1075-7) contains supplementary
material, which is available to authorized users.
A. V. Fin’ko ꢀ V. O. Babikov ꢀ A. S. Pilipenko ꢀ A. V. Butin
Kuban State Technological University, Krasnodar,
Russian Federation
V. T. Abaev
North-Ossetian State University, Vladikavkaz,
Russian Federation
Results and discussion
9
-Furylnaphthofurans 3 were synthesized by treatment of
2-carboxyaryl)difurylmethanes 5 [13, 14] with a mixture
of acetic anhydride and acetic acid in the presence of ZnCl2
I. V. Trushkov (&)
(
Department of Chemistry, M. V. Lomonosov Moscow State
University, Moscow, Russian Federation
e-mail: itrushkov@mail.ru; trush@phys.chem.msu.ru
(
Table 1) [15].
In our preliminary report we demonstrated that napht-
I. V. Trushkov
hofurans 3 undergo recyclization into naphthodifurans 4 in
only moderate yields. So, we opted to optimize this
transformation by screening various reaction conditions
typically applied for furan recyclizations. Specifically, we
treated compounds 3 with a mixture of acetic and hydro-
chloric acids either at room temperature [16, 17] or under
Dmitriy Rogachev Federal Research Center of Pediatric
Hematology, Oncology, and Immunology, Moscow,
Russian Federation
A. V. Butin (&)
Perm State University, Perm, Russian Federation
e-mail: alexander_butin@mail.ru
123

1
712
A. V. Fin’ko et al.
moderate heating [18, 19]. Alternatively, the mixture was
refluxed in benzene solution in the presence of TsOH [20]
isomerization into angular isomer 7, which further isomer-
ized into the final naphthodifuran 4 (Scheme 2).
or HClO /AcOH combination [21]. However, these
4
This mechanistic rationale is supported by our DFT
calculations, which were performed by employing the
B3LYP functional and 6-311G** basis set. This modeling
attempts did not improve the reaction yields from what was
obtained under the earlier described conditions, i.e., when
naphthofurans 3 were heated under reflux with ethanolic
HCl for 20–40 min (Table 1).
0
showed 4-hydroxy-5-(2-furyl)naphtho[1,2-b]furan (7 ,
Fig. 1) to be 24.3 kJ/mol more stable than the isomeric
0
0
TLC monitoring demonstrated that the reaction proceeds
through the formation of an unstable intermediate. Shortened
reaction time and decreased quantity of HCl allowed for its
accumulation in the reaction mixture. Any attempts to isolate
this intermediate, however, were unsuccessful. It is believed
that the described rearrangement proceeded as a cascade
process involving deacylation of 3, followed by protonation
of linear naphthofuran 6 at the C(2) position resulting in its
naphtho[2,3-b]furan 6 . In its turn, 7 is 9.1 kJ/mol less
0
1
(R = R = R = H).
stable than the corresponding naphthodifuran
4
2
3
Isomerization of ortho-(2-furyl)phenols 7 into the cor-
responding benzofuran moiety is analogous to recyclization
of ortho-(2-furyl)anilines into indoles [21]. So, we suppose
that the mechanisms of these two processes are the same.
Recyclization of 6 into 7 has, to the best of our
knowledge, a single analogue in the literature, namely,
recyclization of 4-aminobenzofurans into 4-hydroxyindoles
[22]. This precedent prompted us to believe that 4-amino-
9-furylnaphtho[2,3-b]furans 8 could undergo a related
rearrangement into 5-furyl-4-hydroxybenz[g]indoles 9,
followed by the corresponding transformation of 9 into
benzo[g]furo[2,3-e]indoles 10 (Scheme 3).
Scheme 1
Ph
O
Ph
O
Y
a)
OH
O
Ph
Ph
OH
X
H SO
2
4
O
OH
heat
O
Z
R3
O
Ph
1
2
Ph
To evaluate this assumption and extend the applicability
of the discussed transformation, we attempted to synthesize
4-aminonaphtho[2,3-b]furans from the same starting com-
pounds 5 (Scheme 4). Carboxylic acids 5 were reduced to
b)
OAc
O
R1
R1
R2
HCl
EtOH
R3
R2
O
O
O
the corresponding benzyl alcohols 11 with LiAlH . Oxi-
4
R3
R3
dation of these alcohols with pyridinium chlorochromate
3
4
(PCC) gave aldehydes 12 which were transformed into
9-furylnaphtho[2,3-b]furans 13 by treatment with HClO4.
Table 1 Synthesis and acid-catalyzed rearrangement of 4-acetoxy-9-furylnaphtho[2,3-b]furans 3
R3
OAc
R1
R2
CO H
2
R1
R2
O
Ac O, AcOH
HCl
R1
R2
2
R3
R3
O
ZnCl2
O
EtOH
O
O
O
O
R3
R3
R3
5a-5g
3a-3g
4a-4g
1
R
2
R
3
Entry
R
Yield of 3/%
Yield of 4/%
a
b
c
d
e
f
H
H
Me
Me
Me
Et
31
31
33
28
31
40
37
40
42
42
37
41
48
55
Cl
Br
Br
H
H
H
H
Cl
H
Me
Me
Me
OMe
OMe
g
OMe
1
23

Acid-catalyzed cascade rearrangement
1713
Scheme 2
OAc
OH
OH
R1
R1
R1
HCl
H
R3
R3
R3
EtOH
R2
O
R2
O
R2
O
O
O
O
R3
R3
R3
3
6
R3
R3
H
O
O
OH
R1
R2
R1
R2
R1
R2
R3
H
H+
OH
O
O
O
O
O
7
R3
R3
R3
R3
H+
O
R3
R3
O
O
R1
R2
R1
R2
R1
R2
H
O
O
O
H
H
H
O
O
O
H+
R3
4
R3
R3
OH
O
O
Heating of compounds 15 under reflux in ethanolic HCl
for a short time led to the formation of monoacylated
products 8 (Table 3). This partial hydrolysis of 15 was
found to be more efficient under alkaline conditions
wherein compounds 8 are formed in 70–88 % yields.
Compounds 8 could serve as substrates for an acid-induced
rearrangement. Accordingly, we expected that prolonged
treatment of 15 with ethanolic HCl would afford either the
corresponding benzindoles 9 or benzo[g]furo[2,3-e]indoles
O
OH
O
O
H
O
O
6
', Erel = 33.4 kJ/mol
7', Erel = 9.1 kJ/mol
4', Erel = 0
0
0
0
Fig. 1 Relative energies of model compounds 4 , 6 , and 7
determined at B3LYP/6-311G** level
1
0. Indeed, 15 disappeared after heating under reflux for
Nitration of 13 produced 4-nitro derivatives 14 [15]. Unex-
pectedly, common reducing agents like Raney Ni/N H , Zn/
30–40 min. However, the expected products 9 and/or 10 were
2
4
not detected in the reaction mixture; instead only tar was
obtained. Similarly, when pure compounds 8a and 8b, iso-
lated after alkaline hydrolysis of 15a and 15b, were heated
with ethanolic HCl until full conversion, significant tarring of
the reaction mixture precluded isolation of any product.
On the basis of our previous experience [19, 27], we
supposed that these negative results are caused by com-
NaOH, Fe/AcOH, and Zn/AcOH failed to give 4-amino-
4
naphthofurans 8 (R = H) owing to the formation of either a
complex mixture of unidentified products or polymeric resins
(
the related reduction of 9-nitroanthracene was shown to
proceed efficiently affording 9-aminoanthracene [23–26]).
This observation advocates for rather low stability of amines
4
(R = H). To avoid this issue we decided to convert amines
8
in situ into much more stable amide derivatives. To this end,
4
peting deacylation of N-acylindoles 9 (R = Ac) leading to
0
NH-indoles 9 which undergo oligomerization in ethanolic
reduction of 14 with Zn in Ac O was performed to afford
2
HCl. This problem can be avoided by utilization of the
corresponding N-tosyl derivatives as both N-tosylanilines
and N-tosylindoles are stable under the utilized reaction
conditions. Therefore, we transformed compound 8a into
4
-(diacetylamino)naphthofurans 15 in good yields (Table 2).
The structures of compounds 15 were determined by a
combination of spectral methods and proved unambigu-
ously for 15b by single-crystal X-ray analysis (Fig. 2).
123

1
714
A. V. Fin’ko et al.
R3
R3
R4
R4
Scheme 3
R1
NHR4
N
N
R1
R2
R1
R2
H+
?
H+
?
R3
R2
O
OH
O
O
O
O
R3
R3
R3
8
9
10
Scheme 4
OH
O
R1
CO2H
R1
R2
R1
R2
LiAlH4
Et2O
PCC
CH2Cl2
R2
O
O
O
O
O
O
5
a-5c, 5g
11a-11c, 11g
12a-12c, 12g
NO2
NAc2
R1
R1
R1
HClO4
,4-Dioxane
NaNO2
Zn
1
R2
O
O
AcOH
R2
O
Ac2O
R2
O
O
O
1
3a-13c, 13g
14a-14c, 14g
15a-15c, 15g
Table 2 Yields of compounds 11–15
1
2
R
Entry
R
Yield/%
1
1
12
13
14
15
a
b
c
H
H
92
98
93
90
70
68
66
65
59
63
60
55
30
33
32
24
67
72
71
60
Cl
H
Br
H
g
OMe
OMe
1
2
3
4
its N-tosyl analogue 17 in 78 % yield via tosylation/deac-
ylation sequence (Scheme 5).
(R = R = R = R = H) using DFT calculations employ-
ing the B3LYP functional with the 6-311G** basis set
(Fig. 3). It was found that the most stable cation B is
To our great disappointment, neither prolonged heating
of 16 nor refluxing of isolated compound 17 with ethanolic
HCl afforded the desired recyclization product. The com-
plete consumption of starting compounds was achieved at
ca. 45 min; however, no formation of isolable products was
observed. Therefore, the above explanation of decompo-
sition is inappropriate for compound 17.
0
0
formed by protonation of 6 at the C(5 ) atom of the 9-furyl
group. Cation A, which was proposed as a key intermediate, is
0
significantly less stable than B. Moreover, protonation of 6 at
the C(4) and C(9) atoms produces cations C and D, respec-
tively, which are also more stable than A. Fortunately, the
main transformation of cations B–D is their reversed depro-
tonation. Nevertheless, moderate yields of naphthodifurans 4
can be explained by side reactions via formation of these
cations.
To understand the difference in behaviors of 4-acet-
oxynaphthofurans 3 and their 4-acetylamino analogues 8,
0
0
we studied the protonation of a model compounds 6 and 8
1
23

Acid-catalyzed cascade rearrangement
1715
0
Similar results were obtained by protonation of 8
compounds are also compatible with acids [33, 34]. Furan
rings in both 18 and 19 are not conjugated or fused to
another arene; therefore, they are susceptible to facile
hydrolysis. Even if the lifetime of 18 and 19 is small, it is
enough for decomposition of the starting compound. As a
result, tar is only formed in reactions of 8 and 17.
(
Fig. 4). However, cation G formed by protonation of C(9)
can be stabilized in two ways. First, it can form N,O-acetal
8 which is known to be relatively stable even in the
1
presence of anhydrous acids (Scheme 6) [28–32]. Second,
N-deprotonation can lead to iminoanthracene 19. These
Conclusion
4
-Acetoxy-9-furylnaphtho[2,3-b]furans undergo cascade
0
rearrangement into naphtho[1,2-b:3,4-b ]difurans under
heating with ethanolic HCl. On the contrary, the related
4-acetylamino and 4-tosylamino derivatives do not form
the corresponding benzo[g]furo[2,3-e]indoles under these
reaction conditions but produce tar instead. Density func-
tional theory calculations on model compounds were
employed to explain the obtained results.
Experimental
1 13
H NMR and C NMR spectra were recorded on a Bruker
DPX 300 spectrometer at room temperature; the chemical
shifts d were measured in parts per million with respect to the
1
13
solvent (CDCl , H: d = 7.25 ppm, C: d = 77.2 ppm;
3
1
13
DMSO-d , H: d = 2.50 ppm, C: d = 39.7 ppm). Cou-
6
pling constants (J) are given in Hertz. Multiplicities of signals
are described as follows: s = singlet, d = doublet, t = trip-
let, q = quadruplet, m = multiplet, dd = double doublet,
br = broadened. IR spectra were measured as KBr plates on
InfraLUM FT-02 and InfraLUM FT-801 instruments. Mass
spectra were recorded on a Kratos MS-30 instrument with
70 eV electron impact ionization at 200 °C. Elemental
Fig. 2 Single-crystal X-ray structure of 15b
Table 3 Partial hydrolysis of 15
NAc2
NHAc
R1
R1
HCl/EtOH or
NaOH/EtOH
R2
O
R2
O
O
O
1
5a-15c, 15g
8a-8c, 8g
1
2
R
Entry
R
Yield of 8/%
HCl/EtOH, 1–2 min
NaOH/EtOH
a
b
c
H
H
62
70
65
45
88
75
78
70
Cl
H
Br
H
g
OMe
OMe
123

1
716
A. V. Fin’ko et al.
Scheme 5
Ac
Ts
O
NHAc
N
NHTs
TsCl
NaH
HCl/EtOH
heat, 5 min
O
O
O
O
O
8
a
16
17
Fig. 3 Results of B3LYP/6-
11G** calculations of
protonated 9-furyl-4-
OH
OH
OH
H OH
3
H
H
0
hydroxynaphtho[2,3-b]furan 6
O
O
O
O
H
O
O
O
O
H
H
A
B
C
D
Erel = 23.1 kJ/mol
Erel = 0
Erel = 20.1 kJ/mol
Erel = 15.9 kJ/mol
NH2
NH2
NH2
NH3+
H NH2
H
H
O
O
O
O
O
O
O
H
O
O
O
H
H
E
F
G
H
I
Erel = 0
Erel = 20.5 kJ/mol
Erel = 13.3 kJ/mol
Erel = 27.8 kJ/mol
Erel = 21.7 kJ/mol
0
Fig. 4 Results of calculations of protonated forms of model compound 8
Scheme 6
PG
PG
N
HN
EtO HN PG
O
-
H+
EtOH
O
O
H
O
H
O
H
O
1
9
G'
18
analyses were performed with a Fisons EA-1108 CHNS
elemental analyzer instrument. Melting points were deter-
mined in capillaries with an Electrothermal 9100 capillary
melting point apparatus. Column chromatography was per-
formed on silica gel KSK (50–160 lm, LTD Sorbpolymer).
All the reactions were carried out using freshly distilled and
dry solvents. Compounds 5 were synthesized according to
reported procedures [13, 14]. Crystallographic data (exclud-
ing structure factors) for compound 15b have been deposited
with the Cambridge Crystallographic Data Center as sup-
plementary publication number CCDC 924197. Copies of the
data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (fax: ?44 (0)1223
336033 or e-mail: deposit@ccdc.cam.ac.uk).
1
23

Acid-catalyzed cascade rearrangement
1717
General procedure for synthesis of 4-acetoxy-9-
(1H, d, J = 3.1 Hz, HFur), 6.35 (1H, s, HFur), 6.26 (1H, d,
J = 3.1 Hz, HFur), 3.94 (3H, s, OCH ), 2.53 (3H, s, CH ),
furylnaphtho[2,3-b]furans 3
3
3
1
.49 (6H, s, 2CH ) ppm; C NMR (75 MHz, CDCl3):
3
2
3
3
Compound 5 (5.0 mmol) was refluxed with 10 cm acetic
3
acid, 10 cm acetic anhydride, and 10 mg ZnCl2 until
d = 168.8, 158.3, 156.5, 152.4, 149.9, 146.3, 135.2, 128.0,
124.6, 124.3, 122.8, 118.3, 112.9, 108.4, 107.4, 99.7, 98.5,
55.1, 20.8, 14.4, 13.9 ppm; IR (KBr): mꢀ = 1,762, 1,605,
completion of the reaction (TLC control). The reaction
3
mixture was poured into 50 cm cold water, neutralized
-1
1,431, 1,231, 1,189, 1,037, 794 cm ; MS (70 eV):
?
m/z = 350 (M , 12), 308 (100), 293 (15), 265 (11), 43 (16).
3
with NaHCO , and extracted with CH Cl (3 9 25 cm ).
3
2
2
The combined organic extracts were dried with Na SO ,
2
4
6
,7-Dimethoxy-2-methyl-9-(5-methylfuran-2-yl)naph-
treated with charcoal, and filtered. The solvent was
removed under reduced pressure. Product was isolated by
column chromatography on silica gel with petroleum ether/
CH Cl (4:1) as eluent and recrystallized from petroleum
tho[2,3-b]furan-4-yl acetate (3g, C H O )
2
2 20 6
Starting from 5g, 0.70 g 3g (37 %) was isolated as pale
yellow needles. M.p.: 146–147 °C; R = 0.70 (acetone/
f
2
2
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
2
2
ether/CH Cl .
2
2
CDCl ): d = 7.99 (1H, s, H ), 7.15 (1H, s, H ), 6.89 (1H,
3
Ar
Ar
2
-Methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]furan-4-yl
d, J = 3.2 Hz, HFur), 6.31 (1H, s, HFur), 6.25 (1H, d,
acetate (3a)
Starting from 5a, 0.5 g 3a (31 %) was isolated as pale yellow
J = 3.2 Hz, HFur), 4.01 (3H, s, OCH ), 3.99 (3H, s, OCH ),
3
3
2.52 (3H, s, CH ), 2.48 (3H, s, CH ), 2.47 (3H, s, CH )
3 3 3
13
1
needles. M.p.: 146–147 °C(Ref. [15] 145–147 °C). IR, Hand
C NMR data are identical to those described in Ref. [15].
ppm; C NMR (75 MHz, CDCl ): d = 168.9, 157.3,
3
13
152.0, 150.7, 149.5, 148.7, 146.9, 135.5, 124.8, 120.8,
119.5, 112.7, 107.6, 107.3, 105.2, 99.8, 99.2, 55.8 (2C),
6
-Chloro-2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]-
21.0, 14.5, 14.0 ppm; IR (KBr): mꢀ = 1,756, 1,613, 1,507,
1,481, 1,432, 1,369, 1,265, 1,210, 1,179, 1,162, 1,015,
furan-4-yl acetate (3b)
Starting from 5b, 0.55 g 3b (31 %) was isolated as pale
-
783 cm ; MS (70 eV): m/z = 380 (M , 22), 338 (67),
1
?
yellow needles. M.p.: 141–142 °C (Ref. [15] 140–143 °C).
IR, H and C NMR data are identical to those described
in Ref. [15].
322 (100), 307 (29), 279 (50), 264 (23), 236 (35), 43 (15).
1
13
General procedure for synthesis of naphthodifurans
4a–4g
6
-Bromo-2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]-
furan-4-yl acetate (3c)
3
A suspension of compound 3 (5.0 mmol) in 130 cm 33 %
ethanolic HCl was refluxed until complete dissolution of
the starting compound. Then the reaction mixture was
Starting from 5c, 0.66 g 3c (33 %) was isolated as pale
yellow needles. M.p.: 149–150 °C (Ref. [15] 148–150 °C).
IR, H and C NMR data are identical to theose described in
1
13
3
poured into 500 cm of water and neutralized with sodium
Ref. [15].
carbonate to pH 7. The resulting precipitate was filtered,
dried, dissolved in benzene/hexane (1:1), and passed
through a pad of silica gel. The refined solution was
evaporated under reduced pressure; the residue was
recrystallized from ethanol.
6
-Bromo-2-ethyl-9-(5-ethylfuran-2-yl)naphtho[2,3-b]-
furan-4-yl acetate (3d)
Starting from 5d, 0.6 g 3d (28 %) was isolated as yellow
1
needles. M.p.: 84–86 °C (Ref. [15] 84–86 °C). IR, H and
C NMR data are identical to those described in Ref. [15].
1
3
1
-(2-Methylnaphtho[1,2-b:3,4-b’]difuran-5-yl)-2-propa-
7
-Chloro-2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]-
none (4a, C H O )
1
8 14 3
furan-4-yl acetate (3e)
Starting from 3a, 0.56 g 4a (40 %) was isolated as a pale
yellow solid. M.p.: 94–96 °C; R = 0.62 (acetone/CH Cl /
Starting from 5e, 0.55 g 3e (31 %) was isolated as pale
yellow needles. M.p.: 166–168 °C (Ref. [15] 166–168 °C).
IR, H and C NMR data are identical to those described
f
2
2
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
3
1
13
d = 8.35–8.32 (1H, m, H ), 8.12–8.08 (1H, m, H ),
Ar
Ar
in Ref. [15].
7.59–7.51 (2H, m, H ), 7.08 (1H, s, HFur), 6.71 (1H, s,
Ar
HFur), 3.95 (2H, s, CH ), 2.59 (3H, s, CH ), 2.26 (3H, s,
2
3
6
-Methoxy-2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]-
1
3
CH ) ppm; C NMR (75 MHz, CDCl ): d = 203.5, 154.9,
3
3
furan-4-yl acetate (3f, C H O )
2
1 18 5
149.3, 149.0, 145.8, 125.0 (2C), 124.7, 124.4, 123.8, 120.7,
Starting from 5f, 0.70 g 3f (40 %) was isolated as pale
yellow needles. M.p.: 140–141 °C; R = 0.75 (acetone/
119.0, 113.3, 104.9, 100.1, 43.8, 29.3, 14.2 ppm; IR (KBr):
f
mꢀ = 1,720, 1,588, 1,566, 1,530, 1,440, 1,390, 1,159, 1,108,
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
2
2
-1
81, 948, 815, 764 cm ; MS (70 eV): m/z = 278 (M ,
?
9
CDCl ): d = 8.51 (1H, d, J = 9.8 Hz, H ), 7.21 (1H, dd,
J = 2.7, 9.8 Hz, H ), 7.18 (1H, d, J = 2.7 Hz, H ), 6.89
Ar Ar
3
Ar
27), 235 (100), 207 (17), 179 (18), 178 (30), 149 (10), 55
(16), 43 (19).
123

1
718
A. V. Fin’ko et al.
?
1
2
-(9-Chloro-2-methylnaphtho[1,2-b:3,4-b’]difuran-5-yl)-
(70 eV): m/z = 314/312 (M , 5/15), 271/269 (32/96), 234
(30), 176 (33), 163 (17), 151 (13), 126 (11), 88 (14), 75
(15), 43 (100).
-propanone (4b, C H ClO )
1
8
13
3
Starting from 3b, 0.66 g 4b (42 %) was isolated as yellow
crystals. M.p.: 113–115 °C; R = 0.61 (acetone/CH Cl /
f
2
2
0
1
2
-(9-Methoxy-2-methylnaphtho[1,2-b:3,4-b ]difuran-5-yl)-
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
3
-propanone (4f, C H O )
1
9 16 4
d = 8.27 (1H, s, H ), 8.01 (1H, d, J = 8.7 Hz, H ), 7.44
Ar
Ar
Starting from 3f, 0.74 g 4f (48 %) was isolated as yellow
crystals. M.p.: 138–139 °C; R = 0.54 (acetone/CH Cl /
(
1H, d, J = 8.7 Hz, H ), 7.07 (1H, s, HFur), 6.70 (1H, s,
Ar
f
2
2
HFur), 3.96 (2H, s, CH ), 2.59 (3H, s, CH ), 2.28 (3H, s,
2
3
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
1
3
3
CH ) ppm; C NMR (75 MHz, CDCl ): d = 203.5, 155.5,
3
3
d = 7.96 (1H, d, J = 9.0 Hz, H ), 7.60 (1H, d,
J = 2.4 Hz, H ), 7.16 (1H, dd, J = 2.4, 9.0 Hz, H ),
Ar Ar
Ar
1
49.3, 148.3, 145.6, 130.4, 125.3, 125.1, 122.3, 119.7,
1
19.4, 118.8, 114.1, 104.7, 100.1, 43.6, 29.5, 14.2 ppm; IR
6
3
.98 (1H, s, HFur), 6.67 (1H, s, HFur), 3.98 (3H, s, OCH3),
.91 (2H, s, CH ), 2.57 (3H, s, CH ), 2.24 (3H, s, CH )
(
KBr): mꢀ = 1,716, 1,566, 1,355, 1,136, 1,116, 1,079, 944,
-
60, 808, 777 cm ; MS (70 eV): m/z = 314/312 (M ,
1
?
2
3
3
8
1
3
ppm; C NMR (75 MHz, CDCl ): d = 203.8, 156.9,
54.7, 148.8, 148.6, 144.4, 125.3, 119.6, 119.0, 118.9,
3
1
0/30), 271/269 (33/100), 234 (32), 205 (10), 178 (17), 163
1
(
21), 152 (13), 43 (14).
1
16.6, 113.5, 104.6, 100.1, 99.9, 55.3, 43.7, 29.2,
1
2
-(9-Bromo-2-methylnaphtho[1,2-b:3,4-b’]difuran-5-yl)-
14.1 ppm; IR (KBr): mꢀ = 1,714, 1,570, 1,535, 1,360,
1,220, 1,165, 1,001, 834 cm ; MS (70 eV): m/z = 308
-
1
-propanone (4c)
?
(M , 78), 265 (100), 222 (21), 165 (14), 43 (22).
Starting from 3c, 0.75 g 4c (42 %) was isolated as yellow
1
crystals. M.p.: 135–136 °C (Ref. [12] 135–137 °C). IR, H
and C NMR data are identical to those described in Ref.
1
3
1-(8,9-Dimethoxy-2-methylnaphtho[1,2-b:3,4-b’]difuran-
[
12].
5-yl)-2-propanone (4g, C20H O )
18 5
Starting from 3g, 0.93 g 4g (55 %) was isolated as yellow
crystals. M.p.: 167–168 °C; R = 0.47 (acetone/CH Cl /
1
-(9-Bromo-2-ethylnaphtho[1,2-b:3,4-b’]difuran-5-yl)-
f
2
2
butan-2-one (4d, C H BrO )
2
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
0
17
3
3
Starting from 3d, 0.71 g 4d (37 %) was isolated as yellow
crystals. M.p.: 123–124 °C; R = 0.65 (acetone/CH Cl /
d = 7.60 (1H, s, H ), 7.38 (1H, s, H ), 7.02 (1H, s, HFur),
Ar
Ar
f
2
2
6.55 (1H, s, HFur), 4.07 (3H, s, OCH ), 4.04 (3H, s, OCH ),
3 3
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
3
3
.94 (2H, s, CH ), 2.57 (3H, s, CH ), 2.26 (3H, s, CH )
2
3
3
d = 8.43 (1H, d, J = 1.5 Hz, H ), 7.91 (1H, d, J = 8.7 Hz,
H ), 7.55 (1H, dd, J = 1.5, 8.7 Hz, H ), 7.03 (1H, s,
Ar Ar
13
ppm; C NMR (75 MHz, CDCl ): d = 204.1, 154.2,
Ar
3
1
1
1
1
49.0, 148.7, 148.6, 148.4, 128.4, 119.3, 118.5, 113.6,
HFur), 6.70 (1H, s, HFur), 3.96 (2H, s, CH ), 2.93 (2H, q,
2
11.7, 104.7, 104.0, 100.6, 100.1, 56.1, 56.0, 43.9, 29.5,
4.3 ppm; IR (KBr): mꢀ = 1,713, 1,579, 1,528, 1,492, 1,462,
J = 7.2 Hz, CH ), 2.60 (2H, q, J = 7.2 Hz, CH ), 1.43
2
2
(
3H, t, J = 7.2 Hz, CH ), 1.11 (3H, t, J = 7.2 Hz, CH )
3
-1
;
3
,371, 1,281, 1,246, 1,213, 1,157, 1,006, 844, 798 cm
?
1
3
ppm; C NMR (75 MHz, CDCl ): d = 206.2, 161.3,
3
MS (70 eV): m/z = 338 (M , 36), 295 (100), 280 (14), 251
16), 59 (18), 43 (16).
1
1
1
1
49.6, 148.0, 145.9, 128.0, 125.6, 123.1, 122.7, 120.1,
18.9, 118.5, 114.1, 104.7, 98.7, 42.6, 35.5, 22.0,
2.1, 7.7 ppm; IR (KBr): mꢀ = 1,714, 1,562, 1,519, 1,384,
(
-
1
,356, 1,109, 1,038, 925, 806, 753 cm ; MS (70 eV):
?
Synthesis of [2-(difuranylmethyl)phenyl]methanols 11
m/z = 386/384 (M , 13/13), 329/327 (100/100), 248 (13),
2
32 (16).
Lithium aluminum hydride (100.0 mmol) was added por-
tionwise to an ice-cooled suspension of benzoic acid 5
O and stirred for
3
(50.0 mmol) in 150 cm anhydrous Et
1
2
-(8-Chloro-2-methylnaphtho[1,2-b:3,4-b’]difuran-5-yl)-
2
-propanone (4e, C H ClO )
1
5 h. Then mixture was poured into ice water (caution!) and
neutralized with 6 M hydrochloric acid. The product was
8
13
3
Starting from 3e, 0.64 g 4e (41 %) was isolated as a white
solid. M.p.: 154–155 °C; R = 0.60 (acetone/CH Cl /
3
O (3 9 100 cm ). The extract was dried
extracted with Et
with Na SO
f
2
2
2
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
, treated with charcoal, and filtered. The sol-
3
2
4
d = 8.20 (1H, d, J = 8.7 Hz, H ), 8.04 (1H, d,
J = 2.1 Hz, H ), 7.46 (1H, dd, J = 2.1, 8.7 Hz, H ),
Ar Ar
vent was removed under reduced pressure; the residue was
recrystallized from petroleum ether.
Ar
7
2
.03 (1H, s, HFur), 6.67 (1H, s, HFur), 3.95 (2H, s, CH ),
2
1
.57 (3H, s, CH ), 2.27 (3H, s, CH ) ppm; C NMR
3
[2-[Bis(5-methylfuran-2-yl)methyl]phenyl]methanol
(11a)
Starting from 5a, 13.65 g 11a (92 %) was isolated as a
3
3
(
75 MHz, CDCl ): d = 203.5, 155.1, 149.2, 148.8, 146.2,
3
130.6, 125.1, 124.9, 123.0, 122.0, 118.2, 117.0, 113.3,
1
04.6, 100.0, 43.6, 29.3, 14.1 ppm; IR (KBr): mꢀ = 1,714,
1,605, 1,393, 1,166, 1,086, 940, 892, 814, 763 cm ; MS
white solid. M.p.: 65–67 °C (Ref. [15] 65–67 °C). IR and
H NMR data are identical to those described in Ref. [15].
-
1
1
1
23

Acid-catalyzed cascade rearrangement
1719
1
[5-Chloro-2-[bis(5-methylfuran-2-yl)methyl]phenyl]metha-
and H NMR data are identical to those described in Ref.
[15].
nol (11b)
Starting from 5b, 12.6 g 11b (98 %) was isolated as a
white solid. M.p.: 71–72 °C (Ref. [15] 71–72 °C). IR and
H NMR data are identical to those described in Ref. [15].
5
-Bromo-2-[bis(5-methylfuran-2-yl)methyl]benzaldehyde
(
12c)
1
Starting from 11c, 7.92 g 12c (66 %) was isolated as pale
yellow prisms. M.p.: 85–87 °C (Ref. [15] 85–87 °C). IR
and H NMR data are identical to those described in Ref.
[
5-Bromo-2-[bis(5-methylfuran-2-yl)methyl]phenyl]metha-
1
nol (11c)
Starting from 5c, 14.8 g 11c (93 %) was isolated as a white
[15].
1
solid. M.p.: 75–76 °C (Ref. [15] 75–76 °C). IR and H
NMR data are identical to those described in Ref. [15].
2-[Bis(5-methylfuran-2-yl)methyl]-4,5-
dimethoxybenzaldehyde (12g, C H O )
2
0 20 5
[
2-[Bis(5-methylfuran-2-yl)methyl]-4,5-dimethoxy-
Starting from 11g, 7.74 g 12g (65 %) was isolated as a
white solid. M.p.: 94–95 °C; R = 0.68 (acetone/CH Cl /
phenyl]methanol (11g, C H O )
2
0 22 5
f
2
2
Starting from 5g, 15.39 g 11g (90 %) was isolated as a
white solid. M.p.: 96–97 °C; R = 0.38 (acetone/CH Cl /
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
3
f
2
2
d = 10.22 (1H, s, CHO), 7.40 (1H, s, H ), 6.74 (1H, s,
H ), 6.29 (1H, s, CH), 5.88 (4H, s, H ), 3.93 (3H, s,
Ar Fur
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
Ar
3
d = 6.92 (1H, s, H ), 6.71 (1H, s, H ), 5.86 (2H, d,
J = 3.2 Hz, HFur), 5.84 (2H, d, J = 3.2 Hz, HFur), 5.63
13
Ar
Ar
OCH ), 3.83 (3H, s, OCH ), 2.24 (6H, s, 2CH ) ppm;
3
C
3
3
NMR (75 MHz, CDCl ): d = 189.8, 153.7, 152.0 (2C),
3
(
(
(
1H, s, CH), 4.66 (2H, s, CH ), 3.87 (3H, s, OCH ), 3.75
2 3
151.9 (2C), 148.3, 137.0, 126.8, 112.2, 111.8, 109.1 (2C),
1
3H, s, OCH ), 2.23 (6H, s, 2CH ) ppm; C NMR
3
3
3
106.3 (2C), 56.2, 56.1, 39.6, 13.7 (2C) ppm; IR (KBr):
75 MHz, CDCl ): d = 152.8 (2C), 151.7 (2C), 148.7,
3
mꢀ = 1,684, 1,596, 1,563, 1,512, 1,442, 1,268, 788,
1
6
1
7
48.1, 130.9, 130.4, 112.5, 112.4, 108.5 (2C), 106.2 (2C),
3.0, 56.1, 56.0, 40.6, 13.8 (2C) ppm; IR (KBr): mꢀ = 3,508,
,609, 1,516, 1,462, 1,279, 1,216, 1,165, 1,091, 1,018, 783,
-1
?
7
2
5
55 cm ; MS (70 eV): m/z = 340 (M , 48), 322 (24),
97 (100), 283 (43), 258 (16), 254 (10), 175 (10), 106 (10),
9 (10), 43 (36).
-
1
?
56 cm ; MS (70 eV): m/z = 324 (M - H O, 49), 281
2
(
(
40), 264 (89), 224 (100), 209 (29), 193 (28), 181 (60), 165
28), 152 (26), 119 (25), 91 (28), 77 (26), 65 (25), 51 (28),
General procedure for synthesis
of 9-furanylnaphtho[2,3-b]furans 13
4
3 (27).
3
To a solution of 12 (18.0 mmol) in 50 cm 1,4-dioxane,
General procedure for synthesis
3
.5 cm 70 % HClO was added. Reaction mixture was
0
4
of 2-(difuranylmethyl)benzaldehydes 12
stirred at 40 °C for 20 min. The reaction mixture was
3
poured into 250 cm water, neutralized with NaHCO , and
3
A solution of alcohol 11 (35.0 mmol) in 100 cm dry
3
3
extracted with CH Cl (3 9 100 cm ). The combined
2
2
CH Cl was added dropwise to a suspension of pyridinium
2
2
organic fractions were dried with Na SO , treated with
2
3
chlorochromate (70.0 mmol) in 100 cm dry CH Cl . The
4
2
2
charcoal, and filtered. The solvent was removed under
reduced pressure. Product was isolated by flash chroma-
tography on silica gel with petroleum ether/benzene (5:1)
as eluent and recrystallized from petroleum ether/benzene.
mixture was stirred for 6 h at room temperature. The pre-
cipitate was filtered and washed with hot CH Cl
2
2
3
3 9 100 cm ). The combined solvent was concentrated
(
under reduced pressure. Product was purified by column
chromatographically on silica gel with petroleum ether/
CH Cl (10:1) as eluent. The fraction containing benzal-
2-Methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]furan
2
2
(
13a)
3
dehyde was concentrated to 20 cm and left to crystallize
overnight.
Starting from 12a, 612 mg 13a (59 %) was isolated as
colorless crystals. M.p.: 59–61 °C (Ref. [15] 59–61 °C).
IR, H and C NMR data are identical to those described
1
13
2
-[Bis(5-methylfuran-2-yl)methyl]benzaldehyde (12a)
Starting from 11a, 8.17 g 12a (70 %) was isolated as
colorless prisms. M.p.: 63–65 °C (Ref. [15] 63–65 °C). IR
and H NMR data are identical to those described in Ref. [15].
in Ref. [15].
6-Chloro-2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]-
1
furan (13b)
Starting from 12b, 605 mg 13b (63 %) was isolated as pale
5
-Chloro-2-[bis(5-methylfuran-2-yl)methyl]benzaldehyde
(
12b)
Starting from 11b, 7.06 g 12b (68 %) was isolated as pale
yellow prisms. M.p.: 75–77 °C (Ref. [15] 75–77 °C). IR
yellow crystals. M.p.: 94–95 °C (Ref. [15] 94–96 °C). IR,
H and C NMR data are identical to those described in
Ref. [15].
1
13
123

1
720
A. V. Fin’ko et al.
6
-Bromo-2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]-
d, J = 9.0 Hz, H ), 7.83 (1H, dd, J = 2.0, 9.0 Hz, H ),
Ar Ar
furan (13c)
7.28 (1H, d, J = 3.2 Hz, HFur), 7.19 (1H, s, HFur), 6.54
Starting from 12c, 555 mg 13c (60 %) was isolated as pale
yellow crystals. M.p.: 119–121 °C (Ref. [15] 119–121 °C).
IR, H and C NMR data are identical to those described
(1H, d, J = 3.2 Hz, HFur), 2.63 (3H, s, CH ), 2.54 (3H, s,
3
CH ) ppm; IR (KBr): mꢀ = 1,616, 1,596, 1,572, 1,504,
3
1
13
-1
1,492, 1,320, 1,308, 1,264, 1,236, 800, 792 cm ; MS
?
(70 eV): m/z = 387/385 (M , 48/48), 357/355 (100/99),
in Ref. [15].
314/312 (19/19), 189 (16), 149 (13), 55 (14), 43 (25).
6
,7-Dimethoxy-2-methyl-9-(5-methylfuran-2-yl)naph-
tho[2,3-b]furan (13g, C H O )
2
6,7-Dimethoxy-2-methyl-9-(5-methylfuran-2-yl)-4-nitro-
0 18 4
Starting from 12g, 3.19 g 13g (55 %) was isolated as a
white solid. M.p.: 93–94 °C; R = 0.54 (acetone/CH Cl /
naphtho[2,3-b]furan (14g, C H NO )
6
2
0
17
Starting from 13g, 1.50 g 14g (24 %) was isolated as a red-
orange solid. M.p.: 231–232 °C; R = 0.59 (acetone/
f
2
2
1
petroleum ether = 1:1:2); H NMR (300 MHz, CDCl ):
3
f
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
d = 8.01 (1H, s, H ), 7.70 (1H, s, H ), 7.16 (1H, s, H ),
Ar
Ar
Ar
2
2
6
.95 (1H, d, J = 3.0 Hz, HFur), 6.43 (1H, s, HFur), 6.27
CDCl ): d = 8.27 (1H, s, H ), 8.10 (1H, s, H ), 7.12 (1H,
3
Ar
Ar
(
1H, d, J = 3.0 Hz, HFur), 4.00 (6H, s, 2OCH ), 2.50 (3H,
3
d, J = 3.3 Hz, HFur), 7.01 (1H, s, HFur), 6.32 (1H, d,
1
s, CH ), 2.48 (3H, s, CH ) ppm; C NMR (75 MHz,
3
J = 3.3 Hz, HFur), 4.05 (3H, s, OCH ), 4.00 (3H, s, OCH ),
3
3
3
3
1
3
CDCl ): d = 157.1, 151.9, 150.5, 149.1, 148.1, 147.5,
2.55 (3H, s, CH ), 2.50 (3H, s, CH ) ppm; C NMR
3 3
3
1
28.4, 127.1, 123.8, 116.4, 112.6, 107.6, 106.5, 104.9,
(75 MHz, CDCl ): d = 169.1, 161.3, 153.9, 151.0, 149.1,
3
1
02.3, 97.4, 55.9, 55.7, 14.6, 14.0 ppm; IR (KBr):
148.8, 145.7, 126.9, 124.0, 121.2, 116.3, 115.4, 108.4,
105.7, 103.8, 102.3, 56.0, 55.7, 14.7, 14.0 ppm; IR (KBr):
mꢀ = 1,603, 1,514, 1,476, 1,437, 1,270, 1,238, 1,216, 1,023,
mꢀ = 1,620, 1,503, 1,465, 1,400, 1,260, 1,145, 1,029, 872,
-
1
?
783 cm ; MS (70 eV): m/z = 322 (M , 100), 307 (24),
279 (50), 264 (27), 236 (34), 165 (15), 149 (20), 101 (16),
59 (44), 43 (37).
-
1
?
802 cm ; MS (70 eV): m/z = 367 (M , 55), 337 (100),
321 (32), 310 (12), 294 (25), 279 (17), 251 (21), 235 (10),
178 (11), 169 (15), 57 (13), 43 (33).
General procedure for nitration
of 9-furanylnaphtho[2,3-b]furans 13
General procedure for synthesis of 4-(diacetylamino)-
9-(5-methylfuran-2-yl)-naphtho[2,3-b]furans 15
Sodium nitrite (1.59 g, 23.0 mmol) was added to a solution
3
of 13 (17.0 mmol) in 100 cm glacial acetic acid and
stirred at room temperature for 0.5 h. The reaction mixture
3
To a solution of 14 (4.0 mmol) in 40 cm acetic anhydride,
4.55 g zinc dust (70.0 mmol) was added in small portions.
3
was poured into 500 cm water, neutralized with NaHCO ,
The reaction mixture was refluxed for 3 h, poured into
3
250 cm water, neutralized with NaHCO , and extracted
3
and filtered. Product was recrystallized from acetone.
3
3
with CH Cl (3 9 50 cm ). The combined organic frac-
2
2
2
-Methyl-9-(5-methylfuran-2-yl)-4-nitronaphtho[2,3-b]-
tions were dried with Na SO , treated with charcoal, and
2
4
furan (14a)
Starting from 13a, 350 mg 14a (30 %) was isolated as a
filtered. The solvent was evaporated under reduced pres-
sure. The residue was recrystallized from ethanol.
dark yellow solid. M.p.: 157–158 °C (Ref. [15]
1
13
1
57–159 °C). IR, H and C NMR data are identical to
those described in Ref. [15].
N-Acetyl-N-[2-methyl-9-(5-methylfuran-2-yl)naphtho
[2,3-b]furan-4-yl]acetamide (15a, C H NO )
2
2
19
4
Starting from 14a, 0.97 g 15a (67 %) was isolated as a
yellow solid. M.p.: 166–167 °C; R = 0.50 (acetone/
6
-Chloro-2-methyl-9-(5-methylfuran-2-yl)-4-nitronaph-
f
tho[2,3-b]furan (14b)
Starting from 13b, 430 mg 14b (33 %) was isolated as
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
2
2
CDCl ): d = 8.68–8.65 (1H, m, H ), 7.78–7.74 (1H, m,
3
Ar
a dark orange solid. M.p.: 211–213 °C (Ref. [15]
H ), 7.54–7.51 (2H, m, H ), 6.97 (1H, d, J = 3.0 Hz,
Ar Ar
1
13
211–213 °C). IR, H and C NMR data are identical to
those described in Ref. [15].
HFur), 6.41 (1H, s, HFur), 6.31 (1H, d, J = 3.0 Hz, HFur), 2.54
1
3H, s, CH ), 2.52 (3H, s, CH ), 2.32 (6H, s, 2CH ) ppm; C
3
(
3 3 3
6
-Bromo-2-methyl-9-(5-methylfuran-2-yl)-4-nitronaph-
NMR (75 MHz, CDCl ): d = 173.2 (2C), 160.6, 153.1,
3
tho[2,3-b]furan (14c, C H BrNO )
1
150.8, 145.9, 129.3, 129.0, 127.9, 127.1, 126.0, 125.6, 124.4,
121.1, 114.0, 111.3, 107.7, 99.8, 26.3 (2C), 14.7, 14.0 ppm;
IR (KBr): mꢀ = 1,704, 1,605, 1,554, 1,419, 1,366, 1,234, 983,
8
12
4
Starting from 13c, 2.10 g 14c (32 %) was isolated as a dark
orange solid. M.p.: 222–223 °C; R = 0.57 (acetone/
f
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
-1
?
945, 813, 766 cm ; MS (70 eV): m/z = 361 (M , 45), 319
2
2
DMSO-d ): d = 8.89 (1H, d, J = 2.0 Hz, H ), 8.64 (1H,
(72), 277 (71), 260 (15), 234 (17), 95 (16).
6
Ar
1
23

Acid-catalyzed cascade rearrangement
1721
-
782 cm ; MS (70 eV): m/z = 421 (M , 43), 379 (55),
1
?
N-Acetyl-N-[6-chloro-2-methyl-9-(5-methylfuran-2-
yl)naphtho[2,3-b]furan-4-yl]acetamide
336 (34), 43 (100).
(
15b, C H ClNO )
22 18 4
Starting from 14b, 1.14 g 15b (72 %) was isolated as a
yellow solid. M.p.: 191–192 °C; R = 0.53 (acetone/
Synthesis of 4-(acetylamino)-9-furanylnaphtho[2,3-b]-
furans 8
f
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
2
2
DMSO-d ): d = 8.56 (1H, d, J = 9.2 Hz, H ), 7.90 (1H,
d, J = 2.1 Hz, H ), 7.58 (1H, dd, J = 2.1, 9.2 Hz, H ),
Ar Ar
Method A
A suspension of 15 (4.0 mmol) in 130 cm 33 % ethanolic
HCl was refluxed for 1–2 min. The reaction mixture
6
Ar
3
7
.06 (1H, d, J = 3.2 Hz, HFur), 6.81 (1H, s, HFur), 6.45
3
poured into 500 cm water, neutralized with NaHCO , and
(
1H, d, J = 3.2 Hz, HFur), 2.54 (3H, s, CH ), 2.47 (3H, s,
3
3
1
CH ), 2.24 (6H, s, 2CH ) ppm; C NMR (75 MHz,
3
3
extracted with CH Cl (3 9 50 cm ). The combined
3
3
2
2
DMSO-d ): d = 172.4 (2C), 161.4, 153.2, 150.0, 144.4,
organic fractions were dried with Na SO , treated with
2 4
6
1
31.0, 130.3, 128.6, 128.5, 126.2, 126.1, 124.2, 120.3,
charcoal, and filtered. The solvent was removed under
reduced pressure. Product was isolated by flash chroma-
tography on silica gel with petroleum ether/benzene (1:1)
as eluent and recrystallized from petroleum ether/benzene.
1
14.5, 110.2, 108.1, 100.4, 26.0 (2C), 14.1, 13.5 ppm; IR
(
KBr): mꢀ = 1,724, 1,709, 1,599, 1,389, 1,369, 1,337, 1,273,
1
-
,244, 1,227, 1,105, 1,024, 988, 903, 789 cm ; MS
1
?
(
70 eV): m/z = 397/395 (M , 16/48), 355/353 (33/100),
13/311 (23/70), 297 (10), 268 (13), 43 (24).
3
Method B
Compound 15 (4.0 mmol) was added to a solution of 4.0 g
3
NaOH (100.0 mmol) in 20 cm EtOH. The reaction mix-
N-Acetyl-N-[6-bromo-2-methyl-9-(5-methylfuran-2-
yl)naphtho[2,3-b]furan-4-yl]acetamide
ture was heated for 10 min (TLC monitoring), poured into
(
15c, C H BrNO )
22 18 4
3
3
00 cm water, and extracted with CH Cl (3 9 50 cm ).
2
2 2
Starting from 14c, 1.25 g 15c (71 %) was isolated as a
yellow solid. M.p.: 208–210 °C; R = 0.54 (acetone/
The combined organic fractions were dried with Na SO ,
2
4
f
treated with charcoal, and filtered. The solvent was
removed under reduced pressure. Product was isolated by
flash chromatography on silica gel with petroleum ether/
benzene (1:1) as eluent and recrystallized from petroleum
ether/benzene.
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
2
2
DMSO-d ): d = 8.48 (1H, d, J = 9.6 Hz, H ), 8.06 (1H,
d, J = 2.4 Hz, H ), 7.69 (1H, dd, J = 2.4, 9.6 Hz, H ),
Ar Ar
6
Ar
7
.05 (1H, d, J = 3.3 Hz, HFur), 6.82 (1H, s, HFur), 6.44
(
1H, d, J = 3.3 Hz, HFur), 2.54 (3H, s, CH ), 2.46 (3H, s,
3
1
CH ), 2.24 (6H, s, 2CH ) ppm; C NMR (75 MHz,
3
N-[2-Methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]furan-
3
3
DMSO-d ): d = 172.8 (2C), 161.8, 153.6, 150.5, 144.8,
4-yl]acetamide (8a, C H NO )
20 17
6
3
1
30.6, 129.4, 129.1, 129.0, 126.7, 124.5, 123.9, 120.0,
Compound 8a was obtained from 15a as a beige solid
using method A (0.79 g, 62 %) or B (1.12 g, 88 %).
M.p.: 239–240 °C; R = 0.39 (acetone/CH Cl /petroleum
1
15.0, 110.7, 108.5, 100.8, 26.4 (2C), 14.5, 13.9 ppm; IR
(
KBr): mꢀ = 1,724, 1,596, 1,392, 1,368, 1,276, 1,244, 1,236,
1
f
2
2
-
,228, 792 cm ; MS (70 eV): m/z = 441/439 (M ,
1
?
1
ether = 1:1:2); H NMR (300 MHz, DMSO-d ): d = 10.13
6
1
0/10), 399/397 (17/17), 357/355 (30/30), 317 (15), 232
(1H, br s, NH), 8.41–8.39 (1H, m, H ), 8.11–8.07 (1H, m,
Ar
(
(
14), 203 (24), 189 (13), 175 (19), 151 (14), 51 (12), 43
100).
H ), 7.55–7.47 (2H, m, H ), 6.89 (1H, d, J = 3.3 Hz,
Ar Ar
HFur), 6.56 (1H, s, HFur), 6.39 (1H, d, J = 3.3 Hz, HFur), 2.51
1
3H, s, CH ), 2.45 (3H, s, CH ), 2.25 (3H, s, CH ) ppm; C
3
(
3 3 3
N-Acetyl-N-[6,7-dimethoxy-2-methyl-9-(5-methylfuran-2-
yl)naphtho[2,3-b]furan-4-yl]acetamide
NMR (75 MHz, DMSO-d ): d = 168.4, 157.4, 152.0, 150.3,
6
145.4, 127.9, 126.3, 126.1, 125.3, 125.1, 124.4, 123.8, 123.1,
(
15g, C H NO )
24 23 6
112.9, 107.5, 107.3, 102.1, 22.8, 13.8, 13.3 ppm; IR (KBr):
Starting from 14g, 1.01 g 15g (60 %) was isolated as a pale
yellow solid. M.p.: 179–181 °C; R = 0.44 (acetone/
mꢀ = 3,219, 1,651, 1,529, 1,388, 1,281, 1,254, 1,028, 943,
f
-1
?
7
91, 764 cm ; MS (70 eV): m/z = 319 (M , 53), 276
100), 234 (26), 203 (11), 149 (22), 69 (12), 59 (17), 55 (24),
3 (37).
1
CH Cl /petroleum ether = 1:1:2); H NMR (300 MHz,
2
2
(
DMSO-d6): d = 7.97 (1H, s, H ), 7.06 (1H, d,
J = 3.0 Hz, HFur), 7.01 (1H, s, H ), 6.67 (1H, s, HFur),
Ar
Ar
4
6
.42 (1H, d, J = 3.0 Hz, HFur), 3.90 (3H, s, OCH ), 3.88
3
N-[6-Chloro-2-methyl-9-(5-methylfuran-2-yl)naphtho-
(
3H, s, OCH ), 2.50 (3H, s, CH ), 2.46 (3H, s, CH ), 2.24
3
[2,3-b]furan-4-yl]acetamide (8b, C H ClNO )
3
3
3
20 16
1
6H, s, 2CH ) ppm; C NMR (75 MHz, DMSO-d6):
3
(
Compound 8b was obtained from 15b as a beige solid using
method A (0.99 g, 70 %) or B (1.06 g, 75 %). M.p.: 247–
248 °C; R = 0.44 (acetone/CH Cl /petroleum ether =
3
d = 172.5 (2C), 158.7, 152.3, 149.4, 149.3, 149.1, 145.6,
1
27.0, 123.7, 123.5, 113.5, 108.8, 107.9, 104.9, 100.1,
f
2
2
1
1
00.0 (2C), 55.4, 55.1, 25.8 (2C), 14.0, 13.4 ppm; IR
1:1:2); H NMR (300 MHz, DMSO-d ): d = 10.18 (1H, br
6
(
KBr): mꢀ = 1,708, 1,508, 1,486, 1,261, 1,227, 1,213,
s, NH), 8.46 (1H, d, J = 9.2 Hz, H ), 8.10 (1H, d,
Ar
123

1
722
A. V. Fin’ko et al.
J = 2.1 Hz, H ), 7.51 (1H, dd, J = 2.1, 9.2 Hz, H ), 6.94
Ar Ar
with NH Cl, and extracted with ethyl acetate
4
3
(3 9 50 cm ). The combined organic fractions were dried
(
1H, d, J = 3.2 Hz, HFur), 6.57 (1H, s, HFur), 6.40 (1H, d,
J = 3.2 Hz, HFur), 2.51 (3H, s, CH ), 2.45 (3H, s, CH ), 2.27
3
with Na SO , treated with charcoal, and filtered. The
2
3
4
1
3H, s, CH ) ppm; C NMR (75 MHz, DMSO-d6):
3
(
solvent was removed under reduced pressure. Product was
isolated by flash chromatography on silica gel with
petroleum ether/CH Cl (3:1) as eluent. Recrystallization
3
d = 168.8, 158.5, 152.6, 150.5, 145.1, 129.2, 128.0, 127.6,
1
2
1
26.9, 126.2, 125.7, 123.7, 122.0, 113.7, 108.0, 107.6, 102.6,
3.1, 14.1, 13.6 ppm; IR (KBr): mꢀ = 3,249, 1,660, 1,603,
,527, 1,389, 1,279, 1,098, 1,030, 943, 897, 794 cm ; MS
2
2
from petroleum ether/CH Cl afforded 1.22 g (68 %) 16 as
2 2
-
1
a dark yellow solid. M.p.: 186–187 °C; R = 0.60 (ace-
f
?
70 eV): m/z = 355/353 (M , 13/38), 313/311 (33/100), 295
1
(
(
tone/CH Cl /petroleum
ether = 1:1:2);
H
NMR
2
2
25), 268 (24), 234 (16), 149 (27), 69 (18), 57 (40), 43 (41).
(300 MHz, DMSO-d ): d = 8.70–8.68 (1H, m, H ), 8.05
6
Ar
(
2H, d, J = 8.4 Hz, H ), 7.83–7.80 (1H, m, H ), 7.57–
Ts Ar
N-[6-Bromo-2-methyl-9-(5-methylfuran-2-yl)naphtho-
2,3-b]furan-4-yl]acetamide (8c, C H BrNO )
Compound 8c was obtained from 15c as a beige solid using
7
.46 (2H, m, H ), 7.36 (2H, d, J = 8.4 Hz, H ), 7.01 (1H,
Ar Ts
[
2
0
16
3
d, J = 3.3 Hz, HFur), 6.49 (1H, s, HFur), 6.31 (1H, d,
J = 3.3 Hz, HFur), 2.55 (3H, s, CH ), 2.51 (3H, s, CH ),
3
3
method A (1.03 g, 65 %) or B (1.24 g, 78 %). M.p.: 249–
1
.48 (3H, s, CH ), 1.71 (3H, s, CH ) ppm; C NMR
3
2
3 3
2
51 °C; Rf = 0.42 (acetone/CH Cl /petroleum ether =
2
2
(75 MHz, DMSO-d ): d = 170.9, 160.8, 153.2, 150.4,
1
6
1:1:2); H NMR (300 MHz, DMSO-d ): d = 10.22 (1H, br
6
1
1
1
45.6, 145.3, 135.9, 131.2, 130.1 (2C), 129.2, 129.1 (2C),
28.7, 127.0, 126.0, 125.5, 122.1, 121.5, 114.4, 112.1,
07.8, 100.8, 24.0, 21.7, 14.7, 13.9 ppm; IR (KBr):
s, NH), 8.37 (1H, d, J = 9.3 Hz, H ), 8.25 (1H, d,
Ar
J = 1.8 Hz, H ), 7.61 (1H, dd, J = 1.8, 9.3 Hz, H ), 6.91
Ar Ar
(1H, d, J = 3.3 Hz, HFur), 6.56 (1H, s, HFur), 6.39 (1H, d,
mꢀ = 1,709, 1,594, 1,354, 1,243, 1,208, 1,168, 1,084,
J = 3.3 Hz, HFur), 2.50 (3H, s, CH ), 2.44 (3H, s, CH ), 2.26
3
3
-1
,011, 947, 792, 760 cm ; MS (70 eV): m/z = 318
1
1
3
(
3H, s, CH ) ppm; C NMR (75 MHz, DMSO-d6):
3
?
M - Ts, 18), 303 (10), 276 (60), 260 (22), 203 (12),
(
d = 168.7, 158.4, 152.5, 150.4, 145.0, 128.1, 128.0, 127.4,
1
76 (11), 91 (56), 65 (34), 51 (14), 43 (100).
1
2
1
27.3, 126.3, 125.1, 123.6, 117.7, 113.6, 107.9, 107.5, 102.6,
3.1, 14.0, 13.6 ppm; IR (KBr): mꢀ = 3,248, 1,664, 1,600,
,528, 1,392, 1,280, 1,092, 892, 784 cm ; MS (70 eV):
4-Methyl-N-[2-methyl-9-(5-methylfuran-2-yl)naphtho[2,3-
-1
b]furan-4-yl]benzenesulfonamide (17, C H NO S)
2
5
21
4
?
m/z = 399/397 (M , 46/46), 357/355 (42/42), 312 (13), 232
10), 204 (12), 176 (9), 151 (11), 51 (12), 43 (100).
Compound 17 was obtained as a beige solid from 16 by
methods applied for the synthesis of 8—method A (1.34 g,
(
7
8 %) or B (1.50 g, 87 %). M.p.: 199–200 °C; R = 0.56
f
N-[6,7-Dimethoxy-2-methyl-9-(5-methylfuran-2-yl)naph-
1
(acetone/CH Cl /petroleum ether = 1:1:2);
H
NMR
2
2
tho[2,3-b]furan-4-yl]acetamide (8g, C H NO )
21
2
2
5
(300 MHz, DMSO-d ): d = 8.53–8.50 (1H, m, H ), 7.68–
6
Ar
Compound 8g was obtained from 15g as a white solid using
method A (0.68 g, 45 %) or B (1.06 g, 70 %). M.p.: 265–
7
.65 (1H, m, H ), 7.50 (2H, d, J = 8.4 Hz, H ), 7.41–7.35
Ar Ts
(1H, m, H ), 7.24–7.19 (1H, m, H ), 7.10 (2H, d,
Ar Ar
2
67 °C; R = 0.34 (acetone/CH Cl /petroleum ether =
f
2
2
J = 8.4 Hz, H ), 6.90 (1H, d, J = 3.3 Hz, HFur), 6.68 (1H,
Ts
1
1
:1:2); H NMR (300 MHz, DMSO-d ): d = 10.06 (1H, br
6
s, NH), 6.41 (1H, s, HFur), 6.26 (1H, d, J = 3.3 Hz, HFur),
s, NH), 7.87 (1H, s, H ), 7.35 (1H, s, H ), 6.94 (1H, d,
Ar Ar
2.47 (3H, s, CH ), 2.44 (3H, s, CH ), 2.33 (3H, s, CH ) ppm;
13
3 3 3
J = 3.0 Hz, HFur), 6.45 (1H, s, HFur), 6.38 (1H, d,
J = 3.0 Hz, HFur), 3.92 (3H, s, OCH ), 3.87 (3H, s, OCH ),
C NMR (75 MHz, DMSO-d ): d = 158.7, 152.7, 150.6,
6
3
3
1
46.0, 143.6, 136.4, 129.8, 129.5 (2C), 128.5, 128.0, 127.3
2
.49 (3H, s, CH ), 2.45 (3H, s, CH ), 2.25 (3H, s, CH ) ppm;
3 3 3
(2C), 126.1, 125.0, 124.4, 122.1, 120.2, 113.6, 110.0, 107.5,
1
3
C NMR (75 MHz, DMSO-d ): d = 168.5, 155.9, 151.7,
6
1
01.5, 21.4, 14.4, 13.9 ppm; IR (KBr): mꢀ = 3,276, 1,601,
1
1
1
1
7
49.5, 149.0, 147.8, 146.2, 124.6, 123.5, 123.0, 122.0, 112.6,
07.7, 106.2, 104.3, 102.4, 102.1, 55.2, 55.1, 23.1, 13.9,
3.5 ppm; IR (KBr): mꢀ = 3,244, 1,656, 1,532, 1,508, 1,488,
,472, 1,372, 1,264, 1,216, 1,196, 1,168, 1,044, 1,028,
-1
1
,409, 1,379, 1,330, 1,161, 1,090, 946, 787, 756 cm ; MS
?
70 eV): m/z = 431 (M , 5), 227 (78), 234 (15), 204 (34),
(
1
90 (15), 178 (18), 91 (94), 77 (15), 65 (67), 51 (24), 43 (100).
-1
?
84 cm ; MS (70 eV): m/z = 379 (M , 68), 336 (58), 292
Acknowledgments Financial support was provided by the Russian
Foundation for Basic Research (Grant 10-03-00254-a) and the Min-
istry of Education of the Permskii Krai. The authors would like to
express their special thanks to Dr. V.E. Zavodnik for the accom-
plishment of the X-ray analysis.
(
10), 43 (100).
N-[2-Methyl-9-(5-methylfuran-2-yl)naphtho[2,3-b]furan-
-yl]-N-[(4-methylphenyl)sulfonyl]acetamide
16, C H NO S)
4
(
2
7
23
5
3
Ice-cooled solution of 1.21 g 8a (3.8 mmol) in 25 cm dry
THF was treated with 0.36 g 60 % NaH (15.0 mmol) and
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Acid-catalyzed cascade rearrangement
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