Structure and stereochemistry of cyclodimers obtained by acid treatment of fraws-stilbenes and of W-l-diarylethylamides

Article abstract of DOI:10.1039/a900282k

The reaction of trans-stilbenes and H-1,2-diarylethylamides with ethyl polyphosphate affords indanes and tetralins with three stereogenic centres. The structural and configurational assignment of the cyclodimers is based mainly on the NMR and MS data. A p

Full text of DOI:10.1039/a900282k

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Structure and stereochemistry of cyclodimers obtained by acid
treatment of trans-stilbenes and of N-1,2-diarylethylamides
José M. Aguirre,a Elba N. Alesso and Graciela Y. Moltrasio Iglesias*b
a Department of Basic Science, National University of Luján, Luján, Argentina
b Department of Organic Chemistry, Faculty of Pharmacy and Biochemistry,
University of Buenos Aires, Buenos Aires, Argentina
Received (in Cambridge) 11th January 1999, Accepted 5th March 1999
The reaction of trans-stilbenes and N-1,2-diarylethylamides with ethyl polyphosphate affords indanes and tetralins
with three stereogenic centres. The structural and configurational assignment of the cyclodimers is based mainly on
the NMR and MS data. A possible transition state for the reaction is discussed.
In several communications we have reported that ethyl poly-
phosphate (EPP) can act on type I amides as a satisfactory and
mild cyclodehydration agent to produce dihydroisoquinoline
(DHIQ) and also as an effective deamidation reagent to pro-
duce trans-stilbenes. Furthermore, we have reported that in
some cases cyclodimeric derivatives were obtained as well as
trans-stilbenes (Scheme 1).1 Our previous results, summarised
in Table 1, show that the course of the reaction depends mainly
on the substituents present in the aromatic rings of the starting
amides. We have also documented that the reaction of some
N-acyl-1-arylalkylamines with EPP yields styrenes, but that
in some cases only phenylindanes may be isolated2 (Table 1).
Again, cyclodimerisation depends on the degree and type of
benzene ring substitution.
The cyclodimerisation of stilbenes and styrenes, with acidic
reagents, has been widely described in the literature,3–8 but
though there are no differences of opinion about the prepar-
ation of indane structures starting from styrenes, the situation
is not clear in the case of the dimerisation of stilbenes where the
formation of indanes, tetralins (1,2,3,4-tetrahydronaphthal-
enes) and open dimers has been reported. Walker9 in 1954 and
Battersby and Binks10 in 1958 were the first in reporting the
preparation of a dimer of trans-3,3Ј,4,4Ј-tetramethoxystilbene
originated from N-[1,2-bis(3,4-dimethoxyphenyl)ethyl]acet-
amide subjected to the conditions of the Bischler–Napieralsky
(B–N) reaction; however, they failed to indicate the structure of
the dimer. After that several authors, by treatment of cis- and
of trans-stilbene in different acidic conditions, have reported the
formation of cyclodimerisation products of the 1-benzylindane
type, trisubstituted tetralines and trimeric products.6,7,11,12 As a
rule, published data prove to be incomplete and even contra-
dictory, particularly as concerns the stereochemistry of the final
product.
The present work describes how, on the basis of spectro-
scopic data, it has been possible to perform structural assign-
ment and to determine the stereochemistry of a series of
cyclodimers (CDs), indanes and tetralins with three stereogenic
centres, obtained starting from some N-acyl-1,2-diaryethyl-
amines and trans-stilbenes with EPP (Table 2, Scheme 2). The
probable mechanism leading to cyclodimerisation products is
also discussed: indanes versus tetralins.
Structural assignment of the cyclodimers
The amides 1–6 and the trans-stilbenes 7–9 (Table 2, Scheme 2)
were treated with EPP at 80 ЊC for 8 h. Again it was observed
that the course of the reaction is modified by the substituents as
depicted in Scheme 1, as follows.
a) The prevalence of the “retro-Ritter” reaction (via A) when
the aryl group attached to the C-β is not nucleophilic enough in
the cyclisation position.
b) Whenever the “retro-Ritter” reaction affords a trans-
Table 1 Reaction products of amides with EPP
Dihydroiso-
quinoline (%)
Styrene or
stilbene (%)
Indanes
(%)
Tetralins
(%)
Entry
Amide
Ref.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
PhCHRCH2Ph
PhCHRCH2An
PhCHRCH2Ver
PhCHRCH2Pip
AnCHRCH2Ph
AnCHRCH2An
AnCHRCH2Ver
VerCHRCH2An
VerCHRCH24-NO2Ph
4-NO2PhCHRCH2Ver
AnCHRCH2C6H11
3-AnCHRCH2CH3
VerCHRCH3
77
71
1(b)
1(b)
1(b)
1(b)
1(b)
1(b)
1(b)
1(b)
1(b)
1(b)
2
89
85
78
82
10
33
80
7
8
37a
50a
7b
70
48
51
2
2
2
2
56c
56d
78e
VerCHRCH2CH3
PipCHRCH2CH3
R: NHCHO, Ph: phenyl, An: 4-methoxyphenyl, Ver: 3,4-dimethoxyphenyl, Pip: 3,4-methylenedioxyphenyl. a Mixture of regio- and stereoisomers.
b Mixture of stereoisomers. c Isomer: r-1-methyl-c-3-(3,4-dimethoxyphenyl)-5,6-dimethoxyindane. d Isomer: r-1-ethyl-c-2-methyl-t-3-(3,4-dimethoxy-
phenyl)-5,6-dimethoxyindane. e Isomer: r-1-ethyl-c-2-methyl-t-3-(3,4-methylenedioxyphenyl)-5,6-methylenedioxyindane.
J. Chem. Soc., Perkin Trans. 1, 1999, 1353–1358
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R3
R4
R3
R4
β
R1
R2
R1
R2
α
EPP
N
+
CR
NHCOR
I
via A
R3
R4
R3
R4
R1
R2
R1
R2
+
N
R
R3
R4
R1
R2
R1
R1
R2
R2
R3
R4
R3
R4
R2
and/or
R2
R1
R1
R4
R4
R3
R3
Scheme 1
Table 2 Reaction products of amides and stilbenes with EPP
Compound Stilbene (%) Indanes (%) Tetralins (%)
OCH3
OCH3
R1
R2
VerCHR1CH24-BrPh (1) 25 (7)
VerCHR2CH24-BrPh (2) 26 (7)
53 (7-I, 7-II)
67 (7-I, 7-II)
65 (7-I, 7-II)
NHCOR3
1
2
R
1 = H, R2 = Br, R3 = H
VerCH᎐CH4-BrPh (7)
᎐
R1 = H, R2 = Br, R3 = CH3
VerCHR1CH2Ver (3)
99 (8-I)
99 (8-I)
97 (8-I)
3 R1 = R2 = OCH3, R3 = H
VerCHR2CH2Ver (4)
4 R1 = R2 = OCH3, R3 = CH3
VerCH᎐CHVer (8)
᎐
R1 = R2 = R3 = H
VerCHR1CH2Ph (5)
20 (9)
30 (9)
45 (9-I, 9-II, 9-III)
48 (9-I, 9-II, 9-III)
41 (9-I, 9-II, 9-III)
5
6
VerCHR2CH2Ph (6)
R1 = R2 = H, R3 = CH3
VerCH᎐CHPh (9)
᎐
R1: NHCHO, R2: NHCOCH3, Ph: phenyl, Ver: 3,4-dimethoxyphenyl.
OCH3
+
CD
to discriminate between 13 and 14. The choice between struc-
tures 13 and 14 was made on the basis of the following data:
a) Gusten and Schulte-Frohlinde reported12 that in the mass
spectra of 1-benzylindanes the base peak originates from the
loss of the benzyl group, while in the case of the tetralins it
derives from a retro Diels–Alder type cleavage. Table 3 indicates
the cleavage types presented by the CDs isolated in our reac-
tions that would show the presence of the two types of carbon
skeletons;
R1
R2
OCH3
7
8
R1 = H, R2 = Br
R1 = R2 = OCH3
9 R1 = R2 = H
Scheme 2
stilbene with at least one aryl ring by the substitution of a 3,4-
dimethoxyphenyl group, mixture of diastereoisomeric
cyclodimers may be isolated.
The MW of the compounds isolated in every case duplicates
the value of the corresponding stilbenes. The possible structures
of these compounds would be those indicated as 10, 11, 12, 13
and 14 (Fig. 1). The 13C-NMR spectra show the presence of
four sp3 carbon atoms, while DEPT experiments indicate that
three of these are tertiary carbons and one secondary. These
data allow structures 10, 11 and 12 to be ruled out, but they fail
b) another finding taken into account for the structural
assignment originates from the values of the geminal coupling
constants of the benzyl methylene hydrogen atoms; the value
found in the literature13 is of the order of 13 Hz for the exo-
cyclic benzyl groups and 16 Hz for the endocyclic benzyl groups
(Table 4). Besides, we have recently reported the stereodirected
synthesis of the four racemic diastereoisomers of 1-benzyl-2,3-
diphenylindane,14 and chemical shift data of the carbon atoms
are listed in Table 5, which will be used as model compounds;
c) the correlation spectra H/C: HETCOR and COLOC.
a
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Table 3 Mass spectra: comparative data of cyclodimers of stilbenes
Mϩ
Mϩ/2
M
ϩ Ϫ Bz
M
ϩ Ϫ Bz Ϫ Ar
1,2,3-Triphenyltetralina
1-Benzyl-2,3-diphenylindanea
CD 7-I
360 (3)
180 (100)
269 (11)
191 (8)
360 (19)
640 (7.5)
638 (13.8)
636 (7.3)
640 (1.5)
638 (3.4)
636 (3.6)
600 (9.3)
269 (100)
469 (100)
467 (98.9)
191 (47)
329 (10.5)
331 (10.2)
CD 7-II
CD 8-I
CD 9-I
469 (95.5)
467 (100)
329 (18.0)
331 (17.0)
300 (48.0)
↓ Ϫ31
269 (100)
449 (10.1)
480 (17.1)
389 (100)
251 (40.3)
Bz: C6H5CH2; 4-Br- C6H4CH2; 3,4-(CH3O)2 C6H3CH2. Ar: C6H5; 4-Br- C6H4; 3,4-(CH3O)2 C6H3. a Reference 12.
Table 4 Cyclodimers of stilbenes: 1H-NMR data of aliphatic protons
H-1
H-2
H-3
CH2
CD 7-I
3.54 m
3.87 m
4.62 d
2.31 dd 2.46 dd
Jgem = 13.3
J2,3 = 9.8
JCH ,H1 = 5.4; JCH ,H1 = 10.8
2
2
CD 7-II
CD 8-I
3.85 m
4.16 d
3.01 m
J2,3 = 9.2
3.05 dd
4.14 d
2.92 m
3.36 m
3.21 dd 3.06 dd
Jgem = 15.7
J3,4a = 4.1; J3,4b = 11.5
J1,2 = 10.3
J2,3 = 11.5
Table 5 Cyclodimers of stilbenes: 13C-NMR data of aliphatic carbons
Ar
Ar
Ar
Ar
Ar
Ar
ArCH2CH(Ar)C(Ar)=CHAr
C-1
1-Benzyl-2,3-diphenylindanesa
C-2
C-3
CH2
Ar
12
10
11
(α) r-1, c-2, t-3
(β) r-1, c-2, c-3
(γ) r-1, t-2, c-3
(δ) r-1, t-2, t-3
50.6
50.1
51.9
49.0
59.4
58.8
63.4
56.8
53.3
56.8
59.4
55.6
36.9
34.7
39.6
39.3
Ar
Ar
Ar
Ar
Cyclodimers
Ar
Ar
CD 7-I
CD 7-II
CD 8-I
CD 9-I
CD 9-II
CD 9-III
49.9
51.5
54.1
50.5
51.4
54.9
59.6
62.6
55.4
60.5
63.3
56.9
52.8
59.1
45.8
52.7
58.8
46.2
36.7
39.9
38.9
37.5
39.9
39.9
13
14
Fig. 1
In the particular case of the CD 7-I the mass spectrum shows
a base peak for Mϩ Ϫ Bz; the value of the coupling constant of
the benzyl methylene group is Jgem 13.3; the HETCOR spectrum
a Reference 14.
1
1
indicates the correlation to J of H-13C-NMR: 2.31 and 2.46
(CH2)/36.7; 3.54 (H-1)/49.9; 4.62 (H-3)/52.8 and 3.87 (H-2)/
59.6. Lastly, the COLOC spectrum showed correlation between
the hydrogen atoms of the benzyl methylene group with one of
the quaternary aromatic carbon atoms (136.3) and with one of
the tertiary aromatic carbon atoms (131.2) of a 4-bromophenyl
group (Fig. 2). All these data allow the 1-benzylindane struc-
ture to be assigned unequivocally to compound 7-I and by
analogy to compound 7-II (Fig. 3). In the mass spectrum of CD
8-I a Mϩ/2 cleavage is observed which is characteristic of the
tetralin structures (Table 3); the geminal coupling constant of
the benzyl methylene hydrogen atoms is J 15.7; the HETCOR
tetraline. This assignment was made on the basis of the
comparison of their 13C-NMR spectra (Table 5).
Configurational assignment of the cyclodimers
Stereochemical assignment of the CDs was made taking into
1
account the coupling constants in the H-NMR spectra and
chemical shifts of the benzyl methylene carbon atoms. The
configuration of indane structures 7-I and 7-II was achieved on
the basis of the J2,3 value which in both corresponds to a trans
configuration (J 9.8 and 9.2, respectively, Table 4) and of
the chemical shift value of the methylene carbon atom (36.7
and 39.9 ppm, respectively, Table 5), which indicate a marked
protective γ effect in one of the isomers, thus showing a cis
relationship between the benzyl group in C-1 and the aryl
group linked to C-2. Besides, the comparison of the chemical
shifts of C-1, C-2, C-3 and CH2 agrees with indane models α
and γ (Table 5). Therefore, isomer 7-I has a 1,2-cis,2,3-trans and
7-II a 1,2-trans,2,3-trans configuration (Fig. 3). Tetralin 8-I was
assigned the configuration 1,2-trans,2,3-trans by taking into
account the values of the coupling constants J1,2 10.3 and J2,3
11.5 (Table 4). Configuration assignment of the CDs 9-I to 9-III
spectrum indicates the following correlation to J of H-13C-
NMR: 3.06 and 3.21 (CH2)/38.9; 3.36 (H-3)/54.1; 4.16 (H-l)/
45.8 and 3.05 (H-2)/55.4. Lastly, there is a marked difference
between the 13C spectrum of this CD and the 13C spectra
corresponding to the four model CDs (Table 5). Taken jointly,
these data indicate that the structure of a 1,2,3-triaryltetralin
should be assigned to compound 8-I. CDs 9-I and 9-II formed
1
1
from
N-acyl-[1-(3,4-dimethoxyphenyl)-2-phenylethyl]amine
(amides 5 and 6, Table 2) and from the trans-3,4-dimethoxy-
stilbene were assigned the indane structure and 9-III that of
J. Chem. Soc., Perkin Trans. 1, 1999, 1353–1358
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R1
R1
H
CH3O
Br
CH3O
R2
H
R2
Ar
Ar
H
CH3O
CH3O
CH3O
CH3O
Ar
Ar
H
H
Br
H
D-b
D-a
OCH3
CH3O
CH3O
CH3O
CH3O
OCH3
H
H
H
H
H
Ar
Ar
Ar
H
Br
Br
Ar
H
H
Ar
H
Ar
H
CH3O
CH3O
H
H
A-a
A-b
Fig. 4
Ar
Ar
OCH3
CH3O
CH3O
Ar
CH3O
OCH3
Fig. 2
CH3O
Ar
B-1
OCH3
OCH3
A-1
R1
R1
OCH3
OCH3
R2
R2
CH3O
CH3O
CH3O
CH3O
R1
R1
Ar
Ar
Ar
CH3O
CH3O
CH3O
CH3O
R2
R2
+
+
Ar
OCH3
OCH3
OCH3
A
B
OCH3
OCH3
OCH3
OCH3
OCH3
7-I R1 = Br, R2 = H
9-I R1 = R2 = H
7-II R1 = Br, R2 = H
9-II R1 = R2 = H
Ar
Ar
Ar
OCH3
OCH3
CH3O
CH3O
R1
CH3O
CH3O
+
R2
R2
+
CH3O
CH3O
Ar
D
OCH3
E
OCH3
R1
OCH3
OCH3
Ar
CH3O
CH3O
Ar
OCH3
OCH3
8-I R1 = R2 = OCH3
9-III R1 = R2 = H
Ar
CH3O
CH3O
Fig. 3
Ar
D-1
OCH3
E-1
arises from the comparison of 13C-NMR spectrum data (Table
5): 9-I, 1,2-cis,2,3-trans; 9-II, 1,2-trans,2,3-trans; and 9-III, 1,2-
trans,2,3-trans (Fig. 3).
OCH3
Scheme 3
Scheme 3. Considering the structural differences of the aryl
groups (Ar = phenyl; 3,4-dimethoxyphenyl; and 4-bromo-
phenyl) linked to the carbon atom with the positive charge, it
may be assumed that carbocations A and D possess greater
capacity to be formed as compared to B and E due to the fact
that the positively charged carbon atom is substituted by a 3,4-
dimethoxyphenyl group. Electron-donor methoxy groups con-
tribute to its greater stability. Thus, the CDs that should be
formed are those indicated by A-1 and/or D-1 structures, but if
the aryl group should provide a 4-methoxyphenyl, for instance,
then structures B-1 and E-1 would be formed. On the other
hand, regardless of the route leading to the carbocation
Formation of the 5-membered versus the 6-membered ring.
Mechanisms of cyclodimerisation and source of stereocontrol
Assuming that the process of cyclodimerisation to a 1-benzyl-
indane or to a trisubstituted tetralin is carried out starting
from a dimeric carbocation, it would be possible to explain the
dissimilar course of this reaction (Scheme 4).2 Dimeric carbo-
cations could be formed by the attack of trans-stilbene on the
intermediary nitrilium ion (B–N) or from two molecules of
trans-stilbene by acid treatment. In the cases studied the sub-
strates have at least one aryl group with a 3,4-dimethoxy-
phenyl type substitution, thus leading to the carbocations in
1356
J. Chem. Soc., Perkin Trans. 1, 1999, 1353–1358

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formed in cyclodimerisation is determined by the substituents
EPP
present in the aryl group linked to the C-1 atom of the starting
amide. Thus, strong electron-donor substituents lead to a
6-atom ring (Table 2, compounds 3, 4 and 8), while electron-
acceptor substituents lead to a 5-atom ring (Table 1, entry 9 and
Table 2, compounds 1, 2 and 7). Lastly the phenyl group leads
to cyclodimers with both ring sizes (Table 2, compounds 5, 6
and 9).
N+
C
Experimental
R
General
a
b
The 1H- and 13C-NMR spectra were recorded with a Bruker WP
80 SY FT spectrometer with CDCl3 as solvent, employing
Me4Si as internal standard (δ 0.00). Two dimensional spectra
were recorded on a Bruker AC-300 instrument by using stand-
ard Bruker software. Mass spectra were obtained by direct
injection of the sample as chloroform solutions by using a
Shimadzu GCQP 1000 mass spectrometer operating at an ionis-
ing electron energy of 70 eV. Infrared spectra were obtained
on Shimadzu IR 440 spectrometer. Elemental analyses were
carried out in our laboratories with a Coleman Analyser. Melt-
ing points (uncorrected) were obtained with a Thomas Hoover
apparatus. Preparative thin-layer chromatography (PTLC) was
performed on a 20 × 20 cm glass plate coated with silica gel 60
F254 (0.50 mm).
+
Scheme 4
(Scheme 4), the benzyl carbon atom that provides the bond
forming the dimeric moiety A, B, D or E should be the one
which in the transition state could sustain more efficiently a
positive charge. Lastly, the “monomer” stilbene would contrib-
ute to such a bond the carbon atom that allows the formation
of the more stable carbocation. These considerations explain
the CDs obtained in each reaction. CD 8-I possesses a trisubsti-
tuted tetralin structure. In this case there is only a single carbo-
cation since all the aryl groups are equivalent, so that the more
stable 6-membered ring tends to be formed. In the preparation
of CDs 7-I and 7-II the carbocations with greater stability are A
and D. However, carbocation A would be in a low yield because
the “monomer” condensation step is not favoured, since the
aryl moiety is a 4-bromophenyl group; therefore, the product
obtained is the one which originates from D cyclisation. CDs
9-I, 9-II and 9-III provide an intermediate case. The aryl moiety
is a phenyl group, which facilitates the formation of both
carbocations A and D and cyclisation leads similarly to five-
and to six-membered rings.
Compounds 7-I and 7-II have an identical C-2/C-3 configur-
ation (trans). A possible explanation is to assume that in the
dimeric carbocation D the steric effect of the voluminous aryl
group linked to the sp2 carbon atom is smaller for conformer
D-a than for D-b (Fig. 4) and this arrangement would be
independent of the stereoisomeric relationship of the future
C-1 and C-2 atoms. An identical situation occurs in the prepar-
ation of trisubstituted tetralin 8-I with the 1,2-trans,2,3-trans
configuration, where conformer A-a of carbocation A is that of
lesser steric interaction.
Synthesis of the N-(1,2-diarylethyl)amides
The amides 3, 4, 5 and 6 were prepared as described previ-
ously.15,16 The amides 1 and 2 were prepared from ethanone 15
according to the literature.2
1-(3,4-Dimethoxyphenyl)-2-(4-bromophenyl)ethanone 15
This was prepared from 4-bromophenylacetic acid, 1,2-di-
methoxybenzene and PPA.2 Yield 90%. An analytical sample
was prepared by recrystallisation from ethanol, mp 142–143 ЊC
(Found: C, 60.3; H, 4.9. C16H15BrO3 requires C, 60.0; H, 4.7%);
νmax(mull)/cmϪ1: 1675 (C᎐O); δ : 3.85, 3.90 (6H, s, OCH ), 4.15
᎐
H
3
(2H, s, CH2), 7.02 (3H, m, Ar), 7.50 (4H, m, Ar).
N-[1-(3,4-Dimethoxyphenyl)-2-(4-bromophenyl)ethyl]formamide
1
This was prepared from ketone 15 and formamide.2 Yield 80%.
An analytical sample was prepared by recrystallisation from
ethanol, mp 154–155 ЊC (Found: C, 56.7; H, 5.3; N, 3.9.
C17H18BrNO3 requires C, 56.3; H, 5.0; N 3.8%); νmax(mull)/
cmϪ1: 3350 (NH), 1670 (C᎐O); δ : 3.65 (2H, d, J 7.2, CH2),
᎐
H
1,2
3.79, 3.84 (6H, s, OCH3), 5.22 (1H, m, CH), 6.04 (1H, br s,
NH), 6.70 (2H, d, Ar), 6.77 (1H, s, Ar), 6.91 (2H, d, Ar), 7.35
(2H, d, Ar), 8.12 (1H, s, CHO).
N-[1-(3,4-Dimethoxyphenyl)-2-(4-bromophenyl)ethyl]acetamide
2
It may be observed in compounds 7-I and 7-II, as well as in
compounds 9-I and 9-II, that the configuration between sub-
stituents linked to the C-1 and C-2 atoms is preferably cis, indi-
cating that the formation of the more favoured intermediate
cyclodimeric cation is the one which leads to such stereoiso-
meric relationships, as also happens when indanes are obtained
from styrenes. In all studied cases, the substituent linked to the
stereogenic centre formed in the cyclisation step presents a trans
relationship with respect to the substituent present on the
neighbouring carbon.
This was prepared from amide 1.2 Yield 77%. An analytical
sample was prepared by recrystallisation from ethanol, mp 169–
170 ЊC (Found: C, 56.9; H, 5.6; N, 3.8. C18H20BrNO3 requires C,
57.2; H, 5.3 ; N 3.7%); νmax(neat)/cmϪ1: 3400 (NH), 1675 (C᎐O);
᎐
δH: 1.93 (3H, s, CH3), 3.00 (2H, m, CH2), 3.78, 3.83 (6H, s,
OCH3), 5.10 (1H, m, CH), 6.00 (br s, 1H, br s, NH), 6.70 (2H, d,
Ar), 6.77 (1H, s, Ar), 6.91 (2H, d, Ar), 7.35 (2H, d, Ar).
General procedure for the cyclodimerisation reaction with EPP2
A solution of amide or stilbene (1 mmol) and EPP (2.56 g) in
chloroform–ether was warmed at 80 ЊC for 8 h. After removing
the solvent in vacuo, water and methylene chloride were added
to the crude product. The organic layer was separated, and
Conclusions
It may be concluded that, in the studied cases, the ring size
J. Chem. Soc., Perkin Trans. 1, 1999, 1353–1358
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washed with aqueous NaOH (5%) and water. The organic
extract was dried over MgSO4 and the solvent was removed
in vacuo. Chromatography of the crude product on an alumina
column (eluent benzene–hexane) afforded stilbenes and the
cyclodimer mixtures. The mixture of cyclodimers was separated
by PTLC or recrystallisation. The stilbenes 8 and 9 have been
previously described.16
9-III. The upper band yielded 9-I, the middle band gave the
mixture of 9-II and 9-III and the lower band gave 9-III.
r-1-Benzyl-c-2-phenyl-t-3-(3,4-dimethoxyphenyl)-5,6-
dimethoxyindane 9-I. This compound was isolated as an oil.
δH: 2.5 (2H, m, CH2Ph), 3.50 (1H, m, H-1), 3.82 (1H, m, H-2),
3.52, 3.71, 3.76, 3.85 (12H, s, OCH3), 4.73 (1H, d, J2,3 9.6, H-3),
5.85 (1H, s, Ar), 6.8 (14H, m, Ar); δC: 37.5, 50.5, 52.7, 55.4,
55.7, 60.5, 110.9, 111.3, 111.4, 120.7, 125.5, 126.4, 127.8, 128.2,
128.7, 129.8, 135.8, 137.0, 137.2, 140.1, 140.5, 147.1, 147.3,
148.4. 148.9; m/z: 480 (Mϩ 17.1%), 390 (29.0), 389 (100), 252
(10.2), 251 (40.3), 209 (39.1), 165 (18.0), 151 (28.4), 91 (53.3).
Cyclodimers obtained from amides 1 and 2
These amides rendered stilbene 7 (25 and 26% respectively from
1 and 2) and a mixture of cyclodimers 7-I and 7-II (53 and 67%
respectively). The compounds 7-I and 7-II were obtained as a
mixture. This mixture was heated at reflux with ethanol. The
insoluble phase was filtered off while hot and it was identified
as 7-1. Mp l84–185 ЊC (ethanol). The mother liquors were
cooled and a second product identified as 7-II appeared. It was
filtered and dried. Mp l65–166 ЊC (ethanol).
r-1-(3,4-Dimethoxyphenyl)-t-2,c-3-diphenyl-6,7-dimethoxy-
tetralin 9-III. This compound was isolated as an oil. δH: 3.3 (4H,
m, H-2, H-3, H-4), 3.58, 3.72, 3.73, 3.78 (12H, s, OCH3), 4.29
(1H, d, J1,2 9.6, H-1), 6.75 (15H, m, Ar); δC: 39.9, 46.2, 54.9,
55.4, 55.9, 56.9, 110.5, 110.6, 111.0, 119.6, 121.1, 125.6, 125.8,
125.9, 127.7, 128.0, 128.1, 128.2, 128.4, 129.9, 136.9, 137.8,
139.7, 142.8, 146.8, 146.9, 148.0, 148.3.
trans-1,2-Dimethoxy-4-[2-(4-bromophenyl)ethenyl]benzene 7.
Mp 120–121 ЊC (ethanol) (Found: C, 60.8; H, 4.6. C16H15BrO3
requires C, 60.3; H, 4.7%); νmax(neat)/cmϪ1: 980 (HC᎐CH); δ :
r-1-Benzyl-t-2-phenyl-c-3-(3,4-dimethoxyphenyl)-5,6-
dimethoxyindane 9-II. This compound was obtained as an
inseparable mixture with cyclodimer 9-III. δC (mixture of
cyclodimers 9-II and 9-III): 39.9, 46.2, 51.4, 54.9, 55.4, 55.6,
55.9, 56.9, 58.8, 63.3, 107.0, 107.7, 110.5, 110.6, 111.0, 112.7,
119.6, 120.3, 120.7, 121.1, 125.6, 125.8, 125.9, 126.3, 127.7,
128.0, 128.1, 128.2, 128.4, 128.8, 129.4, 129.7, 129.9, 136.3,
136.6, 136.8, 136.9, 137.2, 137.8, 139.7, 140.0, 142.8, 146.8,
146.9, 147.4, 148.0, 148.3.
᎐
H
3.75, 3.85 (6H, s, OCH ), 6.90 (5H, m, Ar and HC᎐CH), 7.25
᎐
3
(2H, d, Ar-2,6), 7.40 (2H, d, Ar-3,5).
r-1-(4-Bromobenzyl)-c-2-(4-bromophenyl)-t-3-(3,4-dimethoxy-
phenyl)-5,6-dimethoxyindane 7-I. Mp 184–185 ЊC (ethanol). δH:
2.31 (1H, dd, Jgem 13.3, JCH -H-1 10.8, CH2Ph), 2.46 (1H, dd,
2
Jgem 13.3, JCH -H-1 5.4, CH2Ph), 3.54 (1H, m, H-1), 3.87 (1H,
m, H-2), 3.60,2 3.74, 3.76, 3.83 (12H, s, OCH3), 4.62 (1H, d, J2,3
9.8, H-3), 5.92 (1H, s, Ar), 6.46 (1H, s, Ar), 6.70 (4H, m, Ar),
7.29 (7H, m, Ar). The aliphatic hydrogens were assigned by
decoupling experiments. δC: 36.7, 49.9, 52.8, 55.5, 55.6, 55.7,
55.9, 59.6, 107.7, 108.0, 111.1, 111.2, 119.5, 120.1, 120.6, 130.3,
130.7, 131.2, 135.2, 136.3, 136.8, 138.8, 139.1, 147.5, 147.8,
148.6, 148.9; m/z: 640, 638, 636 (Mϩ, 7.5, 13.8, 7.3%), 469 (100),
467 (98.9), 388 (10.5), 331 (10.2), 329 (10.5), 171 (2.8), 169 (3.1),
151 (10.6).
The amide 6, by treatment with EPP, gave the stilbene 9
(30%) and the mixture of CDs 9-I, 9-II and 9-III (48%). The
compounds were separated as was previously described.
Acknowledgements
We are grateful to the CONICET, SECYT (UBA) and SECYT
(UNLu) for financial support of this study.
r-1-(4-Bromobenzyl)-t-2-(4-bromophenyl)-c-3-(3,4-dimethoxy-
phenyl)-5,6-dimethoxyindane 7-II. Mp 165–166 ЊC (ethanol). δH:
2.92 (2H, m, CH2Ph), 3.01 (1H, m, H-2), 3.69, 3.74, 3.80, 3.84
(12H, s, OCH3), 3.85 (1H, m, H-1), 4.14 (1H, d, J2,3 9.2, H-3),
6.86 (13H, m, Ar). The aliphatic hydrogens were assigned by
decoupling experiments. δC: 39.9, 51.5, 55.7, 55.9, 59.1, 62.6,
106.9, 107.9, 110.9, 119.9, 120.0, 120.4, 129.6, 131.1, 131.3,
135.8, 136.3, 136.4, 138.4, 141.5, 147.7, 148.6, 148.9; m/z: 640,
638, 636 (Mϩ, 1.5, 3.4, 3.6%), 469 (95.5), 467 (100), 388 (10.7),
331 (18.0), 329 (17.0), 171 (33.9), 169 (37.1), 151 (19.7).
References
1 (a) J. M. Aguirre, E. N. Alesso, D. G. Tombari. C. Somoza, G. Y.
Moltrasio Iglesias and J. D. Bonafede, An. Asoc. Quim. Argent.,
1985, 73, 391; (b) J. M. Aguirre, E. N. Alesso, D. G. Tombari,
A. F. Ibañez and G. Y. Moltrasio Iglesias, J. Heterocycl. Chem.,
1989, 26, 25; (c) J. M. Aguirre, E. N. Alesso, A. F. Ibañez and G. Y.
Moltrasio Iglesias, Trends Heterocycl. Chem., l993, 3, 95.
2 E. N. Alesso, D. G. Tombari, G. Y. Moltrasio Iglesias and
J. M. Aguirre, Can. J. Chem., 1987, 65, 2568.
3 A. Müller, Acta Chim. Acad. Sci. Hung., 1952, 2, 231.
4 J. MacMillan, I. L. Martin and D. J. Morris, Tetrahedron, l969, 25,
905.
5 W. Baker and J. Enderby, J. Chem. Soc., 1940, 1094.
6 R. Wolovsky and N. Maoz, J. Org. Chem., 1973, 38, 4040.
7 M. Hiscock and G. B. Porter, J. Chem. Soc., Perkin Trans. 2, l972,
79.
8 J. M. Aguirre, E. N. Alesso, D. G. Tombari. C. Somoza, G. Y.
Moltrasio Iglesias and J. D. Bonafede, An. Asoc. Quim. Argent.,
1984, 72, 219.
9 G. N. Walker, J. Am. Chem. Soc., l954, 76, 3999.
10 A. R. Battersby and R. Binks, J. Chem. Soc., 1958, 4333.
11 M. Salzwedel, V. Werner and D. Schulte-Frohlinde, Angew. Chem.,
Int. Ed. Engl., l964, 3, 803.
12 H. Gusten and D. Schulte-Frohlinde, Liebigs Ann. Chem., l976, 22,
29.
13 E. N. Alesso, G. Y. Moltrasio Iglesias and J. M. Aguirre, Aust. J.
Chem., l994, 47, 1237.
Cyclodimer obtained from amides 3 and 4
r-1,t-2,c-3-Tris(3,4-dimethoxyphenyl)-6,7-dimethoxytetralin
8-I. This compound was obtained by treatment of amides 3 and
4 with EPP as the unique product. From both amides the yield
was 99%. Mp 153–156 ЊC (methanol). δH: 3.05 (1H, dd, J1,2
10.3, J2,3 11.5, H-2), 3.06 (1H, dd, J3,4b 11.5, J4a,4b 15.7, H-4b),
3.21 (1H, dd, J3,4a 4.1, J4a,4b 15.7, H-4a), 3.36 (1H, m, J2,3 11.5,
J3,4a 4.1, J3,4b 11.5, H-3), 4.16 (1H, d, J1,2 10.3, H-1), 6.45 (1H,
m, Ar); δC: 38.9, 45.8, 54.1, 54.8, 54.9, 55.0, 55.4, 109.8, 109.9,
110.1, 110.5, 111.1, 111.9, 118.9, 120.1, 120.6, 128.3, 130.7,
134.8, 136.3, 137.2, 146.5, 146.6, 147.4, 147.5, 147.8; m/z: 600
(Mϩ, 9.3%), 449 (10.1), 300 (48.0), 285 (16.5), 270 (32.1), 269
(100), 239 (7.2), 238 (20.1), 225 (9.4), 211 (7.0), 195 (5.2), 165
(6.3), 151 (22.6).
14 J. M. Aguirre, E. N. Alesso, G. Y. Moltrasio Iglesias and J. D.
Mufato, J. Chem. Res. (S), 1998, 464.
15 J. M. Aguirre, E. N. Alesso, D. G. Tombari. A. F. Ibañez, J. D.
Bonafede and G. Y. Moltrasio Iglesias, An. Asoc. Quim. Argent.,
1987, 75, 393.
16 A. Novelli, J. D. Bonafede and M. C. Barrio, Tetrahedron Lett.,
1968, 613.
Cyclodimers obtained from amides 5 and 6
The amide 5 gave, by treatment with EPP, the stilbene 9 (20%)
and the mixture of CDs 9-I, 9-II and 9-III (45%). The com-
pounds 9-I and 9-III were separated by PTLC with benzene as
eluent. The compound 9-II was obtained as a mixture with
Paper 9/00282K
1358
J. Chem. Soc., Perkin Trans. 1, 1999, 1353–1358