Synthesis of a trifluoromethylindolocarbazole, novel cyclic 27- and 36-membered N-benzyltri- and -tetraindoles, and an N-benzyltetraindolyltrimethane

Article abstract of DOI:10.1007/PL00010184

5,11-Dihydro-5,11-dibenzyl-6-trifluoromethylindolo[3,2-b]carbazole (6) and the cyclic N-benzylindole trimer 4 were synthesized from both N-benzylindole-3-methanol (1) and N,N'-dibenzyl-3,3'-diindolylmethane (2) by treatment with trifluoroacetic anhydride. The former also gave the 36-membered cyclic N-benzylindole tetramer 7, and the latter furnished N-benzyl-3-trifluoroacetylindole (8). Heating 1 in aqueous methanol also yielded the trimer 4 along with 2, the N-benzylitriindolyldimethane 3, and the N-benzyltetraindolyltrimethane 5 whose structure and solid-state conformation were determined by X-ray crystallographic analysis. The results are discussed and plausible mechanisms of the reactions leading to 3-8 are presented.

Full text of DOI:10.1007/PL00010184

Monatshefte f uÈ r Chemie 130, 1227±1239 (1999)
Synthesis of a Tri¯uoromethylindolocarbazole,
Novel Cyclic 27- and 36-Membered
N-Benzyltri- and -tetraindoles, and an
N-Benzyltetraindolyltrimethane
Kshetra M. Biswas1 , Haimanti Mallik , Aparna Saha , Sumita Halder ,
and Andrew T. McPhail
;Ã
1
1
1
2
;Ã
1
Department of Chemistry, University College of Science, University of Calcutta, Calcutta 700009,
India
2
Department of Chemistry, Paul M. Gross Chemical Laboratory, Duke University, Durham, North
Carolina 27708-0346, USA
Summary. 5,11-Dihydro-5,11-dibenzyl-6-tri¯uoromethylindolo[3,2-b]carbazole (6) and the cyclic
0
N-benzylindole trimer 4 were synthesized from both N-benzylindole-3-methanol (1) and N,N -
0
dibenzyl-3,3 -diindolylmethane (2) by treatment with tri¯uoroacetic anhydride. The former also gave
the 36-membered cyclic N-benzylindole tetramer 7, and the latter furnished N-benzyl-3-
tri¯uoroacetylindole (8). Heating 1 in aqueous methanol also yielded the trimer 4 along with 2,
the N-benzylitriindolyldimethane 3, and the N-benzyltetraindolyltrimethane 5 whose structure and
solid-state conformation were determined by X-ray crystallographic analysis. The results are
discussed and plausible mechanisms of the reactions leading to 3±8 are presented.
Keywords. Tri¯uoromethylindolocarbazole; Cyclic N-benzylindole tetramer; N-Benzyltetraindolyl-
trimethane; X-Ray crystallographic analysis.
Synthese eines Tri¯uormethylindolocarbazols, neuer cyclischer 27- und 36-gliedriger
N-Benzyltri- und -tetraindole sowie eines N-Benzyltetraindolyltrimethans
Zusammenfassung. 5,11-Dihydro-5,11-dibenzyl-6-tri¯uormethylindolo[3,2-b]carbazol (6) und das
0
cyclische N-Benzylindoltrimer 4 wurden aus N-Benzylindol-3-methanol (1) und N,N -Dibenzyl-
0
3,3 -diindolylmethan (2) durch Behandeln mit Tri¯uoracetanhydrid synthetisiert. Ersteres ergab auch
das 36-gliedrige cyclische N-Benzylindoltetramer 7, letzteres N-Benzyl-3-tri¯uoracetylindol (8).
Erhitzen von 1 in w aÈ ssrigem Methanol f uÈ hrte zum Trimer 4 ± zusammen mit 2, dem N-Benzyl-
triindolylmethan 3 und dem N-Benzyl-tetraindolyltrimethan 5, f uÈ r welches Struktur und Konformation
im festen Zustand durch R oÈ ntgenstrukturanalyse abgeleitet wurden. Die Resultate werden diskutiert,
und plausible Mechanismen f uÈ r die Reaktionen, die zu den Verbindungen 3±8 f uÈ hren, werden
vorgestellt.
à Corresponding authors

1228
K. M. Biswas et al.
Introduction
Indolocarbazoles are known to possess important biological activities [1±3].
Fluoroorganic compounds have been of great interest to synthetic and medicinal
chemists for a long time due to the unique chemical and biological properties
imparted by ¯uorine and also because of their utilization as drugs, pesticides, dyes,
diagnostic agents, etc. [4±9]. Moreover, although several methods are known for
the synthesis of 5,11-dihydroindolo[3,2-b]carbazoles and 5,7-dihydroindolo[2,3-
b]carbazoles [10±13], these often involve many steps, and the yields are usually
low. So far as we are aware, ¯uorine-containing indolocarbazoles are not known in
the literature. Accordingly, we sought to devise a method for the synthesis of
0
tri¯uoromethylindolocarbazoles. For this purpose, we chose the reaction of N,N -
0
dibenzyl-3,3 -diindolylmethane (2) with tri¯uoroacetic anhydride, since the former
can supply two nucleophilic indole moieties, and the latter can provide an
electrophilic carbonyl carbon atom and a tri¯uoromethyl group as required for
constructing the skeleton of the desired compounds. Our results are presented
herein.
Results and Discussion
To prepare the N-benzyldiindolylmethane 2, the indole-3-methanol 1 was heated
in aqueous methanol (cf. Ref. [14]). In addition to 2, the reaction furnished
the triindolyldimethane 3, the tetraindolyltrimethane 5 and the 27-membered cyclic
triindole 4. The structures of 3±5 were established from their NMR and
mass spectroscopic data, and that of 5 was con®rmed by X-ray crystallographic
analysis.
Crystallographic data and data collection parameters for 5 are summarized in
Table 1. A view of the solid-state conformation, with the crystallographic atom
numbering scheme, is presented in Fig. 1; fractional atomic coordinates are given
in Table 2. Bond lengths and angles within the benzylindole moieties agree well
0
and are, as well as the others, in accord with expectations [15]. The C3±C15±C2 ±
000
0
00
00
00
000
C3 ±C15 ±C3 ±C2 ±C15 ±C3 backbone has a helical form characterized by the
ꢀ
following torsion angles (! , ꢀÆ0.2±0.4 ) about the bonds between atoms i and j:
ij
!
!2
0
ˆ � 105.9, !
0
0
ˆ � 11.7, !
0
00 ˆ 144.7, ! 00 00 ˆ � 74.3, ! 00 00 ˆ 2.3,
1
5,2
2 ,3
3 ,15
15 ,3
3 ,2
ꢀ
00 00 ˆ 102.4 . Strain involved in the minimization of unfavourable non-bonded
,15
intramolecular interactions associated with this conformation is re¯ected in the
signi®cant departures of some of the directly bonded atoms from the least-squares
planes through atoms of each of the approximately planar indole units (C8 0.104,
Ê
0
00
00
Ê
Ê
C15 0.133 A to the same side of the N1±C7a plane; C8 0.082, C15 0.079 A to the
0
0
Ê
opposite side of the N1 ±C7a plane from C15 (Á ˆ 0.238 A); C8 0.367 A from
0
0
00
000
000
Ê
the N1 ±C7a plane; C8 0.133, C15 0.109 A to opposite sides of the N1 ±
000
0
00
0
000
C7a plane). Furthermore, whereas methylene carbon atoms C8, C8 , and C8
Ê
(
Á ˆ 0.013, 0.006, 0.013 A, respectively) lie essentially in the least-squares planes
00
Ê
through the phenyl rings to which they are bonded, C8 is displaced by 0.046 A
0
0
00
from the C9 ±C14 plane. The associated indole N atoms in each case also lie
close to, but deviate by signi®cant amounts from, the corresponding phenyl ring
0
00
000
Ê
planes (N1 0.068, N1 0.086, N1 0.279, N1 0.043 A).

Synthesis and Structure of Cyclic Oligoindoles
1229
Table 1. Crystallographic data for 5
Molecular formula
Formula weight
Crystal system
Space group
C H N
63 52 4
865.14
triclinic
1
ꢀ
P1(C )-No. 2
i
Ê
a/A
Ê
b/A
11.960(1)
19.651(2)
11.251(1)
106.01(1)
109.68(1)
92.17(1)
2368(1)
2
Ê
c/A
ꢀ
ꢀ
ꢁ
/
ꢂ/
ꢀ
ꢃ/
V/A
3
Ê
Z
�
3
Dcalcd/g Á cm
1.213
Ê
Radiation (ꢄ/A)
Absorption coef®cient m/cm
T/K
CuK (1.5418)
ꢁ
�
1
5.1
298
Crystal dimensions (mm)
Tmax : Tmin (relative)
Scan type
0.10Â0.20Â0.34
1.00: 0.94
!±2ꢅ
ꢀ
Scan width ( )
ꢀ
0.80‡0.14tanꢅ
ꢅmax
Intensity control re¯s.:
/
75
Å
Å Å
243, 242, 141, 330
<1.0%; 2
10245
Variation; repeat time (h)
Total no. of re¯s. (‡h, Æk, Æl) recorded
No. of non-equiv. re¯s. recorded
Rmerge (on I)
9724
0.033
No. of re¯s. retained (I>2.0ꢀ(I))
No. of parameters re®ned
Extinction correction
5212
605
�
6
1.9(1)Â10
a
R (Rw)
0.047 (0.062)
1.46
b
Goodness-of-®t
Max. shift: esd in ®nal least-squares cycle
3
0.03
Ê
Final Áꢆ(e/A ) max.; min.
0.15; � 0.17
P
P
P
P
P
a
2
2
1=2
2
2
R ˆ
kFoj � jFck= jFoj; Rw ˆ ꢁ wꢁjFoj � jFcj† = wjFoj †
;
wÁ ꢁw ˆ 1=ꢀ ꢁjFoj†,
P
b
2
1=2
Á ˆ ꢁjFoj � jFcj† was minimized; goodness-of-®t ˆ ꢁ wÁ =ꢁNobservations � Nparameters†
In order to synthesize the tri¯uoromethylindolocarbazole 6, 2 was treated with
tri¯uoroacetic anhydride, and in addition to 6, 4 and the tri¯uoroacetylindole 8
were also obtained. Since 2 was prepared from 1, we envisaged that this conversion
could more conveniently be done in situ and our objective might be ful®lled by
replacing 2 by 1. Thus, the reaction of 1 with tri¯uoroacetic anhydride afforded 4
and 6 along with the novel 36-membered cyclic tetraindole 7. Macrocylic indoles
of the type 4 and 7 having suitable substituents and structural variation may be
manipulated to promote molecular recognition and ion binding [16, 17].

1230
K. M. Biswas et al.
Table 2. Non-hydrogen atom fractional coordinates and equivalent isotropic thermal parameters for 5
esd values in parentheses)
(
2
Ê
B /A
eq
Atom
x
y
z
N(1)
C(2)
0.4363(2)
0.4256(2)
0.5358(2)
0.6216(2)
0.7464(2)
0.8012(2)
0.7340(3)
0.6108(2)
0.5557(2)
0.3369(2)
0.3046(2)
0.2143(3)
0.1813(3)
0.2362(3)
0.3244(3)
0.3586(2)
0.5606(2)
0.3854(2)
0.4472(2)
0.3813(2)
0.2720(2)
0.1673(2)
0.0751(3)
0.0849(3)
0.1860(3)
0.2784(2)
0.4279(3)
0.4707(2)
0.5054(3)
0.5449(3)
0.5486(3)
0.5140(3)
0.4739(3)
0.1864(2)
0.2710(2)
0.3257(2)
0.2762(2)
0.2975(2)
0.2324(3)
0.1480(3)
0.1258(2)
0.1899(2)
0.1355(2)
0.2197(2)
0.1937(3)
0.2668(4)
0.3720(1)
0.3097(1)
0.2956(1)
0.3524(1)
0.3677(1)
0.4295(2)
0.4764(2)
0.4627(1)
0.3998(1)
0.4076(1)
0.4629(1)
0.5017(2)
0.5528(2)
0.5638(2)
0.5251(2)
0.4741(1)
0.2341(1)
0.2338(1)
0.1974(1)
0.1329(1)
0.1281(1)
0.0783(1)
0.0938(2)
0.1566(2)
0.2065(1)
0.1918(1)
0.3010(1)
0.2929(1)
0.3540(2)
0.3502(2)
0.2867(2)
0.2245(2)
0.2281(2)
0.0008(1)
0.0563(1)
0.0343(1)
� 0.0389(1)
� 0.0904(1)
� 0.1582(1)
� 0.1759(1)
� 0.1268(1)
� 0.0583(1)
� 0.0024(1)
0.0237(1)
0.0143(2)
� 0.0364(2)
0.1965(2)
0.0973(2)
3.96(4)
3.87(5)
3.58(5)
3.44(5)
4.34(6)
5.42(7)
5.59(7)
4.58(6)
3.63(5)
4.53(6)
4.12(5)
6.42(7)
8.42(9)
7.46(9)
5.85(7)
4.76(6)
4.12(5)
4.46(5)
3.62(5)
3.31(4)
3.59(5)
4.30(6)
5.35(7)
5.88(8)
5.53(7)
4.09(5)
5.24(6)
4.62(6)
6.77(8)
8.33(9)
6.79(8)
6.81(8)
6.12(7)
3.85(4)
3.63(5)
3.45(5)
3.53(5)
4.71(6)
5.81(8)
5.86(8)
5.03(6)
3.79(5)
4.77(6)
4.65(6)
7.63(8)
11.1(1)
C(3)
0.0948(2)
C(3a)
C(4)
0.2003(2)
0.2502(2)
C(5)
0.3543(3)
C(6)
0.4088(3)
C(7)
0.3624(2)
C(7a)
C(8)
0.2592(2)
0.2162(2)
C(9)
0.1441(2)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
0.1612(3)
0.0965(4)
0.0127(3)
� 0.0063(3)
0.0588(2)
� 0.0038(2)
� 0.2051(2)
� 0.1186(2)
� 0.1476(2)
� 0.2567(2)
� 0.3265(2)
� 0.4247(3)
� 0.4569(3)
� 0.3904(2)
� 0.2890(2)
� 0.2161(2)
� 0.3312(2)
� 0.3549(3)
� 0.4575(3)
� 0.5400(3)
� 0.5210(3)
� 0.4159(3)
� 0.0134(2)
� 0.0288(2)
� 0.0606(2)
� 0.1340(2)
� 0.2357(2)
� 0.2833(3)
� 0.2322(3)
� 0.1336(3)
� 0.0848(2)
0.1130(2)
0
N(1 )
0
C(2 )
0
C(3 )
0
C(3a )
0
C(4 )
0
C(5 )
0
C(6 )
0
C(7 )
0
C(7a )
0
C(8 )
0
C(9 )
0
0
0
0
C(10 )
C(11 )
C(12 )
C(13 )
0
C(14 )
0
0
N(1 )
0
0
C(2 )
0
0
C(3 )
0
0
C(3a )
0
0
C(4 )
0
0
C(5 )
0
0
C(6 )
0
0
C(7 )
0
0
C(7a )
0
0
C(8 )
0
0
C(9 )
0
0.2266(2)
0
0
C(10 )
0
0.3386(3)
C(11 )
0.4418(3)

Synthesis and Structure of Cyclic Oligoindoles
1231
Table 2 (continued)
2
Ê
B /A
eq
Atom
x
y
z
0
0
0
0
0
C(12 )
0.3648(4)
0.3912(3)
0.3179(3)
0.4221(2)
0.0352(2)
0.1100(2)
0.1875(2)
0.1595(2)
0.2048(2)
0.1552(2)
0.0652(2)
0.0175(2)
0.0653(2)
� 0.0633(3)
� 0.0374(2)
� 0.1264(3)
� 0.1084(4)
� 0.0014(3)
0.0869(3)
0.0691(3)
0.2872(2)
� 0.0660(2)
� 0.0764(2)
� 0.0556(2)
0.0770(1)
0.2145(1)
0.1622(1)
0.1714(1)
0.2320(1)
0.2662(1)
0.3242(2)
0.3506(2)
0.3180(1)
0.2583(1)
0.2184(2)
0.2750(1)
0.2804(2)
0.3302(2)
0.3755(2)
0.3710(2)
0.3205(2)
0.1282(1)
0.4343(3)
0.3220(3)
12.3(1)
11.2(1)
0
C(13 )
0
C(14 )
0.2178(3)
7.27(8)
4.26(5)
4.60(5)
4.44(6)
3.70(5)
3.60(5)
4.28(6)
5.35(7)
5.61(7)
4.96(6)
4.02(5)
5.76(7)
4.70(6)
6.83(9)
8.2(1)
0
C(15 )
0
� 0.0800(2)
� 0.0393(2)
� 0.0394(2)
0.0861(2)
00
N(1 )
0
00
C(2 )
0
00
C(3 )
00
0
C(3a )
0
0.1709(2)
00
C(4 )
0
0.3083(2)
00
C(5 )
0
0.3583(3)
00
C(6 )
0
0.2753(3)
00
C(7 )
00
0.1396(3)
0
C(7a )
0
0.0893(2)
00
C(8 )
0
� 0.1557(3)
� 0.2147(2)
� 0.3267(3)
� 0.3861(3)
� 0.3347(3)
� 0.2238(3)
� 0.1640(3)
0.1282(2)
00
C(9 )
0
00
00
00
00
00
00
C(10 )
0
C(11 )
0
C(12 )
7.6(1)
0
C(13 )
7.05(9)
6.01(8)
4.42(6)
0
C(14 )
0
C(15 )
The protons and the carbon atom of one N±CH of 6 were shifted down®eld in
2
1 13
its H and C NMR spectra relative to those of the other N±CH moiety,
2
presumably because the protons and the carbon of one N±CH bear six-bond and
2
®ve-bond relationships [18, 19], respectively, with the ¯uorine atoms of its CF3
group, whereas there exists no such relationship with those of the other N±CH2
group. This observation led us to propose structure 6. This assignment was
con®rmed by the fact that the 7-H of 6 resonated further down®eld that its 1-H in
1
the H NMR spectrum. Similarly, 2-H of 8 also resonated down®eld and showed
coupling with ¯uorines in its H NMR spectrum. Solutions of 6 in various solvents
exhibited blue-violet ¯uorescence.
1
Suggested mechanisms of the reactions leading to 3±8 are indicated brie¯y in
Schemes 1±3; they have some analogy to those reported in the literature [20].
This work presents simple methods for the synthesis of macrocyclic indoles 4
and 7, tri¯uoromethylindolocarbazole 6, and tetraindolyltrimethane 5, all of which
appear to be unreported in the literature, from readily available materials and
reagents. Formation of 8 from 2 provides unambiguous experimental evidence to
show that acylation of 3-alkylindoles occurs by initial electrophilic attack at the
3-position followed by migration of the acyl group from the 3- to the 2-position to
furnish the observed 2-acyl-3-alkylindoles as Jackson et al. [20] have speculated,
and contradicts the suggested mechanism [21, 22].

1232
K. M. Biswas et al.
Experimental
Melting points are uncorrected. UV spectra were recorded in ether or ethanol on a Varian Technotron
Series 634 spectrophotometer, IR spectra were taken as KBr pellets on a Perkin Elmer 782
1 13
instrument, H and C NMR spectra in CDCl were determined on a Bruker AM 300L (300 MHz)
3
spectrometer using TMS and CDCl as internal standards, and mass spectra were obtained on Jeol
3
SX-102 or Jeol D-300 instruments. Tri¯uoroacetic anhydride was prepared immediately prior to use.
ꢀ
Petroleum ether indicates the fraction boiling from 60±80 C. Silica gel (60±120 mesh) was used for
1
13
column chromatography. H and C NMR spectroscopic data for only one indole moiety of 4 and 7
and two of 5 are given; data for the other indole moieties are the same. Elemental analysis data
agreed with the calculated values within experimental error. Indole-3-methanol 1 was prepared by

Synthesis and Structure of Cyclic Oligoindoles
1233
Fig. 1. ORTEP diagram (40% probability ellipsoids) showing the crystallographic atom numbering
scheme and solid-state conformation of compound 5; hydrogen atoms have been omitted for clarity
reduction of N-benzylindole-3-carboxaldehyde (0.6 g, 2.5 mmol) with sodium borohydride (190 mg,
5
mmol) in ethanol following the procedure given in Ref. [23].
N-Benzylindole-3-methanol (1; C H NO)
16 15
ꢀ
� 1
M.p.: 92 C; colourless needles (benzene-petroleum ether); yield: 0.59 g (98%); IR: ꢇ ˆ 3360 cm
1
(
hump, OH); H NMR (CDCl ): ꢈ ˆ 4.81 (2H, s, 3-CH OH), 5.22 (3H, s, N-CH , 3-CH OH), 7.06±
3
2
2
2
7
.26 (9H, m, Ar±H), 7.66±7.69 (1H, m, 4-H) ppm.
Reaction of 1 in aqueous methanol
3
3
Compound 1 (2.45 g, 0.0103 mol) was re¯uxed with water (35 cm ) and methanol (90 cm ) for 25 h,
and excess methanol was removed by distillation. The resulting mixture was extracted with ether and
dried (Na SO ). The viscous liquid obtained after removal of the solvent was chromatographed over
2
4
silica gel. Elution of the column with petroleum ether-benzene (9:1) furnished 2±4. Further elution of
the column with petroleum ether-benzene (3:1) afforded 5.
0
0
N,N -Dibenzyl-3,3 -diindolylmethane (2; C H N )
31 26 2
ꢀ
ꢀ
M.p.: 135±137 C (Ref. [24]: m.p.: 137 C); colourless needles (benzene-petroleum ether); yield:
.7 g (31.8%).
0

1234
K. M. Biswas et al.
Triindolyldimethane (3; C H N )
47 39 3
ꢀ
ꢀ
M.p.: 150 C; colourless needles (benzene-petroleum ether (40±60 C)); yield: 0.2 g (9%); UV: ꢄ
1
max
(
ether) ˆ 221(3.43), 240(4.38), 288(4.33) nm (log"); H NMR (CDCl ): ꢈ ˆ 4.12 (2H, s, 15-CH ),
3
2
00 00 0
.28 (2H, s, 15 -CH ), 4.89 (2H, s, 8 -CH ), 5.01 (2H, s, 8-CH ), 5.14 (2H, s, 8 -CH ), 6.31 (1H, s,
2 2 2 2
4
2
2
0
0
13
00
00
-H), 6.69 (1H, s, 2-H), 6.74±7.59 (27H, m, Ar±H) ppm; C NMR (CDCl ): ꢈ ˆ 20.48 (15 -CH ),
3
2
0
00
0.96 (15-CH ), 46.57 (8 -CH ), 49.58 (8-CH ), 49.68 (8 -CH ), 109.18, 109.43, 109.62 (C-7 , C-7,
2
2
2
2
0
0
00
00
0
C-7 ), 111.23, 112.36, 115.34 (C-3 , C-3, C-3 ), 118.73, 118.73, 118.90 (C-4, C-4 , C-4 ), 118.90.
00 0 00 0
1
18.96, 119.26 (C-6 , C-6, C-6 ), 120.88, 121.43, 121.69 (C-5 , C-5, C-5 ), 125.79, 126.38, 126.38
0 0 00 00 00 00
(
C-11, C-13, C-11 , C-13 , C-11 , C-13 ), 126.68, 126.83 (C-2, C-2 ), 127.59, 128.2, 128.2 (C-3a ,
0
00
0
C-3a, C-3a ), 127.17, 127.17, 127.28 (C-12, C-12 , C-12 ), 128.41, 128.41, 128.45 (C-10, C-14,
0
0
00
0
0
00
0
00
C-10 , C-14 , C-10 , C-14 ), 135.42, 136.58, 136.72 (C-7a , C-7a, C-7a ), 137.52, 137.77 (C-9 ,
0
0
‡
C-9), 138.24 (C-2 , C-9 ) ppm; MS (FAB): m/z (%) ˆ 645 (M , 5.5), 439 (M±N-benzyl-3-indolyl,
00), 438 (M±N-benzylindole, 100), 347 (438� PhCH , 100).
1
2
Cyclic trimer (4; C H N )
48 39 3
ꢀ
M.p.: 224 C; white spongy mass (benzene-petroleum ether); yield: 0.025 g (1.1%); UV: ꢄ
1
max
(
ether) ˆ 217 (3.68), 239 (4.45), 287.5 (4.36) nm (log"); H NMR (CDCl ): ꢈ ˆ 4.03 (2H, s, 15-
3
13
CH ), 5.41 (2H, s, 8-CH ), 6.83±6.99 (4H, m, Ar±H), 7.16±7.30 (5H, m, Ar±H) ppm; C NMR
2
2
(
CDCl ): ꢈ ˆ 20.52 (15-CH ), 46.42 (8-CH ), 107.83 (C-3), 109.21 (C-7), 117.36 (C-4), 119.13 (C-
3
2
2
6
7
), 121.08 (C-5), 125.99 (C-11, C13), 127.15 (C-2), 127.60 (C-3a), 128.65 (C-10, C-14), 135.60 (C-
‡
a), 136.30 (C-12), 137.92 (C-9) ppm; MS (FAB): m/z(%) ˆ 657 (M , 59), 566 (M±PhCH , 9.6) 436
2
(
M±N-benzyl-3-methylindole, 12.5).

Synthesis and Structure of Cyclic Oligoindoles
1235
Scheme 1
Tetraindolyltrimethane (5; C H N )
63 52 4
ꢀ
M.p.: 169±170 C; colourless microneedles (benzene-petroleum ether); yield: 0.08 g (3.7%); UV:
1
ꢄmax (ethanol) ˆ 210 (4.87), 218.5 (4.87), 235 (4.94), 288 (4.52) nm (log"); H NMR (CDCl ):
3
0
0
0
ꢈ ˆ 4.30 (2H, s, 15-CH ), 4.62 (2H, s, 15 -CH ), 4.88 (2H, s, 8-CH ), 5.20 (2H, s, 8 -CH ), 6.26 (1H,
2
2
2
2
0
0
s, 2-H), 6.85 (2H, d, J ˆ 7.45 Hz, 10-H, 14-H), 6.94 (2H, d, J ˆ 6.56 Hz, 10 -H, 14 -H), 7.15±7.31
0
13
12H, m, Ar±H), 7.56 (1H, d, J ˆ 7.82 Hz, 4-H), 7.72 (1H, d, J ˆ 7.70 Hz, 4 -H) ppm; C NMR
(
0
0
0
(
CDCl ): ꢈ ˆ 20.44 (15 -CH ), 21.04 (15-CH ), 46.74 (8 -CH ), 49.83 (8-CH ), 109.25 (C-7),
3
2
2
2
2
0
0
0
0
1
09.69 (C-7 ), 112.01 (C-3 ), 112.59 (C-3), 118.81 (C-4), 119.06 (C-4 ), 119.19 (C-6, C-6 ), 120.96

1236
K. M. Biswas et al.
Scheme 2
Scheme 3

Synthesis and Structure of Cyclic Oligoindoles
1237
0
0
0
(
C-5), 121.76 (C-5 ), 125.95 (C-11, C-13), 126.61 (C-11 , C-13 ), 126.76 (C-2), 126.92 (C-12),
0
0
0
0
1
27.26 (C-12 ), 128.04 (C-3a), 128.36 (C-10, C-14), 128.48 (C-10 , C-14 ), 128.84 (C-3a ), 135.46
0
0
0
(
C-7a), 136.98 (C-2 ), 137.19 (C-7a ), 137.77 (C-9), 138.42 (C-9 ) ppm; MS (FAB): m/z(%) ˆ 864
‡
(
M , 6.41), 658 (M±N-benzyl-3-indolyl, 12.06), 657 (M±N-benzylindole, 10.64), 644 (M±N-benzyl-
3
-indolylmethyl, 10.18), 566 (M±N-benzylindole� CH Ph, 6.05), 440 (M±N-benzyl-3-indolyl-
2
methyl±N-benzyl-3-indolyl‡2H,
51.01),
439
(M±N-benzyl-3-indolylmethyl� N-benzyl-3-
indolyl‡H, 91.01), 438 (M±N-benzyl-3-indolylmethyl±N-benzyl-3-indolyl, 89.94), 347 (438-
CH Ph, 66.40), 256 (347� CH Ph, 54.50), 220 (N-benzyl-3-indolylmethyl, 82.48), 91 (CH Ph, 100).
2
2
2
Reaction of 2 with tri¯uoroacetic anhydride
3
3
A solution of tri¯uoroacetic anhydride (5.6 cm , 30 mmol) in dry benzene (55 cm ) was added slowly
3
under a blanket of dry nitrogen to a stirred solution of 2 (1.3 g, 3 mmol) in dry benzene (150 cm ) at
ꢀ
0
±5 C, and the mixture was stirred for 4 h at room temperature. The crude product obtained after
removal of solvent under reduced pressure was chromatographed over silica gel. Elution with a
mixture of benzene and petroleum ether (1:9) gave 6 and 8. Further elution of the column with a
ꢀ
mixture of petroleum ether-benzene (3:1) furnished 4 (yield: 40 mg (2%), m.p.: 224 C).
5,11-Dihydro-5,11-dibenzyl-6-tri¯uoromethylindolo[3,2-b]carbazole (6; C H F N )
33 23 3 2
ꢀ
M.p.: 204 C; yellow prisms (benzene-petroleum ether); yield: 0.5 g (33%), UV/Vis:
(ether) ˆ 259.5 (4.28), 287 (4.28), 333 (4.29), 352 (4.28), 391.5 (3.71), 412.5 (3.82) nm (log");
ꢄ
1
max
H NMR (CDCl ): ꢈ ˆ 5.55 (2H, s, 11-CH ), 5.66 (2H, s, 5-CH ), 7.14±7.52 (16H, m, Ar±H), 8.07
3
2
2
1
3
(
1H, d, J ˆ 7.33 Hz, 1-H), 8.15 (1H, s, 12-H), 8.42 (1H, d, J ˆ 7.96 Hz, 7-H) ppm; C NMR:
ꢈ ˆ 46.38 (11-CH ), 53.1 (5-CH ), 103.05 (C-12), 108.7 (C-4), 111.24 (C-10), 119.21 (C-2), 119.63
2
2
(
C-1), 120.1 (C-8), 120.49 (C-12a), 121.21 (C-6a), 123.23 (C-6b), 124.45 (C-12b), 124.83 (C-7),
00 00 0 0 00 0
1
1
25.91 (C-3 , C-5 ), 126.09 (C-3 , C-5 ), 126.58 (C-3), 126.78 (C-9), 126.99 (C-4 ), 127.45 (C-4 ),
0
0
00
0
0
28.37 (C-2 , C-6 ), 128.77 (C-2 , C-6 ), 136.46 (C-6), 136.77 (C-10a), 137.93 (C-4a), 141.96
‡
(
(
C-11a), 145.41 (C-5a) ppm; MS (EI): m/z(%) ˆ 504 (M , 82.4), 413 (M±CH Ph, 58.4), 343
2
M±CH Ph±CF ±H, 1.9), 322 (M±2ÂCH Ph, 12), 91 (CH Ph, 100).
2
3
2
2
N-Benzyl-3-tri¯uoroacetylindole (8; C H F NO)
17 12 3
ꢀ
M.p.: 104 C; colourless ®ne needles (benzene-petroleum ether); yield: 0.5 g (54%); IR:
1
�
1
ꢇ ˆ 1660 cm (s, COCF ); UV: ꢄ (ethanol) ˆ 211 (4.32), 251 (4.04), 317 (4.07) nm (log"); H
3
max
NMR (CDCl ): ꢈ ˆ 5.40 (2H, s, CH ), 7.17±7.41 (8H, m, Ar±H), 7.98±7.99 (1H, m, 2-H), 8.44 (1H,
3
2
1
3
dd, J ˆ 7.18, 1.5 Hz, 4-H) ppm; C NMR: (CDCl ): ꢈ ˆ 51.20 (C-8), 109.77 (C-3), 110.64 (C-7),
3
1
1
22.74 (C-4), 123.90 (C-6), 124.80 (C-5), 126.86 (C-11, C-13), 127.16 (C-3a), 128.41 (C-12),
29.06 (C-10, C-14), 134.65 (C-9), 136.73 (C-7a), 137.50 (C-2). 8 was found to be identical with a
sample prepared in 75% yield by tri¯uoroacetylation of N-benzylindole [25] with tri¯uoroacetic
anhydride in ether.
3
Reaction of 1 (0.6 g, 3 mmol) with tri¯uoroacetic anhydride (5.6 cm , 30 mmol) following the
procedure mentioned above afforded 4 (60 mg, 11%), 6 (40 mg, 6%), and 7.
Cyclic tetramer (7; C H N )
64 52 4
ꢀ
M.p.: 303±304 C; white spongy mass (benzene-petroleum ether); yield: 0.02 g (4%); UV:
1
ꢄmax(ether) ˆ 228, 289 nm (log"); H NMR (CDCl ): ꢈ ˆ 3.51 (2H, br s, 15-CH ), 6.68 (2H, br s,
3
2
1
3
8
4
-CH ), 6.69 (1H, s, 2-H), 7.16±7.41 (8H, m, Ar±H) ppm; C NMR: (CDCl ): ꢈ ˆ 21.28 (15-CH ),
2
3
2
4.97 (8-CH ), 105.0 (C-3), 108.6 (C-7), 117.14 (C-4), 119.18 (C-6), 120.74 (C-5), 125.95 (C-11,
2

1238
K. M. Biswas et al.
0
C-13), 126.86 (C-2, C-2 ), 128.42 (C-10, C-14), 129.21 (C-3a), 136.03 (C-7a), 137.99 (C-9), 137.41
‡
(
C-12) ppm; MS (FAB): m/z (%) ˆ 876 (M , 37), 785 (M±PhCH , 10), 656 (M±N-benzyl-3-
2
indolylmethyl, 39), 565 (M±N-benzyl-3-(p-tolylmethyl)indole, 30), 431 (45), 382 (31), 289 (38),
38 (32).
1
X-Ray crystal structure analysis of compound 5
X-Ray diffraction quality crystals were grown from a solution 5 in a mixture of isopropanol and
dichloromethane.
Oscillation and Weissenberg photographs yielded preliminary unit-cell and space group
information. An Enraf-Nonius CAD-4 diffractometer (CuKꢁ radiation, graphite monochromator)
was used for all other measurements. Intensity data were corrected for the usual Lorentz and
polarization effects; an empirical absorption correction, based on the ꢉ-dependency of the intensities
ꢀ
of several re¯ections with ꢊ ca. 90 , was also applied. Laue symmetry indicated that the crystals
ꢀ
belonged to the triclinic system, space group P1 or P1; the latter was assumed at the outset and
shown to be correct by the structure solution and re®nement. Unit-cell parameters were derived from
ꢀ
ꢀ
the diffractometer setting angles for 25 re¯ections (36 < ꢅ < 40 ) widely separated in reciprocal
space.
The crystal structure was solved by direct methods. Approximate coordinates for all non-
hydrogen atoms were obtained from an E-map. Atomic positional and thermal parameters (®rst
isotropic, then anisotropic) of these atoms were adjusted by means of several rounds of full-matrix
least-squares calculations. Hydrogen atoms were incorporated at their calculated positions, and an
extinction correction was included as a variable during the later iterations. No unusual features were
present in a ®nal difference Fourier synthesis.
Crystallographic calculations were performed on PDP11/44 and Micro VAX computers by use of
the Enraf-Nonius Structure Determination Package (SDP 3.0) [26]. For all structure-factor
calculations, neutral atom scattering factors and their anomalous dispersion corrections were taken
from International Tables for X-Ray Crystallography, vol. IV, The Kynoch Press, Birmingham, UK
1974.
Acknowledgements
The authors thank the Central Drug Research Institute, Lucknow, India for the mass spectra. H.M. is
grateful to the U.G.C., New Delhi for the award of a Research Associateship.
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Synthesis and Structure of Cyclic Oligoindoles
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Received January 28, 1999. Accepted February 16, 1999