Reactions of the alkyl radical attached to the ring nitrogen of 2-phenylthio-indole, -benzimidazole and -uracil

Article abstract of DOI:10.1039/a705139e

Alkyl radicals have been generated on the 1-N-alkyl group of 2-phenylthioindole, 2-phenylthiobenzimidazole and 6-phenylthiouracil derivatives. These N-alkyl radicals have been generated from the corresponding N-alkyl bromides by the action of triphenyltin hydride-azoisobutyronitrile, triphenyltincobaloxime or by the photolysis of the corresponding N-alkylcobaloxime. Reaction modes differ little with the method of radical generation except for the substantial formation of alkyl phenyl sulfide, a radical substitution product of the alkylcobaloximes, in the photolysis of the cobaloximes. The cobaloxime(II) species, which exists in the reaction system N-alkyl bromide-triphenyltincobaloxime, activates the phenylthio group for the radical substitution, and the lack of the tin hydride makes it possible for the reaction to occur at a higher concentration than the reaction with the hydride reagent.

Full text of DOI:10.1039/a705139e

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Reactions of the alkyl radical attached to the ring nitrogen of
2-phenylthio-indole, -benzimidazole and -uracil
Tomohiro Uetake, Mayumi Nishikawa and Masaru Tada*
Department of Chemistry, Advanced Research Center for Science and Engineering, and
Materials Research Laboratory for Bioscience and Photonics, Waseda University, Okubo,
Shinjuju, Tokyo 169, Japan
Alkyl radicals have been generated on the 1-N-alkyl group of 2-phenylthioindole, 2-phenylthiobenz-
imidazole and 6-phenylthiouracil derivatives. These N-alkyl radicals have been generated from the
corresponding N-alkyl bromides by the action of triphenyltin hydride–azoisobutyronitrile, triphenyltin-
cobaloxime or by the photolysis of the corresponding N-alkylcobaloxime. Reaction modes differ little
with the method of radical generation except for the substantial formation of alkyl phenyl sulfide,
a radical substitution product of the alkylcobaloximes, in the photolysis of the cobaloximes. The
cobaloxime(II) species, which exists in the reaction system N-alkyl bromide–triphenyltincobaloxime,
activates the phenylthio group for the radical substitution, and the lack of the tin hydride makes it possible
for the reaction to occur at a higher concentration than the reaction with the hydride reagent.
cobalt() species, we generated 3-indol-1-ylpropyl 5 (n = 1), 4-
Introduction
indol-1-ylbutyl 5 (n = 2), 3-benzimidazol-1-ylpropyl 10 (n = 1),
4-benzimidazol-1-ylbutyl 10 (n = 2), 3-(3-methyl-6-phenyl-
thiouracil-1-yl)propyl 11 (n = 1, radical instead of Br), and 4-(3-
methyl-6-phenylthiouracil-1-yl)butyl radical 11 (n = 2, radical
instead of Br) by (a) bromide–triphenyltin hydride, (b)
bromide–triphenyltincobaloxime, and (c) the homolysis of ω-
indol-1-yl and ω-benzimidazol-1-yl-alkylcobaloxime.
The indole skeleton is widely formed in natural products such
as the indole alkaloids,1 some of which contain an additional
carbocycle condensed at the nitrogen and the C-2 position of
the pyrrole part as exemplified by vicamine.2 Both the wide
distribution of the indole system in nature and its basic char-
acter as a heterocyclic aromatic system have provided us a stage
for the study of organic reactions.3 Benzimidazole, although
belonging to the same class of aromatic compounds as indole,
has the ability to ligate strongly to transition metals, a property
which may modify its chemical properties in the presence of
transition metal ions. A 6-heteroatom substituent in uracils is
important for biological activity,4 whilst the presence of an α,β-
unsaturated carbonyl moiety and its behaviour toward a radical
species in these compounds is important in relation to their bio-
chemistry and chemistry. Indole, benzimidazole and uracil,
have in common a formal enamine partial structure and we
have studied the cyclization of an alkyl radical attached to the
ring nitrogen both in the presence and absence of the transition
metal complex, bis(dimethylglyoximato)-(4-tert-butylpyridine)-
cobalt(), hereafter referred to as cobaloxime.
The versatility and usefulness of a radical strategy for the
construction of carbocycles has been demonstrated together
with a number of successful examples reported for the radical
annelation of indole5–10 and benzimidazole.11 Caddick et al.
showed the usefulness of the sulfur function in the radical
annelation in which the intramolecular alkyl radical causes an
ipso substitution to yield a carbocycle by the extrusion of the
sulfur function.10 The reactivity of the sulfur functions in
the ipso substitution increases in the order of sulfide, sulfoxide
and sulfone. This result is in accordance with our findings that
the radical attack on sulfur functions has nucleophilic
character.12
H
O
N
O
N
Me
Me
Me
Me
Co
L
N
O
N
O
H
Cobaloxime [Co], L = 4-tert-butylpyridine
Results and discussion
Treatment of 1-(3-bromo-2,2-dimethylpropyl)-2-phenylthio-
1H-indole 1a with triphenyltin hydride gave a reduction
product 2a and a cyclization product 3a. The same treatment
of 4-(4-bromo-3,3-dimethylbutyl)-2-phenylthio-1H-indole 1b
yielded a reduction product 2b and a cyclization product 3b.
Both reactions gave diphenyl disulfide as
a by-product
(Scheme 1 and Table 1). The structures of the products were
SPh
SPh
Me
N
N
(CH2)n
Me
CH2X
Me
(CH2)n
Me
Me
In a series of studies we have demonstrated that the reactivity
of an alkyl radical to a sulfur function is affected by a co-
existing cobalt() species in the reaction system13 and that the
effect is derived from coordination of the sulfur function to
cobalt().14 By Caddick’s criteria, a sulfide has the lowest rad-
icophilicity with respect to an alkyl radical, but we can expect
this to be enhanced in the presence of cobalt() species.
This background information prompted us to investigate rad-
ical annelation on indole, benzimidazole and uracil in the pres-
ence and absence of cobalt() species. To test the effect of
1
2
SPh
Me
N
N
(CH2)n
Me
Me
(CH2)n
CH2SPh
Me
3
4
Scheme 1
J. Chem. Soc., Perkin Trans. 1, 1997
3591

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Table 1 Reaction of ω-(2-phenylthioindol-1-yl)alkyl radical
Yield (%)
Entry
Compd.
X
n
Conditions
2
3
4
(PhS)2
1
2
3
4
5
6
1a
1b
1a
1b
1c
1d
Br
Br
Br
Br
[Co]
[Co]
1
2
1
2
1
2
Ph3SnH–AIBNa
Ph3SnH–AIBNa
Ph3Sn[Co]/heatb
Ph3Sn[Co]/heatc
hvd
22
33
3
8
—
—
58
43
67
74
56
44
—
—
—
—
32
30
36
28
45
41
—
—
hvd
a 1a and 1b 2.0 × 10Ϫ3 mol dmϪ3, Ph3SnH 4.0 × 10Ϫ3 mol dmϪ3. Reflux 6 h in benzene. b 1a 2.0 × 10Ϫ2 mol dmϪ3, Ph3Sn[Co] 6.0 × 10Ϫ2 mol dmϪ3
130 ЊC, 24 h in DMF. c 1b 2.0 × 10Ϫ2 mol dmϪ3, Ph3Sn[Co] 1.2 × 10Ϫ1 mol dmϪ3. 130 ЊC, 24 h in DMF. d 1c and 1d 4.0 × 10Ϫ3 mol dmϪ3, 350 nm, 24 h.
.
deduced from the appearance in the NMR spectrum of the tert-
butyl group as a terminal group in 2a and 2b and the disappear-
ance of the phenylthio group in 3a and 3b. Both the radical
intermediates 5 (n = 1 and 2) are considered to abstract hydro-
gen from triphenyltin hydride at a similar rate because the steric
bulkiness of the radical centres is comparable in those inter-
mediates. Hence the increased yield of 2b from 2a (22–33%) and
the decreased yield of 3b from 3a (58–43%) must be due to the
lower efficiency of 6-exo-trig cyclization compared to 5-exo-
trig cyclization of the intermediate radical 5.15,16 This is a gen-
eral feature of the intramolecular radical addition of the hex-5-
enyl17 and hept-6-enyl radical.18 The extruded phenylthio rad-
ical dimerizes to give diphenyl disulfide. The reactions of the
bromides 1a and 1b with triphenyltincobaloxime, Ph3Sn[Co],
gave the same cyclization products 3a and 3b in better yields
than the reaction with triphenyltin hydride, the result of the
reduction products 2a and 2b being reduced (Scheme 2). The
lack of a hydride reagent made it possible to carry out the
reaction without great dilution and to use the reagent in excess,
in contrast to the reaction with the tin hydride (see footnotes in
Table 1).
It has been established that the longest wavelength band of the
UV absorption is a ligand-to-metal charge transfer (LMCT)
band19 and this excitation causes homolysis of the carbon–
cobalt bond of the organocobaloxime.13,20,21 The radical cycliz-
ation products 3a and 3b, however, are formed in comparable
yields to the reaction with tin hydride. The phenylthiyl radical
formed in the radical cyclization reacts with organocobaloxime
to give the phenyl sulfides 4a and 4b (Scheme 3). The structure
SPh
Me
PhS• + 1c,d
+
[Cobaloxime(II)]
N
(CH2)n
CH2SPh
Me
4c,d
Scheme 3
1
was confirmed by the appearance of signals in the H NMR
spectrum due to the methylene adjacent to the sulfur (δ = 3.05)
and an additional phenylthio group. Thus, the phenylthiyl
radical generated as a by-product of the cyclization yielded the
substitution products 4c and 4d of the organocobaloxime 1c
and 1d instead of the formation of diphenyl disulfide. This type
of reaction producing a sulfide from a thiyl radical and an
organo-cobaloxime has been reported by Huston et al.22 and
us.13d
•
SPh
SPh
Me
N
N
1a,b
Me
Me
(CH2)n
(CH2)n
CH2•
Me
5
N
N
SPh
Me
N
SPh
Me
N
PhS•
+
N
(CH2)n
3
(CH2)n
(CH2)n
CH2X
Me
Me
Me
Me
Me
6
7
Scheme 2
N
N
We had expected that the reactivity would be profoundly
affected by the presence of cobaloxime() species, since it had
been shown that they coordinate to sulfide. The effect of cobal-
oxime(), however, was modest, an unexpected result which
indicates that there is little or no coordination between the
cobaloxime() and the sulfide moiety of the intermediate rad-
ical 5. Nevertheless, the yields of 3a and 3b were improved from
those of the reactions with tin hydride (3a, 58→67%; 3b,
43→74%) by using an excess of triphenyltincobaloxime, where-
as the use of an excess of tin hydride gave decreased yields of 3a
and 3b. Thus, the product yield and the reaction conditions
show the usefulness of triphenyltincobaloxime as a radical gen-
erator. The reaction using triphenyltincobaloxime, however, is
rather slow and an excess (3–6 equiv.) of the reagent is neces-
sary for practical synthesis.
(PhS)2
SPh
Me
N
N
Me
Me
(CH2)n
(CH2)n
CH2SPh
Me
9
8
Scheme 4
N-(ω-Bromoalkyl)benzimidazoles (6a and 6b) and N-(ω-
cobaloximatoalkyl)benzimidazoles 6c and 6d were subjected to
the same reaction conditions as the reactions of the indole
derivatives 1a and 1b, and the results are summarized in Table
2 and Scheme 4. Benzimidazole is a strong nitrogen ligand to
cobalt(), and the radical intermediate of benzimidazole
derivative 10 can coordinate to cobaloxime() (Scheme 5).
In comparison with the reaction of indole derivatives, a gen-
eral feature of the reaction of benzimidazole derivatives with
Next, the intermediate radicals 5a and 5b were generated by
photolyses of the corresponding organocobaloximes 1c and 1d.
3592
J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 Reaction of ω-(2-phenylthiobenzimidazol-1-yl)alkyl radical
Yield (%)
Entry
Compd.
X
n
Conditions
7
8
9
(PhS)2
1
2
3
4
5
6
6a
6b
6a
6b
6c
6d
Br
Br
Br
Br
[Co]
[Co]
1
2
1
2
1
2
Ph3SnH–AIBNa
Ph3SnH–AIBNa
Ph3Sn[Co]/heatb
Ph3Sn[Co]/heatc
hvd
50
35
23
11
—
—
22
64
45
81
36
54
—
—
—
—
35
36
21
46
38
30
—
—
hvd
a 6a and 6b 2.0 × 10Ϫ3 mol dmϪ3, Ph3SnH 4.0 × 10Ϫ3 mol dmϪ3. Reflux 6 h in benzene. b 6a 2.0 × 10Ϫ2 mol dmϪ3, Ph3Sn[Co] 6.0 × 10Ϫ2 mol dmϪ3
.
130 ЊC, 24 h in DMF. c 6b 2.0 × 10Ϫ2 mol dmϪ3, Ph3Sn[Co] 1.2 × 10Ϫ1 mol dmϪ3. 130 ЊC, 24 h in DMF. d 6c and 6d 4 × 10Ϫ3 mol dmϪ3, 350 nm, 24 h.
Table 3 Reaction of ω-(6-phenylthiouracil-1-yl)alkyl radical
N
+
[Cobaloxime(II)]
Yield (%)
SPh
Me
N
Entry
Compd.
n
Conditions
12
13
(PhS)2
(CH2)n
CH2•
1
11a
11b
11a
11b
1
2
1
2
Ph3SnH–AIBNa
Ph3SnH–AIBNa
Ph3Sn[Co]/heatd
Ph3Sn[Co]/heatd
28
76
0
54
5
43
18
b
Me
2
26
61
45
[Co(II)]
10
3c
4e
21
N
a 11a or 11b 3.0 × 10Ϫ3 mol dmϪ3, Ph3SnH 9.0 × 10Ϫ3 mol dmϪ3. Reflux
4 h in benzene. b Considerable amount but not determined. c 13% of
11a was recovered. d 11a or 11b 2.0 × 10Ϫ2 mol dmϪ3, Ph3Sn[Co]
1.2 × 10Ϫ1 mol dmϪ3. 120 ЊC, 24 h in DMF. e 38% of 11b was recovered.
SPh
Me
N
(CH2)n
CH2•
Me
[10] [Co(II)]
however, is overcome by using triphenyltincobaloxime as a rad-
ical generator, which also avoids the high dilution conditions
used to prevent reduction. Radical cyclization using triphenyl-
tin hydride as a radical generator must be carried out at a
concentration of the order of 10Ϫ3 mol dmϪ3 to obtain a prac-
tical yield of the cyclization product. The cyclization using
triphenyltincobaloxime, on the other hand, can be carried
out more conveniently at a higher concentration of the order
of 10Ϫ2 mol dmϪ3. The radical cyclization using the alkyl-
cobaloximes 1c and 6c is not practical because a considerable
amount of the starting cobaloximes is consumed by the sub-
stitution reaction with the phenylthio radical liberated in the
ipso substitution.
Scheme 5
triphenyltin hydride is the increased yields of the hydrogen
abstraction products 7a and 7b. It is also a general trend that
the 2,2-dimethylbutyl radical 10 (n = 2) cyclizes slightly more
efficiently than the 2,2-dimethylpropyl radical 10 (n = 1) under
the same conditions (see entries 1, 2 and entries 5, 6 in Table 2).
This is a reversed trend compared to the case of the ω-indol-1-
yl-2,2-dimethylalkyl radical. Contrary to our expectations,
other features of the radical of the benzimidazole derivative 10
are the same as those of the radical of the indole derivative 5,
and the effect of the coordination with cobaloxime() is less
than profound.
In conclusion, 2-phenylthioindole, 2-phenylthiobenzimid-
azole and 6-phenylthiouracil behave in a manner similar to
that in the reaction with the intramolecular alkyl radical,
although minor modifications are seen. The co-existence of
cobaloxime() species in these radical reactions affects the reac-
tion process only in minor aspects, but the use of triphenyltin
cobaloxime as a radical generator is convenient and profitable
for practical syntheses of indole, benzimidazole and uracil
derivatives having a carbocycle containing the nitrogens of pyr-
role, imidazole and uracil moieties.
Next, 1-(ω-bromoalkyl)-3-methyl-6-phenylthiouracil deriv-
atives 11a (n = 1) and 11b (n = 2) were allowed to react with
O
O
O
MeN
O
MeN
O
MeN
O
(PhS)2
N
N
N
SPh
Me
CH2Br
Me
SPh
Me
(CH2)n
(CH2)n
(CH2)n
Me
Me
Me
Me
11
12
13
Experimental
Scheme 6
General
the triphenyltin radical in the absence and presence of cobal-
oxime() and the results are summarized in Table 3 and Scheme
6. The new appearance of the tert-butyl group and the retention
of the phenylthio group define the structures 12. The appear-
ance of the methylene group connected to the olefinic moiety
and the disappearance of the phenylthio group define the struc-
ture 13. The general trends are the same as those for the indole
and benzimidazole derivatives, but it is noteworthy that the rad-
ical cyclization (ipso substitution) decreases substantially when
the alkyl chain lengthens. Thus, a 6-exo-trig radical addition is
much less efficient than a 5-exo-trig radical addition.
Benzene and DMF were purified by distillation over sodium–
benzophenone and 4 Å molecular sieves, respectively. 1H
NMR spectra were recorded on JEOL JME-EX270 (270
MHz) and Hitachi R-90 (90 MHz) spectrometers in CDCl3
solution using tetramethylsilane as an internal reference.
Chemical shifts and coupling constants are recorded in δ
values and Hz, respectively. IR spectra were recorded on a
Perkin-Elmer 1640 FT-IR spectrometer in chloroform solu-
tion. Mass spectra were recorded on JEOL JMS Automass
150 and JEOL DX-300 (high resolution) spectrometers by
electron impact ionization at 70 eV. Melting points are uncor-
rected. Chromatography was performed using flash silica
(Merck 60, 230–400) under positive pressure. Preparative TLC
was performed using a 20 × 20 × 0.2 cm plate of silica gel
(Merck 60, PF254).
In the indole system, Caddick et al. reported8 that phenyl-
sulfonyl and phenylsulfinyl radicals were better leaving groups
than a phenylthiyl radical, and hence more cyclization product
was obtained from phenylsulfonyl derivatives. This difficulty,
J. Chem. Soc., Perkin Trans. 1, 1997
3593

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All the spectra and elemental analyses were performed using
the facilities of the Materials Characterization Central Labor-
atory of Waseda University.
were poor (<10%), and solvolysis products of the bromides
(alcohol instead of bromide) and the cyclic ethers (from the
alcohols) were obtained in substantial yields.
Compound 11a, an oil; δH(270 MHz) 1.19 (6H, s), 3.30 (3H,
s), 3.59 (2H, s), 4.16 (2H, s), 5.08 (1H, s) and 7.42–7.60 (5H,
m); νmax/cmϪ1 1698, 1680, 1654, 1575, 1466 and 1460; m/z 384
(Mϩ, 9%), 382 (Mϩ, 9), 303 (13), 247 (81), 123 (100) and 77 (18)
(Found: Mϩ, 382.0329. C16H19BrN2O2S requires 382.0351).
Compound 11b, an oil; δH(270 MHz) 1.18 (6H, s), 1.82–1.93
(2H, m), 3.29 (3H, s), 3.36 (2H, s), 4.04–4.15 (2H, m), 5.01 (1H,
s) and 7.43–7.61 (5H, m); νmax/cmϪ1 1694, 1677, 1636, 1578,
1442 and 1418; m/z 398 (Mϩ, 18%), 396 (Mϩ, 18), 261 (14), 234
(29), 201 (28), 123 (49), 83 (37) and 55 (199) (Found: Mϩ,
396.0536. C17H21BrN2O2S requires 396.0508).
Starting materials
(a) Bromides. 1-(3-Bromo-2,2-dimethylpropyl)-2-phenylthio-
1H-indole 1a, 1-(4-bromo-3,3-dimethylbutyl)-2-phenylthio-1H-
indole 1b, 1-(3-bromo-2,2-dimethylpropyl)-2-phenylthiobenz-
imidazole 6a and 1-(4-bromo-3,3-dimethylbutyl)-2-phenylthio-
benzimidazole 6b were prepared by alkylation of 2-phenyl-
thioindole23 and 2-phenylthiobenzimidazole.24
2-Phenylthioindole or 2-phenylthiobenzimidazole (1.0–5.0
mmol), 1,3-dibromo-2,2-dimethylpropane25 or 1,4-dibromo-
2,2-dimethylbutane26 (3.0 equiv.), and powdered potassium
hydroxide (1.2 equiv.) were mixed in 5.0–7.0 cm3 (indole) or
10–15 cm3 of DMF (benzimidazole). The mixture containing
1,3-dibromo-2,2-dimethylpropane was heated at 130 ЊC for
40–48 h, and the mixture containing 1,4-dibromo-2,2-dimethyl-
butane was stirred at room temperature (ca. 20 ЊC) for 16–19 h
under argon. The cooled reaction mixture was treated with
water and extracted with diethyl ether. The extract gave a crude
product after washing with brine, drying, and concentration.
The crude product thus obtained was purified by chroma-
tography on a silica gel column using hexane–ethyl acetate
(50:1) as eluent. The pure products 1a, 1b, 6a and 6b were
obtained in 44, 77, 51 and 73% yields respectively. They are
spectrometrically pure but thermally too unstable to provide
correct elemental analyses.
Compound 1a, an oil; δH(270 MHz) 1.09 (6H, s), 3.42 (2H, s),
4.19 (2H, s), 6.81–7.32 (8H, m), 7.50 (1H, dd, J 8.3 and 0.7) and
7.62 (1H, dd, J 8.3 and 0.7); νmax/cmϪ1 1582, 1471, 1450 and
1310; m/z 375 (Mϩ, 100%), 373 (Mϩ, 100), 238 (81), 205 (77)
and 160 (16) (Found: Mϩ, 373.0488. C19H20BrNS requires
373.0500).
Compound 1b, mp 57.2–58.4 ЊC (hexane–ethanol) (Found:
C, 61.50; H, 5.28; N, 3.33. C20H22BrNS requires C, 61.85; H,
5.71; N, 3.61%); δH(270 MHz) 1.01 (6H, s), 1.05–1.14 (2H, m),
3.24 (2H, s), 4.20–4.44 (2H, m), 6.95 (1H, s), 7.13–7.32 (7H, m),
7.39 (1H, d, J 8.2) and 7.65 (1H, d, J 8.2); νmax/cmϪ1 1582, 1462,
1446 and 1313; m/z 389 (Mϩ, 90%), 387 (Mϩ, 90), 238 (79) and
205 (51).
Compound 6a, an oil; δH(270 MHz) 1.16 (6H, s), 3.44 (2H, s),
4.29 (2H, s), 7.21–7.42 (7H, m), 7.45–7.51 (1H, m) and 7.67–
7.77 (1H, m); νmax/cmϪ1 1582, 1480, 1448, 1369 and 1343; m/z
376 (Mϩ, 13%), 374 (Mϩ, 13), 295 (7), 239 (48), 109 (45) and 55
(100) (Found: Mϩ, 376.0461. C18H19BrN2S requires 376.0433).
Compound 6b, an oil; δH(270 MHz) 1.09 (6H, s), 1.62–1.74
(2H, m), 3.29 (2H, s), 4.15–4.28 (2H, m), 7.22–7.42 (8H, m)
and 7.75–7.81 (2H, m); νmax/cmϪ1 1582, 1463 and 1360; m/z
388 (Mϩ, 12%), 386 (Mϩ, 12), 309 (5), 253 (48), 225 (43) and
51 (100) (Found: Mϩ, 388.0600. C19H21BrN2S requires
388.0609).
1-(3-Bromo-2,2-dimethylpropyl)-3-methyl-6-phenylthio-
uracil 11a and 1-(4-bromo-3,3-dimethyl)butyl-3-methyl-6-
phenylthiouracil 11b were prepared by essentially the same pro-
cedure as the corresponding compounds for the indole and
benzimidazole derivatives but using sodium hydride as a base.
A solution of 3-methyl-6-phenylthiouracil27 (234 mg, 1.0
mmol) in DMF (5.0 cm3) was added to sodium hydride (washed
with hexane; 1.2 mmol) under argon, and the mixture was
stirred for 3.0 h at room temperature (ca. 20 ЊC) to prepare
the sodium salt of uracil. The sodium salt thus formed was
treated with the corresponding dibromides and then heated at
120 ЊC (11a) or 70 ЊC (11b) for 2.0 h. The cooled mixture was
mixed with dilute hydrochloric acid (1 mol dmϪ3) and extracted
with ethyl acetate. Concentration of the extract after washing
with water and drying gave the crude product which was puri-
fied successively by silica gel column chromatography eluting
with hexane–ethyl acetate (1:1) and on a preparative silica gel
TLC plate using the same solvent. The yields of the products
Cobaloximes
A
stirred and cooled suspension of chloro(4-tert-butyl-
pyridine)cobaloxime28 (771 mg, 2.0 mmol) in methanolic
sodium hydroxide (20 cm3, 96 mg, 2.4 mmol) under argon
was treated in small portions with sodium borohydride (38 mg,
1.0 mmol) over a period of 15 min. The cobaloxime() anion
thus obtained was treated with the corresponding bromide
(1.0 mmol) after which the mixture was heated at 50 ЊC for
4.0 h. It was then cooled, diluted with water and extracted
with chloroform. Conventional work-up of the extract gave
the crude product which was purified by silica gel column
chromatography using chloroform–methanol (20:1) as eluent.
Analytical grade organocobaloximes were obtained by the dif-
fusional mixing of the dichloromethane solution with pentane.
Although elemental analyses failed on occasions to give the
correct values because of thermal instability, the 1H NMR
spectra showed that all the cobaloximes were essentially pure.
Compound 1c, orange crystals, mp 164 ЊC (decomp.) (Found:
C, 59.45; H, 6.53; N, 11.29. C36H47CoN6O4S requires C, 60.16;
H, 6.59; N, 11.69%); δH(270 MHz) 0.79 (6H, s), 1.25 (9H, s),
1.72 (2H, s), 2.03 (12H, s), 3.93 (2H, s), 6.91 (1H, s), 7.11–7.42
(9H, m), 7.62 (2H, d, J 6.9) and 8.36 (2H, dd, J 6.9 and 1.3);
νmax/cmϪ1 1616, 1562, 1452 and 1370.
Compound 1d, orange crystals, mp 152 ЊC (decomp.)
(Found: C, 60.32; H, 6.53; N, 11.38. C37H49CoN6O4S requires
C, 60.64; H, 6.74; N, 11.47%); δH(270 MHz) 0.79 (6H, s), 1.24
(9H, s), 1.28–1.37 (2H, m), 1.61 (2H, s), 2.00 (12H, s), 4.01–4.10
(2H, m), 6.87 (1H, s), 7.03–7.38 (9H, m), 7.60 (2H, d, J 6.9) and
8.35 (2H, dd, J 6.9 and 1.3); νmax/cmϪ1 1616, 1561, 1461 and
1379.
Compound 6c, orange crystals, mp 160 ЊC (decomp.) (Found:
C, 58.32; H, 6.42; N, 13.16. C35H46CoN7O4S requires C, 58.40;
H, 6.44; N, 13.62%); δH(270 MHz) 0.82 (6H, s), 1.26 (9H, s),
1.71 (2H, s), 2.12 (12H, s), 4.03 (2H, s), 7.22–7.48 (9H, m), 7.63
(2H, d, J 6.9) and 8.38 (2H, d, J 6.9); νmax/cmϪ1 1616, 1561, 1461
and 1368.
Compound 6d, orange crystals, mp 163 ЊC (decomp.)
(Found: C, 58.23; H, 6.58; N, 13.46. C36H48CoN7O4S requires
C, 58.92; H, 6.59; N, 13.46%); δH(270 MHz) 0.84 (6H, s),
1.25 (9H, s), 1.40–1.51 (2H, m), 1.63 (2H, s), 2.03 (12H, s),
4.10–4.19 (2H, m), 7.18–7.46 (9H, m), 7.71 (2H, d, J 6.9)
and 8.35 (2H, dd, J 6.9 and 1.7); νmax/cmϪ1 1616, 1562, 1463
and 1371.
Reactions of the bromide derivatives of indole (1a and 1b),
benzimidazole (6a and 6b) and uracil (11a and 11b)
(a) Reaction with triphenyltin hydride. A mixture of triphenyl-
tin hydride (40 mg, 0.4 mmol) and AIBN (33 mg, 0.2 mmol) in
benzene (20 cm3) was added over 15 min under argon to a
refluxing solution of one of the bromides (1a, 1b, 6a or 6b)
(0.2 mmol) in benzene (80 cm3). The mixture was then refluxed
for 6 h, cooled and concentrated. The residue was dissolved
in ethyl acetate and stirred with saturated aqueous potassium
fluoride (10 cm3). The organic layer was then separated, dried
and concentrated. The residue was passed through a short
3594
J. Chem. Soc., Perkin Trans. 1, 1997

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column of silica gel using hexane–ethyl acetate (10:1) as eluent
to remove polar by-products, and further purified using a
preparative silica-gel TLC plate and hexane–ethyl acetate
(50:1) as a developing solvent. The results are summarized in
the Tables.
J 6.6); νmax/cmϪ1 1583, 1461 and 1353; m/z 417 (Mϩ, 60%), 308
(8), 238 (38), 193 (93), 123 (100) and 91 (28) (Found: Mϩ,
417.1565. C26H27NS2 requires 417.1585).
Compound 7a, mp 98.4–100.2 ЊC (hexane–ethanol); δH(270
MHz) 1.07 (9H, s), 4.10 (2H, s), 7.18–7.44 (8H, m) and 7.67–
7.76 (1H, m); νmax/cmϪ1 1611, 1582, 1460, 1369 and 1340; m/z
296 (Mϩ, 54%), 281 (15), 225 (34), 187 (13), 161 (11), 91 (87)
and 76 (100) (Found: Mϩ, 296.1341. C18H20N2S requires
296.1347).
Compound 8a, mp 57.8–58.4 ЊC (hexane–ethanol); δH(270
MHz) 1.36 (6H, s), 2.89 (2H, s), 3.84 (2H, s), 7.16–7.29 (3H, m)
and 7.66–7.74 (1H, m); νmax/cmϪ1 1621, 1534, 1454, 1390 and
1312; m/z 186 (Mϩ, 95%), 171 (100), 156 (10), 145 (25), 131 (41)
and 117 (10) (Found: Mϩ, 186.1172. C12H14N2 requires
186.1157).
Compound 9a, mp 68.8–69.4 ЊC (hexane–ethanol); δH(270
MHz) 1.15 (6H, s), 3.08 (2H, s), 4.28 (2H, s), 7.13–7.48 (13H,
m) and 7.66–7.76 (1H, m); νmax/cmϪ1 1582, 1461, 1369 and 1342;
m/z 404 (Mϩ, 7%), 295 (100), 139 (35), 109 (27) and 77 (26)
(Found: Mϩ, 404.1382. C24H24N2S2 requires 404.1381).
Compound 7b, mp 61.6–62.8 ЊC (hexane–ethanol); δH(270
MHz) 0.98 (9H, s), 1.46–1.55 (2H, m), 4.17–4.26 (2H, m), 7.20–
(b) Reactions with triphenyltin(4-tert-butylpyridine)cobal-
oxime. A mixture of the cobaloxime (464 mg, 0.6 mmol for 1a,
6a, 11a and 11b; 928 mg, 1.2 mmol for 1b and 6b) and one of
the bromides (0.2 mmol) in dry DMF (10 cm3) was heated at
130 ЊC for 24 h (1a, 1b, 6a and 6b) or 120 ЊC (11a and 11b)
under argon. The cooled mixture was diluted with ethyl acetate
(filtered in the case of 11a and 11b), washed with saturated
aqueous sodium chloride, dried and concentrated. The residue
was passed through a short column of silica gel using hexane–
ethyl acetate (59:1) (1a, 1b, 6a and 6b) or ethyl acetate (11a
and 11b) to remove the cobaloxime and polar by-products. The
eluate was subjected further to a preparative silica gel TLC
plate using the same solvent as a developing solvent.
Essentially the same procedure was used for the reaction of
the uracil derivatives 6a and 6b except for the amount of the
solvent (35 cm3 of DMF), the amount of the triphenyltincobal-
oxime, and the reaction time (4 h). In this case, the precipitate
formed on treatment with potassium fluoride solution was fil-
tered off, and the filtrate was subjected to the same work-up
procedure as recorded above. The results are summarized in the
Tables.
7.36 (6H, m), 7.37–7.45 (2H, m) and 7.72–7.80 (1H, m); νmax
/
cmϪ1 1582, 1462, 1442 and 1359; m/z 310 (Mϩ, 63%), 253 (90),
225 (100), 109 (30) and 69 (12) (Found: Mϩ, 310.1489.
C19H22N2S requires 310.1504).
(c) Photoreaction of cobaloxime derivatives of indole (1c and
1d) and benzimidazole (6c and 6d). One of the cobaloxime
derivatives 1c, 1d, 6c or 6d (0.06 mmol) was dissolved in benz-
ene (15 cm3) and the solution dipped in an ultrasonic bath and
deaerated by bubbling argon through it via a syringe needle.
The mixture was irradiated for 24 h using a Rayonet Photoreac-
tor (RPR-100) equipped with 350 nm lamps. The residue after
concentration of the reaction mixture was subjected to the
same purification procedure as in the case of reactions with
triphenyltincobaloxime. The results are summarized in the
Tables.
Compound 8b, a white powder; δH(270 MHz) 1.11 (6H, s),
1.92 (2H, t, J 6.3), 2.85 (2H, s), 4.08 (2H, t, J 6.3), 7.18–7.32
(3H, m) and 7.64–7.72 (1H, m); νmax/cmϪ1 1616, 1459 and 1371;
m/z 200 (Mϩ, 50%), 144 (100), 117 (37) and 77 (43) (Found: Mϩ,
200.1291. C13H16N2 requires 200.1313).
Compound 9b, a white powder; δH(270 MHz) 1.09 (6H, s),
1.67–1.75 (2H, m), 2.93 (2H, s), 4.21–4.29 (2H, m), 7.16–7.21
(1H, m), 7.22–7.34 (7H, m), 7.35–7.42 (5H, m) and 7.74–7.82
(1H, m); νmax/cmϪ1 1583, 1463 and 1360; m/z Mϩ 418 (Mϩ,
93%), 309 (100), 253 (58), 239 (66), 109 (58) and 77 (57) (Found:
Mϩ, 418.1553. C25H26N2S2 requires 418.1537).
Compound 2a, an oil; δH(270 MHz) 1.01 (9H, s), 4.02 (2H, s),
6.88–7.26 (8H, m), 7.41 (1H, d, J 7.9) and 7.61 (1H, d, J 7.9);
νmax/cmϪ1 1582, 1478, 1451 and 1366; m/z 295 (Mϩ, 85%), 238
(100), 205 (46), 160 (9), 121 (20) and 91 (42) (Found: Mϩ,
295.1360. C19H21NS requires 295.1395).
Compound 3a, mp 82.4–83.8 ЊC (hexane–ethanol); δH(270
MHz) 1.29 (6H, s), 2.81 (2H, s), 3.80 (2H, s), 6.14 (1H, d, J 0.7),
6.99–7.23 (3H, m) and 7.53 (1H, dd, J 6.9 and 1.0); νmax/cmϪ1
1614, 1554, 1479, 1456 and 1377; m/z 185 (Mϩ, 100%), 170 (48),
144 (24), 129 (66), 115 (14) and 102 (19) (Found: Mϩ, 185.1192.
C13H15N requires 185.1204).
Compound 4a, an oil; δH(270 MHz) 1.09 (6H, s), 3.05 (2H, s),
4.19 (2H, s), 6.90–6.98 (2H, m), 7.06–7.32 (11H, m), 7.50 (1H,
d, J 6.6) and 7.61 (1H, d, J 6.6); νmax/cmϪ1 1582, 1479, 1450 and
1346; m/z 403 (Mϩ, 37%), 294 (58), 238 (100), 205 (40), 165
(15) and 109 (67) (Found: Mϩ, 403.1413. C25H25NS2 requires
403.1428).
Compound 2b, mp 55.4–56.8 ЊC (hexane–ethanol); δH(270
MHz) 0.90 (9H, s), 1.38–1.46 (2H, m), 4.11–4.19 (2H, m), 6.93
(1H, d, J 0.7), 7.16–7.33 (7H, m), 7.50 (1H, d, J 7.9) and 7.64
(1H, d, J 7.9); νmax/cmϪ1 1582, 1460, 1447 and 1352; m/z 309
(Mϩ, 100%), 238 (49), 205 (31), 117 (16) and 91 (24) (Found:
Mϩ, 309.1524. C20H23NS requires 309.1551).
Compound 3b, mp 52.2–53.4 ЊC (hexane–ethanol); δH(270
MHz) 1.01 (6H, t, J 6.6), 1.81 (2H, t, J 6.6), 2.73 (2H, s), 4.05
(2H, t, J 6.6), 6.17 (1H, s) and 7.03–7.62 (4H, m); νmax/cmϪ1
1610, 1547, 1460 and 1358; m/z 199 (Mϩ, 50%), 184 (6), 167
(6), 143 (100) and 130 (19); m/z 199 (Mϩ, 50%), 184 (6), 167 (6),
143 (100), 130 (19) and 115 (21) (Found: Mϩ, 199.1390.
C14H17N requires 199.1361).
Compound 4b, mp 104.4–104.8 ЊC (hexane–ethanol); δH(270
MHz) 1.01 (6H, s), 1.57–1.65 (2H, m), 2.86 (2H, s), 4.15–4.23
(2H, m), 6.92 (1H, s), 7.06–7.41 (13H, m) and 7.63 (1H, d,
Compound 12a, a yellow oil; δH(90 MHz) 1.08 (9H, s), 3.29
(3H, s), 4.01 (2H, s), 5.05 (1H, s) and 7.46–7.63 (5H, m); νmax
/
cmϪ1 1698, 1649, 1442 and 1398; m/z 304 (Mϩ, 100%), 289 (9),
248 (49), 247 (45), 234 (28), 215 (35), 195 (19), 190 (40), 123
(47), 109 (11) and 77 (7) (Found: Mϩ, 304.1280. C16H20N2O2S
requires 304.1245).
Compound 13a, mp 86.1–89.3 ЊC (ethyl acetate); δH(90 MHz)
1.21 (6H, s), 2.70 (2H, d, J 1.3), 3.32 (3H, s), 3.69 (2H, s) and
5.64 (1H, t, J 1.3); νmax/cmϪ1 1703, 1666, 1640, 1382 and 1322;
m/z 194 (Mϩ, 58%), 179 (52), 136 (14), 122 (100), 109 (22), 94
(20) and 81 (43) (Found: Mϩ, 194.1075. C10H14N2O2 requires
194.1055).
Compound 12b, a yellow oil; δH(90 MHz) 1.04 (9H, s), 1.66–
1.76 (2H, m), 3.29 (3H, s), 4.04–4.13 (2H, m), 4.99 (1H, s) and
7.42–7.61 (5H, m); νmax/cmϪ1 1694, 1646, 1575, 1442, 1390 and
1372; m/z 318 (Mϩ, 13%), 261 (4), 201 (13), 167 (13), 149 (41),
123 (23), 85 (27) and 69 (100) (Found: Mϩ, 318.1434.
C17H22N2O2S requires 318.1402).
Compound 13b, mp 138.2–140.1 ЊC (ethyl acetate); δH(90
MHz) 1.05 (6H, s), 1.73 (2H, t, J 6.7), 2.42 (2H, br s), 3.34 (3H,
s), 3.84 (2H, t, J 6.7) and 5.53 (1H, t, J 1.2); νmax/cmϪ1 1668,
1656, 1490 and 1457; m/z 208 (Mϩ, 69%), 193 (32), 180 (7), 165
(11), 152 (13), 140 (89) and 95 (100); m/z 208 (Mϩ, 69%), 193
(32), 180 (7), 165 (11), 152 (13), 140 (89) and 95 (100) (Found:
Mϩ, 208.1259. C11H16N2O2 requires 208.1212).
Acknowledgements
This study was supported by the Annual Project Program of
Waseda University (95A-252) and by a 1997 Grant-in-aid
administered by the Ministry of Education, Sports, and Cul-
ture of Japan. The authors are grateful for this financial
support.
J. Chem. Soc., Perkin Trans. 1, 1997
3595

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Paper 7/05139E
Received 17th July 1997
Accepted 12th August 1997
3596
J. Chem. Soc., Perkin Trans. 1, 1997