Photochemical substitution of polyhalogenothiophene and halogenothiazole derivatives

Article abstract of DOI:10.1039/b004002i

The irradiation of 2,3-diodo-5-nitrothiophene in the presence of aromatic and heteroaromatic compounds gave the corresponding 2-aryl derivatives in high yields. The irradiation of 2,4-diiodo-5-nitrothiophene under the same conditions gave the corresponding 2-aryl derivatives in low yields. The observed difference in the reactivity can be explained on the basis of the hypothesis that the homolytic cleavage of the carbon-iodine bond occurred in a π,π* triplet state. Computational results showed that the lowest triplet state of the 2,3-diiodo isomer is π,π*, while that of the 2,4-isomer is π,π*. The irradiation of 2-bromo-5-nitrothiazole in the presence of benzene or indene gave the corresponding 2-bromo-5-arylthiazole. This behaviour can be explained by considering that the lowest excited triplet state cannot allow the cleavage of the carbon-bromine bond thus electron transfer occurs and leads to the substitution of the nitro group. The photochemical substitution reactions on 2,3-diiodo-5-nitrothiophene can be carried out in large scale using a new flow reactor using a PFTE pipe.

Full text of DOI:10.1039/b004002i

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Photochemical substitution of polyhalogenothiophene and
halogenothiazole derivatives†
Maurizio D’Auria,*a Claudio Distefano,a Franco D’Onofrio,b Giacomo Maurielloa and
Rocco Racioppia
1
a Dipartimento di Chimica, Università della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy
b Centro CNR per lo Studio della Chimica delle Sostanze Organiche Naturali,
Dipartimento di Chimica, Università di Roma “La Sapienza”, P.le A. Moro 2, 00185 Roma,
Italy
Received (in Cambridge, UK) 18th May 2000, Accepted 22nd August 2000
First published as an Advance Article on the web 2nd October 2000
The irradiation of 2,3-diodo-5-nitrothiophene in the presence of aromatic and heteroaromatic compounds gave
the corresponding 2-aryl derivatives in high yields. The irradiation of 2,4-diiodo-5-nitrothiophene under the same
conditions gave the corresponding 2-aryl derivatives in low yields. The observed difference in the reactivity can be
explained on the basis of the hypothesis that the homolytic cleavage of the carbon–iodine bond occurred in a π,σ*
triplet state. Computational results showed that the lowest triplet state of the 2,3-diiodo isomer is π,σ*, while that
of the 2,4-isomer is π,π*. The irradiation of 2-bromo-5-nitrothiazole in the presence of benzene or indene gave the
corresponding 2-bromo-5-arylthiazole. This behaviour can be explained by considering that the lowest excited
triplet state cannot allow the cleavage of the carbon–bromine bond thus electron transfer occurs and leads to the
substitution of the nitro group. The photochemical substitution reactions on 2,3-diiodo-5-nitrothiophene can be
carried out in large scale using a new flow reactor using a PFTE pipe.
The photochemical reaction of halogeno substituted hetero-
cyclic derivatives with aromatic and heteroaromatic compounds
has been the object of our previous research in order to develop
a synthetically useful methodology. We found that a photo-
chemical procedure can be used in order to obtain aryl substi-
tuted furan, thiophene, pyrrole, and imidazole derivatives
bearing an electron-withdrawing group starting from the
corresponding halogeno substituted compounds (Scheme 1).1–10
compounds in order to establish if the photochemical substi-
tution with aromatic compounds can be used with all penta-
atomic heterocyclic compounds bearing electron-withdrawing
groups and if polysubstitution reaction can occur. It is relevant
to note that 3,5-diiodothiophene-2-carbaldehyde gave the
corresponding 3,5-diphenyl derivatives when irradiated in
benzene.4
Finally, in order to use the above described reactions for pre-
parative purposes, we studied a new annular reactor. In recent
years several groups have directed efforts towards the design of
photochemical reactors which can be used for bulk quantities.
Several studies have appeared on the design of photochemical
reactors11–14 and several applications have been reported.15–27
One of the disadvantages connected with the use of immersion
photochemical reactors is the formation of deposits on the out-
side walls of the immersed light source. These deposits diminish
and eventually halt irradiation of the reaction mixture. In such
cases, periodic cleaning of the reactor is required.
In this paper we describe a new continuous flow annular
reactor based on the use of PTFE pipe.
Results and discussion
Scheme 1
In order to study the photochemical behaviour of polyhalo-
genothienyl derivatives, we decided to synthesise 2,3-diiodo-5-
nitrothiophene (4) on the basis of a previous work starting from
2,3,5-triiodothiophene (3) via a nitration with nitric acid and
acetic anhydride (Scheme 2).28 In our hands this reaction not
only gave 4 but also a mixture of 4 and 5 in 2:3 ratio (Scheme 2).
The irradiation of 4 in benzene gave the corresponding
phenyl derivative 6 in quantitative yield (Scheme 3, Table 1).
The same result was obtained by carrying out the reaction in
acetonitrile in the presence of benzene. When 4 was irradiated
in the presence of m-xylene we obtained a mixture where the
only identified products were 3-methylbenzaldehyde (7) and
3-methylbenzyl alcohol (8) (Scheme 3). It is noteworthy that
this is the first example where oxidation of a methyl group of an
In particular, we found that the presence of a nitro group in the
substrates (1f and 1h) allows the reaction to occur and that
substrates with more that one heteroatom (1h) can be used in
this type of reaction.
In this paper we describe the results obtained using both
polyhalogeno substituted nitrothiophenes and 2-bromo-5-
nitrothiazole. We studied the photochemical behaviour of these
† Atomic coefficients of the LSOMO and the HSOMO of the triplet
state of compounds 1f, 4 and 5 (Table S1) and details of the frontier
orbitals of the T1 state of 2-bromo-5-nitrotriazole (Table S2) are avail-
able as supplementary data. For direct electronic access see http://
www.rsc.org/suppdata/p1/b0/b004002i
DOI: 10.1039/b004002i
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This journal is © The Royal Society of Chemistry 2000
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Table 1 Photochemical behaviour of 4
Irradiation
Yield
(%)
Entry
ArH
Solvent
time/h
Product
1
2
3
4
Benzene
Benzene
Thiophene
2-Bromo-
thiophene
2-Chloro-
thiophene
24
24
20
20
6
6
98
77
99
66
Scheme 2
MeCN
MeCN
MeCN
9
10
5
MeCN
18
11
97
Fig. 1 Photochemical apparatus.
Scheme 4
We can see that the reaction of 4 in the presence of aromatic
or heteroaromatic compounds works well when alkyl groups
are not present in the reagent. Polysubstitution products are not
obtained.
To test the possibility of performing the reaction on bulk
quantities, we used as photochemical reactor the apparatus
described in Fig. 1 (see Appendix). To test this apparatus we
used the photochemical decarboxylation of phenylglyoxylic
acid to give benzaldehyde (Scheme 5).29 This reaction occurs
Scheme 3
alkylarene was observed. In fact, 2-iodo-5-nitrothiophene (1f)
and 2-iodo-4(5)-nitroimidazole (1h), irradiated in the presence
of m-xylene, gave the corresponding 2,4-dimethyl derivatives
(Scheme 4). The presence of two iodine atoms probably modi-
fies the oxidation potential of the substrate. Calculation of the
oxidation potentials of 1h and 4 in their triplet states by using
Scheme 5
the PM3 semiempirical method gave 64.0 and 61.1 kcal molϪ1
,
respectively. These data show that the oxidation potential for
2-iodo-4(5)-nitroimidazole 1h is higher than that of 4 and are in
agreement with the experimental results where 4 gave oxidation
products while 1h did not show this type of reaction.
The irradiation of 4 in the presence of thiophene gave the
corresponding bithienyl derivative 9 in quantitative yields
(Scheme 3, Table 1). The same type of result was obtained using
as reagent 2-bromothiophene or 2-chlorothiophene. In this case
also, the bithienyl derivatives 10 and 11 were the only products
recovered (Scheme 3, Table 1). In contrast, the irradiation of 4
in the presence of 2-methylthiophene gave the corresponding
oxidation products 12 and 13 (Scheme 3).
with Φ = 0.7. We tested the efficiency of the reactor at different
fluxes of the solution of the reagent. The results are collected in
Fig. 2. Maintaining the flux at ca. 0.1 ml minϪ1, we observed a
90% conversion of the reagent. At 1 ml minϪ1 the observed
conversion was 54%. Other reaction mixtures were irradiated in
the same way and we obtained the quantitative conversion of
the reagents in all the tests we performed using 0.1–1 ml minϪ1
flux range.
We did not observe the formation of films on the walls of the
coil. The reactor can be used for a long time without modifi-
cation of the optical properties of the coil. The coil can be used
for preparative purposes. The reaction of 4 in benzene using
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Table 2 Photochemical substitution on 5
Irradiation
obtained only through a transposition reaction. We verified that
this transposition did not occur on 4: the irradiation of 4 in
acetonitrile for 24 h did not give transposition products. This
experiment ruled out all the mechanisms involved in thiophene
phototranspositions.30–32 We assume that 6 could be formed
from an intermediate and we verified that a transposition
reaction could occur on the radical derived from the homolytic
cleavage of C–I bond (Scheme 7).
Yield
(%)
Entry
ArH
Solvent
time/h
Product
1
2
3
Benzene
Benzene
Thiophene
—
24
36
36
6
14
6
14
15
20
15
10
7
MeCN
MeCN
8
Scheme 7
Semiempirical calculations (PM3) showed that the ∆Hf of 17
was 1.1 kcal molϪ1 lower than that of 16. The different stability
of the radicals could be the driving force of the observed
transposition.
Furthermore, it is noteworthy that 4 and 5 showed a very
different reactivity in spite of the great similarity of the struc-
tures. The question is can the current hypothesis about the
mechanism of this type of photosubstitution explain this
behaviour. The mechanism of the photoarylation for halothio-
phene derivatives has been investigated.33 Our studies showed
that the excitation of the substrate leads to an n,π* triplet state,
but that this excited state is unable to undergo dissociation of
the carbon–iodine bond. This assertion is demonstrated by the
fact that when the n,π* triplet state was generated by sensitis-
ation with chrysene, it did not produce coupling products.
Thus, the reaction probably occurs in a higher excited (π,σ*,
n,σ*, or σ,σ*) triplet state mainly localised on the carbon–
iodine bond. Furthermore, the interaction between this triplet
state of the substrate and aromatic compounds leads to the
homolytic cleavage of the C–I bond with the formation of both
the radical and a complex between the aromatic compound and
the halogen atom. The formation of this complex was demon-
strated by the presence of a short-lived transient with λmax = 510
nm showing second-order decay kinetics and a half-life of
ca. 0.4 µs in laser flash photolysis. The thienyl radical thus
formed reacts rapidly with the aromatic compound to form the
corresponding arylation product (Scheme 8).33
Fig. 2 Conversion of phenylglyoxylic acid.
0.1 ml minϪ1 gave quantitative formation of the product 6. We
used this reaction up to 10 g scale.
The irradiation of 2,4-diodo-5-nitrothiophene (5) in benzene
gave 2-phenyl-3-iodo-5-nitrothiophene (6) and 5-phenyl-3-
iodo-2-nitrothiophene (14) (Scheme 6, Table 2). The same result
was obtained using acetonitrile as solvent (Scheme 6, Table 2).
When 5 was irradiated in the presence of thiophene only very
low yields of 15 were obtained (Scheme 6, Table 2). Attempts to
Scheme 8
We studied the nature of the lowest triplet state in the case of
compounds 1f, 4, and 5 using semiempirical methods (PM3).
The lowest excited triplet state of 1f showed an energy of 49
kcal molϪ1 and it is a σ,σ* triplet state. The atomic coefficients
of the orbitals involved are collected in the supplementary data
(Table S1). On the basis of the above described mechanism, the
homolytic cleavage of the C–I bond can occur on the lowest
Scheme 6
perform the reaction in the presence of 2-bromo- or 2-chloro-
thiophene did not give any identifiable product.
We have to note that, while 14 is the substitution product of
5, the conversion of 5 to 6 is surprising. Compound 6 can be
J. Chem. Soc., Perkin Trans. 1, 2000, 3513–3518
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excited triplet state of the molecule. The triplet state of 4
showed an energy of 48 kcal molϪ1 and it is a π,σ* triplet state
(Table S1, supplementary data). Also in this case the homolytic
cleavage of the C–I bond can occur in the lowest excited triplet
state. Compound 5 showed a π,π* triplet state at 47 kcal
molϪ1 (Table S1, supplementary data). In this case, the homo-
lytic cleavage of the C–I bond cannot occur in the lowest
excited triplet state. It needs the population of a higher triplet
state and this difference could explain the observed differ-
ences in the reactivity of this compound in comparison with
1f and 4.
iodic acid (13.5 g) were refluxed for 100 h. Then water and
carbon tetrachloride were added. The organic layer was washed
with water, 0.1 M Na2S2O3, and water again. The organic
phase was dried over Na2SO4. The solvent was evaporated and
the residue was crystallised from ethanol to give 2,3,5-
triiodothiophene (44.5 g, 77%). Mp 83–85 ЊC (lit.,36 83–84 ЊC).
δH (DMSO-d6) 7.16 (s, 1 H).
2,3-Diiodo-5-nitrothiophene (4) and 2,4-diiodo-5-nitrothiophene
(5)
2,3,5-Triiodothiophene 3 (8 g) was dissolved in acetic anhydride
(40 ml). The mixture was treated with a mixture of nitric acid
(d 1.52 g mlϪ1) in acetic anhydride (40 ml) at 0 ЊC. The mixture
was stirred for 15 min, then 0.1 M NaHCO3 (100 ml) was
added. The mixture was extracted with diethyl ether. The
organic phase was dried over Na2SO4 and the solvent was evap-
orated. The isomers were separated using preparative TLC on
300 mg of the residue eluting with a mixture of 99:1 n-hexane–
EtOAc. The separation gave 2,4-diiodo-5-nitrothiophene (4)
(180 mg, 46%) and 2,3-diiodo-5-nitrothiophene (5) (120 mg,
31%). 2,4-Diiodo-5-nitrothiophene (4): δH 7.69 (s, 1 H); δC 207,
146, 85, 82; m/z 37 (4%), 69 (10), 81 (27), 97 (4), 111 (3), 127
(10), 164 (9), 208 (50), 224 (30), 238 (5), 254 (4), 323 (25), 335
(3), 351 (4), 365 (3), 381 (100) (Found: C, 12.7; H, 0.3; N, 3.5; S,
8.2. C4HI2NO2S requires C, 12.61; H, 0.26; N, 3.68; S, 8.42%).
2,4-Diiodo-5-nitrothiophene (5): δH 7.45 (s, 1 H); m/z 37 (4%),
69 (7), 81 (29), 97 (3), 111 (3), 127 (9), 164 (5), 208 (40), 224 (50),
238 (5), 323 (4), 351 (19), 365 (2), 381 (100) (Found: C, 12.6; H,
0.2; N, 3.8; S, 8.3. C4HI2NO2S requires C, 12.61; H, 0.26; N,
3.68; S, 8.42%).
Finally we tested the photochemical behaviour of 2-bromo-
5-nitrothiazole (16). The irradiation of 16 in benzene gave a
product (17) where the substitution had occurred on the nitro
group (Scheme 9). The yield of this reaction is low (12%). In
Scheme 9
previous work we reported some examples of photochemical
substitution of the nitro group.34,35 The previous results referred
to reactions between nitrothiophene derivatives and indene.
This is the first result on the photochemical substitution of the
nitro group in the presence of aromatic compounds. We also
tested the photochemical behaviour of this substrate in the
presence of indene. In this case also, the reaction occurred on
the nitro group giving the corresponding coupling product 18 in
reasonable yield (48%) (Scheme 9). To explain this behaviour
we examined the molecular orbitals of the first excited triplet
state of 16 (Table S2, supplementary data).† This is a π,π*
triplet state with an energy of 45 kcal molϪ1: this value does
not allow the cleavage of the C-Br bond (ca. 66 kcal molϪ1).
Probably, the absence of the homolytic cleavage allows the
postulated electron transfer process to occur in the substitution
reactions of the nitro group.35
In conclusion, we have shown that the photochemical substi-
tution reactions of diiodothiophene derivatives can be carried
out giving different results using different substrates. These dif-
ferences can be explained on the basis of a previous reported
mechanism for this type of reaction. We have also shown that
5-nitrothiazole derivatives give an interesting photochemical
substitution reaction where the nitro group is the leaving
group.
2-Phenyl-3-iodo-5-nitrothiophene (6)
2,3-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in ben-
zene (100 ml). The mixture was degassed with nitrogen for 10
min and then irradiated with a 125 W high pressure mercury arc
(Helios-Italquartz) surrounded by a Pyrex water-jacket. At the
end of the reaction (Table 1), the solvent was evaporated to give
pure 6 (85 mg, 98%). δH 7.99 (s, 1 H), 7.7–7.5 (m, 5 H); m/z 331
(100%), 315 (2), 301 (5), 273 (3), 174 (13), 158 (77), 146 (15), 114
(32), 102 (4), 88 (7) (Found: C, 36.4; H, 1.6; N, 4.3; S, 9.7.
C10H6INO2S requires C, 36.27; H, 1.83; N, 4.23; S, 9.68%).
When the reaction was carried out in acetonitrile the following
procedure was used: 2,3-diiodo-5-nitrothiophene 4 (90 mg) was
dissolved in acetonitrile (100 ml) in the presence of benzene
(3 ml). The mixture was degassed with nitrogen for 10 min and
then irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end of
the reaction (Table 1), the solvent was evaporated and the
mixture was purified on preparative TLC giving 60 mg of 6
(77%).
3-Tolualdehyde (7) and 3-methylphenylmethanol (8)
2,3-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in
acetonitrile (100 ml) in the presence of m-xylene (3 ml). The
mixture was degassed with nitrogen for 10 min and then
irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end
of the reaction (Table 1), the solvent was evaporated and the
residue, dissolved in methanol, was analysed by GC-MS. The
analysis showed the presence of 7 and 8. 3-Tolualdehyde: m/z
120 (96%), 91 (100), 65 (9), 51 (3), 39 (5). 3-Methylphenyl-
methanol: m/z 122 (57%), 107 (46), 91 (50), 79 (29), 77 (29), 32
(100).
Experimental
Mass spectra were obtained with a Hewlett-Packard 5971 mass
selective detector on a Hewlett-Packard 5890 gas chromato-
graph. Gas-chromatographic analyses were obtained by using
an OV-1 capillary column between 70–250 ЊC (20 ЊC minϪ1). 1H
NMR spectra were recorded with Bruker 300 AM instrument.
J Values are given in Hz. Elemental analyses were obtained with
a Carlo Erba Elemental Analyser 1106.
3-Iodo-5-nitro-2,2Ј-bithienyl (9)
2,3,5-Triiodothiophene (3)
2,3-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in
acetonitrile (100 ml) in the presence of thiophene (3 ml). The
mixture was degassed with nitrogen for 10 min and then
Thiophene (10.5 g), acetic acid (80 ml), water (36.9 ml), carbon
tetrachloride (30 ml), sulfuric acid (2.1 ml), iodine (38.1 g), and
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irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end of
the reaction (Table 1), the solvent was evaporated to give pure 9
(87 mg, 99%). δH 7.96 (s, 1 H), 7.59 (dd, 1 H, J1 4, J2 1), 7.54 (dd,
1 H, J1 5, J2 1), 7.18 (dd, 1 H, J1 5, J2 4); δC 206.7, 143.5, 137.8,
133.2, 129.6, 129.1, 128.0; m/z 337 (100%), 307 (6), 279 (5), 180
(5), 164 (68), 152 (8), 120 (25), 93 (4), 69 (4) (Found: C, 28.7; H,
1.1; N, 4.3; S, 19.2. C8H4INO2S2 requires C, 28.50; H, 1.20; N,
4.15; S, 19.02%).
zene (100 ml). The mixture was degassed with nitrogen for 10
min and then irradiated with a 125 W high pressure mercury arc
(Helios-Italquartz) surrounded by a Pyrex water-jacket. At the
end of the reaction (Table 2), the solvent was evaporated and
the residue was purified through preparative TLC giving 6
(17 mg, 20%) and 14 (13 mg, 15%). 5-Phenyl-3-iodo-2-
nitrothiophene 14: δH 7.7–7.5 (m, 5 H), 7.42 (s, 1 H); m/z 331
(100%), 315 (7), 301 (7), 273 (18), 241 (11), 207 (11), 174 (6), 158
(61), 146 (21), 128 (11), 114 (25), 102 (11), 77 (10) (Found: C,
36.2; H, 1.9; N, 4.2; S, 9.9. C10H6INO2S requires C, 36.27; H,
1.83; N, 4.23; S, 9.68%). When the reaction was carried out in
acetonitrile the following procedure was used: 2,4-diiodo-5-
nitrothiophene 4 (90 mg) was dissolved in acetonitrile (100 ml)
in the presence of benzene (3 ml). The mixture was degassed
with nitrogen for 10 min and then irradiated with a 125 W high
pressure mercury arc (Helios-Italquartz) surrounded by a Pyrex
water-jacket. At the end of the reaction (Table 2), the solvent
was evaporated and the mixture was purified by preparative
TLC giving 9 mg of 6 (10%) and 6 mg of 14 (7%).
3-Iodo-5-nitro-5Ј-bromo-2,2Ј-bithienyl (10)
2,3-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in
acetonitrile (100 ml) in the presence of 2-bromothiophene
(3 ml). The mixture was degassed with nitrogen for 10 min and
then irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end of
the reaction (Table 1), the solvent was evaporated to give a
residue that was purified via preparative TLC to give pure 10
(72 mg, 66%). δH 7.92 (s, 1 H), 7.31 (d, 1 H, J 1), 7.14 (d, 1 H,
J 1); δC 206.8, 143.5, 137.8, 131.1, 129.6, 129.1, 128.0, 124.3;
m/z 419 (98%), 417 (100), 385 (6), 377 (6), 306 (5), 244 (54),
163 (21), 119 (21) (Found: C, 23.0; H, 0.6; N, 3.4; S, 15.5.
C8H3BrINO2S2 requires C, 23.10; H, 0.73; N, 3.37; S, 15.41%).
4-Iodo-5-nitro-2,2Ј-bithienyl (15)
2,4-Diiodo-5-nitrothiophene
4 (90 mg) was dissolved in
acetonitrile (100 ml) in the presence of thiophene (3 ml). The
mixture was degassed with nitrogen for 10 min and then
irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end of
the reaction (Table 2), the solvent was evaporated and the resi-
due was purified through preparative TLC to give 15 (6 mg,
8%). δH 7.56 (dd, 1 H, J1 4, J2 1), 7.55 (dd, 1 H, J1 5, J2 1), 7.38
(s, 1 H), 7.16 (dd, 1 H, J1 5, J2 4); m/z 337 (60%), 248 (62), 164
(44) (Found: C, 28.4; H, 1.2; N, 4.1; S, 19.1. C8H4INO2S2
requires C, 28.50; H, 1.20; N, 4.15; S, 19.02%).
3-Iodo-5-nitro-5Ј-chloro-2,2Ј-bithienyl (11)
2,3-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in
acetonitrile (100 ml) in the presence of 2-chlorothiophene
(3 ml). The mixture was degassed with nitrogen for 10 min and
then irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end of
the reaction (Table 1), the solvent was evaporated to give pure
11 (95 mg, 97%). δH 7.94 (s, 1 H), 7.35 (d, 1 H, J 1), 7.01 (d, 1 H,
J 1); δC 206.7, 142.4, 137.7, 137.7, 132.0, 128.8, 127.0, 124.2;
m/z 373 (43%), 372 (13), 371 (100), 341 (10), 313 (6), 200 (39),
199 (10), 198 (95), 186 (9), 163 (22), 119 (32), 93 (9), 69 (9)
(Found: C, 26.0; H, 1.0; N, 3.7; S, 17.3. C8H3ClINO2S2 requires
C, 25.86; H, 0.81; N, 3.77; S, 17.26%).
2-Bromo-5-phenylthiazole (17)
2-Bromo-5-nitrothiazole 16 (100 mg) was dissolved in benzene
(100 ml). The mixture was degassed with nitrogen for 10 min
and then irradiated with a 125 W high pressure mercury arc
(Helios-Italquartz) surrounded by a Pyrex water-jacket. After
24 h the solvent was evaporated and the residue was purified
through column chromatography on basic Al2O3 (B I). Elution
with n-hexane–EtOAc 99:1 gave 17 (15 mg, 12%). δH 8.32 (s, 1
H), 7.7–7.5 (m, 5 H); m/z 241 (98%), 239 (100), 160 (29),
134 (74), 116 (17), 102 (10), 89 (17) (Found: C, 45.2; H, 2.4;
N, 5.9; S, 13.5. C9H6BrNS requires C, 45.02; H, 2.52; N, 5.83; S,
13.35%).
Thiophene-2-carbaldehyde (12) and 2-thienylmethanol (13)
2,3-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in
acetonitrile (100 ml) in the presence of 2-methylthiohene (3 ml).
The mixture was degassed with nitrogen for 10 min and then
irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. At the end of
the reaction (Table 1), the solvent was evaporated and the
residue, dissolved in methanol, was analysed by GC-MS. The
analysis showed the presence of 12 and 13. Thiophene-2-
carbaldehyde 12: m/z 112 (100%), 83 (13), 58 (10), 39 (17).
2-Thienylmethanol 13: m/z 114 (100%), 97 (67), 85 (72), 69 (9),
53 (10), 45 (30).
2-Bromo-5-(1H-inden-2-yl)thiazole (18)
2-Bromo-5-nitrothiazole 16 (100 mg) was dissolved in
acetonitrile (100 ml) in the presence of thiophene (3 ml). The
mixture was degassed with nitrogen for 10 min and then
irradiated with a 125 W high pressure mercury arc (Helios-
Italquartz) surrounded by a Pyrex water-jacket. After 5 h the
solvent was evaporated and the residue was purified through
column chromatography on basic Al2O3 (B I). Elution with
n-hexane–EtOAc 99:1 gave 18 (64 mg, 48%). δH 8.45 (s,
1 H), 7.47 (m, 2 H), 7.32 (m, 2 H), 7.18 (s, 1 H); m/z 279
(98%), 277 (100), 160 (29), 134 (74), 116 (17), 102 (10), 89
(17).
Flow reactor
The efficiency of the annular reactor was determined by testing
it with the photochemical decomposition of phenylglyoxylic
acid. A 0.1 M solution of phenylglyoxylic acid in acetonitrile–
water (3:1) (10 ml) was irradiated. The mixture was then
extracted with CH2Cl2 and dried (Na2SO4). The removal of the
solvent gave a crude product that was dissolved in CDCl3 and
analysed by 1H NMR. The chemical conversion was calculated
from the integrated ortho protons of the phenyl ring of phenyl-
glyoxylic acid at δ 8.1 and of benzaldehyde at δ 7.9 ppm with
reference to the meta and para ring protons at δ 7.6 ppm. Φ is
assumed to be 0.7.
Appendix
The photochemical apparatus for preparative purpose is
described in the Fig. 1. The flux of the solution to be irradi-
ated was maintained using a HPLC pump. The PTFE pipe
showed an external diameter of 1.5 mm and an inner diameter
of 1.0 mm. The coil around the lamp used ca. 5 m of the pipe.
We used a 125 W high pressure mercury arc manufactured
by Helios Italquartz (Milan), surrounded by a Pyrex water-
jacket.
2-Phenyl-3-iodo-5-nitrothiophene (6) and 5-phenyl-3-iodo-2-
nitrothiophene (14)
2,4-Diiodo-5-nitrothiophene 4 (100 mg) was dissolved in ben-
J. Chem. Soc., Perkin Trans. 1, 2000, 3513–3518
3517

View Article Online
18 K. Oharu and T. Hamada, Jpn. Kokai Tokkyo Koho, 03 275 138,
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