Easy photochemical preparation of 2-dimethylaminophenylfurans, -pyrroles and -thiophenes

Article abstract of DOI:10.1016/S0040-4020(00)00909-1

2-(4-N,N-dimethylaminophenyl) heterocycles are smoothly obtained from the photolysis of 4-chloro-N,N-dimethylaniline in acetonitrile in the presence of furan, pyrrole, thiophene and some of their methyl derivatives bearing a free α-position. With 2,5-dimethyl heterocycles the arylation occurs with equal efficiency in the β position. In the case of furan, when the irradiation is carried out in methanol, cis/trans 2-aryl-5-methoxy-2,5-dihydro adducts are obtained. The reaction is rationalized as involving heterolytic cleavage of the C-Cl bond in the triplet state of the aniline. The intermediacy of the thus formed triplet aryl cation explains the observed high regio- and chemo-selectivity of the process. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00909-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9383±9389
Easy Photochemical Preparation of
2-Dimethylaminophenylfurans, -Pyrroles and -Thiophenes
*
Benedetta Guizzardi, Mariella Mella, Maurizio Fagnoni and Angelo Albini
Department of Organic Chemistry, University of Pavia, Via Taramelli 10, 27100 Pavia, Italy
Received 7 July 2000; revised 1 September 2000; accepted 21 September 2000
AbstractÐ2-(4-N,N-dimethylaminophenyl) heterocycles are smoothly obtained from the photolysis of 4-chloro-N,N-dimethylaniline in
acetonitrile in the presence of furan, pyrrole, thiophene and some of their methyl derivatives bearing a free a-position. With 2,5-dimethyl
heterocycles the arylation occurs with equal ef®ciency in the b position. In the case of furan, when the irradiation is carried out in methanol,
cis/trans 2-aryl-5-methoxy-2,5-dihydro adducts are obtained. The reaction is rationalized as involving heterolytic cleavage of the C±Cl bond
in the triplet state of the aniline. The intermediacy of the thus formed triplet aryl cation explains the observed high regio- and chemo-
selectivity of the process. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
synthesis of aminophenylheterocycles and of the support
that such reactions could give for understanding the chem-
istry of a little investigated intermediate such as the pheny-
lium cation.
There is an increasing interest in arylated ®ve-membered
heterocycles. Known examples are present among natural
products1 as well as in some oil shale raf®nates2 and have
been prepared for uses ranging from components of switch-
able molecular wires3 to compounds with optical non line-
arity.4 The synthesis is mainly based on the application of
one of the general methods of building the heterocyclic ring
starting from the appropriate arylated open chain precursor.5
The direct formation of the aryl-heterocycle carbon±carbon
bond has found relatively few applications. These generally
involve the reaction between a (hetero)aryl halide and a
metallated (hetero)arene, in most cases under catalyzed
conditions.6 The attack of an aryl cation onto the electron-
rich heterocycle is an attractive alternative, in view of the
facile reaction of electrophiles with such derivatives. This
contrasts with the fact that there are practically no methods
for the generation of aryl cations except those of purely
spectroscopic interest.7 The decomposition of aryldiazo-
nium salts8 or of N-nitroso-N-arylamides9 in the presence
of thiophene, furan or pyrrolecarboxylate does give the
arylated heterocycles, but the reaction involves the aryl
radical rather than the cation.10
Results
As has been previously reported,11 photolysis of 4-chloro-
N,N-dimethylaniline (1) in a polar solvent caused cleavage
of the C±Cl bond and gave N,N-dimethylaniline (5) along
with 2-(40-N,N-dimethylaminophenyl)-4-chloroaniline (6,
see Scheme 1). The irradiation was now carried out in aceto-
nitrile in the presence of 1 M pyrrole (2a). Acidity was
increased during the photoreaction and this caused the
formation of colored products and of a polymeric ®lm on
the reactor wells, resulting in the interruption of the reaction
because of the light-®lter effect. However, acidity could be
controlled either by adding 0.1 M triethylamine or by stir-
ring solid potassium carbonate in the reaction vessel during
the irradiation. Under these conditions coloration was mini-
mized, the reaction proceeded with up to 85% conversion
and 2-(4-dimethylaminophenyl)pyrrole (3a) was formed
and isolated in good yield (64%, see Scheme 1 and Table
1). Careful analysis of the raw photolysed mixture showed
that isomeric 3-(4-dimethylaminophenyl)pyrrole (4a) was
also present, though in a much lesser amount (1%). The
yield of non heterocycle-containing products, the above
mentioned anilines 5 and 6, was much reduced with respect
to that observed in neat acetonitrile.
However, we recently found that irradiation of chloro and
¯uoroanilines causes ef®cient heterolysis of the carbon±
halogen bond and the resulting aminophenylium cation
can be trapped in the presence of benzene.11 Therefore,
we thought it worthwhile to extend the reaction to ®ve-
membered heterocycles, in view both of the interest of a
When 2,4-dimethylpyrrole (2b) was used, the course of the
reaction was similar and again arylation took place at the a
position yielding the 2,3,5-trisubstituted pyrrole 3b. With
both a positions blocked as in 2,5-dimethylpyrrole (2f),
Keywords: photochemistry; arylations; furans; thiophenes; pyrroles.
* Corresponding author. Tel.: 139-0382-507316; fax: 139-0382-507323;
e-mail: albini@chi®s.unipv.it
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00909-1

9384
B. Guizzardi et al. / Tetrahedron 56 (2000) 9383±9389
Scheme 1.
however, arylation in b occurred with reasonable yield to
give product 4f.
With this heterocycle the arylation proceeded with almost
the same yield also in the absence of buffering agents.
Similar irradiation in the presence of thiophene (2c) led
again to a-arylation (product 3c) and in this case the b
isomer was not measurably formed in our experiments.
The reaction in the presence of furan (2d) was less satisfac-
tory due to the enhanced sensitivity to acids of this substrate.
Under the above conditions polymerization was not comple-
tely avoided and the substrate conversion could not be
driven to the same extent. However, at 50% conversion
the 2-arylfuran 3d was formed and could be isolated in a
reasonable yield (32%); analysis of the photolysate showed
the presence of a detectable (1%) amount of isomeric 4d.
The reaction could be completed with the more acid-resis-
tant 2-methylfuran (2e), again with arylation in a, while 2,5-
dimethylfuran (2g) gave, as in the case of the corresponding
pyrrole, the b-arylated derivative 4g.
Table 1. Products from the irradiation of 4-chloro-N,N-dimethylaniline in
acetonitrile in the presence of ®ve-membered heterocycles (1 M)
Heterocycle
Products (% yield)
Arylated heterocycles Further products
None
2a
2b
5 (47)
5 (10)
5 (12)
5 (15)
5 (4)
5 (10)
5 (10)
5 (16)
5 (6)
6 (30)
6 (tr)
6 (7)
6 (5)
6 (3)
6 (tr)
6 (5)
6 (7)
6 (9)
3a (64)
4a (1)
3b (75)
3c (54)
3d (32)
7 (36)
3e (52)
4f (60)
4g (70)
The reaction of furan was also tested in methanol as the
solvent. In this case, the two isomeric 2-aryl-5-methoxy-2,
5-dihydrofurans 7 and 8 were obtained. Only a few related
2-(aryl),12 -(heteroaryl)13 or -(alkyl)14 -2,5-dihydrofurans
are known, and the stereochemistry was generally not
assigned. In the present case, however, the two isomers
could be separated and the steric arrangement unambigu-
ously assigned on the basis of NOESY experiments (see
2c
2da
2db
2e
4d (1)
8 (24)
2f
2g
a At 50% conversion.
b In methanol.

B. Guizzardi et al. / Tetrahedron 56 (2000) 9383±9389
9385
Experimental). The reaction with pyrrole in methanol gave
again aromatic 3a, however, with no solvent addition.
anilines 5 and 6 in neat MeCN to the aminoarylated hetero-
cycles 3 as the main products with 1 M 2. At a lower
concentration of 2, however (e.g. 0.1 M) the effect is
small and the yield of products 5 and 6 is affected only to
a minor degree.
Irradiation in the presence of 1 M methyl furan-2-carboxy-
late (2h) did not lead to new products in a signi®cant amount
and the reaction proceeded in the same way as in the
absence of this additive to give products 5 and 6 and like-
wise no adduct was formed with furfural (2i, some compe-
titive light absorbance in this case). Experiments in the
presence of indole were unsatisfactory because competitive
light-absorption by this heterocycle drastically slowed the
reaction. However, GC±MS examination of the irradiated
solution showed the presence of two peaks with the mole-
cular weight and fragmentation expected for dimethylami-
nophenylindoles.
Thus, unimolecular decomposition of the aniline leads in
every case to a single intermediate that either is reduced
to 5 or adds to undecomposed chloraniline to form diamine
6 in neat acetonitrile. This is trapped in the presence of a
suf®cient amount of ®ve-membered heterocycles 2. As for
the nature of this intermediate, the requirement of a polar
medium suggests that it arises from a heterolytic fragmenta-
tion and the chemical evidence strongly supports such a
view. Only electron rich substrates, such as furan, pyrrole,
thiophene and their alkyl derivatives are effective traps,
competing with another electron-rich trap, aniline 1. This
holds also for indole, as far as competitive light absorption
allows to judge, but not for less electron-rich substrates such
as 2h, i (whereas radical arylation does occur with such
derivatives).9b Thus, an electrophilic reaction is involved
and the intermediate is the 4-(N,N-dimethylamino)-phenyl
carbocation 9 formed by photoinduced heterolysis of the
C±Cl bond from the aniline (see Scheme 2).
Importantly, apart from the case of indole, the time required
for the photochemical conversion of aniline 1 did not
change signi®cantly when the irradiation was carried out
in neat solvent or in the presence of the heterocycles consid-
ered (1 M).
Discussion
The course of the reaction follows in fact the expected
course of electrophilic reactions with ®ve-membered
heterocycles, resulting in aromatic substitution via the
usual addition-elimination mechanism involving p cationic
adduct 10 and its deprotonation. With furan, cation 10
undergoes addition of a nucleophile rather than deprotonat-
ing when the latter is available, and the 2,5-dihydro-5-meth-
oxy adducts 7 and 8 are obtained in methanol, while with the
more aromatic pyrrole the substitution reaction occurs also
in methanol. Again, this difference is in accordance with the
well understood reactivity (substitution vs addition) of these
heterocycles with electrophiles.15
The photodecomposition of chloroanililine 1 in the presence
of ®ve-membered heterocycles (2) leads to ef®cient
aminoarylation of these substrates. This smooth reaction
gives selectively the 2-aryl substituted heterocycles in a
reasonable yield and appears to be a viable entry to such
derivatives, which may be valuable in view of the fact that
related derivatives are of current interest for their non linear
optical properties.4 Furthermore, in the case of furan the
irradiation in methanol gives arylated 2,5-dihydrofurans
strictly related to compounds known for their anti HIV
activity.13 When both a positions are substituted, b aryla-
tion occurs in a similar yield. The reaction is successful with
all the methyl substituted heterocycles we tried, but fails
with electron-withdrawing substituted derivatives such as
ester 2h or aldehyde 2i. Under the mild conditions of the
photochemical reaction the arylation occurs with no signi®-
cant side path except for some reductive dechlorination to
give 5 and competing arylation of the aniline to form 6, both
processes however occurring only to a limited extent in the
presence of 1 M heterocycles.
Thus, the reaction is rationalized according to Scheme 2
with phenyl cation 9 as the key intermediate. The regio-
and chemoselectivity observed require some further discus-
sion, however, in order to place the present results in the
frame of the current view on aryl cations.
First, in the present reaction heterocycles are arylated with a
very high regioselectivity (a/b ratio $98). Speranza and
coll. noticed7 that the decomposition of 1,4-ditritiobenzene
in the presence of heterocycles led to a/b ratios higher than
expected from the `hard' nature of the phenyl cation (4.7 for
2a, 3.4 for 2c, 5.3 for 2d), but these were not as high as
observed here. This may be in part due to the different
structure of the cation (in the present case amino substi-
tuted) and to the different condition (MeCN or MeOH solu-
tions rather than neat heterocycle), but a very high a/b ratio
is typical of the phenyl radical,8±10 rather than of the cation.
This contrasts with the fact that the above-mentioned char-
acteristics of the reaction clearly indicate the cation as the
intermediate.
Mineral acidity is evolved as indicated by the stoichiometry
of the reaction. This has little effect in the case of the rather
acid-resistant thiophene, while in the other cases acid-
induced polymerisation occurs to some degree. However,
this is easily taken care of by buffering the acidity either
by adding an amine or by stirring solid potassium carbonate.
Only in the case of highly acid-sensitive furan this precau-
tion is not fully satisfactory and the yield of the arylated
product 3d is limited to 32%.
The key mechanistic features of the aminoarylation can be
deduced from the observed behavior. Chloroaniline 1 is
photodecomposed only in polar solvents, with a quantum
yield of reaction of ca. 0.8 in acetonitrile (#0.02 in cyclo-
hexane).11 The ef®ciency of the reaction is not signi®cantly
affected by the presence of the additives (#10% effect),
while the product distribution completely changes from
Second, the work by Schuster and colleagues16 where the 4-
diethylamino- and the 4-morpholinophenyl cations have
been produced by photodecomposition of the corresponding
diazonium tetra¯uoroborate in tri¯uoroethanol showed that

9386
B. Guizzardi et al. / Tetrahedron 56 (2000) 9383±9389
Scheme 2.
the generated species were indiscriminate electrophiles,
leading to the tri¯uoroethyl ethers as the virtually exclusive
products. On the contrary, the photodecomposition of
chloroaniline 1 does not give ethers neither in methanol
nor in tri¯uoroethanol, leading in both cases, though in a
different proportion, to reduced aniline 5 and to diamine 6.17
be due to initial electron transfer to give a pair of odd-
electron species (see Scheme 4), a hypothesis which is
again in accord with the better ef®ciency of p rather than
s nucleophiles in view of the lower ionization potential of
the ®rst reagents as compared e.g. to alcohols. In the latter
mechanism, the regioselectivity is dictated by the spin
density in the radical cation of the heterocycle, known to
be much higher in the a position.22 An electron transfer step
has been previously proposed by Speranza and colleagues7
in order to explain the high a/b ratio under their condi-
tions.23
A rationalization of these discrepancies is that both b-decay
from ditritiobenzene (via the ground state) and direct photo-
lysis of the diazonium salt (via the singlet excited state) lead
to singlet phenyl cation. On the contrary, intersystem cross-
ing (ISC) is deemed to be very ef®cient in aniline18 and even
more with chloro substituted
1
(FISC ca. 0.9,
Whatever the exact mechanism, the addition to p nucleo-
philes is consistently an effective reaction and, as shown in
the experiments with substrates 2f and 2g, it occurs ef®-
ciently at the b position when both a positions are substi-
tuted, again consistently with the general pattern of
electrophilic substitution with electron-rich heterocycles.15
kISC.1£109 s21).19 Thus, photodecomposition of 1 is
expected to occur in the triplet manifold (see Scheme 3)
and to give cation 9 in the triplet state. Differently from
parent phenyl cation, the 4-aminophenyl cation has been
calculated to be the ground state species.20 The triplet
state has a large contribution of the diradicalic p5s1 struc-
ture, rather than maintaining the pure p6s0 character of the
singlet cation (see Scheme 4). This makes such a species a
less indiscriminate electrophile and a more easily reduced
species (there is computational support for hydrogen trans-
fer in the intramolecular case, with 2-propylphenyl
cation),21 explaining the high proportion of dehalogenated
aniline 5 in neat MeCN.
In conclusion, this study shows that arylated heterocycles
can be smoothly obtained through a photochemical reaction
via a highly regioselective reaction. Furthermore, the results
The partial radical character of the triplet cation 93 explains
the poor reactivity with s nucleophiles and the ef®cient
addition to excellent p nucleophiles such as the present
®ve-membered heterocycles. The observed regioselectivity
can be rationalized on the basis of the radical character of
the reacting center (see Scheme 4). Alternatively, this may
Scheme 3.
Scheme 4.

B. Guizzardi et al. / Tetrahedron 56 (2000) 9383±9389
9387
suggest that triplet aryl (or at least aminophenyl) cations can
be generated photochemically and are promising synthetic
intermediates in view of their peculiar chemoselectivity.
Jˆ8 Hz, 1H), 6.72 and 7.45 (AA0XX0, 4H, aromatics), 7.14
(dd, Jˆ2, 8 Hz, 2H), 7.18 (dd, Jˆ2 Hz, 1H). dC (300 MHz
CDCl3): 40.4 (NMe2), 43.1 (NMe2), 112.3 (CH), 118.6
(CH), 126.3, 126.5 (CH), 128,9, 129.0 (CH), 130.9 (CH),
135.8, 149.4, 149.8.
Experimental
2-(40-N,N-Dimethylaminophenyl)pyrrole (3a). Light
yellow solid, mp dec. .1608C; [Found: C, 77.25, H, 7.45,
N, 15.30. C12H14N2 requires C, 77.38, H, 7.58, N, 15.04%];
dH (300 MHz CDCl3): 3.02 (s, 6H, ±NMe2), 6.27 (dd, Jˆ6,
2.5 Hz, 1H, H-4), 6.35 (m, 1H, H-3), 6.81 (m, 1H, H-5), 6.75
and 7.35 (AA0XX0, 4H, aromatics), 8.3 (broad, exch, 1H,
NH). dC (300 MHz CDCl3): 40.55 (NMe2), 103.8 (CH),
109.6 (CH), 112.8 (2 CH), 117.5 (CH), 121.7, 124.9 (2
CH), 132.7, 149.1. GC/MS: tR 15.18 min: m/z (EI) 186
(100), 171 (30), 144 (18), 115 (15), 63 (8). The analysis
of the photolysed solution revealed traces (,2%) of a
peak at tR 16.00 min with fragmentation m/z (EI) 186
(100), 171 (35), 144 (18), 115 (25), 63 (8). In view of the
similarity with spectrum of 3a (see above), this was attrib-
uted to 3-(40-N,N-dimethylaminophenyl)pyrrole (4a).
General
4-Chloro-N,N-dimethylaniline (1, prepared by methylation
of the aniline) and methyl furan-2-carboxylate (2h, prepared
by methylation of the acid) and the other reagents (of
commercial origin) were distilled or recrystallised before
use. For the irradiations, spectroscopic grade solvents
were used as received.
1H and 13C NMR spectra were recorded by means of a
Brucker 300 MHz spectrometer and the chemical shifts
are reported relative to TMS. Elemental analyses were
effected by a Carlo Erba 1106 elemental analyser. The
GC±MS analyses were performed using a IS40 instrument
®tted with a J&W DB-5 column, 30 m£0.25 mm with ®lm
thickness 0.25 mm. The carrier was helium at 0.6 mL/min
and samples (1 ml) were injected by splitless injection. The
total run time was 30 min with the initial oven temperature
808C (4 min), rising at a rate of 108C/min to 2508C.
2-(40-N,N-Dimethylaminophenyl)-3,5-dimethylpyrrole
(3b). Light yellow solid, mp 92±948C; [C, 78.36, H, 8.59, N,
13.05. C14H18N2 requires C, 78.46, H, 8.47, N, 13.07%]; dH
(300 MHz CDCl3): 2.15 (s, 3H, CH3), 2.25 (s, 3H, CH3),
2.95 (s, 6H, ±NMe2), 5.8 (s, 1H, H-4), 6.8 and 7.2 (AA0XX0,
4H, aromatics), 7.8 (broad, exch, 1H, NH). The chemical
shift of the signal attributed to H-4 (5.8 ppm) was character-
istic of a hydrogen in b position. The value ®ts with that of
the other pyrrole derivatives obtained, where the hydrogens
in the b position were consistently shielded as compared to
those in the a position. dC (300 MHz CDCl3): 12.1 (CH3),
12.9 (CH3), 40.6 (NMe2), 109.5 (CH), 111.4, 112.7 (2 CH),
114.4, 122.6, 126.1, 127.2 (2 CH), 148.6.
Preparative irradiations
In a typical experiment a solution of 780 mg aniline 1
(0.05 M) in 100 mL acetonitrile containing one of hetero-
cycles 2 (1 M) was irradiated for 3 h in an immersion well
apparatus ®tted with an high pressure mercury arc (125 W,
water-cooled through a quartz jacket) after 15 min ¯ushing
with argon and maintaining a slow gas ¯ux during the irra-
diation. Anhydrous potassium carbonate (2 g) was added
and the solution magnetically stirred during the experiment.
In an alternative procedure, irradiations were carried out by
using 20 mL portions of the same solutions in a number of
quartz tubes which were capped after ¯ushing with argon for
15 min and externally irradiated by means of 6£15 W phos-
phor coated lamps for 3 h. In this case, the solution was
made 0.1 M triethylamine. The progress of the reaction
was monitored by GC and GC±MS.
2-(40-N,N-Dimethylaminophenyl)thiophene (3c). Colour-
less solid, mp 118±1208C, CH3OH, lit.25 121±1228C; [C,
70.85, H, 6.52, N, 6.83. C12H13 NS: C, 70.90, H, 6.45, N,
6.89%]; dH (300 MHz CDCl3): 3.02 (s, 6H, ±NMe2), 6.8
and 7.5 (AA0XX0, 4H, aromatics), 7.05 (t, Jˆ4 Hz, 1H,
H-4), 6.81 (m, 2H, H-3 and H-5); dC (300 MHz CDCl3):
40.4 (NMe2), 112.5 (2 CH), 120.8 (CH), 122.6 (CH),
126.8 (2 CH), 127.7 (CH), 138.2, 145.1, 149.8. GC/MS: tR
15.17 min; m/z 203 (100), 187 (33), 205 (15), 115 (38). In
the GC±MS analysis of the photolyzed solution no traces of
the 3-substituted derivative was found.
Products isolation and identi®cation
The irradiated solution was evaporated under reduced pres-
sure and the residue chromatographed on silica gel 60 HR
by eluting with cyclohexane±ethyl acetate mixtures. The
arylated heterocycles were obtained as solids or oils from
the fractions (by repeating the chromatography in the case
of unsatisfactory separation) and characterised by elemental
analysis, GC±MS and NMR as detailed in the following.
2-(40-N,N-Dimethylaminophenyl)furan (3d). Colourless
solid, mp 65±678C; [Found: C, 76.75, H, 7.12, N, 7.41.
C12H13 NO requires: C, 76.98, H, 7.00, N, 7.48%]; dH
(300 MHz CDCl3): 3.05 (s, 6H, ±NMe2), 6.45 (m, 2H,
H-3 and H-4), 7.42 (t, Jˆ2 Hz, 1H, H-5), 6.8 and 7.6
(AA0XX0, 4H, aromatics); dC (300 MHz CDCl3): 40.4
(NMe2), 101.9 (CH), 111.3 (CH), 112.3 (2 CH), 119.7,
124.9 (2 CH), 140.6 (CH), 149.7, 154.7. GC/MS: tR
13.01 min; m/z 187 (100), 172 (12), 171 (18), 158 (25),
144 (14), 115 (30). The analysis of the photolysed solution
revealed traces (,1%) of a peak at tR 13.10 min with frag-
mentation m/z 187 (100), 171 (55), 144 (45), 115 (40). In
view of the similarity to the above spectrum of 3d, this
was recognised as 3-(40-N,N-dimethylaminophenyl)furan
(4d).
1
The structures were deduced from the results of H, 13C,
DEPT-135 and 2D correlated experiments.
2-(40-N,N-Dimethylaminophenyl)-4-cloroaniline
(6).
Colourless oil which solidi®es on standing, mp 40±428C,
lit.24 oil; [Found: C, 77.82, H, 7.83, N, 10.05. C16H19N2Cl
requires C, 77.87, H, 7.76, N, 10.19%]; dH (300 MHz
CDCl3) 2.55 (s, 6H, NMe2), 3.05 (s, 6H, ±NMe2), 6.9 (d,

9388
B. Guizzardi et al. / Tetrahedron 56 (2000) 9383±9389
2-(40-N,N-Dimethylaminophenyl)-5-methylfuran (3e).
White solid, mp 68±708C (CH3OH); [C, 77.62, H, 7.45,
N, 6.42. C13H15NO requires C, 77.58, H, 7.51, N, 6.96%];
dH (300 MHz CDCl3): 2.4 (s, 3H, CH3), 3.01 (s, 6H,
±NMe2), 6.4 (d, Jˆ3 Hz, 1H, H-3), 6.4 (d, Jˆ3 Hz, 1H,
H-4), 6.8 and 7.6 (AA0XX0, 4H, aromatics); dC (300 MHz
CDCl3): 13.6 (CH3), 40.4 (NMe2), 102.7 (CH), 107.2 (CH),
112.4 (2 CH), 120.2, 124.4 (2 CH), 149.4, 150.3, 153.0.
220 (3), 191 (3), 163 (3), respectively, both consistent with a
structure of 4-(40-N,N-dimethylaminophenyl)indole. The
slow progress of the reaction discouraged preparative
efforts.
Acknowledgements
Partial support of this work by CNR, Rome, and MURST,
Rome, is gratefully acknowledged.
3-(40-N,N-Dimethylaminophenyl)-2,5-dimethylpyrrole
(4f). Light yellow solid, mp 90±928C; [C, 78.25, H, 8.52, N,
12.97. C14H18 N2 requires C, 78.46, H, 8.47, N, 13.07%]; dH
(300 MHz CDCl3): 2.15 (s, 3H, CH3), 2.25 (s, 3H, CH3),
3.02 (s, 6H, ±NMe2), 6.0 (s, 1H, H-4), 6.8 and 7.2 (AA0XX0,
4H, aromatics), 7.6 (broad, exch, 1H, NH); dC (300 MHz
CDCl3): 12.8 (CH3), 13.3 (CH3), 41.3 (NMe2), 106.7 (CH),
112.9 (2 CH), 114.6, 118.2, 122.2, 125.3, 128.2 (2 CH),
148.5.
References
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4. Mignani, G.; Leising, F.; Meyrueix, R.; Samson, H.
Tetrahedron Lett. 1990, 31, 4743.
3-(40-N,N-Dimethylaminophenyl)-2,5-dimethylfuran (4g).
Colourless solid, mp 38±418C; [C, 78.25, H, 8.05, N, 6.45.
C14H17 NO requires C, 78.10, H, 7.96, N, 6.51%]; dH
(300 MHz CDCl3): 2.2 (s, 3H, CH3), 2.25 (s, 3H, CH3),
3.0 (s, 6H, ±NMe2), 6.1 (s, 1H, H-4), 6.85 and 7.22
(AA0XX0, 4H, aromatics); dC (300 MHz CDCl3): 12.8
(CH3), 13.3 (CH3), 40.6 (NMe2), 106.9 (CH), 112.7 (2
CH), 121.1, 122.8, 128.0 (2 CH), 144.5, 148.9, 149.2.
5. Bean, G. P. In Pyrroles; Jones, R. A., Ed.; Wiley: New York,
1985; Vol. 1, p. 105; Gronowitz, S. In Thiophene and its deriva-
tives; Gronowitz, S., Ed.; Wiley: New York, 1989; Vol. 1, p. 1;
Katritzky, A. A.; Li, J.; Gordeev, M. F. J. Org. Chem. 1993, 58,
3038.
6. Representative examples: Itahara, T. J. Org. Chem. 1985, 50,
5272; Ohta, A.; Akita, Y.; Ohkuwa, T.; Chiba, M.; Fukunaga, R.;
Miyahji, A.; Nakata, T.; Tani, N.; Aoyagi, Y. Heterocycles 1990,
31, 1951; Reuter, K. H.; Scott, W. J. J. Org. Chem. 1993, 58, 4722;
Roth, G. P.; Farina, V.; Liebeskind, L. S.; Cabrera, E. P.
Tetrahedron Lett. 1995, 36, 2191; Kang, S. K.; Yamaguchi, T.;
Hong, R. K.; Kim, T. H.; Pyun, S. J. Tetrahedron 1997, 53, 3027.
7. An example is the decay of 1,4-ditritiobenzene, see Filippi, A.;
Occhiucci, G.; Speranza, M. Can. J. Chem. 1991, 69, 732; Filippi,
A.; Occhiucci, G.; Sparapani, C.; Speranza, M. Can. J. Chem.
1991, 69, 740.
(2S,5R)/(2R,5S)
2-(40-N,N-Dimethylaminophenyl)-5-
methoxy-2,5-dihydrofuran (7). Colourless oil; [Found:
C, 71.35, H, 7.77, N, 6.34. C13H17NO2 requires C, 71.21,
H, 7.81, N, 6.39%]; dH (300 MHz CDCl3): 2.15 (s, 6H,
NMe2), 3.45 (s, 3H, OMe), 5.62 (m, 1H, H-2), 5.76 (dt,
Jˆ1.3 and 1.2 Hz, 1H, H-5), 5.86 (ddd, Jˆ6, 1.2 and
2.3 Hz, 1H, H-3), 6.14 (dt, Jˆ6 and 1.2 Hz, 1H, H-4), 6.9
and 7.2 (AA0XX0, 4H, aromatics); dC (300 MHz CDCl3):
40.5 (NMe2), 54.8 (OMe), 87.6 (CH-2), 109.3 (CH-5), 112.3
(CH), 125.5 (CH), 128.0, 128.07 (CH), 135.7, 150.4. A
NOESY experiment showed a NOE correlation between
the methoxy group and the aromatic hydrogens at
7.2 ppm, thus identifying the stereochemistry.
8. Maggioni, A.; Tubul, A.; Brun, P. Synthesis 1997, 631; Oae, Z.;
Yoshihara, M. Zh. Org. Khim. 1996, 32, 282.
9. (a) Degani, I. Ann. Chim. (Rome) 1961, 51, 434. (b) Rinkes, I. J.
Rec. Trav. Chim. Pays-Bas 1943, 62, 116.
10. Beadle, J. R.; Korzeniowski, S. H.; Rosenberg, D. E.; Garcia-
Slanga, B. J.; Gokel, G. W. J. Org. Chem. 1984, 49, 1594;
Ruchardt, C.; Hassmann, V. Liebigs Ann. Chem. 1980, 908.
11. Fagnoni, M.; Mella, M.; Albini, A. Org. Lett. 1999, 1, 1299.
12. Majima, T.; Pac, C.; Nakasone, A.; Sakurai, H. J. Am. Chem.
Soc. 1981, 103, 4499.
(2R,5R)/(2S,5S)
2-(40-N,N-Dimethylaminophenyl)-5-
methoxy-2,5-dihydrofuran (8). Colourless oil; [Found:
C, 71.32, H, 7.88, N, 6.32. C13H17 NO2 requires C, 71.21,
H, 7.81, N, 6.39%]; dH (300 MHz CDCl3): 2.15 (s, 6H,
NMe2), 3.4 (s, 3H, OMe), 5.8 (m, 1H, H-2), 5.9 (ddd,
Jˆ6, 1.2 and 2.4 Hz, 1H, H-3), 5.94 (dt, Jˆ4 and 1.2 Hz,
1H, H-5), 6.2 (dt, Jˆ6 and 1.2 Hz, 1H, H-4), 6.9 and 7.2
(AA0XX0, 4H, aromatics); dC (300 MHz CDCl3): 40.9
(NMe2), 54.4 (OMe), 87.03 (CH-2), 109.2 (CH-5), 112.5
(CH), 125.9 (CH), 127.2, 127.7 (CH), 136.2, 150.6. The
fact that the coupling constant between H-2 and H-5
(4 Hz) was larger than that observed with isomer 7
(1.2 Hz) supported a trans arrangement for these two
protons. No signi®cant NOE correlation was found in the
NOESY experiment.
13. Abdel-Megied, A. E. S.; Pedersen, E. B.; Nielsen; C. M.
Synthesis 1991, 313; Nair, V.; Lyons, A. G.; Purdy, D. F.
Tetrahedron 1991, 47, 8949.
14. Mallams, A. K. J. Am. Chem. Soc. 1969, 91, 7505; Kawajima,
I.; Sugihara, S.; Enda, J. Tetrahedron Lett. 1983, 24, 1061; Ghosh,
A. K.; McKee, S. P.; Thompson, W. J. J. Org. Chem. 1991, 56,
6500; Florent, J. C.; Monneret, C. Carbohydr. Res. 1980, 81, 225;
Durgnat, J. M.; Warm, A.; Vogel, P. Synth. Commun. 1992, 22,
1883; Lacourt-Gadras, B.; Grignon Dubois, M.; Rezzonico, B.
Carbohydr. Res. 1992, 235, 281; Warm, A.; Vogel, P. J. Org.
Chem. 1986, 51, 5348.
15. Bird, C. W.; Cheeseman, G. W. In Comprehensive
Heterocyclic Chemistry, Katritzky, A. R., Rees, C., Eds.;
Pergamon: Oxford, 1984; Vol. 4, p 39.
Attempted reaction with indole. GC±MS analysis of the
photolised solution of 1 in the presence of 1 M indole
showed the presence of two new peaks, at tR 17.44 min
with fragmentation m/z 236 (100), 219 (5), 191 (7), 163
(3) and at tR 19.45 min with fragmentation m/z 236 (100),
16. Gasper, S. M.; Devadoss, C.; Schuster, G. B. J. Am. Chem.
Soc. 1995, 117, 5206.
17. Unpublished results from the author's laboratory.

B. Guizzardi et al. / Tetrahedron 56 (2000) 9383±9389
9389
18. Previtali, C. M. J. Photochem. 1985, 31, 233.
19. Koutek, B.; Musil, L.; Velek, J.; Soucek, M. Collect. Czech.
Chem. Commun. 1985, 50, 1753.
23. On the other hand, the present reaction has no mechanistic
analogy with the synthesis of bithienyls and phenylthiophenes by
irradiation of iodothiophenes, see Antonioletti, R.; D'Auria, M.;
De Mico, G.; Piancatelli, G.; Scettri, A. Tetrahedron 1985, 41, 341
and therein quoted references.
20. Aschi, M.; Harvey, J. N. J. Chem. Soc., Perkin Trans. 2 1999,
1059.
21. Hori, K.; Sonoda, T.; Harada, M.; Yamanaki-Nishida, S.
Tetrahedron 2000, 56, 1429.
24. Bellavita, V. Gazz. Chim. Ital. 1935, 65, 632.
25. Bruzzi, L.; Degani, I.; Tundo, A. Boll. Chim. Fac. Ind.
Bologna 1961, 19, 40; Tundo, A. Boll. Chim. Fac. Ind. Bologna
1960, 18, 102.
22. Davis, A. G.; Julia, L.; Yazdi, S. N. J. Chem. Soc., Perkin
Trans. 2 1989, 239; Rao, D. N. T.; Symons, M. C. R. J. Chem.
Soc., Perkin Trans. 2 1983, 135; Shiotani, M.; Nagata, Y.; Tasaki,
M.; Sohmo, S.; Shida, T. J. Phys. Chem. 1983, 87, 1170.