Synthesis of 4,8-diarylcinnolines and quinazolines with potential applications in nonlinear optics. Diazines. Part 28

Article abstract of DOI:10.1016/S0040-4020(00)00448-8

New 4,8-diarylbenzodiazines have been synthesized using cross-coupling reactions and regioselective metalation at the peri-position C₈ of the benzene moiety of various cinnolines and quinazolines. Some of these compounds have been tested to assess their nonlinear optical properties. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00448-8

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 5499±5507
Synthesis of 4,8-Diarylcinnolines and Quinazolines with Potential
Applications in Nonlinear Optics. Diazines. Part 28
*
 Â
V. Gautheron Chapoulaud, N. Ple, A. Turck and G. Queguiner
 Â
Laboratoire de Chimie Organique Fine et Heterocyclique, UPRES-A 6014 IRCOF-INSA, B.P. 08, 76131 Mont St Aignan Cedex, France
Received 8 December 1999; accepted 26 May 2000
AbstractÐNew 4,8-diarylbenzodiazines have been synthesized using cross-coupling reactions and regioselective metalation at the peri-
position C8 of the benzene moiety of various cinnolines and quinazolines. Some of these compounds have been tested to assess their
nonlinear optical properties. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
As a matter of fact, famous examples resulting from that
concept are p-aminonitrobenzene (pNA) and 4-N,N-
dimethylamino-40-nitrostilbene (DANS).
For nearly 20 years, nonlinear optics (NLO) and electro-
optics (EO) have received growing attention, because of
their great importance in opto-electronic technology, e.g.
optical telecommunications or computer optical signal
processing.1±9
A polarized p-system can be generated by fusing or linearly
connecting heteroaromatic systems of different electron
densities. Moreover, the introduction of aromatic rings
improves the transparencyÐnonlinearity trade-off and the
thermal stability, these two factors being critical for electro-
optical applications.10±12
Development of more suitable NLO materials is nowadays
greatly needed. One of the chosen solutions is the prepa-
ration of organic NLO components that have already shown
numerous advantages compared to commercially available
inorganic devices. Some of these advantages are an ef®cient
tailorability and an extremely fast NLO response.4±9
The aromatic moieties investigated in this work are cinno-
lines and quinazolines disubstituted at the 4 and 8 positions
by benzene rings bearing electron-donating or withdrawing
groups or other heteroarenes such as thiophene.
The most investigated effects are the second-harmonic
generation (SHG) and the Pockels effect. The molecular
property responsible for these second-order optical effects
is the ®rst-order hyperpolarizability b.
In order to perform such a study, we have synthesized and
characterized a number of 4,8-diarylcinnolines and quin-
azolines. The molecular ®rst-order hyperpolarizability b
of some of those compounds has been measured by
Hyper-Rayleigh Scattering (HRS) in CHCl3 at 1320 nm.
Most of the organic compounds exhibiting high b values are
basically dipolar and polarizable materials presenting a
p-electronic conjugated system substituted by electron-
donating (D) and electron-withdrawing (A) groups that
lead to internal charge transfer (CT).
Results
The Pd-catalyzed cross-coupling reactions of arylboronic
acids or aryl trialkylstannanes with haloarenes provide
highly ef®cient and ¯exible methods to synthesize unsym-
metrical heterobiaryls.13±20 We have prepared numerous
4,8-diarylbenzodiazines by selective cross-coupling reac-
tions involving 4-chlorocinnoline or quinazoline as starting
materials. Indeed the carbon-chloride bond on diazine
moiety is highly polarized thus allowing easy oxidative
insertion of Pd(0). The following sequence of reactions is
used as a general synthetic route (Scheme 1).
Amino and nitro groups are known to be respectively very
strong electron-donating and electron-withdrawing sub-
stituents as indicated by their high Hammett s values.
They allow an asymmetric charge distribution, one of the
conditions necessary to obtain ef®cient NLO compounds.6
Keywords: metalation; benzodiazines; nonlinear optics.
* Corresponding author. Tel.: 133-2-3552-29-00; fax: 133-2-3552-29-62;
e-mail: guy.queguiner@insa-rouen.fr
A ®rst cross-coupling reaction under Suzuki conditions of
various arylboronic acids with 4-chlorobenzodiazines was
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00448-8

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V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
Scheme 1.
Scheme 2.
performed and afforded the corresponding 4-aryl deriva-
tives.
nation of the corresponding 4-hydroxycinnoline 2 synthe-
sized in two steps from 2-iodoaniline.21,24 The cross-
coupling reaction was then carried out with various substi-
tuted arylboronic acids under Suzuki conditions, affording
the related 4-arylcinnolines 4±6 in good yields (Scheme 2).
This sequence provides a new route to cinnolines substituted
at the 4 position by an aryl moiety, the latter being usually
dif®cult to obtain by the standard Widman±Stoermer
synthesis.25,26
In previous papers,21±23 we have reported the unexpected
lithiation and functionalization of the benzene moiety of
various benzodiazines and more particularly of cinnolines
and quinazolines. In these two cases, the exceptional
reactivity towards metalation at the C8 position, peri to
the nitrogen atom, enabled us to form 4-aryl-8-lithiobenzo-
diazines, which were afterwards reacted with iodine to lead
to 4-aryl-8-iodobenzodiazines. Another cross-coupling
reaction afforded 4,8-diarylbenzodiazines.
In a previous paper, we have reported that treatment of
4-chlorocinnoline 3 with lithium 2,2,6,6-tetramethylpiperi-
dide (LTMP) followed by reaction with iodine led to
a mixture of 4-chloro-3-iodocinnoline and 4-chloro-3,8-
diiodocinnoline.21 This result reveals a higher reactivity
towards metalation at C3 than at C8. In order to obtain
only the monoiodo derivative at the C8 position, the C3
Synthesis of 4,8-diarylcinnolines
The starting 4-chlorocinnoline 3 was obtained by chlori-
Scheme 3.

V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
5501
Scheme 4.
position has to be protected by a substituent that would
allow the iodination via metalation and could be easily
removed after the cross-coupling reaction. The trimethyl-
silyl group has been chosen and introduced at the C3
position by metalation of 4-arylcinnolines.
boronic acids carried out with compound 20 afforded the
related 4-aryl-6,7-dimethoxyquinazolines 21±23 in good
yields (86±95%). These compounds were afterwards
reacted with lithium alkylamides, then iodine as the electro-
phile to give 4-aryl-6,7-dimethoxy-8-iodoquinazolines 24
and 25. It must be pointed out that, as for the related
cinnolines, all attempts to lithiate compound 22 have failed,
probably because of the presence of a nitro group. In this
case, only starting material and degradation products were
isolated.
Treatment of compounds 4±6 with 1.1 equivalents of LDA
(lithium diisopropylamide) as the metalating agent and
trimethylsilyl chloride as the electrophile according to the
`in situ trapping technique'27 led to compounds 7±9
(Scheme 3). Compounds 7 and 9 were obtained with good
yields (respectively 96 and 67%) whereas silylation of
compound 5 nearly failed. Only 3% of compound 8 was
isolated, besides starting material and degradation products.
This low yield could be explained by the reaction of the
nitro group with the metalating agent to undergo oxido-
A further cross-coupling reaction under Suzuki or Stille
conditions completed the synthesis of 4,8-diaryl-6,7-
dimethoxyquinazolines 26±30 (81±98%) (Scheme 6).
reduction side reactions.28,29
A further lithiation of
Measurements
compounds 7 and 9 with LTMP, followed by reaction
with iodine, afforded the 8-iodo derivatives 10 (88%) and
11 (72%) (Scheme 3).
The NLO measurements of the mb values of compounds
14, 26 and 29 are reported in Table 1. In this scalar product,
m is the ground-state dipole moment and b the vector part
of the hyperpolarizability tensor of the molecule.
Cross-coupling reactions of various arylboronic acids or
(2-thienyl)-trimethylstannane with compounds 10 and 11
have been performed, leading to 4,8-diaryl-3-trimethyl-
silyl-cinnolines 12±15 (Scheme 4).
These preliminary results indicate that 4,8-diarylbenzo-
diazines have appreciable nonlinear optical properties, the
quinazoline derivatives giving better results. Further and
complete measurements will be performed with the other
compounds.
Desilylation of compounds 12±15 has been carried out in
THF with tetra-n-butylammonium ¯uoride (TBAF) and
furnished the expected 4,8-diarylcinnolines 16±19 in good
yields (66±95%) (Scheme 5).
Conclusion
In summary, 4,8-diarylcinnolines 16±19 were synthesized
in ®ve steps from 4-chlorocinnoline 3 with overall yields
varying from 25 to 58%.
We have synthesized new 4,8-diarylbenzodiazines using
cross-coupling reactions. The regioselective functionalization
Synthesis of 4,8-diarylquinazolines
Following a similar synthetic route, we have prepared 4,8-
diarylquinazolines starting from 4-chloro-6,7-dimethoxy-
quinazoline 20.30 The choice of this derivative was directed
by the high reactivity and regioselectivity observed during
lithiation at the C8 position.23 In this case, the presence of
two methoxy groups on the benzene moiety makes it more
reactive towards lithiation than the free C2 position; thus the
protection of this position was not needed.
As before, a ®rst cross-coupling reaction of various aryl-
Scheme 5.

5502
V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
Scheme 6.
Table 1. Longest wavelength absorption maxima lmax, transparency limits
cut-off in CHCl3 and mb (HRS measurement at 1320 nm in CHCl3)
boronic acids were synthesized by halogen±metal exchange
followed by reaction with trimethylborate from the
commercially available 1-bromo-4-tri¯uoromethylbenzene
or 1-bromo-4-methoxybenzene.
l
Compound
l
max (nm)
lcut-off (nm)
mb£10248 esu
m (D)a
14
26
29
355
350
360
440
400
420
38
35
48
7.21
3.46
5.61
Procedure A for direct lithiation by lithium alkylamide
(LTMP or LDA)
a m Dipolar moment determined by the semi-empirical PM3 method.
A solution of n-butyllithium (1.6 M or 2.5 M in hexane) was
added to cold (2508C), stirred and anhydrous tetrahydro-
furan (15 mL) under an atmosphere of dry argon. Then
2,2,6,6-tetramethylpiperidine (TMPH) or diisopropylamine
(DIPAH) was added. The mixture was warmed to 08C. After
20 min, the temperature was lowered to 2788C and the
benzodiazine dissolved in 5 mL of THF was added. After
a time t1 at 2788C, iodine was introduced and stirring was
continued for a time t2 at 2788C. Hydrolysis was then
carried out using a solution of 35% aqueous hydrochloric
acid, ethanol and tetrahydrofuran (1/4/5). At room tempera-
ture, the solution was made slightly basic with saturated
sodium hydrogen carbonate solution and decolorized with
sodium thiosulphate. After concentration, the residue was
extracted with dichloromethane (3£15 mL). The combined
organic extracts were dried over magnesium sulphate and
evaporated. The crude product was puri®ed by column
chromatography on silica gel.
by iodine of the C8 position of the benzene moiety of various
cinnolines and quinazolines has been carried out by the
metalation of this peri position. The nonlinear optical
properties of some of these compounds have been measured
and interesting and promising results have been observed.
Synthesis of other new diarylbenzodiazines and measure-
ments of their ®rst-order hyperpolarizability b are in
progress.
Experimental
Melting points were determined on a Ko¯er hot-stage. The
1H, 13C and 19F NMR spectra were recorded in deutero-
chloroform on a Bruker AC 200 instrument. Microanalyses
were performed on a Carlo Erba CHNOS 1160 apparatus.
The IR spectra were obtained as potassium bromide pellets
with a Perkin±Elmer FTIR 1650 spectrophotometer.
Procedure B for `in situ trapping' metalation
All reagents were of commercial quality and were
purchased from Aldrich Chemical Co. or Acros. The
Pd(0)-catalyst Pd(PPh3)4 was prepared according to
the literature.31 4-Tri¯uoromethyl- and 4-methoxyphenyl-
The benzodiazine dissolved in 5 mL of THF and trimethyl-
silyl chloride were simultaneously introduced at 2788C into
the solution containing the metalating agent (LTMP or
LDA) prepared according to procedure A. The mixture

V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
5503
was then stirred for a time t at 2788C. The following steps
are similar to procedure A.
carbonate solution, the mixture was extracted with dichloro-
methane (3£15 mL). The combined organic layers were
dried over magnesium sulphate and evaporated. Puri®cation
by ¯ash column chromatography (silica gel, eluent:
dichloromethane/ethyl acetate (8/2)) afforded 1.73 g
(77%) of 3 as a yellow solid, mp 77±788C (lit.18: 788C);
1H NMR (CDCl3): d 9.36 (s, 1H, H3); 8.56 (d, Jˆ8.3 Hz,
1H, H8); 8.20 (d, Jˆ7.8 Hz, 1H, H5); 7.93 (m, 2H, H6,7).
General cross-coupling procedure C of arylboronic acid
with halobenzodiazine
A mixture of the halobenzodiazine (2 mmol), the arylboronic
acid (1.4 equiv.), Pd(PPh3)4 (0.05 equiv.), aqueous 2 M
potassium carbonate (2 equiv.) and ethanol (1 mL) in
degassed toluene or dimethoxyethane (15 mL) was heated
under re¯ux and under nitrogen for 15±67 h. The reaction
mixture was cooled, diluted with 15 mL of water and
dichloromethane (1/1) and the organic layer separated.
The aqueous layer was extracted with dichloromethane
(3£15 mL), the combined organic extracts were dried over
magnesium sulphate and evaporated. The crude product was
puri®ed by column chromatography on silica gel.
4-(40-Tri¯uoromethylphenyl)cinnoline (4). Coupling of
4-tri¯uoromethylphenylboronic acid (1.4 equiv.) with 3
(328 mg, 2 mmol) according to the general procedure C
(DME, tˆ44 h) gave after puri®cation by column chroma-
tography (silica gel, eluent: petroleum ether/ethyl acetate
(6/4)) 466 mg (85%) of 4 as a yellow solid, mp 124±1258C;
1H NMR (CDCl3): d 9.28 (s, 1H, H3); 8.66 (d, Jˆ8 Hz, 1H,
H8); 7.90 (m, 5H, 5Harom); 7.74 (m, 2H, 2Harom); 19F NMR
(CDCl3): d 263; IR: n 3064, 1326, 1108, 770, 611 cm21
.
Anal. Calcd for C15H9F3N2 (274.24): C, 65.69; N, 10.22; H,
3.31. Found: C, 65.57; N, 10.14; H, 3.29.
General cross-coupling procedure D of heteroaryl
trialkylstannane with halobenzodiazine
4-(30-Nitrophenyl)cinnoline (5). Coupling of 3-nitro-
phenylboronic acid (1.4 equiv.) with 3 (328 mg, 2 mmol)
according to the general procedure C (DME, tˆ40 h) gave
after puri®cation by column chromatography (silica gel,
eluent: dichloromethane/ethyl acetate (8/2)) 442 mg (88%)
of 5 as a yellow solid, mp 182±1838C; 1H NMR (CDCl3): d
9.30 (s, 1H, H3); 8.69 (d, Jˆ8.3 Hz, 1H, H8); 8.46 (m, 2H,
A mixture of the halobenzodiazine (2 mmol), the heteroaryl
trialkylstannane (1.2 equiv.) and Pd(PPh3)4 (0.05 equiv.) in
degassed toluene (15 mL) was heated under re¯ux under
nitrogen for 39±48 h. The following steps are similar to
procedure C.
2HPhNO ); 7.90 (m, 5H, 5Harom); IR: n 1523, 1352, 766,
2
691 cm21. Anal. Calcd for C14H9N3O2 (251.25): C, 66.93;
N, 16.72; H, 3.61. Found: C, 66.85; N, 16.68; H, 3.87.
4-Chlorocinnoline (3). Into 50 mL of degassed triethyl-
amine were successively introduced cuprous iodide
(3.13 g, 0.36 equiv.), trimethylsilylacetylene (13 mL,
2 equiv.), after 10 min of stirring bis(triphenylphosphine)
palladium dichloride (300 mg, 0.007 equiv.) and ®nally
after 30 min of stirring, amino-2-iodobenzene (10 g,
45.6 mmol). The mixture was heated under re¯ux for
24 h, cooled and ®ltered. The ®ltrate was dried over mag-
nesium sulphate and evaporated. Puri®cation by column
chromatography (silica gel, eluent: dichloromethane/
petroleum ether (4/6)) afforded 8.15 g (95%) of (20-amino-
phenyl)trimethylsilylacetylene 1 as a colorless oil; 1H NMR
(CDCl3): d 7.31 (d, Jˆ8.2 Hz, 1H, H3); 7.13 (dd, Jˆ8.2 and
7.5 Hz, 1H); 6.68 (m, 2H, 2Harom); 4.24 (s, 2H, NH2); 0.29
(s, 9H, Si(CH3)3).
4-(40-Methoxyphenyl)cinnoline (6). Coupling of 4-meth-
oxyphenylboronic acid (1.4 equiv.) with
3 (328 mg,
2 mmol) according to the general procedure C (DME,
tˆ16 h) gave after puri®cation by column chromatography
(silica gel, eluent: petroleum ether/ethyl acetate (5/5))
1
406 mg (86%) of 6 as a yellow solid, mp 80±818C; H
NMR (CDCl3): d 9.18 (s, 1H, H3); 8.51 (d, Jˆ8.4 Hz, 1H,
H8); 7.98 (d, Jˆ8.2 Hz, 1H, H5); 7.72 (m, 2H, H6/7); 7.45 (d,
Jˆ8.7 Hz, 2H, 2HPhOCH ); 7.04 (d, Jˆ8.7 Hz, 2H, 2HPhOCH );
3
3
3.85 (s, 3H, OCH3); IR: n 3020, 1607, 1514, 1492, 1241,
838, 784 cm21. Anal. Calcd for C15H12N2O (236.27): C,
76.25; N, 11.86; H, 5.12. Found: C, 75.86; N, 11.67; H, 5.14.
4-(40-Tri¯uoromethylphenyl)-3-trimethylsilylcinnoline
(7). Metalation of 4 (860 mg, 3.14 mmol) according to
procedure B with n-BuLi 1.6 M (1.1 equiv., 2.16 mL),
DIPAH (1.2 equiv., 0.49 mL) and trimethylsilyl chloride
(1.1 equiv., 0.48 mL), tˆ2 h, gave after puri®cation by
column chromatography (silica gel, eluent: petroleum
ether/ethyl acetate (6/4)) 1.04 g (96%) of 7 as a yellow
solid, mp 97±988C; 1H NMR (CDCl3): d 8.58 (d, Jˆ
To a solution of the amino derivative 1 (2 g, 10.6 mmol)
dissolved in 20 mL of water were cautiously added at 08C
15 mL of a 6N aqueous hydrochloric acid solution, then,
dropwise, 5 mL of an aqueous solution of sodium nitrite
(1.1 g, 15.9 mmol), keeping the mixture temperature
below 08C. After 30 min, the mixture was heated under
re¯ux for 3 h, cooled then neutralized with saturated
aqueous sodium hydrogen carbonate solution. After concen-
tration, the precipitate was ®ltered and washed with
dichloromethane. 4-Hydroxycinnoline 2 (1.1 g, 73%) was
obtained as a pale brown solid, mp 234±2358C (lit.32:
2348C).
8.5 Hz, 1H, H8); 7.82 (m, 3H, 2HPhCF 1Harom); 7.65 (td,
3
Jˆ8.5, 6.8 and 1.2 Hz, 1H, Harom); 7.48 (d, Jˆ8 Hz, 2H,
2HPhCF ); 7.39 (d, Jˆ8.5 Hz, 1H, H5); 0.17 (s, 9H,
3
Si(CH3)3); 19F NMR (CDCl3): d 263; IR: n 2950, 1325,
. Anal. Calcd for
1166, 1123, 834, 774, 616 cm21
C18H17F3N2Si (346.43): C, 62.41; N, 8.09; H, 4.95. Found:
C, 62.33; N, 8.16; H, 4.67.
A mixture of 4-hydroxycinnoline 2 (2 g, 13.7 mmol), phos-
phorus oxychloride (1.94 mL, 20.5 mmol) and anhydrous
pyridine (0.33 mL, 4.1 mmol) dissolved in chlorobenzene
(50 mL) was re¯uxed for 1 h. After cooling, concentration
and neutralization with saturated aqueous potassium
4-(30-Nitrophenyl)-3-trimethylsilylcinnoline (8). Metala-
tion of 5 (1.3 g, 5.18 mmol) according to procedure B

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V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
with n-BuLi 1.6 M (1.1 equiv., 3.6 mL), DIPAH (1.2 equiv.,
0.82 mL) and trimethylsilyl chloride (1.1 equiv., 0.80 mL),
tˆ4 h, gave after puri®cation by column chromatography
(silica gel, eluent: petroleum ether/ethyl acetate (5/5))
according to the general procedure C (toluene, tˆ40 h)
gave after puri®cation by column chromatography (silica
gel, eluent: petroleum ether/ethyl acetate (8/2)) 543 mg
1
(60%) of 12 as a yellow solid, mp 188±1898C; H NMR
(CDCl3): d 7.82 (m, 4H, 4HPhCF ); 7.68 (m, 1H, H6); 7.49
1
52 mg (3%) of 8 as a yellow solid, mp 112±1138C; H
NMR (CDCl3): d 8.68 (d, Jˆ8.5 Hz, 1H, H8); 8.42 (m,
3
(m, 3H, 2HPhOCH 1H7); 7.33 (dd, Jˆ8.4 and 1.3 Hz, 1H,
3
1H, HPhNO ); 8.25 (m, 1H, HPhNO ); 7.96±7.66 (m, 4H,
H5); 7.08 (d, Jˆ8.7 Hz, 2H, 2HPhOCH ); 3.90 (s, 3H,
2
2
3
4Harom); 7.38 (d, Jˆ8.1 Hz, 1H, H5); 0.17 (s, 9H,
Si(CH3)3); IR: n 1528, 1354, 841, 761 cm21. Anal. Calcd
for C17H17N3O2Si (323.43): C, 63.13; N, 12.99; H, 5.30.
Found: C, 63.37; N, 12.76; H, 5.12.
OCH3); 0.16 (s, 9H, Si(CH3)3); 19F NMR (CDCl3): d 263;
IR: n 2956, 1607, 1326, 1248, 1176, 1121, 840 cm21. Anal.
Calcd for C25H23F3N2OSi (452.55): C, 66.35; N, 6.19; H,
5.12. Found: C, 66.22; N, 6.02; H, 5.01.
Another fraction afforded 880 mg (68%) of starting
material.
Another fraction afforded 190 mg (25%) of desilylated
product 16.
4-(40-Methoxyphenyl)-3-trimethylsilylcinnoline (9). Meta-
lation of 6 (567 mg, 2.40 mmol) according to procedure B
with n-BuLi 1.6 M (2.2 equiv., 3.30 mL), DIPAH (2.4
equiv., 0.76 mL) and trimethylsilyl chloride (2.2 equiv.,
0.68 mL), tˆ2 h, gave after puri®cation by column chroma-
tography (silica gel, eluent: petroleum ether/ethyl acetate (6/
4)) 499 mg (67%) of 9 as a yellow solid, mp 115±1168C; 1H
NMR (CDCl3): d 8.50 (d, Jˆ8.5 Hz, 1H, H8); 7.77 (m, 1H,
Harom); 7.54 (m, 2H, 2Harom); 7.22 (d, Jˆ8.6 Hz, 2H,
2HPhOCH ); 7.04 (d, Jˆ8.6 Hz, 2H, 2HPhOCH ); 3.89 (s, 3H,
8-(20-Thienyl)-4-(40-tri¯uoromethylphenyl)-3-trimethyl-
silylcinnoline (13). Coupling of (2-thienyl)-trimethylstan-
nane (1.2 equiv.) with 10 (945 mg, 2 mmol) according to the
general procedure D (toluene, tˆ48 h) gave after puri®-
cation by column chromatography (silica gel, eluent: petro-
leum ether/ethyl acetate (8/2)) 711 mg (83%) of 13 as a
1
yellow solid, mp 161±1628C; H NMR (CDCl3): d 8.14
0
(d, Jˆ7.6 Hz, 1H, H7); 7.97 (d, Jˆ3.6 Hz, 1H, H3 thienyl);
7.83 (d, Jˆ8.1 Hz, 2H, 2HPhCF ); 7.65 (dd, Jˆ8.2 and
3
0
7.6 Hz, 1H, H6); 7.58 (d, Jˆ5.1 Hz, 1H, H5 thienyl); 7.50 (d,
3
3
OCH3); 0.16 (s, 9H, Si(CH3)3); IR: n 2954, 1607, 1514,
1248, 888, 834, 772 cm21. Anal. Calcd for C18H20N2OSi
(308.45): C, 70.09; N, 9.08; H, 6.54. Found: C, 70.15; N,
9.02; H, 6.68.
Jˆ8.1 Hz, 2H, 2HPhCF ); 7.26 (m, 2H, 2Harom); 0.18 (s, 9H,
3
Si(CH3)3); 19F NMR (CDCl3): d 263; IR: n 1326, 1122,
833 cm21. Anal. Calcd for C22H19F3N2SSi (428.55): C,
61.66; N, 6.54; H, 4.47; S, 7.48. Found: C, 61.91; N, 6.25;
H, 4.53; S, 7.62.
8-Iodo-4-(40-tri¯uoromethylphenyl)-3-trimethylsilylcinno-
line (10). Metalation of 7 (154 mg, 0.45 mmol) according to
procedure A with n-BuLi 1.6 M (4 equiv., 1.12 mL), TMPH
(4.1 equiv., 0.31 mL), t1ˆ1 h, followed by reaction with
iodine (2 equiv., 226 mg), t2ˆ2 h, gave after puri®cation
by column chromatography (silica gel, eluent: petroleum
ether/ethyl acetate (6/4)) 185 mg (88%) of 10 as a pale
4-(40-Methoxyphenyl)-8-(40-tri¯uoromethylphenyl)-3-
trimethylsilylcinnoline (14). Coupling of 4-tri¯uoro-
methylphenylboronic acid (1.4 equiv.) with 11 (869 mg,
2 mmol) according to the general procedure C (toluene,
tˆ40 h) gave after puri®cation by column chromatography
(silica gel, eluent: petroleum ether/ethyl acetate (6/4))
1
1
yellow solid, mp 1798C (decomp.); H NMR (CDCl3): d
787 mg (87%) of 14 as a yellow solid, mp 188±1898C; H
NMR (CDCl3): d 7.92 (m, 2H, 2Harom); 7.69 (m, 5H,
8.45 (dd, Jˆ6 and 2 Hz, 1H, H7); 7.83 (d, Jˆ8 Hz, 2H,
2HPhCF ); 7.47 (d, Jˆ8 Hz, 2H, 2HPhCF ); 7.36 (m, 2H, H5/6);
5Harom); 7.30 (d, Jˆ8.7 Hz, 2H, 2HPhOCH ); 7.09 (d,
3
3
3
0.17 (s, 9H, Si(CH3)3); 19F NMR (CDCl3): d 263; IR: n
2960, 1322, 1174, 1131, 1066, 832, 618, 547 cm21. Anal.
Calcd for C18H16F3IN2Si (472.32): C, 45.77; N, 5.93; H,
3.41. Found: C, 45.88; N, 5.98; H, 3.56.
Jˆ8.7 Hz, 2H, 2HPhOCH ); 3.94 (s, 3H, OCH3); 0.18 (s, 9H,
3
Si(CH3)3); 19F NMR (CDCl3): d 262.7; IR: n 1609, 1516,
1324, 1250, 1123, 837 cm21
.
Anal. Calcd for
C25H23F3N2OSi (452.55): C, 66.35; N, 6.19; H, 5.12.
Found: C, 66.63; N, 5.90; H, 5.15.
8-Iodo-4-(40-methoxyphenyl)-3-trimethylsilylcinnoline
(11). Metalation of 9 (120 mg, 0.39 mmol) according to
procedure A with n-BuLi 1.6 M (4 equiv., 0.97 mL),
TMPH (4.1 equiv., 0.28 mL), t1ˆ45 min, followed by
reaction with iodine (2 equiv., 198 mg), t2ˆ1 h, gave after
puri®cation by column chromatography (silica gel, eluent:
dichloromethane) 122 mg (72%) of 11 as a yellow solid, mp
4-(40-Methoxyphenyl)-8-(30-nitrophenyl)-3-trimethylsilyl-
cinnoline (15). Coupling of 3-nitrophenylboronic acid
(1.4 equiv.) with 11 (869 mg, 2 mmol) according to the
general procedure C (toluene, tˆ40 h) gave after puri®-
cation by column chromatography (silica gel, eluent: petro-
leum ether/ethyl acetate (5/5)) 619 mg (72%) of 15 as an
orange solid, mp 115±1168C; 1H NMR (CDCl3): d 8.61 (s,
1H, HPhNO ); 8.32 (d, Jˆ8.2 Hz, 1H, HPhNO ); 8.20 (d,
1
144±1458C; H NMR (CDCl3): d 8.39 (d, Jˆ7.2 Hz, 1H,
H7); 7.51 (d, Jˆ8.5 Hz, 1H, H5); 7.29 (dd, Jˆ8.5 and
2
2
7.2 Hz, 1H, H6); 7.20 (d, Jˆ8.6 Hz, 2H, 2HPhOCH ); 7.04
Jˆ7.7 Hz, 1H, H7); 7.82 (m, 1H, Harom); 7.62 (m, 3H,
3
(d, Jˆ8.6 Hz, 2H, 2HPhOCH ); 3.91 (s, 3H, OCH3); 0.18 (s,
3Harom); 7.28 (d, Jˆ8.6 Hz, 2H, 2HPhOCH ); 7.09 (d, Jˆ
3
3
9H, Si(CH3)3); IR: n 1605, 1514, 1248, 1024, 835,
773 cm21. Anal. Calcd for C18H19IN2OSi (434.35): C,
49.77; N, 6.45; H, 4.41. Found: C, 49.82; N, 6.41; H, 4.40.
8.6 Hz, 2H, 2HPhOCH ); 3.94 (s, 3H, OCH3); 0.18 (s, 9H,
3
Si(CH3)3); IR: n 1526, 1350, 1249, 839, 740 cm21. Anal.
Calcd for C24H23N3O3Si (429.55): C, 67.11; N, 9.78; H,
5.40. Found: C, 67.18; N, 9.67; H, 5.42.
8-(40-Methoxyphenyl)-4-(40-tri¯uoromethylphenyl)-3-
trimethylsilylcinnoline (12). Coupling of 4-methoxyphe-
nylboronic acid (1.4 equiv.) with 10 (945 mg, 2 mmol)
Another fraction afforded 179 mg (25%) of desilylated
product 19.

V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
5505
8-(40-Methoxyphenyl)-4-(40-tri¯uoromethylphenyl)cinno-
line (16). TBAF (1 M in THF, excess, 2 mL) and H2O
(1 mL) were added to 12 (120 mg, 0.27 mmol) dissolved
in 10 mL of THF. The mixture was then gently re¯uxed
for 22 h, cooled and diluted with 10 mL of water. After
separation of the organic layer, the aqueous layer was
extracted with dichloromethane (3£20 mL). The combined
organic layers were dried over magnesium sulphate and
concentrated. Puri®cation by column chromatography
(silica gel, eluent: petroleum ether/ethyl acetate (6/4))
afforded 96 mg (95%) of 16 as a yellow solid, mp 221±
TBAF (1 M in THF, 3 equiv., 0.8 mL) and H2O (1 mL)
were added to 15 (120 mg, 0.28 mmol) dissolved in
10 mL of THF. The mixture was then gently re¯uxed for
20 h. The following treatments are similar to compound 16.
Puri®cation by column chromatography (silica gel, eluent:
petroleum ether/ethyl acetate (5/5)) afforded 76 mg (76%)
of 19 as a yellow solid, mp 205±2068C; 1H NMR (CDCl3):
d 9.34 (s, 1H, H3); 8.64 (s, 1H, HPhNO ); 8.34 (d, Jˆ7.8 Hz,
2
1H, Harom); 8.16 (m, 2H, 2Harom); 7.88 (m, 2H, 2Harom); 7.71
(dd, Jˆ8 and 7.8 Hz, 1H, Harom); 7.56 (d, Jˆ8.2 Hz, 2H,
2HPhOCH ); 7.15 (d, Jˆ8.2 Hz, 2H, 2HPhOCH ); 3.95 (s, 3H,
3
3
1
2228C; H NMR (CDCl3): d 9.28 (s, 1H, H3); 7.89±7.70
(m, 9H, 4HPhCF 12HPhOCH 1H5/6/7); 7.09 (d, Jˆ8.6 Hz,
OCH3); 13C NMR (CDCl3) d 55.89 (OCH3), 115.06, 116.07,
123.15, 126.08, 126.63, 129.94, 131.15, 131.46, 131.67,
137.76, 140.25 (Ph and Ar), 145.37 (C-3), 148.35, 161.09,
167.86, 168.04 (Ph and Ar); IR: n 1608, 1532, 1352, 1250,
837, 787, 700 cm21. Anal. Calcd for C21H15N3O3 (357.37):
C, 70.58; N, 11.76; H, 4.23. Found: C, 70.73; N, 11.55; H,
4.26.
3
3
2H, 2HPhOCH ); 3.91 (s, 3H, OCH3); 13C NMR (CDCl3) d
3
55.57 (OCH3), 113.97, 114.33, 123.19, 123.71, 125.47,
126.10, 126.15, 127.89, 130.46, 130.59, 130.95, 131.06,
131.78, 132.41, 132.48 (Ph and Ar), 144.07 (C-3), 159.92
(Ph or Ar);); 19F NMR (CDCl3): d 263; IR: n 1606, 1509,
1323, 1246, 1174, 1134, 1067, 851, 829, 789 cm21. Anal.
Calcd for C22H15F3N2O (380.37): C, 69.47; N, 7.36; H, 3.97.
Found: C, 69.80; N, 7.03; H, 4.17.
6,7-Dimethoxy-4-(40-tri¯uoromethylphenyl)quinazoline
(21). Coupling of 4-tri¯uoromethylphenylboronic acid
(1.4 equiv.) with 2027 (450 mg, 2 mmol) according to the
general procedure C (toluene, tˆ40 h) gave after puri®-
cation by column chromatography (silica gel, eluent: petro-
leum ether/ethyl acetate (5/5)) 635 mg (95%) of 21 as a
8-(20-Thienyl)-4-(40-tri¯uoromethylphenyl)cinnoline (17).
TBAF (1 M in THF, 1.2 equiv., 0.7 mL) and H2O (1 mL)
were added to 13 (250 mg, 0.58 mmol) dissolved in 10 mL
of THF. The mixture was then gently re¯uxed for 24 h. The
following treatments are similar to compound 16. Puri®-
cation by column chromatography (silica gel, eluent:
petroleum ether/ethyl acetate (8/2)) afforded 181 mg
1
white solid, mp 187±1888C; H NMR (CDCl3): d 9.20 (s,
1H, H2); 7.86 (m, 4H, 4HPhCF ); 7.40 (s, 1H, Harom); 7.20 (s,
3
1H, Harom); 4.08 (s, 3H, OCH3); 3.91 (s, 3H, OCH3); 19F
NMR (CDCl3): d 263; IR: n 1617, 1505, 1328, 1140,
1105, 847 cm21. Anal. Calcd for C17H13F3N2O2 (334.30):
C, 61.08; N, 8.38; H, 3.92. Found: C, 61.37; N, 8.12; H,
4.22.
1
(87%) of 17 as a yellow solid, mp 191±1928C; H NMR
(CDCl3): d 9.30 (s, 1H, H3); 8.18 (m, 1H, Harom); 7.97±7.59
(m, 8H, 8Harom); 7.23 (m, 1H, 1Harom); 13C NMR (CDCl3) d
123.29, 124.89, 126.34, 126.39, 127.42, 128.80, 129.05,
130.09, 130.71, 132.12, 134.88 (Ph and Ar), 144.72 (C-3);
19F NMR (CDCl3): d 263; IR: n 1324, 1120, 844,
701 cm21. Anal. Calcd for C19H11F3N2S (356.37): C,
64.04; N, 7.86; H, 3.11; S, 9.00. Found: C, 64.36; N, 7.57;
H, 3.11; S, 8.87.
6,7-Dimethoxy-4-(30-nitrophenyl)quinazoline (22). coupling
of 3-nitrophenylboronic acid (1.4 equiv.) with 2027 (450 mg,
2 mmol) according to the general procedure C (toluene,
tˆ24 h) gave after puri®cation by column chromatography
(silica gel, eluent: ethyl acetate/ethanol (9/1)) 535 mg (86%)
of 22 as a white solid, mp 234±2358C; 1H NMR (CDCl3): d
Another fraction gave 33 mg (13%) of starting material.
9.24 (s, 1H, H2); 8.70 (s, 1H, HPhNO ); 8.44 (d, Jˆ8.4 Hz, 1H,
2
HPhNO ); 8.17 (d, Jˆ7.8 Hz, 1H, HPhNO ); 7.79 (dd, Jˆ7.8
2
2
4-(40-Methoxyphenyl)-8-(40-tri¯uoromethylphenyl)cinno-
line (18). TBAF (1 M in THF, 1.7 equiv., 1 mL) and H2O
(1 mL) were added to 14 (260 mg, 0.58 mmol) dissolved in
10 mL of THF. The mixture was then gently re¯uxed for
24 h. The following treatments are similar to compound 16.
Puri®cation by column chromatography (silica gel, eluent:
petroleum ether/ethyl acetate (7/3)) afforded 145 mg (66%)
of 18 as a yellow solid, mp 206±2078C; 1H NMR (CDCl3):
d 9.32 (s, 1H, H3); 8.11 (dd, Jˆ7.6 and 2.2 Hz, 1H, H7);
7.94±7.77 (m, 6H, 6Harom); 7.56 (d, Jˆ8.7 Hz, 2H,
2HPhOCH ); 7.14 (d, Jˆ8.7 Hz, 2H, 2HPhOCH ); 3.94 (s, 3H,
and 8.4 Hz, 1H, HPhNO ); 7.44 (s, 1H, Harom); 7.22 (s, 1H,
2
Harom); 4.11 (s, 3H, OCH3); 3.93 (s, 3H, OCH3); IR: n 1534,
1504, 1349, 1238, 859, 690 cm21. Anal. Calcd for
C16H13N3O4 (311.30): C, 61.73; N, 13.50; H, 4.21. Found:
C, 61.86; N, 13.21; H, 4.40.
6,7-Dimethoxy-4-(40-methoxyphenyl)quinazoline (23).
Coupling of 4-methoxyphenylboronic acid (1.4 equiv.)
with 2027 (450 mg, 2 mmol) according to the general pro-
cedure C (toluene, tˆ38 h) gave after puri®cation by
column chromatography (silica gel, eluent: ethyl acetate)
533 mg (90%) of 23 as a pale yellow solid, mp 144±
3
3
OCH3); 13C NMR (CDCl3) d 55.56 (OCH3), 114.81, 125.74,
125.22, 125.40, 126.57, 130.902, 131.18, 131.44, 131.51,
134.87, 140.55, 142.00 (Ph and Ar), 145.01 (C-3), 148.18,
160.83 (Ph or Ar); 19F NMR (CDCl3): d 262.8; IR: n 1602,
1328, 1127, 1111, 1069, 841, 830, 787 cm21. Anal. Calcd
for C22H15F3N2O (380.37): C, 69.47; N, 7.36; H, 3.97.
Found: C, 69.69; N, 7.14; H, 4.06.
1
1458C; H NMR (CDCl3): d 9.12 (s, 1H, H2); 7.72 (d,
Jˆ8.4 Hz, 2H, 2HPhOCH ); 7.33, 7.32 (2£s, 2H, H5/8); 7.05
3
(d, Jˆ8.4 Hz, 2H, 2HPhOCH ); 4.03 (s, 3H, OCH3); 3.88, 3.87
3
(2£s, 6H, 2£OCH3); IR: n 1608, 1504, 1258, 1237, 1176,
1137, 1026, 860, 832 cm21. Anal. Calcd for C17H16N2O3
(296.33): C, 68.91; N, 9.45; H, 5.44. Found: C, 69.25; N,
9.11; H, 5.46.
Another fraction gave 89 mg (34%) of starting material.
6,7-Dimethoxy-8-iodo-4-(40-tri¯uoromethylphenyl)quin-
azoline (24). Metalation of 21 (100 mg, 0.30 mmol) according
4-(40-Methoxyphenyl)-8-(30-nitrophenyl)cinnoline (19).

5506
V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
to procedure A with n-BuLi 1.6 M (4 equiv., 0.75 mL),
DIPAH (4.1 equiv., 0.16 mL), t1ˆ1 h, followed by reaction
with iodine (2 equiv., 152 mg), t2ˆ2 h, gave after puri®-
cation by column chromatography (silica gel, eluent:
petroleum ether/ethyl acetate (6/4)) 91 mg (66%) of 24 as
quinazoline (28). Coupling of (2-thienyl)-trimethylstannane
(1.2 equiv.) with 24 (920 mg, 2 mmol) according to the
general procedure D (toluene, tˆ39 h) gave after puri®-
cation by column chromatography (silica gel, eluent: petro-
leum ether/ethyl acetate (8/2)) 725 mg (87%) of 28 as a
1
1
a pale yellow solid, mp 172±1738C; H NMR (CDCl3): d
yellow solid, mp 135±1368C; H NMR (CDCl3): d 9.32
(s, 1H, H2); 7.89 (m, 4H, 4HPhCF ); 7.80 (dd, Jˆ3.6 and
9.35 (s, 1H, H2); 7.87 (m, 4H, 4HPhCF ); 7.29 (s, 1H, H5);
3
3
3.92 (s, 3H, OCH3); 3.86 (s, 3H, OCH3); 19F NMR (CDCl3):
d 263; IR: n 2938, 1323, 1150, 800, 605, 559 cm21. Anal.
Calcd for C17H12F3IN2O2 (460.19): C, 44.37; N, 6.09; H,
2.63. Found: C, 44.21; N, 6.21; H, 2.67.
Jˆ1 Hz, 1H, H3 thienyl); 7.58 (dd, Jˆ5.2 and Jˆ1 Hz, 1H,
0
0
H5 thienyl); 7.28 (s, 1H, H5); 7.25 (dd, Jˆ5.2 and Jˆ3.6 Hz,
1H, H4 thienyl); 3.94 (s, 3H, OCH3); 3.87 (s, 3H, OCH3); 13
C
0
NMR (CDCl3) d 56.23, 61.06 (OCH3), 103.87, 120.93,
125.87, 125.92, 126.73, 127.91, 130.19, 130.95, 141.49,
146.68 (Ph and Ar), 153.05 (C-2), 153.82, 163.7 (Ph and
Ar); 19F NMR (CDCl3): d 263; IR: n 2944, 1467, 1327,
1167, 1121, 694 cm21. Anal. Calcd for C21H15F3N2O2S
(416.42): C, 60.57; N, 6.73; H, 3.63. Found: C, 60.84; N,
6.46; H, 4.02.
Another fraction gave 18 mg (18%) of starting material.
6,7-Dimethoxy-8-iodo-4-(40-methoxyphenyl)quinazoline
(25). Metalation of 23 (100 mg, 0.34 mmol) according to
procedure A with n-BuLi 1.6 M (4 equiv., 0.86 mL),
TMPH (4.1 equiv., 0.24 mL), t1ˆ1 h, followed by reaction
with iodine (2.5 equiv., 215 mg), t2ˆ2 h, gave after puri®-
cation by column chromatography (silica gel, eluent: petro-
leum ether/ethyl acetate (4/6)) 119 mg (84%) of 25 as a
6,7-Dimethoxy-4-(40-methoxyphenyl)-8-(40-tri¯uorometh-
ylphenyl)quinazoline (29). Coupling of 4-tri¯uoromethyl-
phenylboronic acid (1.4 equiv.) with 25 (844 mg, 2 mmol)
according to the general procedure C (toluene, tˆ52 h) gave
after puri®cation by column chromatography (silica gel,
eluent: petroleum ether/ethyl acetate (5/5)) 758 mg (86%)
of 29 as a beige solid, mp 161±1628C; 1H NMR (CDCl3): d
1
beige solid, mp 154±1558C; H NMR (CDCl3): d 9.30
(s, 1H, H2); 7.74 (d, Jˆ8.8 Hz, 2H, 2HPhOCH ); 7.45 (s,
3
1H, H5); 7.08 (d, Jˆ8.8 Hz, 2H, 2HPhOCH ); 4.02 (s, 3H,
3
OCH3); 3.91 (s, 6H, 2£OCH3); IR: n 1606, 1474, 1249,
1071, 1034, 798 cm21. Anal. Calcd for C17H15IN2O3
(422.22): C, 48.36; N, 6.63; H, 3.58. Found: C, 48.46; N,
6.53; H, 3.82.
9.18 (s, 1H, H2); 7.81 (d, Jˆ8.8 Hz, 2H, 2HPhOCH ); 7.79 (d,
3
Jˆ8.1 Hz, 2H, 2HPhCF ); 7.64 (d, Jˆ8.1 Hz, 2H, 2HPhCF );
3
3
7.55 (s, 1H, H5); 7.12 (d, Jˆ8.8 Hz, 2H, 2HPhOCH ); 3.97 (s,
3
3H, OCH3); 3.93 (s, 3H, OCH3); 3.74 (s, 3H, OCH3); 13C
NMR (CDCl3) d 55.87, 56.39, 61.64 (OCH3), 105.86,
114.63, 125.22, 125.27, 130.45, 131.62, 131.88, 138.14,
145.38 (Ph and Ar), 153.41 (C-2), 153.79, 161.52, 165.96
(Ph and Ar); 19F NMR (CDCl3): d 262.7; IR: n 1607, 1474,
1397, 1332, 1114 cm21. Anal. Calcd for C24H19F3N2O3
(440.42): C, 65.45; N, 6.36; H, 4.35. Found: C, 65.75; N,
6.06; H, 4.48.
6,7-Dimethoxy-8-(40-methoxyphenyl)-4-(40-tri¯uorometh-
ylphenyl)quinazoline (26). Coupling of 4-methoxyphenyl-
boronic acid (1.4 equiv.) with 24 (920 mg, 2 mmol)
according to the general procedure C (toluene, tˆ67 h)
gave after puri®cation by column chromatography (silica
gel, eluent: petroleum ether/ethyl acetate (6/4)) 793 mg
1
(90%) of 26 as a beige solid, mp 182±1838C; H NMR
(CDCl3): d 9.25 (s, 1H, H2); 7.91 (m, 4H, 4HPhCF ); 7.46
3
(d, Jˆ8.8 Hz, 2H, 2HPhOCH ); 7.32 (s, 1H, H5); 7.08 (d,
6,7-Dimethoxy-4-(40-methoxyphenyl)-8-(30-nitrophenyl)-
quinazoline (30). Coupling of 3-nitrophenylboronic acid
(1.4 equiv.) with 25 (844 mg, 2 mmol) according to the
general procedure C (DME, tˆ44 h) gave after puri®cation
by column chromatography (silica gel, eluent: dichloro-
methane/ethyl acetate (7/3)) 676 mg (81%) of 30 as a
3
Jˆ8.8 Hz, 2H, 2HPhOCH ); 3.94 (s, 3H, OCH3); 3.90 (s, 3H,
3
OCH3); 3.71 (s, 3H, OCH3); 13C NMR (CDCl3) d 55.88,
56.43, 61.75 (OCH3), 106.28, 114.67, 121.28, 123.05,
126.81, 129.071, 130.12, 131.64, 135.92, 137.94, 148.39
(Ph and Ar), 153.39 (C-2), 153.84, 161.58 (Ph and Ar);
19F NMR (CDCl3): d 263; IR: n 2939, 1465, 1323, 1244,
1159, 1121, 848 cm21. Anal. Calcd for C24H19F3N2O3
(440.42): C, 65.45; N, 6.36; H, 4.35. Found: C, 65.36; N,
6.43; H, 4.36.
1
beige solid, mp 229±2308C; H NMR (CDCl3): d 9.17 (s,
1H, H2); 8.42 (s, 1H, HPhNO ); 8.32 (d, Jˆ8.2 Hz, 1H,
2
HPhNO ); 7.86 (d, Jˆ7.7 Hz, 1H, HPhNO ); 7.80 (d, Jˆ
2
2
8.7 Hz, 2H, 2HPhOCH ); 7.69 (dd, Jˆ8.2 and 7.7 Hz, 1H,
3
HPhNO ); 7.57 (s, 1H, H5); 7.13 (d, Jˆ8.7 Hz, 2H, 2HPhOCH );
2
3
6,7-Dimethoxy-8-phenyl-4-(40-tri¯uoromethylphenyl)-
quinazoline (27). Coupling of phenylboronic acid
(1.4 equiv.) with 24 (920 mg, 2 mmol) according to the
general procedure C (toluene, tˆ44 h) gave after puri®-
cation by column chromatography (silica gel, eluent: petro-
leum ether/ethyl acetate (8/2)) 804 mg (98%) of 27 as a pale
3.98 (s, 3H, OCH3); 3.94 (s, 3H, OCH3); 3.78 (s, 3H, OCH3);
13C NMR (CDCl3) d 53.15, 56.36, 61.61 (OCH3), 95.61,
104.08, 108.87, 126.12, 128.23, 130.41, 131.24, 149.99
(Ph and Ar), 153.59 (C-2); IR: n 1607, 1528, 1475, 1407,
1348, 1251, 1175, 1036, 812 cm21. Anal. Calcd for
C23H19N3O5 (417.42): C, 66.18; N, 10.07; H, 4.59. Found:
C, 66.55; N, 9.72; H, 4.76.
1
brown solid, mp 167±1688C; H NMR (CDCl3): d 9.25 (s,
1H, H2); 7.91 (m, 4H, 4HPhCF ); 7.52 (m, 5H, 5HPh); 7.34 (s,
3
1H, H5); 3.95 (s, 3H, OCH3); 3.72 (s, 3H, OCH3); 19F NMR
(CDCl3): d 262.9; IR: n 2938, 1600, 1474, 1407, 1325,
1244, 1113, 852, 815, 753 cm21
.
Anal. Calcd for
Acknowledgements
C23H17F3N2O2 (410.39): C, 67.31; N, 6.83; H, 4.18.
Found: C, 67.08; N, 6.77; H, 4.19.
We thank Dr I. Ledoux (CNET Bagneux) for her collabora-
tion and the determination of the mb values by the Hyper-
Rayleigh Scattering (HRS) method.
6,7-Dimethoxy-8-(20-thienyl)-4-(40-tri¯uoromethylphenyl)-

V. Gautheron Chapoulaud et al. / Tetrahedron 56 (2000) 5499±5507
5507
15. Mitchell, M. B.; Wallbank, P. J. Tetrahedron Lett. 1991, 32,
2273.
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