Synthesis of Azobenzenes from Quinone Acetals and Arylhydrazines

Article abstract of DOI:10.1021/jo0498011

Direct reaction between quinone bisacetals and arylhydrazines gives azobenzenes. The presence of catalytic amounts of cerium ammonium nitrate strongly accelerates the reaction. When the bisacetal has a substituent at the 2,5-cyclohexadiene framework, only one regioisomer is formed. The method represents a simple, mild, and novel synthetic access to differently substituted azocompounds in high to excellent yield.

Full text of DOI:10.1021/jo0498011

Syn th esis of Azoben zen es fr om Qu in on e Aceta ls a n d
Ar ylh yd r a zin es
M. Carmen Carre n˜ o,* Gerardo Fern a´ ndez Mudarra, Est ´ı baliz Merino, and Mar ´ı a Ribagorda
Departamento de Qu ´ı mica Org a´ nica (C-I), Facultad de Ciencias, Universidad Aut o´ noma de Madrid,
Cantoblanco, 28049 Madrid, Spain
carmen.carrenno@uam.es
Received February 4, 2004
Direct reaction between quinone bisacetals and arylhydrazines gives azobenzenes. The presence
of catalytic amounts of cerium ammonium nitrate strongly accelerates the reaction. When the
bisacetal has a substituent at the 2,5-cyclohexadiene framework, only one regioisomer is formed.
The method represents a simple, mild, and novel synthetic access to differently substituted
azocompounds in high to excellent yield.
In tr od u ction
scope of reactions employing diazonium salts presents
characteristic problems. Phenols and anilines are the
usual activated aromatic compounds used for the cou-
pling of diazonium salts. The method is highly pH
dependent, and the substitution partner of the resulting
azoarene is limited. Moreover, handling diazonium salts,
especially when dried, is highly risky. In some cases, this
leads to the generation of diazonium salts in situ, thus
water-sensitive compounds cannot be employed. Not-
withstanding this risk, coupling of isolated diazonium
Azobenzenes have found important applications as
1
dyes. In recent years, an enormous interest has emerged
in their light-driven reversible cis-trans isomerization.
The photoisomerization of the azo linkage has found
2
important applications in either biologic or physical-
chemical3 systems, such as liquid crystals
4,5
or their
6
a
6,7
dopant agents, molecular switches, photoresponsive
8
9
10
gels, ion shuttles, crown ethers, or calixarenes and
different molecular devices.11 Coupling of diazonium salts
with activated aromatic compounds is the most common
14
salts with organometallics or coupling in the presence
15
of Cu salts have also been reported to synthesize
1
2,13
procedure for synthesizing azobenzenes.
However, the
azoarenes. The Mills coupling of anilines with nitroso
derivatives16 also allows the synthesis of asymmetrically
(1) (a) Zollinger. H. Diazo Chemistry I. Aromatic and Heteroaromatic
substituted azo derivatives, and the Wallach rearrange-
Compounds; VCH: New York, 1994. (b) Zollinger, H. Color Chemis-
try: Synthesis, Properties and Applications of Organic Dyes and
Pigments; VCH: Weinheim, Germany, 1987. (c) Gordon, P. F.; Gregory,
P. Organic Chemistry in Colour; Springer: New York, 1983. (d) The
Chemistry of Synthetic Dyes; Venkataraman, K., Ed.; Academic
Press: New York, 1970; Vols. 1-7.
ment of azoxy compounds1
6b,17
has been shown to be
general enough to synthesize azo phenols. Albeit less
general, other procedures such as the reduction of nitro
compounds,18 the dehydrogenation of arylhydrazines,
19
(2) Behrendt, R.; Renner, C.; Schenk, M.; Wang, F.; Wachtreitl, J .;
20
and the rearrangement of aryl triazenes also allow the
Oesterhelt, D.; Moroder. L. Angew. Chem., Int. Ed. 1999, 38, 2771 and
references therein.
synthesis of azo compounds. Recently, a two-step syn-
thesis based on the Pd-catalyzed reaction of N-Boc aryl
hydrazines with aryl halides followed by the oxidation
(3) Delaire, J . A.; Nakatani. K. Chem. Rev. 2000, 100, 1817-1845.
(4) Ikeda, T.; Tsutsumi, O. Science 1995, 268, 1873-1875.
(5) Sasaki, T.; Ikeda, T.; Ikimura, K. J . Am. Chem. Soc. 1994, 116,
6
25-628.
(6) (a) Pieraccini, S.; Masiero, S.; Spada, G. P.; Gottarelli, G. Chem.
(14) (a) Barbero, M.; Degani, I.; Dighera, S.; Fochi, R.; Perracino,
P. Synthesis 1998, 1235-1237 and references therein. (b) Neumann,
W. P.; Wicence, C. Chem. Ber. 1991, 2297-2301.
Commun. 2003, 598-599. (b) Liang, X.; Asanuma, H.; Komiyama, M.
J . Am. Chem. Soc. 2002, 124, 1877-1883.
(
7) For comprehensive reviews see: (a) Chem Rev. 2000, 100, 1685-
(15) Cohen, T.; Lewarchik, R. J .; Tarino, J . Z. J . Am. Chem. Soc.
1974, 96, 7753-7760.
1
890 (monographic issue). (b) Molecular Switches; Feringa, B. L., Ed.;
Wiley-VCH: Weinheim, Germany, 2001. (c) Willner, I.; Willner, B. In
Bioorganic Photochemistry: Biological Applications of Photochemical
Switches; Morrison, H., Ed.; Wiley: New York, 1993; Vol. 2, pp 1-110.
(16) See for instance: (a) Davey, M. H.; Lee, V. Y.; Miller, R. D.;
Marks, T. J . J . Org. Chem. 1999, 64, 4976-4979. (b) Boyer, J . H. In
The Chemistry of Nitro and Nitroso Groups, Part 2; Feuer, H., Ed.;
Interscience: New York, 1961; pp 278-283. (c) Curtin, D. Y.; Tveten,
J . L. J . Org. Chem. 1961, 26, 1764-1768.
(17) Cox, R. A.; Buncel, E. In The Chemistry of Hydrazo, Azo, and
Azoxy Groups; Patai, S., Ed.; Wiley: Chichester, UK, 1975; pp 775-
859.
(18) For recent examples see: (a) Gowda, S.; Gowda, D. C. Synthesis
2002, 4, 460. (b) Dey Laskar, D.; Projapati, D.; Sandhu, J . S. J . Chem.
Soc., Perkin Trans. 1 2000, 67. (c) Wen-hao, W.; Tomohiro, T.; Kodaka,
M.; Okumo, H. J . Org. Chem. 2000, 65, 8979.
(19) Newbold, B. T. In The Chemistry of Hydrazo, Azo, and Azoxy
Groups. Part 1; Patai, S., Ed.; Wiley: Chichester, UK, 1975; pp 543-
564.
(8) Murukami, K.; Aoki, M.; Nishi, T.; Ikeda, A.; Shinkai, S. J . Chem.
Soc., Chem. Commun. 1991, 1715-1718.
9) Murakami, H.; Kawabuchi, A.; Kotoo, K.; Kutinake, M.; Na-
kashima, N. J . Am. Chem. Soc. 1997, 119, 7605-7606.
10) Shinkai, S.; Nakaji, T.; Nishida, Y.; Ogawa, T.; Manabe, O. J .
Am. Chem. Soc. 1980, 102, 5860-5865.
11) Balzani, V.; Scandola, F. In Supramolecular Photochemistry;
Ellis Horwood: Chichester, UK, 1991.
12) (a) Hegarty, A. F. In The Chemistry of Diazonium and Diazo
Groups, Part 2; Patai, S., Ed.; Wiley: New York, 1978; pp 545-551.
b) Sch u¨ ndeh u¨ tte, K. H. In Houben-Weyl, Methoden der organischen
Chemie; Stroh, R., Ed.; Thieme: New York, 1965; Bd X/3, S. 226ff.
13) General review of the synthesis of azobenzenes: Szelle, I.;
Zollinger, H. Top. Curr. Chem. 1983, 112, 1-66.
(
(
(
(
(
(
(20) Shine, H. J . In Aromatic Rearrangements; Elsevier: New York,
1967.
1
0.1021/jo0498011 CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/20/2004
J . Org. Chem. 2004, 69, 3413-3416
3413

Carre n˜ o et al.
of the resulting hydrazines has been reported.21 Although
noteworthy progress have been made in the development
of complementary strategies for the synthesis of such
compounds, there remains a need for additional ap-
proaches. In connection with a program directed at the
synthetic explotation of quinone derivatives, we recently
found an efficient synthesis of N-arylquinone imine
acetals based on the reaction of quinone bisacetals with
anilines in the absence of any added catalyst.22 The
available evidence suggested that the reaction was
catalyzed by an acidic radical cation formed in situ by
the one-electron oxidation of the arylamines.23 To check
the behavior of arylhydrazines in a similar process, we
examined their reaction with quinone bisacetals taking
into account the possible formation of radical cations from
hydrazines.24 Although quinones have been extensively
TABLE 1. Rea ction s of Bisa ceta l 2 w ith Ar ylh yd r a zin es
1
entry
1
R1 R2 R3 R4 R5 solvent time
3
yield (%)
1
2
3
4
5
6
7
8
9
1a NO2
1b NO2
H
H
H
H
H
H
F
F
H
H
NO2
H
NO2
H
H
H
F
CF3
H
H
H
H
H
H
F
F
F
H
H
H
H
H
H
H
H
F
F
H
H
MeCN 5 min 3a 99
MeCN 19 h
MeCN 19 h
MeCN 3 h
CHCl3 18 h
CHCl3 48 h
CHCl3 18 h
CHCl3 24 h
MeCN 27 h
MeCN 7 d
3b 71
3c 66
3d 83
3e 69
3f 78
3g 77
3h 72
a
1c
H
1d Br
1e CF3
1f
1g
1h
1i
F
F
F
H
H
b
b
3i 25 (80)
3j 43 (79)
2
5
employed in synthesis, the only reports related to
similar reactions on benzoquinone derivatives we have
found are related to the synthesis of mono- and dini-
trobenzeneazo-4-hydroxy benzenes26 and other azophe-
10 1j
OMe
a
A 90:10 mixture of 3c and 4,4-dimethoxy-2,5-cyclohexadienone
was formed (ratio determined by H NMR). Reaction carried
437
1
b
out in the presence of CAN, time 18 h.
nols from p-benzoquinone and phenylhydrazines in the
absence of catalysts,27 or in the presence of H
SO
.
28
We
plexes33 or as umpolung reagents for quinones,34 but to
2
4
now report a new, experimentally simple, and high-
yielding procedure to synthesize azobenzenes by direct
reaction of quinone bisacetals with arylhydrazines and
show that it is general enough for the preparation of
asymmetrically substituted derivatives. The bis- and
monoacetals of quinones are frequently used as synthetic
our knowledge, this is their first application as starting
materials for azobenzenes.
Resu lts a n d Discu ssion
The starting bis-dimethyl acetal of p-benzoquinone 2
is commercially available whereas 2-p-tolylsulfinyl-1,1,4,4-
tetramethoxy-2,5-cyclohexadiene 5 and the 2-methoxy
substituted analogue 7 were readily accessible by anodic
equivalents to overcome reactivity and/or selectivity
problems2
9,30
that emerge from quinones themselves.
Such derivatives allow the regioselective preparation of
3
5
2
9b
oxidation of 2-p-tolylsulfinyl-1,4-dimethoxybenzene and
aromatic systems. Monoacetals are of special value as
regiospecific quinone equivalents for 1,4-conjugate addi-
1
,2,4-trimethoxybenzene,36 respectively, using KOH as
tions31 and Diels-Alder and Heck reactions. The
30
32
electrolyte in a methanolic solution.
In the endeavor to search for a simple synthetic
procedure, we checked the direct reaction of arylhydra-
zines 1 with quinone bisacetal 2 in different solvents
bisacetals have been utilized to produce carbene com-
(21) (a) Kim, K.-Y.; Shin, J .-T.; Lee, K.-S.; Cho, C.-G. Tetrahedron
(
CH
results are shown in Table 1. Thus, 2,4-dinitrophenyl-
hydrazine 1a reacted with 2 in CH CN in a few minutes
3 2 2 3
CN, CH Cl , CHCl ) at room temperature. The best
Lett. 2004, 45, 117-120. (b) Lim, Y.-K.; Lee, K.-S.; Cho, C.-G. Org.
Lett. 2003, 5, 979-982.
(22) Carre n˜ o, M. C.; Cuerva, J . M.; Ribagorda, M.; Echavarren, A.
3
M. Angew. Chem., Int. Ed. 1999, 38, 1449-1452.
23) Schmittel, M.; Burghart, A. Angew. Chem., Int. Ed. Engl. 1997,
6, 2551-2589.
24) (a) Nelsen, S.; Pladziewic, J . R. Acc. Chem. Res. 2002, 35, 247-
54. (b) Nelsen, S. S.; Ismagilov, R. F.; Gentile, K. E.; Powell, D. R. J .
to give azocompound 3a , which was isolated pure from
the solution by filtration (entry 1, 99% yield). o- and
p-nitrophenylhydrazines 1b and 1c reacted more slowly
than 1a , but led to azobenzenes 3b and 3c in good yields
(entries 2 and 3). Bromo derivative 1d afforded azoben-
zene 3d after 3 h in 83% yield (entry 4). With fluoro-
substituted arylhydrazines 1e-h (entries 5-8), best
yields were reached in chlorinated solvents which allowed
the isolation of azobenzenes 3e-h in 69-78% yield. In
contrast, unsubstituted phenylhydrazine 1i and arylhy-
drazine 1j, bearing an electron-donating p-OMe group at
the aromatic ring, reacted with 2 much more slowly and
in lower yields (entries 9 and 10).
(
3
(
2
Am. Chem. Soc. 1999, 121, 7108-7114.
(25) (a) The Chemistry of Quinonoid Compounds; Rappoport, Z.,
Patai, S., Eds.; J ohn Wiley and Sons: New York, 1988; Vol. 2. (b)
Thomson, R. H. Naturally Occurring Quinones, Recent Advances;
Chapman and Hall: New York, 1987.
(
26) Borsche, W. J ustus Liebigs Ann. Chem. 1908, 357, 171-191.
(27) (a) Smith, L. I.; Irwin, W. B.; Guss, C. O. J . Am. Chem. Soc.
1
941, 63, 1036-1043. (b) J oshi, S. S.; Deorha, D. S.; J oshi, P. C. J .
Indian Chem. Soc. 1961, 38, 395-396.
28) (a) Naemura, K.; Wakebe, T.; Hirose, K.; Tobe, Y. Tetrahe-
(
dron: Asymmetry 1997, 8, 2585-2595. (b) Naemura, K.; Nishikawa,
Y.; Fuji, J .; Hirose, K.; Tobe, Y. Tetrahedron: Asymmetry 1997, 8, 873-
8
82. (c) Naemura, K.; Takeuchi, S.; Hirose, K.; Tobe, Y.; Kaneda, T.;
Sakata, Y. J . Chem. Soc., Perkin Trans. 1 1995, 213-219. (d) Naemura,
K.; Takeuchi, S.; Asada, M.; Ueno, K.; Hirose, K.; Tobe, Y.; Kaneda,
T.; Sakata, Y. J . Chem. Soc., Perkin Trans. 1 1995, 1429-1435. (e)
Kaneda, T.; Ishizaki, Y.; Misumi, S. J . Am. Chem. Soc. 1988, 110,
3 3
We showed that the presence of Et N in the CH CN
solution of 1a and 2 inhibited the reaction. This evidence
reinforced our initial assumption on the existence of an
acidic species triggering the reaction. The active species
2
970-2972. (f) Fierz-David, H. E.; Blangey, L.; Streit, H. Helv. Chim.
Acta 1946, 29, 1718-1764.
29) (a) Swenton, J . S. In The Chemistry of Quinonoid Compounds;
(
Rappoport, Z., Patai, S., Eds.; J ohn Wiley: New York, 1988; Vol. 2,
(33) D o¨ tz, K. H.; Popall, M.; Mueller, G.; Ackermann, K. J . Orga-
nomet. Chem. 1990, 383, 93-111.
Part 2, pp 899-962. (b) Swenton, J . S. Acc. Chem. Res. 1983, 16, 74-
8
1.
(
(
(34) Swenton, J . S.; Anderson, D. K.; J ackson, D. K.; Narasimhan,
L. J . Org. Chem. 1981, 46, 4825-4826.
30) Breuning, M.; Corey, E. J . Org. Lett. 2001, 3, 1559-1562.
31) Imbos, R.; Brilman, M. H.; Pinesche, M.; Feringa, B. L. Org.
(35) Carre n˜ o, M. C.; Garc ´ı a Ruano, J . L.; Mata, J . M.; Urbano, A.
Tetrahedron 1991, 47, 605-614.
(36) Henton, D. R.; Anderson, K.; Manning, M. J .; Swenton, J . S. J .
Org. Chem. 1980, 45, 3422-3433.
Lett. 1999, 1, 623-625.
(
32) Imbos, R.; Minnaard, A. J .; Feringa, B. L. J . Am. Chem. Soc.
2
002, 124, 184-185.
3
414 J . Org. Chem., Vol. 69, No. 10, 2004

Synthesis of Azobenzenes
SCHEME 1 a
TABLE 2. Rea ction s of Bisa ceta l 5 a n d 7 w ith
Ar ylh yd r a zin es 1 in th e P r esen ce of CAN
entry acetal
1
R2 R3 R4 R5 R6 time 6/8 yield (%)
1
5
5
5
5
7
7
7
7
7
7
7
1a NO2
H
H
F
NO2
H
F
CF3
NO2
H
H
F
CF3
CF3
H
H
F
F
H
H
F
30 min 6a 85 (77)a
1f
1g
1h
F
F
F
1 h
2 h
6f 98 (45)a
a
3
4
5
6
7
8
9
0
1
6g 60 (59)
F
F
F
2 h
1 h
1 h
1 h
5 min
5 min
1 h
6h 98 (98)a
8a 99
8e 96
8f 99
8g 98
8h 98
8k 88
8i 85
1a NO2
1e CF3
H
H
H
F
F
H
H
H
H
F
F
F
H
H
H
F
F
H
H
1f
1g
1h
1k
1i
F
F
F
H
H
1
1
H
H
a
Reagents and conditions: (i) CAN (3% mol), CH3CN, rt.
1 h
a
Experiments carried out in the absence of CAN, reaction times
increased the yields for 6a ,f-h (Table 2, entries 1-4).
Reactions of 1,1,2,4,4-pentamethoxy-2,5-cyclohexadi-
enone 7 with arylhydrazines bearing electron-withdraw-
ing substituents 1a ,e-h ,k occurred in excellent yields
(Table 2, entries 5-10). Even phenylhydrazine 1i (Table
2, entry 11) afforded 8i in 85% yield. Asymmetrically
substituted bisacetals 5 and 7 reacted exclusively by the
less hindered acetal group to give azo derivatives bearing
a C-3 substituent at the 4-methoxy-substituted aromatic
moiety.
ranged from 3 to 4 days.
could be a radical cation resulting from one-electron
oxidation of 1a by air. The higher acidity of the radical
cation resulting from hydrazines bearing electron-
withdrawing substituents38 is in accordance with the
best results achieved with 1a -h . Such an acidic
species must catalyze the condensation of the hydra-
zine with one of the acetal groups of 2 forming an
intermediate hydrazone,39 which evolve into the azocom-
pound by MeOH elimination. Following this reasoning,
we carried out the reaction of 2 with phenylhydrazines
i and 1j in the presence of a one-electron oxidant such
as (NH [Ce(NO ] (CAN) and observed a remarkable
increase of the reaction rate, being 3i and 3j obtained in
8 h in 80% and 79% yield, respectively (Table 1, entries
and 10, footnote b).
To extend this excellent procedure, we have examined
the reaction of some arylhydrazines with other quinone
derivatives. We have achieved the synthesis of azophenol
12 in 88% isolated yield by reacting p-benzoquinone 9
with 4-trifluoromethyl-2,3,5,6-tetrafluorophenylhydra-
zine 1h in acetonitrile solution in the presence of CAN
(3 mol %). Amino-substituted azobenzene 13 and the (p-
tolylsulfinyl)methyl-substituted analogue 14 were also
synthesized in excellent yields by reaction of perfluori-
1
4
)
2
3 6
)
1
9
On the other hand, no reaction was observed with
4
1
alkylhydrazines such as benzyl and N,N-dimethylhydra-
zine. These observations also pointed to the existence of
an intermediate radical cation catalyzing the reaction,40
easily formed from aromatic hydrazines.
The excellent yields and shorter reaction times reached
in the presence of CAN were shown to be general for
other quinone bisacetals. Thus, 2-p-tolylsulfinyl-substi-
tuted bisacetal 5 also reacted with arylhydrazines 1a ,f-h
to yield azobenzenes 6a ,f-h (Table 2, entries 1-4,
footnote a). An essential point to reach good yields in
nated p-tolylhydrazine 1h with quinone monoacetal 10
and p-quinol derivative 114
2,43
(Scheme 1). These results
showed that our protocol can be successfully applied to
1,4-benzoquinones and derivatives with doubly conju-
gated carbonyl groups. In addition, starting from [(S)R]-
11, optically pure [(S)R]-14 {[R]20
D
3
+132 (c 1, CHCl )}
was formed, showing that the configurational integrity
of the sulfoxide withstood the reaction conditions.
In summary, we have reported a new synthesis of
azobenzenes bearing a variety of substituents on the
aromatic fragments from quinone bisacetals and aryl
hydrazines. The presence of catalytic amounts of CAN
significantly increases the reaction rates and improves
the yields when the arylhydrazines bear electron-donat-
ing substituents. Taking into account that quinone bisac-
etals are easily obtained by anodic oxidation of 1,4-
dimethoxybenzenes, this method opens a direct and
simple access to a wide range of substituted azobenzenes
under very mild conditions. The reaction was extended
to 4,4-disubstituted-2,5-cyclohexadienones and p-benzo-
3
these experiments was the use of dry CH CN to avoid
partial transformation of 5 into 3-p-tolylsulfinyl-4,4-
dimethoxy-2,5-cyclohexadien-1-one.35 Again, catalytic
amounts of CAN decreased the reaction times and
(
37) 4,4-Dimethoxy-2,5-cyclohexadienone 4: Henton, D. R.; Chenard,
B. L.; Swenton, J . S. J . Chem. Soc., Chem. Commun. 1979, 326-327.
38) Zhang, X.-M.; Bordwell, F. G.; Bares, J . E.; Cheng, J . P.; Petrie,
B. C. J . Org. Chem. 1993, 58, 3051-3059.
39) Although not isolated, the intermediate formation of an hydra-
(
(
zone had been proposed to explain the replacement of phenolic OH
groups by azoaryl substituents in two steps promoted by thallium or
lead acetates and followed by acid-catalyzed reaction with arylhydra-
zines: (a) Taylor, E. C.; J agdmann, G. E.; McKillop, A. J . Org. Chem.
(41) Taylor, R. J . K.; Alcaraz, L.; Kapfer-Eyer, I.; Macdonald, G.;
Wei, X.; Lewis, N. Synthesis 1998, 5, 775-790.
(42) Compound 14 is also available from the dimethyl acetal of the
p-quinol 11.
1
978, 43, 4385-8. (b) Von Hecker, E.; Lattrell, R. J ustus Liebigs Ann.
Chem. 1963, 662, 48-66.
40) CAN could also act as a Lewis acid, but the easy reaction
(
occurring from 2,4-dinitrophenylhydrazine in the absence of CAN
pointed to a different active acidic species.
(43) Carre n˜ o, M. C.; P e´ rez Gonz a´ lez, M.; Fischer, J . Tetrahedron
Lett. 1995, 36, 4893-4896.
J . Org. Chem, Vol. 69, No. 10, 2004 3415

Carre n˜ o et al.
quinone, integrating interesting substituents to the
azobenzenes. Nevertheless, the use of bisacetals instead
of quinones themselves avoids the frequently observed
reduction to the hydroquinone systems. To our knowl-
edge, the present report is the first of such a mild, high-
yielding, and feasible synthesis of azocompounds from
commercially available or easily accessible materials.
were added 2,4-difluorophenylhydrazine 1f (1.0 mmol) and
1
4 2 3 6
6.7 mg (3% mol) of (NH ) [Ce(NO ) ]. The resulting mixture
was stirred at room temperature for 4 days. Water (10 mL)
was then added and the mixture was extracted with AcOEt
(
3 × 20 mL). The combined organic layers were dried over
MgSO , the solvent was removed in vacuo, and the crude
4
product was purified by column chromatography (AcOEt/
hexane 1:10) to give azocompound 6f as a brown oil (98% yield).
1
H NMR δ 8.58 (d, 1H, 7.96, J ) 2.4 Hz), 7.99 (dd, 1H, J ) 8.7
and 2.4 Hz), 7.62-7.60 (AA′, 2H, Tol), 7.21-7.19 (BB′, 2H, Tol),
7
Exp er im en ta l Section
.45 (ddd, 1H, J ) 9.1, 5.9, and 3.2 Hz), 7.14-7.08 (m, 2H),
Gen er a l P r oced u r e for th e Syn th esis of Azoben zen es
6.93 (d, 1H, J ) 8.9 Hz), 3.85 (s, 3H, OMe), 2.32 (s, 3H, Me).
13
(
Met h od A): Syn t h esis of 4′-Met h oxy-2-t r iflu or om et h -
yla zoben zen e (3e). To a solution of 3,3,6,6-tetramethoxy-1,4-
cyclohexadiene 2 (1.3 g, 6.5 mmol) in CH CN (10 mL), was
C NMR δ 158.7 (d, J ) 247 Hz), 158.0, 156.2 (dd, J ) 254
and 2.8 Hz), 147.1, 141.6, 141.5, 141.1 (dd, J ) 34.1 and 5.7
Hz), 134.9, 129.7 (2C), 127.5, 125.4 (2C), 120.0, 118.5 (dd, J )
25.6 and 8.5 Hz), 117.8 (dd, J ) 22.7 and 8.5 Hz),111.2, 104.0
(d, J ) 25.6 Hz), 56.1, 21.3. EM (m/z) 386 (28.5), 370 (100),
3
added 2-trifluoromethyphenylhydrazine 1e (6.5 mmol). The
resulting mixture was stirred at room temperature for 18 h,
then the solvent was removed and the crude mixture was
purified by column chromatography (AcOEt/hexane 1:40) to
279 (19), 257 (9), 229 (87), 139 (19), 113 (49), 63 (22). HRMS
+
(EI) calcd for C20
H
16
N
2
O
2
F
2
S (M ) 386.0888, found 386.0901.
1
give azobenzene 3e as an orange oil (69% yield). H NMR δ
7
7
1
1
1
2
.99-7.95 (AA′, 2H), 7.04-7.00 (XX′, 2H), 7.81 (dd, 2H, J )
.9 and 4.0 Hz), 7.63 (ddd, 1H, J ) 7.5 and 1.1 Hz), 7.5 (ddd,
Ack n ow led gm en t. This work was supported by the
Comunidad de Madrid (Grants 07N/0066/2001 and 07N/
1
3
H, J ) 7.5 and 1.2 Hz), 3.91 (s, 3H, OMe). C NMR δ 162.7,
49.7, 147.2, 132.5, 129.7, 128.0 (c, J ) 30.5 Hz), 125.5 (2C),
24.1 (c, J ) 274.7 Hz), 116.2, 114.3 (2C), 55.6. EM (m/z)
0
015/2002). M.R. thanks Comunidad Aut o´ noma de
Madrid for a postdoctoral grant and E.M. thanks the
MCYT for a predoctoral grant.
80(40), 135 (48), 121 (10), 107 (100), 92 (37), 77 (52), 64 (20).
+
HRMS (EI) calcd for C14
80.0823.
Gen er a l P r oced u r e for th e Syn th esis of Azoben zen es
H
11
N
2
OF
3
(M ) 280.0822, found
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
2
1
13
tails and spectral data ( H and C NMR) for compounds
e,f,h ,j, 6f-h , 8a ,h ,k , 12, 13, and 14. This material is
3
in th e P r esen ce of CAN (Meth od B): Syn th esis of 4′-
Meth oxy-3′-p-tolylsu lfin yl-2,5-d iflu or oa zoben zen e (6f).
available free of charge via the Internet at http://pubs.acs.org.
3
To a solution of the bisacetal 2 (1.0 mmol) in CH CN (2 mL)
J O0498011
3
416 J . Org. Chem., Vol. 69, No. 10, 2004