Benzotriazole-Assisted Aromatic Ring Annulation: Efficient and General Syntheses of Polysubstituted Naphthalenes and Phenanthrenes

Article abstract of DOI:10.1021/jo961597x

(Benzotriazol-1-ylmethyl)benzenes and -naphthalenes 1a-f, easily accessible from benzyl bromides and benzotriazole, readily undergo lithiation and subsequent 1,4-addition to α,β-unsaturated aldehydes and ketones. Intramolecular cyclization of the products, induced by acetic acid-hydrobromic acid or polyphosphoric acid (PPA), followed by simultaneous dehydration and debenzotriazolylation furnishes a wide range of polysubstituted naphthalenes 7a-f and of phenanthrenes 9 and 11 in moderate to good yields in one-pot procedures. If compounds 1 are first lithiated and reacted with electrophiles, the resulting alkylation products undergo similar annulation reactions with α,β-unsaturated carbonyl compounds to provide the more highly substituted naphthalenes 6a,b and phenanthrenes 10a,b in moderate overall yields.

Full text of DOI:10.1021/jo961597x

J . Org. Chem. 1997, 62, 721-725
721
Ben zotr ia zole-Assisted Ar om a tic Rin g An n u la tion : Efficien t a n d
Gen er a l Syn th eses of P olysu bstitu ted Na p h th a len es a n d
P h en a n th r en es
Alan R. Katritzky,* Guifen Zhang, and Linghong Xie
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received August 19, 1996X
(Benzotriazol-1-ylmethyl)benzenes and -naphthalenes 1a -f, easily accessible from benzyl bromides
and benzotriazole, readily undergo lithiation and subsequent 1,4-addition to R,â-unsaturated
aldehydes and ketones. Intramolecular cyclization of the products, induced by acetic acid-
hydrobromic acid or polyphosphoric acid (PPA), followed by simultaneous dehydration and
debenzotriazolylation furnishes a wide range of polysubstituted naphthalenes 7a -f and of
phenanthrenes 9 and 11 in moderate to good yields in one-pot procedures. If compounds 1 are
first lithiated and reacted with electrophiles, the resulting alkylation products undergo similar
annulation reactions with R,â-unsaturated carbonyl compounds to provide the more highly
substituted naphthalenes 6a ,b and phenanthrenes 10a ,b in moderate overall yields.
In tr od u ction
CH(OR)2] with aromatic aldehydes followed by cyclization
with dilute sulfuric acid,2g,12 which are limited by the
availability of annulating reagents; (iv) other annulation
methods, which include an elegant tandem conjugate
addition-aldol reaction, followed by an acid-catalyzed
construction of the naphthalene ring,2e and an anionic
annulation via o-allylbenzamides.13
Highly substituted naphthalenes and phenanthrenes
are common features of numerous biologically significant
natural products and pharmaceuticals,1 and improved
methods for their construction are highly desired.2 The
most important reported annulation routes to naphtha-
lenes include the following: (i) Diels-Alder reactions of
benzynes,2d,f,3-5 o-quinodimethanes,2ah,6 isobenzofurans,7
and isoquinolinium salts;8 however, in many cases either
the diene or the dienophile must be symmetrical in order
to control the regiochemistry; (ii) Michael addition of
R-carbanions of benzene derivatives followed by intramo-
lecular cyclization with an ester group at the ortho
position,9-11 which is most useful for the preparation of
naphthols with electron-withdrawing substituents, es-
pecially COR and CO2R groups; (iii) condensations of
â-metallo derivatives of protected propanals [MCH2CH2-
The most important routes to phenanthrenes include
(i) Diels-Alder reactions of naphthynes,2i,k (ii) palladium-
catalyzed cyclocarbonylation of 3-naphthylallyl acetates,2l
and (iii) intramolecular C-C coupling of 2,2′-dialkox-
ystilbenes with low-valent titanium.2j All require the
synthesis of functionalized substrates to facilitate the
annulation step.
Benzotriazole-assisted syntheses of a wide range of
useful organic compounds have blossomed in our labora-
tory due to the unique properties of the benzotriazolyl
group as both a good anion-stabilizing group and a good
leaving group.14 Recently, we have demonstrated that
1-benzylbenzotriazoles 1 can undergo lithiation and the
resulting anions react with aldehydes and ketones fol-
lowed by ZnBr2-assisted rearrangement to furnish one-
carbon chain-extended or ring-expanded R-aryl alkyl
ketones.15 We now report that 1-benzylbenzotriazoles
and 1-(naphthylmethyl)benzotriazoles 1 can function as
1,3-dipole synthons in Michael addition-cyclization routes
to provide a wide range of polysubstituted naphthalenes
(6 and 7) and phenanthrenes (9-11).
X Abstract published in Advance ACS Abstracts, J anuary 1, 1997.
(1) For examples, see: (a) Medarde, M.; Ramos, A. C.; Caballero,
E.; Lo´pez, J . L.; de Clairac, R. P.-L.; Feliciano, A. S. Tetrahedron Lett.
1996, 37, 2663. (b) Ward, R. S. Nat. Prod. Rep. 1995, 12, 183. (c) Perri,
S. T.; Moore, H. W. Tetrahedron Lett. 1987, 28, 4507. (d) Shibuya, M.;
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T. F., III; Rapoport, H. J . Org. Chem. 1983, 48, 4222. (f) Bremmer, M.
L.; Khatri, N. A.; Weinreb, S. M. J . Org. Chem. 1983, 48, 3661.
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P.; Keay, B. A. J . Org. Chem. 1996, 61, 2885. (b) Nishino, H.; Kajikawa,
S.; Hamada, Y.; Kurosawa, K. Tetrahedron Lett. 1995, 36, 5753. (c)
Shishido, K.; Yamashita, A.; Hiroya, K.; Fukumoto, K.; Kametani, T.
Tetrahedron Lett. 1989, 30, 111. (d) Matsumoto, T.; Hosoya, T.;
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T.; Seki, M.; Takahashi, M.; Ohmizu, H.; Iwasaki, T. Tetrahedron Lett.
1990, 31, 5487. (f) Reinecke, M. G.; Mazza, D. D. J . Org. Chem. 1989,
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Nakatsuka, M.; Saegusa, T. J . Am. Chem. Soc. 1982, 104, 7609. (i)
Este´vez, J . C.; Este´vez, R. J .; Castedo, L. Tetrahedron Lett. 1992, 33,
6883. (j) Banerji, A.; Nayak, S. K. J . Chem. Soc., Chem. Commun. 1991,
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Iwasaki, M.; Matsuzaka, H.; Hiroe, Y.; Ishii, Y.; Koyasu, Y.; Hidai, M.
Chem. Lett. 1988, 1159.
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S. J . Org. Chem. 1983, 48, 3439.
Resu lts a n d Discu ssion
P r ep a r a t ion of 1-Ben zylb en zot r ia zoles a n d 1-
(Naph th ylm eth yl)ben zotr iazoles 1 an d in Situ P r ep-
a r a tion a n d Rea ction s w ith r,â-Un sa tu r a ted Ca r -
bon yl Com p ou n d s of Th eir Lith io Der iva tives. 1-(4-
Methylbenzyl)benzotriazole (1a ),16 1-benzylbenzotriazole
(12) Loozen, H. J . J . J . Org. Chem. 1975, 40, 520.
(13) Sibi, M. P.; Dankwardt, J . W.; Snieckus, V. J . Org. Chem. 1986,
51, 271.
(14) For reviews, see: (a) Katritzky, A. R.; Rachwal, S.; Hitchings,
G. J . Tetrahedron 1991, 47, 2683. (b) Katritzky, A. R.; Yang, Z.; Cundy,
D. J . Aldrichim. Acta 1994, 27, 31. (c) Katritzky, A. R.; Lan, X. Chem.
Soc. Rev. 1994, 363. (d) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis
1994, 445.
(10) Broom, N. J . P.; Sammes, P. G. J . Chem. Soc., Chem. Commun.
1978, 162.
(11) Hauser, F. M.; Rhee, R. P. J . Org. Chem. 1978, 43, 178.
(15) Katritzky, A. R.; Xie, L.; Toader, D.; Serdyuk, L. J . Am. Chem.
Soc. 1995, 117, 12015.
(16) Gibson, M. S. J . Chem. Soc. 1956, 1076.
S0022-3263(96)01597-6 CCC: $14.00 © 1997 American Chemical Society

722 J . Org. Chem., Vol. 62, No. 3, 1997
Katritzky et al.
Sch em e 1
Sch em e 2
(1b),16 and 1-(4-methoxybenzyl)benzotriazole (1c)17 were
synthesized according to previously reported procedures.
1-(3-Methoxybenzyl)benzotriazole (1d ), 1-(naphth-1-yl-
methyl)benzotriazole (1e), and 1-(naphth-2-ylmethyl)-
benzotriazole (1f) were prepared in good yields from the
reaction of the corresponding benzyl and naphthylmethyl
halides with benzotriazole (Scheme 1). All of these
benzotriazole derivatives can be easily prepared on a
large scale.
Due to the electron-withdrawing ability of the benzo-
triazolyl group, compounds 1 can be easily lithiated.
Accordingly, lithio derivatives of 1a -f were prepared in
situ as deep green solutions in THF under argon by
stirring compounds 1 with n-butyllithium at -78 °C for
ca. 30 min, which readily underwent 1,4-addition with a
variety of R,â-unsaturated aldehydes and ketones. As
an example, treatment of the lithio derivative of 1a with
chalcone at -78 °C for 2 h and then 20 °C overnight
provided the expected 1,4-addition product 4a in 62%
yield (Scheme 2), accompanied by the formation of the
corresponding 1,2-addition product (25%). Both the 1,4-
addition product 4a and the 1,2-addition product, 1,3-
diphenyl-3-hydroxy-4-(benzotriazol-1-yl)-4-(4-methylphe-
nyl)butene-1, were isolated and characterized.
Syn th esis of P olysu bstitu ted Na p h th a len es 6 a n d
7. For the preparation of naphthalenes, it is not neces-
sary to separate the intermediates 4, and the transfor-
mation can be accomplished in one pot. Accordingly, the
intermediates 4 thus produced were shown in each case
to be capable of in situ cyclization assisted by acetic acid
and hydrobromic acid (for 7a -d ) or polyphosphoric acid
(for 7e and 7f) to provide a wide variety of polysubsti-
tuted naphthalenes 7 regiospecifically in moderate to
good yields. The reason for the use of PPA instead of
acetic acid and hydrobromic acid in the cases of 7e and
7f is to avoid the demethylation of the methyl ether
moiety present in the molecules by hydrobromic acid. The
formation of naphthalenes 7 is envisaged to proceed via
Michael addition of the anions of 1 to R,â-unsaturated
carbonyl compounds to form intermediates 2, which are
then protonated to the ketones 4. Acid-promoted cycliza-
tion of 4 followed by concurrent dehydration and deben-
zotriazolylation afforded the desired products 7.
Significantly, additional substituents can be readily
introduced into the 4-positions of the products (Scheme
2). Thus, as examples, the lithio derivative of 1a was
first reacted with alkyl halides. The intermediates 3 thus
produced, without separation, were treated with butyl-
lithium followed by R,â-unsaturated carbonyl compounds.
The resulting addition products upon exposure to acetic
acid and hydrobromic acid cyclized and aromatized to
naphthalenes 6a and 6b in 40% and 33% overall yields
starting from 1a .
When (benzotriazol-1-ylmethyl)benzenes with para-
electron-donating substituents such as 1a and 1c are
used as substrates, two possible cyclization pathways
exist. As exemplified by the reaction of 1c with chalcone
(Scheme 3), the ring closure of the resulting ketone could
have occurred directly at the 2-position to give naphtha-
lene 7e or first at the more reactive 1-position to give
the corresponding spiro intermediate cation 8, followed
by the migration of either the a or b bond to give two
regioisomers 7e and 7f. However, the single isomer 7e
was obtained. The other expected regioisomer 7f was not
detected, indicating that the direct C2 ring closure might
be operative under the present reaction conditions.
However, while we view the spiro intermediate 8 as
unlikely, it cannot be ruled out as an intermediate to 7e
from the available information. Discrimination between
structures 7e and 7f was accomplished by the successful
preparation of 7f from the reaction of 1-(3-methoxyben-
zyl)benzotriazole (1d ) with chalcone (Scheme 3). In this
case, the methoxy group caused the 2-position to be more
reactive than the 1-position, leading unambiguously to
the directly cyclized product 7f.
(17) Katritzky, A. R.; Lan, X.; Lam, J . N. Chem. Ber. 1991, 124, 1819.

Benzotriazole-Assisted Aromatic Ring Annulation
J . Org. Chem., Vol. 62, No. 3, 1997 723
Sch em e 3
Sch em e 5
Substituted phenanthrenes can also be prepared from
2-(benzotriazol-1-ylmethyl)naphthalene (1f) as exempli-
fied by the annulation of 1f with 4-phenyl-3-buten-2-one
(Scheme 5). However, in this case, cyclization could occur
at both 1- and 3-positions, leading to a mixture of two
possible products 1-methyl-3-phenylphenanthrene (11)
and 1-methyl-3-phenylanthracene (12) with phenan-
threne 11 largely predominant. Compounds 11 and 12
were separated in 50% and 10% yields, respectively, and
identified by their NMR spectra and elemental analyses.
A 1H doublet at 8.9 ppm (5-proton) in the 1H NMR
spectrum of compound 11 is characteristic of the phenan-
threne system.
Con clu sion
The aromatic ring annulation of (benzotriazol-1-ylm-
ethyl)benzenes and (benzotriazol-1-ylmethyl)naphtha-
lenes 1 with R,â-unsaturated carbonyl compounds via
Michael addition-acidic cyclization sequences thus pre-
sents a general, simple and efficient protocol for the
construction of polysubstituted naphthalenes and phenan-
threnes. An attractive feature of this methodology is that
by appropriate choice of R,â-unsaturated aldehydes and
ketones, as well as benzyl halides, it makes readily
available a wide range of polysubstituted naphthalenes
and phenanthrenes. Naphthalenes (6a ,b and 7a -f) and
phenanthrenes (9, 10a ,b, and 11) prepared in the present
work are novel except 7a and 7f. Compounds 7a and 7f
were prepared previously via the acidic rearrangement
of the suitably substituted 4H-pyran derivatives,18 which
themselves were available only by multistep synthesis.
Sch em e 4
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined with
a hot-stage apparatus and are uncorrected. NMR spectra were
taken in CDCl3 with tetramethylsilane as the internal stan-
dard for 1H (300 MHz) or solvent as the internal standard for
13C (75 MHz). Tetrahydrofuran was distilled under nitrogen
immediately prior to use from sodium/benzophenone. All
reactions with air-sensitive compounds were carried out under
an argon atmosphere. Column chromatography was conducted
with silica gel 230-400 mesh. 1-(4-Methylbenzyl)benzotria-
zole (1a ),16 1-benzylbenzotriazole (1b),16 and 1-(4-methoxyben-
zyl)benzotriazole (1c)17 were prepared according to previously
reported procedures.
P r ep a r a tion of 1-Ben zylben zotr ia zole 1d a n d 1-(Na p h -
th ylm eth yl)ben zotr ia zoles 1e a n d 1f. Gen er a l P r oce-
d u r e. To a solution of an appropriate benzyl chloride or
naphthylmethyl chloride (50 mmol) in toluene (100 mL) was
added benzotriazole (55 mmol). The mixture was refluxed for
48 h and then washed with sodium hydroxide (2 N, 60 mL) to
Syn th esis of P olysu bstitu ted P h en an th r en es. Fol-
lowing a similar protocol, polysubstituted phenanthrenes
can be readily accessed by the annulation of (benzotria-
zol-1-ylmethyl)naphthalenes with R,â-unsaturated alde-
hydes and ketones. Accordingly, as an example, reaction
of the anion of 1e with 4-phenyl-3-buten-2-one, followed
by HOAc-HBr-induced cyclization and subsequent aro-
matization, furnished disubstituted phenanthrene 9 in
41% yield (Scheme 4). If 1e is first lithiated and alkyl-
ated, the alkylation products can undergo similar annu-
lation reactions with R,â-unsaturated carbonyl com-
pounds to afford trisubstituted phenanthrenes 10a and
10b in ca. 40% overall yields starting from 1e.
(18) Dimroth, K.; Kroke, H.; Wolf, K. Ann. Chem. 1964, 678, 202.

724 J . Org. Chem., Vol. 62, No. 3, 1997
Katritzky et al.
remove the excess benzotriazole. To the organic layer was
added hydrochloric acid (25%) until no product remained in
the organic layer based on TLC. The aqueous layer was
neutralized with NaOH (10 N) until pH ≈ 5. The solid was
filtered and dissolved in CH2Cl2 (60 mL). The solution was
washed with water (50 mL) and dried over MgSO4. Removal
of the solvent gave pure compound 1.
acid (30 mL) and hydrobromic acid (48% in water, 30 mL) were
added. The mixture was refluxed under argon overnight. On
cooling, the mixture was extracted with CH2Cl2 (4 × 50 mL).
The extract was washed subsequently with NaOH (2 N, 60 mL)
and H2O (60 mL) and dried over MgSO4 (for 7a -d , 9, 11 and
12); (ii) PPA (15 g) was added. The mixture was heated at 70
°C overnight and poured into ice-water (30 mL). The mixture
then was extracted with CHCl3 (4 × 40 mL). The combined
organic layer was washed subsequently with H2O (60 mL),
NaOH (2 N, 60 mL), and H2O (60 mL) and dried over MgSO4
(for 7e and 7f). After the solvent was evaporated, the residue
was purified by column chromatography to give the pure
product.
1,7-Dim eth yl-3-p h en yln a p h th a len e (7a ). Hexane was
used as the eluent to give the pure compound: yield 54%; mp
40-41 °C; 1H NMR δ 7.84 (s, 1H), 7.78-7.74 (m, 2H), 7.69 (d,
J ) 7.1 Hz, 2H), 7.55 (s, 1H), 7.47-7.42 (m, 2H), 7.35-7.30
(m, 2H), 2.70 (s, 3H), 2.54 (s, 3H); 13C NMR δ 141.3, 137.3,
135.4, 134.1, 132.1, 132.0, 128.7 (2C), 128.6, 128.2, 127.3 (2C),
1-(3-Meth oxyben zyl)ben zotr ia zole (1d ): yield 81%; mp
1
54-55 °C; H NMR δ 8.06 (d, J ) 8.1 Hz, 1H), 7.41-7.22 (m,
4H), 6.88-6.80 (m, 3H), 5.81 (s, 2H), 3.74 (s, 3H); 13C NMR δ
160.0, 146.3, 136.2, 132.8, 130.0, 127.3, 123.8, 120.0, 119.7,
113.8, 113.2, 109.7, 55.2, 52.1. Anal. Calcd for C14H13N3O:
C, 70.28; H, 5.48; N, 17.56. Found: C, 70.65; H, 5.51; N, 17.65.
1-(Na p h th -1-ylm eth yl)ben zotr ia zole (1e): yield 80%; mp
1
149-150 °C; H NMR δ 8.19 (d, J ) 8.1 Hz, 1H), 8.05-8.02
(m, 1H), 7.87-7.82 (m, 2H), 7.54-7.46 (m, 2H), 7.43-7.38 (m,
1H), 7.30-7.25 (m, 4H), 6.28 (s, 2H); 13C NMR δ 146.3, 133.8,
133.1, 131.1, 129.9, 129.5, 128.8, 127.3, 127.0, 126.7, 126.2,
125.1, 123.8, 122.9, 120.0, 110.0, 50.8. Anal. Calcd for
C17H13N3: C, 78.74; H, 5.05; N, 16.20. Found: C, 78.51; H,
5.03; N, 16.25.
127.1, 126.4, 124.0, 123.1, 22.1, 19.5. Anal. Calcd for C18H16
C, 93.06; H, 6.94. Found: C, 92.84; H, 7.09.
:
1,3-Dip h en yl-7-m eth yln a p h th a len e (7b). Hexane was
used as the eluent to give the pure compound: yield 49%; mp
100-101 °C; 1H NMR δ 7.97 (s, 1H), 7.78 (d, J ) 8.2 Hz, 1H),
7.67-7.65 (m, 4H), 7.53-7.36 (m, 7H), 7.31-7.25 (m, 2H), 2.38
(s, 3H); 13C NMR δ 141.0 (2C), 140.1, 137.1, 135.8, 132.4, 131.0,
130.1 (2C), 128.8 (2C), 128.5 (2C), 128.3 (2C), 127.3 (2C), 127.2
(2C), 126.8, 125.2, 124.7, 21.9. Anal. Calcd for C23H18: C,
93.84; H, 6.16. Found: C, 94.31; H, 6.36.
1-Meth yl-3-p h en yln a p h th a len e (7c). Hexane was used
as the eluent to give the pure compound: yield 41%; mp 62-
63 °C (lit.18 mp 67-68 °C); 1H NMR δ 8.00-7.97 (m, 1H), 7.89-
7.86 (m, 2H), 7.71 (d, J ) 7.1 Hz, 2H), 7.58 (s, 1H), 7.51-7.43
(m, 4H), 7.38-7.32 (m, 1H), 2.73 (s, 3H); 13C NMR δ 141.2,
138.2, 134.8, 133.9, 131.8, 128.8 (3C), 127.4 (2C), 127.2, 126.3,
126.0, 125.8, 124.2, 124.0, 19.5.
2-Eth yl-3-p h en yl-6-m eth yln a p h th a len e (7d ). Hexane
was used as the eluent to give the pure compound: yield 55%;
mp 52-53 °C; 1H NMR δ 7.72 (d, J ) 8.5 Hz, 1H), 7.69 (s,
1H), 7.58 (s, 1H), 7.55 (s, 1H), 7.43-7.36 (m, 5H), 7.29 (d, J )
8.5 Hz, 1H), 2.74 (q, J ) 7.5 Hz, 2H), 2.49 (s, 3H), 1.13 (t, J )
8.5 Hz, 3H); 13C NMR δ 142.0, 140.7, 139.1, 134.9, 132.0, 131.3,
129.4 (2C), 128.1, 128.0 (3C), 126.9, 126.8, 126.5, 126.2, 26.5,
21.7, 15.2. Anal. Calcd for C19H18: C, 92.64; H, 7.36. Found:
C, 92.30; H, 7.52.
1,3-Dip h en yl-7-m eth oxyn a p h th a len e (7e). Hexane:m-
ethylene chloride (6:1) was used as the eluent to give the pure
compound: yield 75%; mp 117-118 °C (lit.18 mp 117-118 °C);
1H NMR δ 7.98 (s, 1H), 7.84 (d, J ) 9.0 Hz, 1H), 7.73-7.67
(m, 3H), 7.57-7.41 (m, 7H), 7.36-7.31 (m, 1H), 7.23-7.16 (m,
2H), 3.75 (s, 3H); 13C NMR δ 157.9, 141.0 (2C), 139.6, 135.9,
132.0, 130.1, 129.9 (2C), 129.7, 128.8 (2C), 128.4 (2C), 127.3
(2C), 127.2 (2C), 127.1, 125.2, 118.7, 104.5, 55.2. Anal. Calcd
for C23H18O: C, 89.00; H, 5.85. Found: C, 89.08; H, 5.87.
1,3-Dip h en yl-6-m eth oxyn a p h th a len e (7f). Hexane:m-
ethylene chloride (6:1) was used as the eluent to give the pure
compound: yield 69%; oil; 1H NMR δ 7.78 (s, 1H), 7.66 (d, J )
9.3 Hz, 1H), 7.56 (d, J ) 7.1 Hz, 2H), 7.41-7.14 (m, 9H), 7.06
(d, J ) 2.5 Hz, 1H), 6.92 (dd, J ) 9.3, 2.5 Hz, 1H), 3.71 (s,
3H); 13C NMR δ 157.8, 141.0, 140.8 (2C), 138.6, 135.5, 130.0
(2C), 128.8 (2C), 128.3 (2C), 127.5, 127.4 (2C), 127.3 (2C), 126.3,
124.5, 124.3, 118.7, 106.4, 55.2. Anal. Calcd for C23H18O: C,
89.00; H, 5.85. Found: C, 89.20; H, 5.91.
1-(Na p h th -2-ylm eth yl)ben zotr ia zole (1f): yield 75%; mp
150-151 °C; H NMR δ 8.06 (d, J ) 6.9 Hz, 1H), 7.76-7.72
(m, 4H), 7.47-7.43 (m, 2H), 7.33-7.28 (m, 4H), 5.94 (s, 2H);
13C NMR δ 146.2, 133.0, 132.9, 132.7, 132.0, 128.9, 127.7,
127.6, 127.3, 126.6, 126.5, 126.4, 124.9, 123.8, 119.9, 109.7,
52.3. Anal. Calcd for C17H13N3: C, 78.74; H, 5.05; N, 16.20.
Found: C, 78.36; H, 5.10; N, 16.32.
1
Rea ction of 1-(4-Meth ylben zyl)ben zotr ia zole (1a ) w ith
Ch a lcon e. P r ep a r a tion of 1,3-Dip h en yl-4-ben zotr ia zol-
1-yl-4-(4-m eth ylp h en yl)bu ta n -1-on e (4a ) a n d 1,3-Dip h e-
n yl-3-h yd r oxy-4-b en zot r ia zol-1-yl-4-(4-m et h ylp h en yl)-
bu ten e-1. To a solution of 1-(4-methylbenzyl)benzotriazole
(1a ) (1.12 g, 5 mmol) in THF (80 mL) at -78 °C under argon
was added n-BuLi (2.2 mL, 2.5 M in hexane, 5.5 mmol). After
1 h, chalcone (1.1 g, 5.5 mmol) in THF (10 mL) was added.
The reaction mixture was stirred at -78 °C for an additional
2 h and then allowed to warm to room temperature overnight.
Water (60 mL) and Et2O (80 mL) were added to the mixture,
and the organic layer was separated. The aqueous layer was
extracted with Et2O (2×50 mL) and the combined organic
extracts were dried over MgSO4. After the solvent was
removed, the crude mixture was separated by column chro-
matography (ethyl acetate:hexanes ) 1:5) to give pure 4a and
1,3-diphenyl-3-hydroxy-4-benzotriazol-1-yl-4-(4-methylphenyl)-
butene-1.
1,3-Dip h en yl-4-b en zot r ia zol-1-yl-4-(4-m et h ylp h en yl)-
bu ta n -1-on e (4a ): yield 62%; mp 187-188 °C; 1H NMR δ 8.02
(d, J ) 8.3 Hz, 1H), 7.74 (d, J ) 7.1 Hz, 2H), 7.53-7.40 (m,
3H), 7.38-7.28 (m, 3H), 7.25-7.03 (m, 7H), 6.94 (d, J ) 7.9
Hz, 2H), 6.19 (d, J ) 10.1 Hz, 1H), 4.91 (dt, J ) 10.1 and 3.5
Hz, 1H), 3.61 (dd, J ) 16.8 and 10.1 Hz, 1H), 3.31 (dd, J )
16.8 and 3.5 Hz, 1H), 2.17 (s, 3H); 13C NMR δ 197.9, 145.9,
139.9, 137.8, 136.8, 134.1, 133.3, 132.9, 129.1 (2C), 128.4 (4C),
128.3 (2C), 128.0 (2C), 127.6 (2C), 127.4, 127.0, 124.0, 119.9,
109.8, 67.3, 46.0, 41.6, 21.0. Anal. Calcd for C29H25N3O: C,
80.72; H, 5.84; N, 9.74. Found: C, 80.66; H, 5.89; N, 9.78.
1,3-Dip h en yl-3-h yd r oxy-4-ben zotr ia zol-1-yl-4-(4-m eth -
1
ylp h en yl)bu ten e-1: yield 25%; mp 229-230 °C; H NMR δ
7.92 (d, J ) 8.5 Hz, 1H), 7.54 (d, J ) 7.4 Hz, 2H), 7.42-7.37
(m, 4H), 7.29-7.04 (m, 11H), 6.47 (s, 2H), 6.33 (s, 1H), 5.57
(s, 1H), 2.27 (s, 3H); 13C NMR δ 144.7, 143.7, 138.3, 136.7,
133.3, 131.9, 131.7, 130.8, 129.0 (2C), 128.8 (2C), 128.4 (2C),
128.3 (2C), 127.8, 127.6, 127.1, 126.6 (2C), 124.9 (2C), 124.2,
120.0, 109.2, 80.2, 69.3, 21.1. Anal. Calcd for C29H25N3O: C,
80.72; H, 5.84; N, 9.74. Found: C, 80.49; H, 5.56; N, 9.41.
Gen er a l P r oced u r e for th e P r ep a r a tion of Na p h th a -
len es 7a -f, P h en a n th r en es 9 a n d 11, a n d An th r a cen e 12.
To a solution of an appropriate 1-benzylbenzotriazole or
1-(naphthylmethyl)benzotriazole 1 (5 mmol) in THF (80 mL)
at -78 °C under argon was added n-BuLi (2.2 mL, 2.5 M in
hexane, 5.5 mmol). After 1 h, the appropriate R,â-unsaturated
aldehyde or ketone (5.5 mmol) in THF (10 mL) was added.
The reaction mixture was stirred at -78 °C for an additional
2 h and then allowed to warm to room temperature overnight.
After the THF was distilled off under argon, (i) glacial acetic
1-Meth yl-3-p h en ylp h en a n th r en e (9). Hexane was used
as the eluent to give the pure compound: yield 41%; mp 124-
125 °C; 1H NMR δ 8.69 (s, 1H), 8.67 (d, J ) 9.4 Hz, 1H), 7.83-
7.77 (m, 2H), 7.72-7.70 (m, 2H), 7.66-7.58 (m, 2H), 7.55-
7.49 (m, 2H), 7.47-7.41 (m, 2H), 7.35-7.30 (m, 1H), 2.67 (s,
3H); 13C NMR δ 141.6, 138.7, 135.2, 131.9, 130.7, 130.6, 129.9,
128.8 (2C), 128.5, 127.5 (2C), 127.2, 127.1, 126.7, 126.5, 126.4,
122.9, 122.6, 119.2, 20.0. Anal. Calcd for C21H16: C, 93.99;
H, 6.01. Found: C, 93.83; H, 6.05.
2-P h en yl-4-m eth ylp h en a n th r en e (11). Hexane was used
as the eluent to give the pure compound: yield 50%; mp 143-
1
144 °C; H NMR δ 8.91 (d, J ) 7.9 Hz, 1H), 7.97 (d, J ) 2.2
Hz, 1H), 7.91 (dd, J ) 7.9 and 2.2 Hz, 1H), 7.78-7.73 (m, 5H),

Benzotriazole-Assisted Aromatic Ring Annulation
J . Org. Chem., Vol. 62, No. 3, 1997 725
7.65-7.56 (m, 2H), 7.52-7.47 (m, 2H), 7.41-7.21 (m, 1H), 3.20
(s, 3H); 13C NMR δ 140.5, 138.2, 136.1, 134.2, 133.5, 131.5,
130.3, 129.2, 128.9 (2C), 128.8, 128.2, 127.5, 127.4, 127.3 (3C),
125.8, 125.7, 125.4, 27.5. Anal. Calcd for C21H16: C, 93.99;
H, 6.01. Found: C, 93.95; H, 6.03.
1H), 7.53-7.34 (m, 12H), 2.64 (s, 3H), 2.44 (s, 3H); 13C NMR
δ 142.6, 141.0, 137.8, 137.4, 135.2, 131.5, 131.0, 130.2 (2C),
130.1, 129.9 (2C), 129.5, 128.3, 128.2 (2C), 128.0 (2C), 127.0,
126.7, 125.5, 124.7, 21.7, 16.4. Anal. Calcd for C24H20: C,
93.46; H, 6.54. Found: C, 93.05; H, 6.78.
1-Meth yl-3-p h en yla n th r a cen e (12). Hexane was used as
the eluent to give the pure compound: yield 10%; mp 102-
103 °C; 1H NMR δ 7.77 (d, J ) 9.0 Hz, 1H), 7.67 (s, 2H), 7.65
(d, J ) 8.6 Hz, 2H), 7.64-7.34 (m, 6H), 7.28 (s, 1H), 7.07 (t, J
) 7.8 Hz, 1H), 2.52 (s, 3H); 13C NMR δ 145.3, 140.4, 135.2,
133.8, 133.1, 132.5, 130.4, 129.0 (2C), 128.9 (2C), 128.3, 128.1,
127.9, 127.6, 127.2, 127.0, 126.4, 125.5, 124.8, 21.1; HRMS
calcd for C21H16 268.1252 (M+), found 268.1249.
1-Eth yl-2,4-d ip h en yl-6-m eth yln a p h th a len e (6b): yield
33%; oil; 1H NMR δ 8.08 (d, J ) 8.6 Hz, 1H), 7.73 (s, 1H), 7.52-
7.33 (m, 11H), 7.27 (s, 1H), 3.04 (q, J ) 7.5 Hz, 2H), 2.43 (s,
3H), 1.28 (t, J ) 7.5 Hz, 3H); 13C NMR δ 142.8, 141.0, 137.5,
137.3, 136.6, 135.0, 131.6, 130.3, 130.2 (2C), 129.6, 129.4 (2C),
128.2 (3C), 128.0 (2C), 127.0, 126.7, 125.7, 124.8, 22.6, 21.7,
16.0; HRMS calcd for C25H22: 322.1721 (M+), found 322.1735.
1,4-Dim eth yl-2-p h en ylp h en a n th r en e (10a ): yield 37%;
Gen er a l P r oced u r e for th e P r ep a r a tion of Na p h th a -
len es 6a ,b a n d P h en a n th r en es 10a ,b. To a solution of an
appropriate 1-benzylbenzotriazole or 1-(naphthylmethyl)ben-
zotriazole 1 (5 mmol) in THF (80 mL) at -78 °C under argon
was added n-BuLi (2.1 mL, 2.5 M in hexane, 5.5 mmol). After
1 h, methyl iodide (for 6a and 10a ,b) or ethyl iodide (for 6b)
(6.5 mmol) was added, and the mixture was stirred at -78 °C
for 2 h. The THF and an excess amount of MeI or EtI were
evaporated under vaccum, and the residue was again dissolved
in THF (80 mL). To the solution at -78 °C under argon was
added n-BuLi (2.2 mL, 2.5 M in hexane, 5.5 mmol). After 1 h,
the appropriate R,â-unsaturated ketone in THF (10 mL) was
added. The reaction mixture was stirred at -78 °C for an
additional 2 h and then allowed to warm to room temperature
overnight. After the THF was distilled off under argon, glacial
acetic acid (30 mL) and hydrobromic acid (48% in water, 30
mL) were added. The mixture was refluxed under argon
overnight. On cooling, the mixture was extracted with CH2-
Cl2 (4 × 50 mL). The extract was washed subsequently with
NaOH (2 N, 60 mL) and H2O (60 mL) and dried over MgSO4.
After the solvent was evaporated, the residue was purified by
column chromatography using hexane as the eluent to give
the pure product.
1
mp 114-115 °C; H NMR δ 8.78 (d, J ) 6.3 Hz, 1H), 7.94-
7.89 (m, 2H), 7.74 (d, J ) 8.9 Hz, 1H), 7.58-7.55 (m, 2H),
7.49-7.36 (m, 6H), 2.88 (s, 3H), 2.74 (s, 3H); 13C NMR δ 143.3,
142.4, 133.5, 131.9, 131.7, 131.6, 131.4, 130.4, 130.0 (2C),
129.7, 128.6, 128.3, 128.2 (2C), 126.9, 126.8, 125.9, 124.8,
123.0, 24.7, 20.0. Anal. Calcd for C22H18: C, 93.58; H, 6.42.
Found: C, 93.65; H, 6.46.
1-Meth yl-2,4-d ip h en ylp h en a n th r en e (10b): yield 40%;
mp 126-127 °C; 1H NMR δ 8.82-8.79 (m, 1H), 7.89-7.85 (m,
1H), 7.80 (d, J ) 9.1 Hz, 1H), 7.62-7.37 (m, 14H), 2.96 (s,
3H); 13C NMR δ 143.0, 142.3, 141.1, 138.4, 133.5, 132.0, 131.9,
131.3, 130.4 (3C), 130.0 (2C), 129.5, 128.6, 128.2 (5C), 127.2,
127.0, 126.8, 126.1, 125.0, 124.9, 24.8. Anal. Calcd for
C
27H20: C, 94.15; H, 5.85. Found: C, 94.17; H, 5.93.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 6b and 12 (4 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
1,6-Dim eth yl-2,4-d ip h en yln a p h th a len e (6a ): yield 46%;
1
mp 140-141 °C; H NMR δ 8.06 (d, J ) 8.7 Hz, 1H), 7.73 (s,
J O961597X