Novel heteroatom-substituted trityl radical analogues: Preparation and properties of diaryl(benzotriazol-2-yl)methyl radical dimers

Full text of DOI:10.1021/jo980618f

9992
J . Org. Chem. 1998, 63, 9992-9994
Novel Heter oa tom -Su bstitu ted Tr ityl
Ra d ica l An a logu es: P r ep a r a tion a n d
P r op er ties of
Dia r yl(ben zotr ia zol-2-yl)m eth yl Ra d ica l
Dim er s‡
Alan R. Katritzky,* Baozhen Yang, and
David P. M. Pleynet
F igu r e 1.
Center for Heterocyclic Compounds, Department of
Chemistry, University of Florida,
Sch em e 1
Gainesville, Florida 32611-7200
Received April 3, 1998
Since Gomberg’s discovery of the triphenylmethyl
radical at the beginning of this century,1a-c a wealth of
information has been amassed on the structure and
stability of these types of hydrocarbon radicals.2a-d It is
now widely accepted that triphenylmethyl radicals are
in equilibrium with their dimers3a,b which possess a
cyclohexadiene structure 1 as shown in Figure 1.
However, heteroarylmethyl radicals have received little
attention.4a,b Furthermore, to the best of our knowledge,
no account of a hydrocarbon radical of this type with the
central carbon atom directly attached to a heteroatom
had been published until our recent report5 which
described diaryl(benzotriazol-1-yl)methyl radicals and
their conversion into dimers accompanied with phenan-
thridines resulting from the opening of the five-mem-
bered ring of the benzotriazol-1-yl moiety. In our en-
deavor to eliminate the alternative ring-opening pathway
previously observed,5 we investigated the behavior of
diaryl(benzotriazol-2-yl)methyl radicals, believed to be
more stable due to the structure of the benzotriazol-2-yl
moiety.6 We now report the results of these studies.
P r ep a r a tion of Dia r yl(ben zotr ia zol-2-yl)m eth yl
Ra d ica ls a n d Dim er iza tion . The diaryl(benzotriazol-
2-yl)methanes 2a -i were obtained as previously re-
ported.7 The corresponding radicals were obtained from
diaryl(benzotriazol-2-yl)methanes 2a -i according to the
protocol previously described for diaryl(benzotriazol-1-
yl)methanes.5 In line with our previous results, applica-
tion of this treatment to substrates 2a -e led to the
‡ The products formed by the combination of these radicals and those
described in the present paper are described as “dimers” because they
are formed by dimerization and they are similar in structure to dimers
formed from trityl radicals. However, we emphasize that we have no
evidence that such dimerization are reversible.
(1) (a) Gomberg, M. J . Am. Chem. Soc. 1900, 22, 757. (b) Gomberg,
M. Ber. Dtsch. Chem. Ges. 1900, 33, 3150. (c) Gomberg, M. Chem. Rev.
1925, 1, 91.
(2) (a) Ballester, M. Pure Appl. Chem. 1967, 123 and references
therein. (b) Sabacky, M. J .; J ohnson, C. S., J r.; Smith, R. G.; Gutowsky,
H. S.; Martin, J . C. J . Am. Chem. Soc. 1967, 89, 2054. (c) Sholle, V.
D.; Rozantsev, E. G. Russ. Chem. Rev. (Engh. Transl.) 1973, 42, 1011
and references therein. (d) Carilla, J .; Fajar´ı, L.; J ulia´, L.; Riera, J .;
Viadel, L. Tetrahedron Lett. 1994, 35, 6529.
(3) (a) Wieland, H. Ber. Dtsch. Chem. Ges. 1909, 42, 3020. (b)
Lankamp, H.; Nauta, W. Th.; MacLean, C. Tetrahedron Lett. 1968,
249.
(4) (a) Mangini, A.; Pedulli, G. F.; Tiecco, M. Tetrahedron Lett. 1968,
4941. (b) Mangini, A.; Pedulli, G. F.; Tiecco, M. J . Heterocycl. Chem.
1969, 6, 271.
dimers 4, 5a , 5b, 5d , and 6 in fair-to-good yields (Tables
1 and 2). All of these dimers were formed from R,para-
dimerization, and as before,5 no R,R- or R,ortho-dimer-
ization products were observed. In the case of substrate
2c in which Ar1 and Ar2 were different and each had its
para-position unsubstituted, the dimerization process
intriguingly took place regioselectively at the 4-position
of the 2-methylphenyl group, giving rise to dimer 4.
Dimerizations occurred when one para-position was
substituted, as illustrated by the formation of dimers 5b
and 5d . When the respective para-positions of each aryl
group were substituted (substrates 2f-i), no R,R- or
R,ortho-dimerization occurred. Compound 2f gave 1,1-
(5) Katritzky, A. R.; Yang, B.; Dalal, N. S. J . Org. Chem. 1998, 63,
1467.
(6) Katritzky, A. R.; Rachwal, S.; Hitchings, G. J . Tetrahedron. 1991,
47, 2683.
(7) Katritzky, A. R.; Yang, B. J . Heterocycl. Chem. 1996, 33, 607.
10.1021/jo980618f CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/26/1998

Notes
J . Org. Chem., Vol. 63, No. 26, 1998 9993
Ta ble 1. NMR Da ta of Dim er s 4, 5a , 5b, 5d , a n d 6
13C NMR
benzotriazol-2-yl
C-4
compd
1H NMR
Ta
Qb
C-3a
C-5
others
5a
7.83-7.88 (m, 4H), 7.27-7.40 (m, 16H),
7.19-7.22 (m, 4H), 7.12-7.16 (m, 4H)
73.6 83.9 144.3, 143.5 118.7, 118.3 126.5, 126.4 142.6, 142.3, 137.9, 137.8, 130.7,
130.3, 128.7, 128.6, 128.5, 128.0,
127.6, 127.4
5b
4
7.83-7.88 (m, 4H), 7.25-7.38 (m, 12H),
7.02-7.21 (m, 10H), 2.33 (s. 3H),
2.32 (s, 3H)
73.5 83.8 144.3, 143.5 118.7, 118.3 126.3, 126.4 142.7, 142.5, 139.3, 138.4, 138.0,
137.8, 134.8, 130.6, 130.3,
130.2, 129.3, 128.7, 128.3,
127.9, 127.6, 127.2, 21.1, 21.0
7.84-7.89 (m, 4H), 7.55 (s, 1H),
7.04-7.38 (m, 20H), 6.75-6.78 (m, 1H),
2.25 (s, 3H), 1.44 (d, 3H, J ) 2.5 Hz)
70.6 83.8 144.3, 143.6 118.7, 118.4 126.3, 126.4 142.8, 142.7, 141.3, 139.5, 137.6,
136.6, 136.2, 132.1, 130.7,
130.6, 130.3, 130.2, 129.7,
128.7, 128.6, 128.5, 128.0,
127.7, 127.4, 127.3, 125.6,
21.5, 19.4
5d
6
7.80-7.86 (m, 4H), 7.23-7.36 (m, 15H),
7.06-7.18 (m, 8H)
72.9 83.3 144.4, 143.5 118.6, 118.3 126.6, 126.6 142.5, 141.9, 140.7, 137.8, 136.2,
134.6, 134.2, 131.9, 130.6,
130.1, 130.0, 128.9, 128.2,
127.8, 127.4
76.1 84.7 144.0, 143.8 118.8, 118.3 126.5, 126.2 143.4, 141.0, 140.9, 140.7, 140.5,
7.85-7.88 (m, 2H), 7.80-7.83 (m, 2H),
7.52 (d, 1H, J ) 7.0 Hz), 7.44 (d, 1H,
J ) 8.1 Hz), 7.14-7.38 (m, 12H),
139.9, 134.9, 134.3, 132.7,
131.6, 131.3, 130.9, 130.8,
130.7, 130.6, 129.4, 128.6,
128.2, 125.5, 34.3, 34.2,
32.6, 32.0
6.97-7.04 (m, 2H), 6.94 (s, 1H),
6.82 (d, 1 H, J ) 8.0 Hz), 6.71 (s, 1H),
6.14 (t, 2H, J ) 8.4 Hz), 2.65-3.25 (m, 8H)
a
b
Tertiary carbon. Quaternary carbon.
Ta ble 2. P r ep a r a tion of Dim er s 4, 5a , 5b, 5d , a n d 6
yield
(%)
mp
(°C)
CHN anal.
found (calcd)
HRMS M+
found (calcd)
compd
mol formula
4
5a
C
C
40H32N6
38H28N6
52
75
120-123
115-118
596.268 (596.269)
C: 80.52 (80.26)
H: 5.00 (4.96)
N: 14.56 (14.78)
C: 80.12 (80.51)
H: 5.60 (5.41)
N: 13.60 (14.08)
C: 71.60 (71.47)
H: 4.30 (4.26)
5b
5d
6
C
C
C
40H32N6
82
80
55
116-119
118-120
192-195
596.257 (596.269)
636.169 (636.160)
620.258 (620.269)
38H26Cl2N6
N: 12.62 (13.16)
42H32N6
di(4-dimethylaminophenyl)pentane (7f) by displacement
of the benzotriazolyl group (benzotriazole was also iso-
lated), assisted by the presence of the strongly electron-
donating dimethylamino groups. The corresponding
diaryl ketones 3g-i (in yields of 80-85%) probably
resulted from the oxidation of radical intermediates. It
is evident that substitution at one para-position does not
prevent the R,para-dimerization process, whereas sub-
stitution at both para-positions prohibits it. Our findings
are in agreement with previous reports.3b,5
P r oof of Str u ctu r e of Dim er s 4, 5a , 5b, 5d , a n d 6.
Products 4, 5a , 5b, 5d , and 6 were analyzed and
characterized by NMR (Table 1) and CHN analysis or
HRMS (Table 2). The NMR spectra clearly reveal that
the two different benzotriazol-2-yl groups are nonequiva-
lent. Thus, every dimer gives two sets of benzotriazol-
2-yl signals in its 13C NMR spectrum (Table 1). This is
illustrated with dimer 5a (Figure 2), for which all the
assignments were confirmed by 2D, APT spectra, and
NOE experiments.
The NMR data recorded for dimers 4, 5a , 5b, 5d , and
6 differ from those reported for a trityl dimer exhibiting
a cyclohexadiene structure8 and confirm the structure of
the given dimers. This structure, shown in Figure 2 for
dimer 5a , is similar to the one observed and previously
reported for dimers obtained from diaryl(benzotriazol-1-
yl)methyl radicals.5
F igu r e 2.
In the MS spectra of dimers 4, 5a , 5b, 5d , and 6, the
molecular ion and molecular fragments were observed
and the base peak was found at M+ - 118, accounting
for the easy loss of a benzotriazolyl group to relieve steric
strain as previously observed.5
The reaction mechanism for the formation of the
dimers 4, 5a , 5b, 5d , and 6 is similar to the one
previously reported for diaryl(benzotriazol-1-yl) meth-
anes,5 with the exception that no phenanthridine prod-
ucts due to the ring opening of the benzotriazolyl moiety
were detected. In the present report, dimers were
obtained in high yields, probably due to the greater
stability of the benzotriazol-2-yl structure, which is less
inclined to ring opening than the isomeric benzotriazol-
1-yl structure. For instance, compounds 2a and 2b
produced dimers in high yields (75% and 82%, respec-
(8) Neumann, W. P.; Penenory, A.; Stewen, U.; Lehnig, M. J . Am.
Chem. Soc. 1989, 111, 5845.

9994 J . Org. Chem., Vol. 63, No. 26, 1998
Notes
Sch em e 2
In conclusion, the dimers 4, 5a , 5b, 5d , and 6 of diaryl-
(benzotriazol-2-yl)methyl radicals were readily obtained
using the procedure described for the generation of
diaryl(benzotriazol-1-yl)methyl radicals. Owing to the
more stable nature of the benzotriazol-2-yl (i.e., less
susceptible to ring opening than the benzotriazol-1-yl
moiety), dimers were obtained in fair-to-good yields
without any other side product. The dimeric structure
was proven to be different from that of trityl radical
dimers (by NMR). Further heteroaryl substituted trityl
radicals have been prepared and studied and are the
subject of a future paper.
Exp er im en ta l Section
P r ep a r a tion of Dim er s 4, 5a , 5b, 5d , a n d 6 (Gen er a l
P r oced u r e). To a solution of diaryl(benzotriazol-2-yl)methane
(2 mmol) in dried THF (20 mL) was added n-BuLi (1.1 mL, 2 M
solution in hexane, 2.2 mmol) at -78 °C under nitrogen. The
reaction mixture was stirred at -78 °C for 10 min, and iodine
(254 mg, 1 mmol) solution in THF (5 mL) was added. After 20
min of stirring at -78 °C, water (5 mL) was added to quench
the reaction. The mixture was allowed to warm to room
temperature, washed with sodium bisulfate solution (2 × 20 mL),
and extracted with ethyl acetate (3 × 20 mL). The combined
organic extracts were dried over MgSO4. After removal of the
solvent under vacuum, the residue was purified by column
chromatography (see Tables 1 and 2).
tively), whereas their counterparts containing a benzo-
triazol-1-yl group gave dimers in lower yields (44% and
59%, respectively).
Rea ctivity of th e Dim er s 4, 5a , 5b, 5d , a n d 6.
Treatment of dimer 5a with hydrochloric acid in meth-
ylene chloride at room temperature for 4 h gave the
hydroxyl derivative 8a in which one benzotriazol-2-yl
group was lost (Scheme 2), as evidenced by 1H NMR. The
integration of the low field signal (7.82-7.86 ppm)
revealed two protons instead of the four in the case of
5a , and a new single signal appeared at 3.14 ppm,
accounting for the hydroxyl group. The 13C NMR spec-
trum of 8a also confirmed that there was only one
benzotriazol-2-yl group present.
P r ep a r a tion of 4-Dip h en ylh yd r oxym eth yl-r-[p h en yl-
(ben zotr ia zol-2-yl)] Tolu en e (8a ). A mixture of dimer 6a
(0.564 g, 1 mmol), methylene chloride (10 mL), and concentrated
hydrochloric acid (2 mL) was stirred at room temperature for 4
h. The mixture was neutralized by an aqueous solution of NaOH
(2 N, 2 × 10 mL), washed with water, extracted with ethyl
acetate (3 × 10 mL), and dried over MgSO4. After removal of
the solvent under vacuum, the residue was purified by column
chromatography to give 8a (0.420 g, 90%): mp 87-89 °C; 1H
NMR (CDCl3) δ 7.82-7.86 (m, 2H), 7.20-7.35 (m, 22H), 3.14 (s,
1H); 13C NMR δ 147.0, 146.6, 144.2, 137.9, 137.1, 128.6, 128.4,
128.3, 128.2, 127.9, 127.8, 127.2, 126.4, 118.3, 81.7, 73.7. Anal.
Calcd for C32H25N3O: C, 82.20; H, 5.39; N, 8.99. Found: C,
81.83; H, 5.58; N, 8.62.
Upon treatment with LDA at -78 °C, substrate 5a
gave product 9a (98%) after losing one of the benzotriazol-
2-yl groups (Scheme 2). Compound 9a is red due to the
1
highly conjugated system. The H NMR and 13C NMR
P r ep a r a tion of 1-Dip h en ylm eth ylen e-4-[p h en yl(ben zo-
tr ia zol-2-yl)m eth ylen e]-2,5-cycloh exa d ien e (9a ). To a solu-
tion of 5a (0.564 g, 1 mmol) in dried THF (30 mL) was added
LDA (0.72 mL, 1.5 M in hexane, 1.1 mmol) at -78 °C under
nitrogen. The reaction mixture was stirred for 10 min and
turned red. After the mixture warmed to 0 °C, water (2 mL)
was added to quench the reaction. The reaction mixture was
extracted with ethyl acetate (2 × 20 mL). The combined organic
extracts were dried over MgSO4, and the solvent was removed
under vacuum to give product 9a as a red solid in a yield of
98% (0.440 g): mp 120-122 °C; 1H NMR δ 6.42 (dd, 1H, J )
10.1, 1.4 Hz), 6.79 (dd, 1H, J ) 10.0, 1.3 Hz), 6.85 (d, 1H, J )
1.3 Hz), 6.87 (d, 1H, J ) 1.8 Hz), 7.10-7.31 (m, 17H), 7.79-
7.82 (m, 2H); 13C NMR δ 145.0, 144.6, 141.3, 141.2, 135.7, 132.9,
131.9, 131.4, 131.3, 131.2, 129.8, 128.9, 128.5, 128.1, 128.0, 127.0,
125.8, 125.0, 118.2. Anal. Calcd for C32H23N3: C, 85.50; H, 5.16;
N, 9.35. Found: C, 85.24; H, 5.49; N, 9.55.
spectra of 9a suggest that the structure of 9a possesses
a cyclohexadiene structure analogous to that previously
encountered with the trityl radical dimer.3b Compound
9a was also obtained by heating dimer 5a with metha-
nolic sodium hydroxide at 60 °C for 12 h or by reacting
it with MeMgBr. Similar results were obtained when
diaryl(benzotriazol-1-yl)methanes were subjected to simi-
lar treatments.5
Cr ossover Rea ction . As is well documented, the
dimers of trityl radicals undergo reversible dissociation
to the corresponding radicals in solution.3b To investigate
possible dissociation in solution, we carried out a cross-
over experiment in which dimers 5a and 5b were mixed
and dissolved in THF. After 10 h of stirring at room
temperature, no new dimers were observed (monitored
by TLC). Further stirring for an additional 10 h under
reflux led to the recovery of starting materials 5a and
5b with no new dimers generated. This experiment
confirms that dimers 4, 5a , 5b, 5d , and 6 have a different
structure from that of the trityl radical dimer. The same
observations (no new dimer generated) were made when
a similar crossover experiment was carried out with
diaryl(benzotriazol-1-yl)methanes.5
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
starting materials 2 and 2D NMR spectra of 5b (6 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.
J O980618F