Convenient synthesis of 1H-benzotriazolylalkylphenols

Article abstract of DOI:10.1080/00397911.2011.563452

(Chemical Equation Presented) A simple, efficient, and environmentally benign method has been developed for the exclusive formation of synthetically significant 1H-benzotriazol-1-ylalkylphenols from hydroxybenzyl alcohols and benzotriazole. Copyright Tayl

Full text of DOI:10.1080/00397911.2011.563452

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Convenient Synthesis of 1H-
Benzotriazolylalkylphenols
Vitalij A. Osyanin a , Natalia E. Sidorina a & Yuri N. Klimochkin a
a Organic Chemistry Division, Samara State Technical University,
Samara, Russia
Available online: 31 Oct 2011
To cite this article: Vitalij A. Osyanin, Natalia E. Sidorina & Yuri N. Klimochkin (2012): Convenient
Synthesis of 1H-Benzotriazolylalkylphenols, Synthetic Communications: An International Journal for
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Synthetic Communications1, 42: 2639–2647, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.563452
CONVENIENT SYNTHESIS OF 1H-
BENZOTRIAZOLYLALKYLPHENOLS
Vitalij A. Osyanin, Natalia E. Sidorina, and
Yuri N. Klimochkin
Organic Chemistry Division, Samara State Technical University,
Samara, Russia
GRAPHICAL ABSTRACT
Abstract A simple, efficient, and environmentally benign method has been developed for the
exclusive formation of synthetically significant 1H-benzotriazol-1-ylalkylphenols from
hydroxybenzyl alcohols and benzotriazole.
Keywords Aza-Michael reaction; benzotriazole; 1H-benzotriazol-1-ylalkylphenols;
2- and 4-hydroxybenzyl alcohols; quinone methides
INTRODUCTION
In recent years, much attention has been focused on the use of benzotriazole
(BtH) methodology as a versatile synthetic tool.[1–3] In this respect, an important
application of the benzotriazole methodology is the use of 1H-benzotriazol-
1-ylalkylphenols as intermediates for the preparation of chromane and benzofuran
derivatives,[4,5] condensed sulfur heterocycles,[6] substituted phenols,[7,8] and 1,1-
bis(2-hydroxyaryl)alkanes.[9] It was found that 2-(1-benzotriazolylalkyl)phenols
react with a variety of nucleophiles including alcohols, Grignard reagents, thiols,
amines, amides, and active methylene compounds through o-quinone methide
formation and Michael addition to give o-substituted phenols.[7,9,10] Besides, the
methylene groups in 2-(1H-benzotriazol-1-ylalkyl)phenols are capable of undergoing
lithiation and the resultant anions can be quenched with various electrophiles such as
alkyl halides, aldehydes, and ketones to give substituted 2-(1H-benzotriazol-1-
ylalkyl)phenols.[10]
Received January 9, 2011.
Address correspondence to Vitalij A. Osyanin, Samara State Technical University, Samara, Russia.
E-mail: vosyanin@mail.ru
2639

2640
V. A. OSYANIN, N. E. SIDORINA, AND Y. N. KLIMOCHKIN
o-Quinone methides are important intermediates in many chemical and bio-
logical processes. These reactive species are efficient DNA alkylating and cross-
linking agents, and play a key role in the biological action of several antibiotics such
as mitomycin and anthracyclines.[11] o-Quinone methides act as heterodienes in inter-
and intramolecular cycloadditions with olefins to give various substituted chromanes.
Like vinyl ketones, o- and p-quinone methides also act as acceptors in Michael addi-
tions to afford ortho- and para-substituted phenols. Most of the methods reported to
date for generating quinone methides involve photolysis, high-temperature ther-
molysis, and=or use of highly derivatized or structurally complex precursors.[12–14]
One effective approach for the generation of quinone methides is the use of 1H-
benzotriazolylalkylphenols.[9,10]
Preparation of 2-(1H-benzotriazol-1-ylmethyl)phenols has been previously
effected by refluxing of 1-hydroxymethylbenzotriazole with phenols in acetic acid.[7]
It should be noted that phenols with electron-withdrawing substituents in the ring
remain inert under the reaction conditions and do not give the corresponding 2-
(1H-benzotriazol-1-ylmethyl)phenols. In addition, para-isomers can be prepared
only from 2,6-disubstituted phenols.
Unsubstituted 2-(1H-benzotriazol-1-ylmethyl)phenol has been also obtained
from 2-(1H-benzotriazol-1-ylmethyl)aniline.[15] Another method for the preparation
of these compounds is the base-catalyzed reaction of benzotriazole with 2- and
4-hydroxybenzyl halogenides. However, preparation of such precursors by direct
halogenmethylation is difficult because of their instability.[16]
We now report a general, simple procedure for the synthesis of 2- and 4-
(1H-benzotriazol-1-ylalkyl)phenols (2a–I) from the corresponding 2- and 4-hydroxy-
benzyl alcohols and benzotriazole (Scheme 1).
The reaction has been carried out by heating equimolar amounts of the
reagents at 160 ꢀC for 15 min (method A) under solvent-free conditions. Refluxing
in dimethylformamide (DMF) was also found to be a successful procedure in the
preparation of 1H-benzotriazol-1-ylalkylphenols (method B). The isolated yields
are reasonable, between 68% and 86%. Products can be easily purified from impuri-
ties by single recrystallization. The reaction was repeated on several different scales
(up to 100 mmol), all with comparable yields. The results are summarized in Table 1.
A mechanism accounting for the formation of 1H-benzotriazol-1-ylalkylphe-
nols is depicted in Scheme 2.
The hydroxybenzyl alcohol loses a molecule of water to give the quinone
methide. A nucleophilic attack on the methylene group of quinone methide by the
nitrogen atom of the benzotriazole produces the corresponding 1H-benzotriazol-
1-ylalkylphenols. The driving force of the reaction is the resulting rearomatization
of the molecule.
It is known that hydroxybenzyl alcohols are termally unstable, and at tempera-
tures above 100 ꢀC they rapidly undergo polycondensation. Nevertheless, in this case
the crude products contained only negligible impurities of polymeric products.
o-Quinone methides are known to be very reactive and unstable intermediates. As
a consequence of this reactivity, di- and trimerization in which one molecule acts
as heterodiene and another as dienophile has led to some chroman fused-ring
systems.[17] However, in all experiments no o-quinone methide dimer or trimer was
encountered. Besides, no 2H-isomers were isolated from reaction mixtures.

1H-BENZOTRIAZOLYLALKYLPHENOLS
2641
Scheme 1. Synthesis of 1H-benzotriazol-1-ylalkylphenols. R1¼R2¼R3¼H (a); R1¼R3¼H, R2¼NO2 (b);
R1¼CH3, R2¼NO2, R3¼H (c); R1¼R3¼H, R2¼Br (d); R1¼CH3, R2¼H, R3¼NO2 (e); R1¼R2¼R3¼H
(f); R1¼R2¼H, R3¼NO2 (g); R1¼CH3, R2¼R3¼H (h); R1¼R2¼H, R3¼OCH3 (i); R1¼H, R2¼Br,
R3¼OCH3 (j); R1¼CH3, R2¼OCH3, R3¼H (k); R1¼R3¼H, R2¼CHO (l).
Although it is known that p-quinone methides that are more stable and conse-
quently are formed more readily than their corresponding o-quinone methides, no
differences between them were found under reaction conditions.
Both the generation of quinone methides and the thermodynamic stability of
the resulting adducts were shown to be highly responsive to both the presence of sub-
stituents on the aromatic ring and the nature of the leaving group at the benzylic pos-
ition of their precursors.[18] Electron-donating groups facilitate quinone methide
generation, wheras electron-withdrawing groups strongly suppress initial formation
of quinone methide, making the resulting 1H-benzotriazol-1-ylalkylphenols more
stable. At the same time, the leaving-group ability of benzotriazole is not sufficient
to regenerate the quinone methide. Thus, the 1H-benzotriazol-1-ylalkylphenols,
electron-donating and electron-withdrawing substituents remain stable under reac-
tion conditions.
It is known that quinone methides can be generated by elimination of phenol
Mannich base methiodides, so 2-(1H-benzotriazol-1-ylmethyl)-4-methoxyphenol
(2m) was prepared from benzotriazole and (2-hydroxy-5-methoxybenzyl)trimethyl-
ammonium iodide by heating in DMF (Scheme 3).
Table 1. 1H-Benzotriazol-1-ylalkylphenols (2a–l)
Compound
Yield (%)a (method)
2a
2b
2c
2d
2e
2f
77 (A), 62 (B)
86 (A)
69 (A)
72 (A)
68 (A)
82 (A)
81 (A)
82 (A)
81 (A)
71 (A)
78 (B)
2g
2h
2i
2j
2k
2l
68 (B)
aIsolated yield.

2642
V. A. OSYANIN, N. E. SIDORINA, AND Y. N. KLIMOCHKIN
Scheme 2. Plausible mechanism for the synthesis of 1H-benzotriazol-1-ylalkylphenols.
Scheme 3. Synthesis of 2-(1H-benzotriazol-1-ylmethyl)-4-methoxyphenol (2m).
1
The structures of 2a–m were confirmed by their infrared (IR), H NMR spec-
tral data, and elemental analysis. The IR spectra of 1–13 contain strong absorption
bands at 3400–2500 cmꢁ1 characteristic of O-H stretching vibrations, associated by
the intermolecular hydrogen bond. The methylene and methine (in compounds 2c,
1
2e, 2h, 2k, 2l) signals in H NMR spectra shift downfield because of the electron-
withdrawing benzotriazole group and appear at d 5.47–6.60 ppm. Broad singlets at
d 8.91–11.05 ppm were assigned to OH protons.
An easy ecofriendly laboratory procedure under solvent-free conditions is pre-
sented for the hydroxybenzylation of the benzotriazole with o- and p-hydroxybenzyl
alcohols. Synthesis of 2a–m by the suggested procedures takes less time, does not
require an excess of any reagents or the use of any metal catalysts, and can be per-
formed under neutral reaction conditions. The method is general for o- and p-hydro-
xybenzyl alcohols containing both electron-withdrawing and electron-donating
substituents; it allows preparation of 1H-benzotriazol-1-ylalkylphenols of high
purity in good yields.
EXPERIMENTAL
FTIR spectra were taken on a Shimadzu FTIR-8400S spectrophotometer
in KBr pellets. 1H NMR spectra were recorded on a Brucker AM 400-MHz
spectrometer in dimethylsulfoxide (DMSO-d6) using tetramethylsilane (TMS) as an
internal reference. Chemical shifts and coupling constants were recorded in units of
parts per million (ppm) and hertz (Hz), respectively. Melting points were determined
on an Electrothermal melting-point apparatus and are uncorrected. Elemental
analyses were performed on a EuroVector EA-3000 instrument. Electrospray
ionization–mass spectrometry (EI-MS) spectra were obtained on a Finnigan Trace
DSQ spectrometer (70 eV). Thin-layer chromatography (TLC) was carried out on

1H-BENZOTRIAZOLYLALKYLPHENOLS
2643
aluminium-backed silica-gel plates (Merck 60 F254) with visualization of components
by ultraviolet (UV) light (254 nm) or exposure to I2. Noncommercial hydroxybenzyl
alcohols were prepared according to the well-known methods.[19–21]
General Experimental Procedures for the Synthesis of 1H-
Benzotriazolylalkylphenols (2a–I)
Method A. A mixture of 1 g (8.4 mmol) of benzotriazole and 8.4 mmol of the
appropriate hydroxybenzyl alcohol was added to a opened round-bottom flask
equipped with a mechanical stirrer and thermometer. The flask was placed in a pre-
liminary heated metal bath, and the reaction mixture was stirred at 160 ꢀC for
15 min. After completion of the reaction, the mixture was cooled to room tempera-
ture and washed with cold dichloromethane, and the crude product was purified by
recrystallization.
Method B. A mixture of 1 g (8.4 mmol) of benzotriazole and 8.4 mmol of
the appropriate hydroxybenzyl alcohol in DMF (10 ml) was refluxed for 2 h. The
resulting solution was cooled to room temperature and then poured into 50 ml of
rapidly stirred water to yield a solid product, which was dried and purified by
recrystallization.
Characterization Data of the 1H-Benzotriazolylalkylphenols (2a–m)
2-(1H-1,2,3-Benzotriazol-1-ylmethyl)phenol (2a). Colorless crystals; mp
1
171–172 ꢀC (ethylacetate) (lit. mp 168–170 ꢀc)[7], H NMR, d, ppm: 5.85 (s, 2H,
CH2), 6.74 (t, 1H, H-4, J ¼ 7.4 Hz), 6.87 (d, 1H, H-6, J ¼ 7.4 Hz), 7.05 (d, 1H,
H-3, J ¼ 7.7 Hz), 7.13 (dd, 1H, H-5, J ¼ 8.0 Hz, J ¼ 1.8 Hz), 7.35 (t, 1H, HBt-5,
J ¼ 8.2 Hz), 7.48 (t, 1H, HBt-6, J ¼ 7.9 Hz), 7.77 (d, 1H, HBt-7, J ¼ 8.4 Hz), 8.03 (d,
1H, HBt-4, J ¼ 8.4 Hz), 9.95 (s, 1H, OH); IR, n, cmꢁ1: 3300–2500 (OH), 1601,
1508, 1497, 1464, 1433, 1400, 1352, 1319, 1267, 1229, 1161, 1136, 1086, 852, 770,
760, 746; EI-MS (70 eV) m=z (% int.): 225 (Mþ, 59), 196 (Mþ – CHO, 65), 180
(10), 168 (Mþ – CHO – N2, 33), 167 (20), 119 C6H5N3þ, 8), 117 (16), 107 (C7H7O,
100). Anal. calcd. for C13H11N3O, %: C, 69.32; H, 4.92; N, 18.66. Found, %: C,
69.37; H, 4.88; N, 18.71.
2-(1H-1,2,3-Benzotriazol-1-ylmethyl)-4-nitrophenol (2b). Yellow crystals;
1
mp 241–242 ꢀC (ethanol–DMF); H NMR, d, ppm: 5.95 (s, 2H, CH2), 7.03 (d, 1H,
H-6, J ¼ 8.3 Hz), 7.41 (t, 1H, HBt-6, J ¼ 8.4 Hz), 7.55 (t, 1H, HBt-5, J ¼ 8.4 Hz),
7.81–7.84 (m, 2H, HBt-7, H-5), 7.92 (s, 1H, H-3), 8.02 (d, 1H, HBt-4, J ¼ 8.3 Hz),
11.05 (s, 1H, OH); IR, n, cmꢁ1: 3300–2500 (OH), 1620, 1593, 1527 (NO2), 1497,
1447, 1339 (NO2), 1300, 1273, 1088, 748; EI-MS (70 eV) m=z (% int.): 270 (Mþ,
39), 241 (Mþ – CHO, 10), 196 (14), 195 (Mþ – CHO – NO2, 26), 167 (Mþ – CHþO
– NO2 – N2, 24), 152 (C7H6NO3þ, 100), 139 (7), 106 (C7H6Oþ, 40), 105 (C7H5O ,
17). Anal. calcd. for C13H10N4O3, %: C, 57.78; H, 3.70; N, 20.74. Found, %: C,
57.85; H, 3.64; N, 20.63.
2-[1-(1H-1,2,3-Benzotriazol-1-yl)ethyl]-4-nitrophenol (2c). Yellow crys-
tals; mp 246–248 ꢀC (ethanol–DMF); 1H NMR, d, ppm: 1.73 (d, 3H, CH3,

2644
V. A. OSYANIN, N. E. SIDORINA, AND Y. N. KLIMOCHKIN
J ¼ 7.7 Hz), 5.82 (q, 1H, CH, J ¼ 7.7 Hz), 7.15 (d, 1H, H-6, J ¼ 8.0 Hz), 7.38 (t, 1H,
HBt-6, J ¼ 8.0 Hz), 7.50 (t, 1H, HBt-5, J ¼ 8.0 Hz), 7.68–7.72 (m, 2H, HBt-7, H-5),
7.91 (s, 1H, H-3), 8.38 (d, 1H, HBt-4, J ¼ 7.6 Hz), 9.94 (s, 1H, OH); IR, n, cmꢁ1
:
3300–2500 (OH), 1620, 1593, 1524 (NO2), 1497, 1458, 1435, 1385, 1335 (NO2),
1296, 1277, 1242, 1153, 1103, 756; EI-MS (70 eV) m=z (% int.): 284 (Mþ, 80), 255
(Mþ – CHO, 12), 241 (66), 209 (37), 195 (46), 166 (C8H8NOþ3 , 100), 149 (23), 120
(C8H8Oþ, 76), 119 C6H5N3þ, 43). Anal. calcd. for C14H12N4O3, %: C, 59.15; H,
4.23; N, 19.72. Found, %: C, 59.23; H, 4.18; N, 19.65.
2-(1H-1,2,3-Benzotriazol-1-ylmethyl)-4-bromophenol
(2d). Colorless
crystals; mp 184–185 ꢀc (ethanol–ethylacetate); 1H NMR, d, ppm: 5.84 (s, 1H,
CH2), 6.83 (d, 1H, H-6, J ¼ 8.7 Hz), 7.24 (d, 1H, H-3, J ¼ 2.5 Hz), 7.31 (dd, 1H,
H-5, J ¼ 8.7 Hz, J ¼ 2.5 Hz), 7.39 (t, 1H, HBt-5, J ¼ 7.5 Hz), 7.53 (t, 1H, HBt-6,
J ¼ 7.5 Hz), 7.79 (d, 1H, HBt-7, J ¼ 8.4 Hz), 8.03 (d, 1H, HBt-4, J ¼ 8.4 Hz), 10.16
(br. s, 1H, OH); IR, n, cmꢁ1: 3200–2500 (OH), 1593, 1497, 1454, 1420, 1346,
1277, 1227, 1169, 1126, 1092, 814, 771, 744; EI-MS (70 eV) m=z (% int.) (for 79Br iso-
tope): 303 (Mþ, 47), 274 (Mþ – CHO, 27), 196 (Mþ – CO – Br, 78), 185 (C7H6BrOþ,
100), 168 (26), 167 (44), 139 (13), 117 (53), 106 (C7H6Oþ, 14). Anal. calcd. for
C13H10BrN3O, %: C, 51.32; H, 3.29; N, 13.82. Found, %: C, 51.40; H, 3.24; N, 13.68.
2-[1-(1H-1,2,3-Benzotriazol-1-yl)ethyl]-6-nitrophenol (2e). Yellow crys-
1
tals; mp 91–92 ꢀ (ethanol); H NMR, d, ppm: 2.07 (d, 3H, CH3, J ¼ 7.2 Hz), 6.60
(q, 1H, CHCH3, J ¼ 7.2 Hz), 7.06 (t, 1H, H-4, J ¼ 8.1 Hz), 7.39 (t, 1H, HBt-5,
J ¼ 8.1 Hz), 7.50 (t, 1H, HBt-6, J ¼ 8.1 Hz), 7.59 (d, 1H, H-3, J ¼ 7.5), 7.69 (d, 1H,
HBt-7, J ¼ 8.4 Hz), 7.97 (d, 1H, H-5, J ¼ 8.4 Hz), 8.04 (d, 1H, HBt-4, J ¼ 8.1 Hz),
10.78 (br. s, 1H, OH); IR, n, cmꢁ1: 3271 (OH), 3094, 3055, 1612, 1589, 1539
(NO2), 1447, 1381, 1350 (NO2), 1300, 1273, 1246, 1196, 1122, 899, 841, 760, 744;
EI-MS (70 eV) m=z (% int.): 284 (Mþ, 79), 255 (Mþ – CHO, 4), 241 (32), 221 (8),
209 (10), 195 (13), 180 (23), 166 (C8H8NOþ3 , 16), 139 (8), 119 C6H5N3þ, 16), 118
(100). Anal. calcd. for C14H12N4O3, %: C, 59.15; H, 4.23; N, 19.72. Found, %: C,
59.33; H, 4.16; N, 19.75.
4-(1H-1,2,3-Benzotriazol-1-ylmethyl)phenol (2f). Colorless crystals; mp
1
170–171 ꢀc (ethanol); H NMR, d, ppm: 5.60 (s, 2H, CH2), 6.79 (d, 2H, H-2,6,
J ¼ 7.1 Hz), 7.36 (d, 2H, H-3,5, J ¼ 7.1 Hz), 7.50–7.70 (m, 2H, HBt-5,6), 7.83–8.10
(m, 2H, HBt-4,7), 9.65 (br. s, 1H, OH); IR, n, cmꢁ1: 3300–2600 (OH), 1632, 1603,
1515, 1457, 1382, 1365, 1321, 1269, 1233; EI-MS (70 eV) m=z (% int.): 225 (Mþ,
99), 196 (Mþ – CHO, 100), 180 (27), 168 (Mþ – CHO – N2, 27), 167 (19), 119
C6H5Nþ3 , 32), 107 (C7H7O, 98), 106 (C7H6O, 16). Anal. calcd. for C13H11N3O, %:
C, 69.32; H, 4.92; N, 18.66. Found, %: C, 69.38; H, 4.85; N, 18.72.
4-(1H-1,2,3-Benzotriazol-1-ylmethyl)-2-nitrophenol (2g). Yellow crystals;
1
mp 187–189 ꢀ (ethanol); H NMR, d, ppm: 5.96 (s, 2H, CH2), 7.12 (d, 1H, H-6,
J ¼ 8.1 Hz), 7.38–7.58 (m, 2H, HBt), 7.90 (d, 1H, H-5, J ¼ 8.1 Hz), 8.01–8.07 (m, 2H,
HBt), 8.47 (s, 1H, H-3), 11.02 (br. s, 1H, OH); IR, n, cmꢁ1: 3256 (OH), 1632, 1574,
1539 (NO2), 1489, 1454, 1442, 1423, 1339 (NO2), 1285, 1254, 1219, 1153, 1122,
1088, 748; EI-MS (70 eV) m=z (% int.): 270 (Mþ, 100), 241 (Mþ – CHO, 23), 196
(22), 195 (Mþ – CHO – NO2, 36), 167 (Mþ – CHO – NO2 – N2, 56), 152
(C7H6NOþ3 , 89), 139 (12), 119 C6H5N3þ, 10), 106 (C7H6Oþ, 66), 105 (C7H5Oþ, 26).

1H-BENZOTRIAZOLYLALKYLPHENOLS
2645
Anal. calcd. for C13H10N4O3, %: C, 57.75; H, 3.70; N, 20.74. Found, %: C, 57.85; H,
3.64; N, 20.80.
4-[1-(1H-1,2,3-Benzotriazol-1-yl)ethyl]phenol (2h). Colorless crystals; mp
1
68–70 ꢀc (ethanol–water); H NMR, d, ppm: 2.03 (d, 3H, CH3, J ¼ 7.3 Hz), 6.19
(q, 1H, CHCH3, J ¼ 7.3 Hz), 6.72 (d, 2H, H-2,6, J ¼ 8.4 Hz), 7.20 (d, 2H, H-3,5,
J ¼ 8.4 Hz), 7.36 (t, 1H, HBt-5, J ¼ 7.0 Hz), 7.46 (t, 1H, HBt-6, J ¼ 7.0 Hz), 7.68 (d,
1H, HBt-7, J ¼ 8.4 Hz), 8.02 (d, 1H, HBt-4, J ¼ 8.1 Hz), 9.38 (br. s, 1H, OH); IR, n,
cmꢁ1: 3400–2500 (OH), 1612, 1593, 1516, 1450, 1377, 1269, 1238, 1207, 1169,
1103, 1061, 833, 783, 744; EI-MS (70 eV) m=z (% int.): 239 (Mþ, 59), 210 (Mþ
– CHO, 18), 196 (30), 167 (11), 121 (C8H9Oþ, 88), 120 (C8H8Oþ, 59), 119
C6H5Nþ3 , 100), 91 (99). Anal. calcd. for C14H13N3O, %: C, 70.29; H, 5.44; N,
17.57. Found, %: C, 70.35; H, 5.37; N, 17.65.
4-(1H-1,2,3-Benzotriazol-1-ylmethyl)-2-methoxyphenol
(2i). Colorless
1
crystals; mp 75–76 ꢀc (ethanol); H NMR, d, ppm: 3.73 (s, 3H, CH3O), 5.83 (s,
2H, CH2), 6.73–6.78 (m, 2H, H-5,6), 7.02 (s, 1H, H-3), 7.38 (t, 1H, HBt-5,
J ¼ 7.5 Hz), 7.51 (t, 1H, HBt-6, J ¼ 7.5 Hz), 7.81 (d, 1H, HBt-7, J ¼ 8.6 Hz), 8.03 (d,
1H, HBt-4, J ¼ 8.6 Hz), 8.96 (br. s, 1H, OH); IR, n, cmꢁ1: 3400–2600 (OH), 1612,
1524, 1454, 1431, 1273, 1246, 1223, 1157, 1130, 1111, 1038, 960, 849, 829, 802,
787, 741; EI-MS (70 eV) m=z (% int.): 255 (Mþ, 100), 226 (Mþ – CHO, 22), 211
(25), 196 (43), 183 (22), 167 (18), 166 (14), 137 (C8H9Oþ2 , 80), 122 (25), 119
C6H5Nþ3 , 100). Anal. calcd. for C14H13N3O2, %: C, 65.88; H, 5.10; N, 16.47. Found,
%: C, 66.78; H, 5.06; N, 16.40.
4-(1H-1,2,3-Benzotriazol-1-ylmethyl)-2-bromo-6-methoxyphenol
(2j).
Colorless crystals; mp 158–159 ꢀc (ethanol); 1H NMR, d, ppm: 3.78 (s, 3H,
CH3O), 5.85 (s, 2H, CH2), 7.05 and 7.09 (d, 2H, H-3,5, J ¼ 1.2 Hz), 7.40 (t, 1H,
HBt-5, J ¼ 6.8 Hz), 7.54 (t, 1H, HBt-6, J ¼ 6.8 Hz), 7.87 (d, 1H, HBt-7, J ¼ 8.4 Hz),
8.04 (d, 1H, HBt-4, J ¼ 8.4 Hz), 9.45 (br. s, 1H, OH); IR, n, cmꢁ1: 3300–2500
(OH), 1605, 1582, 1501, 1454, 1423, 1288, 1273, 1231, 1184, 1103, 1049, 787, 741;
EI-MS (70 eV) m=z (% int.) (for 79Br isotope): 333 (Mþ, 95), 304 (Mþ – CHO,
17), 289 (Mþ – CHO – CH3, 15), 274 (23), 215 (C8H8BrOþ2 , 71), 211 (61), 183
(57), 172 (14), 166 (20), 154 (22), 135 (C8H7Oþ2 , 12), 120 (18), 119 C6H5N3þ, 27).
Anal. calcd. for C14H12BrN3O2, %: C, 50.33; H, 3.59; N, 12.57. Found, %: C,
50.43; H, 3.39; N, 12.63.
4-[1-(1H-1,2,3-Benzotriazol-1-yl)ethyl]-2-methoxyphenol (2k). Colorless
crystals; mp 155–156 ꢀc (ethanol–water); 1H NMR, d, ppm: 2.05 (d, 3H, CH3,
J ¼ 6.9 Hz), 3.72 (s, 3H, CH3O), 6.16 (q, 1H, CHCH3, J ¼ 6.9 Hz), 6.72 (d, 1H,
H-6, J ¼ 8.1 Hz), 6.78 (dd, 1H, H-5, J ¼ 8.1 Hz, J ¼ 1.2 Hz), 6.99 (d, 1H, H-3,
J ¼ 1.2 Hz), 7.36 (t, 1H, HBt-5, J ¼ 7.7 Hz), 7.46 (t, 1H, HBt-6, J ¼ 8.4 Hz), 7.70 (d,
1H, HBt-7, J ¼ 8.4 Hz), 8.02 (d, 1H, HBt-4, J ¼ 7.7 Hz), 8.91 (s, 1H, OH); IR, n,
cmꢁ1: 3300–2700 (OH), 1612, 1524, 1454, 1435, 1292, 1273, 1242, 1157, 1126,
1038, 783, 742, 733; EI-MS (70 eV) m=z (% int.): 269 (Mþ, 93), 240 (Mþ – CHO,
3), 226 (12), 211 (20), 208 (12), 183 (15), 180 (11), 151 (C9H11Oþ2 , 100), 150
(C9H10Oþ2 , 80), 135 (36), 121 (26), 119 C6H5Nþ3 , 35). Anal. calcd. for
C15H15N3O2, %: C, 66.91; H, 5.58; N, 15.61. Found, %: C, 67.01; H, 5.64; N, 15.54.

2646
V. A. OSYANIN, N. E. SIDORINA, AND Y. N. KLIMOCHKIN
5-(1H-1,2,3-Benzotriazol-1-ylmethyl)-2-hydroxybenzaldehyde (2l). Col-
1
orless crystals; mp 138–140 ꢀc (ethanol); H NMR, d, ppm: 5.93 (s, 2H, CH2), 6.99
(d, 1H, H-3, J ¼ 8.0 Hz), 7.40 (t, 1H, HBt, J ¼ 8.1 Hz), 7.51–7.56 (m, 2H, HBt),
7.69 (s, 1H, H-6), 7.85 (d, 1H, H-4, J ¼ 8.0 Hz), 8.05 (d, 1H, HBt, J ¼ 8.1 Hz),
10.23 (s, 1H, CHO), 10.76 (br. s, 1H, OH); IR, n, cmꢁ1: 3230–2950 (OH), 2851,
1682 (CO), 1612, 1501, 1450, 1381, 1350, 1300, 1277, 1254, 1231, 1157, 1134,
1111, 945, 833, 783, 760, 741; EI-MS (70 eV) m=z (% int.): 253 (Mþ, 100), 224
(Mþ – CHO, 57), 196 (62), 168 (16), 167 (15), 135 (C8H7Oþ2 , 82), 133 (C8H5Oþ2 ,
58), 119 C6H5Nþ3 , 16), 105 (C7H5O, 13). Anal. calcd. for C14H11N3O2, %: C,
66.40; H, 4.35; N, 16.60. Found, %: C, 66.50; H, 4.28; N, 16.53.
2-(1H-1,2,3-Benzotriazol-1-ylmethyl)-4-methoxyphenol (2m). A mixture
of 1 g (8.4 mmol) of benzotriazole and 2.8 g (8.4 mmol) of (2-hydroxy-5-methoxyben-
zyl)trimethylammonium iodide in DMF (15 ml) was refluxed for 2 h. The resulting
solution was cooled to room temperature and then poured into 50 ml of rapidly stir-
red saturated water solution of sodium chloride to yield a solid product, which was
dried, and purified by recrystallization from toluene to give 1.18 g (55%) of colorless
crystals, m.p. 138–140 ꢀC. 1H NMR, d, ppm: 3.66 (s, 3H, OCH3), 5.47 (s, 2H, CH2),
7.08 (d, 1H, H-6, J ¼ 8.3 Hz), 7.44 (t, 1H, HBt-6, J ¼ 8.4 Hz), 7.50 (t, 1H, HBt-5,
J ¼ 8.4 Hz), 7.70–7.78 (m, 2H, HBt-7, H-5), 7.88 (s, 1H, H-3), 8.02 (d, 1H, HBt-4,
J ¼ 8.2 Hz), 9.42 (br. s, 1H, OH). IR, n, cmꢁ1: 3300–2500 (OH), 1601, 1512, 1454,
1435, 1311, 1273, 1254, 1227, 1215, 1157, 1092, 1041, 806, 768, 744; EI-MS (70 eV)
m=z (% int.): 255 (Mþ, 73), 226 (Mþ – CHO, 35), 212 (26), 184 (25), 167 (18), 156
(10), 154 (9), 137 (C8H9Oþ2 , 89), 136 (C8H8Oþ2 , 27), 117 (100). Anal. calcd. for
C14H13N3O2, %: C, 65.88; H, 5.10; N, 16.47. Found, %: C, 66.77; H, 5.04; N, 16.38.
ACKNOWLEDGMENT
The study was financially supported by the Federal Program Scientific and
Pedagogical Staff of Innovative Russia in 2009–2013 (Projects N P1104 and
02.740.11.0632).
REFERENCES
1. Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Properties and synthetic utility of
N-substituted benzotriazoles. Chem. Rev. 1998, 98, 409–548.
2. Katritzky, A. R.; Rogovoy, B. V. Benzotriazole: An ideal synthetic auxiliary. Chem. Eur.
J. 2003, 9, 4586–4593.
3. Katritzky, A. R.; Manju, K.; Singh, S. K.; Meher, N. K. Benzotriazole-mediated amino-,
amido, alkoxy-, and alkylthio-alkylation. Tetrahedron 2005, 61, 2555–2581.
4. Katritzky, A. R.; Lan, X.; Zhang, Z. Novel routes to 1-aryl-1,4-dihydro-3(2H)-isoquino-
linones and 2-substituted or 2,3-disubstituted benzofurans by intramolecular cyclizations.
J. Heterocycl. Chem. 1993, 30, 381–387.
5. Katritzky, A. R.; Lan, X. o-(a-Benzotriazolylalkyl)phenols: Novel precursors of
o-quinone methides. Synthesis 1992, 8, 761–764.
6. Rumpf, N.; Gro¨schl, D.; Meier, H.; Oniciu, D. C.; Katritzky, A. R. An alternative route
to 2H-naphtho[1,2-b]thiete and its cycloaddition products. J. Heterocycl. Chem. 1998, 35,
1505–1508.

1H-BENZOTRIAZOLYLALKYLPHENOLS
2647
7. Katrizky, A. R.; Lan, X.; Lam, J. N. o-(a-Benzotriazolylalkyl)phenols: Versatile inter-
mediates for the synthesis of substituted phenols. Chem. Ber. 1991, 124, 1809–1817.
8. Rivera, A.; Duarte, Y.; Gonzalez-Salas, D.; Rios-Motta, J.; Zaragoza, G. X-ray
and hydrogen-bonding properties of 1-((1H-benzotriazol-1-yl)methyl)naphthalen-2-ol.
Molecules 2009, 14, 1234–1244.
9. Katritzky, A. R.; Zhang, Z.; Lang, H.; Lan, X. o-(a-Benzotriazolylalkyl)phenols: Novel
precursors for the preparation of 1,1-bis(2-hydroxyaryl)alkanes. J. Org. Chem. 1994, 59,
7209–7213.
10. Katritzky, A. R.; Zhang, Z.; Lan, X.; Lang, H. o-(a-Benzotriazolylalkyl)phenols: Novel
precursors for the preparation of ortho-substituted phenols via intermediate o-quinone
methide. J. Org. Chem. 1994, 59, 1900–1903.
11. Rokita, S. E., Ed., Quinone Methides; Hoboken, NJ: Wiley, 2009.
12. Van De Water, R. W.; Pettus, T. R. R. o-Quinone methides: Intermediates underdevel-
oped and underutilized in organic synthesis. Tetrahedron 2002, 58, 5367–5405.
13. Wan, P.; Barker, B.; Diao, L.; Fisher, M.; Shi, Y.; Yang, C. Quinone methides: relevant
intermediates in organic chemistry. Can. J. Chem. 1996, 74, 465–475.
14. Wan, P.; Brousmiche, D. W.; Chen, C. Z.; Cole, J.; Lukeman, M.; Xu, M. Quinone
methide intermediates in organic photochemistry. Pure Appl. Chem. 2001, 73, 529–534.
15. Biagi, G.; Giorgi, I.; Livi, O.; Scartoni, V.; Barili P. L.; Calderone, V.; Martinotti, E.
New 5-substituted-1-(2-hydroxybenzoyl)-benzotriazoles, potassium channel activators.
Farmaco 2001, 56, 827–834.
16. Taylor, L. D.; Grasshoff, J. M.; Pluhar, M. Use of o- and p-hydroxybenzyl functions as
blocking groups which are removable with base. J. Org. Chem. 1978, 43, 1197–1200.
17. Bolon, D. A. Generation of o-quinone methides in solution: Trimerization. J. Org. Chem.
1970, 35, 715–719.
18. Weinert, E. E.; Dondi, R.; Colloredo-Melz, S.; Frankenfield, K. N.; Mitchell, C. H.;
Freccero, M.; Rokita, S. E. Substituents on quinone methides strongly modulate forma-
tion and stability of their nucleophilic adducts. J. Am. Chem. Soc. 2006, 128, 11940–11947.
19. Osyanin, V. A.; Sidorina, N. E. Synthesis of imidazo[2,1-b][1,3]benzoxazines from 2-halo-
genimidazoles and salicylic alcohols. Izv. Vuzov. Khimiya I Khim. Tekhnologiya, 2005, 48
10, 83–85.
20. Stoermer, R.; Behn, K. Synthese aromatischer aikohole mit formaldehyd. Chem. Ber.,
1901, 34, 2455–2460.
21. Treadwell, E. M.; Neighbors, J. D.; Wiermer, D. F. A cascade cyclyzation appoach to
Schweinfurthin B. Org. Lett. 2002, 4, 3639–3642.