Aqueous micellar medium in organic synthesis: Alkylations and Michael reactions of benzotriazole

Article abstract of DOI:10.1246/bcsj.74.2133

The feasibility of aqueous micelles of cetyltrimethylammonium bromide in catalyzing C-N bond formation has been studied with respect to N-alkylations of benzotriazole (Bt). Alkylations with various alkylating agents and the addition of Bt across activated double bonds in the Michael fashion occurred successfully in fair-to-good yields in the aqueous micellar regime. These reactions provided a mixture of N-1 and N-2 alkylated products, with a marked preference for N-1 over N-2 isomers. Micellar catalysis has been evaluated experimentally to indicate over a 50% micellar contribution to these alkylations in contrast to their aqueous counterparts. Since, N-alkyl benzotriazoles are of potential biological interest, the present micellar procedure offers a convenient alternative to other available methods.

Full text of DOI:10.1246/bcsj.74.2133

c. Jpn.
© 2001 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 74, 2133–2138 (2001) 2133
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Aqueous Micellar Medium in Organic Synthesis: Alkylations and
Michael Reactions of Benzotriazole
Aqueous Micellar Medium in Organic Synthesis
S. H. Mashraqui et al.
Sabir Hussain Mashraqui,* Sukeerthi Kumar, and Chandrasekhar Dayal Mudaliar
01
33
38
SJA8
09-2673
035
Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai 400 098, India
(Received February 2, 2001)
The feasibility of aqueous micelles of cetyltrimethylammonium bromide in catalyzing C–N bond formation has
been studied with respect to N-alkylations of benzotriazole (Bt). Alkylations with various alkylating agents and the addi-
tion of Bt across activated double bonds in the Michael fashion occurred successfully in fair-to-good yields in the aque-
ous micellar regime. These reactions provided a mixture of N-1 and N-2 alkylated products, with a marked preference
for N-1 over N-2 isomers. Micellar catalysis has been evaluated experimentally to indicate over a 50% micellar contribu-
tion to these alkylations in contrast to their aqueous counterparts. Since, N-alkyl benzotriazoles are of potential biologi-
cal interest, the present micellar procedure offers a convenient alternative to other available methods.
01
01
.3
The N-alkylations of benzotriazole have been widely inves-
tigated under both homogeneous and PTC conditions using an
assortment of basic catalysts and conditions.1 These reactions
invariable provide a mixture of both N-1 and N-2 alkylation
products, though in many cases, marked preferences for N-1
over N-2 alkylations are observed. The formation of regioiso-
mers in benzotriazole alkylations has been attributed to the ex-
istence of H-1 and H-2 tautomeric forms of benzotriazole (re-
action 1, Scheme 1).2
In recent years, various organized media, such as micelles,
zeolites and clays have been attracting interest as promising
new reaction domains to study the reactivity, selectivity and
catalysis in various chemical and biochemical processes.3 Ac-
cording to literature, micelles have been used extensively to in-
vestigate the kinetic and thermodynamic aspects of chemical
processes. However, relatively little attention has been devot-
ed to exploiting micelles for synthetically useful processes.
We have recently described the potential of aqueous micelles
of the cationic surfactant, cetyltrimethylammonium bromide
(CTAB), as an efficient and convenient medium for executing
synthetically useful reactions, namely the aldol condensations,
Michael reactions and C–S bond formations.4–6 In a continua-
tion to this work, we presently studied the micellar catalyzed
alkylations (generalized reaction 2, Scheme 1) and Michael re-
actions of benzotriazole so as to offer a new reaction medium
to carry out the synthesis of alkylated benzotriazoles, many of
which are known to possess varied biologically activity,3 and
also to observe any favorable influence of micelles on the regi-
oselectivity of these alkylations.
We first examined the alkylation of Bt 1 with benzyl chlo-
ride on the 10 mmol scale in weakly alkaline aqueous CTAB
micelles (CTAB; 50 mg, 1.35 × 10−4 mol (> cmc) in 100 mL
of 0.02 M NaOH). Because of the high acidity of the N–H
bond of benzotriazole (pKa of 8.2),7 a fairly dilute NaOH solu-
tion has been used to effect the complete N-deprotonation of
benzotriazole. The above mentioned micellar reaction was
vigorously stirred at room temperature until the reaction was
judged by TLC to be complete (16 h, Table 1). The crude
Scheme 1.

2134 Bull. Chem. Soc. Jpn., 74, No. 11 (2001)
Aqueous Micellar Medium in Organic Synthesis
Table 1. N-Alkylation of Benzotriazolea)
Entry
Alkyl halides: R–X
Products Time/hb) Ratio of N1/N2e) Yield/%f)
1
2
3
4
5
6
7
2a; R = PhCH2; X = Cl
3a/4a
3b/4b
3c/4c
3d/4d
3e/4e
3f
16
4
4
24
48
48c)
48d)
70:30
80:20
80:20
68:32
55:45
100:0
100:0
84
88
84
63
69
55
35
2b; R = PhCOCH2; X = Cl
2c; R = CH2COOC2H5; X = Br
2d; R = CH2CHwCH2; X = Br
2e; R = PhCH2CH2; X = Br
2f; R = CH3CH2CH2; X = Br
2g; R = CH3CH2CH2CH2; X = Br
3g
a) All reactions were carried out at room temperature using 10 mmol scale of benzotriazole and
alkyl halide. b) Reaction time refers to > 90% conversion. c) Ca. 55% conversion. d) Ca. 35%
conversion. e) Ratio determined by quantitative separation on SiO2 column chromatography. f)
Yields are not optimised.
product obtained upon a work-up showed two compounds,
azoles in 63% yield in 68:32 ratio (entry 4, Table 1).
which were readily resolved by SiO2 column chromatography
to afford the known N-1-3a and N-2-4a benzylbenzotriazoles
in 70:30 ratio, the combined yield being 84%. Although, the
regioselectivity is moderate, the successful alkylation of Bt
with benzyl chloride in high yield confirms the potential of mi-
cellar medium in catalyzing C–N bond formation. Additional-
ly, the reaction condition is very mild, easy to execute and eco-
nomical.
The micellar alkylations of Bt with simple alkyl halides,
such as phenethyl bromide, propyl bromide, and n-butyl bro-
mide, proceeded comparatively sluggishly (entries 5 to 7 Table
1) compared to the activated alkyl halides (entries 1 to 4, Table
1). Thus, the alkylation of Bt with phenethyl bromide in mi-
celles required 48 h for complete conversion, giving N-1-3e
and N-2-4e products in 55:45 ratio (entry 5, Table 1). Howev-
er, alkylations with propyl bromide and butyl bromide were
found to be incomplete even after 48 h, showing ca. 55% and
35% conversions, respectively. Interestingly, practically a sin-
gle product, characterized as N-1-propylbenzotriazole 3f and
N-1-butylbenzotriazoles 3g, was obtained in these reactions.
In order to assess micellar catalysis towards alkylation reac-
tions, we simultaneously performed N-benzylation of Bt under
micellar and plain aqueous conditions without added CTAB,
keeping all other conditions identical. After 10 h of reactions,
we found upon product analysis 75% and 35% conversions in
micellar and aqueous media (N1/N2 ratio 67:33 in aqueous
medium), respectively. A similar comparison of the slower re-
acting propyl bromide revealed ca. 28% reaction after 48 h in
the presence of CTAB micelles, but only 9% in the aqueous
medium during the same reaction time. These experiments
clearly demonstrate the contribution of micellar catalysis to be
in excess of 50% to the overall reaction. The comparatively
slower reactions of low polar phenethyl bromide, propyl and
butyl bromides (entries 5 to 7, Table 1) may in part be due their
deeper residency in the hydrophobic domain of the micelles,
rendering them relatively inaccessible to attack by polar N-
benzotriazole anions.
In order to discern between the type of catalysis either being
due to a phase-transfer effect or micellar aggregation, we per-
formed N-benylation of benzotriazole in aqueous medium con-
taining tetrabutylammonium bromide (TBAB), a conventional
phase-transfer catalyst. An analysis of these reactions contain-
ing various concentrations of TBAB ranging from 1 to 5 wt%
after 10 h revealed conversion to N-benzyl benzotriazole be-
tween 33–37%, which is nearly the same as observed in a pure
aqueous medium. This result clearly rules out any involve-
ment of phase-transfer type catalysis in the benzylation. We
can therefore conclude that the much higher conversions ob-
served in aqueous CTAB (ca. 75% N-benylation) after 10 h re-
action time were due to micellar aggregation.
The highest regioselectivity for the N-benzylation of benzo-
triazole to date has been reported by Katritzky8 in refluxing
benzene solvent (91% of N-1 isomer) using an excess of Bt, it-
self, serving as the base. In other conditions, the N-1/N-2 ratio
reportedly varies from 85:15 in KOH/xylene9 to 73:27 in
C2H5ONa/C2H5OH systems.10 It may be noted that there is a
close parallel in the regioselectivity of the N-benzylation of
benzotriazole reported in the alcoholic medium and that ob-
served by us in the aqueous CTAB micelles. This similarity in
the regioselectivity in alcohol and micellar media promoted us
to probe the comparative rates of alkylation in these two me-
dia. Thus, we performed N-benzylation of benzotriazole with
benzyl chloride both in aqueous micelles (conc. ca. 1 cmc) and
in the ethanol solvent, keeping the substrates and alkali con-
centrations identical. A product analysis after 4 h of reaction
revealed ca. 47% and 52% conversion to N-benzylbenzotriaz-
ole, with the ratio of N1/N2 being 70: 30 and 74:26 in the mi-
celles and alcohol medium, respectively. Such a close parallel
in chemical yields and regioselectivity of the N-benzylation of
benzotriazole in alcohol and micellar media at least qualita-
tively supports the proposed similarity in the polarity of these
two reaction domains.11
In order to evaluate and extend the scope, we carried out
alkylations of Bt with a few activated as well as simple alkylat-
ing agents. Our results are collected in Table 1. The reaction
of an activated alkylating agent, phenacyl chloride, with Bt in
CTAB micelles, as expected, occurred relatively faster, pro-
ducing a copious white precipitate of the product just after 4 h
of reaction time. Two compounds, corresponding to N-1-3b
and N-2-phenacylbenzotriazoles 4b were isolated by SiO2 col-
umn chromatography in 80:20 ratio, respectively, in yields of
88%. The micellar N-alkylation of Bt with ethyl bromoace-
tate, during 4 h of reaction led to N-1-3c and N-2-4c alkylated
products in 80:20 ratio in good yield. The alkylation of Bt
with allyl bromide furnished N-1-3d and N-2-4d allylbenzotri-
A reaction of benzotraizole with bis(2-chloroethyl) ether 4

S. H. Mashraqui et al.
Bull. Chem. Soc. Jpn., 74, No. 11 (2001) 2135
Scheme 2.
in 2:1 proportion was carried out in aq CTAB micelles so as to
preferentially generate dialkylated products. Since only little
conversion was discernible after 6 h at room temperature, we
conducted the reaction at an elevated temperature of 70 °C,
whereby the reaction proceeded smoothly. After 7 h, the reac-
tion was extractively worked up to afford a complex mixture of
products. The crude product was chromatographed on a SiO2
column, resulting in the isolation of three compounds in pure
form (Scheme 2).
Micellar Catalyzed Michael Addition to Benzotriazole:
A few reports exist concerning the addition of Bt across elec-
tron-deficient alkenes under base catalysis. Good12 and
Moffat13 have described the addition reactions of Bt with 1,4-
naphthoquinone, chalcones, acrylonitrile, cinnamaldehyde etc.
in the presence of pyridine or Triton B as a catalyst, and isolat-
ed the corresponding N-1 adducts in 25 to 65% yields.
Euglero14 has shown by NMR analysis that the addition of
acrylonitrile on Bt gives both N-1 and N-2 products, the latter
being the kinetically controlled product. We investigated the
addition of Bt with a few representative examples of electron-
deficient olefins under a micellar medium to ascertain the fea-
sibility and regioselectivity of these additions (Scheme 3).
We first attempted a reaction between benzotriazole 1 and
chalcone 8 in alkaline aqueous CTAB micelles on the 10 mmol
scale. The resultant milky reaction was vigorously stirred for
24 h at room temperature. The crude product, upon SiO2 col-
umn chromatography, gave two compounds, a major polar, N-
1 adduct 9, mp 106–107 °C (Ref. 13, 106 °C) and an unknown,
less polar N-2 adduct 10 (mp 102–104 °C) in a combined yield
of 79% (80:20 ratio). The minor product was assigned the
structures as the N-2 adduct 10 based on its 1H NMR data. A
4-proton multiplet due to H-4 and H-7 of the benzotriazole
moiety and two ortho-protons of the phenacyl ring appeared
together in the region of δ 7.8 to 8.2; the remaining 10 aromat-
ic protons were found to be clubbed together between δ 7.2–
7.7. A one-proton double doublet centered at δ 6.7 (J = 10 Hz
and 4 Hz) can be assigned to N–CH–Ph, whereas two ethylene
protons (diestereotopic in nature) adjacent to the carbonyl
group appear individually at δ 3.7 (J = 18 and 4 Hz) and δ 5.0
(J = 18 and 10 Hz). Thus, the micellar process not only pro-
vides higher yields (79% compared to 65% reported in the
literature13), but also affords hitherto unreported N-2 adduct
10.
A low polar compound obtained as an oil (mol formula
C10H12ClN3O) was assigned the structure N-2 mono-alkylation
1
product 5 based on its 300 MHz H NMR data. Triplets cen-
tered at δ 4.8 and 4.18 are due to N–CH2 and –O–CH2CH2–
N–, respectively. The remaining four methylene protons
(ClCH2CH2O–) are seen as two overlapping triplets between δ
3.4–3.7. A characteristic A2B2 pattern for four aromatic pro-
tons appearing at δ 7.7 and 7.8 is indicative of the structure as
the symmetrical N-2 alkylated product 5. The second compo-
nent, with intermediate polarity (mp 75–76 °C), was a dialky-
lated product to which we assign the structure as unsymmetri-
cal N-1, Nꢀ-2-(oxydiethylene)bis(benzotriazole) 6. The un-
symmetrical nature of this compound is evident from the ap-
pearance of two overlapping multiplets, one between δ 3.8–4.4
and the other between δ 4.7–5.1, which could be assigned to
the –CH2OCH2– and –N–CH2CH2OCH2CH2–N– groups, re-
spectively. In the aromatic region, we noticed a downfield
shifted multiplet (3H, δ 7.8–8.2) arising from the H-4 proton
of the N-1 and Hꢀ-4 and the Hꢀ-7 protons of the Nꢀ-2 linked
benzotriazole moieties of 6. A complex multiplet integrating
for 5H (δ 7.2–7.6) can be accounted for by the remaining aro-
matic protons (H-5, H-6, H-7 of N-1 and Hꢀ-5, Hꢀ-6 of Nꢀ-2
linked aromatic ring). The most polar compound (mp 80–82
°C) showed triplets centered at δ 3.8 and 4.6 (J = 8 Hz each)
due to O–CH2– and –N–CH2– protons, respectively. A one-
proton multiplet (δ 7.95) is for the H-4 proton, whereas an
overlapping multiplet (3H) located between δ 7.0–7.3 is for the
remaining H-5, H-6 and H-7 protons of the aryl ring. These
data support the symmetric, bisN-1,Nꢀ-1-(oxydiethyl-
ene)bis(benzotriazole) 7 for this compound. The other possi-
ble product(s), such as N-1,Nꢀ-1-(oxydiethylene)bis(benzotri-
azole), though likely to be present in minor amounts in the
crude product, could not be isolated.
Consistent with the reduced electrophilicity of the 3ꢀ,4ꢀ-me-
thylenedioxychalcone 11, its micellar-catalyzed addition on Bt
proceeded slower than that of the simple chalcone 8. However,
practically a single adduct (ca. 97% purity, 65% yield), charac-
terized as the N-1 adduct 12, was isolated from the 3ꢀ,4ꢀ-meth-
ylenedioxychalcone reaction. The structure follows from its
1H NMR spectrum, particularly the appearance of a three-pro-
ton multiplet downfield located at δ 8.0 arising out of H-4 of

2136 Bull. Chem. Soc. Jpn., 74, No. 11 (2001)
Aqueous Micellar Medium in Organic Synthesis
Scheme 3.
the benzotriazole moiety and two ortho protons of the phena-
cyl ring. The remaining aromatic protons (9H) appear as an
overlapping multiplet in the range of δ 6.45 to 7.70.
above, this reaction was slower, giving only 50% conversion
after 72 h. Adducts N-1 17 and N-2 18 were isolated by SiO2
column chromatography in a 60:40 ratio. The structure of the
N-1 adduct 17 is deduced from the unsymmetric multiplet in
1:3 proton ratio for its aromatic protons, whereas the structure
of the N-2 18 is based on its characteristic A2B2 type multiplet
observed for its aromatic protons in 1H NMR spectrum.
Conclusion: The present work clearly demonstrates the
viability of aqueous CTAB micelles as a useful reaction do-
main in various alkylation reactions of benzotriazole. In spite
of moderate regioselectivity, the procedure is mild, economi-
cal, and easy to execute. In addition, we have provided experi-
mental evidence for micellar catalysis. In some micellar-cata-
lyzed Michael additions, in addition to the N-1 adduct, we
have also isolated for the first minor, N-2 adducts which have
not been more easily isolated under the homogeneous condi-
tions.
In contrast to the highly successful micellar additions of Bt
discussed above, the attempted addition of Bt on these 3ꢀ,4ꢀ-
methylenedioxychalcone in aqueous medium without CTAB
produced less than 10% of the corresponding Michael adducts.
Therefore, these Michael reactions are also subjected to con-
siderable micellar catalysis, affording much higher product
yields. Further, in agreement with a literature report, we found
these reactions to also be reversible in micelles. Thus, when
pure N-1 adduct 9 was stirred under alkaline micellar condi-
tion for a period of 4 h, we detected by tlc both N-1 and N-2
adducts (9 and 10) as well as the starting chalcone 8, which
strongly supports the reversible nature of these processes.
The micellar-catalyzed reaction of Bt 1 with acrylonitrile 13
occurred smoothly, affording the known N-1 adduct 14 (mp 79
°C, Ref. 13 mp 79–80 °C) together the unknown N-2 adduct 15
being isolated for the first time (N-1/N-2 ratio 70:30; yield
69%) from the present micellar condition. The structure of the
N-2 adduct 15 readily follows from the characteristic symmet-
rical A2B2-type coupling of aromatic protons (δ 7.5–7.75).
The Michael addition of maleic ester 16 to 1, a reaction which
is not reported in the literature, was also investigated in CTAB
micelles. Compared to the other Michael processes described
Experimental
The melting points (uncorrected) were determined on a Gallen-
kamp melting-point apparatus. IR spectral data were recorded on
a Shimadzu FTIR-4200 Spectrophotometer as a KBr disk or oil
film. 1H NMR spectra were recorded on Varian EM-360-L, 60
MHz, and 300 MHz Spectrometers with TMS as internal standard.

S. H. Mashraqui et al.
Bull. Chem. Soc. Jpn., 74, No. 11 (2001) 2137
7.5 (m, 3H), and 7.8–7.9 (m, 1H).
General Procedure: Alkylation of Benzotriazole with
Benzyl Chloride: Benzotriazole 1 (1.19 g, 10 mmol) and ben-
zyl chloride 2a (1.26 g, 10 mmol) were added to an alkaline
CTAB solution (40 mg of cetyltrimethylammonium bromide, ca. 1
× 10−4 mol dissolved in 100 mL of distilled water containing 0.50
g NaOH). The reaction mixture was then stirred at room tempera-
ture for 16 h. Thereafter, it was diluted with water and extracted
with a 4:1 v/v petroleum ether–ethyl acetate solvent system. The
organic extract, after drying over anhyd. Na2SO4, was concentrat-
ed to give a semisolid residue, which was chromatographed by
SiO2 using hexane: ethyl acetate (90:10) to give a less-polar prod-
uct, N-2-benzylbenzotriazole 4a as a colorless oil (Ref. 15, oil)
Preparation of N-1-3e and N-2-Phenethylbenzotriazoles 4e:
A micellar reaction of benzotriazole 1 (1.19 g, 10 mmol) with
phenethyl bromide 2e (1.85 g, 10 mmol) was stirred for 48 h. Pu-
rification of the crude product obtained upon a work-up was
achieved by SiO2 column chromatography (petroleum ether:ethyl
acetate, 80:20) to separate the two isomers. The less-polar N-2-
phenethylbenzotriazole 4e was isolated as a solid; mp 70 °C (0.70
g, 31%) (Ref. 17, mp 71 °C); IR (KBr disk) 3000, 1600 and 1570
cm−1, 1H NMR (60 MHz, CDCl3) δ 3.40 (t, J = 7 Hz, 2H), 4.9 (t,
J = 7 Hz, 2H), 7.0–7.3 (m, 7H), 7.8 (m, 2H). The more-polar, N-
1-isomer 3e was isolated as an oil (Ref. 17, mp 37 °C) in 38%
yield (0.858 g). IR (oil film) 3000, 1600 and 1620 cm−1; 1H NMR
(60 MHz, CDCl3) δ 3.20 (t, J = 7 Hz, 2H), 4.65 (t, J = 7 Hz, 2H),
6.8–7.3 (m, 8H), 7.8 (m, 1H).
(0.531 g, 25%). IR (oil film) 3000 and 1560 cm−1; H NMR (60
1
MHz, CDCl3) δ 5.8 (s, 2H), 7.1–7.5 (m, 7H), 7.84 (m, 2H). The
more-polar, N-1-benzylbenzotriazole 3a was obtained as a solid,
and crystallised from ethanol to give white crystals, mp 114.0 °C
(Ref. 15, mp 114 °C) (1.23 g, 59%). IR (KBr disk) 3000, 1620
Preparation of N-1-Propylbenzotriazole 3f: A micellar re-
action of benzotriazole 1 (1.19 g, 10 mmol) with propyl bromide
2f (1.23 g, 10 mmol) was carried out following the general proce-
dure. The oil obtained after a work-up and purification afforded
N-1-propylbenzotriazole 3f in 55% yield (0.885 g) (Ref. 8, oil).
1
and 1600 cm−1, H NMR (60 MHz, CDCl3) δ 5.89 (s, 2H), 7.2–
7.4 (m, 8H), 8.05 (m, 1H).
Preparation of N-1-3b and N-2-Phenacylbenzotriazoles 4b:
A micellar reaction of benzotriazole 1 (1.19 g, 10 mmol) with
phenacyl chloride 2b (1.54 g, 10 mmol) was performed under the
same condition as described in general procedure. The crude
product obtained upon work-up was chromatographed over SiO2
(hexane:ethyl acetate, 90:10) to separate the two isomers. The
less-polar N-2 phenacylbenzotriazole 4b eluted out first as a solid;
mp 157 °C (Ref. 15, mp 156–158 °C) (0.42 g, 17%). IR (KBr
IR (oil film) 3000, 1600 and 1620 cm−1 1H NMR (60 MHz,
;
CDCl3) δ 0.9 (t, J = 7 Hz, 3H), 2.0 (m, 2H), 4.58 (t, J = 7 Hz,
2H), 7.36 (m, 3H), 7.8 (m, 1H).
Preparation of N-1-Butylbenzotriazole 3g: A micellar re-
action of benzotriazole 1 (1.19 g, 10 mmol) with butyl bromide 2g
(1.37 g, 10 mmol) gave after a work-up and purification of the
crude product N-1-butylbenzotriazole 3g as oil (Ref. 1, oil) (0.613
disk) 3000, 1680 and 1560 cm−1; H NMR (60 MHz, CDCl3) δ
g, 35%). IR (oil film) 3000, 1600 and 1620 cm−1; H NMR (60
1
1
6.0 (s, 2H), 7.1–7.7 (m, 5H), 7.9–8.2 (m, 4H). Further elution
with the same solvent gave the more-polar N-1-phenacylbenzotri-
azole 3b as a colourless solid; mp 116 °C (Ref. 15, mp 116–117
°C) (1.70 g, 71% yield). IR (KBr disk) 3000, 1680, 1620 and
1600 cm−1; 1H NMR (60 MHz, CDCl3) δ 6.05 (s, 2H), 7.1–7.7 (m,
6H), 7.9 (m, 3H).
MHz, CDCl3) δ 1.0 (t, J = 7 Hz, 3H), 1.3–2.4 (m, 4H), 4.6 (t, J =
7 Hz, 2H), and 7.1–8.2 (m, 4H).
Preparation of Bis Alkylation Compounds: Reaction of
Benzotriazole with Bis(2-chloroethyl) Ether 4: A micellar re-
action of benzotriazole 1 (1.19 g, 10 mmol) with bis(2-chloroeth-
yl) ether 4 (1.43 g, 10 mmol) was heated to 70 °C when the reac-
tion was complete in 7 h. The oil obtained upon a work-up was
chromatographed on SiO2 (hexane:ethyl acetate, 90:10) to give
three compounds. The less-polar product, 2-[2-(2-chloroeth-
yl)ethyl]benzotriazole 5, was obtained in 13% yield (0.28 g). IR
Preparation of N-1-3c and N-2-(Ethoxycarbonylmeth-
yl)benzotriazoles 4c: A micellar reaction of benzotriazole 1
(1.19 g, 10 mmol) with ethyl bromoacetate 2c (1.67 g, 10 mmol)
was performed at room temperature for 4 h; thereafter, the reac-
tion was extractively worked-up to give a crude product. This was
subjected to SiO2 column chromatography (eluent, petroleum
ether–ethyl acetate, 80:20) to separate N-1 and N-2 isomers. The
less-polar, ethyl 2-benzotriazolylacetate 4c was isolated as a solid;
mp 120–21 °C, (Ref. 15, mp 121 °C) in 16% yield (0.35 g). IR
1
(oil film) 3000, 1600, 1570, 1150 and 760 cm−1; H NMR (300
MHz, CDCl3) δ 3.4–3.7 (tt, 4H), 4.18 (t, J = 7Hz, 2H), 4.8 (t, J =
7 Hz, 2H), 7.3 (m, 2H), 7.8 (m, 2H). Found: C, 52.9; H, 5.35; Cl,
15.54; N, 18.32%. Calcd for C10H12ClN3O: C, 53.2; H, 5.32; Cl,
15.74; N, 18.62%.
(KBr disk) 3000, 1760 and 1560 cm−1
;
1H NMR (60 MHz,
An intermediate product, identified as 1,2ꢀ-(oxydiethyl-
ene)bis(benzotriazole) 6, was obtained in 32% yield (0.986 g); mp
CDCl3) δ 1.2 (t, J = 7 Hz, 3H), 4.2 (q, 2H), 5.4 (s, 2H), 7.3–7.6
(m, 2H), 7.6–7.9 (m, 2H). The more-polar, ethyl 1-benzotriazo-
lylacetate 3c was isolated in 68% yield (1.51 g) mp 81 °C (Ref.
15, mp 81–82 °C). IR (KBr disk) 3000 and 1760 cm−1; 1H NMR
(60 MHz, CDCl3) δ 1.1 (t, J = 7 Hz, 3H), 4.1 (q, 2H), 5.3 (s, 2H),
7.3–7.7 (m, 3H), 7.9–8.2 (m, 1H).
1
75–76 °C. IR (KBr) 3000, 1600, 1620, 1570 and 1150 cm−1; H
NMR (300 MHz, CDCl3) δ 3.8–4.2 (m, 4H), 4.7–5.1 (m, 4H), 7.2–
7.6 (m, 5H), 7.8–8.28 (m, 3H). Found: C, 62.54; H, 5.05; N,
26.98%. Calcd for C16H16N6O: C, 62.33; H, 5.19; N, 27.27%. A
more-polar compound obtained as a solid, mp 80–82 °C, was
identified as 1,1ꢀ-bis(oxydiethylene)bis(benzotriazole) 7 (yield
22%, 0.69 g). IR (KBr disk) 3000, 1600, 1620 and 1500 cm−1; 1H
NMR (300 MHz, CDCl3) δ 3.8 (t, 4H), 4.6 (t, 4H), 7.0–7.3 (m,
6H), 7.9 (m, 2H). Found: C, 62.5; H, 5.35; N, 27.6%. Calcd for
C16H16N6O: C, 62.33; H, 5.19; N, 27.27%.
General Procedure for the Preparation of Michael Adducts
with Benzotriazole: To an aqueous CTAB solution (100 mL,
0.001 M) were added benzotriazole 1 (1.19 g, 10 mmol), chalcone
8 (2.08 g, 10 mmol) and 1 mL of 10% NaOH solution. The reac-
tion was stirred at room temperature for 24 h and extracted in di-
ethyl ether, dried, and concentrated to give a semi-solid residue.
The crude was subjected to SiO2 column chromatography (80:20,
Preparation of N-1-3d and N-2-Allylbenzotriazoles 4d:
A
micellar reaction of benzotriazole 1 (1.19 g, 10 mmol) with allyl
bromide 2d (1.2 g, 10 mmol) was carried out for a period of 24 h.
The crude product obtained upon the usual work-up was purified
by SiO2 column chromatography (petroleum ether:ethyl acetate,
80:20) to give the less-polar N-2-allylbenzotriazole 4d (0.34 g,
21%) as an oil (Ref. 16, oil); IR (oil film) 3000, 1570, 980 and 920
cm−1; 1H NMR (60 MHz, CDCl3) δ 5.0–5.4 (m, 4H), 5.5–6.0 (m,
1H), 7.0–7.3 (m, 2H), 7.5–7.7 (m, 2H). The more-polar N-1-allyl-
benzotriazole 3d was obtained as colourless oil (Ref. 16, oil) (0.68
1
g, 42%). IR (oil film) 3000, 1620, 1600, 980 and 930 cm−1; H
NMR (60 MHz, CDCl3) δ 5.0–5.4 (m, 4H), 5.5–6.0 (m, 1H), 7.0–

2138 Bull. Chem. Soc. Jpn., 74, No. 11 (2001)
Aqueous Micellar Medium in Organic Synthesis
petroleum ether:hexane) to afford two isomeric adducts. The
less-polar Michael adduct, N-2 10, was isolated in 16% yield
(0.52 g); mp 102–104 °C. IR (KBr disk) 1680, 1600 and 1570
cm−1; 1H NMR (60 MHz, CDCl3) δ 3.8–4.8 (m, 2H), 6.7–7.0 (m,
1H), 7.2–7.7 (m, 10H), 7.8–8.2 (m, 4H). MS m/z 327 (M+), 222,
120, 105 (base peak), 91, 77. Found: C, 76.9; H, 5.23; N, 12.9%.
Calcd for C21H17N3O: C, 77.06; H, 5.19; N, 12.84%.
N, 13.98%. Anal. Calcd for C14H17N3O4: C, 57.73; H, 5.84; N,
14.4%.
References
1
a) R. Boehm, Pharmazie, 33, 83 (1978). b) J. Elguero, S.
The major product, N-1 Michael adduct 9, was obtained in 2.08
g, 63% yield, mp 106–107 °C (Ref. 13, mp 106 °C). IR (KBr
Julia, J. M. Del Mazo, and L. Avila, Org. Prep. Proced. Int., 16,
299 (1984). c) L. J. Mathias and D. Burkett, Tetrahedran Lett., 49,
4709 (1979). d) K. Sukata, Bull. Chem. Soc. Jpn., 56, 280 (1983).
e) H. Aixi and Z. Zhaoqiong, Goodeng Xuexiao Huaxue Xuebao,
10, 769 (1989); Chem. Abstr., 112, 198239g (1989). f) M.
Searcey, J. B. Lee, and P. L. Pye, Chem. Ind. (London), 1989, 569.
1
disk) 1680, 1600 and 1620 cm−1; H NMR (60 MHz, CDCl3) δ
3.5–5.8 (m, 2H), 6.5 (dd, 1H), 7.1–7.6 (m, 11H), 7.8–8.2 (m, 3H).
Reaction of Benzotriazole with 3ꢀ,4ꢀ-Methylenedioxychal-
cone: The reaction of benzotriazole 1 (1.19 g, 10 mmol) with
3ꢀ,4ꢀ-methylenedioxychalcone 11 (2.52 g, 10 mmol) under the
same conditions as described above afforded after an extractive
work-up a single component as the N-1 Michael adduct 12 (2.42
g, 65%) (mp 128–130 °C). IR (KBr disk) 1680, 1600, 1620 and
1020 cm−1; 1H NMR (60 MHz, CDCl3) δ 3.6–5.1 (m, 2H), 5.9 (s,
2H), 6.3–6.7 (m, 1H), 6.8–7.7 (m, 9H), 7.8–8.2 (m, 3H). MS m/z
371 (M+), 252 (base peak), 119, 91, 77; Found: C, 70.9; H, 4.72;
N, 11.55%. Calcd for C22H17N3O3: C, 71.15; H, 4.58; N, 11.32%.
2
a) “The Tautomerism of Hetreocycles, Adv. Heterocycl.
Chem.,” Supplement 1, ed by J. Elguero, C. Marzin, A. R.
Katrizky, and P. Linda, Academic Press, New York (1976). b) N.
K. Roberts, J. Chem. Soc., 1963, 5556. c) P. Mauret, J. P. Fayet, J.
Elguero, and J. de Mendoza, J. Chim. Phys., 71, 115 (1974).
3
a) F. Sporatore, M. I. La Rotonda, G. Paglietti, E.
Ramundo, C. Silipo, and A. Vittoria, Farmaco, Ed. Sci., 33, 901
(1978); Chem. Abstr., 90, 103903 (1978). b) R. E. Deal and R. V.
Kendall, Jpn. Kokai., 78121762 (1978); Chem. Abstr., 88, 190843.
c) American Cyanamid CO., Belg. Patent 853179 (1977); Chem.
Abstr., 88, 190843. d) R. E. Diehl and R. V. Kendall, US Patent
4240822 (1980); Chem. Abstr., 94, 134160 (1980). e) H.
Wamhoff, “Comprensive Heterocyclic Chemistry,”1st ed, by K. T.
Potts, Pergamon Press, U.K. (1984), Vol. 5, p. 669.
Reaction of Benzotriazole with Acrylonitrile:
A
micellar
reaction of benzotriazole 1 (1.19 g, 10 mmol) with acrylonitrile 13
(0.53 g, 10 mmol) was carried under the same condition as de-
scribed above. The oil obtained after extractive work-up was
chromatographed on SiO2 (petroleum ether:hexane, 80:20) to
separate the N-1 and N-2 adducts. The N-2 adduct 15 obtained in
21% yield (0.361 g) mp 90–91 °C was crystallised from ethanol.
4
C. D. Mudaliar and S. H. Mashraqui, J. Chem. Res., (S),
1
IR (KBr disk) 3000, 2200 and 1570 cm−1; H NMR (60 MHz,
174 (1994).
CDCl3) δ 3.2 (t, J = 7 Hz, 2H), 5.0 (t, J = 7 Hz, 2H), 7.2–7.5 (m,
5
C. D. Mudaliar and S. H. Mashraqui, Org. Prep. Proced.
2H), 7.7–8.0 (m, 2H).
Found: C, 62.62; H, 4.67; N, 32.38%.
Int., 29, 584 (1997).
Calcd for C9H8N4: C, 62.79; H, 4.65; N, 32.55%.
6
(1992).
7
C. D. Mudaliar and S. H. Mashraqui, J. Chem. Res., (S), 98
The N-1 adduct 14 obtained in 48% yield (0.84 g) mp 79 °C
(Ref. 13, mp 79–80 °C) was crystallised from ethanol. IR (KBr
J. E. Fagel, Jr and G. W. Ewing, J. Am. Chem. Soc., 73,
disk) 3000, 2250, 1620 and 1600 cm−1
;
1H NMR (60 MHz,
4360 (1951).
CDCl3) δ 3.15 (t, J = 7 Hz, 2H), 4.9 (t, J = 7 Hz, 2H), 7.2–7.7 (m,
3H), 7.9–8.2 (m, 1H).
8
9
A. R. Katritzky and J. Wu, Synthesis, 1994, 597.
F. Krollp feiffer, H. Potz, and A. Rosenberg, Ber. Dtsch.
Reaction of Benzotriazole with Maleic Ester 16: Reaction
of benzotriazole 1 (1.19 g, 10 mmol) with maleic ester 16 (1.72 g,
10 mmol) was proceeded slowly; after 72 h an extractive work-up
gave an oil, which was chromatographed (hexane:ethyl acetate,
80:20) to afford three compounds. The unreacted starting materi-
al was recovered (0.86 g, 50%). The less-polar N-2 adduct 18 was
obtained in 20% yield (0.58 g) (mp 68–70 °C). IR (KBr disk)
Chem. Ges., 71B, 596 (1938).
10 J. Torres, J. L. Lavandera, P. Cabildo, R. H. Claramunt, and
J. Elguero, J. Heterocycl. Chem., 25, 771 (1988).
11 J. H. Fendler, “Membrane Mimetic Chemistry,” Wiley In-
terscience, New York, (1982).
12 R. H. Good and M. Bellas, Res. Discl., 182, 299 (1979).
13 R. H. Willey, N. R. Smith, D. M. Johnson, and J. Moffat, J.
Am. Chem. Soc., 76, 4933 (1954).
1
1740 and 1565 cm−1; H NMR (60 MHz, CDCl3) δ 1.2 (t, J = 7
Hz, 6H), 3.5 (d, 2H), 4.2 (q, 4H), 6.05 (t, J = 7 Hz, 1H), 7.2–7.5
(m, 2H), 7.7–8.0 (m, 2H). MS m/z 291 (M+), 246, 218 (base
peaks), 146, 118, 91, 77; Found: C, 57.53; H, 5.76; N, 14.28%.
Calcd for C14H17N3O4: C, 57.73; H, 5.84; N, 14.4%.
14 A. De La Cruz, J. Elguero, and M. A. Goyapllar, J. Hetero-
cycl. Chem., 25, 225 (1988).
15 A. R. Katritzky, Kuzmierkiewicz, and J. V. Greenhill, Recl.
Trav. Chim. Pays-Bas, 110, 369 (1991).
The N-1 adduct 17 was obtained in 29% yield (0.844 g) as a
viscous oil. IR (oil film) 1740, 1620 and 1600 cm−1; 1H NMR (60
MHz, CDCl3) δ 1.1 (tt, 6H), 3.4 (m, 2H), 3.9–4.3 (m, 4H), 5.8 (t,
1H), 7.2–7.5 (m, 3H), 7.8–8.0 (m, 1H); Found: C, 57.42; H, 5.59;
16 C. W. Rees and R. C. Storr, J. Chem. Soc., Chem. Com-
mun., 1969, 1478.
17 a) H. Suschitzky and B. W. Ashton, J. Chem. Soc., 1957,
4559. b) A. P. Miller, S. African 7606, 188 (1977).