N-alkylation of 2,4,5-triphenyl imidazole derivatives using a new phase transfer reagent under PTC conditions

Article abstract of DOI:10.1081/SCC-100105320

The phase transfer catalyzed N-alkylation of 2,4,5-triphenyl imidazole derivatives using a new phase transfer reagent namely, 2-benzilidine-N,N,N,N′,N′,N′-hexaethyl propane-1,3-diammonium dibromide have been described. The structures of all the 14 compounds have been established by spectroscopic means.

Full text of DOI:10.1081/SCC-100105320

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N-ALKYLATION OF 2,4,5-TRIPHENYL IMIDAZOLE
DERIVATIVES USING A NEW PHASE TRANSFER
REAGENT UNDER PTC CONDITIONS
Joseph Paul Jayachandran a & Maw-Ling Wang b
a Department of Chemical Engineering, National Chung Cheng University, Chiayi, 621,
Taiwan, R. O. C
b Department of Chemical Engineering, National Chung Cheng University, Chiayi, 621,
Taiwan, R. O. C
Published online: 15 Aug 2006.
To cite this article: Joseph Paul Jayachandran & Maw-Ling Wang (2001) N-ALKYLATION OF 2,4,5-TRIPHENYL IMIDAZOLE
DERIVATIVES USING A NEW PHASE TRANSFER REAGENT UNDER PTC CONDITIONS, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:18, 2743-2752, DOI: 10.1081/
SCC-100105320
To link to this article: http://dx.doi.org/10.1081/SCC-100105320
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SYNTHETIC COMMUNICATIONS, 31(18), 2743–2752 (2001)
N-ALKYLATION OF 2,4,5-TRIPHENYL
IMIDAZOLE DERIVATIVES USING
A NEW PHASE TRANSFER REAGENT
UNDER PTC CONDITIONS
Joseph Paul Jayachandran and Maw-Ling Wang*
Department of Chemical Engineering,
National Chung Cheng University,
Chiayi, Taiwan 621, R.O.C
ABSTRACT
The phase transfer catalyzed N-alkylation of 2,4,5-triphenyl
imidazole derivatives using a new phase transfer reagent
namely, 2-benzilidine-N,N,N,N0,N0,N0-hexaethyl propane-
1,3-diammonium dibromide have been described.The
structures of all the 14 compounds have been established by
spectroscopic means.
Phase transfer catalysis (PTC) is presently well recognized as a general
methodology for promoting reactions between water-soluble reagents and
water-insoluble organic substrates.1–3 The advances of the same in the recent
years have made a remarkable impact in organic synthesis and are being
enormously employed in a multitude of organic transformations.The
primary advantages of PTC in organic syntheses are high product yield,
*Corresponding author.
2743
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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JAYACHANDRAN AND WANG
large reaction rates, and high selectivity of the desired products.The main
principle in PTC involves the continuous formation of a lipophilic ion-pair
of an anionic reactant with a lipophilic cation such a tetraalkyl-ammonium
ion and the transport of the anionic reactant from the aqueous phase into
the organic phase where it effectively reacts with a second reactant.
N-alkylation of aromatic compounds involving nitrogen heterocycles
are important reactions in organic syntheses.Conventional procedures insist
the use of polar aprotic solvents under strictly anhydrous conditions.4
N-alkylation of nitrogen heterocycles namely, indole and pyrrole can also
be achieved by using various bases such as sodium amide, potassium,
sodium hydroxide in hexamethylphosphoric triamide, KOH in DMSO and
thallium(I) ethoxide.5–9 Makosza10 synthesised N-alkylindoles and N-butyl-
carbazole under PTC conditions.The advantages of performing N-alkylation
under base-catalyzed PTC conditions coupled with the importance of
N-alkylation in pharmaceuticals, agricultural, chemical, and other products
have led N-alkylation to be among the most widely used applications of PTC.
We have synthesized and characterized a novel phase transfer reagent,
namely, 2-benzilidine-N,N,N,N0,N0,N0-hexaethylpropane-1,3-diammonium
dibromide (Dq–Br) and studied its utility in simple dichlorocarbene addition
to olefins11 and in the synthesis of 2-mercaptobenzimidazole derivatives.12
Acetophenone, when reacted with excess aqueous formaldehyde in the
presence of CaO at 60ꢀC gave 1-phenyl-2,4,8,10-tetraoxaspiro[5.5] undecane
(1).The spiro compound 1 was brominated by refluxing with hydrobromic
acid (48% solution) resulting in the formation of dibromocompound 2.The
compound 2 was quaternised with excess triethylamine using dry acetonitrile
as a solvent under reflux to yield the desired Diquat, Dq–Br.It was found
to be highly hygroscopic.The structures were confirmed by spectroscopic
means.A detailed procedure for the synthesis of the Diquat, Dq–Br is
reported elsewhere.11
Control experiments of dichlorocarbene addition to olefins in the
absence of the catalyst resulted in 1% conversion in 3 h.Preliminary
studies17,18 on the catalytic abilities of the new Diquat, Dq–Br, revealed
its synthetic utility under PTC/OHÀ conditions.Control experiments in
the preparation of 2-mercaptobenzimidazole derivatives in the absence of
the catalyst under specified conditions proceed with low conversions.High
yields of products were obtained using the new Diquat, Dq–Br.

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2,4,5-TRIPHENYL IMIDAZOLE DERIVATIVES
2745
In continuation of our studies related to the utility of a new phase
transfer reagent, we report N-alkylation of 2,4,5-triphenyl imidazole deriva-
tives using the new phase transfer reagent (Dq–Br) under PTC conditions.
EXPERIMENTAL
General: 1H NMR (400 MHz) and 13C NMR (100 MHz) were recorded
on a BRUKER-AM-400 NMR spectrometer with TMS as an internal stan-
dard.Mass spectra were obtained on a JEOL JMS-100 mass spectrometer at
ionization potential, 12 eV.The infrared spectra were measured on a
PERKIN-ELMER model 983 IR spectrometer.Liquid chromatography
was carried out using Shimadzu LC-9A instrument.
General Procedure for the N-Alkylation of
2,4,5-Triphenyl Imidazole Derivatives
A 150 ml cm3 three-necked round bottomed flask fitted with double
walled condenser was charged with 100 mg of 2,4,5-triphenyl imidazole deri-
vative (the different imidazole derivatives were prepared according to the
reported procedures) dissolved in 20 cm3 dichloromethane, 45 cm3 w/w
NaOH and 10 mol% Dq–Br (based on the substrate amount).The contents
were conditioned for 10 min with thermostat maintained at 50ꢀC.Alkyl
halide (n-butyl bromide/ethyl bromide/allyl bromide ¼ 10 mL) was added
to the reaction vessel and stirred for 5 h at 500 rpm.Samples were withdrawn
from the organic layer at regular intervals of time and were analyzed using
HPLC model LC 9A (Shimadzu) having an absorbance detector (254 nm,
SPD-6A) and column, Merck RP-8 (5 mm).The eluent was acetonitrile/
water ¼ 50 : 50 with flow rate 1.2 ml/min. To the cold reaction, ether (30 mL)
was added, washed repeatedly with deionized water and dried over anhy-
drous magnesium sulfate.The excess, low boiling alkyl bromides were also
removed.The compound was purified using silica gel column chromatogra-
phy.The spectral properties were in agreement with the expected products.
SPECTRAL DATA
1-Butyl-2-(40-methoxyphenyl)-4,5-diphenyl Imidazole (1)
1H NMR (400 MHz, CDCl3): d ¼ 7.8–7.0 (m, 14H, Aromatic), 3.85
(s, 3H, -OCH3), 3.8 (t, 2H, -NCH2), 1.3–1.2 (m, 2H, -CH2), 0.98–0.94

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JAYACHANDRAN AND WANG
Table 1. N-Alkylations of Triphenyl Imidazole Derivatives under PTC Conditions
a
S.No.
Substrate
Product
% Conv.
1
87
2
90
3
89
4
88
5
77
6
80
(continued )

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2,4,5-TRIPHENYL IMIDAZOLE DERIVATIVES
2747
Table 1. Continued
a
S.No.
Substrate
Product
% Conv.
7
82
79
78
8
9
10
11
12
80
85
83
(continued )

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JAYACHANDRAN AND WANG
Table 1. Continued
Product
a
S.No.
Substrate
% Conv.
13
14
80
87
a% conversion by HPLC.
(m, 2H, -CH2), 0.6 (t, 3H, -CH3). nmax/cmÀ1: 2950, 1612, 1475, 1250, 1188,
1038, 838.MS ( m/z): 384 (Mþ, 45), 383 (100), 382 (77), 381 (8), 353 (13), 105
(9).HRMS: m/z, Calculated: 382.5055, Found: 382.5039.
1-Ethyl-2-(40-fluorophenyl)-4,5-diphenyl Imidazole (2)
1H NMR (400 MHz, CDCl3): d ¼ 7.8–7.1 (m, 14H, Aromatic), 3.9 (q,
2H, -CH2), 1.0 (t, 3H, -CH3). nmax/cmÀ1: 2981, 1728, 1653, 1480, 1270, 1118,
647.MS ( m/z): 371 (Mþ, 17), 344 (43), 343 (100), 342 (100), 342 (66), 341 (13),
313 (6), 165 (8), 104 (6).HRMS: m/z, Calculated: 370.4695, Found: 370.4087.
1-Ethyl-2-(40-methylphenyl)-4,5-diphenyl Imidazole (3)
1H NMR (400 MHz, CDCl3): d ¼ 7.8–7.0 (m, 14H, Aromatic), 3.9
(q, 2H, -CH2), 2.4 (s, 3H, -CH3), 1.0 (t, 3H, -CH3). nmax/cmÀ1: 2990, 1600,
1480, 1381, 1070, 960, 829.MS ( m/z): 367 (Mþ, 4), 340 (26), 339 (100),
338 (100), 338 (48), 337 (10), 309 (4), 165 (7), 118 (4), 104 (5), 91 (4), 77
(4).HRMS: m/z, Calculated: 367.5085, Found: 367.4982.
1-Ethyl-2,4,5-triphenyl Imidazole (4)
1H NMR (400 MHz, CDCl3): d ¼ 7.8–7.0 (m, 15H, Aromatic), 4.0
(q, 2H, -CH2), 1.0 (t, 3H, -CH3). nmax/cmÀ1: 2974, 1891, 1600, 1444, 1272,

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2749
1072, 849, 741.MS ( m/z): 326 (Mþ, 24), 325 (100), 324 (44), 323 (8), 295
(4), 178 (3), 104 (8), 89 (3).HRMS: m/z, Calculated: 324.4253, Found:
324.4171.
1-Butyl-2,4,5-tris( p-methoxyphenyl) Imidazole (5)
1H NMR (400 MHz, CDCl3): d ¼ 7.8–6.9 (m, 12H, Aromatic), 3.85 (s,
3H, -OCH3), 3.83 (s, 3H, -OCH3), 3.80 (t, 2H, -CH2), 3.70 (s, 3H, -OCH3),
1.3 (m, 2H, -CH2), 1.0 (m, 2H, -CH2), 0.6 (t, 3H, -CH3). nmax/cmÀ1: 2980,
1887, 1725, 1612, 1450, 1225, 1025, 825.MS ( m/z): 444 (Mþ, 34), 443 (100),
442 (75), 44 (9), 413 (6), 386 (5), 135 (12), 134 (15), 105 (6), 57 (9).HRMS:
m/z, Calculated: 442.5585, Found: 442.5310.
1-Butyl-2-(40-bromophenyl)-4,5-bis( p-methoxyphenyl)
Imidazole (6)
1H NMR (400 MHz, CDCl3): 7.9–6.8 (m, 12H, Aromatic), 3.86
(s, 3H, -OCH3), 3.81 (t, 2H, -CH2), 3.75 (s, 3H, -OCH3), 1.3 (m, 2H,
-CH2), 0.91 (m, 2H, -CH2), 0.6 (t, 3H, -CH3). nmax/cmÀ1: 2985, 1700,
1600, 1475, 1237, 1012, 825.MS ( m/z): 494 (Mþ, 27), 493 (98), 492 (74),
491 (74), 491 (100), 490 (49), 443 (8), 184 (8), 154 (32), 137 (15), 135 (65), 107
(11), 105 (12), 77 (12), 57 (8).HRMS: m/z, Calculated: 491.4281, Found:
491.4111.
1-Butyl-2-(40-fluorophenyl)-4,5-bis( p-methoxyphenyl) Imidazole (7)
1H NMR (400 MHz, CDCl3): 7.8–6.8 (m, 12H, Aromatic), 3.9 (s, 3H,
-OCH3), 3.80 (t, 2H, -CH2), 3.75 (s, 3H, -OCH3), 1.30 (m, 2H, -CH2), 0.9
(m, 2H, -CH2), 0.6 (t, 3H, -CH3). nmax/cmÀ1: 2990, 1737, 1612, 1462, 1250,
1162, 1050, 838.MS ( m/z): 432 (Mþ, 27), 431 (100), 430 (74), 401 (4), 374
(5), 135 (23), 122 (9).HRMS: m/z, Calculated: 430.5225, Found: 430.5089.
1-Butyl-2-(40-nitrophenyl)-4,5-bis( p-methoxyphenyl) Imidazole (8)
1H NMR (400 MHz, CDCl3): 8.2–6.8 (m, 12H, Aromatic), 3.95 (t, 2H,
-CH2), 3.90 (s, 3H, -OCH3), 3.73 (s, 3H, -OCH3), 1.3 (m, 2H, -CH2), 1.0 (m,
2H, -CH2), 0.6 (t, 3H, -CH3). nmax/cmÀ1: 2992, 1712, 1612, 1275, 1150, 1037,

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JAYACHANDRAN AND WANG
812.MS ( m/z): 459 (Mþ, 29), 458 (100), 457 (71), 442 (14), 412 (10), 356 (5),
135 (13), 77 (5), 57 (12).HRMS: m/z, Calculated: 457.5300, Found: 457.5079.
1-Allyl-2,4,5-tris( p-methoxyphenyl) Imidazole (9)
1H NMR (400 MHz, CDCl3): d ¼ 8.0–6.8 (m, 12H, Aromatic),
5.15–4.90 (m, 3H, -CH ¼ CH2), 3.84 (m, 2H, -CH2), 3.82 (s, 3H, -OCH3),
3.79 (s, 3H, -OCH3), 3.70 (s, 3H, -OCH3). nmax/cmÀ1: 2995, 1725, 1615,
1512, 1262, 1038, 850.MS ( m/z): 427 (Mþ, 36), 386 (27), 293 (7), 192 (5),
136 (13), 135 (100), 105 (11), 91 (11), 81 (10), 57 (28), 41 (35).HRMS: m/z,
Calculated: 426.5157, Found: 426.4991.
1-Allyl-2-(40-bromophenyl)-4,5-bis( p-methoxyphenyl)
Imidazole (10)
1H NMR (400 MHz, CDCl3): d ¼ 8.0–6.6 (m, 12H, Aromatic),
5.21–4.89 (m, 3H, -CH ¼ CH2), 3.81 (s, 3H, -OCH3), 3.79 (m, 2H, -CH2),
3.71 (s, 3H, -OCH3). nmax/cmÀ1: 2992, 1712, 1600, 1512, 1263, 1025, 825.MS
(m/z): 475 (Mþ, 77), 435 (23), 280 (5), 183 (19), 135 (100), 115 (10), 105 (16), 91
(12), 77 (19), 41 (36).HRMS: m/z, Calculated: 475.3853, Found: 475.3096.
1-Allyl-2-(40-fluorophenyl)-4,5-bis( p-methoxyphenyl)
Imidazole (11)
1H NMR (400 MHz, CDCl3): d ¼ 8.2–6.71 (m, 12H, Aromatic),
5.27–4.79 (m, 3H, -CH ¼ CH2), 3.84 (s, 3H, -OCH3), 3.80 (m, 2H, -CH2),
3.77 (s, 3H, -OCH3). nmax/cmÀ1: 2995, 1737, 1612, 1512, 1262, 1050, 837.
MS (m/z): 416 (Mþ, 31), 415 (100), 414 (58), 375 (19), 374 (45), 373 (16), 359
(9), 281 (9), 135 (68), 123 (46), 105 (15), 77 (13), 41 (28).HRMS: m/z,
Calculated: 414.4797, Found: 414.4675.
1-Ethyl-2-(40-chlorophenyl)-4,5-bis( p-methoxyphenyl)
Imidazole (12)
1H NMR (400 MHz, CDCl3): d ¼ 8.0–6.9 (m, 12H, Aromatic), 3.85 (s,
3H, -OCH3), 3.84 (s, 3H, -OCH3), 3.72 (q, 2H, -CH2), 1.0 (t, 3H, -CH3).
n
max/cmÀ1: 2838, 1722, 1656, 1599, 1225, 1017, 832.MS ( m/z): 418 (Mþ, 60),

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2,4,5-TRIPHENYL IMIDAZOLE DERIVATIVES
2751
415 (100), 389 (5), 299 (13), 271 (18), 162 (12), 135 (79).HRMS: m/z,
Calculated: 418.9230, Found: 418.9012.
1-Ethyl-2-(40-methylphenyl)-4,5-bis( p-methoxyphenyl)
Imidazole (13)
1H NMR (400 MHz, CDCl3): d ¼ 7.55–6.71 (m, 12H, Aromatic), 3.87
(s, 3H, -OCH3), 3.83 (q, 2H, -CH2), 3.71 (s, 3H, -OCH3), 2.38 (s, 3H, -CH3),
0.97 (t, 3H, -CH3). nmax/cmÀ1: 2987, 1738, 1612, 1487, 1250, 1100, 825.MS
(m/z): 400 (Mþ, 28), 399 (100), 398 (68), 369 (5), 134 (6), 91 (5), 69 (6), 57 (8).
HRMS: m/z, Calculated: 398.5015, Found: 398.4989.
1-Ethyl-2-(40-bromophenyl)-4,5-diphenyl Imidazole (14)
1H NMR (400 MHz, CDCl3): d ¼ 7.90–7.28 (m, 14H, Aromatic), 3.87
(q, 2H, -CH2), 1.1 (t, 3H, -CH3). nmax/cmÀ1: 2977, 1731, 1676, 1476, 1238,
1179, 1072, 833.MS ( m/z): 431 (Mþ, 34), 403 (100), 325 (14), 211 (13), 178
(7), 165 (19), 105 (40), 77 (15), 57 (8).HRMS: m/z, Calculated: 431.3751,
Found: 431.3114.
ACKNOWLEDGMENT
The authors thank the National Science Council, Taiwan, ROC for
the financial support under contract no.NSC87-2214-E007-012.
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8. Heanery, H.; Ley, S.V. J. Chem. Soc., Perkin Trans. 1 1973, 499.
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Received in Japan August 1, 2000

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