Cathodic reduction of phenacyl azides

Article abstract of DOI:10.1021/ol990200j

(matrix presented). The electrochemical reduction of phenacyl azides (1a-e) leads to the formation of 2-aroyl-4-arylimidazoles (2a-e) (70-80% yield). 1a-e were prepared from phenacyl bromides and sodium azide and were reduced in aprotic DMF-LiClO₄

Full text of DOI:10.1021/ol990200j

ORGANIC
LETTERS
1999
Vol. 1, No. 10
1521-1522
Cathodic Reduction of Phenacyl Azides
Bele´n Batanero, Jose´ Escudero, and Fructuoso Barba*
Department of Organic Chemistry, UniVersity of Alcala´, 28871 Alcala´ de Henares,
Madrid, Spain
fructuoso.barba@uah.es
Received July 29, 1999
ABSTRACT
The electrochemical reduction of phenacyl azides (1a−e) leads to the formation of 2-aroyl-4-arylimidazoles (2a−e) (70−80% yield). 1a−e were
prepared from phenacyl bromides and sodium azide and were reduced in aprotic DMF-LiClO medium at the mercury cathode in a divided cell
4
and under controlled potential.
Little attention has been paid to the cathodic reduction of
azides. The electroreduction of azides was studied under
protic conditions.1 In this paper it was concluded that
depending on the group directly linked to the azide function,
one can obtain either an amine group with extrusion of
dinitrogen or a loss of azide anion.
The enolate a acts as an electrogenerated base,3 which
abstracts a proton from another substrate molecule to give a
new enolate (b). This new enolate loses a N2 molecule to be
transformed into anion c, which is a strong base. Reaction
with the starting azide affords phenyl glyoxal imino inter-
Recently we have studied the cathodic reduction of
phenacyl azide thiosemicarbazones under aprotic conditions.2
They afford N-substituted imidazolethiones in good yield.
Due to the interest in these reactions and the mechanistic
uncertainty, we have further studied the cathodic reduction
of phenacyl azides (1) under aprotic conditions.
Scheme 1
After only 10% of the expected current for a theoretical
2F process, the current fell to zero. At this point, analysis of
the cathodic solution was performed. Surprisingly, no phena-
cyl azide remained; the products were 2-aroyl-4-arylimida-
zole (2) (70-80%), 2-(2-aroyl-1-arylethenyl)-4-arylimidazole
(3), and other minority products (e.g., acetophenone).
The rationalization of these results is sumarized as
follows: In a first step, the cleavage of the C-N3 bond takes
place in a 2F process as was demonstrated in a previous
paper.2 In this way an amount of the corresponding enolate
(a) is formed.
(1) Lund, H. Oesterreich. Chem. Z. 1967, 68, 43.
(2) Batanero, B.; Escudero, J.; Barba, F. Synthesis 1999, in press.
(3) Baizer, M. M. Organic Electrochemistry, 3rd ed.; Lund, H., Baizer,
M. M., Eds.; Marcel Dekker: New York 1991; pp 1265-1272.
10.1021/ol990200j CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/20/1999

mediate and the enolate b, which continues reacting accord-
ing to Scheme 1 until all the substrate is consumed.
Pinner4 described the formation of 2-benzoyl-4-phenylimi-
dazole (2a) when phenyl glyoxal was heated in the presence
of ammonia. The reaction is believed to involve a dimer-
ization of the phenyl glyoxal imino intermediate followed
by dehydration.
Boyer and Straw5 prepared 2a by pyrolysis of phenacyl
azide. In this case, the postulated intermediate was again the
phenyl glyoxal imino derivative.
this reason condensation before cyclization is proposed for
the formation of 3.
A series of 2,4-disubstituted imidazoles have been prepared
using this efficient and convenient procedure.6
Acknowledgment. This study was supported by the
spanish Ministery of Education and Culture. PB97-0753.
OL990200J
of phenacyl bromides (25 mmol) in methanol (40 mL) were poured over
an aqueous solution of sodium azide (1.63 g, 25 mmol, 40 mL) in an ice
bath. After 2 h, the phenacyl azides were obtained in almost quantitative
yields by removing the solvent under reduced pressure to dryness (azides
can be explosiVe compounds and appropiate caution should be taken with
these and related compounds), extracting the crude reaction mixture with
Et2O (80 mL) and water (80 mL), and drying the ethereal solution with
MgSO4. The electrochemical reductions were carried out at -1 V (vs SCE)
using a concentric cell with two compartments separated by a porous (D3)
glass tubing diaphragm and equipped with a magnetic stirrer. The solvent
supporting electrolyte (SSE) was DMF-LiClO4. Anhydrous solid K2CO3
(2.0 g, 145 mmol) was added to the anodic compartment for “in situ”
neutralization of the generated perchloric acid. Other details: anode,
platinum; anolyte, LiClO4 (0.42 g, 4.0 mmol) in dry DMF (10 mL); Cathode,
mercury pool (20 cm2); catholyte, LiClO4 (1.5 g, 14 mmol) containing the
corresponding phenacyl azide (2.0 mmol) in dry DMF (30 mL). At the end
of the electrolysis (it was considered finished when the current fell to zero)
the cathodic solution was poured onto ice water (500 mL). After 12 h, the
precipitated solid was filtered and dried under reduced pressure and
chromatographed on a silica gel (17× 2.5 cm) column, using toluene/
methanol (40/1)as eluent. 2-Benzoyl-5-phenylimidazole (2a): 70%; mp
197-199 °C (lit.4 mp 196-198 °C); IR (KBr) ν 3274, 1618, 1290, 1168,
690; 1H NMR (300 MHz, DMSO) δ 13.6 (bs, 1H), 8.58 (d, 2H, J ) 7 Hz),
8.08 (s, 1H, CHd), 7.92 (m, 2H), 7.2-7.8 (m, 6H);13C NMR (75.4 MHz,
DMSO) δ 118.7, 125.0, 127.3, 128.4, 128.7, 130.7, 133.2, 133.8, 136.1,
143.0, 144.8, 180.9; MS m/e (relative intensity) EI 249 (M+ + 1, 4), 248
(M+, 26), 220(26), 142(9), 116(21), 105(58), 77(100), 51(40). 2-(p-
Methoxybenzoyl)-5-(p-methoxyphenyl)imidazole (2b): 71%; mp 216-
218 °C; IR (KBr) ν 3271, 1607, 1250, 1164, 832; 1H NMR (300 MHz,
DMSO) δ 13.4 (bs, 1H), 8.7 (d, 2H, J ) 8.7 Hz), 7.8-8 (m, 3H), 6.9-7.2
(m, 4H), 3.87 (s, 3H, MeO), 3.78 (s, 3H, MeO);13C NMR (75.4 MHz,
DMSO) δ 55.2, 55.5, 113.5, 113.7, 114, 114.4, 117.0, 126.1, 126.5, 127.1,
128.6, 132.9, 133.1, 142.7, 144.7, 158.5, 163.2, 178.9; MS m/e (relative
intensity) EI 309 (M+ + 1, 10), 308 (M+, 52), 280 (13), 265 (20), 135
(100), 107 (13), 92 (32), 77 (40), 63 (13). Anal. Calcd for C18 H16 N2 O3:
C, 70.13; H, 5.19; N, 9.09. Found: C, 69.87; H, 5.31; N, 9.12. 2-(p-
Methylbenzoyl)-5-(p-methylphenyl)imidazole (2c): 80%; mp 198-200
°C; IR (KBr) ν 3275, 1617, 1289, 1168, 821; 1H NMR (300 MHz, DMSO)
δ 13.5 (bs, 1H), 8.68 (d, 2H, J ) 8.1 Hz),), 8.16 (s, 1H, CHd), 7.9-8.1
(m, 2H), 7.2-7.6 (m, 4H), 2.67 (s, 3H, Me), 2.58 (s, 3H, Me); 13C NMR
(75.4 MHz, DMSO) δ 20.8, 21.2, 117.8, 124.7, 125.6, 127, 128.9, 129.1,
130.7, 133.4, 136.2, 142.8, 144.6, 180.2; MS m/e (relative intensity) EI
277 (M+ + 1, 17), 276 (M+, 80), 248 (100), 119 (84), 91 (77), 77 (10), 71
(58), 57 (69). Anal. Calcd for C18 H16 N2 O: C, 78.26; H, 5.79; N, 10.14.
Found: C, 77.97; H, 5.91; N, 9.92. 2-(p-Chlorobenzoyl)-5-(p-chlorophen-
yl)imidazole (2d): 76%; mp 218-220 °C. IR (KBr) ν 3272, 1613, 1291,
To confirm our electrochemical proposal, the acetophenone
enolate was prepared from acetophenone and sodium hydride.
This enolate was added in small amounts to a solution of
phenacyl azide in DMF. N2 evolution was observed inme-
diately, and a check on the reaction medium showed that
the starting azide had disappeared. The products and their
distribution were closely similar to those of the electrochemi-
cal reduction. The dimerization and dehydration are shown
in Scheme 2.
Scheme 2
Formation of the secondary product 3 is possible via
condensation of 2 with an acetophenone enolate. However
when a solution of 2 was chemically treated with acetophe-
none sodium enolate in DMF, no reaction was observed. For
1
1167, 833; H NMR (300 MHz, DMSO) δ 13.65 (bs, 1H), 8.64 (d, 2H, J
(4) Pinner, A. Ber. Dtsch. Chem. Ges. 1905, 38, 1531.
(5) Boyer, J. H.; Straw D. J. Am. Chem. Soc. 1952, 74, 4506.
) 8.4 Hz), 8.18 (s, 1H, CHd), 7.45-8.1 (m, 6H);13C NMR (75.4 MHz,
DMSO) δ 119.5, 126.7, 127.5, 128.5, 131.3, 131.6, 132.5, 135, 138.2, 142,
144.6, 179.5; MS m/e (relative intensity) EI 318 (M+ + 2, 23), 316 (M+,
36), 290 (30), 288 (46), 141 (34), 139 (100), 113 (28), 111 (82), 89 (9), 75
(36). Anal. Calcd for C16 H10 N2 O Cl2: C, 60.57; H, 3.15; N, 8.83. Found:
C, 60.87; H, 3.15; N, 8.71. 2-(p-Bromobenzoyl)-5-(p-bromophenyl)-
imidazole (2e): 77%; mp 252-254 °C (lit.4 mp 245-247 °C); IR (KBr)
(6) General Experimental Information. Electrolyses were carried out
using an Amel potentiostat Model 552 with an electronic integrator Amel
Model 721. Mass spectra (EI, ionizing voltage 70 eV) were determined
using a Hewlett-Packard Model 5988A mass-selective detector equipped
with a Hewlett-Packard MS Chem Station. IR spectra of the compounds
were recorded as dispersions in KBr or as film on NaCl plates, using Perkin-
Elmer Model 583 spectrometer. 1HNMR (300 MHz) and 13CNMR (75.4
MHz) spectra were recorded using a Varian Unity 300 apparatus with CDCl3
or DMSO-d6 (1H, 13C) as internal standard. Melting points (mp) were
determined on a Reichert Thermovar microhot stage apparatus and are
uncorrected. Elemental analyses were performed using a Perkin-Elmer model
240-B analyzer. Cyclic voltammetry was run on a Metrohm apparatus Model
663 VA Stand and a Scanner VA E612. The potential values are given in
volts (vs SCE). Analytical HPLC was performed on a Hewlett-Packard 5033
instrument, using a reverse-phase column and 80% methanol/water as the
eluent. All products were purified by silica gel 60 (230-400 mesh) using
toluene/methanol (20/1 or 40/1) as eluent. Phenacyl bromides are com-
mercially available and have been used without purification. Phenacyl azides
(1) were prepared according to Boyer and Straw (Boyer, H. J.; Straw D. J.
Am. Chem. Soc. 1953, 75, 1642) with the following modifications: solutions
1
ν 3271, 1613, 1290, 1169, 830; H NMR (300 MHz, DMSO) δ 13.7 (bs,
1H), 8.53 (d, 2H, J ) 8.5 Hz), 8.19 (s, 1H, CHd), 7.8-8. (m, 4H), 7.6-
7.7. (m, 2H);13C NMR (75.4 MHz, DMSO) δ 119.5, 126.9, 127.2, 131.5,
131.6, 131.9, 132.6, 132.8, 134.8, 141.8, 144.5, 179.6; MS m/e (relative
intensity) EI 408 (M+ + 4, 21), 406 (M+ + 2, 44), 404 (M+, 22), 380 (21),
378 (42), 376 (22), 299 (11), 297 (11), 185 (100), 183 (100), 157 (90), 155
(90), 76 (48), 75 (48). 2-(2-benzoyl-1-phenylethenyl)-4-phenylimidazole
(3a): 18%; mp 158-160 °C; IR (KBr) ν 3066, 1686, 1625, 1584, 1278,
1229, 1021; 1H NMR (300 MHz, CDCl3) δ 13.4 (bs, 1H), 7.9-8.1 (m,
6H), 7.43-7.63. (m, 10H), 6.4 (s, 1H, dCH); 13C NMR (75.4 MHz, DMSO)
δ 101.5, 118.5, 126, 128.0, 128.2, 128.4, 128.6, 128.8, 129.0, 129.3, 130.1,
131.1, 133.4, 133.6, 134.6, 144.2, 152.3, 192.7; MS m/e (relative intensity)
EI 351 (M+ + 1, 1), 350 (M+, 3), 250 (25), 105 (100), 77 (38), 51 (7).
Anal. Calcd for C24 H18 N2 O: C, 82.28; H, 5.14; N, 8.0. Found: C, 82.48;
H, 5.1; N, 8.1.
1522
Org. Lett., Vol. 1, No. 10, 1999