J. N. Moorthy, I. Neogi / Tetrahedron Letters 52 (2011) 3868–3871
3871
as well as IBX. No product formation was observed when the reac-
tion was carried out between aldehyde and 1,2-phenylenediamine
in the absence of IBA or IBX. Longer reaction durations did not
influence the isolated yields appreciably. As for the work-up of
the reactions, DMSO was first distilled out in vacuo at ca. 60–
65 °C, and the reaction mixture was treated with NaHCO3 solution
to remove the iodo acid formed in the reaction mixture.11
grateful to CSIR, India for a senior research fellowship. We thank
Mr. Keshab Parida for his help in the preliminary experiments.
Supplementary data
Supplementary data associated with this article can be found, in
Generality of the methodology was examined for a series of
benzyl alcohols bearing both electron-donating as well as elec-
tron-withdrawing groups. As shown in Table 1, the yields of benz-
imidazoles isolated are impressive, and range from 45% to 87%.
Lower yields were isolated for highly electron-rich 4-N,N-dimethy-
laminobenzyl alcohol and electron-poor p-nitrobenzyl alcohol
(entries 3 and 6). Otherwise, all aliphatic, allylic, and benzylic alco-
hols were found to undergo reactions smoothly to afford the corre-
sponding benzimidazoles in moderate to excellent isolated yields.
To probe the reaction mechanism, progress of the reaction of
p-methoxybenzyl alcohol was monitored by 400 MHz 1H NMR
spectroscopy, cf. Supplementary data. Following the addition of
1,2-phenylenediamine to the aldehyde formed subsequent to
oxidation of benzyl alcohol with IBX in DMSO, disappearance pro-
gressively of the aldehyde signal with concomitant appearance of
the signal corresponding to the benzimidazole product was
observed. The other noteworthy feature is the formation of
o-iodobenzoic acid as the end product of IBX. Clearly, IBA—the
I(III) species derived from IBX via oxidation of alcohols—is further
reduced to o-iodobenzoic acid (Scheme 2). Thus, IBX undergoes
overall 4e reduction. In other words, IBA is involved in the forma-
tion of the benzimidazole. Indeed, we established, in an indepen-
dent experiment, that the reaction of p-methoxybenzaldehyde
and 1,2-phenylenediamine leads to the corresponding benzimid-
azole in the presence of a molar equiv of IBA. Of course, o-iodoben-
zoic acid was observed as the reduction product. Overall, a
sequence of reactions entailing the oxidation of alcohol with IBX,
formation of Schiff base with 1,2-phenylenediamine and subse-
quent cyclization and IBA-mediated dehydrogenation lead to benz-
imidazoles. The one-pot procedure should prove highly
advantageous for labile aldehydes in particular.
Benzimidazoles were also accessed from arylmethyl bromides
in one pot by treatment of the latter with 1.5–1.6 equiv of IBX in
DMSO at 65–70 °C; as mentioned at the outset, we have previously
shown that benzyl bromides are converted to benzaldehydes at
slightly elevated temperatures in DMSO. Thus, after conversion of
arylmethyl bromide to the corresponding aldehyde with IBX in
DMSO at 65–70 °C as monitored by TLC analysis, the reaction
mixture was brought to room temperature, and 1.5–1.6 equiv of
1,2-phenylenediamine was introduced. Subsequently, the reaction
mixture was stirred until the disappearance of the aldehyde.
Regular work-up led to isolation of benzimidazole.11 As shown in
Table 2, yields of the isolated benzimidazoles are moderate
(45–80%) with the exception of mesityl bromide (entry 7).
References and notes
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In conclusion, a convenient and effective one-pot synthetic
strategy has been uncovered for benzimidazoles starting from pri-
mary alcohols and arylmethyl bromides using IBX as the reagent. It
is shown that 1.1 equiv of IBX suffices for two consecutive oxida-
tive transformations involving an overall 4e-redox process that
leads to o-iodobenzoic acid as the end product of IBX. Given that
IBX is a mild and non-toxic reagent, the one-pot protocol described
herein for the benzimidazoles—the end products of a consecutive
reaction—clearly attests to a new dimension in the applications
of IBX, which we continue to explore.
11. General procedure for the one-pot conversion of alcohols to benzimidazoles: In a
typical experiment, the primary alcohol (0.5–0.6 mmol) and IBX (1.1 equiv)
were stirred in DMSO at ca. 20 °C. Once the oxidation of alcohol to aldehyde
was complete, as judged from TLC analysis, o-phenylenediamine (1.1 equiv)
was introduced into the reaction mixture and the reaction mixture was
allowed to stir at room temperature until the aldehyde disappeared. At the end
of the reaction, DMSO was removed under high vacuum, and the residue was
treated with 1.0 M NaHCO3 solution until the pH was 8–9. The organic matter
was extracted with ethyl acetate. Regular work-up followed by silica-gel
column chromatography led to pure benzimidazoles, which were
characterized spectroscopically.
For conversion of benzyl bromides to benzimidazoles, the same procedure as
above was followed except that the initial conversion to aldehydes was
conducted at 70 °C. Once the halide was completely converted to the
corresponding aldehyde, the reaction temperature was lowered to rt and o-
phenylenediamine was introduced.
Acknowledgments
J.N.M. is thankful to the Department of Science and Technology
(DST), India for funding through Ramanna fellowship. I.N. is