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Notes
Chem. Pharm. Bull. 49(3) 324—326 (2001)
Vol. 49, No. 3
Selective Electrocatalytic Oxidation of N-Alkyl-N-methylanilines to
N-Alkylformanilides Using Nitroxyl Radical
Yoshitomo KASHIWAGI* and Jun-ichi ANZAI
Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980–8578, Japan.
Received September 28, 2000; accepted December 1, 2000
Electrocatalytic oxidation of N-alkyl-N-methylanilines was studied using 4-benzoyloxy-2,2,6,6-tetramethyl-
piperidinyl-N-oxyl as a nitroxyl radical. The reaction with N-alkyl-N-methylanilines led to direct formation of N-
alkylformanilides in the presence of H2O in reaction media in adequate conversion (Ͼ75.8%), high current effi-
ciency (Ͼ89.2%) and high selectivity (Ͼ93.8%).
Key words mediator; nitroxyl radical; electrocatalytic oxidation; N-alkyl-N-methylaniline; N-alkylformanilide
Nitroxyl radicals such as 4-benzoyloxy-TEMPO (4-ben- height corresponded to oxidation of 1, although N,N-di-
zoyloxy-2,2,6,6-tetramethylpiperidinyl-N-oxyl) (1) are usu- methylaniline is not electroactive below ϩ0.8 V vs. Ag/AgCl
ally stable organic radicals, and oxidized species (i.e., at a glassy carbon electrode. This means that 1 is electrocat-
oxoammonium ions) can be easily prepared electrochemi- alytically active for the oxidation of N,N-dimethylaniline.
cally by one-electron oxidation (Chart 1).1) Oxoammonium
Based on the cyclic voltammmetry results, the preparative
ions such as 2 are known to be specific and useful oxidants electrolysis of N,N-dimethylaniline was performed at ϩ0.8 V
for several functional groups, and nitroxyl radicals have been vs. Ag/AgCl. During the electrolysis, the substrates and
used extensively as catalysts for the electrooxidation of alco- products were occasionally analyzed by GC and HPLC. The
hols,1) thiols,2) naphthols,3) and methylquinolines.4) Semmel- consumption of N,N-dimethylaniline and formation of N-hy-
hack and Schmid5) have developed the electrooxidation of droxymethyl-N-methylaniline and N-methylformanilide are
amines to nitriles and carbonyl compounds with TEMPO as plotted against electrolysis time in Fig. 2. A variation in the
a nitroxyl radical catalyst, and MacCorquodale et al.6) have rate of conversion was observed and N-methylformanilide
demonstrated that, based on ESR and cyclic voltammetry, only becomes important when a substantial quantity of N-hy-
poly(TEMPO-4-acrylic ester) acts as an efficient catalytst for droxymethyl-N-methylaniline is formed. It is clear that the
electrochemical oxidation of amines. We have also achieved electro-oxidation reaction of N,N-dimethylaniline to N-
the electrocatalytic oxidation of amines to nitriles on a methylformanilide by 1 is sequential. One mmol of N,N-di-
graphite felt (GF) electrode coated with a thin poly (acrylic methylaniline is consumed almost completely in about 20 h
acid) layer with immobilized 4-amino-TEMPO.7) However, to yield N-methylformanilide. The current efficiency in the
most of this work prior has employed primary amine com- electrolysis is 94.5% during the course of electrolysis, and a
pounds as substrates. On the other hand, Hunter et al.8,9) re- small amount of N-methylaniline was observed (95.9% se-
ported stoichiometric oxidation of N-alkyl-N-methylanilines lectivity). The turnover number based on 1 (given by ratio of
to N-alkylformanilides with 1-oxo-2,2,6,6-tetramethylpiper- mole of productϫ4/mole of 1) was calculated to be 35.8 at
idinum chloride as oxidizing agent. From the viewpoint of 20 h of electrolysis.
electrosynthesis, we report in this paper a preparative electro-
The preparative results for oxidation for four N-alkyl-N-
catalytic oxidation of N-alkyl-N-methylanilines to N-alkyl- methylanilines are shown in Table 1. The alkyl groups cho-
formanilides using 1.
sen were ethyl, n-butyl, isopropyl, and benzyl. All N-alkyl-N-
methylanilines were oxidized to the corresponding N-alkyl-
formanilides in adequate current efficiency (89.2—96.1%)
Results and Discussion
Cyclic voltammetry was used to check the possibility of
electron-transfer from oxidatively generated 2 to N,N-di-
methylaniline. The cyclic voltammogram of 1 in the presence
of N,N-dimethylaniline, H2O and 2,6-lutidine in CH3CN so-
lution is shown in Fig. 1. 2,6-Lutidine is used as a weak base
to avoid the inhibitory effect of a high acid concentration1,5)
and to an abstract proton from substrate.10,11) The reversible
wave at ϩ0.68 V vs. Ag/AgCl, which corresponds to the 1/2
couple became irreversible; an increase in the catalytic peak
Fig. 1. Cyclic Voltammograms of 0.02 M 1 in the Presence (——) and Ab-
sence (- - - - - -) of 0.2 M N,N-Dimethylaniline, 0.8 M 2,6-Lutidine and 0.3 M
H2O in CH3CN of 0.1 M NaClO4 at Scan Rate of 50 mV·sϪ1
Chart 1. A Reversible Redox System Based on 1
To whom correspondence should be addressed. e-mail: kashi@mail.pharm.tohoku.ac.jp
© 2001 Pharmaceutical Society of Japan