Anodic cleavage of several ketone N-phenylsemicarbazones into methyl N-phenylcarbamate and the corresponding dimethyl acetals

Article abstract of DOI:10.1080/00397911.2012.667184

Several ketone N-phenylsemicarbazones were electrooxidized in the presence of potassium iodide and a base using methanol as the solvent to give nearly commensurate amounts of methyl N-phenylcarbamate and the corresponding dimethyl acetals. Continuous evolution of gaseous nitrogen was observed from the anolyte during the electrooxidation. The reactions were carried out under very mild reaction conditions and are presumed to proceed through a four-electron oxidation process, in which the iodide ion plays an important role as an electron carrier.

Full text of DOI:10.1080/00397911.2012.667184

This article was downloaded by: [University of Oklahoma Libraries]
On: 15 April 2013, At: 14:12
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Anodic Cleavage of Several Ketone N-
Phenylsemicarbazones into Methyl N-
Phenylcarbamate and the Corresponding
Dimethyl Acetals
Shinnosuke Nishikawa a , Haruki Yamamori a , Kousuke Ohashi a
Mitsuhiro Okimoto a , Masayuki Hoshi a & Takashi Yoshida a
,
a Department of Biotechnology and Environmental Chemistry, Kitami
Institute of Technology, Hokkaido, Japan
Accepted author version posted online: 27 Dec 2012.Version of
record first published: 04 Apr 2013.
To cite this article: Shinnosuke Nishikawa , Haruki Yamamori , Kousuke Ohashi , Mitsuhiro Okimoto ,
Masayuki Hoshi & Takashi Yoshida (2013): Anodic Cleavage of Several Ketone N-Phenylsemicarbazones
into Methyl N-Phenylcarbamate and the Corresponding Dimethyl Acetals, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 43:13, 1766-1771
To link to this article: http://dx.doi.org/10.1080/00397911.2012.667184
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 43: 1766–1771, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.667184
ANODIC CLEAVAGE OF SEVERAL KETONE
N-PHENYLSEMICARBAZONES INTO METHYL
N-PHENYLCARBAMATE AND THE CORRESPONDING
DIMETHYL ACETALS
Shinnosuke Nishikawa, Haruki Yamamori, Kousuke Ohashi,
Mitsuhiro Okimoto, Masayuki Hoshi, and Takashi Yoshida
Department of Biotechnology and Environmental Chemistry, Kitami Institute
of Technology, Hokkaido, Japan
GRAPHICAL ABSTRACT
Abstract Several ketone N-phenylsemicarbazones were electrooxidized in the presence of
potassium iodide and a base using methanol as the solvent to give nearly commensurate
amounts of methyl N-phenylcarbamate and the corresponding dimethyl acetals. Continuous
evolution of gaseous nitrogen was observed from the anolyte during the electrooxidation.
The reactions were carried out under very mild reaction conditions and are presumed to
proceed through a four-electron oxidation process, in which the iodide ion plays an impor-
tant role as an electron carrier.
Keywords Dimethyl acetal; electron carrier; electrooxidation; iodonium ion; ketone
N-phenylsemicarbazone; methyl N-phenylcarbamate
INTRODUCTION
Aldehydes and ketones can be readily converted to the corresponding
N-phenylsemicarbazones via condensation reactions using equivalent amounts of
N-phenylsemicarbazide. The resulting semicarbazone derivatives are often used for
identification of carbonyl compounds based on their known melting points.[1] The
N-phenylsemicarbazone is the oxidized form of parent N-phenylsemicarbazide.
Although a few reports are found regarding oxidation of ketone semicarbazones via
typical chemical methods using oxidizing reagents,[2–9] to the best of our knowledge,
Received December 22, 2011.
Address correspondence to Mitsuhiro Okimoto, Department of Biotechnology and Environmental
Chemistry, Kitami Institute of Technology, 165 Kitami, Koen-cho, Hokkaido 090-8507, Japan. E-mail:
okimotmt@mail.kitami-it.ac.jp
1766

ANODIC CLEAVAGE OF KETONE N-PHENYLSEMICARBAZONES
1767
there are no reports on the oxidation of ketone N-phenylsemicarbazones via
electrooxidative methods in MeOH.[10–12] Our studies focused on the electrooxida-
tion of nitrogenous organic compounds, such as amines, enamines, and hydrazones,
not only from the viewpoint of synthesis but also of the reactivities of the
substrates.[13–21] During our investigation, we observed a novel and interesting
behavior of ketone N-phenylsemicarbazone (1) under anodic conditions.
RESULTS AND DISCUSSION
At the beginning of the electrooxidation, almost all of substrate 1 existed as an
insoluble fine powder in the anolyte because of its poor solubility in MeOH. Upon
passage of electric current and under vigorous stirring, substrate 1 gradually
dissolved into the anolyte. Interestingly, during the electrooxidation, continuous
evolution of nitrogen gas from the anolyte was observed, which clearly indicates
the decomposition of 1. At the same time, gas–liquid chromatographic (GC) analysis
of the anolyte indicated the immediate formation of methyl N-phenylsemicarbamate
(2) and the corresponding dimethyl acetal (3). After the electric current passage of
nearly 4 FmolÀ1 of electrical current, most of 1 was dissolved, and the evolution
of gaseous nitrogen ceased.
First, the optimal reaction conditions for the electrooxidative decomposition of
1 were determined using acetophenone semicarbazone (1f) as a model substrate. The
types of the supporting electrolytes, along with the corresponding yields of 2 and
acetophenone dimethylacetal (3f), are listed in Table 1.
Table 1. Anodic cleavage of acetophenone phenylsemicarbazone into methyl N-phenylcarbamate and
acetophenone dimethyl acetala
Supporting electrolyte (mmol)
Yield (%)b
Entry
Electrolyte
Mediator
2
3f
1
2
NaOMe (5.0)
None
None
KI (7.5)
KI (7.5)
NaI (7.5)
KBr (7.5)
KCl (7.5)
KI (7.5)
KI (7.5)
KI (7.5)
None
11
95
78
91
13
15
90
91
69
12
10
55
26
94
94
88
30
25
83
94
94
20
16
30
3
NaOMe (2.5)
NaOMe (2.5)
NaOMe (2.5)
NaOMe (2.5)
NaOAc (2.5)
NaOH (2.5)
4
5
6
7
8
9
KO(t -Bu) (2.5)
NaClO4 (5.0)
LiClO4 (5.0)
p-TsON(Et)4 (5.0)
10
11
12
None
None
a1f (2.03 g, 8 mmol), MeOH (40 mL), constant current: 0.3 A, current passed: 4.2 FmolÀ1, rt (ca. 20 ꢀC).
bYields were determined by GC analysis using the internal standard (phenyl ether) method.

1768
S. NISHIKAWA ET AL.
Remarkably, the use of merely 1 equivalent of KI (relative to 1f) was the most
effective in the formation of 2 and 3f (95% and 94% yields, respectively, entry 2).
One drawback, however, was that the terminal voltage tended to surpass 20V during
the first half step; this was easily resolved by the addition of NaOMe (ca. 0.3 equivalents
relative to 1f) without affecting the yield of 3f (entry 3). However, the yield of 2
decreased from 95% to 78%. Substitution of KI with KBr (entry 5) or KCl (entry 6)
resulted in poor yields of 2 and 3f with unreacted 1 remaining within the electrolytic cell.
The use of a stronger base such as KO(t-Bu) (entry 9) resulted in a yield of 3f
(94%), comparable as that of NaOMe. The use of a weaker base such as NaOAc
(entry 7) gave a somewhat lower yield of 3f (83%). In regards to the mediator, the
yields of 3f were less than 30% for electrooxidation reactions that lacked KI (entries
1, 5, 6, and 10–12), illustrating the critical role of KI (source of iodide ions) in the
decomposition reactions of 1f (entries 2–4 and 7–9). Significant differences in the
yields of 3f were observed by varying the amounts of KI (5 mmol, 91%; 2 mmol,
70%; 1 mmol, 49%) and NaOMe (2.5 mmol, 94%; 10 mmol, 70%; 20 mmol, 49%).
Immediately upon the start of the electrooxidation reactions, the yields of 2 and
3f were proportional to the amount of current passed: 34% and 35% after the electric
current passage of 1.5 FmolÀ1, respectively and then 65% and 69% after 3.0 FmolÀ1
,
respectively. In other words, these reactions are highly efficient (more than 86%)
during the early stages. Theoretically, most of 1f was consumed after a small excess
amount of electric current (4.2 FmolÀ1) was passed.
Based on the 50 results, the optimal reaction conditions were applied the
electrooxidative cleavage of various ketone N-phenylsemicarbazones 1a–s, as listed
in Table 2. For alkyl ketone N-phenylsemicarbazones 1a–c, e, the yields of the decom-
posed products varied between 68 to 85% of 2 and 58 to 67% of 3b, c, and e, respect-
ively. However, in the case of 1d, the yields of 2 and 3d unexpectedly decreased after
the current passage of 3.0 FmolÀ1. Compound 3a could not be detected clearly by gas
chromatography (GC) because of the low boiling point. For 1a–e, the electrooxida-
tions were carried out in the absence of NaOMe, which was found to decrease the
yields of the products. Alkyl aryl ketones 1f–o gave decomposed products in moderate
to good yields (2, 64–95%, and 3, 63–94%), except in the case of 1o. For the benzophe-
none substrates, although good yields were obtained for 1p (98% of 2 and 74% of 3p),
lower yields were observed for the substituted benzophenone N-phenylsemicarba-
zones 1q–s, in which the parent substituted benzophenones were formed as the
by-product in the yields of 20% to 36%. As a note, the solubilities of 1p–s, which con-
tain three aromatic rings, were improved using t-BuOH as a cosolvent with MeOH.
Following the electrooxidations, decomposed products 2 and 3 were readily
isolated using silica-gel column chromatography. As a note, the phenyl-amido group
(PhNHCO-) of 1 can be used repeatedly as a component of parent N-phenylsemicar-
bazide by refluxing isolated 2 with a small excess of hydrazinehydrate in EtOH.
Although the reaction pathway of these electrooxidiations still needs to be fully
investigated, it is clear that iodide ions play an important role as electron carriers. As
illustrated in Scheme 1, the anodic cleavage may involve the consumption of 3
equivalents of MeOH and elimination of four protons through a four-electron
oxidation process.
In conclusion, the electrooxidation of ketone N-phenylsemicarbazone resulted
in cleavage to methyl N-phenylsemicarbamate and the corresponding dimethyl acetal

ANODIC CLEAVAGE OF KETONE N-PHENYLSEMICARBAZONES
1769
Table 2. Anodic cleavage of ketone phenylsemicarbazones into methyl N-phenylcarbamate and the
corresponding dimethyl acetalsa
1
Yields (%)b
Entry
R1
R2
Current passed (FmolÀ1
)
2
3
ac
bc
cc
dc
ec
f
Me
Me
4.0
4.2
4.2
3.0
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.2
4.1
4.9
4.9
4.9
4.9
85
82
84
52
68
95
88
80
64
85
78
68
64
83
45
98
93
62
71
—
66
58
52
67
94
86
77
91
85
79
63
84
75
40
74
55
45
51
-(CH2)5-
-(CH2)2 -CH(t -C4H9)-(CH2)2-
n-C3H7
Me
Me
n-C3H7
n-C6H13
Ph
g
Me
Me
p-Me C6H4
p-MeO C6H4
p-Cl C6H4
p-Me C6H4
Ph
h
i
Me
Et
j
k
i-Pr
i-Bu
l
p-MeO C6H4
Ph
m
n
n-Bu
Me
3-Pyridyl
2-Furyl
Ph
oc
pd
qd
rd
sd
Me
Ph
p-Me C6H4
p-MeO C6H4
p-Cl C6H4
p-Me C6H4
p-MeO C6H4
p-Cl C6H4
a1 (8 mmol), KI (7.5 mmol), NaOMe (2.5 mmol), MeOH (40 mL), constant current: 0.3 A, rt (ca. 20 ꢀC).
bDetermined by GC analysis using the internal standard method.
cElectrolysis was carried out in the absence of any base.
dt-BuOH (20 mL) was used as a cosolvent. The amount of NaOMe was increased to 5.0 mmol.
with generation of gaseous nitrogen. In addition to this interesting behavior of 1
under anodic conditions in MeOH, the reaction may be applicable for the prep-
aration of various organic compounds. Moreover, the advantages of our method
include (1) very mild reaction conditions (ca. 20 ꢀC), (2) absence of harsh toxic
reagents, such as metal oxidants or special reagents, and (3) a simple one-pot
reaction.
Scheme 1. Reaction pathway of indirect anodic oxidation.

1770
S. NISHIKAWA ET AL.
EXPERIMENTAL
Ketone N-phenylsemicarbazones were prepared in good yields (83–95%) via
typical condensation reactions between N-phenylsemicarbazide and a small excess
of the ketone by refluxing in EtOH for 1–5 h. Preparative-scale electrooxidations
were carried out in a tall 50-mL beaker equipped with a fine frit cup as the cathode
compartment with a nickel coil cathode, along with a cylindrical platinum net anode
(50 mesh).
A solution of acetophenone N-phenylsemicarbazone 1f (8 mmol) in MeOH
(40 mL) containing KI (7.5 mmol) and NaOMe (2.5 mmol) was electrooxidized under
a constant current (0.3 A). During the course of the electrooxidation, the anolyte was
magnetically stirred at ca. 20 ꢀC, and the composition of the reaction mixture was
monitored by GC (FFAP, 1.5 m) analysis. Passage of the electric current was contin-
ued until almost all of the substrate was dissolved. Upon electric current passage of
4.2 F molÀ1, the reaction mixture was concentrated in vacuo (ca. 10 mL) at approxi-
mately 50 ꢀC. The resulting oily residue was treated with water (ca. 30 mL), then
extracted with ethyl ether (3 Â 40 mL), and dried over sodium sulfate overnight.
After removal of the solvent in vacuo, the crude mixture of 2 and 3f were purified
by silica-gel column chromatography using ether=hexane (3:5) as the eluent. The
electrooxidation products were identified by comparison against authentic samples
using GC analysis, high-resolution mass, and=or IR spectroscopy.
REFERENCES
1. Shriner, R. L.; Buson, R. C. The Systematic Identification of Organic Compounds, 3rd ed.;
Wiley: New York, 1948; vol. 231, pp. 262–266.
2. Braun, J. V.; Steindorff, A. Zur kenntniss des c-conice¨ıns, I. Chem. Ber. 1905, 38,
3094–3107.
3. Barton, D. H. R.; Lester, D. J.; Ley, S. V. Regeneration of ketones from hydrazones, oxi-
mes, and semicarbazones by benzeneseleninic anhydride. Chem. Commun. 1977, 445–446.
4. Bird, J. W.; Diaper, D. G. M. Preparative conversion of oximes to parent carbonyl
compounds by cerium(IV) oxidation. Can. J. Chem. 1969, 47, 145–150.
5. Pilgram, K.; Skiles, R. D.; Pollard, G. E. 1-Phenyl-3,3,4-trialkyl-1,2,4-triazolidine-5-ones
via cyeloisomerization of ketone 4-alkyl-2-phenylsemicarbazones. J. Heterocycl. Chem.
2009, 13, 1257–1263.
6. Yang, R. Y.; Dai, L. X. Hypervalent iodine oxidation of N-acylhydrazones and
N-phenylsemicarbazone: An efficient method for the synthesis of derivatives of 1,3,4-
oxadiazoles and D3-1,3,4-oxadiazolines. J. Org. Chem. 1993, 58, 3381–3383.
7. Cameron, A. M.; West, P. R.; Warkentin, J. Oxidations with lead tetraacetate, III:
Cyclization of ketosemicarbazones to 2-imino-D3-1,3,4-oxadiazolines. J. Org. Chem.
1969, 34, 3230–3233.
8. Prakash, O.; Gujral, H. K.; Rani, N.; Singh, S. P. Hypervalent iodine oxidation of hydra-
zones of some nitrogen heterocyclic ketones and aldehydes: An efficient synthesis of fused
1,2,3-triazoloheterocycles. Synth. Commun. 2000, 30, 417–425.
9. Zhang, G. S.; Chai, B. An efficient, selective, and inexpensive supported oxidant for the
regeneration of carbonyl compounds from oximes, semicarbazones, 4-phenylsemicarba-
zones, and p-nitrophenylhydrazones. Synth. Commun. 2000, 30, 1849–1855.
10. Lund, H. Electroo¨rganic preparations, VI: Reduction of compounds containing the
azomethine group. Acta Chem. Scand. 1959, 13, 249–267.

ANODIC CLEAVAGE OF KETONE N-PHENYLSEMICARBAZONES
1771
11. Refaey, S. A. M.; Hassan, A. A.; Shehata, H. S. Electrochemical behavior of some
substituted thiosemicarbazones and their reaction products with tetracyanoethylene. Int.
J. Electrochem. Sci. 2008, 3, 325–337.
12. Lotfi, B.; Mustafa, B.; Leila, B.; Salima, M. Electrocyclization of semicarbazone: A novel
route of green synthesis of 2,5-disubstituted-1,3,4-oxadiazoles. Int. J. Electrochem. Sci.
2011, 6, 1991–2000.
13. Chiba, T.; Okimoto, M.; Nagai, H.; Takata, Y. Electrochemical oxidation of enamine in
the presence of organic anions. J. Org. Chem. 1979, 44, 3519–3523.
14. Chiba, T.; Okimoto, M.; Nagai, H.; Takata, Y. Electrochemical oxidation of benzophenone
hydrazone. J. Org. Chem. 1983, 48, 2968–2972.
15. Okimoto, M.; Chiba, T. Electrochemical oxidation of ketone acylhydrazones and their
HCN adducts in NaCN-MeOH (transformation of ketones to nitriles). J. Org. Chem.
1990, 55, 1070–1076.
16. Chiba, T.; Okimoto, M. Electrooxidative cyclization of N-acylhydorazones of aldehydes
and ketones to D3-1,3,4-oxadiazolines and 1,3,4-oxadiazoles. J. Org. Chem. 1992, 57,
1375–1379.
17. Okimoto, M.; Nagata, Y.; Takahashi, Y. Electrooxidative conversion of aldehyde and
ketone phenylhydrazones into the phenylazo methoxy compounds. Bull. Chem. Soc.
Jpn. 2003, 76, 1447–1448.
18. Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.; Komata, M.; Tomozawa, K.; Chiba,
T. Electrooxidative cyclization of benzylideneaminothiophenols to the corresponding
2-arylbenzothiazoles. Heterocycles 2008, 75, 35–42.
19. Okimoto, M.; Numata, K.; Tomozawa, K.; Shigemoto, T.; Hoshi, M.; Takahashi, Y.
Electrooxidative conversion of dibenzoylbenzene dihydrazones into the corresponding
bis-diazo compounds and bis-dimehtyl acetals. Aust. J. Chem. 2005, 58, 560–563.
20. Okimoto, M.; Takahashi, Y.; Nagata, Y.; Numata, K.; Sasaki, G. Electrochemical
oxidation of benzylic amines into the corresponding imines in the presence of catalytic
amount of KI. Synth. Commun. 2005, 35, 1989–1995.
21. Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.; Komata, M.; Tomozawa, K.; Chiba, T.
Anodic oxidation of ketone allylhydrazones into the corresponding azines. Synth. Commun.
2008, 38, 3320–3328.