Reversible addition and elimination of alcohols by vicinal tetracarbonyl compound

Article abstract of DOI:10.1016/j.tetlet.2015.12.112

In this Letter, we report reversible addition and elimination of alcohols by acyclic vicinal tetracarbonyl compounds. First, the reversible fixation and release behavior of alcohols by an acyclic vicinal tetracarbonyl compound, 1,4-diphenyl-1,2,3,4-butanetetraone (DPBT) was investigated. On the basis of the results, the addition of alcohol to DPBT was carried out to provide the alcohol adduct of DPBT, which has a hemiacetal structure. Furthermore, we discovered the reaction of DPBT with 2 equi amount of methanol.

Full text of DOI:10.1016/j.tetlet.2015.12.112

Accepted Manuscript
Reversible Addition and Elimination of Alcohols by Vicinal Tetracarbonyl
Compound
Shinya Maeda, Atsushi Sudo, Takeshi Endo
PII:
S0040-4039(15)30525-6
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.12.112
TETL 47159
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
14 September 2015
16 December 2015
28 December 2015
Please cite this article as: Maeda, S., Sudo, A., Endo, T., Reversible Addition and Elimination of Alcohols by Vicinal
Tetracarbonyl Compound, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.12.112
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Tetrahedron Letters
journal homepage: www.elsevier.com
Reversible Addition and Elimination of Alcohols by Vicinal Tetracarbonyl Compound
Shinya Maeda, Atsushi Sudo, Takeshi Endo
Molecular Engineering Institute, Kinki University, Kayanomori 11-6, Iizuka, Fukuoka 820-8555, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
In this paper, we report reversible addition and elimination of alcohols by acyclic vicinal
tetracarbonyl compound. First, the reversible fixation and release behavior of alcohols by an
acyclic vicinal tetracarbonyl compound, 1,4-diphenyl-1,2,3,4-butanetetraone (DPBT) was
investigated. On the basis of the results, the addition of alcohol to DPBT was carried out to
provide the alcohol adduct of DPBT, which has a hemiacetal structure. Furthermore, we
discovered the reaction of DPBT with 2 equivalent amount of methanol.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Vicinal tetracarbonyl
Reversibility
Hemiketal
Introduction
Vicinal tricarbonyl compounds and their reactions have been of
interest in the field of organic chemistry. For example, 1,2,3-
indanetrione, dehydroascorbic acid, and alloxan are such
tricarbonyl compounds, of which reactivity has been
investigated.1,2,3,4,5 Recently, we have focused our attention on
1,3-diphenyl-1,2,3-propanetrione (DPPT), a vicinal tricarbonyl
compound with an acyclic structure.6,7,8 DPPT is a highly
electrophilic compound, of which center carbonyl group is
activated by the adjacent two carbonyls to be highly reactive with
various nucleophiles such as water and alcohols.9-11 In the course
of our investigations on the reactivity of DPPT with alcohols, its
equilibrium nature has been clarified.12 Based on this equilibrium
nature, a reversible crosslinking-decrosslinking system using a
polystyrene derivative bearing DPPT analogue in the side chain
has been constructed.13
applicable to construction of reversible polymerization-
depolymerization and reversible crosslinking-decrosslinking
systems.
Result and Discussion
The route for the synthesis of DPBT is depicted in Scheme
117,18,19. In the first step, acetophenone was oxidized by selenium
dioxide into phenylglyoxal20. The second step is the benzoin
condensation of phenylglyoxal catalyzed by potassium cyanide,
which gave benzoyl formoin. In the third step, benzoyl formoin
was oxidized by nitric acid to afford hydrate of DPBT. Heating
the hydrate of DPBT at 100 °C in vacuo resulted in dehydration
and sublimation of DPBT.
Besides, vicinal tetracarbonyl compounds consisted of four
contiguous carbonyl groups have been also an interesting object of
research. So far, a couple of 1,4-diaryl-1,2,3,4-butanetetraone
have been synthesized and their photo-induced reactions have
been investigated.14 On the other hand, these tetracarbonyl
compounds are highly electrophilic similarly to tricarbonyl
compounds. For example, 1,4-diphenyl-1,2,3,4-butanetetraone
readily reacts with hydroxylamine to afford the corresponding
dioxime.15
2,2,7,7-Tetramethyl-3,4,5,6-octanetetrone readily
reacts with o-phenylenediamine to afford the corresponding
quinoxaline.16
Herein we report a new aspect of reactivity of 1,4-diphenyl-
1,2,3,4-butanetetraone (DPBT). The focus of this report is the
reaction behavior of DPBT with a series of alcohols with different
steric factors. The most significant finding in this study described
herein is the equilibrium nature of the reaction, which would be
* Corresponding author. Tel.: +81 948 22 7210; fax: +81 94
8 21 9132; e-mail addresses: tendo@moleng.fuk.kindai.ac.jp,
tendo@me-jsr.fuk.kindai.ac.jp (T. Endo).
Scheme 1. Synthesis of DPBT

2
Tetrahedron
1
The structure of DPBT was confirmed by NMR. In the H-
methanol. Compared to these reactions, the reaction of 2-hexanol,
a secondary alcohol with more sterically demanding than the two
primary alcohols, was much slower. Besides, DPBT did not react
with 2-methyl-2-pentanol, a tertiary alcohol, showing the strong
dependence of the reaction efficiency on bulkiness of alcohols.
NMR spectrum, signals assignable to the phenyl groups were
observed (Figure 1) (Full spectrum: Figure S5 in Supporting
Information). In the 13C-NMR spectrum of DPBT, the two
sequential carbonyl carbon gave two peaks at 188.3 and 186.8 ppm
(Figure S6 in Supporting Information). The IR spectrum showed
absorption at 1727, 1664, and 1642 cm-1 (Figure S7 in Supporting
Information).
Figure 2. Time-dependences of conversion of DPBT in its
reactions with various alcohols in CDCl3 at ambient temperature
In the reactions of DPBT with 1-hexanol and 2-hexanol, the
conversions of DPBT plateaued after 1 h, to imply that the
reactions reached the equilibriums. This equilibrium nature is
analogous to that reported previously for the reaction of 1,3-
diphenyl-1,2,3-propanetrione (DPPT) with alcohols. In Table 1,
the reaction times required for reaching the equilibriums and the
conversions at those points in the reactions of DPBT with alcohols
are listed. Table 1 also shows comparative data collected from the
time-conversion relationships of the reactions of DPPT with the
same alcohols. Comparison of the data for the reactions of DPBT
with those for the reactions of DPPT clarified that DPPT was more
reactive than DPBT.
Next, the reaction of 3, a monohydrate of DPBT, with 1-
hexanol was investigated (Scheme 3). Monohydrate 3 and an
equimolar amount of 1-hexanol were dissolved in CDCl3, and the
resulting solution was analyzed with 1H-NMR. Figure 3 shows the
obtained 1H-NMR spectra, which confirmed the presences of 3 and
4c (Full spectrum: Figure S8 in Supporting Information). In
addition, the spectra also revealed the presence of DPBT, which
would mediate the inter-conversion between 3 and 4c. The content
ratios of these three compounds were plotted against reaction time
(Figure 4). Monohydrate 3 was consumed gradually, while the
amount of adduct 4c increased accordingly. DPBT formed
immediately in the very early stages and its content ratio did not
change significantly throughout the reaction.
Figure 1. 1H-NMR spectra of DPBT and the reaction mixture of
containing adduct 4a
The reactions of DPBT with various alcohols was investigated
(Scheme 2). To a 0.75 M solution of DPBT in chloroform-d
(CDCl3), an equimolar amount of alcohol was added at room
1
temperature, and the resulting solution was analyzed with H-
NMR spectroscopy to obtain the corresponding time-conversion
plots, which are shown in Figure 2. During the reactions, the
intensities of the signals attributable to the aromatic protons of
DPBT decreased, while new signals that implied the formation of
adduct 4 gained their intensities. Based on the comparison of the
signal intensities, the conversions of DPBT were calculated.
Scheme 2. Reaction behaviors of DPBT with alcohols
First, the reaction of DPBT with methanol was performed.
Upon adding methanol to a 0.75 M solution of DPBT in CDCl3,
the reaction proceeded smoothly to permit complete consumption
of DPBT within 20 min. Figure 1 shows the 1H-NMR spectrum
measured at 20 min after the reaction started. It clarified that
DPBT was consumed completely and converted into the
corresponding adduct with methanol.
Next, reactions with 1-hexanol and benzyl alcohol were
investigated. As shown in Figure 2, DPBT reacted with these
primary alcohols smoothly but more slowly than the reaction with
Scheme 3. Reversible reactions between monohydrate 3 and
DPBT-alcohol adduct 4c
1.1.

Table 1. Time to reach equilibrium and conversion on DPBT in the addition of various alcohols
Reactions of DPBT with alcohols
Reactions of DPPT with alcoholsa
Alcohol
Time to reach
equilibrium (h)
Conversion at the
equilibrium (%)
Time to reach
equilibrium (h)
Conversion at the
equilibrium (%)
Methanol
Benzyl alcohol
1-Hexanol
0.2
100
95
0.3
18
18
64
100
80
3
6
6
81
84
2-Hexanol
53
51
a The data are extracted from the previously reported time-conversion relationships6.
Figure 3. 1H-NMR spectrum of a mixture containing monohydrate
3, DPBT, and adduct 4a, formed by the treatment of 3 with 1-
hexanol
Scheme 4. Formation of adduct 5 by the reaction of DPBT with 2
equivalent amount of methanol.
In addition, X-ray crystallography confirmed its structure
(Figure S11 in Supporting Information). When 5 was dissolved
in CDCl3 for the structural analysis and kept it at room temperature,
the solution colored gradually to yellow. After 20 h, the solution
was analyzed by 1H-NMR to find 5 underwent dissociation to form
4a (Figure 5) (Full spectrum: Figure S12 in Supporting
Information). After 60 h, 5 was converted to 4a almost completely.
Figure 4. Time-dependences of the content ratios of 3, DPBT, and
4c upon mixing 3 and hexanol in CDCl3 ([3]0:[hexanol]0=0.75 M)
at r.t.
These results confirmed that monohydrate 3 and adduct 4c is in
an equilibrium through the formation of DPBT as the intermediate.
Next, DPBT was treated with an excess amount of methanol,
with expecting formation of 1:2 adduct of DPBT and methanol
(Scheme 4). The resulting solution was allowed to stand for 2
weeks, leading to precipitation of a small amount of a white crystal.
1H-NMR and IR analyses of this crystal revealed it was 5, a 1:2
adduct of DPBT and methanol (Full spectrum showed Figure S9,
Figure S10 in Supporting Information).
Figure 5. 1H-NMR spectra measured for the dissociation reaction
of 5 into 4a and methanol

4
Tetrahedron
EXPERIMENTAL SECTION
Materials.
Chloroform and chloroform-d (CDCl3) were distilled and
stored on molecular sieves 4A (MS 4A). Methanol, benzyl alcohol,
1-hexanol, 2-hexanol, 2-methyl-2-pentanol were purchased from
Sigma-Aldrich Japan and were distilled over CaH2 prior to use.
Selenium dioxide was purchased from Wako Pure Chemical
Industries Co., Ltd. and used as received. Acetophenone and
potassium cyanide were purchased from Tokyo Chemical Industry
Co., Ltd. and used as received. Nitric acid was purchased from
Sigma-Aldrich Japan and used as received.
Experimental Section
Reaction of DPBT with alcohols
Figure 6. Time dependences of contents of 5 and 4a for the
dissociation reaction of 5
DPBT (120 mg, 0.450 mmol) was dissolved in dry CDCl3 (0.60
mL) under argon. To the solution, alcohol (0.54 mmol) was added
at room temperature. A small portion of the solution was
transferred into an NMR tube and analyzed with H-NMR to
determine conversions of DPBT.
1
Conclusions
The reaction of 1,4-diphenyl-1,2,3,4-butanetetraone (DPBT), a
compound bearing four carbonyl moieties linked linearly, with
alcohols was investigated to clarify its equilibrium nature for the
first time. DPBT reacted efficiently with primary and secondary
alcohols to afford the corresponding mixtures of DPBT-alcohol
adducts 4 and DPBT at the equilibriums. The times to reach the
equilibriums and the corresponding conversions at the equilibrium
were shorter and higher respectively than those observed for the
Reaction of 3,3-dihydroxy-1,4-diphenyl-1,2,4-butanetrione (3)
with 1-hexanol
Under argon, 3 (129 mg, 0.454 mmol) was dissolved in CDCl3
(0.6 mL). To the solution, 1-hexanol (67.7 μL, 0.54 mmol) was
added. A small portion of the solution was transferred into an
NMR tube and analyzed with 1H-NMR to determine conversion of
3.
reactions of 1,3-diphenyl-1,2,3-propanetrione (DPPT),
a
tetracarbonyl compound, investigated previously, to imply the
higher electrophilicity of DPBT than DPPT. Based on the
equilibrium nature, a reversible system between the monohydrate
of DPBT and its adduct with alcohol through the formation of
DBPT was constructed. Another interesting reaction discovered
in this work was the reaction of DPBT with a two equivalent
amount of methanol. The reaction gave the corresponding 1:2
adduct 5a, which underwent dissociation into 1:1 adduct 4a and
methanol. In the present work, chloroform and chloroform-d were
used as solvents. These solvents can decompose gradually to
release HCl and DCl, which may catalyze the reactions, i.e., the
hydration of DPBT, the addition of alcohols to DPBT, and the
dissociations of the adducts. Such catalysis promoting the
reactions would be valuable and thus would be investigated in
detail in the future work.
Synthesis
butanedione (5)
of
2,3-dihydro-2,3-methoxy-1,4-diphenyl-1,4-
DPBT (120 mg, 4.50 mmol) was dissolved in MeOH (20 mL)
under argon. The solution was stirred at room temperature for 2
weeks. The resulting precipitate was collected by filtration with
suction to obtain 5 as a colorless crystal (78.7 mg, 0.238 mmol,
5.3 %): 1H-NMR (400 MHz, CDCl3) δ 3.09 (s, 6H, OMe), 5.70 (s,
2H, OH), 7.49 (t, J=15.5, 4H, Ph), 7.61 (t, J=14.7, 2H, Ph), 8.51
(d, J=8.7, 4H, Ph). IR(ATR):3397, 1671, 1593, 1575, 1448, 1305,
1241, 1184, 1103, 1052, 992, 966, 941, 873 (Figure S10 in
Supporting Information)
The equilibrium nature of the reaction of DPBT with alcohols is
potentially applicable to various reversible systems such as
reversible polymerization-depolymerization systems and
crosslinking-decrosslinking systems that would be useful for
chemical recycling of polymer materials.
Elimination of methanol from 5
A solution of 5 (5.00 mg, 15.1 mmol) in dry CDCl3 (0.60 mL)
was prepared and stored under argon. At designated times, the
solution was analyzed with 1H-NMR.
Measurements.
References
1
NMR spectra (400 MHz for H; 100.6 MHz for 13C) were
1) Endo T., Fujiwara, E, Okawara M., J. Polym. Sci., Polym.
Sci., Polym. Chem. Ed., 1981, 19, 1091-1099
recorded on a JEOL NMR spectrometer model JNM-ECS 400 with
tetramethylsilane (TMS) as an internal standard. Chemical shift δ
and coupling constant J are given in ppm and Hz, respectively. IR
spectra were obtained on a Thermo Scientific Nicolet iS10 and
wavenumber ν is given in cm-1. Single crystal X-ray analysis was
2) Wasserman H. H., Parr J., J. Acc. Chem. Res. 2004, 37,
687-701
3) Endo T., M.Okawara, Bull. Chem. Soc. Jpn. 1979, 52,
performed on
diffractometer with Mo−Kα radiation (λ = 0.71073 Å).
a
Bruker Smart ApexCCD-based X-ray
3473-3474
4) Schonberg A, Singer E., Tetrahedron 1978, 34, 1285-1300.

5) Joullie M.M., Tompson T. R., Nemeroff N. H.,
Tetrahedron 1991, 47, 8791-8830.
6) Dei T., Morino K., Sudo A., Endo T., J. Polym. Sci. Part
(A), Polym. Chem., 2011. 49, 2245-2251
7) Dei T., Morino K., Sudo A., Endo T., J. Polym. Sci. Part
(A), Polym. Chem., 2012, 50, 2616-2625
8) Feng, P., Song S., Zhang L.; Jiao N. Synlett 2014, 25,
2717–2720
9) Bowden K., Rumpal S., J. Chem. Res., (S) 1997, 35-35
10) Hirama M., Fukazawa Y., Ito S., Tetrahedron Lett. 1978,
19, 1299-1302
11) Moubasher R., Othman A.M., J. Am. Chem. Soc. 1950,
72, 2667-2669
12) Morino K., Sudo A, Endo T, Macromolecules 2012, 45,
4494-4499
13) Yonekawa M., Furusho Y., and Endo T.,
Macromolecules, 2012, 45 (16), 6640–6647
14). Yonekawa M, Furusho Y, Sei Y, Takata T, Endo.,
Tetrahedron 2013, 69, 4076–4080.
15. Yonekawa M, Furusho Y, Takata T, Endo T, J Polym Sci
Part A Polym Chem 2014, 52, 921–928
16) Mordecai B. R., Emil C. K., Menahem K., J. Royal
Netherlands Chem. Soc., 1979, 98, 85
17) Wolfe S., Pilgrim W. R., Garrard T.F., Chamberlain P.,
Canadian J. of Chem., 1971, 49, 1099-1105
18) Robin M. B., Gleiter R., Chem. Rev, 2000, 100, 1121-
1164
19) Ruggi P., Dahn H., Fries P., Helv. Chim. acta, 1946, 21,
302
20) Riley H. L., Morley J. F, Friend N. A. C., J. Chem. Soc.,
1932, 1875-1883

Graphical Abstract
Reversible Capture and Release of Alcohols
by 1,2,3,4-Tetraketone
Shinya Maeda, Atsushi Sudo, Takeshi Endo
Molecular Engineering Institute, Kinki University, Kayanomori 11-6, Iizuka, Fukuoka 820-8555, Japan