Synthesis of Peroxy-Containing Acetylenic Alcohols and Ethers Derived from γ-Amino Ketones

Article abstract of DOI:10.1023/A:1025648821889

A series of peroxy-containing tertiary alcohols were prepared by the reactions of lithium peroxy acetylenides with γ-amino ketones. The reactions of the intermediate lithium peroxy alcoholates with alkyl iodides in the presence of hexamethylphosphoramide yielded the corresponding peroxy ethers. The thermal stability of the compounds synthesized was evaluated by thermal analysis.

Full text of DOI:10.1023/A:1025648821889

Russian Journal of General Chemistry, Vol. 73, No. 4, 2003, pp. 591 595. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 4, 2003,
pp. 625 629.
Original Russian Text Copyright
2003 by Dikusar, Kozlov, Popova, Moiseichuk, Yuvchenko.
Synthesis of Peroxy-Containing Acetylenic Alcohols and Ethers
Derived from -Amino Ketones
E. A. Dikusar, N. G. Kozlov, L. A. Popova,
K. L. Moiseichuk, and A. P. Yuvchenko
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Institute of Chemistry of New Materials, National Academy of Sciences of Belarus, Minsk, Belarus
Received April 26, 2001
Abstract A series of peroxy-containing tertiary alcohols were prepared by the reactions of lithium peroxy
acetylenides with -amino ketones. The reactions of the intermediate lithium peroxy alcoholates with alkyl
iodides in the presence of hexamethylphosphoramide yielded the corresponding peroxy ethers. The thermal
stability of the compounds synthesized was evaluated by thermal analysis.
Previously [1, 2] we reported on the possibility of
preparing acetylenic amino peroxy alcohols and their
derivatives by the reactions of lithium peroxy acetyl-
enides IIa and IIb with p-dimethylamino- or p-di-
ethylaminobenzaldehydes and 2e-methyldecahydro-
quinol-4-one. Here we report on the synthesis of
acetylenic peroxy-containing tertiary alcohols Va Vf
by the reactions of lithium peroxy acetylenides IIa
and IIb with -amino ketones IIIa IIIc which, in
turn, are prepared by condensation of cyclohexanone
and isocamphanone with benzalaniline and benzal-
toluidine. The reaction occurred at 15 20 C;
peroxy alcohols Va Vf were isolated in 74 89%
yields.
BuLi
RMe2COOCMe2C CH
RMe2COOCMe2C CLi
Ia, Ib
IIa, IIb
R
R
IIa, IIb
O
OLi
NH
2
NH
1
6
4
3
OO
IIIa, IIIb
5
R
R
IV
OR
NH
H2O or R I
NH
OO
R
Va Vd, Vg Vi
H2O or
R I
IIa, IIb
NH
4
3
5
NH
1
OO
2
6
OO
OR
Ve, Vf, Vj
O
OLi
R
IIIc
IV
R
I, II, R = Me (a), Et (b); III, R = H (a), Me (b); V, R = Me, R = R = H (a); R = Et, R = R = H (b); R = R = Me, R =
H (c); R = Et, R = Me, R = H (d); R = Me, R = H (e); R = Et, R = H (f); R = R = R = Me (g); R = Et, R = R = Me
(h); R = R = Me, R = Et (i); R = R = Me (j).
1070-3632/03/7304-0591$25.00 2003 MAIK Nauka/Interperiodica

592
DIKUSAR et al.
The starting amino ketones IIIa and IIIb contain a
1-(5 ,5 ,6 -trimethyl-2 -oxobicyclo[2.2.1]hept-3 -yl)-1-
phenylmethylamine IIIc give singlets at 0.81 and
0.87 ppm, and the methyl group at C6 , a doublet at
0.90 ppm (3J 7.5 Hz). The bridge geminal protons
(anti and syn) give a doublet at 1.58 ppm and a multi-
plet at 2.0 ppm (2J 10 Hz), respectively. A broadened
singlet at 2.21 ppm and a multiplet at 2.0 ppm were
cyclohexanone ring in the chair conformation with an
-substituent (relative to the carbonyl group) in the
equatorial position. Amino ketone IIIc contains a
bicyclo[2.2.1]heptane fragment with the methyl group
at C5 and a substituent at C3 in the exo position.
1
The structure of IIIa IIIc was determined by H
assigned to the bridgehead protons at C1 and C4 ,
respectively. The endo-C6 H proton gives a quartet at
1.58 ppm, and the proton in the amino group at C1,
a broadened singlet at 5.55 ppm. The doublet of dou-
NMR spectroscopy. In the spectra of N-phenyl-1-(2 -
oxocyclohexyl)-1-phenylmethylamine IIIa and N-p-
tolyl-1-(2 -oxocyclohexyl)-1-phenylmethylamine IIIb,
we identified the signals of aromatic protons at 6.39
7.36 ppm and of the cyclohexane ring protons at
1.80 2.90 ppm. In addition, the spectrum of IIIb
contains a CH3 Ar singlet at 2.18 ppm.
3
blets at 2.45 ppm (3J 2.5, J 12) belongs to the C3 H
proton. The C1H proton in the -position relative to
the amino group gives a doublet at 4.19 ppm (3J
12 Hz), which corresponds to the dihedral angle be-
tween the C1 H and C3 H bonds of 180 . The multi-
plets at 7.32 (5H), 7.0 (2H), and 6.53 ppm (3H) be-
long to the aromatic protons.
The NH proton gives a broadened singlet at
4.7 ppm, and the proton at the C1 atom in -position
relative to N, a doublet at 4.6 ppm (3J 8 Hz). The
doublets at 2.30 and 2.35 ppm (J 12 Hz) belong to the
1
geminal protons of the C3 atom in the cyclohexane
ring. A doublet of doublets (3J 8, 3J 3 Hz) at
2.78 ppm belongs to the C1 H proton.
Analysis of the H NMR spectrum of amino ketone
IIIc in comparison with the spectra of the model com-
pounds [4] shows that the substituent at the C3 atom
of the isocamphane skeleton is in the exo position, as
indicated by the vicinal coupling constant of the C3 H
and C4 H protons, equal to 2.5 Hz. It is evident from
consideration of the Dreiding model and the Newman
projection along the C3 C1 bond in IIIc that the
steric arrangement of the phenyl-containing substitu-
ents prevents attack of the carbonyl group from the
endo side. Therefore, in the reactions with lithium
peroxy acetylenides IIa and IIb, the bulkiest acetylene-
containing substituent adds to the C2 atom from the
exo side, yielding the endo isomers of alcohols Ve
and Vf.
Consideration of the Dreiding models for IIIa and
IIIb, taking also into account the vicinal coupling
constant of protons at C1 and C1 (8 Hz) [3], shows
that the proton at C1 in the cyclohexane ring of amino
ketones IIIa and IIIb is in the axial position, and the
dihedral angle between the C H bonds C1 H and
C1 H is about 40 in the Newman projection along
the C1 C1 bond.
Apparently, phenyl-containing substituents at the
C1 atom of amino ketones hinder attack by lithium
peroxy acetylenides of the keto group of amino ke-
tones IIIa and IIIb from the axial side of the molecule.
Therefore, we suggest that the ethynyl substituent
adds to amino ketones IIIa and IIIb from the equa-
torial side, yielding axial isomers of alcohols Va Vd.
Reactions of the intermediate lithium peroxy alco-
holates IV with alkyl iodides in the presence of hexa-
methylphosphoramide gave the corresponding peroxy
ethers Vg Vj in 59 66% yields.
R
In contrast to acetylenic peroxy-containing hy-
droxydecahydroquinolines [2], peroxy-containing ace-
tylenic alcohols and ethers Va Vj derived from -ami-
no ketones do not react with carboxylic acids and
methyl iodide to give the corresponding salts.
Ha
H
NH
O
Compounds Va Vj are viscous slightly colored
liquids readily soluble in common organic solvents
and stable in prolonged storage at 0 5 C without air
access in the dark. The yields and analytical data are
given in Table 1; the H NMR data, in Table 2; and
the IR and UV data, in Table 3.
1
He
H
NH
O
The thermal stability of Va Vj was evaluated by
thermal analysis. The results for the first decomposi-
tion step are listed in Table 4. It is seen that the ther-
mal stability of peroxides Va Vj is relatively high.
The methyl groups at C5 in the starting N-phenyl-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 4 2003

SYNTHESIS OF PEROXY-CONTAINING ACETYLENIC ALCOHOLS AND ETHERS
Table 1. Properties of peroxides Va Vj
593
Found, %
Calculated, %
H
M
Comp.
no.
Yield, %
Formula
C
H
N
C
N
found
calculated
Va
Vb
Vc
Vd
Ve
Vf
Vg
Vh
Vi
77
74
87
89
82
87
63
59
66
61
77.54
77.69
77.64
77.99
79.03
79.12
77.98
78.11
78.18
79.44
8.61
8.83
8.81
9.03
8.74
8.91
8.93
9.13
9.22
8.83
3.10
3.04
3.04
2.90
2.60
2.33
2.60
2.80
2.64
2.50
C28H37NO3
C29H39NO3
C29H39NO3
C30H41NO3
C32H43NO3
C33H45NO3
C30H41NO3
C31H43NO3
C31H43NO3
C33H45NO3
77.20
77.47
77.47
77.71
78.49
78.69
77.71
77.95
77.95
78.69
8.56
8.74
8.74
8.91
8.85
9.00
8.91
9.07
9.07
9.00
3.22
3.12
3.12
3.02
2.86
2.78
3.02
2.93
2.93
2.78
412.8
435.8
421.0
440.9
470.3
480.6
420.3
451.8
448.0
488.3
435.6
449.6
449.6
463.7
489.7
503.7
463.7
477.7
477.7
503.7
Vj
Table 2. 1H NMR spectra of peroxides Va Vj
Comp.
no.
1H NMR spectrum, , ppm
Va 1.25 s (9H, Me3COO), 1.35 2.80 m [10H, CH, OH, and (CH2)4], 1.53 s (6H, Me2C), 4.68 d (1H, CHNH, J 7.1 Hz),
6.45 7.50 m (10H, 2Ph)
Vb 0.90 t (3H, Me), 1.22 s (6H, Me2COO), 1.30 2.20 m [12H, CH, OH, CH2, and (CH2)4], 1.55 s (6H, Me2C), 4.70 d
(1H, CHNH, J 7.1 Hz), 6.50 7.50 m (10H, 2Ph)
Vc 1.21 s (9H, Me3COO), 1.35 2.40 m [10H, CH, OH, and (CH2)4], 1.52 s (6H, Me2C), 2.21 s (3H, p-MeC6H4),
4.91 d (1H, CHNH, J 7.1 Hz), 6.55 7.55 m (9H, p-C6H4 and Ph)
Vd 0.89 t (3H, MeCH2), 1.20 s (6H, Me2COO), 1.30 2.40 m [12H, CH, OH, CH2, and (CH2)4], 1.50 s (6H, Me2C),
2.21 s (3H, p-MeC6H4), 4.92 d (1H, CHNH, J 7.1 Hz), 6.55 7.55 m (9H, p-C6H4 and Ph)
Ve 0.80 d (3H, C6Me, J 7.0 Hz), 0.91 s (3H, C5Me endo), 1.05 s (3H, C5Me exo), 1.25 s (9H, Me3C), 1.55 s
(6H, Me2C), 1.55 2.60 m (7H, OH, 4CH, and CH2), 4.40 d (1H, CHNH, J 8.3 Hz), 6.45 7.45 m (10 H, 2Ph)
Vf 0.65 1.05 m (12H, C5Me2, C6Me, and MeCH2), 1.20 s (6H, Me2COO), 1.52 s (6H, Me2C), 1.45 2.60 m (9H, OH,
4CH and 2CH2), 4.40 d (1H, CHNH, J 8.3 Hz), 6.45 7.50 m (10H, 2Ph)
Vg 1.22 s (9H, Me3COO), 1.30 2.30 m [9H, CH, and (CH2)4], 1.35 s (6H, Me2C), 2.22 s (3H, p-MeC6H4), 3.32 s
(3H, MeO), 4.72 d (1H, CHNH, J 4.5 Hz), 6.20 7.50 m (9H, p-C6H4 and Ph)
Vh 0.89 t (3H, MeCH2), 1.15 s (6H, Me2COO), 1.32 s (6H, Me2C), 1.30 2.30 m [11H, CH, CH2, and (CH2)4], 2.22 s
(3H, p-MeC6H4), 3.32 s (3H, MeO), 4.73 d (1H, CHNH, J 4.5 Hz), 6.20 7.50 m (9H, p-C6H4, and Ph)
Vi 1.19 t (3H, MeCH2), 1.20 s (9H, Me3COO), 1.40 s (6H, Me2C), 1.30 2.30 m [9H, CH, and (CH2)4], 2.22 s (3H,
p-MeC6H4), 3.25 3.88 m (2H, MeCH2), 4.81 d (1H, CHNH, J 4.5 Hz), 6.25 7.50 m (9H, p-C6H4, and Ph)
Vj 0.82 d (3H, C6Me, J 7.0 Hz), 0.90 s (3H, C5Me endo), 1.00 s (3H, C5Me exo), 1.21 s (9H, Me3COO), 1.50 s (6H,
Me2C), 1.45 2.50 m (6H, 4CH, and CH2), 3.36 s (3H, MeO), 4.54 d (1H, CHNH, J 8.0 Hz), 6.40 7.50 m (10H, 2Ph)
Peroxy alcohols Va Vd with the cyclohexane frag-
ment (axial isomers) start to decompose at a noticeable
rate with a pronounced exothermic effect only at 130
135 C. Peroxy alcohols Ve and Vf with the isocam-
phane fragments (endo isomers) exhibit somewhat
lower thermal stability and decompose at 124 125 C.
Peroxy ethers Vg Vj derived from peroxy alcohols
Vc Ve by replacement of the hydroxy group by meth-
oxy and ethoxy groups show noticeably higher ther-
mal stability. They start to decompose at 140 145 C,
i.e., at temperatures 8 24 C higher than those of
thermolysis of peroxy alcohols Vc Ve.
EXPERIMENTAL
The IR spectra were recorded on a Specord IR-75
1
spectrophotometer (thin films). The H NMR spectra
were taken on a Tesla BS-567A spectrometer in
CDCl3, internal reference TMS. The UV spectra were
recorded on a Specord UV-Vis spectrophotometer
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 4 2003

594
DIKUSAR et al.
Table 3. IR and UV spectra of peroxides Va Vj
Comp.
no.
UV spectrum, max, nm
(
1
IR spectrum, , cm
3
1
10 , l mol 1 cm )
Va 3630 3250 s (OH); 3415 v.s (NH); 3090 m, 3060 m, 3040 m (CHAr); 2990 v.s, 207 (28), 248 (14), 292 (5)
2940 v.s, 2870 v.s (CHAlk); 1610 v.s, 1510 v.s (skeleton vibrations of Ar); 755 v.s,
710 v.s (CHAr)
Vb 3630 3200 s (OH); 3415 v.s (NH); 3090 m, 3060 m, 3030 m (CHAr); 2985 v.s, 205 (28), 248 (14), 295 (5)
2930 v.s, 2875 v.s, 2860 v.s (CHAlk); 1510 v.s (skeleton vibrations of Ar); 760 v.s,
710 v.s (CHAr)
Vc 3625 3150 s (OH); 3400 v.s (NH); 3080 w, 3055 m, 3025 m (CHAr); 2980 v.s, 208 (45), 245 (18), 290 (4)
2940 v.s, 2860 v.s (CHAlk); 1610 v.s, 1590 v.s, 1520 v.s (skeleton vibrations of Ar);
760 v.s, 710 v.s (CHAr)
Vd 3635 3160 s (OH); 3405 v.s (NH); 3085 w, 3060 m, 3030 m (CHAr); 2980 v.s, 208 (44), 244 (18), 290 (4)
2940 v.s, 2880 v.s, 2860 v.s (CHAlk); 1610 v.s, 1595 v.s, 1520 v.s (skeleton vibra-
tions of Ar); 755 v.s, 710 v.s (CHAr)
Ve 3620 3150 s (OH); 3405 v.s (NH); 3090 w, 3060 m, 3025 m (CHAr); 2975 v.s, 206 (30), 246 (15)
2930 v.s, 2870 s (CHAlk); 1600 v.s, 1500 v.s (skeleton vibrations of Ar); 745 v.s,
700 v.s, 690 v.s (CHAr)
Vf 3620 3225 s (OH); 3400 v.s (NH); 3085 w, 3055 m, 3025 m (CHAr); 2975 v.s, 205 (29), 249 (14)
2940 v.s, 2870 s (CHAlk); 1595 v.s, 1495 v.s (skeleton vibrations of Ar); 755 m,
745 v.s, 695 v.s, 685 v.s (CHAr)
Vg 3400 v.s (NH); 3080 w, 3060 m, 3025 s (CHAr); 2980 v.s, 2930 v.s, 2855 v.s, 208 (45), 248 (18), 295 (4)
825 s (CHAlk); 1600 v.s, 1580 v.s, 1515 v.s (skeleton vibrations of Ar); 745 v.s,
705 m, 700 v.s (CHAr)
Vh 3405 v.s (NH); 3080 w, 3060 m, 3025 s (CHAr); 2980 v.s, 2930 v.s, 2875 s, 2855 s, 209 (45), 248 (18), 295 (3)
2820 m (CHAlk); 1600 v.s, 1580 v.s, 1515 v.s (skeleton vibrations of Ar); 745 v.s,
705 m, 700 v.s (CHAr)
Vi 3395 v.s (NH); 3090 w, 3060 m, 3030 m (CHAr); 2980 v.s, 2940 v.s, 2865 v.s 205 (43), 246 (18), 295 (4)
(CHAlk); 1605 v.s, 1585 v.s, 1510 v.s (skeleton vibrations of Ar); 755 v.s, 725 m,
705 v.s (CHAr)
Vj 3405 v.s (NH); 3090 w, 3060 m, 3030 m (CHAr); 2980 v.s, 2940 v.s, 2875 s, 206 (28), 249 (12)
2825 s (CHAlk); 1600 v.s, 1505 v.s (skeleton vibrations of Ar); 770 v.s, 750 v.s,
705 v.s, 695 s (CHAr)
4
(1 10 M methanolic solutions). The thermal be-
havior of the compounds was studied on a Paulik
Paulik Erdey derivatograph under argon at a linear
The starting peroxy alkynes Ia and Ib [7] and butyl-
lithium [8] were prepared by published procedures.
-Amino ketones IIIa IIIc. A 0.1-mol portion of
appropriate azomethine (benzalaniline or benzaltolu-
idine) was dissolved in 20 ml of ethanol and heated
to 60 C; 0.1 mol of appropriate ketone (cyclohexa-
none or isocamphanone) and a drop of concentrated
HCl were added, and the mixture was heated for an
additional 5 min. After cooling, the crystalline precip-
itate of -amino ketone was washed with 10% ammo-
nia and water, dried, and recrystallized from methan-
ol. IIIa, mp 140 141 C, yield 92% (published data
[9]: mp 139 140 C, yield 90% [9]); IIIb, mp 127
129 C, yield 95% (published data [9]: mp 116 118 C,
yield 97% [9]); IIIc, mp 156 157 C, yield 90%.
1
heating rate of 7 deg min (sample weight 100 mg,
DTA 1/10, DTG 1/10). The purity of the compounds
was checked by thin-layer chromatography on 20-cm-
high Silufol plates, eluent hexane diethyl ether (3 : 1),
developer N,N-dimethyl-p-phenylenediamine hydro-
chloride. Column chromatography was performed on
Al2O3 L 40/250 m, neutral, Brockmann grade II, and
on silica gel L 100/160 m. Determination of the con-
tent of available oxygen by iodometric titration using
concentrated HCl [6] gave overestimated results, prob-
ably due to the presence of the C C bond. The molec-
ular weights were determined cryoscopically in ben-
zene.
Acetylenic peroxy-containing tertiary alcohols
Va Vf. A solution of 0.025 mol of butyllithium in
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SYNTHESIS OF PEROXY-CONTAINING ACETYLENIC ALCOHOLS AND ETHERS
595
Table 4. Characteristics of the first step of thermolysis of
Va Vj (thermal analysis data)
The reaction was complete in 18 h at 20 23 C. Then
100 ml of hexane was added, and the organic layer
was washed with water and 30% NaOH and dried
over CaCl2. The solvent was removed. Compounds
Vg Vj were purified by column chromatography on
Al2O3, eluent hexane.
Tdec
,
C
Weight
loss,
%
Comp.
no.
onset
end
maximum
Va
Vb
Vc
Vd
Ve
Vf
Vg
Vh
Vi
133
131
135
130
125
124
143
140
151
149
198
202
200
195
190
208
216
200
215
212
170
173
176
175
165
164
180
175
175
174
23
24
22
23
19
22
23
22
21
23
REFERENCES
1. Dikusar, E.A., Yuvchenko, A.P., Murashko, V.L.,
Makhnach, S.A., and Moiseichuk, K.L., Zh. Obshch.
Khim., 2000, vol. 70, no. 5, p. 791.
2. Dikusar, E.A., Kozlov, N.G., and Moiseichuk, K.L.,
Zh. Obshch. Khim., 2001, vol. 71, no. 6, p. 981.
3. Gordon, A.J. and Ford, R.A., The Chemist’s Companion.
A Handbook of Practical Data, Techniques, and
References, New York: Wiley, 1972. Translated under
the title Sputnik khimika, Moscow: Mir, 1976, p. 297.
Vj
hexane was added in an argon flow over a period of
0.5 h to a vigorously stirred solution of 0.03 mol of
peroxy alkynes Ia and Ib in 50 ml of absolute ether,
cooled to 40 to 20 C. The mixture was stirred for
an additional 1 h, after which 0.02 mol of -amino
ketones IIIa IIIc was added, and the mixture was
warmed to 20 23 C over a period of 1 2 h, stirred for
an additional 3 4 h, and allowed to stand for 18 h at
room temperature. Then 100 ml of hexane was added,
and the organic layer was washed with water and
dried over MgSO4. The solvent was removed. Perox-
ides Va Vf were purified by column chromatography
on silica gel, eluent hexane or hexane diethyl ether,
3 : 1.
4. Kozlov, N.G., Popova, L.A., Biba, V.I., Potkina, T.N.,
and Korshuk, V.K., Zh. Obshch. Khim., 1988, vol. 58,
no. 11, p. 2593.
5. Wendlandt, W.Wm., Thermal Methods of Analysis,
New York: Interscience, 1964.
6. Mair, R.D. and Graupner, A.J., Anal. Chem., 1964,
vol. 36, no. 1, p. 194.
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Ol’dekop, Yu.A., Vestsi Akad. Navuk Bel. SSR, Ser.
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tsezii (Methods of Organometallic Chemistry. Lithium,
Sodium, Potassium, Rubidium, and Cesium), Moscow:
Nauka, 1971, book 1, pp. 99, 554.
Acetylenic peroxy ethers Vg Vj. A 0.012-mol por-
tion of methyl or ethyl iodide and 3 ml of hexameth-
ylphosphoramide were added to a solution containing
0.01 mol of lithium peroxy alcoholates IV formed as
intermediates in syntheses of peroxy alcohols Va Vf.
9. Kozlov, N.G., Vorob’eva, G.V., and Stremok, I.P.,
Vestsi Akad. Navuk Bel. SSR, Ser. Khim. Navuk, 1969,
no. 2, p. 89.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 4 2003