Synthesis of phosphorylated derivatives of isatin with sterically hindered phenol fragments

Article abstract of DOI:10.1080/10426507.2016.1138308

The synthesis of N-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]methylisatins has been performed by the addition of isatin and 5-butylisatin to the double bond of dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidene)methylphosphonate. Subsequent functionalization of the compounds synthesized with thiosemicarbazide hydrochloride, 3-(3?,5?-di-tert-butyl-4?-hydroxyphenyl)propionic acid hydrazide, and isonicotinic acid. Hydrazide gave isatin derivatives containing several pharmacophore fragments. Each of them has the ability to the increase the antioxidant and biological activities of these compounds.

Full text of DOI:10.1080/10426507.2016.1138308

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Synthesis Of Phosphorylated Derivatives Of Isatin
With Sterically Hindered Phenol Fragments
Sergey V. Bukharov, Alexander R. Burilov, Yulia N. Oludina, Roza G.
Tagasheva, Viktor V. Syakaev, Rashid Z. Musin & Gulnara N. Nugumanova
To cite this article: Sergey V. Bukharov, Alexander R. Burilov, Yulia N. Oludina, Roza G.
Tagasheva, Viktor V. Syakaev, Rashid Z. Musin & Gulnara N. Nugumanova (2016): Synthesis Of
Phosphorylated Derivatives Of Isatin With Sterically Hindered Phenol Fragments, Phosphorus,
Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2016.1138308
To link to this article: http://dx.doi.org/10.1080/10426507.2016.1138308
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Date: 16 March 2016, At: 09:57

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SYNTHESIS OF PHOSPHORYLATED DERIVATIVES OF ISATIN WITH
STERICALLY HINDERED PHENOL FRAGMENTS
Sergey V. Bukharov1, Alexander R. Burilov*2, Yulia N. Oludina1, Roza G. Tagasheva1,
Viktor V. Syakaev2, Rashid Z. Musin2, Gulnara N. Nugumanova1
1Kazan National Research Technological University, Russia, 420015 Kazan,
68 Karl Marx st.
2 A.E. Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Center of
Russian Academy of Sciences Russia, 420088 Kazan, 8 Akademika Arbuzova st.
E-mail: burilov_2004@mail.ru
Abstract: The synthesis of N-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]
methylisatins has been performed by the addition of isatin and 5-butylisatin to the double bond
of dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidene)methylphosphonate. Subsequent
functionalization of the compounds synthesized with thiosemicarbazide hydrochloride, 3-(3’,5’-
di-tert-butyl-4’-hydroxyphenyl)propionic acid hydrazide, and isonicotinic acid. Hydrazide gave
isatin derivatives containing several pharmacophore fragments. Each of them has the ability to
the increase the antioxidant and biological activities of these compounds.
Keywords: isatin, phosphonate, sterically hindered phenol, antioxidants
1
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INRTODUCTION
Isatin and its derivatives attracted the attention of the researchers for many years due to
their high and various reactivity, as well as biological activities [1, 2]. Large number of
substitution reactions, condensate, and transform five-member heterocycles of isatin derivatives
were described. On the other hand, there are very rare examples of their addition by multiple
bonds. For example, products synthesis of addition of isatin in three-component system
composed of isatin, acetylene derivative, and trialkyl(aryl)phosphite is reported. Reaction
proceeds through the preliminary formation of the activated ethylene adduct and subsequent
addition of isatin with cleavage of N-H bond of heterocycle. Reaction of isatin with acetylene
derivatives in the presence of triphenylphosphine proceeds according to the similar scheme
[4].[5], Formation of the product by addition of isatin to acetylenes activated by the addition of
alkylisocyanide was described. Direct addition of isatin to fumaric acid diethyl ether under
sufficiently hard conditions in ionic liquid at basic catalysis by means of diazabicyclooctane was
performed by the authors from [6].
Earlier, we reported condensation of isatin with 3,5-di-tert-butyl-4-hydroxybenzylacetate
1 in dipolar aprotic solvent (DMF) [7]. It is known [7,8] that benzylacetate 1 generates high-
reactive 2,6-di-tert-butyl-4-methylenecyclohexa-2,5-dienone 2 under these conditions (Scheme
1).
Thus, condensation mentioned above can be considered as in situ addition of isatin to
methylenequinone 2.
2
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RESULTS AND DISCUSSION
In this work, we performed addition of isatins 3а and 3b to dimethyl-(3,5-di-tert-butyl-4-
oxo-2,5-cyclohexadienylidene)methylphosphonate 4 (Scheme 2).
Reactions of isatins 3а and 3b with methylenequinone 5 were performed at temperatures
of 60-70оС with triethylamine as a catalyst.
The
synthesized
N-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]
methylisatins 5а and 5b are hybrid structures which are of interest as multifunctional
antioxidants and biologically active substances. Subsequent functionalization of compounds 5а
and 5b by the reactions with thiosemicarbazide hydrochloride 6, 3-(3’,5’-di-tert-butyl-4’-
hydroxyphenyl)propionic acid hydrazide 7, and isonicotinic acid hydrazide 8 gave isatin
derivatives 9 - 11 containing several pharmacophore fragments. Each of them has the ability to
the increase of the antioxidant and biological activities of these compounds (Scheme 3).
It is known that, for acylhydrazones of carbonyl compounds, the spatial structures are
realized, which are determined by cis/trans–isomerism of amide group hindered by the rotation
around N–N bond and geometric isomerism (E/Z) at С=N double bond [9]. ZN–N–conformation
of hydrazones is usually not realized due to steric hindrances leading to violation of coplanarity
of С=N–NH fragment and, consequently, n–π conjugation [10,11]. Thus, for compounds 10-11,
realization of the following forms can be anticipated (Scheme 4):
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The chemical shift of N-H proton (12.5-14 ppm) of compounds 10a,b and 11, as well as
9a,b, which does not depend on their concentration (see Table 1), indicates on the presence of
strong intramolecular hydrogen bond and existence of these compounds as Z-isomers relative to
С=N – bond. In 1Н NMR spectrum of compound 10b, there are signals of N-H proton of both Z
and E (δ N-H ~ 9.5 ppm [8]) isomer. Z-to-Е isomer ratio equals to 5/1. Intrinsic doubling of
signals of СН2О and Н-4 protons in the spectra of compounds 10а,b (see Fig. 1) confirms the
presence of cis- and trans- forms relative to С(О)-N – bond [8]. This is also indicated by
doubling of low-field signals of N-H protons of these compounds. The intensity ratio of the
signals of the protons of СН2О, Н-4, and N-H groups related to cis- and trans- forms of
compounds 10а,b corresponds to 4/1 and 3/1, respectively (Table 1, Figure 1).
CONCLUSION
Relatively rarely observed addition of the isatin derivatives to a carbon-carbon double
bond was performed. We have been synthesized phosphorylated sterically hindered phenolic
isatin derivatives containing several pharmacophoric moieties. Each of them can enhance the
antioxidant and the biological activity of the compounds cited above. Phosphorylated
thiosemicarbazone and acylhydrazone containing hindered phenolic fragments were obtained
mainly as Z isomer. The intramolecular hydrogen bonds in these isomers stabilize the C=N
bonds. It is established in the presence of cis- and trans-forms with respect to C(O)-N – bond in
the obtained compounds.
EXPERIMENTAL
4
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31
1Н NMR and Р spectra were recorded on a Bruker MSL-400 (Germany, Karlsruhe)
instrument with the working frequency of 400 and 162 MHz, respectively, relative to the signals
31
of residual protons of deuterated solvent (DMSO-d6, CDCl3). Р NMR - relative to external
standard, namely, 85% H3PO4, at 20оС. IR spectra were recorded from KBr with a Bruker Vector
22 Fourier spectrometer (Germany, Karlsruhe) in the range from 400 to 3800 cm-1. The study
mass spectra was conducted on the device (DFS) Thermo Electron Corporation (Germany). The
method of ionization: electron impact. The energy of the ionizing electrons was 70 eV, the ion
source temperature 290°C. Used capillary column ID-BPX5, length—60 m, diameter—0.32-
mm. Carrier Gas-helium. Processing mass spectral data was performed using the program
“Xcalibur”. Purity of the sample prior to entering the device diluted in chromatographically pure
acetone was at a concentration about 1% wt.
Dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidene)methylphosphonate 4
was synthesized according to the available method [12].
General procedure for the preparation of 5(a,b), 9(a,b), 10(a,b), 11.
1-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]-1Н-indole-2,3-dione 5a. A
solution of isatin (0.07 g, 0.45 mmol) and dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-
cyclohexadienylidene)methylphosphonate (0.14 g, 0.43 mmol) and triethylamine (0.25 mL) in
o
DMF (3 mL) was stirred at 60 С for 30 min. The reaction mixture was cooled to room
temperature, treated with 10% aqueous solution of NaCl (200 mL) and the precipitate formed
was filtered, washed with water, and dried in air to a constant weight. Yield 0.177 g (87%),
1
yellow crystals, mp 155-160 oС. Н NMR spectrum (CDCl3, δ, ppm): 1.40 s (18 Н, СМе3), 3.74
5
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d (3Н, ОСН3, 3JH-P = 10.8 Hz), 3.80 d (3Н, ОСН3, 3J H-P = 10.8 Hz), 5.32 s (1H, OH), 6.03 d (1Н,
СН, 2JH-P = 24.5 Hz), 7.09 t (1Н, Н5, 3J = 7.4 Hz), 7.45 d (1Н, Н7, 3J = 7.4 Hz), 7.46 s (2Н, Н8),
7.50 t (1Н, Н6, 3J = 7.4 Hz), 7.60 d (1Н, Н4, 3J = 7.4 Hz). 13С NMR spectrum (CDCl3, δ, ppm):
1
2
29.7 (СМе3), 33.9 (СМе3), 51.2 d (СН, JС-Р = 159 Hz), 52.9 d (СН3О, JС-Р = 7.5 Hz), 53.4 d
(СН3О, 2JС-Р = 6.4 Hz), 114.2, 117.5, 121.0, 123.4, 124.6, 125.6 d (2JС-Р = 8.0 Hz), 136.0, 137.6,
149.4, 153.7 (CAr). 157.7 (C2=O), 182.0 (C3=O). 31P NMR spectrum (CDCl3, δ, ppm): 22.1.
HRMS(EI) calculated for С25H32NO6P 473.1967, found 473.2015.
1-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]–5-butyl-1Н-indole-2,3-dione
5b. A solution of butylisatin (1.2 g, 5.9 mmol), dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-
cyclohexadienylidene)methylphosphonate (2 g, 6.1 mmol) and triethylamine (0.1 mL) in DMF
(30 mL) was stirred at 70oС for 8.5 h. The reaction mixture was treated with an 10% aqueous
solution of NaCl (200 mL) and the precipitate formed was filtered, washed with water, and dried
1
in air to a constant weight. Yield 3.2 g (98%), vinous powder, mp 95°С. Н NMR spectrum
(CDCl3, δ, ppm): 0.92 t (3Н, Ме), 1.35-1.45 m (2Н, СН2), 1.40 s (18 Н, СМе3), 1.50-1.60 m
3
3
(2Н, СН2), 2.55 t (2Н, CH2Ar), 3.74 d (3Н, ОСН3, JH-P = 10.9 Hz), 3.80 d (3Н, ОСН3, J H-P
=
2
3
10.9 Hz), 5.31 s (1H, OH), 6.01 d (1Н, СН, JH-P = 24.5 Hz), 7.31 br. d (1Н, Н6, J = 8.3 Hz),
7.35 d (1Н, Н7, 3J = 8.3 Hz), 7.42 br. s (1Н, Н4), 7.45 s (2Н, Н8). 13С NMR spectrum (CDCl3, δ,
ppm): 13.3 (СН3), 21.6 (СН2), 29.7 (СМе3), 32.7 (СН2), 33.9 (СМе3), 34.1 (СН2Ar), 51.1 d (СН,
2
2
1JС-Р = 159 Hz), 52.9 d (СН3О, JС-Р = 7.2 Hz), 53.4 d (СН3О, JС-Р = 6.6 Hz), 114.0, 117.6,
121.1, 124.2, 125.7 d (2JС-Р = 8.0 Hz), 135.9, 137.7, 138.3, 147.3, 153.7 (CAr). 157.9 (C2=O),
182.3 (C3=O). 31P NMR spectrum (CDCl3, δ, ppm): 23.1. HRMS(EI) calculated for С29H40NO6P
529.2593, found 529.2605.
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Thiosemicarbazone
1-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]1Н-
indole-2,3-dione 9a. A solution of isatin phosphonate (2 g, 4.2 mmol) and thiosemicarbazide
hydrochloride (0.54 g, 4.2 mmol) in ethanol (100 mL) was stirred at 70oС for 3.5 h. The reaction
mixture was treated with an 10% aqueous solution of NaCl (200 mL) and the precipitate formed
was filtered, washed with water, and dried in air to a constant weight. Yield 1.6 g (69%), yellow
1
powder. mp 123-125oС. Н NMR spectrum (CDCl3, δ, ppm): 1.40 s (18 Н, СМе3), 3.71 d (3Н,
3
ОСН3, JH-P = 10.8 Hz), 3.80 d (3Н, ОСН3, 3J H-P = 10.8 Hz), 5.30 s (1H, OH), 6.04 d (1Н, СН,
2JH-P = 24.7 Hz), 6.77 br. s (1Н, NH2), 7.08 t (1Н, Н5, 3J = 7.6 Hz), 7.32 t (1Н, Н6, 3J = 7.6 Hz),
3
3
7.44 s (2Н, Н8), 7.44 d (1Н, Н7, J = 7.6 Hz), 7.57 d (1Н, Н4, J = 7.6 Hz), 12.80 s (1H, NH).
1
13С NMR spectrum (CDCl3, δ, ppm): 29.7 (СМе3), 33.9 (СМе3), 50.7 d (СН, JС-Р = 159 Hz),
2
2
52.9 d (СН3О, JС-Р = 7.0 Hz), 53.4 d (СН3О, JС-Р = 6.6 Hz), 113.3, 118.9, 120.0, 121.3, 122.9,
125.6 d (2JС-Р = 7.7 Hz), 130.8, 130.9, 135.9, 141.7, 153.7 (CAr, C=N). 160.3 (C=O), 179.5
(C=S). 31P NMR spectrum (CDCl3, δ, ppm): 22.2. HRMS(EI) calculated for С26H36N4O5PS
547.2144, found 547.2195.
Thiosemicarbazone 1-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]-5-butyl-
1Н-indole-2,3-dione 9b. A solution of butylisatin phosphonate (2 g, 3.8 mmol) and
thiosemicarbazide hydrochloride (0.5 g, 3.9 mmol) in ethanol (100 mL) was stirred at 70oС for
5.5 h. The reaction mixture was treated with a 10% aqueous solution of NaCl (200 mL) and the
precipitate formed was filtered, washed with water, and dried in air to a constant weight. Yield
1
2.25 g (98%), yellow powder, mp 103°С (with decomposition). Н NMR spectrum (CDCl3, δ,
ppm): 0.93 t (3Н, Ме), 1.25-1.45 m (2Н, СН2), 1.41 s (18 Н, СМе3), 1.53-1.65 m (2Н, СН2),
3
3
2.59 t (2Н, CH2Ar), 3.71 d (3Н, ОСН3, JH-P = 10.8 Hz), 3.79 d (3Н, ОСН3, J
= 10.8 Hz),
H-P
7
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2
3
5.29 s (1H, OH), 6.02 d (1Н, СН, JH-P = 24.5 Hz), 6.54 br. s (1Н, NH2), 7.13 dd (1Н, Н6, J =
8.2 Hz, 4J = 1.7 Hz), 7.35 d (1Н, Н7, 3J = 8.2 Hz), 7.39 s (1Н, Н4, 4J = 1.7 Hz), 7.44 s (2Н, Н8),
13
7.55 br. s (1Н, 1Н, NH2), 9.59 s, 12.83 s (1H, NH). С NMR spectrum (CDCl3, δ, ppm): 13.4
(СН3), 21.7 (СН2), 29.7 (СМе3), 33.1 (СН2), 33.9 (СМе3), 34.6 (СН2Ar), 50.6 d (СН, 1JС-Р = 159
2
2
Hz), 52.9 d (СН3О, JС-Р = 7.2 Hz), 53.4 d (СН3О, JС-Р = 6.6 Hz), 113.1, 118.8, 119.8, 121.4,
125.7 d (2JС-Р = 7.7 Hz), 131.0, 131.2, 135.8, 137.7, 139.8, 153.6 (CAr, C=N). 160.4 (C=O), 179.5
(C=S). 31P NMR spectrum (CDCl3, δ, ppm): 21.7. HRMS(EI) calculated for С34H44N4O5PS
603.2769, found 603.2820.
Acylhydrazone
3-(3,5-di-tert-butyl-4-hydroxyohenyl)-propionic
acid
1-
[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]-2-oxo-1,2-dihydroindole-(3E)-
ylidene]-hydrazide 10a. A solution of isatin phosphonate (2 g, 4.2 mmol), 3(3’,5’-di-tert-butyl-
4’-hydroxyphenyl)propionic acid hydrazide (1.24 g, 4.2 mmol), and triethylamine (2 mL) in
ethanol (50 mL) was stirred at 80oС for 8 h. The reaction mixture was cooled to room
temperature, and precipitate was filtered, washed with ethanol, and dried in air to a constant
weight. Yield 2.9 g (93%), yellow crystals, mp 137-139 С. 1Н NMR spectrum (CDCl3, δ, ppm):
1.40 s (18 Н, СМе3), 1.46 s (18 Н, СМе3), 2.75 br. t (trans-Z isomer), 3.16 br. t (cis-Z isomer)
3
[2H, СН2С(О)], 3.01 br. t [2H, ArCH2CH2C(O)], 3.70 d (3Н, ОСН3, JH-P = 10.9 Hz), 3.79 d
3
2
(3Н, ОСН3, J
= 10.9 Hz), 5.11 s (1H, OH), 5.29 s (1H, OH), 6.04 d (1Н, СН, JH-P = 24.8
H-P
Hz), 7.05 -7.15 br. m (3Н, Н5, Н9), 7.31 t (1Н, Н6, 3J = 7.8 Hz), 7.40 – 7.47 br. m (3Н, Н7, Н8),
7.60 d (cis-Z isomer), 7.84 br. d (trans-Z isomer) (1Н, Н4, 3J = 7.8 Hz), 12.47 s, (cis-Z isomer),
12.98 s (trans-Z isomer) (1H, NH). cis-Z/trans-Z isomer ratio is 4/1. 13С NMR spectrum (CDCl3,
δ, ppm): 29.7 (СМе3), 29.9 (СМе3), 30.2 [ArCH2CH2C(O)], 33.8 (СМе3), 33.9 (СМе3), 33.9
8
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1
[CH2C(O)], 50.7 d (СН, JС-Р = 158 Hz), 52.9 (СН3О), 53.3 (СН3О), 112.9, 119.6, 119.7, 121.5,
122.8, 124.5, 125.5, 130.2, 131.1, 131.4, 135.5, 135.8, 141.3, 151.7, 153.6 (CAr, C=N). 160.1
(C2=O), 175.1 (C=O). 31P NMR spectrum (CDCl3, δ, ppm): 21.8. HRMS(EI) calculated for
С42H58N3O7P 747.4012, found 747.4083
Acylhydrazone
3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic
acid
1-
[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]-2-oxo-1,2-dihydroindole-5-
butyl-(3E)-ylidene]-hydrazide 10b. A solution of butylisatin phosphonate (2 g, 3.8 mmol),
3(3’,5’-di-tert-butyl-4’-hydroxyphenyl)propionic acid hydrazide (1.1 g, 3.8 mmol), and
trifluoroacetic acid (0.05 mL) in ethanol (100 mL) was stirred at 70oС for 5.5 h. The reaction
mixture was cooled to room temperature, treated with a 10% aqueous solution of NaCl (200
mL), and the precipitate formed was filtered, washed with water, and dried in air to a constant
1
weight. Yield 2.7 g (88%), yellow crystals, mp 88°С (with decomposition). Н NMR spectrum
(CDCl3, δ, ppm): 0.93 t (3Н, Ме), 1.35-1.50 m (38Н, СН2, CMe3), 1.52-1.64 m (2Н, СН2), 2.59 t
(2Н, CH2Ar), 2.75 br. t (trans-Z isomer), 3.16 br. t (cis-Z isomer), 3.24 br. t (Е isomer) [2H,
СН2С(О)], 3.01 br. t [2H, ArCH2CH2C(O)], 3.67 – 3.83 m (6Н, ОСН3), 5.10 br. s (1H, OH),
5.28 br. s (1H, OH), 6.01 d (Z isomer), 6.19 d (Е isomer) (1Н, СН, 2JH-P = 24.8 Hz), 6.98 – 7.73
m (7Н, ArH), 9.44 s (Е isomer), 12.48 s (cis-Z isomer), 12.98 s (trans-Z isomer) (1H, NH). Z/E
isomer ratio is 5/1, cis-Z/trans-Z isomer ratio is 2.5/1. 13С NMR spectrum (CDCl3, δ, ppm): 13.4
(СН3), 21.8 (СН2), 29.7 (СМе3), 29.9 (СМе3), 30.3 [ArCH2CH2C(O)], 33.5 (СН2), 33.8 (СМе3),
1
33.9 (СМе3), 33.9 [CH2C(O)], 34.0 (СН2Ar), 50.7 d (СН, JС-Р = 159 Hz), 52.9 (СН3О), 53.3
(СН3О), 112.7, 115.2, 119.5, 121.6, 123.3, 124.3, 124.6, 125.6, 130.3, 130.7, 131.2, 131.8,
135.5, 135.7, 137.7, 139.3, 140.5, 151.7, 153.6 (CAr, C=N). 160.2 (C2=O), 171.0, 175.1 (C=O).
9
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31P NMR spectrum (CDCl3, δ, ppm): 21.9, 24.3. HRMS(EI) calculated for С46H66N3O7P
803.4638, found 803.4669.
Isonicotinic acid hydrazone 1-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)]-
5-butyl-1Н-indole-2,3-dione 11. A solution of isatin phosphonate (3 g, 6.3 mmol), isonicotinic
acid hydrazide (0.85 g, 6.2 mmol), and acetic acid (0.05 mL) in ethanol (100 mL) was stirred at
80oС for 8.5 h. The reaction mixture was cooled to room temperature, treated with an 10%
aqueous solution of NaCl (200 mL), and the precipitate formed was filtered, washed with water,
and dried in air to a constant weight. Yield 2.8 g (75%), yellow crystals. mp 130оС (with
1
3
decomposition). Н NMR spectrum (CDCl3, δ, ppm): 1.41 s (СМе3), 3.72 d (3Н, ОСН3, JH-P
=
10.8 Hz), 3.80 d (3Н, ОСН3, 3JH-P = 10.8 Hz), 5.31 s (1Н, ОН), 6.08 d (1Н, СН, 2JH-P = 25.3 Hz),
7.15 t (1Н, Н5, 3J = 7.4 Hz), 7.36 t (1Н, Н6, 3J = 7.4 Hz), 7.44 s (2Н, Н8), 7.47 d (1Н, Н7, 3J =
13
7.4 Hz), 7.87 br. s (3Н, Н4, Н9), 8.87 br. s (2Н, Н10), 14.10 s (1Н, NH). С NMR spectrum
(CDCl3, δ, ppm): 29.7 (СМе3), 33.9 (СМе3), 51.0 d (СН, 1JС-Р = 159 Hz), 53.0 (СН3О, 2JС-Р = 6.6
Hz), 53.3 (СН3О, 2JС-Р = 6.6 Hz), 113.3, 118.9, 120.7, 121.0, 121.5, 123.4, 125.4 (2JС-Р = 7.2 Hz),
131.4, 135.3, 136.0, 138.7, 141.6, 150.5, 153.7 (CAr, C=N). 161.1 (C=O), 161.7 (C=O). 31P NMR
spectrum (CDCl3, δ, ppm): 21.6. HRMS(EI) calculated for С31H37N4O6P 592.2450, found
592.2482.
ACKNOWLEDGMENTS
The work was supported by the Russian Foundation for Basic Research (grant №. 15-43-02088-
а).
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[7] Nugumanova, G. N.; Bukharov, S. V.; Tagasheva, R. G.; Kurapova, M. V.; Syakaev, V. V.;
Mukmeneva, N. A.; Gurevich, P. A.; Burilov, A. R. J. Org. Chem., 2007, 12, 1796-1801.
[8] Nugumanova, G. N.; Tagasheva, R. G.; Bukharov, S. V.; Krivolapov, D. B.; Litvinov, I. A.;
Syakaev, V. V.; Mukmeneva, N.A.; Burilov, A. R. Russ. Chem. Bull., 2009, 9, 1934-1938.
[9] Flegontov, S. A.; Titova, Z. S.; Buzikin, B. I.; Kitaev, Y. P. Bull. Acad. Sci. USSR, Div.
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[10] Litvinov, I. A.; Kataeva, O. N.; Ermolaeva, L. V.; Vagina, G. A.; Troepolskaya, T. V.;
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Galkin, V.I. Mendeleev Commun. 2009, 19, 37-38.
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Table 1 Position of signals of N-H proton in 1Н NMR spectra of solutions of compounds 9-11 (in
CDCl3)
Compound
С/mol·L -1
2·10 -3
δ, ppm N-H
12.84
Z-9а
5·10 -2
12.82
Z-9b
2·10 -3
12.84
5·10 -2
12.83
Z-10a (cis- С(О)-
2·10 -3
12.50
N)
5·10 -2
2·10 -3
12.47
13.01
Z-10a
С(О)-N)
(trans-
5·10 -2
2·10 -3
12.98
12.51
Z-10b (cis- С(О)-
N)
5·10 -2
2·10 -3
12.48
13.01
Z-10b
С(О)-N)
(trans-
5·10 -2
2·10 -3
5·10 -2
2·10 -3
5·10 -2
12.98
9.45
E-10b
9.45
Z-11
14.12
14.10
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7.92 7.88 7.84 7.80 7.76 7.72 7.68 7.64 7.60 7.56 7.52
(ppm)
3.35 3.30 3.25 3.20 3.15 3.10 3.05 3.00 2.95 2.90 2.85 2.80 2.75 2.70 2.65
(ppm)
Figure 1 Fragments of 1Н NMR spectrum of acylhydrazone 10а
13
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Scheme 1
14
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t-Bu
O
O
P
O
1
O
R
O
t-Bu
O
4
7
3
2
5
6
1
t-Bu
OH
O
R
4
1
N
O
2
N
R
O P
O
2
H
R
O
t-Bu
1
2
R
R
1
2
3a
3b
R
R
H
Bu
H
H
5a
5b
H
H
H
Bu
Scheme 2
15
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NNHC(S)NH2
t-Bu
OH
R1
4
7
5
6
O
1
R1
R2
N
8
R2
9a
9b
H
Bu
H
H
O
P
O
O
t-Bu
.
H2NNHC(S)NH2 HCl
6
t-Bu
HO
O
t-Bu
OH
t-Bu
NHNH2
9
NNHC(O)CH2CH2
t-Bu
OH
t-Bu
t-Bu
7
R1
5a,b
4
5
6
O
1
N
7
R1
R2
8
R2
O
10a
10b
H
H
O
P
N
O
Bu
H
O
NHNH2
8
9
10 N
NNHC(O)
4
5
6
t-Bu
OH
t-Bu
O
1
N
7
8
O
P
O
O
11
Scheme 3
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O
R
C
O
O
C
R
C
O
C
1
1
N
N
NR
N
.
NR
N
N
H
O
N
H
R
N
O
N
R
1
1
NR
NR
.
H
.
.
H
.
O
.
O
cis, Z
cis, E
trans, Z
trans, E
Scheme 4
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t-Bu
O
O
P
O
R1
O
O
t-Bu
O
4
7
3
2
5
6
R1
t-Bu
OH
O
4
1
N
O
R2
N
O
O
P
R2
H
O
t-Bu
H2NNHC(S)NH2 HCl
R1
R2
R1
R2
6
3a
3b
H
Bu
H
H
5a
5b
H
Bu
H
H
t-Bu
HO
NH2NH2
NNHC(S)NH2
t-Bu
OH
t-Bu
O
R1
t-Bu
O
4
7
N
7
5
6
O
NHNH2
1
R1
R2
N
8
8
R2
9a
9b
H
Bu
H
H
O
P
O
O
10 N
9
NNHC(O)
4
t-Bu
OH
t-Bu
R1
5
6
t-Bu
O
1
N
.
7
9
8
NNHC(O)CH2CH2
R1
OH
t-Bu
4
5
6
O
P
t-Bu
OH
t-Bu
O
1
N
O
7
O
8
R2
R2
11
O
P
O
10a
10b
H
H
H
O
Bu
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