Search

An efficient method for the synthesis of 1,2-bisphosphoryl compounds based on the addition of hydrophosphoryl derivatives to O,O-diethyl vinylphosphonate was developed. The reaction proceeds in mild conditions under catalysis with tri-n-butylphosphine and leads to the formation of the corresponding target products with high yield.

Dialkyl [2-(piperazin-1-yl)ethyl]phosphonates were obtained by the reactions of piperazine with dialkyl vinylphosphonates. The addition of 2-(piperazin-1-yl)ethanamine to diethyl vinylphosphonate involves the primary exocyclic amino group of the heterocyclic compound.

Diethyl vinylphosphonate reacted with octyl- and dodecylamines to give the corresponding addition products which underwent dealkylation via elimination of ethylene molecule with formation of crystalline zwitterionic ethyl 2-(alkylammonio)ethylphoshonates.

Reaction of two-fold excess of diethyl 3-methyl-1,2-butadienylphosphonate with 1,10-diaza-18-crown-6 leads to the formation of an adduct whose molecule includes two 1-phosphoryl-3-methyl-2-butene fragments bound together by a crown bridge with the anti location of organophosphorus groups relative to the macrocycle plane. The 1,2-multiple bond of the phosphonate is involved in the reaction. Extraction properties of the diphosphorylated crown ether toward alkali metal picrates were studied.

The reaction of 1,2-diaminoethane with vinylphosphonate occurs as the addition of the amino group to the β -carbon atom of the unsaturated substrate to give 1:1 and 1:2 adducts. The nucleophilic addition of 2-aminoethanol at the β -position of the double bond of vinylphosphonates involves only the amino group and leads to the formation of hydroxy β -aminoethylphosphonates or zwitterions depending on conditions.

New and previously known β-aminoethylphosphonates were synthesized by addition of primary and secondary amines to vinylphosphonates, and their IR and NMR spectra were examined. Diethyl 2-diethylaminoethylphosphonate and diethyl 2-morpholinoethylphosphonate were found to be stronger bases than the corresponding aminomethylphosphonates, but all these are weaker bases than their precursors, nonphosphorylated amines. Distribution constants of β-aminophosphonates between water and some organic solvents were determined and compared with those of their α-amino homologs.

Dialkyl 3-methyl-1,2-butadienylphosphonates take up 2-aminoethanol, butylamine, diethylamine, and morpholine in such a way that the amino nitrogen atom adds at the central carbon of the allene triad. The reactions with primary amines lead to the corresponding 1-phosphoryl-2-amino-1-butenes and isomeric 1-phosphoryl-2-iminobutanes, while secondary amines give rise to 1,2- and 2,3-enamines.

Reaction of 2-acetyl-5-methyl-2H-1,2,3-diazaphosphole with ethane-1,2-dithiol at −30°C leads to the formation of 2-acetyl-3-(β-mercaptoethylthio)-5-methyl-1,2,3-diaza-phospholene. On heating, this product forms 2-(β-mercaptoethylthio)-1,3,2-dithia-phospholane, 1,2-bis(1,3,2-dithiaphospholanyl)-dithioethane, and N-acetyl-N′-isopropilidene-hydrazine.

The reactions of dialkyl 3-methylbuta-1,2-dien-1-ylphosphonates with 1,2-diaminoethane lead to the formation of symmetrical N,N′-bis(1-dialkoxyphosphoryl-3-methylbut-1-en-2-yl)-1,2-diaminoethanes.

Alkenylphosphonates containing aminoorganyl groups in the β-position with respect to the phosphoryl fragment are promising from the practical viewpoint as biologically active compounds. With a view to obtain new derivatives of this series, we examined reactions of allenylphosphonates with ethylenediamine. The reaction of diethyl propa-1,2-dienylphosphonate (Ia) with ethane-1,2-diamine was accompanied by strong heat evolution, and it led to the formation of a thick oily product. The IR spectrum of this product lacked absorption band at 1960 cm typical of the C=C=C triad, but bands corresponding to stretching vibrations of C=C bond (1635 cm) and NH and NH2 groups (3200–3360 cm) appeared. In the H NMR spectrum of the product (DMSO-d6) we observed a doublet signal at δ 1.95 ppm (3H, CH3C=, JPH = 1.9 Hz), which indicated the absence of terminal H2C= group. Also, a doublet signal was present at δ 3.41 ppm (JPH = 12.5 Hz) due to CH= proton in the α-position with respect to phosphorus, whereas there was no signal assignable to protons in PCH2 methylene group with a characteristic coupling constant JPH of 18– 22 Hz. These findings allowed us to exclude theoretically possible imine structure [1, 2]. Signals from the ethoxy groups in the phosphoryl fragment were located in the expected regions, at δ , ppm: 1.03 t (6H, CH3CH2, JHH = 7.1 Hz) and 4.01 m (4H, CH2O). Only one phosphorus signal was present at δP 27.5 ppm in the P NMR spectrum (DMSO-d6) The above data led us to conclude that phosphonate Ia reacts with ethane-1,2-amine via attack by the amino nitrogen atom in the latter on the central sp-hybridized carbon atom of the cumulene fragment to produce enamine structure, diethyl 2-(2-aminoethylamino)prop-1-en-1-ylphosphonate (II) (Scheme 1). It should be noted that compound II is capable of undergoing enamine–imine tautomerism, depending on the solvent. In CDCl3, the adduct exists as mixtures of several tautomers, as follows from the presence of additional signals in the P NMR spectrum, δP 22.44, 22.62, 26.07, 26.58, and 26.67 ppm. In the H NMR spectrum of a solution in CDCl3 we observed a doublet from methylene protons at δ 2.54 ppm (2H, PCH2C, JPH = 22.4 Hz), while no signal assignable to terminal methylene group H2C was present. These data indicated formation of imino tautomer III. The presence of numerous signals in the P NMR spectrum (CDCl3) may also be attributed to Z/E isomerism of different tautomers. The H NMR spectrum was also strongly complicated. On the other hand, we cannot rule out initial isomerization of allenylphosphonate Ia into propynylphosphonate, followed by addition of ethylenediamine to the triple bond. Enamine II was also synthesized by reaction of diethyl prop-2-yn-1-ylphosphonate with ethylenediamine. By reaction of ethylenediamine with 2.5 equiv of diethyl, diisopropyl, and dibutyl propa-1,2-dienylphosphonates Ia–Ic we obtained bis-phosphonates IV–VI (Scheme 2). The P NMR spectra of IV–VI contained only one signal. Compounds IV–VI displayed in the ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 9, pp. 1399–1400. © Pleiades Publishing, Ltd., 2013. Original Russian Text © N.G. Khusainova, E.P. Pogodina, A.V. Gerasimov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 9, pp. 1415–1416.

Trichloro(o-phenylenedioxy)phosphorane reacts with 1,2-alkadienylphosphonates with selective replacement of the alkoxy group in the phosphinoyl moiety, yielding the corresponding 1,2-alkadienylchloro- phosphonates and o-phenylene chlorophosphate.

Dialkyl 3-methylbuta-1,2-dienyl- and vinylphosphonates take up imidazole at the β-carbon atom in the unsaturated fragment to give the corresponding β-(1H-imidazol-1-yl)alkenyl-and alkylphosphonates.

Development of methods for the synthesis of new aminophosphoryl compounds is an important field of modern organoelement chemistry due to wide potential of using them as biologically active substances, extractants, and membrane carriers [1–3]. Of particular interest are phosphonates functionalized by pharmacophoric nitrogen-containing heterocyclic fragments. With the goal of obtaining such derivatives, we have studied the reaction of diethyl vinylphosphonate (1) with 1,3-benzothiazol-2-amine (2). An equimolar mixture of compounds 1 and 2 was heated for 25 h at 70°C. Repeated washing of the reaction mixture with hexane until constant refractive index gave a thick yellow transparent oil. The P NMR spectrum of the product contained only one signal at δP 28 ppm, indicating that the reaction was selective. The reaction of vinylphosphonate 1 with aminobenzothiazole 2 can take two paths involving attack on the β-carbon atom of the vinyl group by the endocyclic nitrogen atom of 2 with formation of adduct 3 (path a) or by the exocyclic amino nitrogen atom with formation of adduct 4 (path b). The H NMR spectrum of the product contained the following signals (CDCl3), δ, ppm: 1.36 t (6H, CH3CH2O, JHH = 7.06 Hz), 2.28 m (2H, PCH2, JPH = 18.6, JHH = 7.6 Hz), 3.82 m (2H, CH2N), 4.15 m (4H, CH3CH2O), 5.71 br.s (NH), 7.10–7.50 m (4H, Harom). We previously studied the reaction of diethyl 3-methylbuta-1,2-dien-1-ylphosphonate with 2-aminobenzothiazole [4], and the structure of the product was determined by X-ray analysis. It was found that the addition involved the endocyclic nitrogen atom. Taking these data into account, we presumed that the addition of phosphonate 1 to aminobenzothiazole 2 yields diethyl 2-[2-imino-1,3-benzothiazol-3(2H)-yl]ethylphosphonate (3). The above given H and P NMR spectral data are consistent with structure 3. Yield 64%, nD = 1.5553. Found, %: C 49.23; H 5.81. C13H19N2O3PS. Calculated, %: C 49.67; H 6.05. The H and P NMR spectra were recorded on a Varian Unity-300 spectrometer a t 300 and 121.4 MHz, respectively. The chemical shifts were measured relative to the residual proton signal of the solvent (H) or 85% H3PO4 (P, external standard). This study was funded by the subsidy allocated to Kazan Federal University for the project part of the state assignment in the sphere of scientific activities. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 4, pp. 593–594. © Pleiades Publishing, Ltd., 2015. Original Russian Text © N.G. Khusainova, E.P. Pogodina, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 4, pp. 609–610.

A sociological survey was made in the Sariasiysk and Uzun districts of the Surkhandaryinsk Region in October 2010 within the project UZB-809-G04-M "Consolidation of the achieved results and support of measures to eliminate malaria in Uzbekistan". These districts were selected due to the high susceptibility and vulnerability of the areas and to the results of surveys within the Global Fund project during 2005-2010. The results of the inquiry demonstrate progress in a number of indicators of awareness about malaria. In particular, 63% of the population knew the main symptoms of malaria, 65% could call main ways to prevent malaria; 97% was aware of that insecticide-impregnated canopies were the basic means of protection against mosquito bites, and 80% told all basic measures that could reduce the size of mosquitoes and to prevent their reproduction. Public population in the Sariasiysk district was much better than that in the Uzun district. Men were well aware than women; young people were less aware than adults. Awareness among persons with higher education exceeded that among those without professional education. Medical workers are the main source of information for the population. The role of mass media and local bodies was lower. Most of the population expressed their readiness to obtain expanded information on malaria.

The mercapto group of the heterocyclic compound (I) and the 1,2-double bond of allenylphosphonate (II) are involved in the reaction.

In 2008, the major malaria vectors An.superpictus and An. pulcherrimus amounted up to 50 specimens per premise in the Surkhandaryinsk and Kashkadaryinsk Regions. The high density of larvae in the water reservoirs (as many as 30-50 specimens per square meter) and rice fields (8-60 specimens per square meter) was noted in the Surkhandaryinsk, Namangan, Ferghana, and Tashkent Regions. There is a high susceptibility of the territory due to increased migration between Uzbekistan, Kyrgyzstan, and Tajikistan. In 2008, a total of 4,958,685 subjects passed through 68 border checkpoints, among them there were 835 (0.02%) individuals with suspected infectious diseases, including malaria. The foci of irrigation-ditch area and their conjugate foci of the floodplain-river one of the Surkhandaryinsk Region are most dangerous. Analysis of the trend of malaria foci showed a reduction in the number of new active foci from 44 in 2006 to 6 to 2008. The increased number of residual inactive and sanitized foci suggests that the malaria situation has considerably improved.

Dialkyl 3-methylbuta-1,2-dienyl- and vinylphosphonates take up imidazole at the β-carbon atom in the unsaturated fragment to give the corresponding β-(1H-imidazol-1-yl)alkenyl-and alkylphosphonates.

The addition of morpholino-, piperidino-, and N,N-diethyldithiocarbamate anions to 1,2-propadiene- and 1,2-butadienephosphonates proceeds on the electrophilic 1,2-double bond of the allene system with the formation of linear dithioesters. 1-Vinylallenylphosphonates add dithiocarbamate anions on the 1,3-conjugated system of multiple bonds, forming a mixture of stereoisomeric dithioesters with a diene structure.

New and previously known β-aminoethylphosphonates were synthesized by addition of primary and secondary amines to vinylphosphonates, and their IR and NMR spectra were examined. Diethyl 2-diethylaminoethylphosphonate and diethyl 2-morpholinoethylphosphonate were found to be stronger bases than the corresponding aminomethylphosphonates, but all these are weaker bases than their precursors, nonphosphorylated amines. Distribution constants of β-aminophosphonates between water and some organic solvents were determined and compared with those of their α-amino homologs.

The reaction of 1,2-ethanedithiol with diethyl vinylphosphonate in the presence of EtONa occurs as the addition of the sulfhydryl group to the β-carbon atom of the substrate to give 1 : 1 and 1 : 2 adducts. The nucleophilic addition of 2-mercaptoethanol at the β position of the multiple bond of diethyl vinyl-, diethyl allenyl-, and diethyl prop-1-ynylphosphonates involves only the sulfhydryl group.

Alkenylphosphonates containing aminoorganyl groups in the β-position with respect to the phosphoryl fragment are promising from the practical viewpoint as biologically active compounds. With a view to obtain new derivatives of this series, we examined reactions of allenylphosphonates with ethylenediamine. The reaction of diethyl propa-1,2-dienylphosphonate (Ia) with ethane-1,2-diamine was accompanied by strong heat evolution, and it led to the formation of a thick oily product. The IR spectrum of this product lacked absorption band at 1960 cm typical of the C=C=C triad, but bands corresponding to stretching vibrations of C=C bond (1635 cm) and NH and NH2 groups (3200–3360 cm) appeared. In the H NMR spectrum of the product (DMSO-d6) we observed a doublet signal at δ 1.95 ppm (3H, CH3C=, JPH = 1.9 Hz), which indicated the absence of terminal H2C= group. Also, a doublet signal was present at δ 3.41 ppm (JPH = 12.5 Hz) due to CH= proton in the α-position with respect to phosphorus, whereas there was no signal assignable to protons in PCH2 methylene group with a characteristic coupling constant JPH of 18– 22 Hz. These findings allowed us to exclude theoretically possible imine structure [1, 2]. Signals from the ethoxy groups in the phosphoryl fragment were located in the expected regions, at δ , ppm: 1.03 t (6H, CH3CH2, JHH = 7.1 Hz) and 4.01 m (4H, CH2O). Only one phosphorus signal was present at δP 27.5 ppm in the P NMR spectrum (DMSO-d6) The above data led us to conclude that phosphonate Ia reacts with ethane-1,2-amine via attack by the amino nitrogen atom in the latter on the central sp-hybridized carbon atom of the cumulene fragment to produce enamine structure, diethyl 2-(2-aminoethylamino)prop-1-en-1-ylphosphonate (II) (Scheme 1). It should be noted that compound II is capable of undergoing enamine–imine tautomerism, depending on the solvent. In CDCl3, the adduct exists as mixtures of several tautomers, as follows from the presence of additional signals in the P NMR spectrum, δP 22.44, 22.62, 26.07, 26.58, and 26.67 ppm. In the H NMR spectrum of a solution in CDCl3 we observed a doublet from methylene protons at δ 2.54 ppm (2H, PCH2C, JPH = 22.4 Hz), while no signal assignable to terminal methylene group H2C was present. These data indicated formation of imino tautomer III. The presence of numerous signals in the P NMR spectrum (CDCl3) may also be attributed to Z/E isomerism of different tautomers. The H NMR spectrum was also strongly complicated. On the other hand, we cannot rule out initial isomerization of allenylphosphonate Ia into propynylphosphonate, followed by addition of ethylenediamine to the triple bond. Enamine II was also synthesized by reaction of diethyl prop-2-yn-1-ylphosphonate with ethylenediamine. By reaction of ethylenediamine with 2.5 equiv of diethyl, diisopropyl, and dibutyl propa-1,2-dienylphosphonates Ia–Ic we obtained bis-phosphonates IV–VI (Scheme 2). The P NMR spectra of IV–VI contained only one signal. Compounds IV–VI displayed in the ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 9, pp. 1399–1400. © Pleiades Publishing, Ltd., 2013. Original Russian Text © N.G. Khusainova, E.P. Pogodina, A.V. Gerasimov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 9, pp. 1415–1416.

Heating 3-methyl-1,2-butadienyl phosphonates with piperazine leads to the formation of 2-piperazinyl-butenyl phosphonates containing the enamine functionality. From the reaction of piperazine with four equivalents of 1,2-butadienyl phosphonate a bis(phosphonate) is obtained, in which the piperazine bridge links two phosphorylbutene fragments.

Addition of propane-1-thiol and ethane-1,2-dithiol to 3,3-dimethylallenylphosphonate occurs at the 1,2-double bond of the cumulene system.

Reactions of 2-mercaptobenzimidazole with 3-methylbuta-1,2-dienylphosphonates involve the mer- capto group of the heterocyclic compound and the 1,2- double bond of allenylphosphonate.

Mixing an excess of 3-methyl-1,2-butadienylphosphonate with 1,2-diaminoethane, 1,2-diaminopropane, or 4,7,10-trioxa-1,13-tridecandiamine leads to the formation of bis-(aminoalkenylphosphonates).

High reactivity of allene derivatives of the tetracoordinated phosphorus atom in the nucleophilic addition reactions opens a possibility of the effective synthesis on their basis of new β-amino-functionalized organophosphorus compounds. The latter are promising for the use as biologically active compounds, metal extractants, and membrane carriers [1–3]. In this work the results of the study of the reaction between 3-methyl-1,2-butadienylphosphonates I and 4,9-dioxa-1,12-dodecanediamine II are presented. On mixing diamine II with two-fold excess of phosphonate I the oily adduct III was obtained. It was washed with СН2Cl2 to the constant value of nD. In the IR spectra of compound III the stretching vibrations band of allene triad (1955 cm) is absent, and strong bands at 1200 (Р=О), 1590 (С=С), 3300– 3500 cm (NH) appear. The absence of the proton signals of phosphorus methylene group with the spinspin coupling constant JPH 20–22 Hz and of the proton signals of two methyl groups at the double bond makes it possible to ascribe to compounds IIIа and IIIb the enamine structure. Compounds IIIа and IIIb possess effective antimycotic activity.

Addition of propane-1-thiol and ethane-1,2-dithiol to 3,3-dimethylallenylphosphonate occurs at the 1,2-double bond of the cumulene system.