THE STUDY OF 2-CHLORO-5,5-DIMETHYL-2-OXO-1,3,2-DIOXAPHOSPHORINANE IN SOLUTIONS BY MOLECULAR DYNAMICS METHODS USING IR AND RAMAN SPECTROSCOPY

Abstract

2-Chloro-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane has been studied in CCl₄, CHCl₃ and CD₃CN solutions by IR and Raman line shape analysis. Equilibrium process of dimerization and ring conversion in CCl₄ solutions have been considered. On the contrary to the commonly expected dominance of the conformer with the equatorial oriented P[dbnd]O bond for 2-halo-2-oxo-1,3,2-dioxaphosphorinanes, it was found that for the 2-chloro derivative both conformers are nearly equally distributed. It has been shown that the interactions induced absorption is an important mechanism of relaxation in the studied compound and this mechanism gives significant contribution to the total IR band broadening, while the interaction induced light scattering is negligible. The obtained results show that the molecular dynamics method can be useful in studying cyclic compounds in solutions.     

Synthesis and Biological Activity of 4-Chloromethyl-substituted 1,3,2-Dioxaphosphorinanes Phosphates and Amidophosphates

A series of 2-N and 2-O-substituted 2-oxo-4-chloromethyl-1,3,2-dioxaphosphorinanes were prepared by reaction of amines and alcohols with 2-oxo-2-chloro-4-chloromethyl-1,3,2-dioxaphosphorinane. The structure of compounds obtained was proved by means of ¹H and ^{1 3}C NMR spectroscopy. Some cyclic amidocyclophosphates possessed biological activity as inhibitors of mitotic fission and of Na⁺/H⁺ exchange.     

Thermochemistry of Heteroatomic Compounds XXI: Heat Capacities of Some Derivatives of Methylphosphonic and Dithiophosphorus Acids

The heat capacities of 2,4-dimethyl-2-oxo-(I)-, 2,5,5-trimethyl-2-oxo(II)-1,3,2-dioxaphosphorinanes, methylphosphonic acid (III), O,O-dimethyl(IV)-, O,O-diethyl(V)-, O,O-di-isopropyl(VI)esters of dithiophosphorus acid, 4,5-dimethyl-2-thiono-2-mercapto-1,3,2-dioxaphospholane(VII), and 4-methyl-2-thiono-2-mercapto-1,3,2-dioxaphosphorinane(VIII) were determined using the scanning calorimetry.     

2-(5-O-nitro-1,4:3,6-dianhydro-D-glucit-2-yloxy)-5-R-5-nitro-2-oxo-1,3,2-λ5-dioxaphosphorinanes: synthesis and structure

5,5-Disubstituted 1,3,2-dioxaphosphorinanes were synthesized by the reaction of (5-O-nitro-1,4:3,6-dianhydro-D-glucit-2-yl) phosphochloridate with 2-nitro-2-R-propane-1,3-diols in the presence of organic bases. The structure of 5-bromo-5-nitro-2-(5-O-nitro-1,4:3,6-dianhydro-d-glucit-2-yloxy)-2-oxo-1,3,2-λ⁵-dioxaphosphorinane was established by X-ray diffraction.     

Phosphorinane and Enol Rings in One Molecule. Evidence for Reciprocal Stabilization of Half-Chair Conformations

Abstract.

The X-ray crystal structure of 2-(2′,4′-dioxo-3′-pentyl)-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane (2) reveals significant half-chair distortion of the axially oriented cisenol ring. The molecule also undergoes in-plane deformations. R(O...O) = 2.410 Å in the enol moiety indicates a very strong hydrogen bonding. The enol content, δ_OH and thermodynamic parameters for the axial-equatorial conformational and keto-enol equilibriums were obtained from ¹H, ³¹P NMR and IR measurements in comparison with the planar 4,6-dimethyl isomer (1) containing equatorially oriented enol ring. The X-ray single crystal structure of 5,5-dimethyl-2-(methoxycarbonyl-3′-oxo-2′-butyl)-2-oxo-1,3,2-dioxaphosphorinane (3) reveals the unusual half-chair conformation of the dioxaphosphorinane cycle disposed a trans-enol ring substituent. ¹H, ³¹P NMR and IR solution data support the same structure displays a strong conformational preference while the minor forms are chair conformers with an axial or equatorial cis-enol ring.     

Conformational and configurational analysis of 2-phenoxy-2-oxo-1,3,2-dioxaphosphorinanes. Conformational and configurational dependence upon conformation of the diol precursor

Diastereomeric 5-tert-butyl-4-methyl-2-phenoxy-2-oxo-1,3,2-dioxaphosphorinanes were synthesized, and studied by NMR and computational methods in order to determine their predominant conformations as well as their relative configurations. The study was performed assuming a novel criteria, in which, the conformation and configuration of the diastereomeric 5-tert-butyl-4-methyl-2-phenoxy-2-oxo-1,3,2-dioxaphosphorinanes depend upon the conformation of the corresponding diol precursors. In other words, the orientation or pseudo orientation of the groups into the ring framework of the heterocyclic is initially acquired by the direct phosphorylation reaction with the diol precursor in the most stable conformation, and then, once the heterocyclic is formed, the final conformation is dictated by stereoelectronic and steric effects.     

Stereospecificity of alkylation of phosphite anion in electrochemical version of the Michaelis-Becker reaction

Benzylation ofcis2-hydro-2-oxo-4-methyl-1,3,2-dioxaphosphorinane in the electro-chemical version of the Michaelis-Becker reaction occurs stereospecifically with retention of the stereochemistry of the hydrophosphoryl center and affords stereochemically pure 2-benzyl-2-oxo-4-methyl-1,3,2-dioxaphosphorinane (yield 60–70 %). The structure of this compound was determined by X-ray diffraction analysis. The mechanism of the process was discussed.Translated fromIzvestiya Akademii Nauk. Seriva Khimicheskaya, No. 2, pp. 444–446, February, 1996.     

The preparation of some cyclic phosphonates and their use in olefin synthesis

The preparation and the use in olefin synthesis of two 5-membered cyclic phosphonates, 2-carbethoxy-methyl 4,5-dimethyle-2-oxo-1,3,2-dioxaphospholane (4b) and 2-cyanomethyl-4,5-dimethyl-2-oxo-1,3,2-diox-aphospholane (4c) and the 6-membered phosphonates, 2-carbalkoxymethyl-5,5-dimethyl-2-oxo-1,3,2-diox-aphosphorinanes (5a and 5b) and 2-cyanomethyl-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane (5c) are described. Reactions of 4b with aromatic and aliphatic aldehydes lead to preferential formation of cis-olefins. Reactions of the other cyclic phosphonates with aldehydes lead to various mixtures of cis and trans olefins.     

13C Kinetic Isotope Effect of the Pudovik Reaction

Abstract

¹³C kinetic isotope effect (KIE) was determined by means of ¹³C NMR for the carbonyl atom in 2-nitrobenzaldehyde in its reaction with 2H-2-oxo-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane in acetonitrile at 25°C. The observed isotope effect k₁₂/k₁₃ = 1.0238 ± 0.0031 evidences that the formation of the P?C bond in the Pudovik reaction catalyzed by triethylamine is less advanced than the π-bond breakage of the aldehyde carbonyl group.     

Nucleophilic transformations of cyclic phosphate triesters

Reactions of cyclic phosphate triesters, such as 2-ethoxy-1,3,2-dioxaphospholane 2-oxide, with Grignard reagents such as phenyl-, alkyl-, ethynyl-, and allyl-magnesium halides result in ring opening leading to the corresponding phosphonates, via nucleophilic attack of carbon on the phosphorus atom. Treatment of 2-ethoxy-1,3,2-dioxaphospholane 2-oxide with sodium borohydride yields ethyl 2-hydroxyethyl phosphite. This reaction is exclusive for the five-membered cyclic system: under these conditions acyclic phosphate triesters, such as triethyl phosphate, are unreactive and the analogous six-membered ring system, 2-ethoxy-1,3,2-dioxaphosphorinane 2-oxide reacts only partially to give unidentified phosphate esters and traces of phosphonate products. Both compounds were inert to NaBH₄.     

Quantum-Chemical Investigation of Reaction Mechanism of 2-R-4-Oxo-5,6-Benzo-1,3,2-Dioxaphosphorinanes with Chloral and Fluoral

Abstract

Reaction of 2-R-4-oxo-5,6-benzo-1,3,2-dioxaphosphorinanes I with chloral leading to formation of seven-membered heterocycles - 1,4,2-dioxaphosphepines is characterized by the high degree of stereoselectivity. We investigated the model reactions of 2-R-4-oxo-1,3,-dioxaphosphorin-5-enes with CX₃CHO by PM3 and ab initio methods in STO-3G, 3-21G, 6-31G*, MP2/6-31G* basis set and also DFT method (B3LYP).     

Benzaldehyde N,N-Dimethylhydrazone in the Reaction with 4-Oxo-2-pentafluorophenoxy-5,6-benzo- 1,3,2-dioxaphosphorinane. Preparation and Spatial Structure of 4-Dimethylamino-2,5-dioxo-2-pentafluorophenoxy-3-phenyldihydro-6,7-benzo-1,4,2-oxazaphosphepine

Benzaldehyde N,N-dimethylhydrazone with 4-oxo-2-pentafluorophenoxy-5,6-benzo-1,3,2-dioxaphosphorinane is capable to yield with high stereoselectivity a product of the phosphorus heterocycle expansion: unstable to hydrolysis 4-dimethylamino-2,5-dioxo-2-pentafluorophenoxy-3-phenyldihydro-6,7-benzo-1,4,2-oxazaphosphepine. The configuration of the prevailing isomer of the latter was determined by X-ray diffraction study.     

反式-2-取代硫代氨基脲基-4-芳基-5,5-二甲基-2-氧-1,3,2-二氧磷杂环己烷的立体选择性合成及立体化学研究

首先合成了重要的磷酰异硫氰酸酯中间体3, 然后便捷、高产率且立体选择性地合成了反式-2-取代硫代氨基脲基取代的新型六元磷杂环, 其立体化学通过2D NOESY NMR确证. 所有合成的化合物均进行了元素分析和光谱表征, 其中目标产物的13C NMR表征为1,3,2-二氧磷杂环己烷衍生物的碳骨架表征提供了难得的依据. 在溶剂DMSO-d6中, 所有产物均异构化, 生成磷原子的差向异构体. 这一研究结果证明了C4—H 以及31P NMR谱图与立体结构的相关性.     

Spectroscopic study of the conformation of 1,3,2-dioxaphosphorinanes with a P=S bond

5,5- Dimethyl-2-thio-2-phenoxy- and 5,5-dimethyl-2-thio-2-ethoxy-1,3,2-dioxaphosphorinanes exist in the liquid state and in solution in a three-component equilibrium featuring two chair forms with equatorial orientation of the P=S bond differing in the orientation of the OPh or OEt groups and a chair form with an axial P=S bond. The P=S bond in 4-methyl-2-thio-2-phenoxy-1,3,2-dioxaphosphorinane occupies the equatorial position.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 479–482, February, 1990.     

Synthesis and Spatial Structure of 2,5-Dioxo-4-Dialkoxy-Phosphoryl-4-Aryl-6,7-Benzo-1,3,2-Dioxaphosphepines

Abstract

Phosphorus (111) containing dcrivatives of salicylic acid easily react with carbonyl compounds with formation of cycloexpansion products - 1,3,2- or 1,4,2-dioxaphosphepines. For the first time we have shown that dialkyl-l-oxólkylphosphonates react with 2-R-4-oxo-5,5-benzo-1,3,2-dioxaphosphorinanes and yield 1,3,2-dioxaphosphepines (I) with high stereoselectivity. The configuration of the preferable diastereoisomer (IId) has been determined by X-ray analysis. The hydrolysis of compounds (IIa-c) leads to formation of 2-hydroxy-2-oxo-1,3,2-dioxaphosphepines (III). The structure of phosphepine (IIIb) in crystal is shown on the figure. The work is supported by the Leading Scientific School Foundation of Russia (grant N 96-15-97330) and the Russian Foundation for Basic Research (grant N 98-03-33266).     

Simultaneous Formation of Cage and Spirane Pentaalkoxyphosphoranes in Reaction of 5,5-Dimethyl-2-(2-oxo-1,2-diphenylethoxy)-1,3,2-dioxaphosphorinane with Hexafluoroacetone

Russian Journal of General Chemistry - The reaction of hexafluoroacetone with 5,5-dimethyl-2-(2-oxo-1,2-diphenylethoxy)-1,3,2-dioxaphosphorinane occurs in two simultaneous directions: through the...     

Reactions of some 2-oxo-1,3,2-oxathiaphospholanes and 2-oxo-1,3,2-phosphorinanes with phosphorus pentachloride

2-Phenoxy- and 2-dialkylamino-2-oxa-1,3,2-oxathiaphospholanes react with PCl₅ with ring opening and formation of the corresponding acid chlorides of thiophosphoric acid. Under analogous conditions, 2-phenoxy-2-oxo-1,3,2-oxathiaphosphorinanes do not react with PCl₅, while acid chlorides of thiophosphoric acid are formed in low yield along with other products in the reaction of 2-dialkylamino-2-oxo-1,3,2-oxthiaphosphorinanes with PCl₅.A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Science Center, Russian Academy of Sciences, 420083 Kazan. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2676–2678, November, 1992.     

ZERO VALENT METAL COMPLEXES OF 5,5-DIMETHYL-2-R-1,3,2-DIOXAPHOSPHORINANES

Abstract

The preparation and characterization of some Ni(0) and Pt(0) complexes of 5,5-dimethyl-2-phenoxy-1,3,2-dioxaphosphorinane is reported. This phosphite, which contains a single six-membered ring, displays donor-acceptor properties intermediate to P(OCH₂)₃CR and trialkyl or triaryl phosphites. The conformation of the ligand in the complexed form is proposed to be a chair ring with an axial phenoxy group.     

Synthesis of poly(alkylene phosphate)s with n-containing bases in the side chains. III. N1-Oxoethyleneuracil on the poly(trimethylene phosphate) chain

Poly(2-hydro-2-oxo-1,3,2-dioxaphosphorinane) was quantitatively chlorinated, and the resulting polymer was reacted with excess of imidazole, giving the highly reactive polyesteramide. This polymer, treated with N¹-hydroxyethyluracil, gave polyphosphates with N¹-oxoethyleneuracil in the side chains. The final polymers (M?_n ≈ 10⁴) as well as the intermediate products were characterized by ¹H-, ¹³C- and ³¹P-NMR spectroscopy.     

Synthesis and biological activities of optical isomers of 2-(4-diphenylmethyl-1-piperazinyl)ethyl 5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dim ethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate dihydrochloride (NIP-101).

Six optical isomers of 2-(4-diphenylmethyl-1-piperazinyl)ethyl 5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate dihydrochloride (NIP-101, 1.2HCl.2H2O), a potent calcium antagonist, were successfully prepared by using optically active (2R,4R)-(-)- and (2S,4S)-(+)-2,4-pentanediols, and cis-2,4-pentanediol and optically active (S)-(+)-2-methoxy-2-phenylethanol. Their proton nuclear magnetic resonance investigations demonstrate that the 1,3,2-dioxaphosphorinane group is conformationally constrained around the C-P bond. Calcium-antagonistic and hypotensive activities of the optical isomers were examined and found to depend mainly on the absolute configuration at a stereogenic center in the 1,4-dihydropyridine ring rather than the configuration of the 1,3,2-dioxaphosphorinane moiety.