Reactions of 4-chloromethyl-1,3,2-dioxathiolane 2-oxides with sodium phenoxide. A reinvestigation

The reactions of 4-chloromethyl-1,3,2-dioxathiolane 2-oxides with PhONa in EtOH are accompanied by ring opening under the action of the ethoxide ion rather than leading to a rearrangement of the starting molecule as has been assumed previously. Under conditions precluding competition with other nucleophiles, the phenoxide anion smoothly replaces the chlorine atom in chloromethyl-substituted cyclic sulfites. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1774–1777, October, 2000.     

Synthesis and antimicrobial activity of novel phosphorus heterocycles with exocyclic p-C link

Several new class of phosphorus heterocyclic compounds containing exocyclic P-C link such as 6-(2'-chloroethyl)/(allyl)/(benzyl)-1,2,4,8,10,11-hexachloro-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxides (5-7), 2-(2"-chloroethyl)/(allyl)-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihdro-2H-1,3,2-benzoxazaphosphorin 2-oxides (9, 10), 2-(2"-chloroethyl-2,3-dihydro-3-(4'-bromophenyl)-1H-naphth[1,2-e][1,3,2]-oxazaphosphorin 2-oxide (12), 2-(2"-chloroethyl)/(allyl)-2,3-dihydro-5-benzoyl-1H-1,3,2-benzodiazaphosphole 2-oxides (14, 15), 4-phenyl-2-(2"-chloroethyl)-1H-1,3,3a,5,6-pentaza-2-phosphapentalene 2-oxide (17) and 4-benzyl-2-(2"-chloroethyl)-1H-1,3,3a,5,6-pentaza-2-phospha-pentalene 2-oxide (19) were synthesized by reacting equimolar quantities of corresponding diol (4)/diamines (13, 16, 18), 2-cyclohexylaminomethyl-4-t-butylphenol (8) and 1-(4'-bromoanilinomethyl)-2-naphthol (11), with respective phosponyl dichlorides (1-3) in dry toluene/toluene-tetrahydro-furan/pyridine in the presence of triethylamine at various temperatures. Their structures were established by IR, (1)H-, (13)C- and (31)P-NMR spectral data. The mass spectral data were given for compounds 9, 12 and 15. The title compounds were screened for antibacterial activity against Staphylococcus aureus and Escherichia coli and antifungal activity on Aspergillus niger and Helminthosporium oryzae. Most of the compounds possess significant activity.     

Novel heterocycles. 3. Synthesis of fused 1,3,2-benzodiazaphosphorin ring systems

Novel fused tricyclic phosphorus heterocycles 9 and 11 and the tetracycle 15 were synthesized by cyclization of 1-haloalkyl (or 3-haloalkyl)-2,3-dihydro-1,3,2-benzodiazaphosphorin-4(1H)one 2-oxides with sodium hydride. Some spectral data of the products are also discussed.     

PHOSPHORUS-NITROGEN COMPOUNDS. PART 52.1 THE SYNTHESIS OF SOME 1,3,2-BENZODIAZAPHOSPHORINE 2-OXIDES AND 2-SULPHIDES

Abstract

The reactions of 4-methyl-2-[N-(p-toluidinyl)methyl]aniline with phosphorus oxychloride, thiophosphoryl chloride, and their derivatives yield 1,3,2-benzodiazaphosphorine 2-oxides and 2-sulphides. Their ¹H NMR and infrared spectra are discussed. Related 1,3,2-benzodiazophosphorine and 1,3,2-dibenzodiazaphosphocine 2-oxides and 2-sulphides are compared.     

Stereochemistry of heterocycles

A number of previously undescribed alkyl-1,3,2-dioxaborinanes were synthesized by condensation of substituted 1,3-diols with alkylboron dichlorides or dibutyl isopropylborate. It was shown by PMR spectroscopy that the 2,5-dialkyl-1,3,2-dioxaborinane molecules are conformationally homogeneous and do not contain an axial substituent in the 5 position, whereas the 2-isopropyl-5,5-dimethyl-1,3,2-dioxaborinane molecules exist in a state of rapid ring inversion, and introduction of methyl substituents in the 4, 4, and 6 positions of the 1,3,2-dioxaborinane ring leads to distortion of the ring conformation and conformational heterogeneity of the investigated sample. The observed regularities are explained from the position of intensive oxygen-boron electron exchange in the heteroring. It is concluded that the 2,5-dialkyl-1,3,2-dioxaborinane molecules have primarily a conformation with a semiplanar form.See [1] for communication XLVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp, 26–30, January, 1978     

A simple and convenient protocol for the synthesis of seven- and eight-membered phosphorus heterocycles

A simple procedure for the synthesis of eight-membered 6-(2-chloroethyl)/bis(2-chloroethyl)-amino-12-oxo-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxides (3a–b) and seven-membered 6-(2-chloroethyl)/bis-(2-chloroethyl)aminodibenzo[d,f][1,3,2]dioxaphosphepin 6-oxides (5a–b) from cyclocondensation of equimolar ratios of 2,2′-dihydroxybenzophenone (1) and 2,2′-dihydroxybiphenol (4), respectively with 2-chloroethylphosphonicdichloride (2a) and bis(2-chloroethyl)phosphoramidic dichloride (2b) in dry toluene in the presence of triethylamine at 45–50 °C is described. All synthesized compounds possessed significant growth inhibition for their antibacteria against ‘Bacillus subtilis’ and ‘Klebsiella pneumonia’ and antifungi activity on “Curvularia lunata” and “Aspergillus niger.”     

Synthesis of 6-Alkyl Carbamato/Alkyl Thiocarbamato-2,10-dichloro-12-trichloromethyl-12 H -dibenzo[d,g][1,3,2]-dioxaphosphocin 6-Oxides

6-Alkylcarbamato/alkylthiocarbamato-2,10-dichloro-12-trichloromethyl-12 H -dibenzo [d,g][1,3,2]-dioxaphosphocin 6-oxides have been synthesized by the condensation of 2,2-bis(2-hydroxy-5-chlorophenyl)-1,1,1-trichloroethane with dichlorophosphinyl carbamates of different alcohols/thiols in the presence of triethylamine in dry toluene and were characterized by different spectral studies.     

Specific Features of Reaction of 2-R-Benzo[e][1,3,2]dioxaphosphinin-4-ones with Perfluorodiacetyl. Synthesis and Steric Structure of 4′,5′-Bis(trifluoromethyl)-4-oxo-2-(2,2,3,3-tetrafluoropropoxy)-2λ 5-spiro[benzo[e][1,3,2]dioxaphosphinine-2,2′-[1,3,2]dioxaphosphole]

2-R-benzo[e][1,3,2]dioxaphosphinin-4-ones react with perfluorodiacetyl under mild conditions to form relatively labile spirophosphoranes containing a 1,3,2-dioxaphosphole ring. These compounds gradually convert to more stable 2-R-4,5-bis(trifluoromethyl)-1,3,2λ⁵-dioxaphosphole 2-oxides and diastereometic 2-R-4-(trifluoroacetyl)-4-(trifluoromethyl)benzo[f][1,3,2λ⁵]dioxaphosphepine 2-oxides, whose structure was confirmed by means of NMR and IR spectroscopy. The structure of 4′,5′ -bis(trifluoromethyl)-4-oxo-2-(2,2,3,3-tetrafluoropropoxy)-2λ ⁵-spiro[benzo[e][1,3,2]dioxaphosphinine-2,2′-[1,3,2]dioxaphosphole] was confirmed by X-ray diffraction analysis.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 4, 2005, pp. 587–599.Original Russian Text Copyright © 2005 by Konovalova, Mironov, Ivkova, Zagidullina, Gubaidullin, Litvinov, Kurykin.     

Reactions of Arylenedioxytrihalophosphoranes with Acetylenes: XV.<Superscript>1</Superscript> Reaction of 2,2,2-Tribromo-4,6-di-<Emphasis Type="Italic">tert</Emphasis>-butylbenzo-1,3,2λ<Superscript>5</Superscript>-dioxaphospholedioxaphosphole with Pent-1-yne

2,2,2-Tribromo-4,6-di-tert-butylbenzo-1,3,2λ⁵-dioxaphospholedioxaphosphole reacted with a terminal alkyne, pent-1-yne, to give a mixture of two isomeric 1,2-benzoxaphosphinine derivatives, 6,8- and 5,7-di-tert-butyl-2-bromo-4-propylbenzo-1,2λ⁵-oxaphosphinin-2-oxides, at a ratio of 5.9: 1. The regioselectivity of substitution of oxygen in the dioxaphosphole fragment by carbon differs from that observed previously in the reaction with 4,6-di-tert-butyl-2,2,2-trichlorobenzo-1,3,2λ⁵-dioxaphosphole: the minor isomer was formed as a result of substitution of the oxygen atom in the ortho position with respect to one tert-butyl group of the initial phosphole.     

A novel preparation of cyclic sulfites through photosulfoxidation of alkenes

The cyclic sulfite, 4-ethyl-5-methyl-1,3,2-dioxathiolane 2-oxide, has been prepared by the photosulfoxidation of trans-2-pentene, and the quantum yield for the reaction has been determined. The proposed mechanism involves the reaction of a charge transfer complex formed between sulfur dioxide and the alkene, and is consistent with the participation of the triplet state of the former.     

New approach to cyclic sulfites and sulfates through reactions of sulfur oxychlorides with glycidols

Reactions of 2,3-epoxyalcohols (glycidols) with thionyl chloride or sulfuryl chloride afford cyclic sulfites or sulfates, respectively. These reactions yield predominantly 4-chloroalkyl-1,3,2-dioxathiolane oxides. The configuration of the C(4) atom in the latter compounds exactly corresponds to that of the C(2) atom of the parent glycidol, whereas the configuration of the exocyclic atom is almost completely reversed with respect to that of the C(3) atom of the precursor. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1586–1593, September, 2000.     

Enzymatic resolution of a 1,2-cyclic sulphite glycerol derivative

cis-2-Oxo-5-hydroxymethyl-1,3,2-dioxathiolane 2a can be efficiently resolved by a lipase from Pseudomonas cepacia-catalysed acylation reaction with vinylbutyrate. Compound 2a was directly prepared from glycerol in one step. This first lipase-catalysed resolution of a cyclic sulphite derivative provides a potentially useful activated chiral synthon.     

Design and synthesis of boron containing 2,4-disubstituted-phthalazin-1(2H)-one and 3,7-disubstituted-2H-benzo[b][1,4] oxazine derivatives as potential HGF-mimetic agents

We synthesized boron containing 2-(4-methoxybenzyl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioaborolan-2-yl)phenyl) phthalazin-1(2H)-one 3 and 7-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2H-benzo[b][1,4] oxazine 8. The reaction of compound 2 with B₂pin₂ using potassium acetate as the base and Pd(PPh₃)₂Cl₂ as the catalyst, produced the corresponding boron-containing derivative 3 as a white solid in 65% yield. Alternatively, we have synthesized compound 8 as a yellow solid in 59% yield using the Miyaura borylation reaction. The potassium trifluoro(4-(-methyl-2H-benzo[b][1,4]oxazine-3-yl)phenylborate 9 was then obtained after treatment of 8 with aqueous solution of KF₂H in methanol as white solid product in 60% yield. The biological activities of the synthetic compounds are currently being evaluated.     

<Emphasis Type="Italic">N</Emphasis>-β-Nitroxyethyl derivatives of 1,1’-[methylenebis(oxy)]bis(triaz-1-ene 2-oxides)

Synthetic procedures towards new N-β-hydroxyethyl- and N-β-bromoethylated 1,1’-[methyl enebis(oxy)]bis(triaz-1-ene 2-oxides) were developed. N-β-Nitroxyethyl[methylenebis(oxy)]- bis(triaz-1-ene 2-oxides) were first synthesized by nitration of N-β-hydroxyethyl derivatives and nucleophilic substitution of the bromine atom of N-β-bromoethyl derivatives. The first representative of a new class of energetic compounds, namely, (1-nitroxymethoxy)triaz-1-ene 2-oxide, was synthesized.     

ISOQUINO[2,1-c][1,3,2] BENZODIAZAPHOSPHORINE DERIVATIVES: NEW POTENTIAL AGENTS FOR CANCER CHEMOTHERAPY

Abstract

Three derivatives of 2-chloro-5,8,9,13b-tetrahydro-5-methyl-6H-Isoquino[2,1 -GI[1,3,2]benzodiazaphosphorine 6-oxides as well as its sulphides were synthesized with the aim of evaluating their antitumor properties. Three of the twenty one compounds were found to be significantly active (inhibition of tumor growth > 80%) in the Ehrlich ascites carcinoma screen. Several structure-activity relationships were indicated for antitumor activity in this screen. An aziridinyl substituted derivative, bis-(2-chloroethyl)amino substitution (3) also exhibited significant activity against the growth of P-388 lymphocytic Leukemia cells in male BDF, mice (% T/C = 147; % T/C > 125 is considered significant). The reference for activity comparison is cyclophosphamide or cytoxan i.e. [bis(2-chloroethyl)aino]-5,6-dihydro-2H-1,3,2-oxazaphosphorinane 2-oxide [having TIC × 100 = 339 at a dose of 65 mg/kg]     

Structural characteristics of 2-halo-1,3,2-dithiarsenic compounds and tris-(pentafluorophenylthio)-arsen

The combination of various dithiols and AsX₃ (X = F, Cl) produces the series of cyclized halo-arsenic dithiolate compounds: 2-chloro-1,3,2-dithiarsolane [AsCl(SCH₂CH₂S)] (1), 2-iodo-1,3,2-dithiarsolane [AsI(SCH₂CH₂S)] (2), 2-chloro-1,3,2-dithiarsenane [AsCl(SCH₂CH₂CH₂S)] (3), 2-iodo-1,3,2-dithiarsenane [AsI(SCH₂CH₂CH₂S)] (4), 3-chloro-4H,7H-5,6-benz-1,3,2-dithiarsepine [AsCl(SCH₂)₂(C₆H₄)] (5), 1,2-bis-dithiarsolan-2-ylmercapto-ethane [As₂(SCH₂CH₂S)₂(SCH₂CH₂S)] (6) and tris-(pentafluorophenylthio)-arsen [As(SC₆F₅)₃] (7). The geometry around As for these compounds is best described as trigonal pyramidal with varying degrees of distortion. Compound 1 crystallizes in two polymorphic forms with similar structural parameters. The compounds have been characterized by IR, ¹H, ¹⁹F, and ¹³C NMR, X-ray crystallography and GC-MS.     

Aminoamidines

Reactions ofN-aryl- andN-methyl-amidines and -amides of -amino acids with RPCl₂ afford 4-aryl(methyl)imino and 4-oxo-1,3,2-diazaphospholanes. 4-Phenylimino-1,3,2-diazaphosphorinane was obtained in a similar way by the interaction of N(1), N(2)-diphenyl--anilinoisobutyramidine with PhPCl₂.For communication 5 see ref. 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1116–1121, June, 1993.     

Fluordiazadiphosphetidine, 24. Mitt.: Reaktion monosubstituierter Fluordiazadiphosphetidine mit Kaliumfluorid/Kronenether

Summary The reactivity of some monosubstituted fluorodiazadiphosphetidines towards potassium fluoride utilizing 18-crown-6-ether as a phase transfer catalyst has been studied. The following compounds were investigated: 2,2,2,4,4-pentafluoro-4-methoxy-1,3-dimethyl-1,3,2⁵,4⁵-diazadiphosphetidine, 2,2,2,4,4-pentafluoro-4-methylamino-1,3-dimethyl-1,3,2⁵,4⁵-diazadiphosphetidine, 2,2,2,4,4-pentafluoro-4-methylthio-1,3-dimethyl-1,3,2⁵,4⁵-diazadiphosphetidine, and a 1:1 mixture of 2,2,2,4,4-pentafluoro-4-(N²,N²-dimentyl-hydrazino)-1,3-dimethyl-1,3,2⁵,4⁵-diazadiphosphetidine and 2,2,2,4,4-pentafluoro-4-methylamino-1,3-dimethyl-1,3,2⁵,4⁵-diazadiphosphetidine. All reactions proceeded in a similar way and led to the disubstituted derivates of the starting materials and the potassium salt K₂(CH₃NPF₄)₂. In this way 2,2,4,4-tetrafluoro-2-methylamino-4-(N²,N²-dimethylhydrazino)-1,3-dimethyl-1,3,2⁵,4⁵-diazadiphosphetidine has been synthesized for the first time and a new way has been found for the synthesis of several compounds reported in literature.

Verstorben     

Novel heterocycles. 2. Synthesis of the 1,3,2-benzodiazaphosphorin ring system

A series of 1,3-disubstituted-2,3-dihydro-1,3,2-benzodiazaphosphorin-4(1H)one 2-oxides was prepared by a method involving the treatment of an appropriate anthranilamide with phosphorus trichloride. Tricyclic diazaphosphorins 24 and 28 were also prepared. Some spectral data of the products are also discussed.     

The facile addition of fluorosulfuric acid to an epoxide

Fluorosulfuric acid, a very poor nucleophile, was found to add to several epoxides, yielding 1,3,2-dioxathiolane 2,2-dioxides. These cyclic sulfates could also be obtained by reacting the epoxides with sulfur trioxide. The intermediacy of the fluorosulfate of a 1,2-diol, which readily cyclized in base, has been demonstrated in one case.