107-19-7

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A possibility of the O→Csp 1,4-migration of the R3Si group in silyl ethers of terminal acetylenic alcohols upon treatment with organolithium reagents (RLi) was studied. In the case of 3-trimethylsilyloxypropyne, depending on the nature of RLi, the heterolysis of the Si—O bond occurs either by the action of acetylide formed as a result of deprotonation with the formation of 3-trimethylsilylprop-2-yn-1-ol trimethylsilyl ether, or by the action of the metalation agent with the formation of propargyl alcohol. The realization of the O→Csp 1,4-migration of the Me3Si group requires the use of mild organolithium reagents (lithium hexamethyldisilazanide and diisopropylamide). Silyl ethers having steric hindrance at the carbon atom bonded to the reaction center or around the silicon atom do not react with the studied organolithium reagents.

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Reaction of (OC)2ON2WH (1) with acetic acid or phenol, respectively, yields an acetato or a phenolato complex (OC)nON2WX; n = 1, X = CH3COO (2a); n =2, X = PhO (2b). 1 reduces aliphatic, α,β-unsaturated or aromatic aldehydes in the presence of acetic acid or phenol to yield alcohols in most cases.Crotonaldehyde reacts with 1 and phenol to produce butyraldehyde.

The kinetics of visible ligth-induced oxidation of ethyne and propyne by NO2 in solid Ar has been monitored as a function of photolysis wavelength.CW dye and Ar ion laser emission was used for irradiation, and FT-infrared spectroscopy for the measurement of product growth.Determination of the wavelength dependence of quantum efficiencies from the kinetic measurements revealed that the photolysis threshold of HCCH + NO2 lies approximately 6 kcal mol-1 higher than that of CH3CCH + NO2.This and other parameters derived from the product growth measurements, and the formyl methyl iminoxy radical trapped in the case of the CH3CCH + NO2 reaction are interpreted in terms of a direct O transfer mechanism.The proposed path involves large-amplitude O transfer from photoexcited NO2 to the CC group to yield a transient ketocarbene.Formation of iminoxy radical is attributed to trapping of the ketocarbene by NO cage coproduct, which is in competition with Wolff rearrangement to yield ketene.From the structure of the iminoxy radical, it is inferred that the photoinduced O transfer from NO2 to the unsymmetrical CC bond of propyne is completely regioselective, leading exclusively to the carbene transient with oxygen at the terminal carbon.This regiochemical outcome is interpreted in terms of potential energy profiles for central and terminal carbon attack of the triple bond.

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Vinylic tellurides were synthesized by the addition of organotellurols to acetylenic alcohols and the regioselectivity of the reaction was evaluated.

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Photochemical reaction of ethyne*NO2 and propyne*NO2 pairs isolated in solid Ar has been observed at wavelengths as long as 582 nm (HCCH*NO2) and 615 nm (CH3CCH*NO2).Continuous wave dye laser radiation was used to excite the reactants, and the chemistry was monitored by FT-infrared spectroscopy.In the case of ethyne + NO2, the sole products were CH2=C=O and NO.The reaction of NO2 with propyne gave methylketene plus a trapped intermediate, CH3C(=NO.)C(=O)H (formyl methyl iminoxy radical).Infrared spectra of this radical are reported for the first time.Product identification was based on D, 18O, and 15N isotopic substitution.Selective interconversion with tuned visible laser light revealed the presence of four conformers, most probably originating from isomerism about the C-C and the C=N bonds.Photoelimination of NO from the iminoxy radical was observed at wavelengths as long as 625 nm.Propynol and methylketene could be identified among the secondary photolysis products.

The carboxylation of propargylic alcohols containing a silyl group at the terminal position was conducted in a CO2 atmosphere at atmospheric pressure in the presence of a nickel catalyst and diethylzinc. Here, CO2 was used as not only the C1 source but also the promoter of the COH cleavage processes for the oxidative addition of propargylic alcohols.

Daptomycin (DAP) is a calcium (Ca2+)-dependent FDA-approved antibiotic drug for the treatment of Gram-positive infections. It possesses a complex pharmacophore hampering derivatization and/or synthesis of analogues. To mimic the Ca2+-binding effect, we used a chemoenzymatic approach to modify the tryptophan (Trp) residue of DAP and synthesize kinetically characterized and structurally elucidated regiospecific Trp-modified DAP analogues. We demonstrated that the modified DAPs are several times more active than the parent molecule against antibiotic-susceptible and antibiotic-resistant Gram-positive bacteria. Strikingly, and in contrast to the parent molecule, the DAP derivatives do not rely on calcium or any additional elements for activity.

The method comprises the following steps: taking potassium hydroxide or potassium alcoholate as a catalyst, and reacting with acetylene below 0.15 mpa pressure in an aromatic hydrocarbon or aliphatic hydrocarbon organic solvent to form propinyl alcohol. The reaction end point material is a 'liquid - liquid' two-phase system and is separated by sedimentation. The product is recovered by hydrolysis separation, extraction purification and rectification separation, and the yield of propargol in the product can reach 71% - 73%.

Two new examples of structurally characterized β-diketiminate analogues i.e., conjugated bis-guanidinate (CBG) supported palladium(II) complexes, [LPdX]2; [L= {(ArHN)(ArN)–C=N–C=(NAr)(NHAr)}; Ar = 2,6-Et2-C6H3], X = Cl (1), Br (2) have been reported. The synthesis of complexes 1–2 was achieved by two methods. Method A involves deprotonation of LH by nBuLi followed by the treatment of LLi (insitu formed) with PdCl2 in THF, which afforded compound 1 in good yield (75 %). In Method B, the reaction between free LH and PdX2 (X = Cl or Br) in THF allowed the formation of complexes 1 (Yield 73 %) and 2 (Yield 52 %), respectively. Moreover, these complexes were characterized thoroughly by several spectroscopic techniques (1H, 13C NMR, UV/Vis, FT-IR, and HRMS), including single-crystal X-ray structural and elemental analyses. In addition, we tested the catalytic activity of these complexes 1–2 for the hydroboration of carbonyl compounds with pinacolborane (HBpin). We observed that compound 1 exhibits superior catalytic activity when compared to 2. Compound 1 efficiently catalyzes various aldehydes and ketones under solvent-free conditions. Furthermore, both inter- and intramolecular chemoselectivity hydroboration of aldehydes over other functionalities have been established.

The invention discloses a method for synthesizing propargyl alcohol. The method includes hydrolyzing 1, 3-dichloropropene in saturated alkali metal carbonate solution to obtain 3-chloropropene alcohol; removing hydrogen chloride from the 3-chloropropene alcohol under the condition of the presence of a polar solvent dimethyl sulfoxide and hydroxide of alkali metal so as to obtain the propargyl alcohol. The method has the advantages that the 1, 3-dichloropropene is used as a raw material, the raw material can come from wide sources, is inexpensive and is easily available, the propargyl alcohol is easy to dehydrate, energy can be saved, and environments can be protected; the propargyl alcohol obtained by the aid of the method is high in yield and purity.

The invention discloses a trigeneration continuous production method for propiolic alcohol, 1,4-butinodiol and urotropine, and belongs to the technical field of chemical engineering. According to the method, a formaldehyde aqueous solution (10%-37% wt) and acetylene are taken as raw materials for synthesizing propiolic alcohol and co-producing 1,4-butinodiol and urotropine, the reaction temperature is 80-120 DEG C, the pressure is 1.0-2.5 MPa, and propiolic alcohol with the purity of 99.5% or more, a 1,4-butinodiol aqueous solution and a urotropine aqueous solution are obtained. The conversion rate of formaldehyde in the whole technology is 100%, and the method has the advantages of safety and environment friendliness.

The rates of ammonolysis of alkyl benzoate and phenylacetate esters in liquid ammonia increase with the acidity of the leaving group alcohol and show relatively large Bronsted βlg values of -1.18 and -1.34, respectively, when plotted against the aqueous pKa of the alcohol. The Bronsted βlg obtained using the pKa of the leaving group alcohol in liquid ammonia is significantly reduced to ~ -0.7, which indicates that the rate-limiting step involves a reaction of the tetrahedral intermediate with little C-OR bond fission in the transition state. The solvolysis reaction is subject to significant catalysis by ammonium ion, which, surprisingly, generates a similar Bronsted βlg indicating little interaction between the ammonium ion and the leaving group. It is concluded that the rate-limiting step for the ammonium-ion-catalysed solvolysis of alkyl esters in liquid ammonia is the diffusion-controlled protonation of the zwitterionic tetrahedral intermediate T+- to give T+, which is rapidly deprotonated to give T0 which is compatible with the rate-limiting step for the uncatalysed reaction being the formation of the neutral T0 by a 'proton switch'. Copyright 2013 John Wiley & Sons, Ltd. The rates of ammonolysis of alkyl benzoate and phenylacetate esters in liquid ammonia increase with the acidity of the leaving group alcohol and show relatively large Bronsted βlg values of -1.18 and -1.34, respectively, when plotted against the aqueous pKa of the alcohol. The Bronsted βlg obtained using the pKa of the leaving group alcohol in liquid ammonia is significantly reduced to ~ -0.7, which is compatible with the rate limiting step for the uncatalysed reaction being the formation of the neutral T0 by a 'proton switch'. Copyright

A novel carbon catalyst with -SO3H, -OH and -COOH functional groups was prepared from glycerol pitch by in situ partial carbonization and sulfonation with sulfuric acid. The activity of the catalyst was investigated through tetrahydropyranylation and dehydropyranylation of a wide variety of alcohols and phenols at room temperature by changing the solvent medium from dichloromethane to methanol. Excellent yields, short reaction times, easy and quick isolation of the products and reusability of the catalyst are the main attractions of this method. The novel carbon catalyst holds great potential in the green chemical processes.

In this article, a mild and efficient protocol for the tetrahydropyranylation and tetrahydrofuranylation of various aliphatic and benzylic alcohols and phenols into their corresponding THP and THF ethers (with 3,4-dihydro- 2H-pyran, DHP and 2,3-dihydrofuran, DHF) has been developed using a catalytic amount of anhydrous FePO4 at room temperature and relatively short reaction times in good to excellent yields.

Hydration of a wide range of alkynes to the corresponding ketones has been afforded in high yields at room temperature by using gold(I)-phosphine complexes as catalyst, with no acidic cocatalysts required. Suitable substrates covering alkyl and aryl terminal alkynes, enynes, internal alkynes, and propargylic alcohols, including enantiopure forms, are cleanly transformed to the corresponding ketones in nearly quantitative yields. Acid-labile groups present in the substrates are preserved. The catalytic activity strongly depends on both the nature of the phosphine coordinated to the gold (I) center and the softness of the counteranion, the complex AuSPhOsNTf2 showing the better activity. A plausible mechanism for the hydration of alkynes through ketal intermediates is proposed on the basis of kinetic studies. The described catalytic system should provide an efficient alternative to mercury-based methodologies and be useful in synthetic programs.

The coupling of the homocuprate of the bislactim ether of cyclo-(-L-Val-Gly-) (9) with primary propargyl halides produces the allenyl-substituted bislactim ethers 11 in a highly diastereoselective manner, whereas the alkylation of the lith-iated bislactim ether of cyclo-(-L-Val-Gly-) yields the proparg-yl-substituted bislactim ethers 12. Subsequent hydrolysis affords, after protection of the amino group, the methyl α- allenylglycinates 15, the α-allenylglycines 16, and the methyl α-propargylglycinates 17.

A one-pot sequential CuI-catalyzed azide-alkyne cycloaddition (CuAAC) strategy is presented for the synthesis of constitutionally unsymmetrical cyclobis(paraquat-p-phenylene)-based rotaxanes in good yields from simple starting materials. The methodology consists of performing multiple CuAAC reactions to stopper a pseudorotaxane in a stepwise manner, the order of which is controlled through silyl-protection and AgI-catalyzed deprotection of a terminal alkyne. The methodology is highlighted by the synthesis of an amphiphilic branched [4]rotaxane. The methodology increases the ability to access ever more complicated mechanically interlocked compounds to serve in devices as sophisticated and functional molecular machinery.

Highly selective deprotection of tert-butyldimethylsilyl ethers at room temperature has been described using sulfated SnO2 as an efficient solid catalyst. Copyright Taylor & Francis Group, LLC.

t-Butyldimethylsilyl (TBDMS) ethers have been efficiently and selectively deprotected using silica supported sodium hydrogen sulfate (NaHSO4·SiO2) as a heterogeneous catalyst at room temperature to regenerate the parent alcohols in high yields.

The invention relates to a method for producing propargyl alcohol by reacting an aqueous formaldehyde solution containing acetylene on a catalyst comprising copper acetylide at an operating pressure of 1 to 15 bar and a temperature of 70 to 120 °C without forming a continuous gas phase. According to the inventive method, the aqueous formaldehyde solution contains an organic solvent for acetylene while the catalyst is located in a fluid bed.

Four 4-methyl-3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2′-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2′-Methyl-2′-ethyl-4-methyl DCK (7b) was more potent (EC50 = 0.22 μM, TI > 175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC50 = 0.0059 μM, TI > 6600). Four 4-methyl-3′,4′- di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2′-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2′-Methyl-2′-ethyl-4-methyl DCK (7b) was more potent (EC 50 = 0.22 μM, TI > 175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC50 = 0.0059 μM, TI > 6600). The bioassay results indicated that the 2′-substituents had a strong effect on the anti-HIV activity, and gem-dimethyl substitution at the 2′-position was greatly preferable to larger alkyl substituents or hydrogen atoms.

Tetrahydropyran and tetrahydrofuran containing natural products, drugs and agrochemicals often possess carbon-carbon bonds adjacent to the heteroatom. Consequently, new methods for the construction of anomeric carbon-carbon bonds are of considerable importance. We have devised a new strategy to access these systems that requires the treatment of O-glycoside alkynyl tributylstannane derivatives of furanyl and pyranyl lactols with Lewis acid to effect oxygen to carbon rearrangements. This leads to the formation of the corresponding carbon linked alkynol products that can be further manipulated to produce key structural motifs and building blocks for the assembly of complex molecules.

The present invention provides a method for separating and recovering propargyl alcohol from a product mixture containing a solvent, water and propargyl alcohol, which alleviates the problems of prior art and which can separate and recover propargyl alcohol in a simple operation at an advantageous thermal energy without requiring a large distillation unit or a complicated separation operation or step. The method for separation and recovery of propargyl alcohol according to the present invention is characterized by subjecting, to distillation at a pressure of 100 to 150 mmHg, a propargyl alcohol-containing product mixture obtained by reacting paraformaldehyde with acetylene in the presence of a catalyst in a polar solvent.

The invention concerns a method for preparing a benzylic-type ether from an aromatic compound. The inventive method for preparing a benzylic-type ether from an aromatic compound is characterised in that it consists in: in a first step, acylating an aromatic compound by reacting said aromatic compound with an acylating agent, in the presence of an efficient amount of zeolite or a Friedel-Crafts catalyst leading to a ketonic compound; in a second step, reducing the carbonyl group into carbinol leading to a benzylic alcohol; in a third step, etherifying the hydroxyl group, by reacting the benzylic alcohol with another alcohol, in the presence of an efficient amount of zeolite.

The second-order rate constants k2 (M-1 s-1) for the alkaline hydrolysis of substituted alkyl benzoates, C6H5CO(O)R (R = CH3, CH2Cl, CH2CN, CH2C≡CH, CH2C6H5, CH2CH2Cl, CH2CH2OCH3), were measured in aqueous 2.25 M n-Bu4NBr and in 80% (v/v) DMSO solution at several temperatures. The log k values were analyzed using the equation log k = log k0 + ρσ + δEsB. The EsB scale has been proposed for the steric effect of alkyl substituents in the alkyl part of esters: EsB = (log kR - log kCH(3))H+, where k is the rate constant for the acidic hydrolysis of substituted alkyl benzoates or acetates in water. As polar substituent parameters, both Taft σ* and σI constants were used. The dual parameter treatments of the log k values with σ and EsB constants gave excellent correlations (R = 0.997). For 2.25 M n-Bu4NBr, 80% (v/v) DMSO and pure water at 25 °C, calculated susceptibilities to the inductive effect of alkyl substituents ρ* were found to be 2.07, 2.21 and 1.64, respectively. The corresponding ρI values were 4.64, 4.94 and 3.64. The dependence of ρI on solvent and temperature in the alkaline hydrolysis of substituted alkyl benzoates was similar to that observed earlier for meta- and para-substituents in the alkaline hydrolysis of substituted phenyl benzoates and tosylates. The substituent dependence of the activation energy, E, was found to be completely caused by the polar effect. Susceptibility to steric effect in the alkaline hydrolysis of alkyl benzoates (δ ≈ 1) appeared to be independent of the solvent and temperature. Copyright

Novel spiropyran compounds, particularly with photochromic properties, are disclosed, as well as photochromic compositions and ophthalmic articles (e.g. lenses) containing said compounds. The photochromes have been designed so as to have a high colorability, a high sensitivity to activating radiation breaking the pyran ring, to be entirely or practically free from coloration in a non activated (non exposed) state, to have an intense coloration following activation and a high coverage of the visible spectrum in combination with at least one other photochrome, and to have high rates of coloration/decoloration. The spiropyrans are easily produced and photochemically stable, and are, e.g., of formula (i), wherein L=(a);(b).

Hydroxyeicosatetraenoic acid analogs and methods of their use in treating dry eye disorders are disclosed.

Provided are a titanium-containing solid catalyst useful for producing an epoxy compound from an olefin compound and a peroxide, and a process for producing an epoxy compound using said catalyst. The titanium-containing solid catalyst is obtainable by calcination of a titanium alkynyl alkoxide supported on a silica gel.

a process for the preparation of indanones of the formula II from, indanones of the formula I or of indanones of the formula IIa from indanones of the formula Ia comprises reacting an indanone of the formula I or Ia with a coupling component.

The hydrolysis of tetrahydropyranyl ethers to alcohols catalysed by β-cyclodextrin proceeds in water under neutral conditions.

A propargylic alcohol, enriched in the (R)-enantiomer, has the formula wherein R is C1-4 alkoxy, halogen, or C1-4 alkyl optionally substituted by OH or halogen. This is prepared by the steps of: (a) enantioselective (R)-esterification of the racemic alcohol using any acyl donor and a first enzyme; (b) removal of the untreated (S)-alcohol; and (c) enantioselective hydrolysis of the (R)-ester, using a second enzyme.

Disclosed are 4- and 5-alkynyloxindoles as well as 4- and 5-alkenyloxindoles that inhibit or modulate protein kinases, in particular JNK protein kinases. The compounds of the invention and their pharmaceutically acceptable salts, and prodrugs of said compounds, are useful as anti-inflammatory agents, particularly useful in the treatment of rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing the foregoing compounds, methods for the treatment and/or control of inflammation, particularly in the treatment or control of rheumatoid arthritis using these compounds, as well as intermediates useful in the preparation of compounds of the invention.

Omega chain modified 15-HETE derivatives and methods of their use for treating dry eye are disclosed.

15-HETE derivatives with enhanced metabolic stability and methods of their use for treating dry eye are disclosed.

2,2-Difluoro HETE derivatives and methods of their use for treating dry eye are disclosed.

The synthesis of a series of diacetylenic compounds related to the natural product falcarindiol has been carried out. Unsymmetrical diacetylenes were prepared by a modification of the Cadiot-Chodkiewicz coupling reaction, while a Glaser coupling was used to prepare symmetrical diacetylenes. These compounds have been tested for in vitro cytotoxic activity against Hep-G2, and H-4-II-E cell lines. Diacetylenes with additional unsaturation at C-1, 2, appended with hydroxyl groups at C-3 and C-8, or with long hydrophobic chains, exhibited IC50 values in the micromolar range.

Alcohols and phenols are tetrahydropyranylated rapidly in high yields in the presence of lithium bromide and dichloromethane at room temperature. Deprotection of these THP ethers can also be effected readily by mere change of the solvent to methanol and refluxing with excess lithium bromide. Due to neutral reaction conditions employed, the method is also compatible with compounds having acid sensitive functional groups.

Disclosed are novel 4-alkenyl- and 4-alkynyl oxindoles having the formula and the pharmaceutically acceptable salts thereof, wherein R1, R2, R3, a, b, and X are as defined herein. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast and colon tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I and II as well as intermediates useful in the preparation of the compounds of formula I and II.

One-pot procedure was developed for preparing glycidyl propargyl ether, involving reaction of acetylene with paraformaldehyde and treatment of the resulting propargyl alcohol with epichlorohydrin.

Compounds of formula I: STR1 wherein R, R1, R2, R3, and R4 have any of the values defined in the specification, and their pharmaceutically acceptable salts, are inhibitors of aromatase, and are useful for treating diseases such as breast cancer, in mammals. Also disclosed are pharmaceutical compositions, processes for preparing compounds of formula (I) and intermediates useful for preparing compounds of formula I.

Sarcodictyin A and B, eleutherobin, and bioactive analogs thereof synthesized using solid phase and solution phase chemistries. The synthetic method employs an attachment of common precursors, e.g., compounds 1880 or 200, on a solid support for generating conjugates 230 and 240, followed by standard chemical manipulations. A combinatorial library of sarcodictyins and eletherobin analogs was constructed with modified C-8 ester, C-15 ester and C-4 ketal functionalities and was screened for activity with respect to tubulin polymerization and cytotoxic activity against tumor cells, including Taxol-resistant lines. Compounds 600, 610, 630, 660-700, 730, 760, 850, and 920 were identified to be of equal or superior biological activities as compared to their corresponding natural product.

A kinetic study of the acid-catalyzed loss of alkoxide and thiolate ions from alkoxide and thiolate ion adducts, respectively, of benzylidene Meldrum's acid (1-H), methoxybenzylidene Meldrum's acid (1-OMe), and thiomethoxybenzylidene Meldrum's acid (1-SMe) is reported. The reactions appear to be subject to general acid catalysis, although the catalytic effect of buffers is weak and the bulk of the reported data refers to H+-catalysis. α-Carbon protonation and, in some cases, protonation of one of the carbonyl oxygens to form an enol compete with alkoxide or thiolate ion expulsion. This rendered the kinetic analysis more complex but allowed the determination of pK(a) values and of proton-transfer rate constants at the α-carbon. In conjunction with previously reported data on the nucleophilic addition of alkoxide and thiolate ions to the same Meldrum's acid derivatives, rate constants for nucleophilic addition by the respective neutral alcohols and thiols could also be calculated. Various structure-reactivity relationships are discussed that help define transition-state structures. Comparisons with similar reactions of alkoxide ion adducts of β-alkoxy-α-nitrostilbenes provide additional insights.

Selective deprotection of t-butyldimethylsilyl ethers has been achieved under mild conditions using an aqueous solution of zinc tetrafluoroborate.

The nucleophilic vinylic substitution (S(N)V) reactions of methoxybenzylidene Meldrum's acid (5-OMe) follow the common two-step mechanism involving a tetrahedral intermediate. With thiolate and alkoxide ions, this intermediate is shown to accumulate to detectable levels and a detailed kinetic study allowed the determination of the rate constants of the various elementary steps. With OH- as the nucleophile, the intermediate cannot be observed; it is shown that this is the result of the intermediate rapidly breaking down to products by a pathway not available in the reactions with the thiolate or alkoxide ions. Comparison of structure-reactivity data for the reactions of 5-OMe with those of benzylidene Meldrum's acid (5-H) and β-methoxy-α-nitrostilbene (4-OMe) reveal a complex interplay of steric effects, π-donor and π-acceptor resonance effects, and anomeric effects.

Examination of alcoholic solutions of dimethyl acetylphosphonate (1) and dimethyl benzoylphosphonate (2) by 31P NMR spectroscopy reveals the presence of considerable amounts of hemiketals. Because of the great difference between the 31P chemical shifts of acylphosphonates (ca. 0 ppm) and their hemiketals (17-21 ppm), 31P NMR spectroscopy is a uniquely suitable method for studying the rates and equilibria of hemiketal formation of acylphosphonates with different alcohols. The equilibrium constants Kf, K′f (K′f = Kf[ROH]), pseudo-first-order rate constants k′f, the second order rate constants, kf for hemiketal formation from dimethyl acetylphosphonate with various alcohols, as well as the reverse reaction rate constants, kr to starting materials, were determined. The kinetic isotope effect of 2.8 for the forward reaction kf (EtOH addition) and the backward reaction kr indicates a general catalysis pathway. On the other hand, the calculated values of the enthalpies of activation ΔH? = 10.37 kcal mol-1 (forward), ΔH? = 13.66 kcal mol-1 (backward) and the entropies of activation, ΔS? = -17.25 cal mol-1 K-1 (forward), ΔS? = -9.82 cal mol-1 K-1 (backward) are not in accord with high molecularity of the reaction (1 cal = 4.184 J). Our analysis led to the conclusion that this is probably due to the fact that the transition state is mainly reactant-like with the development of only limited extent of bond formation. Various plausible reaction pathways for hemiketal formation are discussed. In addition, we have calculated the value of 2.65 σ* for the P(O)(OMe)2 group based on proton affinity obtained from heats of formation (ΔHf) of applying the MNDO techniques. The following linear correlation between pKa values and PA values of hemiketals of the form (Me)(R)C(OH)(OCH2X) was developed: pKa = PA - 356.58 + 9.18 [σ*(Me) + σ*(R) + 0.2σ*(X)].

This invention pertains to phosphosulfonates, having the general formula STR1 wherein Y is phenyl, naphthyl, benzyl, a (C5 -C8)cycloalkyl, a 5-membered heteroaromatic ring, a 6-membered heteraromatic ring, a fused 5,6-membered heteroaromatic ring, or a fused 6,6-membered heteroaromatic ring; and X is oxygen or sulfur; and R1 and R2 are each independently selected from substituted or unsubstituted alkyl, alkoxy, alkylthio, alkenyloxy, alkynyloxy, haloalkoxy, cyanoalkoxy, alkoxyalkoxy, cycloalkyloxy, cycloalkylalkoxy, alkylideneiminooxy, chloro, amino, phenyl or phenoxy; or R1 and R2 are both alkoxy, taken together with the phosphorus atom to form a 6-membered oxygen-containing ring; compositions containing these compounds and their use as herbicides.

The rate of solvolysis of esters of o-nitrobenzenesulfonic acid with water and C1-C4 alcohols is satisfactorily described by two-parametric Hammett-Taft equation with predominating effect of the electronic factor σ*. The effect of the structure of the hydrocarbon rest in the sulfonic ester group does not fit to this relationship.

Competitive progesterone antagonists, including two novel steroids, viz., 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one and 11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, inhibit formation of endometrial glands at below their ovulation inhibiting dose and the abortive dose, and thus achieve oral contraception in females without adversely affecting the menstrual cycle and without risk of aborting a previous implanted fertilized egg or a fetus.

A process is described for the preparation of the core azobicyclo[7.3.1]tridecaenediyne moiety of the antitumor antibiotic dynemicin. The synthesis allows efficient production of the enediyne as a stable, compound in good yield from the adamantyl N-protected azabicyclo[7.3.1]tridecadiyne. The adamantyl protecting group is employed in the starting material, N-adamantyl dihydroquinoline or N-adamantyl 6-methoxy quinoline. Also disclosed are process for the synthesis of 3-hydroxy-6-methoxyquinoline and several N-substituted derivatives of azobicyclo[7.3.1]tridecaenediyne. Solid tumor and leukemia assays were performed on the analogs of dynemicin. The results suggest a method that these compounds will useful in treating certain types of leukemias and solid tumors. The disclosed synthesis provides a route to new dynemicin intermediates and analogs which will allow development of second and third generation dynemicins.

N-(Substituted 2-hydroxyphenyl)- and N-(substituted 2-hydroxypropyl)carbamates based on masked active benzoxazolones (model A) and oxazolidinones (model B), respectively, were synthesized and evaluated as potential drug delivery systems.A series of alkyl and aryl N-(5-chloro-2-hydroxyphenyl)carbamates 1 related to model A was prepared.These are open drugs of the skeletal muscle relaxant chlorzoxazone.The corresponding 4-acetamidophenyl ester named chloracetamol is a mutual prodrug of chloroxazone and acetaminophen.Chlorzacetamol and two other mutual prodrugs of active bezoxazolones and acetaminophen were obtained in a two-step process via condensation of 4-acetamidophenyl 1,2,2,2-tetrachloroethyl carbonate with the appropiate anilines.Based on model B, two mutual prodrugs of acetaminophen and active oxazolidinones (metaxalone and mephenoxalone) were similarly obtained using the appropiate amines.All the carbamate prodrugs prepared were found to release the parent drugs in aqueous (pH 6-11) and plasma (pH 7.4) media.The detailed mechanistic study of prodrugs 1 carried out in aqueous medium at 37 deg C shows a change in the Broensted-type relationship log t1/2 vs pKa of the leaving groups ROH: log t1/2 = 0.46pKa - 3.55 for aryl and trihalogenoethyl esters and log t1/2 = 1.46pKa - 16.03 for alkyl esters.This change is consistent with a cyclization mechanism involving a change in the rate-limiting step from formation of a cyclic tetrahedral intermediate (step k1) to departure of the leaving group ROH (step k2) when the leaving group ability decreases.This mechanism occurs for all the prodrugs related to model A.Regeneration of the parent drugs from mutual prodrugs related to model B takes place by means of a rate-limiting elimination-addition reaction (E1cB mechanism).This affords acetaminophen and the corresponding 2-hydroxypropyl isocyanate intermediates which cyclize at any pH to the corresponding oxazolidinone drugs.As opposed to model A, the rates of hydrolysis of mutual prodrugs of model B clearly exhibit a catalytic role of the plasma.It is concluded from the plasma studies that the carbamate substrates can be enzymatically transformed into potent electrophiles, i.e., isocyanates.In the case of the present study, the prodrugs are 2-hydroxycarbamates for which the propinquity of the hydroxyl residue and the isocyanate group enforces a cyclization reaction.This mechanistic particularity precludes their potential toxicity in terms of potent electrophiles capable of modifying critical macromolecules.

diphenyl-t-butoxyslyl (i.e.DPTBOS) derivatives of alcohols are selectively cleaved by nonahydrated sodium sulphide in ethanol, the order of reactivity being: primary ca. secondary>>tertiary.The corresponding t-butyldimethylsilyl and diphenyl-t-butylsilyl derivatives remain unaffected in these conditions.