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Ruthenium-based oxides with rutile structure were examined regarding their properties in electrocatalytic ethene oxidation in acid media. A possible promoting effect of chloride ions toward oxirane formation was explored. Online differential electrochemical mass spectrometry combined with electrochemical polarization techniques were used to monitor the potential dependence of organic products resulting from ethene oxidation as well as the reaction solution decomposition products. Quantum chemical modeling by means of density functional theory was employed to study key reaction steps. The ethene oxidation in acid media led to CO2, whereas oxirane was formed in the presence of 0.3 M Cl-. In the Cl- promoted oxidation on RuO2, oxirane and a small amount of CO2 were the only detected electro-oxidation products at potentials below the onset of Cl2 and O2 evolution, resulting from Cl- and water oxidation. It is demonstrated here that the epoxidation is a surface-related electrocatalytic process that depends on the surface properties. Cl acts as the epoxidation promoter that switches off the combustion pathway toward CO2 and enables the epoxidation reaction channel by surface reactive sites blocking. The proposed epoxidation mechanism implies binuclear (recombination) mechanism for O2 evolution reaction on considered surfaces.

Halide assays are important for the study of enzymatic dehalogenation, a topic of great industrial and scientific importance. Here we describe the development of a very sensitive halide assay that can detect less than a picomole of bromide ions, making it very useful for quantifying enzymatic dehalogenation products. Halides are oxidised under mild conditions using the vanadium-dependent chloroperoxidase from Curvularia inaequalis, forming hypohalous acids that are detected using aminophenyl fluorescein. The assay is up to three orders of magnitude more sensitive than currently available alternatives, with detection limits of 20 nM for bromide and 1 μM for chloride and iodide. We demonstrate that the assay can be used to determine specific activities of dehalogenases and validate this by comparison to a well-established GC-MS method. This new assay will facilitate the identification and characterisation of novel dehalogenases and may also be of interest to those studying other halide-producing enzymes.

Previous theory of structure-energy relations is extended to mechanisms with three concerted reaction events.Data for 25 reactions (five alcohols, five acid catalysts) are examined on the basis of four different mechanisms.Only one of the mechanisms fits well.It involves concerted C...O bond formation, proton donation by the acid catalyst, and proton acceptance by a water molecule, according to H2O + HOCH2R + H2C=O + HOOCCH2R' -> H2OH(+) + RCH2OCH2OH + (-)OOCCH2R'.The fit for this mechanism is decisively good in three practically independent tests.The contrast between the present mechanism and that which fits the base-catalyzed reaction (which does not involve HOH as a reagent) can be explained as due to peculiarities of relative acid-base properties of RCH2OCH2OH and H2O.No inconsistency appears with other data.Transition-state coordinates for the acid-catalyzed reaction are tabulated.Progress of C...O bond formation, though variable within the reaction series, is well ahead of that of the proton transfers.Further analysis of the theoretical free-energy surfaces indicates that disparity of progress of the concerted reaction events reaches a maximum at the transition state.

Kinetics of breakdown are reported for the ethyl, methyl, 2-chloroethyl, and 2,2,2-trifluoroethyl hemiacetals of α-bromoacetophenone, the hemiacetals being generated by the aqueous bromination of the appropriate α-alkoxystyrene.Acid catalysis is characterized by a Broensted α value of 0.6 and a β1g (for H+) of 0.3.With these values the transition state has been located on a reaction coordinate diagram for the class e mechanism of acid catalysis and a comparison made with positions of transition states for acetaldehyde and formaldehyde hemiacetals.With changing electrophilicity of the carbonyl there is a consistent shift in the position of the transition state, but the effect is relatively small.The base-catalyzed breakdowns of the ethyl and 2-chloroethyl hemiacetals have β vlues near 0.7, significantly higher than the values associated with analogous formaldehyde and acetaldehyde hemiacetals.The difference can be explained in terms of the reaction coordinate diagram of the class n base mechanism, recognizing the decreased susceptibility of the ketone to nucleophilic addition.With the trifluoroethyl hemiacetal, buffer dilution plots are curved and there is a downward break in the rate-pH profile.These are explained by a mechanism-hemiacetal hemiacetal anion -> product-where at low buffer concentrations or low H+ concentration the deprotonation step is rate-limiting.As shown through a kinetic analysis, rate-limiting proton transfer is a result of a large rate constant for anion breakdown (ca. 8E8 s-1).Thus, at low buffer concentration breakdown occurs more quickly than reprotonation.The curvature arises because the buffer acid provides efficient protonation.At high buffer concentration the deprotonation step is (approaching) a rapid equilibrium preceding rate-limiting breakdown.Comparison with the other two hemiacetals shows that the behavior of the trifluoroethyl compound is predictable on the basis of structure-reactivity correlations.A reaction with rate-limiting proton transfer is enforced by the very short lifetime of the hemiacetal anion.

A new product, ethylene glycol, was identified from BCNU decomposition.The variation of ethylene glycol yield with pH indicates that there are two competing mechanisms of decomposition.At pH 7.4 the decomposition is predominantly through 2-chloroethyldiazohydroxide, and chloroethanol and acetaldehyde are the major products.At pH 5, the decomposition is predominantly through 4,5-dihydro-1,2,3-oxadiazole and 2-hydroxyethyldiazohydroxide, and ethylene glycol and acetaldehyde are the major products.Deuterium labeling shows that atboth pH's the acetaldehyde arises through a mechanism involving a hydride shift.At pH 5 in the presence of bromide, 2-bromoethanol is a major product and deuterium labeling shows that the hydroxyl is predominantly on the carbon which bore the chlorine in BCNU.

Rate constants and structure-reactivity coefficients for the breakdown of acetaldehyde and acetaldehyde-d4 hemiacetals were determined in water and deuterium oxide by trapping the acetaldehyde formed with α-effect nucleophiles. General-base catalysis by substituted acetate and cacodylate ion catalysts represents equilibrium ionization of the hemiacetal CL3CL(OL)OR (L = H or D) to form the hemiacetal anion, CL3CL(O-)OR followed by rate-determining general-acid catalysis of the cleavage of the hemiacetal anion to form acetaldehyde and ROL. Solvent isotope effects for the catalytically active proton kpBH/kpBD = 0.9-2.5 do not change significantly with changes in the pK of the catalyst or the leaving group alcohol. The increase in the secondary αβ-deuterium isotope effects kαβH/kαβD = 1.21-1.30 with decreases in the pK of the leaving group alcohol can be described by the interaction coefficient pyy′ = ?ρn/-?pK1g = -0.069. The increase in Br?nsted β = 0.48-0.72 with decreases in the pK of the leaving group alcohol in water can be described by the interaction coefficient pxy′, = ?β/-?pK1g = 0.090 and in D2O by pxy′ = 0.078. The interaction coefficients and the observation of both solvent and secondary deuterium isotope effects are consistent with a coupling between proton transfer to the leaving group oxygen and changes in hybridization about the central carbon in the transition state for cleavage of the hemiacetal anion. The results are discussed in the context of proposals for stable hydrogen-bonded protons in concerted acid- and base-catalyzed reactions in water.

Reactions of gold(III) complexes with ethylene and propylene in water provide the first such examples not accompanied by reduction of the gold. HAuC14 and AuCL3(TPPTS) produce organic products (alcohol, aldehyde/ketone, etc.) with gold reduction to the metal. However, [Au(bipy)CL2] Cl in water produces the gold(III) β-hydroxy complexes, [Au(bipy)(CH2CH2OH)2]X (X =Cl, PF6) and [Au(bipy)(CH2CH(OH)CH3]Cl, which are stable in solution. These complexes could not be isolated, but were characterized by NMR and high-resolution mass spectra. [Au(terpy)Cl]CL2 fails to react with ethylene in water, even at elevated temperatures. DFT computations were performed to investigate the reaction mechanism.

In an NMR spectroscopic study the cleavage of epoxides [ethylene, propylene, and cis/trans-butylene oxide] by chromyl chloride giving access to oxochromium(VI) alkoxides was shown to proceed via a bimolecular rate-determining step where two molecules of a complex CrO2Cl2...epoxide collide. Subsequently one Cl ligand at the first Cr center attacks the backside of an epoxide molecule complexed at the Cr center of a second CrO2Cl2...epoxide molecule and vice versa. The trans-opening of the epoxides was proved by determining the configuration of the chlorohydrins resulting from hydrolysis of the corresponding alkoxide products in the cases of cis- and trans-butylene oxide. The NMR data provide evidence that each oxochromium(VI) alkoxide adopts one preferred conformation in solution although DFT calculations did not indicate any special stabilizing effects. The product formation was rationalized by DFT calculations concerning the thermodynamics of the reactions.

Electrolyzed anode water (EAW) markedly extended the vase life of cut carnation flowers. Therefore, a flower-senescence hormone involving ethylene decomposition by EAW with potassium chloride as an electrolyte was investigated. Ethylene was added externally to EAW, and the reaction between ethylen and the available chlorine in EAW was examined. EAW had a low pH value (2.5), a high concentration of dissolved oxygen, and extremely high redox potential (19.2 mg/l and 1323 mV, respectively) when available chlorine was at a concentration of about 620 microns. The addition of ethylene to EAW led to ethylene decomposition, and an equimolar amount of ethylene chlorohydrine with available chlorine was produced. The ethylene chlorohydrine production was greatly affected by the pH value (pH 2.5, 5.0 and 10.0 were tested), and was faster in an acidic solution. Ethylene chlorohydrine was not produced after ethylene had been added to EAW at pH 2.6 when available chlorine was absent, but was produced after potassium hypochlorite had been added to such EAW. The effect of the pH value of EAW on the vase life of cut carnations was compatible with the decomposition rate of ethylene in EAW of the same pH value. These results suggest that the effect of EAW on the vase life of cut carnations was due to the decomposition of ethylene to ethylene chlorohydrine by chlorine from chlorine compounds.

β-Substituted ethyl acetates, XCH2CH2OCOCH3, have been prepared, and their hydrolysis by acetylcholinesterase has been studied.Log of enzymic reactivity, normalized for intrinsic reactivity in hydrolysis by hydroxide, log(kcat/Km)n, rises linearly with increasing refraction volume, MR (or RD25), for substrates with β-X = H, Cl, Br, CH3CH2, (CH3)2CH, (CH3)2S+, (CH3)3N+, and (CH3)3C.Larger substituents may by accommodated, (CH3)3Si and (CH3CH2)3N+, with no further increase in rate.Substrates with β-substituents CH3S, CH3S(O), (CH3)3N+(OH), and CH3S(O2) are less reactive than consistent with the relation with MR by factors of 5-40, indicating that hydrophobic surface and desolvation of the substrate-enzyme interface may be necessary for maximum reactivity correlated with MR.Values of log (kcat/Km)n for substrates with β-substituents X = CH3S, Cl, Br, CH3CH2, (CH3)2CH, (CH3)3C, and (CH3)3Si rise linearly with increasing hydrophobicity, ?, but reactivity of substrates with X = (CH3)3N+ and (CH3)2S+ are more reactive than consistent with a relation to ? by factors of 300 and 40 and with X = CH3S(O2), CH3S(O), and (CH3)2N+(OH), by factors of 7-100.Reactivity appears related to (i) volume of the β-substituent and its fit in its subsite, which is trimethyl rather than anionic, and (ii) the hydrophobicity of its surface.

An expression is derived which relates catalysis by undissociated H3PO4 in aqueous H2PO4-/HPO42- buffer solutions of pH ca. 7 to buffer ratio and the Broensted exponent α for the system.This expression predicts that H3PO4 catalysis will be significant when α is near unity but will have reached negligible proportions by the time α has dropped to 0.6-0.7.These predictions are borne out by experimental data for the hydrolysis of several 2- alkoxy-2-phenyl-1,3-dioxolanes.

Lipases have been found to act as stereoselective catalysts in polycondensation reactions between racemic diesters and achiral diols (or vice versa) in organic solvents.Optically active trimers and pentamers have been formed as a result.

Rate constants and structure-reactivity parameters for general acid and general base catalysis of the reactions of acetaldehyde with water and alcohols at 25 deg C and ionic strength 1.0 (KCl) were determined by trapping the carbonyl group formed upon cleavage of acetaldehyde hydrate or hemiacetal with semicarbazide or hyrazine.The Broensted coefficients of α=0.50-0.59 for general acid catalysis by a class e mechanism are larger than those for the corresponding reactions with formaldehyde.The difference is described by a normalized interaction coefficient pxy'=0.067=δα/-δ?=δρ/δpKHB.The increase in α with decreasing pKa of the alcohol is described by the coefficient pxy=0.020=δα/-δpKlg=δβlg/-δpKHB.A small increase in βlg for the acetaldehyde compared with formaldehyde reactions corresponds to a normalized coefficient pyy'=0.014=Δβlg/-δ?=δr/-δpKlg.These coefficient are consistent with a concerted reaction mechanism and a largely diagonal reaction coordinate on an energy contour diagram that is defined by the structure-reactivity parameters; there may be a larger vertical than horizontal component to the reaction coordinate.A stepwise mechanism is excluded by a requirement for rate constants that would have to be in the range 1E13-1E18 s-1 for proton transfer and for decomposition of the dipolar addition species R.Extrapolated rate constants for the cleavage of R in the range 1E20-1E23 s-1 suggest that the concerted mechanism is enforced by the absence of a significant lifetime for R.The general base catalyzed reactions show a decrease in βlg and an increase in β for acetaldehyde compared with formaldehyde that correspond to normalized values of pyy'=-0.052=δβlg/-δ?=δρ/-δpKlg and pxy=0.042=δβ/-δρ=δ?/-δpKBH.The increase in Broensted β values with decreasing pKa of the leaving group and the increase in βlg with decreasing catalyst pKa are described by an interaction coefficient pxy'=0.07=δβ/-δpKlg=δβlg/-δpKBH, and upward curvature in the dependence of log k on the pKa of the leaving group (an "anti-Hammond effect") is described by a value of py'=-0.20=δβlg/-δpKlg.These interaction coefficients and a value of px=0=δβ/-δpKBH from the linear Broensted plots correspond to a reaction coordinate that is rotated 57 deg clockwise from the vertical on an energy contour diagram that is defined by the structure-reactivity parameters, with β for proton transfer on the x axis.The results support a fully concerted reaction mechanism with an important component of proton transfer in the transition state.Rate constants for "water-catalyzed" reaction are consistent with those for buffer bases; there is no evidence for a cyclic mechanism involving proton transfer through water.Hydroxyde ion catalysis of the reaction represents specific base catalysis.The equilibrium constant for acetaldehyde hydration was found to be Kb=1.2+/-0.1 at 25 deg C, ionic strength 1.0.

We have found chlorine kinetic isotope effects on the dehalogenation catalyzed by haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 to be 1.0045 ± 0.0004 for 1,2-dichloroethane and 1.0066 ± 0.0004 for 1-chlorobutane. The latter isotope effect approaches the intrinsic chlorine kinetic isotope effect for the dehalogenation step. The intrinsic isotope effect has been modeled using semiempirical and DFT theory levels using the ONIOM QM/QM scheme. Our results indicate that the dehalogenation step is reversible; the overall irreversibility of the enzyme-catalyzed reaction is brought about by a step following the dehalogenation.

The aqueous decomposition of the title nitrosoureas under various pH conditions was studied kinetically to generalize their hydrolytic mechanisms. The relative decomposition rates of these analogs were related to the break-off ability of the halogen moiety, which also affected the preference in their reaction pathways. 5 refs.

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Two new agents based upon the structure of the clinically active prodrug laromustine were synthesized. These agents, 2-(2-chloroethyl)-N-methyl-1,2- bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide (1) and N-(2-chloroethyl)-2- methyl-1,2-bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide (2), were designed to retain the potent chloroethylating and DNA cross-linking functions of laromustine, and gain the ability to methylate DNA at the O-6 position of guanine, while lacking the carbamoylating activity of laromustine. The methylating arm was introduced with the intent of depleting the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). Compound 1 is markedly more cytotoxic than laromustine in both AGT minus EMT6 mouse mammary carcinoma cells and high AGT expressing DU145 human prostate carcinoma cells. DNA cross-linking studies indicated that its cross-linking efficiency is nearly identical to its predicted active decomposition product, 1,2-bis(methylsulfonyl) -1-(2-chloroethyl)hydrazine (90CE), which is also produced by laromustine. AGT ablation studies in DU145 cells demonstrated that 1 can efficiently deplete AGT. Studies assaying methanol and 2-chloroethanol production as a consequence of the methylation and chloroethylation of water by 1 and 2 confirmed their ability to function as methylating and chloroethylating agents and provided insights into the superior activity of 1.

Bismuth trichloride as mild reagent, has been found to be a worthful catalyst for tetrahydropyranylation of 1°,2°,3°, allylic, benzylic alcohols, and symmetric di-ols. At room temperature the reagent THP(3,4-dihydro-2H-pyran) was successfully employed as pyranylating agent in presence of BiCl3catalyst without the use of a solvent and the yields of the products were found to be 90-96%. Further, the depyranylation of alcohols was achieved in quantitative yield by simple addition of MeOH using the same catalyst. The developed method was showed good chemo-selectivity in symmetrical diols for mono THP protection.

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The invention relates to a method for producing chloroethanol and dichloroethane through ethylene glycol chlorination. According to the method, ethylene glycol is taken as a raw material, a cobalt compound, a manganese compound and an iron compound are taken as active components, and a zinc compound is taken as an active catalyst of an active auxiliary agent, so that the reaction of chloroethanol and dichloroethane can be effectively catalyzed, and high chloroethanol yield is obtained. The method solves the problems of poor selectivity and difficulty in organic acid catalyst recovery in the chloroethanol and dichloroethane preparation reaction in the prior art, and also avoids the problems of high ethylene oxide production cost, difficulty in storage and transportation and the like in the chloroethanol process taking ethylene oxide as a raw material.

The invention provides a method for preparing halogen ethyl alcohol. The method comprises the following step: (1) halogen alcoholization: adding halogen hydride, H2O2, ethylene and a Ti heteroatom-containing molecular sieve into a reaction device, and carrying out halogen alcoholization reaction to obtain the halogen ethyl alcohol. The invention also provides a method for preparing ethylene oxide with a halogenohydrin method. The method comprises the following steps: (1) halogen alcoholization: adding halogen hydride, H2O2, ethylene and a Ti heteroatom-containing molecular sieve into the reaction device, and carrying out the halogen alcoholization reaction to obtain the halogen ethyl alcohol; (2) saponification: carrying out saponification reaction on the halogen ethyl alcohol in the step (1) and a hydroxide of alkali metal, and separating to obtain the ethylene oxide and alkali halide metal salt; optionally (3) electroosmosis: carrying out bipolar membrane electroosmosis on alkali halide metal salt obtained in step (2) to obtain the hydroxide of alkali metal and the halogen hydride. According to the methods, the halogen ethyl alcohol or the ethylene oxide can be prepared at extremely high selectivity and yield, and the discharging of waste water and waste residues can be drastically lowered.

The invention relates to the field of synthesis of chemical raw materials, and discloses a method for preparing high-purity chlorohydrins. The preparation method comprises the following steps: a, mixing a raw material 1, 4-dichloro-2-butene and an ozonization reaction solvent; agitating; charging ozone to perform ozonization reaction; tracking the reaction through gas chromatography; and stopping the ozonization reaction until raw materials disappear; and b, charging nitrogen to remove the ozone from a reaction flask; adding a reducing agent to reduce at -10-30 DEG C; agitating; recovering the solvent under a normal pressure condition; and distilling and collecting fractions under normal pressure to obtain the high-purity chlorohydrins. The preparation method is simple and convenient in process route, small in pollution, high in yield, fast in reaction speed, and simple in post-treatment; the chlorohydrins have the purity exceeding 99%, and thus the industrial value is relatively high.

The reactions of [WCl6] with a series of ethers have been performed in chlorinated solvent and elucidated by means of analytical, spectroscopic and DFT methods. The addition of tetrahydropyran (thp) or 1,4-dioxane to [WCl6] resulted in the reversible formation of the adducts WCl6···L [L = thp (1a), 1,4-dioxane (1b)], detected in solution by NMR spectroscopy. The reaction of [WCl6] with thp in a molar ratio of 1:2 in chloroform at reflux afforded [WOCl4(thp)] (2a), which was isolated in 51 % yield. [WOCl4(OMe2)] (2b) and [WOCl3(OMe2)2] (3a) were isolated in yields of 53 and 18 %, respectively, from the reaction of [WCl6] with an excess of dimethyl ether. [WOCl3(OEt2)2] (3b) was the only identified metal compound produced from the reaction of [WCl6] and OEt2(1:2 molar ratio). According to NMR studies, the oxide ligand in 2a,b and 3a,b was generated by double C–O bond cleavage involving one equivalent of organic reactant. The 1:1 reaction of [WCl6] with 1,2-diethoxyethane led to [WCl5(κ1-OCH2CH2OEt)] (4) and a minor amount of [WCl4(κ2-EtOCH2CH2OEt)] (5). The aryl oxide compound [WCl5(OPh)] (6) was prepared in 62 % yield from the reaction of [WCl6] and anisole by selective Csp3–O bond activation. The prolonged heating of a mixture of [WCl6] and diphenyl ether in 1,2-dichloroethane led to the isolation of the WVcomplex [WCl5(OPh2)] (7). The molecular structures of 2a and 3a were ascertained by X-ray diffraction.

There are provided methods and systems for an electrochemical cell including an anode and a cathode where the anode is contacted with a metal ion that converts the metal ion from a lower oxidation state to a higher oxidation state. The metal ion in the higher oxidation state is reacted with hydrogen gas, an unsaturated hydrocarbon, and/or a saturated hydrocarbon to form products.

A new method for the transformation of glycerol into mono- and dichlorohydrins has been studied. With trimethylchlorosilane as chlorinating agent and acetic acid as catalyst, mono- and dichlorohydrins have been obtained in high yields and selectivity. In fact, under different reaction conditions, the synthesis of α-monochlorohydrin (3-chloropropan-1,2-diol) or α,γ-dichlorohydrin (1,3-dichloropropan-2-ol) as predominant product has been achieved. This process was also exploited for the valorisation of the crude mixture of glycerol and monochlorohydrin (glyceric mixture), a by-product from an earlier BioDiesel production. A reaction mechanism has been proposed based on investigations on the chlorination of different alcohols.

A process for producing a chlorohydrin, an ester of a chlorohydrin, or a mixture thereof including the steps of contacting, in a hydrochlorination reactor, a multihydroxylated aliphatic hydrocarbon, an ester of a multihydroxylated aliphatic hydrocarbon, or a mixture thereof with a source of a hydrogen chloride, in the presence of a hydrophobic or extractable carboxylic acid catalyst is provided.

(Chemical Equation Presented) An esterase from Bacillus subtilis (BS2) allows the fast and selective removal of allyl, 2-chloroethyl, and 2,2,2-chloroethyl esters under mild conditions in high yields. In addition, BS2 easily hydrolyzes phenacyl esters, while the hydrolysis of sterically hindered diphenylmethyl esters is slow, requiring longer reaction time and higher enzyme/substrate ratio.

The present invention relates to a process for converting a multihydroxylated-aliphatic hydrocarbon or ester thereof to a chlorohydrin, by contacting the multihydroxylated-aliphatic hydrocarbon or ester thereof starting material with a source of a superatmospheric partial pressure of hydrogen chloride for a sufficient time and at a sufficient temperature, and wherein such contracting step is carried out without substantial removal of water, to produce the desired chlorohydrin product; wherein the desired product or products can be made in high yield without substantial formation of undesired overchlorinated byproducts. In addition, certain catalysts of the present invention may be used in the present process at superatmospheric, atmospheric and subatmospheric pressure conditions with improved results.

The propensity of sodium borohydride to reduce the carbonyl group in eleven α-substituted and two aromatic esters has been investigated by experiments and at the B3LYP/6-31++G(d,p)//HF/6-31G(d,p) level of theory. The chemoselectivities in nine of these reductions have been examined by experiments. Experimental results agree well with the calculated order of activation energies for hydride transfer to the ester carbonyl group. Methyl α-bromoacetate reduces faster than methyl α-fluoroacetate. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Treatment of tetrahydropyranyl (THP) ethers with silica sulfuric acid in methanol provides a simple and efficient process for deprotection of these ethers and the parent alcohols are obtained in excellent yields.

A zirconium borohydride piperazine complex (Ppyz)Zr(BH4) 2Cl2, obtained by the reaction of an ethereal solution of ZrCl4 and LiBH4 with piperazine is a stable, selective and efficient reducing agent. (Ppyz)Zr(BH4)2Cl 2 reduces aldehydes, ketones, silylethers, α, β-unsaturated carbonyl compounds and esters. The reactions were performed in diethyl ether at room temperature or under reflux, and the yields of the corresponding alcohols were excellent. The selective reduction of aldehydes in the presence of ketones and complete regioselectivity in the reduction of α,β-unsaturated carbonyl groups were observed.

2-Chloroethylphosphonic acid dialkylesters (bis-(2-chloroethyl), dimethyl, diethyl, dipropyl, dibutyl and dipentylesters) were hydrolyzed in order to obtain 2-chloroethylphosphonic acid, used as a plant growth regulator. Experiments were made in neutral or acid conditions, in order to find optimal conditions for esters hydrolysis. The obtained 2-chloroethylphosphonic acid was tested, regarding its biological activity, on melon, cucumber, blackcurrant and bilberry.

Mild and efficient method for deprotection of silyl ethers to alcohols is described using Caro's acid supported on silica gel. Reactions are carried out in dichloromethane at room temperature and their parent hydroxy compounds obtained in good to excellent yields. Using this procedure, tetrahydropyranyl ethers (THP) remain intact during desilylation reaction.

A mild and efficient method for the deprotection of aryl t-butyldimethysilyl (TBS) ethers is described. The protecting group TBS could be cleaved from aryl silyl ethers using cesium carbonate in DMF-H2O at room temperature to give the corresponding phenols in excellent yields. The reaction conditions allowed selective deprotection of aryl TBS-protected phenols in the presence of TBS, phenyloxycarbonyl or tetrahydropyranyl-protected alcohols.

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

The tris(trimethylsilyl)silyl (sisyl) group is a photolabile protecting group for primary and secondary alcohols. Sisyl (tris(trimethylsilyl)silyl) ethers 2b-11b of a number of primary and secondary alcohols 2a-11a were prepared in yields ranging from 70-97%. The resulting silyl ethers were stable to aqueous bases, Grignard reagents and Wittig reagents as would be expected for bulky alkoxysilanes. They were also stable to selected fluoride salts including CsF. The sisyl ethers could be cleaved using photolysis at 254 nm in under 30 minutes to give the starting alcohols in yields ranging from 62-95%. The photolytic behaviour of sisyl ethers was examined in more detail using 2,3-dimethyl-1,3-butadiene as a silylene trap. The regiochemistry of the oligosilane fragmentation to silylenes was shown to be dependent upon the alkoxy group. The hydrolytic stability of three was compared with the analogous t-butyldimethylsilyl ethers. The relative stability of the two silyl groups can be altered by choice of solvent: in acetic acid/water the ease of hydrolysis followed the order ROSi(SiMe3)3 > ROSiMe2t-Bu; the inverse order was observed in CDCl3 using p-TsOH·H2O. Pseudo-first-order rate constants for the acidic hydrolysis of primary, benzylic, and secondary sisyl ether in AcOH/THF/H2O were determined to be 3.74 x 10-2 s-1, 1.94 x 10-2 s-1, and 1.30 x 10-2 s-1, respectively. The analogous rate constants for the TBS ethers were determined to be 6.04 x 10-3 s-1, 3.53 x 10-3 s-1, and 3.49 x 10-3 s-1, respectively.

The thermal degradation of mustard gas (ClCH2CH2SCH2CH2Cl, HD ), with and without 5% added water, is examined. GC/MS, LC/MS and NMR were employed to comprehensively analyze the products. After 75 days at 90°C, 91% HD remains (80% with 5% water). After 40 days at 140°C, 30% HD remains (24% with 5% water) and black tar precipitates form. The apparent Ea is 22.4 kcal/mol. Major products include Q (ClCH2CH2SCH2CH2SCH2CH2Cl), 1,2-dichloroethane, polysulfides and 1,4-dithiane. With 5% water, oxygenates such as 1,4-thioxane and 2-chloroethanol are produced as are numerous sulfonium ions, including S-(2-chlorethyl)-1,4-dithianium, a major component of mustard heels. The decomposition does not go to completion due to the equilibrium nature of the reaction at these temperatures.

A compound having the formula I STR1 in which R1, R2 independently are OH, OOC--R3 or O--R3, and R3 is an unsubstituted or substituted C1 -C6 alkyl, alkenyl, alkynyl or phenyl group. The compound is useful as a natriuretic and anti-hypertensive agent.

Several 2-alkoxycarbonyl- and 2-aryloxycarbonyl- 1,2-bis(methylsulfonyl)-1-(7-chloroethyl)hydrazines, conceived as thiolysable prodrugs of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine, were synthesized and their antineoplastic activity evaluated against the L1210 leukemia in mice. In addition to producing 'cures' of mice bearing this tumor, many of the analogues were preferentially activated by glutathione (GSH) and/or glutathione S-transferase (GST), making them potentially useful in the treatment of multidrug resistant tumors with increased intracellular levels of GSH and/or GST.

The use of the tris(trimethylsilyl)silyl (sisyl) group as a photolabile protecting group for primary and secondary alcohols was demonstrated. Sisyl ethers of a number of alcohols (yields 70-97%) were stable to many synthetic protocols, but could be deprotected using photolysis to give the starting alcohols (yields 62-95%).

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)].

The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism.

Oxidation of nine aliphatic primary alcohols by benzyltrimethylammonium tribromide (BTMAB) in aqueous acetic acid leads to the formation of corresponding aldehydes.The reaction is first order with respect to BTMAB.Michaelis-Menten type kinetics were observed with respect to the alcohol.The formation constants for the alcohol-BTMAB complexes and the rates of their decomposition, at different temperatures, have been evaluated.The oxidation of ethanol exhibited a substantial kinetic isotope effect.Addition of benzyltrimethylammonium and bromide ions did not affect the rate.Tribromide ion has been postulated as the reactive oxidizing species.The reaction is subject to both the polar and steric effects of the substituents.A mechanism involving transfer of a hydride ion from the alcohol to the oxidant has been proposed.

The base sequence selectivity of DNA alkylation for a series of structurally related 1,3-dialkyl-3-acyltriazenes was examined with calf thymus DNA or polymers containing the sequences GGG, CGC, TGT, and AGA. The reaction products at the N7 and the O6 positions of guanine were identified, quantitated, and then correlated with the decomposition rates of the triazenes, 1-(2-chloroethyl)-3-methyl-3-carbethoxy- (CMC), 1-(2-chloroethyl)- 3-methyl-3-acetyl- (CMA), 1-(2-hydroxyethyl)-3-methyl-3-carbethoxy- (HMC), 1- (2-hydroxyethyl)-3-methyl-3-acetyl-(HMA), and 1,3-dimethyl-3-acetyl- (DMA). The results of these studies revealed that DNA sequences with runs of purines were more reactive toward alkylation by all of the triazenes tested, irrespective of whether the alkylation was measured by N7, O6, or total guanine adducts. Within this generalization, the (hydroxyethyl)triazenes showed a preference for the AGA sequence, while the (chloroethyl)triazenes favored the GGG sequence. The structure of the 3-acyl group of the triazene also played a role in the extent of alkylation of a particular sequence of DNA. Both the (chloroethyl)- and the (hydroxyethyl)triazenes produced higher alkylation product yields for the 3-carbethoxytriazenes as compared with the 3-acetyl derivatives for most of the sequences examined. These overall patterns correlated well with the order of decomposition of the triazenes at 37 °C: HMC > DMA > HMA > CMC > CMA. This study has demonstrated how varying the structure of 1,3-dialkyl-3-acyltriazenes can modulate DNA alkylation, a finding which may be important in the design of new triazene antitumor agents.

The reaction of malononitrile with aliphatic alkyl nitrites in aqueous basic media to give the corresponding oxime product HON=C(CN)2 goes through a mechanism involving a rate-limiting reaction between the alkyl nitrite and the carbanion CH(CN)2.

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.

A catalytic antibody was developed to selectively cleave the alcohol ester of 4-nitrophenylacetyl moiety while also tolerating a wide variety of structural variation on the alcohol portion of the molecule. The basis to the success of this study was that antibody epitope recognition was directed toward only key elements contained within the 4-nitrophenylacetyl group and not the entire haptenic molecule. This study offers the potential application of catalytic antibodies as practical reagents for the selective deprotection of complex multifunctionalized molecules possessing class similar protecting groups. Such a chemoabzymatic approach could eventually minimize synthetic complications which can arise from functional group protection in the synthesis of complex natural products.

The rate constants for the acid-catalysed hydrolysis of 1-(1-alkoxyethyl)uracils and 1-alkoxymethyluracils have been determined.With both series of compounds, the hydrolysis rate is rather insensitive to the polar nature of the alkoxy group, in striking contrast with the hydrolysis of the corresponding analogues of adenine and cytosine nucleosides, which react via rate-limiting formation of an oxocarbenium ion intermediate.Furthermore, it has been shown that 3',5'-cyclic monophosphates of thymidine and uridine undergo hydrolysis of the N-glycosidic bond 760 and 260 times as fast as their parent nucleosides, while the cyclic monophosphates of 2'-deoxyadenosine and adenosine are depurinated much more slowly than the corresponding nucleosides.On this basis it is suggested that 4-oxopyrimidine nucleosides are hydrolysed by opening of the sugar ring.To obtain further evidence for this exceptional mechanism, comparative kinetic measurements with some seco- and 3'-C-alkyl nucleosides of uracil and adenine have been carried out.

Study and comparison of the pH-independent hydrolysis of eight alkyl nitrites shows 3-nitroso-1,2-glyceryl dinitrate, a putative intermediate in the biotransformation of glyceryl trinitrate, to be unexpectedly reactive and too labile to be detected as a biotransformation intermediate in aqueous solution, suggesting a role for neighbouring group participation by the β-nitrate group.

The trifluoroethoxide-catalyzed trifluoroethanolysis and the hydroxide-catalyzed hydrolysis of a series of phenyldimethylsilyl ethers were examined. A Bronsted plot of the logarithm of the second-order rate constant KTFE for reaction with trifluoroethanol against the pKLG is not linear. The nonlinear plot might be taken as evidence for a change in rate-determining step of a reaction that proceeds through a pentavalent intermediate. However, the Bronsted plot for the hydroxide-catalyzed hydrolysis, where all the leaving groups are of lower pKa than hydroxide, has an identical shape as the Bronsted plot for the trifluoroethanolysis reaction. Therefore, the unusual shape of the Bronsted plots is not due to a change in rate-determining step. It is suggested that the results are most consistent with a one-step concerted mechanism and not with a mechanism involving a pentavalent intermediate.

The hydrolysis of alkyl formates with leaving groups in the range pKa = 12-16 is catalyzed by substituted acetate anions. There is an increase in the Br?nsted β value for general base catalysis with decreasing pKa of the leaving alcohol and a complementary increase in -β1g with decreasing pKa of the catalyzing base, both of which are consistent with a value of pxy = ?β/-pK1g = ?β1g/-?pKBH ? 0.11. This result supports a class n mechanism of general base catalysis, in which a proton is abstracted from the nucleophilic water molecule by the base catalyst in the transition state; it is not consistent with the kinetically equivalent class e mechanism of electrophilic catalysis by general acids of a reaction with hydroxide ion, by proton donation to the leaving alcohol. Solvent deuterium isotope effects in the range kH2O/kD2O = 3.6-5.3 for the buffer-independent reaction and 2.5-2.8 for catalysis by CHaCOO- support concerted proton transfer and O-C bond formation. The secondary isotope effect for catalysis of the hydrolysis of LCOOMe by acetate ion is kD/kH = 1.05. Both nucleophilic and general base mechanisms of catalysis by acetate anions are observed for the hydrolysis of substituted phenyl formates with leaving groups of pKa = 7.1-10.1. A small value of β = 0.12 for general base catalysis of the hydrolysis of phenyl formate and p-methylphenyl formate represents catalysis of the addition of water by hydrogen bonding of water to the base catalyst. On the other hand, a larger value of β = 0.35 and a decrease in kH2O/kD2O to 1.2 were observed for general base catalysis of the hydrolysis of p-nitrophenyl formate. It is suggested that the increase in β with decreasing pK1g (an apparent "anti-Hammond effect") may be accounted for by a change in mechanism, from catalysis of a stepwise reaction of phenyl and p-methylphenyl formates to concerted general base catalysis of formyl transfer to water for the reaction of p-nitrophenyl formate.

The products and mechanism of hydrolytic decomposition of a series of 1,,3-dialkyl-3-acyltriazenes were studied in both acidic and neutral buffers.In the acidic region, the products are alkyl alcohols derived from the N(1) alkyl group and amides derived from the intact N(3) portion of the molecule.The solvent deuterium isotope effect (kH2O/kD2O)) is less than 1.0.The mechanism is specific acid catalyzed, involving rapid reversible protonation of the 3-acyl group followed by scision of the N(2)-N(3) bond to generate an amide and an alkyl diazonium ion.The (2-hydroxyethyl)diazonium ion gives ethylene glycol and acetaldehyde, while the (2-chloroethyl)diazonium ion yields 2-chloroethanol.In the neutral region, the products are similar to those found in acidic buffers, alkyl alcohols, and amides.At this pH the (2-chloroethyl)diazonium ion produces ethylene glycol and acetaldehyde in addition to 2-chloroethanol.The solvent deuterium isotope effect (kH2O/kD2O) is greater than 1.0.The mechanism involves unimolecular heterolylsis of the N(2)-N(3) bond to form an amide anion and an alkyldiazonium ion.The methyldiazonium ion leads to incorporation of deuterium in the methyl group of the products, indicating the existence of an equilibrium between the metastable methyldiazonium ion and diazomethane.

The results of studying the acid hydrolysis of methyl, ethyl, isopropyl, butyl, tert-butyl, pentyl, 2-bromoethyl, 2-chloroethyl and 2-ethoxyethyl nitrites in water show that the reaction is not, as widely accepted in the literature, catalysed by nucleophiles (Cl-, Br-, etc.), but is however subject to general acid catalysis.These findings, and the observed values of the solvent isotope effect, suggest that the substrate is protonated in the rate-controlling step of the reaction.Further, the relative reactivities of the various substrates investigated suggest a concerted mechanism in which the proton transfer occurs concurrently with the breaking of the O-N bond via a slightly imbalanced transition state.

The kinetics in 25percent (v/v) dioxane-water of the alkaline hydrolysis, followed by UV spectrometry, of several alkyl phenylcarbazates (Ar-NH-NHCOOR, with Ar = phenyl, 4-chlorophenyl, 4-fluorophenyl, 3,4-dichlorophenyl and R = methyl, ethyl, propyl, chloroethyl, trichloroethyl) are discussed.The pKa of trichloroethyl phenylcarbazate is 14.12 at 25 deg C.The pH profiles, the activation entropy of -40 cal mol-1 K-1, the kinetic solvent isotope effect, kOH-/kOD-, of 3.45, the general-base catalysis and the effect of the leaving group and of the substituent on the aromatic ring are in agreement with the involvement of a BAc2 reaction scheme.

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The chemical decomposition of N-(2-chloroethyl)-N-nitrosocarbamoyl (Q(NO)) prolinamide and valinamide were studied under physiological conditions. The volatile products were identified with GC. Q(NO)-Pro-NH2 gave twice the amount of ethylene glycol and only one-fifth of the 2-chloroethanol produced by Q(NO)-Val-NH2 or BCNU, pointing to different pathways of their decomposition. The carbamoylating activity was also investigated in the presence of cyclohexylamine, and it was found to lead mainly to intramolecular carbamoylation with the formation of hydantoin derivatives.

The feasibility of cycloalkylation reactions in the presence of Friedel-Crafts catalysts was demonstrated in a nimber of aryl hydroxyalkyl sulfides (1-5), and benzyl hydroxyalkyl sulfides (6-7).Treatment of compounds (1-7) with Friedel-Crafts catalysts gave diaryl disulfides, diaryl sulfides, arene thiols, chlorohydrins, aryl chloroalkyl sulfides, aryl alkenyl sulfides and cyclization products.It is noteworthy to mention that cyclization products were isolated only in cases where the hydroxyl group is linked to a tertiary carbon atom as in compounds 3 and 7.A suitable reaction pathway is suggested to rationalize the formation of the various reaction products.