541-41-3

Dissolved hexachlororuthenate(IV) effectively catalyzes the photodecomposition of chloroform to hydrogen chloride and phosgene under near-UV (λ > 345 nm) irradiation, whereby RuCl62- is not itself photocatalytically active, but is photochemically transformed into a species that is active, possibly RuCl5(CHCl3)-. Conversion to a photoactive species during irradiation is consistent with the acceleration of the decomposition rate during the early stages and with the apparent inverse dependence of the decomposition rate on the initial concentration of RuCl62-. The displacement of Cl - by CHCl3 in the coordination sphere to create the photoactive species is consistent with the retardation of photodecomposition by both Cl- and H2O. The much smaller photodecomposition rate in CDCl3 suggests that C-H bond dissociation occurs during the primary photochemical event, which is also consistent with the presence of a CHCl3 molecule in the first coordination sphere. In the presence of RuCl62-, chloroform decomposes under near-UV irradiation to phosgene and hydrogen chloride. The photoactive species is suggested to be RuCl5(CHCl3) -.

The invention belongs to the field of fine chemical engineering, and particularly relates to a new production process of a hexazinone key raw material WT-02, which comprises the procedures of high-pressure reaction, Oppenauer oxidation, acyl chloride amination and condensation. The method has the advantages of short steps, single solvent, simple post-treatment, wide raw material source, low price, low comprehensive cost and the like.

Chloroformates are key reagents for synthesizing carbonates and carbamates. The present study reports a novel photo-on-demand in situ synthesis of chloroformates with a CHCl3 solution containing a primary alkyl alcohol. It further allowed the one-pot synthesis of carbonates and carbamates through subsequent addition of alcohols or amines, respectively.

The invention provides a method for preparing ethyl chloroformate, and relates to the technical field of organic matter synthesis. The method for preparing the ethyl chloroformate includes filling reaction towers with 45-55 L of ethyl alcohol; simultaneously stirring and cooling the ethyl alcohol in the reaction towers until the temperature of the ethyl alcohol reaches 3-6 DEG C, filling the reaction towers with phosgene at the flow velocity of 25-35 m/h, to be more specific, heating the reaction towers until the temperatures of the reaction towers reach 12-20 DEG C when the reaction towersstart to be filled with the phosgene, filling the reaction towers with the phosgene for the phosgene filling time of 2-2.5 h, continuing to carry out stirring reaction for 0.6-1 h after the reactiontowers finish being filled with the phosgene, and collecting products. The reaction towers are provided with stirrers, brine cooling reflux condensers, thermometers, gas leading-in openings and tail gas exhaust openings. The method for preparing the ethyl chloroformate has the advantages of little side reaction, high ethyl chloroformate reaction yield and high product purity.

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.

Rhomboid proteases form one of the most widespread intramembrane protease families. They have been implicated in variety of human diseases. The currently reported rhomboid inhibitors display some selectivity, but their construction involves multistep synthesis protocols. Here, we report benzoxazin-4-ones as novel inhibitors of rhomboid proteases with a covalent, but slow reversible inhibition mechanism. Benzoxazin-4-ones can be synthesized from anthranilic acid derivatives in a one-step synthesis, making them easily accessible. We demonstrate that an alkoxy substituent at the 2-position is crucial for potency and results in low micromolar inhibitors of rhomboid proteases. Hence, we expect that these compounds will allow rapid synthesis and optimization of inhibitors of rhomboids from different organisms.

In this paper, we present fluorescent photoremovable protecting groups (FPRPG) based on bis-acetyl carbazole for the release of two different functional groups such as carboxylic acids, alcohols, thiols, and amines in a sequential fashion. Dual-arm caged bis-acetyl carbazoles with different combinations of two unlike functional groups were synthesized. Photophysical studies showed that caged bis-acetyl carbazoles are blue fluorescent and their emission properties are sensitive to the environment. Sequential photorelease of two different functional groups by bis-acetyl carbazole was analyzed by HPLC, UV and emission spectroscopy. The mechanism of the dual release by bis-acetyl carbazole was investigated and supported by TD-DFT calculations. To demonstrate the applicability of the dual release ability of bis-acetyl carbazole FPRPG, we synthesized a drug delivery system (DDS) in which one arm of bis-acetyl carbazole is linked to the carboxylic functional group of chlorambucil (CBL) and the other arm is attached to the hydroxyl group of ferulic acid ethyl ester (FAEE). In vitro studies showed that our DDS presents excellent properties such as photoregulated dual drug delivery, cellular uptake, and biocompatibility.

The kinetics and mechanism of the reaction of atomic chlorine with ethyl formate [Cl + CH3CH2O(C=O)H, reaction 1] have been examined. These experiments were performed at pressures of 760-950 Torr and temperatures from 297 to 435 K. Reactants and products were quantified by gas chromatography-flame ionization detector (GC/FID) analysis. The initial mixture contained ethyl formate, Cl2, and N2. Cl atoms were generated by UV photolysis of this initial mixture at 360 nm, which dissociates Cl2. The rate constant of reaction 1 was measured at 297 K relative to that of the reaction Cl + C2H5Cl (reaction 2), yielding the rate constant ratio k1/k2 = 1.09 ± 0.05. The final products formed from reaction 1 are ethyl chloroformate, 1-chloroethyl formate, and 2-chloroethyl formate. These products result from the reactions with Cl2 of the three free radicals formed by H atom abstraction from ethylformate in reaction 1. Based on the molar yields of these three chlorinated products, the yields of the three radicals formed from reaction 1 at 297 K are (25 ± 3) mole percent of CH3CH2O(C=O); (67 ± 5) mole percent of CH3CHO(C=O)H; and (8 ± 2) mole percent of CH2CH2O(C=O)H. A second phase of this experiment measured the rate constant of the decarboxylation of the ethoxy carbonyl radical [CH3CH2O(C=O) → CO2 + C2H5, reaction 4] relative to the rate constant of its reaction with Cl2 [CH3CH2O(C=O) + Cl2 → CH3CH2O(C=O)Cl + Cl, reaction 3a]. Over the temperature range 297 to 404 K at 1 atm total pressure, this ratio can be expressed by k4/k3a = 1023.56±0.22 e-(12700±375)/RT molecules cm-3. Estimating the value of k3a (which has not been measured) based on similar reactions, the expression k4 = 5.8 × 1012 e-(12700)/RT s-1 is obtained. The estimated error of this rate constant is ± a factor of 2 over the experimental temperature range. This rate expression is compared with recent ab initio calculations of the decarboxylation of the analogous methoxy carbonyl radical.

Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10 μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate.

1-(Hydroxyacetyl)pyrene has been introduced as a new fluorescent phototrigger for alcohols and phenols. Alcohols and phenols were protected as their corresponding carbonate esters by coupling with fluorescent phototrigger, 1-(hydroxyacetyl)pyrene. Photophysical studies of caged carbonates showed that they all exhibited strong fluorescence properties. Irradiation of the caged carbonates by visible light (≥410 nm) in aqueous acetonitrile released the corresponding alcohols or phenols in high chemical (95-97%) and quantum (0.17-0.21) yields. The mechanism for the photorelease was proposed based on Stern-Volmer quenching experiments and solvent effect studies. Importantly, 1-(hydroxyacetyl)pyrene showed as a phototrigger for rapid photorelease of the biologically active molecule adenosine. In vitro biological studies revealed that 1-(hydroxyacetyl)pyrene has good biocompatibility, cellular uptake property and cell imaging ability. The Royal Society of Chemistry and Owner Societies 2012.

The gas-phase elimination kinetics of selected ethyl esters of 2-oxo-carboxylic acid have been studied over the temperature range of 270-415 °C and pressures of 37-114 Torr. The reactions are homogeneous, unimolecular, and follow a first-order rate law in a seasoned static reaction vessel, with an added free radical suppressor toluene. The observed overall and partial rate coefficients are expressed by the following Arrhenius equations: Ethyl oxalyl chloride log koverall (s-1)=(13.22 ± 0.45) - (179.4 ± 4.9) kJ mol-1 (2.303 RT)-1 Ethyl piperidineglyoxylate log k(CO2) (s-1)=(12.00 ± 0.30) - (191.2 ± 3.9) kJ mol-1 (2.303 RT)-1 log k(CO) (s-1)=(12.60 ± 0.09) - (210.7 ± 1.2) kJ mol-1 (2.303 RT)-1 log kt(overall) (s -1)=(12.22 ± 0.26) - (193.4 ± 3.4) kJ mol-1 (2.303 RT)-1 Ethyl benzoyl formate log k(CO2) (s -1)=(12.89 ± 0.72) - (203.8 ± 9.0) kJ mol-1 (2.303 RT)-1 log k(CO) (s-1)=(13.39 ± 0.31) - (213.3 ± 3.9) kJ mol-1 (2.303 RT)-1 log kt(overall) (s-1)=(13.24 ± 0.60) - (205.8 ± 7.6) kJ mol-1 (2.303 RT)-1 The kinetic and thermodynamic parameters of these reactions, together with those reported in the literature, lead to consider three different mechanistic pathways of elimination.

The chloride form of the polystyrene-divinylbenzene anion exchange resin Amberlite IRA-900 was found to catalyze the photodecomposition of carbon tetrachloride in ethanol at wavelengths above 350 nm. With sulfate, bromide, and perchlorate as counterions, the resin was inactive. The major products are acetaldehyde, phosgene, chloroform, and hydrogen chloride. The photoreaction is much slower under 1.0 atm O2 than under air, while in deoxygenated solutions it is also much slower and produces no phosgene. Much of the observed behavior can be explained by a model in which the poly(styrene-co- divinylbenzene) matrix absorbs light and transfers energy to CCl4, which undergoes photodissociation, assisted by a chloride ion to stabilize the chlorine atom as Cl2-. Two major reaction channels for the trichloromethyl radicals produced by photodissociation are proposed, one in which CCl3 abstracts hydrogen from ethanol and the other involving addition of O2 to form trichloromethylperoxy radicals.

The invention provides novel azulene derivatives of general formula I wherein R1 to R6 have the significance given in the description, as well as their tautomers, enantiomers, diastereomers, racemates and physiologically compatible salts or esters and substances which are hydrolyzed or metabolized in vivo to compounds of formula I. The invention is also concerned with a process and intermediates for the manufacture of the above compounds, pharmaceutical compositions which contain such compounds as well as the use of these compounds in the treatment of inflammatory conditions.

The invention relates to the products of formula (I): STR1 in which: R1 =represents hydrogen, aryl, arylcarbonyl, arylthio, alkylcarbonyl, R2, R3 represent in particular halogen, mercapto, acyl, carboxy, nitro, cyano, amino, carbamoyl, R4, --OR4 with R4 representing in particular hydrogen, alkyl, alkenyl, alkynyl, acyl, amino, --(CH2)m1 --S(O)m2 --X--R10 with m1=0 to 4, m2=0 to 2, X represents a single bond or --NH--, --NH--CO--, --NH--CO--NH--, and R10 represents alkyl, alkenyl or aryl, and Y represents optionally substituted aryl, these products being in all isomer forms and salts, their use as medicaments.

Reaction of the title imines with diphenyldiazomethane gives a Δ3- 1,3,4-triazoline, which leads, after loss of dinitrogen, to a transient azomethine ylide. Subsequent elimination of ethyl or methyl chloroformate gives the unexpected 1,1-diphenyl-4,4-dichloro-2-aza-1,3-butadiene.

Acetic acid derivatives of the formula STR1 wherein L, M, T and Q have the significance given in the description, can be used for the treatment or prophylaxis of illnesses which are caused by the binding of adhesive proteins to blood platelets and by blood platelet aggregation and cell-cell adhesion, and are manufactured by cleaving protecting groups in the corresponding protected compounds or by converting the cyano group into the amidino group in corresponding nitriles.

The invention relates to the new use and the new products of formula (I): STR1 in which: R1 =represents hydroxyl, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, formyl, cycloalkyl, optionally interrupted by heteroatoms, R2, R3 represent in particular halogen, mercapto, acyl, carboxy, nitro, cyano, amino, carbamoyl, R4, --OR4 with R4 representing in particular hydrogen, alkyl, alkenyl, alkynyl, acyl, amino, --(CH2)m1 --S(O)m2 --X--R10 with m1=0 to 4, m2=0 to 2, X represents a single bond or --NH--, --NH--CO--, --NH--CO--NH--, and R10 represents alkyl, alkenyl or aryl, and Y represents optionally substituted aryl, these products being in all the isomer forms and the salts, as medicaments.

Described herein are novel imidazopyridine derivatives of the formula I STR1 wherein R is STR2 and R1, R2, R3 and R4 are as defined in Patent Claim 1, and their salts, which exhibit antagonistic properties towards angiotensin II and can be used for the treatment of hypertension, aldosteronism, cardiac insufficiency and increased intraocular pressure, and of disorders of the central nervous system.

Pharmaceutical compositions for the treatment of cataract containing N-acetyl-L-cysteine derivatives of formula STR1 (wherein R and R1 have the meanings reported in the specification) are described.

Heat-sensitive recording materials contain an electron-donating chromogenic compound and an electron-attracting compound. The recording materials also contain at least one compound represented by the following formula: STR1 wherein R1 and R3 mean a hydrogen atom or an alkyl, aralkyl or aryl group, R2 and R4 denote an alkyl, alkenyl, aralkyl or aryl group, X1, X2, Y1 and Y2 stand for an oxygen or a sulfur atom, and --Z1 -- and --Z2 -- are a specific aromatic group. Also provided are phenol compounds represented by the following formula: STR2 wherein R1, R2, X1 and Y1 have the same meanings as defined above; R5 and R6 are a hydrogen or halogen atom or an alkyl, alkoxy, aralkyl, aryl or hydroxyl group; p and q stand for an integer of 1-4; R5 and R6 may be either the same or different when p and q represent an integer of 2 or greater; and --Z3 -- means a specific divalent group.

Pharmaceutical compositions for the treatment of cataract containing N-acetyl-L-cysteine derivatives of formula (wherein R and R1 have the meanings reported in the specification) are described.

A compound of the formula: STR1 wherein R1 is a hydrogen atom or a lower alkyl group, R2 is a hydrogen atom or a conventional protecting group for a carboxyl group, R0 is a hydrogen atom or a conventional protecting group for a hydroxyl group, X is a protected or unprotected amino group, a carboxyl group, a lower alkoxycarbonyl group, an ar(lower)alkyloxycarbonyl group, a cyano group, a hydroxyl group, a lower alkyloxy group, a lower alkylthio group, a lower alkylsulfonyl group or a group of either one of the following formulas: STR2 wherein R3 and R4, which may be the same or different, each represents a hydrogen atom or a lower alkyl group, or they are taken together to represent an alkylene chain to form, in combination with the adjacent nitrogen atom, a 3- to 7-membered cyclic amino group, wherein Z represents --NH-- or --O-- and R5 represents an amino group, a mono(lower)alkylamino group, a di(lower)alkylamino group, a lower alkyloxy group or a lower alkyl group, STR3 wherein R6 represents a hydrogen atom or a lower alkyl group, wherein R7 represents a mono(lower)alkylamino group, a di(lower)alkylamino group or a lower alkyloxy group, or STR4 wherein R8, R9 and R10, which may be the same or different, each represents a hydrogen atom or a lower alkyl group, Y represents a hydrogen atom, a conventinal protecting group for an amino group or a group of either one of the following formulas: STR5 wherein R11 and R12, which may be the same or different, each represents a hydrogen atom or a lower alkyl group or STR6 wherein R6 is as defined above and n is an ingeter of 1 to 6, and a pharmacologically acceptable salt thereof, which is useful as an antimicrobial agent.

Magnesium oxide is an effective reagent for the carbon-acylation of malonates with either acyl chlorides or chloroformates.Various malonic esters (methyl, ethyl, isopropyl and isobutyl) were easily alkoxycarbonylated to give the corresponding methanetricarboxylic esters.The reaction scope and limitations have been elaborated.

N-acyl munchnones were generated for the first time by a novel acylation/desilylation reaction of 5-siloxyoxazoles.These munchnones partially equilibrated through ring-chain valence tautomerism and afforded two cycloadducts with DMAD.

A quantitative analysis of the effect of the characteristics of the medium on the phosgenation rate of alcohols was made by means of the parameters of the Koppel-Palm equation.An equation is proposed which describes the effect of the solvent on the reaction rate and which takes account of the interdependence of the components of nonspecific and specific solvation.The applicability of the proposed equation to other solvolytic reactions was demonstrated.An equation is obtained which makes it possible to asses the phosgenation rate of alcohols in relation to the properties of the medium and the structure of the alcohol.

The kinetics of the reaction of phosgene with various aliphatic alcohols were investigated in heptane and dioxane and without a solvent.The effects of the polarity of the medium the structure of the alcohol, and the activation parameters of the process are consistent with an addition-elimination mechanism.

Rate coefficients for pyrolytic elimination of ethyl, isopropyl, and t-butyl carbonates, and of di-t-butyl carbonate have been measured over a 50 K range for each compound.The relative rates at 600 K are 1:29.6:2934:3526 and the rate spread for the primary, secondary, and tertiary compounds is inconsistent with that obtained from elimination of a range of other esters including alkyl phenyl carbonates.The least reactive compounds are found to be more reactive than predicted, probably owing to a combination of the greater Ei character of their transition states and the high nucleophilicity of the carbonyl group in dialkyl carbonates.Rate data for pyrolysis of S-ethyl, S-isopropyl, and S-t-butyl O-methyl carbonates give the relative rates at 600 K as 1:22:1074.The But:Pri rate ratio (49:1) is therefore greater than the Pri:Et ratio, as it is for all other related eliminations; this confirms that the literature results (which show the converse) are in error.The seemingly anomalous relative reactivities of thiolacetates and thiolcarbonates as compared with their oxygen-containing analogues is also shown to be consistent with the effect of variable polarity of the transition state in ester pyrolysis upon the importance of carbonyl group nucleophilicity, and this also accounts for the relative reactivities of thiol-, thion-, and dithio-acetates.Steric acceleration appears less important for carbonates than for acetates, since the rate for di-t-butyl carbonate (statistically corrected) is lower than for t-butyl methyl carbonate, whereas pivalates are more reactive than acetates.

This disclosure describes compounds of the class of 6-[D-α-(substituted-coumarin-3-carboxamido)phenylacetamido]penicillanic acids which possess antimicrobial activity.

There are prepared 7-azabenzimidazoles of the formula STR1 where R1 and R2 are the same or different and are hydrogen, C1 -C6 -alkyl or C2 -C6 -alkanol or --NR1 R2 is a 5 to 7 membered saturated heterocyclic ring having either one nitrogen atom, one nitrogen atom and one oxygen atom or two nitrogen atoms, R3 is hydroxy, an amino group, a mono C1 -C6 -Alkylamino group, a di-C1 -C6 -alkylamino group, or a C2 -C6 -alkylamino, di-C1 -C6 -alkylamino, mercapto, C1 -C6 -alkylmercapto, hydroxy or C1 -C6 -alkoxy, R5 is hydrogen or halogen and A is a C2 -C6 -alkylene group or a salt of such compound. Preferably R1 and R2 are two equal C1 -C6 -alkyl groups or --NR1 R2 is piperidino, pyrrolidino, morpholino, homopiperidino, piperazino or homopiperazino, R3 is hydroxy, mercapto, C1 -C4 -alkoxy, C1 -C4 -alkylmercapto or C1 -C6 -alkylmino, mercapto, C1 -C6 -alkylmercapto, hydroxy or C1 -C6 -alkoxy and R5 is hydrogen and salts thereof. The compounds are useful in treating ulcers and gastritis.

-

A naphthalimide derivative having the formula STR1 wherein R is an alkyl, or cycloalkyl, an aralkyl, a haloalkyl, an alkoxyalkyl, a hydroxyalkyl, an N,N-dialkylaminoalkyl, an unsubstituted or halogen-, alkyl-, alkoxy- or hydroxy-substituted aryl, or an ammoniumalkyl; X is a group of the formula, STR2 wherein A is STR3 or an unsubstituted or halogen-substituted arylene, or a group of the formula, STR4 wherein R1 is hydrogen, an alkyl, phenyl, a hydroxyalkyl, or an alkoxyalkyl; Y is --CO--, --COO--, --CONR3 -- (where R3 is hydrogen or an alkyl), or --SO2 --; R2 is hydrogen, an alkyl, a cycloalkyl, an aralkyl, a haloalkyl, an alkyl- or aryl-substituted amino-alkyl, an unsubstituted or halogen-, alkyl-, alkoxy-, hydroxy-, amino- or alkylamino-substituted aryl, a group of the formula, STR5 (where R, R1 and Y are as defined above and R4 is a bivalent group), or a group of the formula, (where R5 is direct linkage or a bivalent group; Q+ is a substituted ammonium, a cycloammonium or a hydrazinium; and α- is an anion), Which is useful for optically brightening an organic polymer material.

Disclosed are antibacterial penicilins of the formula SPC1 Wherein Y" is a residue for a strong nucleophile and processes for preparing same.