Synthesis of dimethyl heterocyclic‐o‐dicarboxylates using dimethyl acetylenedicarboxylate

Dimethyl acetylenedicarboxylate (DMAD) is a very important and useful reagent for the preparation of dimethyl heterocyclic‐o‐dicarboxylates, which are key intermediates in the synthesis of fused pyridazine derivatives. The synthesis of thiopyranes by the Diels‐Alder reaction of dithiocarboxylate derivatives, synthesis of various cyclazines by [2 + 8] cycloaddition reactions, and synthesis of dimethyl pyrazolo[3,4‐b]pyridine‐5,6‐dicarboxylates and polycyclic heterocycles containing the 1,6‐naphthyridine ring system by the reaction of o‐aminonitrile compounds with DMAD are described here.     

A facile sulfenylchlorination of alkenes with Me2SO/(COCl)2

The sulfenylchlorination of a series of alkenes is investigated by using the combined reagent of dimethyl sulfoxide and oxalyl chloride. The corresponding β-chloro sulfides were obtained in mediate to good yields. Most of the terminal alkenes give the Markovnikov adducts mainly and the sulfenylchlorination of cyclic alkenes is stereospecific to produce the adducts with trans configuration. Methanesulfenyl chloride is supposed to be the real species for sulfenylchlorination.     

Methylation of 5-Phenyl-1,4-benzodiazepin-2-one derivatives with N,N-dimethylformamide-dimethyl acetal

A novel method for N-methylation of the cyclic amide in the 1,4-benzodiazepine ring system is presented. Methods traditionally used involve treatment of the 1,4-benzodiazepinone anion with an alkyl halide. It has been demonstrated that these derivatives can be methylated on the amide nitrogen atom by use of dimethyl-formamide dimethyl acetal which acts as both reagent and solvent for the reaction.     

Totalsynthese von Betalainen

Total Synthesis of Betalaines cis-4-Oxo-2,6-piperidinedicarboxylic acid dimethyl ester ( 10 ) was transformed (44%) into the semicarbazone of 2,3-dihydrobetalamic acid dimethyl ester ( 13/14 ) by a modified Horner-Wittig reagent 12 . Oxidation of 13/14 afforded 41% of a mixture of stereoisomers of betalamic-acid-dimethyl-ester semicarbazone ( 4 ), key intermediate for the synthesis of betalaine pigments. The utility of 4 in this respect was demonstrated on a small scale by its conversion to the dimethyl ester of indicaxanthine ( 9 , 11%) and to the trimethyl ester of betanidine ( 7 , 87%). Hydrolysis of 7 gave betanidine ( 6 ). We further describe the synthesis of the trimethyl ester of an oxidized form of betalamic acid ( 20/21 ) as well as model condensation reactions on the carbonyl group of cyclohexanone, cis-4-oxo-2,6-diphenylpiperidine ( 23 ) and its N-formyl derivative 27 . Reaction of 4-oxo-1,2,3,4-tetrahydro-2,6-pyridinedicarboxylic-acid dimethyl ester ( 40 ) with acetic anhydride or with triethyloxonium tetrafluoroborate resulted in O-acylation or in O-alkylation along with dehydrogenative aromatization to yield the derivatives 39 or 42 , respectively, of chelidamic acid.     

Stereoselectivity of the reaction of mercuric acetate with dimethyl bicyclo[2.2.2]oct-2-en-5,6-cis-endo-dicarboxylate

The stereoselelectivity of the reaction of mercuric acetate with dimethyl bicyclo[2.2.2]oct-2-en-5, 6-cis-endo-carboxylate in acetic acid was studied. One of the reaction products is formed when the reagent attacks the double bond from the sterically less accessible side. The nature of the orientation effect of the carboxylate groups is discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1646–1648, September, 1993.     

Study On Dimethyl Carbonate Synthesis from Methyl Nitrite And CO1

Recently, dimethyl carbonate (DMC) has attracted much attention as a less toxic reagent in relation to environmental problem. DMC is a novel reagent for methylation and carbonylation in place of toxic dimethyl sulfate and phosgene, respectively. DMC is also a promising fuel additive because it can improve octane number.     

The chemical ionization mass spectra of 2-tert-butyl-substituted 1,3-cycloalkanediol diacetates and dimethyl ethers

The chemical ionization (CI) mass spectra of the 2-tert-butyl-substituted 1,3-cyclopentane- and 1,3-cyclohexanediol diacetates and dimethyl ethers have been determined using isobutane and methane as reagent gases. From the differences in the spectra of these compounds, it clearly follows that steric and conformational effects are expresssed in the CI mass spectra. The relative impact of these effects, however, is strongly dependent on diol derivatization and 2-alkyl substitution.     

Preparation and cyclization of 4‐chloro‐5,5‐dimethyl‐3‐formyl‐1,2‐oxathiolene 2,2‐dioxide

Chloroformylation of 5,5‐dimethyl‐1,2‐ oxathiolan‐4‐one 2,2‐dioxide 4 with Vilsmeier reagent (DMF/POCl₃) led to the formation of cyclic β‐chloro‐vinylaldehyde (4‐chloro‐5,5‐dimethyl‐3‐formyl‐1,2‐oxathiolene 2,2‐dioxide 5 ). Compound 5 reacted with formamidine, o‐aminophenol, 1,2‐phenylenediamine, aminopyrazole, and aminotetrazole to give the corresponding heterocyclic compounds. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:200–204, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20094     

Stereochemistry of α,α′-difluorosuccinic acids

Treatment of both dimethyl (?)-D-tartrate (IVa) and dimethyl (+)-L- tartrate (Va) with sulfur tetrafluoride gave dimethyl meso-α,α′-difluorosuccinate (Ia). The same reagent converted dimethyl meso-tartrate (IlIa) to a racemic mixture of dimethyl D- and L-α,α′-difluorosuccinate (IIa). This outcome resulting from the replacement of hydroxyl by fluorine with inversion of configuration at one and retention of configuration at the other chiral carbon atom can be rationalized by assuming the formation of a cyclic intermediate. This is opened by a subsequent S_N2 reaction with fluoride ion followed by a four-center displacement of sulfuroxy group by fluorine. The respective configurations of the dimethyl α,α′-difluorosuccinates Ia and IIa were established by ¹H and ¹⁹F NMR using an optically active chemical shift reagent and confirmed by converting the esters to the corresponding acids and these in turn to the cis- and trans-α,α′-difluorosuccinic anhydrides, respectively.     

S‐Trifluoromethylation of Thiols by Hypervalent Iodine Reagents: A Joint Experimental and Computational Study

The radical trifluoromethylation of thiophenol in condensed phase applying reagent 1 (3,3‐dimethyl‐1‐(trifluoromethyl)‐1λ³,2‐benziodoxol) has been examined by both theoretical and experimental methodologies. On the basis of ab initio molecular dynamics and metadynamics we show that radical reaction mechanisms favourably compete with polar ones involving the S‐centred nucleophile thiophenol, their free energies of activation, ΔF^≠, lying between 9 and 15 kcal mol^?1. We further show that the origin of the proton activating the reagent is important. Hammett plot analysis reveals intramolecular protonation of 1 , thus generating negative charge on the sulfur atom in the rate‐determining step. The formation of a CF₃ radical can be thermally induced by internal dissociative electron transfer, its activation energy, ΔF^≠, amounting to as little as 10.8 and 2.8 kcal mol^?1 for reagent 1 and its protonated form 2 , respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion.     

Kinetics of Alkylated Biladiene-a,c Deprotonation

The kinetics of deprotonation of 1,3,7,13,17,19-hexamethyl-2,8,12,18-tetrabutylbiladiene-a,c dyhydrobromide on treatment with nucleophilic reagents (pyridine, dimethylformamide, dimethyl sulfoxide) in carbon tetrachloride was measured by electron absorption spectroscopy in the temperature range of 293.15–303.15 K. The effects of the reactant concentrations, the temperature, and the electron-donor properties of the nucleophilic reagent on the kinetics of deprotonation of biladiene-a,c as the salt with HBr are discussed.     

Novel oligo-m-carboranylenemethylenesilanes

A method has been developed for the obtaining of new oligo(dimethyl)silanes comprising 1,7-bis(methyl)-m-carboranyl units and bearing the terminal chlorosilyl or methoxysilyl groups. Reactions of such oligomers with an excess of benzylmagnesium chloride or 1-chloromagnesiummethyl-m-carborane lead to oligo-m-carboranylenemethylenesilanes containing the terminal benzylsilyl or m-carboranylmethylenesilyl groups. The novel oligomers are highly viscous liquids possessing a high heat resistance and also a resistance towards the treatment with a strong alkaline reagent.

     

Concise Synthesis of Dimethyl (2-Oxopropyl)phosphonate and Homologation of Aldehydes to Alkynes in a Tandem Process

The synthesis of dimethyl (diazomethyl)phosphonate, a useful reagent for the homologation of aldehydes to alkynes, is described as a one-pot process and comprises the generation of the azide transfer agent, diazotransfer to dimethyl (2-oxopropyl)phosphonate, and methanolysis, followed by a simple extraction protocol. Previously described syntheses for this bulk product are much more elaborate. The homologation of aldehydes to alkynes can also be extended to a single-step process by adding the aldehyde directly to the reaction mixture prior to isolation of the reagent. The homologation process using dimethyl (diazomethyl)phosphonate was shown to proceed also in nonprotic solvents with mild bases, emphasizing the importance of a facile access to the reagent. The oxidation of alcohols to the required aldehydes was performed by a TEMPO-mediated process using chloramine-T as electron acceptor.     

Hypervalent Iodine Reagents: Thiol Derivatization with a Tetrafluoroethoxy Coumarin Residue for UV Absorbance Recognition

A new hypervalent iodine reagent ( 5 ) based on 1,2‐dihydro‐3,3‐dimethyl‐1,2‐benziodoxole containing a 4‐methyl‐7‐tetrafluoroethoxycoumarin unit as a specific UV absorber was prepared and fully characterized, including X‐ray crystal structural analysis. The high reactivity of this compound towards thiols has been exploited for the selective tagging of several targets with the UV chromophore coumarin, including e.g . glutathione.     

Fluorescein dye derivative: Synthesis,characterization, quantum chemical and promising antimicrobial activity studies

The dimethyl sulfite as an alkylating as well as alkoxylating reagent is well known in synthetic organic as well as organometallic chemistry for a long time. Herein, we have utilized dimethyl sulfite as an alkylating reagent and reacted with fluorescein derivative, N-fluorescein-lactam-hydrazine ( B ). This reaction leads to the generation of tetramethylated fluorescein lactam hydrazine ( A ). The newly designed and synthesized molecule ( A ) has been characterized by ¹H, ¹³C NMR and HRMS data. The antimicrobial activity of the synthesized alkylated fluorescein derivative has been tested against E. coli, P. aeruginosa, Salmonella typhimurium and S. aureus microbial agents. Time-kill assay results also confirmed that fluorescein derivative is a potent antimicrobial agent and revealed that the time-kill assay of fluorescein derivative is value-added than the well-known antibiotic. In addition, quantum chemical study was used to analyze its activity trend and correlated with the experimental data. The computed results of DFT revealed that the lipophilicity as well as the LUMO-HOMO band gap (ΔE_LUMO-HOMO = 4.75 eV) of compound A make it more suitable as an antimicrobial agent to match with in vitro antimicrobial experimental results. The MIC and MBC values of compound A were observed to be lower in contrast to fluorescein and ampicillin for all the tested bacterial strains, which were approximately 3- to 4-fold lower than MIC and MBC values of the later. Results obtained from the study clearly indicate that compound A has better antimicrobial and bactericidal activity in comparison to ampicillin and fluorescein. Synthesized compound can be a better substitute of traditionally used antibiotics, Ampicillin.     

Chemical ionization over a wide range of pressures. 1. Mass spectra of dimethyl esters of maleic and fumaric acids

Conclusions By using chemical ionization over a wide range of pressures, from 0.01 torr to atmospheric pressure, and also by selecting the reagent gas, different mass spectra of isomers can be obtained, which are suitable for their reliable identification.Under ionization conditions at atmospheric pressure in helium (reagent ions [H(H₂O)_n]⁺), peaks of cluster ions [MGH]⁺ and [2M+1]⁺ are observed in the spectrum of dimethyl fumarate, which are absent in the case of the cis-isomer.Under the conditions of chemical ionization at a normal pressure (0.4-0.2 torr) of the reagent gases Me₃CH, n-C₇H₁₆ and at an ionic source temperature of 50°C, a stereospecific fragmentation of dimethyl maleate [MH]⁺-MeOH is observed, which is absent in the case of the the trans-isomer.In the chemical ionization spectra at reduced pressure of the reagent gases MeOH, EtOH, i-PrOH (0.01 torr), a peak of the cluster ion [MGH]⁺ is observed for dimethyl fumarate, which is absent in the spectra of the cis-isomer.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 815–819, April, 1985.     

A new tris-annulation reagent prepared from a butadiene telomer,and its application to steroid synthesis

Reaction of 1,7-octadien-3-one with dimethyl malonate, followed by the reduction of the ketone produced dimethyl (3-hydroxy-7-octenyl)malonate, which was converted to 9-decen-5-olide after hydrolysis and decarboxylation. Reaction of vinylmagnesium chloride with the lactone and the subsequent acylation afforded 7-acetoxy-1,11-dodecadien-3-one. This is a new tris-annulation reagent. (±)-D-homo-19-norandrosta-4-en-3-one was synthesized by using this tris-annulation reagent.     

Direct Olefination of Alcohols with Sulfones by Using Heterogeneous Platinum Catalysts

Carbon‐supported Pt nanoparticles (Pt/C) were found to be effective heterogeneous catalysts for the direct Julia olefination of alcohols in the presence of sulfones and KOtBu under oxidant‐free conditions. Primary alcohols, including aryl, aliphatic, allyl, and heterocyclic alcohols, underwent olefination with dimethyl sulfone and aryl alkyl sulfones to give terminal and internal olefins, respectively. Secondary alcohols underwent methylenation with dimethyl sulfone. Under 2.5 bar H_2, the same reaction system was effective for the transformation of alcohol OH groups to alkyl groups. Structural and mechanistic studies of the terminal olefination system suggested that Pt⁰ sites on the Pt metal particles are responsible for the rate‐limiting dehydrogenation of alcohols and that KOtBu may deprotonate the sulfone reagent. The Pt/C catalyst was reusable after the olefination, and this method showed a higher turnover number (TON) and a wider substrate scope than previously reported methods, which demonstrates the high catalytic efficiency of the present method.     

Kinetics and mechanism of oxidation of dimethyl sulphoxide by sodium bromate-sodium bisulphite reagent in aqueous medium

Rates of oxidation of dimethyl sulphoxide (DMSO) by HOBr producedin situ from sodium bromate-sodium bisulphite reagent have been studied iodometrically in aqueous medium. The order in [DMSO] is one when [DMSO] < 001 mol dm^-3, fractional when [DMSO] is between 0.01 and 0.5mol dm^-3 and zero when (DMSO) > 0.5 mol dm^-3. Different rate laws are operative under these three conditions though HOBr is the effective oxidizing species in all the cases. A mechanism involving an intermediate four-membered cyclic transition state between DMSO and HOBr (formation constantK), which decomposes in a slow step with a rate constant(k) has been proposed. Thermodynamic parameters for the adduct formation step and activation parameters for the first-order decomposition of the adduct step have been evaluated in the temperature range 308–323 K. Activation parameters have also been determined while the orders in [DMSO] are unity and zero. The reaction product has been identified as dimethyl sulphone (DMSO₂).     

Probing the Effects of Reagent Gas Pressure and Ion Source Temperature for Dimethyl Ether Chemical Ionization of Tricyclic Antidepressants in an External Source Ion Trap Mass Spectrometer

This study examines the reagent gas pressure and ion source temperature dependence for dimethyl ether chemical ionization (DME CI) mass spectra recorded with an external source ion trap mass spectrometer (ITMS). Information for better controls of the reagent gas pressure in order to obtain fair CI spectra is provided. The origin of M^+? ions observed in DME CIMS is discussed in detail. Furthermore, the ion source temperature effect on the DME CI is also investigated.