Synthesis and antimicrobial evaluation of some novel dithiolane,thiophene, coumarin,and 2-pyridone derivatives

Novel 2-cyano-N-[1-(naphtha-2-yl)ethylidene] acetohydrazide 1 was utilized as key intermediate for the synthesis of some new dithiolane, thiophene, coumarin, 2-pyridone, and other related products containing a hydrazide moiety. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H NMR and mass spectra). The antimicrobial activity of the synthesized compounds was evaluated.     

The diastereoselectivity of the addition of tricarbonyl-(η6-2-lithiothiophene) chromium(O) complexes on aldehydes

It has been shown that the reactions of tricarbonyl(η⁶ -2-lithiothiophene)chromium(O) with various arene carboxaldehydes yields mixtures of unequal amounts of diastereoisomers, which can be separated by flash chromatography. The structures of the products have been established by ¹H NMR spectroscopy and by independent synthesis. A novel synthesis of tricarbonyl(η⁶-thiophene)-chromium(O) (1) is described.     

Synthesis of spiro pyrrolidines via formal [3+2] cycloaddition of unusual enones and cis-3-benzoyl-1-cyclohexyl-2-phenylaziridine

The synthesis of a new class of spiro[tetrahydronaphthalen-one/butenolide]pyrrolidines has been accomplished by the 1,3-dipolar cycloaddition of azomethine ylide generated by thermal ring opening of cis-3-benzoyl-1-cyclohexyl-2-phenylaziridine with (E)-2-arylidene-1,2,3,4-tetrahydronaphthalen-1-ones and (E)-3-arylidene-5-phenyl-Δ^4,5-butenolides. The structures of the products were confirmed by spectroscopic techniques as well as single crystal X-ray analysis of one of the products.     

Convergent syntheses of carbon-13 labeled midazolam and 1′-hydroxymidazolam

For the purpose of drug interaction studies, the stable-isotope labeled [¹³C₃]midazolam and its metabolite, 1′-hydroxy-[¹³C₃]midazolam were synthesized in four and five steps in overall yields of 25.5% and 14.2%, from 7-chloro-5-(2-fluorophenyl)-2-(N-nitrosomethylamino)-3H-1,4-benzodiazepine, respectively, by a convergent synthesis, in which a key imidazoline ring formation was achieved by the facile reaction of [¹³C]2-aminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine with varying ethyl imidate hydrochlorides. The scrambling of C-3 and C-4 labeling in intermediate diamine, and consequently in the final products, as well as the formation of a Δ^4,5 isomer of 1′-hydroxy-[¹³C₃]midazolam was observed and explained.     

Novel Synthesis,Characterization of N1,N1,N4,N4-tetrakis (2-hydroxyethyl) terephthalamide (THETA) and Terephthalic Acid (TPA) by Depolymerization of PET Bottle Waste Using Diethanolamine

Chemical depolymerization of poly(ethylene terephthalate) (PET) waste is a possible remedy to huge amount of solid waste generation as it results in degradation products that possess a potential of recyclability. PET bottle waste was depolymerized by aminolysis using diethanolamine. Novel synthesis of N¹, N¹,N⁴,N⁴-tetrakis (2-hydroxyethyl) terephthalamide (THETA) with 73-76% yield and terephthalic acid (TPA) with 78-82% yield was achieved. The purified products were analyzed by FTIR, melting point, DSC, DTG and ¹H-NMR. THETA has various applications in the synthesis of rigid polyurethane foam, unsaturated polyester resins and also as a cross linking agent/ hardener for epoxy resins.     

Steroid total synthesis. IV.(+)-13 -ethyl-17 -ethynyl-17 -hydroxy-gon-4-en-3-one

The title compound (Norgestrel), a potent progestational agent, has been prepared by a new total synthesis. The scheme is based on earlier work with BCD-tricyclic intermediates, condensation of 2-ethyl-cyclopentane-1,3-dione with 2-[2-diethylamino-ethyl]-6-[4-t-butoxy-pentyl]-tetrahydropyran-2-ol being the key step. The synthesis features the addition of acetylene to a Δ⁵⁽¹⁰⁾-4-oxa-17-keto intermediate, followed by a novel transformation to the final product.     

4,5‐Dihydro‐1,2,3‐oxadiazole: A Very Elusive Key Intermediate in Various Important Chemical Transformations

4,5‐Dihydro‐1,2,3‐oxadiazoles are postulated to be key intermediates in the industrial synthesis of ketones from alkenes, in the alkylation of DNA in vivo, and in the decomposition of N‐nitrosoureas; they are also a subject of great interest for theoretical chemists. In the presented report, the formation of 4,5‐dihydro‐1,2,3‐oxadiazole and the subsequent decay into secondary products have been studied by NMR monitoring analysis. The elusive properties evading characterization have now been confirmed by ¹H, ¹³C, and ¹⁵N NMR spectroscopy, and relevant 2D experiments at very low temperatures. Our experiments with suitably substituted N‐nitrosoureas using thallium(I) alkoxides as bases under apolar conditions answer important questions on the existence and the secondary products of 4,5‐dihydro‐1,2,3‐oxadiazole.     

Acetone Dimethyl Hydrazone: Useful Synthon+ for the Synthesis of Pheromones with Keto and Spiro Ketal Functions

The use of α-lithiated dimethyl hydrazones as an efficient enolate equivalent for the alkylation of ketones has been reported^1,2,3. Due to the ragioselectivity exhibited by acetone dimethyl hydrazone (1) towards the formation of bis alkylated products, we have used the easily avaiLable (1) as a convenient synthon for achieving a short and simple synthesis of pheromones, 1,7-dioxaspiro (5,5) undecane4 (2) and Z-6-Heneicosen-11-one (2). The key step in both the syntheses is the regioselective bis alkylation of (1) using butyl lithium as a base, as shown in Scheme I.     

Double Tetrametaphosphates Ca2-xMx IIP4O12

Abstract

The thermal synthesis of Ca₂-_xM_x ^IIP₄O₁₂ (M^II=Mn, Co; x=0,5 -1,5) starts from a mixture of carbonates of the respective metals and phosphoric acid. Formation of the products has been followed by TA (thermal analyses) under quasi-isothermal-isobaric conditions and compared with that of simple tetrametaphosphates at the same conditions (Refs 1,2). Distinct effect of water vapour pressure on the condensation reaction course is indicated; enhanced pressure retards the reactions and shifts them to higher temperatures, but it favours formation of the desired condensation intermediates and, especially, increases the yield of the double tetrametaphosphate. Monoclinic structure of the microcrystalline products obtained has been confirmed. The lattice parameters have been determined, and their shift to lower values with increasing x has been observed. The TA methods have been used to follow thermal stability of the products and to determine the temperatures of melting and of reversible transition to higher linear phosphates (polyphosphates). For these vitreous products we have determined their softening temperatures, and temperature, heat, and energy of the recrystallization connected with reverse formation of the double tetrametaphosphates. The reversible transition is also used for synthesis of the pure products (Ref. 3) which appear to be promissing as special inorganic pigments (Ref. 4).     

The synthesis and biological activity of new 7-[2-(cyanomethyl)piperazinyl]- and 7-[3-(cyanomethyl)piperazinyl]quinolone antibacterials

Some novel 7-[2- or 3-(cyanomethyl)piperazinyl]quinolones have been prepared. Most notable, 2-cyanomethyl-piperazine 5 and 1-methyl-2-cyanomethylpiperazine 8 at the quinolone C-7 position produce products with good in vitro antibacterial activity. The key step in the synthesis of these products involves the regioselective deprotection of the benzyl group in function of the time reaction.     

Asymmetric synthesis of chiral β-iodo Baylis–Hillman esters using MgI2 as promoter via a one-pot three-component reaction

An asymmetric synthesis of β-iodo-α-(hydroxyalkyl)acrylates has been developed involving conjugate addition of I⁻ to menthyl propiolates to give β-iodo allenolate intermediates which undergo 1,2-addition to form β-iodo Baylis–Hillman products. Modest diastereoselectivities (37–58% de) and excellent yields (80–87%) were obtained when (1R,2S,5R)-(−)-menthol was used as a chiral auxiliary. The two diastereoisomers of the product were separated by silica gel chromatography to give diastereomerically pure products.     

Self-reproduction of chirality on α-aminophosphonates: asymmetric synthesis of α-alkylated diethyl pyrrolidin-2-yl-phosphonate

A simple method for the asymmetric synthesis of α-substituted diethyl pyrrolidin-2-yl-phosphonate is described. The chiral oxazolopyrrolidine phosphonate was alkylated diastereospecifically with an alkyl halide. The key intermediate is an α-phosphonate-stabilized carbanion that can be alkylated without loss of optical activity and a single enantiomer of product was formed exclusively in 10-80% yield. The configurational assignment of the products relied on ¹H-¹H NOESY analysis of the alkylated oxazolopyrrolidine phosphonates. This represents an unprecedented case of self-regeneration of stereocenters (SRS) of cyclic aminophosphonates. The enantiomerically pure α-aminophosphonate diethyl-(2S)-(2-methylpyrrolidin-2-yl)-phosphonate, a surrogate of 2-methyl proline, was obtained upon hydrogenolysis of the chiral auxiliary in 83% yield.     

Synthesis of 7H-indolo[1,2-a]quinolinium derivatives via oxidative photocyclization of 3H-indolium salts using blue LED photoreactor

Oxidative photocyclization of 1-phenyl-2-(2-arylethenyl)-3,3-dimethyl-3H-indolium perchlorates leading to 7H-indolo[1,2-a]quinolinium salts was investigated. The synthesis was performed under Vis irradiation. Blue LEDs emitting at 454.5 nm were used as the light source. The reaction progress was followed by UV-Vis spectroscopy. The products were characterized by IR, ¹H and ¹³C NMR spectroscopy. Reaction time depended on the position of the UV-Vis absorption band of both the substrates and products. The results revealed that the application of blue LED photoreactor makes the synthesis of 7H-indolo[1,2-a]quinolinium easier and more convenient.     

Synthesis of Benzofuryl Substituted Unsymmetrical Ureas Under Microwave Irradiation

A series of 2-benzofuryl substituted unsymmetrical ureas were synthesized by reactions of benzofuroyl isocyanate, which was prepared from benzofuroyl azide by Curtius rearrangement, with various aromatic amines, 2-amino-5-(benzo-2-furyl)-1,3,4-thiadiazole, and 2-amino-5-aryloxymethylene-1,3, 4-thiadiazoles under microwave irradiation. Compared to conventional methods, this synthesis has the advantages of mild reaction conditions, easy handling, and high yields. The products have been characterized by analytical and spectral (IR and ¹ H NMR) data.     

Synthesis of 2-(4-amino substituted benzylidene) indanone analogues from aromatic nucleophilic substitution (SNAr) reaction

A novel, efficient and convenient procedure has been developed for the synthesis of 2-(4-amino-substituted benzylidene)indanone derivatives. In the first step, the reaction of 4-fluorobenzaldehyde with 5, 6-dimethoxy-2, 3-dihydro-1H-inden-1-one in the presence of NaOH in EtOH was described. In the next step, a variety of aliphatic and aromatic amines were reacted with 2-(4-fluorobenzylidene)-5, 6-dimethoxy-2, 3-dihydro-1H-Inden-1-one via aromatic substitution (S_NAr) reaction to produce 2-(4-aminobenzylidene)-5, 6-dimethoxy-2, 3-dihydro-1H-Inden-1-one derivatives as a novel class of 1-indanones. These products have been successfully prepared in good to excellent yields. ^1?H and ^13?C NMR, FT-IR spectroscopy and CHN analysis supported the proposed structures of the products.     

New substituted 2-aminomethyl-2-oxo-2λ5-perhydro-[1,3,2]oxazaphospholo [3,4-a]pyridine: Design,synthesis and antimicrobial activity

The synthesis of a new series of P-heterocyclic compounds, substituted 2-aminomethyl-2-oxo-2λ⁵-perhydro-[1,3,2]oxazaphospholo[3,4-a]pyridine derivatives 8(a-j), was accomplished. A key intermediate, 2-(chloromethyl)-2-oxo-2λ⁵-perhydro-[1,3,2]oxazaphospholo[3,4-a]pyridine (6) was primarily synthesized by the condensation of (±)-2-piperidinemethanol (4) and chloromethylphosphonic dichloride (5); subsequently, it was treated with various heterocyclic amines/benzylamines/aminoacid esters, 7(a-j) to obtain the desired products. The structures of the newly synthesized compounds were elucidated by ¹H, ¹³C, and ³¹P NMR spectroscopy, mass spectra and elemental analyses. The biological potency of title products was investigated by screening in vitro antimicrobial activity. The bio-screening data revealed that most of the synthesized derivatives showed potent growth of inhibition against fungi while compared with bacteria. Particularly, compounds 8c and 8i against bacterial strains, and 8a and 8f against fungi exhibited promising activity.     

Total Synthesis of Arylnaphthalene Lignans through a Photochemical Key Step

The total syntheses of three arylnaphthalene lignans ( ANL s) were developed: Vitrofolal E ( 1 ), Noralashinol C ( 2 ), and Ternifoliuslignan E ( 3 ). These natural products have in common a missing substituent in 2-position of the naphthalene moiety ( 2H-ANL s). The key step of these syntheses is a regioselective intramolecular Photo-Dehydro-Diels-Alder (PDDA) reaction with (1,7)naphthalenophanes as primary products. A further improvement of the photochemical step was achieved by triplet sensitization with xanthone, allowing the use of more efficient UVA lamps. It should be noted that this work is a continuation of a previous publication about the total synthesis of lignans using the PDDA reaction.^[1]     

Enantioselective Iridium‐Catalyzed Allylic Substitution with 2‐Methylpyridines

An enantioselective iridium‐catalyzed allylic substitution with a set of highly unstabilized nucleophiles generated in situ from 2‐methylpyridines is described. Enantioenriched 2‐substituted pyridines, which are frequently encountered in natural products and pharmaceuticals, could be easily constructed by this simple method in good yields and excellent enantioselectivity. The synthetic utility of the pyridine products is demonstrated through the synthesis of a key intermediate of a reported Na⁺/H⁺ exchanger inhibitor and the total synthesis of (−)‐lycopladine A.     

Synthesis,characterization and coordination chemistry of substituted β-amino dicarbonyls

An efficient and facile method for the synthesis of novel structurally diverse β-amino dicarbonyl compounds is described by exploring the aza-Michael addition reaction in an aqueous medium as a key step. Thereby, 2-(aryl-disubstituted-amino-1-yl-methyl)-malonic acid diethyl esters were achieved in a good to excellent yields. These products were easily isolated with enough purity just by using simple recrystallization. The crystals of the compounds (17) and (24) have been obtained and studied by X-ray crystallographic analyses.     

Synthetic studies on trans-clerodane diterpenoids and congeners : stereocontrolled total synthesis of (±)-4-methylene-9α-(3-oxobutyl)-5β, 8β,9β-trimethyl-trans-decalin and related intermediates

A stereocontrolled total synthesis of the title compound, a marine natural product as well as a degradation product of sigmosceptrellins and palauolide, has been accomplished by a simple route broadly applicable to certain trans-clerodanes and congeners. In addition, the synthesis of two key degradation products of ilimaquinone, which can serve as trans-clerodane precursors, and 4,4-ethylene-dioxy-9α-(2-hydroxyethyl)-5β, 8β,9β-trimethyl-trans-decalin, an intermediate employed earlier in a total synthesis of (±)-annonene, are described.