Bis-(cyanoacetamide)alkanes in heterocyclic synthesis: synthesis of bis-heteryl(carboxymido)alkanes and bis-(heteryl)alkanes of thiophene,pyrrole, thiazole and pyrimidinone series

Bis-N-substituted cyanoacetamides 3a and b reacted with active methylene-containing compounds 2a–c and elemental sulfur to give bis-thiophene 4a and b and bis-pyrrole 6a and b derivatives. Compounds 4a and b reacted with ethyl cyanoacetate 2a to afford bis-thienopyrimidine derivatives 5a and b; on the other hand, 6a and b reacted with cyanothioacetamide 2c to give the corresponding bis-thioxopyrrolopyrimidine derivatives 7a and b. Compounds 7a and b reacted with methyl iodide to give the corresponding bis-2-S-methylpyrrolopyrimidine derivatives 8a and b, which could be, in turn, cyclized into the bis-pyrazolopyrrolopyrimidine derivatives 9a and b by refluxing with hydrazine hydrate. On the other hand, 7a and b reacted with ethyl chloroacetate to yield the corresponding bis-thienopyrrolopyrimidine derivatives 10a and b. Finally, compounds 3a and b reacted with phenylisothiocyanate and elemental sulfur to give the corresponding bis-2-thioxoaminothizole derivatives 11a and b.     

Towards near-IR emissive rhenium tricarbonyl complexes: Synthesis and characterisation of unusual 2,2′-biquinoline complexes

Diethyl-2,2′-biquinoline-4,4′-dicarboxylate (debq) reacts with pentacarbonylbromorhenium in toluene to give fac-[Re(CO)₃(debq)Br]; subsequent reaction with AgOTf in MeCN affords the cationic complex fac-[Re(CO)₃(debq)(MeCN)]OTf. X-ray crystallographic data on fac-[Re(CO)₃(debq)Br] show that the debq ligand is coordinated in a bidentate fashion at an angle of 32° from the equatorial plane of the complex: DFT calculations confirm this as the lowest energy conformation. fac-[Re(CO)₃(debq)Br] and fac-[Re(CO)₃(debq)(MeCN)]OTf both possess ¹MLCT absorptions in the visible region, the former most red-shifted to ca. 465 nm. Both complexes demonstrated unusual luminescent properties: in solution, emission appears to be dominated by ligand-centred processes, whereas only ³MLCT emission, tailing into the near-IR, was observed in the solid state at 671 (τ = 59 ns) and 711 nm (τ = 19 ns) for fac-[Re(CO)₃(debq)(MeCN)]OTf and fac-[Re(CO)₃(debq)Br], respectively. However, the debq ligand is not labile in these complexes, which are robust to competing ligands and coordinating solvents.     

Synthesis and derivatization of angular 3-chloro-3-chlorosulfenyl naphtho[1,2-b]pyran(4H)-4-ones with evaluation of antiviral activity

Angular 2,3-dihydronaphtho[1,2-b]pyran(4H)-4-ones 1a,b react with an excess of thionyl chloride to give the α-chlorosulfenyl chlorides 2a,b, which are reduced by iodide ion to give the corresponding 1,3,4-oxadithiino derivatives 3a,b. However, the aducts 4a,b and 5a,b were obtained by reduced 2a,b with iodide ion in the presence of 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene, respectively. Direct oxidation of 2a,b afford 3,3-dichloronaphthopyran-4-ones 6a,b, whilst conversion to the sulfenamides 7a,b prior to oxidation provides 3-chloronaphthopyranones 8a,b. While α-chloro β-oxo sulfenyl chlorides 2a,b undergo straight forward substitution with 1-methylpiperazine and with potassium cyanide to give 9a,b and 10a,b, respectively. Some of the prepared products were selected and tested for their antiviral activity against herpes simplex virus type-1 (HSV-1). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with test compounds. Compound 5a showed moderate effect against HSV-1.     

Unsaturated sulfur compounds from reactions of lithiated methylazines with carbon disulfide and electrophiles

2-Methylpyridine (1a), 2,6-dimethylpyridine (1b), 2-methylpyrazine (1c) and 2-methylquinoline (1d) were treated with lithium diisopropylamide (LDA) in THF at low temperature followed by carbon disulfide to give the dianion (5). Reactions of dianion (5) with iodomethane, 1,2-dibromoethane, ethyl chloroacetate, α -chloroacetonitrile or phenacyl bromide gave 6a–c, 6e, 9, 10, 11, 12 and 13, respectively. Reactions of dianion (5) with 1,2-dibromoethene gave the dithiocarboxylic acids (14a–c) rather than a dithiolene, and reaction of dianion (5a) with aqueous ammonium persulfate gave 15. Treatment of 2-methylpyridine (1a) with lithium diisopropylamide (LDA) and 2-bromopyridine afforded tetra-2-pyridylmethane (18) as the main product.     

Ketene N,S-acetals in heterocyclic synthesis: Part 1: Synthesis of N-phenyl-2-ylidene and 2,5-diylidene-4-thiazolidinone derivatives

Ketene N,S-acetal potassium salts (2a–g), prepared via reaction of active methylenes (1a–g) with phenyl isothiocyanate in the presence of potassium hydroxide, were allowed to react with ethyl chloroacetate or chloroacetamide to afford the corresponding 2-ylidene-4-thiazolidinones (3a–g) in good yields. Compounds (3a–g) reacted with a variety of aromatic aldehydes to afford the corresponding 5-arylidene-2-ylidene-4-thiazolidinone derivatives (10a–e). Reaction of compound (3a) with triethylorthoformate afforded 5-ethoxymethylene-2-ylidene-4-thiazolidinone derivative (7), which was allowed to react with ammonia or phenyl hydrazine to give the corresponding enamino or hydrazino derivatives (8a) or (8b), respectively.     

Monomers for adhesive polymers, 17.a Synthesis,photopolymerization and adhesive properties of polymerizable phosphonic acids bearing urea groups

Four polymerizable phosphonic acids bearing urea groups 4a, 4b, 9a, and 9b as well as the 10-(methacryloyloxy)decylphosphonic acid 10 were synthesized in four to six steps. They were characterized by ¹H, ¹³C, and ³¹P NMR spectroscopy and by high-resolution mass spectroscopy. Contrary to methacrylates 4a and 4b, methacrylamides 9a and 9b were hydrolytically stable in deuterated water/deuterated ethanol solutions. The photopolymerization behavior of acidic monomers 4a, 4b, 9a, 9b, and 10 and their corresponding phosphonates were studied using a differential scanning calorimeter. Homopolymerizations and copolymerizations with N-butyl-N-ethylacrylamide were carried out. The presence of a urea group was found to significantly increase the rate of polymerization. Monomers bearing a phosphonic acid group were more reactive than their corresponding phosphonates. Self-etch adhesives based on monomers 4a, 4b, 9a, and 9b were able to provide a strong bond between a composite and the dental hard tissues (dentin and enamel). The presence of a urea group led to a significant increase in the shear bond strength to both dentin and enamel.     

β-Aminocrotononitrile in heterocyclic synthesis: Synthesis of polysubstituted pyridines as precursors to bicycles and polycycles

β-aminocrotononitrile (1) reacted with either cyanothioacetamide to give (3) or malononitrile to afford an anion (5). Pyridine-2(1H)-thione (4) was obtained by boiling of (3) in ethanol and Et ₃N or treatment of (5) with H ₂S, respectively. The reaction of anion 5 with isothiocyanates (6) gave N-substituted pyridine-2(1H)-thiones (7). N-Substituted pyridine-2(1H)-thiones (7) can be used for the preparation of pyrido[2,3-d]pyrimidines (8a–e) and (10a–e), or the preparation of pyrido[1,2-a]pyrimidines (12a–d). 1,8-Naphthyridine derivatives (14a–d) and (16a–e) can also be obtained from pyridine-2(1H)-thione (7). Finally, 1,8-naphthyridine derivatives (16a–e) can be used for the preparation of tetracyclic compounds 17a–c and 18a,b.     

Glycerol esters from the reaction of glycerol with dicarboxylic acid esters

Mono- and di-esterified glycerols were synthesized by the base catalyzed reaction of glycerol with aliphatic dicarboxylic acid esters (C₂−C₉): 2,3-dihydroxy-propyl oxalate (2), 1,3 dioxalyloxy propan-2-ol (3), 1,3-dimethoxyoxalyloxy propan-2-ol (5), 2,3-dihydroxy-propyl malonate (6), 2,3-dihydroxy-propyl methyl malonate (7), 2,3-dihydroxy-propyl methyl succinate (8), 1,3-dimethoxysuccinyloxy propan-2-ol (9), 2,3-dihydroxy-propyl methyl glutarate (10), 1,3-dimethoxyglutaryloxy propan-2-ol (11), 2,3-dihydroxy-propyl methyl azelate (14), and 1,3-dimethoxyazelyloxy propan-2-ol (15). Their structures were elucidated by spectrometric methods. Compounds 8, 10, 2,3-dihydroxy-propl methyl adipate (12) and 14 were found to possess surface active properties and the ability to reduce the interfacial tension between paraffin and water.     

Pyridine-2(1H)-thione in heterocyclic synthesis: synthesis and antimicrobial activity of some new thio-substituted ethyl nicotinate,thieno[2,3-b]pyridine and pyridothienopyrimidine derivatives

3-(4-Bromophenyl)-2-cyanoprop-2-enethioamide (1) reacted with ethyl 3-oxo-3-phenylpropanoate (2) to give ethyl 4-(4-bromophenyl)-5-cyano-2-phenyl-6-thioxo-1,6-dihydropyridine-3-carboxylate (3). Compound 3 was taken as a starting material for the synthesis of thio-substituted ethyl nicotinate derivatives 5a–d, which underwent cyclization to the corresponding thieno[2,3-b]pyridines 6a–d. Also 3 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 7, which upon diazotization gave the diazonium derivative 8. Compound 6a condensed with dimethylformamide–dimethylacetal to afford thieno[2,3-b]pyridine derivative 9, which reacted with different amines 10a–e to afford the pyridothienopyrimidine derivatives 12a–e through the Dimroth rearrangement. Moreover, compound 6a reacted with different reagents to give pyridothienopyrimidine derivatives 14a and b, 17 and pyrazolothienopyridine derivative 18. In addition, acetylating compound 6c with chloroacetylchloride afforded the 3-[(2)-chloroacetylamino]thieno[2,3-b]pyridine derivative 20, which upon cyclization yielded the corresponding 2-chloromethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivative 21. Some of the newly synthesized compounds were screened in vitro for their antimicrobial activities.

     

Desulfurization of aromatic polysulfides with triphenylphosphine

The room temperature reaction of bis(4-methylbenzene) di- (3), tri- (4) and tetrasulfide (5) with triphenylphosphine has been followed by ¹H NMR. Mechanistic aspects of the cleavage of 3 and the desulfurization of 4 and 5, with concomitant formation of triphenylphosphine sulfide, are discussed. While tetrasulfide 5 is desulfurized over 10× faster than trisulfide 4, preliminary experiments indicate that 5 is not sufficiently reactive to efficiently transfer a sulfur atom to oligodeoxyribonucleotides.     

Facile synthesis and characterization of novel bis(2-S-alkylpyridines) and bis(3-aminothieno[2,3-b]pyridines) incorporating 1,3-diarylpyrazole moiety

3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1) is condensed with acetophenone to afford the corresponding unsaturated carbonyl compound 4 whose potassium salt is reacted with 1,4-dibromobutane to afford the bis-unsaturated carbonyl compound 3. Both carbonyl compounds 3 and 4 are reacted with 2-cyanoethanethioamide, through Michael addition reaction followed by cyclocondensation, to prepare the starting materials bis(pyridine-2(1H)-thione) derivative 5 and pyridine-2(1H)-thione derivative 8. Two synthetic routes to synthesize the target materials 7 and 14 are described to get the most efficient method for preparation and maximum yield%. The first route came from the direct alkylation of the bis(pyridine-2(1H)-thione) derivative 5 using iodomethane (6a) and benzyl chloride (6b) to afford the corresponding bis(2-S-alkylpyridine) derivatives 7a,b. The reaction of 5 with halo-containing compounds 10a–d to synthesize the target materials bis(3-aminothieno[2,3-b]pyridine) derivatives 14a–d failed under various reaction conditions. The second route involves the reaction of pyridine-2(1H)-thione derivative 8 with 6a,b and 10a–d to afford the corresponding 2-S-alkylpyridine derivatives 9a,b and 3-aminothieno[2,3-b]pyridine derivatives 13a–d, through the formation of 2-S-alkylpyridine derivatives 12a–d followed by a Thrope-Ziegler reaction, whose potassium salts reacted with 1,4-dibromobutane to afford the corresponding target materials 7a,b and 14a–d, respectively. The structures of target molecules were elucidated using elemental analyses and spectral data.     

Reactivity of N-thioamido amidines with halogenated alkyl derivatives: synthesis of 4,5-disubstituted 2-alkylaminothiazoles

2-Bromoacetate ethyl ester 4, 2-chloroacetonitrile 5, 2-bromo-1-(4-nitrophenyl)ethanone 6, and 2-chloroacetone 7 react with N-thioamido amidines 3 to yield the corresponding 4,5-disubstituted 2-alkylamino thiazoles 8, 9, 10, and 11 after the release of an amine molecule. The reaction of the amidines 3 with benzyl bromide 12, 4-chlorobutyronitrile 13, 3-bromopropionate ethyl ester 14, 3-chloropropionate ethyl ester 15, and 4-nitrobenzyl chloride 16 does not lead to the cyclic derivatives but gives opened-ring intermediates 17, 18, 19, 20, and 21. The cyclization mechanism is discussed on the basis of the study of the opened-ring intermediates which have been isolated in some cases and the AM1 and PM3 semi-empirical energetic calculations.     

Oxyfunctionalization of novel diaryl- and triaryl-isothiazolium salts: the first isolable crystalline 3-hydroperoxyisothiazole

The synthesis of novel monocyclic di- and triphenyl-substituted hydroperoxysultims rac-cis 7 and 8 and sultams 11 and 12, as well as the 3-oxosultams 15 and 16, by oxidation of corresponding salts 1 and 2 with H₂O₂ in acetic acid is described. For the first time, it was possible to isolate a 3-hydroperoxide (3a) and also to determine the position of the primary oxidizing attack on the C-3 atom of isothiazolium salts 1, which have generally a much lower oxidation reactivity. Novel 3-hydroxysultams 13 and 14 were obtained by oxidation reaction of salts 1 and 2 with magnesium monoperoxyphthalate (MMPP) in acetonitrile in the ultrasound bath.     

Stochastic Ordering in the Qualitative Assessment of the Performance of Simultaneous Schemes for Bivariate Processes

Abstract

Misleading signals (MS) are likely to happen while using a simultaneous scheme to control the mean vector (μ) and the covariance matrix (Σ) of a bivariate process. They correspond to valid signals that lead to a misinterpretation of a shift in μ (resp. Σ) as a shift in Σ (resp. μ). Following previous work, focused on the quantitative assessment of the probabilities of misleading signals (PMS) in simultaneous schemes for bivariate processes, we now make use of stochastic ordering to qualitatively assess the impact of changes in μ and Σ in those probabilities.     

Antitermitic Activities of Abietane-type Diterpenes from <Emphasis Type="Italic">Taxodium distichum</Emphasis> Cones

Eight known abietane-type diterpenes were isolated from the weak acidic fraction of the n-hexane extract from cones of Taxodium distichum, one of the extant, living fossil conifers. They were identified as 6,7-dehydroroyleanone (1), taxodal (2), taxodione (3), salvinolone (4), 14-deoxycoleon U (5), 5,6-dehydrosugiol (6), sandaracopimaric acid (7), and xanthoperol (8). The structures of these compounds were determined by comparison of NMR spectral data with published data. The antitermitic (termicidal and antifeedant) activities of the compounds 1–8 against the subterranean termite, Reticulitermes speratus Kolbe, were evaluated. Compounds 1 and 3 showed potent termicidal activity, and 5 and 8 showed potent antifeedant activity. Compound 1 was found to be one of the representative bioactive compounds in the n-hexane extract of T. distichum cones. Compounds 1–8, with the exception of 7, were oxides of ferruginol (9). Therefore, the presence of various oxidation forms of the abietane-type structure reflects their various bioactivities.     

Alternate poly(amide-imide)s based on 1,4-and 1,3-bis(4-trimellitimido)benzene and their mixtures

Several series of alternate poly(amide-imide)s [P(A-alt-I)s] were synthesized by aromatic dicarboxylic acid (I- p or I- m), which was prepared by the condensation of p-phenylenediamine (or m-phenylenediamine), trimellitic anhydride, and various aromatic diamines by means of direct polycondensation. A diimide-diacid (I- p) with a p-phenylene group was used to synthesize P(A-alt-I)s III, and P(A-alt-I)s IV were synthesized by a diimide-diacid (I- m) prepared from m-phenylenediamine. Another series of P(A-alt-I)s V was synthesized from both I- p and I- m (1/1 mole) with various diamines. Polymers of series III have low inherent viscosities and limited solubility, but polymers of series IV have high degrees of polymerization. Series V copolycondensated from I- p and I- m has improved solubility and degrees of polymerization relative to series III. The degree of crystallinity was found to be III > V > IV. Glass transition temperatures for most of series III were not observed below 400 °C, and those of series IV and V were in the range of 238–325 °C and 262–328 °C, respectively. The 10% weight loss temperatures in nitrogen or in air of these three series are all in the range of 482–582 °C. Because series V has limited solubility for casting into films from DMAc solutions, two diamines were selected to synthesize series VI by changing the I- p/I- m ratio. Solubility was improved when the content of I- p in diimide-diacid was less than 15%, and the degree of crystallinity reduced as the content of I- p in diimide-diacid decreased. Polymers containing a few I- p showed an increase in the initial modulus.     

Synthesis and biological activity of some more heterocyclic compounds containing benzothiophene moiety

3-Chloro-1-benzothiophene-2-carbonylchloride 1 was allowed to react with hydrazine hydrate to give carbohydrazide 2. The reaction of 3-chloro-1-benzothiophene-2-carbohydrazide 2 with potassium thiocyanate gave compound 3, which was cyclized to form thioxotetrahydropyrimidine 4, thiazoles 5a–e, triazoles 7a–e and oxadiazoles 10a–h. The structures of all the synthesized compounds were confirmed by spectral data and have been screened for antimicrobial, analgesic and anthelmintic activities.

     

Fatty Acids in Heterocyclic Synthesis Part XII: Synthesis of Surfactants from Pyrazole, Isoxazole, Pyrimidine and Triazine, Incorporating the 1,3,4-Thiadiazole Moiety Having Dyeing and Antimicrobial Activities

The titled compounds were prepared from 2-amino-5-heptadecyl[1,3,4]thiadiazole (1). Diazotization of (1) produced (2) which was coupled with active methylene compounds and gave azo ⇌ hydrazono derivatives (3A, 3B) _a–d . It was found that there is regio-specificity for addition of different nucleophiles to these tautomers; thus, nitrogen nucleophiles such as hydrazine hydrate, hydroxylamine hydrochloride and thiourea were reacted via Azo tautomer (3A) to yield pyrazole, isoxazole and pyrimidine respectively (5-7), while carbon nucleophiles as phenylisocyanate was reacted via the hydrazono tautomer (3B) and produced triazine derivatives (4). Additionally, the diazonium chloride (2) was coupled with alkaline 2-naphthol and produced 2-(5-heptadecyl-[1,3,4]thiadiazol-2-yl)-1,2-dihydro-3-oxa-1,2-diaza-cyclopenta[a]naphthalene (8). UV–visible spectra of the synthesized colored compounds (2-8) showed λ _max at 374–398 nm, while screening these compounds in vitro against micro-organisms (including structure-activity relationship SAR study) revealed high antibacterial and moderate antifungal activities. Propoxylation of compounds 1, 3, 5, 6, 7 and 8 with 3, 5, 7 mol of propylene oxide produced nonionic surfactants I(a–c)–IX(a–c) having surface active properties so, it is clear that the tested surfactants can be used in the manufacture of dyes, drugs, cosmetics, emulsifiers, pesticides, luminphores for optical applications and many other industries with low toxicity to human beings and the environment owing to their high solubility and good biodegradability.     

Synthesis of polyfunctionally substituted pyridine-2-(1H)-thiones containing a sulfone moiety

1-Phenyl-2-(phenylsulfonyl)ethanone (1) reacts with DMFDMA to give enamine 2, which upon treatment with cyanothioacetamide affords 3-cyano-5-benzenesulfonyl-4-phenylpyridine-2(1H)-thione (4), a compound that can also be obtained by the reaction of 1-benzenesulfonyl-1-benzoyl-2-ethoxyethene (3) with cyanothioacetamide. The reaction of 2-thiocarbamoylacetamide (8a) and N-phenyl-2-thiocarbamoylacetamide (8b) with 3-aryl-2-benzenesulfonylacrylonitrile (9a– c) affords 10a–f. The methylation of 10d–f with methyl iodide results in the formation of S-methyl derivatives (12a–c). Compound 12c can be obtained by the reaction of 13 with 9c.     

Air Quality Profile of Inorganic Ionic Composition of Fine Aerosols at Two Sites in Mumbai City

The levels of PM ₁₀ , PM _2.5 , and NO ₂ were studied at a kerbsite and ambient site in Mumbai. Measurements were also made for eight inorganic ions (F ^? , Cl ^? , NO ₃ ^? , SO ^2? ₄ , Na ⁺ , K ⁺ , NH ₄ ⁺ , Ca ²⁺ , and Mg ²⁺ ) in the PM _2.5 fraction. During the study period, PM _2.5 , PM ₁₀ and NO ₂ levels ranged between 11–91, 18–125, and 8–64 μ g m ^{? 3} at a ambient site whereas at the kerbsite the ranges were 10–176, 21–189, and 4–55 μ g m ^?3 respectively. Average PM _2.5 values were 42 μ g m ^{? 3} at ambient and 69 μ g m ^?3 at the kerbsite. The measured ions accounted for about 50% of the PM _2.5 mass. Non-sea-salt (nss) sulfate contributed 91% and 85% of the ionic mass at the ambient and kerbsite sites respectively. Due to biomass sources of K, only about 5% of K ⁺ was from seas salt. The average equivalent ratio of NH ₄ ⁺ to nss- SO ² ₄ ^? , and NO ₃ ^? was over 1, indicating high source strength of ammonia.