5-Pyrenylidene-hydantoin, 2-thiohydantoin derivatives: synthesis,S- and N-alkylation

5-Pyrenylidene-2-thiohydantoin derivatives 2a–d were prepared by condensation of pyrene-1-carboxaldehyde with 2-thiohydantoin derivatives. Compounds 2a,b undergo Mannich reaction with formaldehyde and morpholine to give the corresponding Mannich products 3a,b respectively. S- and N-monoalkyl-5-pyrenylidene-hydantoin derivatives 5a,b and 6a,b were prepared by reaction of 5-pyrenylidene-2-thiohydantoin sodium salts with 1,3-dioxolan-methylsulfate derivatives. Deprotection of the products afforded 5-pyrenylidene-hydantoin (7), S- and N-dihydroxy derivatives 8a,b and 9a,b respectively. Reaction of 2a with methyl iodide afforded the corresponding S-methyl derivative 10, which reacted with secondary amines such as morpholine and piperidine afforded the glycocymidine derivatives 11a,b. Reaction of 2a with (2,3,4,6-tetra-O-acetyl-α-? D-glucopyranosyl)bromide afforded a mixture of S- and N-glucoside derivatives 12 and 13 respectively. Deprotection of 12 afforded compound 7, while deprotection of 13 furnished 5-Pyrenylidene-3-? D-glucopyranosyl-2-thiohydantoin (14). Reaction of 7 with propargyl chloride in DMF afforded the monoalkynyl- and bis-alkynyl-hydantoin derivatives 15 and 16, respectively. Reaction of 15 with p-bromophenyl-ether derivative 17 yielded the bis-alkynyl derivative 18.     

Synthesis and application of some new oxazole derivatives as antimicrobial agents

5-(p-Acetylphenyl)-2-phenyloxazole ( I ) was condensed with aromatic aldehydes to furnish chalcones 2a-e . Cyclocondensation of 2a-e with hydrazine hydrate and with phenyl hydrazine led to the formation of pyrazoline derivatives 3a-e and 4a-e respectively. Similarly, 2a was interacted with hydroxylamine to give isoxazoline ( 5 ). On the other hand, condensation of 1 with phenyl hydrazine yielded hydrazone 6 which on treatment with Vilsmeier reagent (DMF/POCl₃) gives 5-[p-(4-formyl-1-phenylpyrazol-3-yl)phenyl]-2-phenyloxazole ( 7 ). Also, a few derivatives of 7 have been prepared. Moreover, all compounds were screened for their antimicrobial activity against some strains of bacteria and fungi.     

Synthesis of Optically Active 4-Hydroxypyrazolidin-3-ones as precursors for β-amino-α-hydroxycarboxylic acid derivatives

The cis or trans-glycidic esters 1 or 7 give ring transformations with hydrazines affording optically active 4-hydroxypyrazolidin-3-ones 3 and 4 or 6 or 9 and 10 , respectively, in different regioselectivities. 4-Hydroxypyrazolidin-3-ones 3 and 9 can serve as precursors for enantiomerically pure β-amino-α-hydroxycarboxylic acid amides 5 and 11 by hydrogenation in the presence of Raney-Ni.     

Stereospecific synthesis ofcis andtrans fatty esters

Theerythro andthreo isomers of methyl 9,10-dihydroxyoctadecanoate and thethreo isomer of methyl 12,13-dihydroxy-cis-9-octadecenoate were converted into methylcis- andtrans-9-octadecenoate and methylcis-9,rans-12-octadecadienoate, respectively, by reaction of the dihydroxy ester with triethyl orthoformate to give the 2-ethoxy-1,3-dioxolane which was thermally decomposed to the unsaturated ester.     

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.     

(Z)-7-Tricosene and Monounsaturated Ketones as Sex Pheromone Components of the Australian Guava Moth Coscinoptycha improbana: Identification, Field Trapping, and Phenology

Pheromone gland extracts of the Australian guava moth Coscinoptycha improbana (Lepidoptera: Carposinidae), contained four compounds that elicited responses from male moth antennae in gas chromatography-electroantennogram detection (GC-EAD) analyses. These were identified by GC-mass spectrometry as (Z)-7-tricosene (Z7-23Hy), (Z)-7-octadecen-11-one (Z7-11-one-18Hy), (Z)-7-nonadecen-11-one (Z7-11-one-19Hy), and (Z)-7-tricosen-11-one (Z7-11-one-23Hy) at a ratio of 65:23.5:1.5:10, respectively. Z7-23Hy, Z7-11-one-18Hy, and Z7-11-one-23Hy have not previously been reported as lepidopteran sex pheromone components. Z7-11-one-18Hy was active as a single component, and was synergized by Z7-11-one-23Hy but not Z7-11-one-19Hy, although the latter compound was weakly attractive as a single component. Addition of Z7-23Hy further increased attraction. The amount of the major pheromone component, Z7-11-one-18Hy in female pheromone gland extracts was estimated to be 16.4 ng/female (N = 8). Phenological data gathered over a 12-mo period in 2002 and 2003 using the binary blend indicated that moths are active throughout the year. The pheromone has already been employed to monitor the spread of C. improbana in New Zealand and detect its presence in Queensland, Australia.     

A convenient synthesis of functionalized alkoxyamines as initiators for living free radical polymerization

Summary 2,2,6,6-Tetramethylpiperidine- 1-oxyl (TEMPO) was reacted with ethylbenzene (la), 1-bromo-4-ethylbenzene (lb), and 4-ethylphenyl acetate (lc), respectively, using tert-BuOOWCo(OAc)·4H₂O in acetonitrile at room temperature. The reactions produced the respective TEMPO-adducts (2a, 2b, and 2c) in the yields of 37, 44, and 45 %, which were based on TEMPO. Similarly, TEMPO was reacted with 4-ethylphenyl 2,3,6,2',3',4',6'-hepta-O-acetyl-β-D-cellobioside (1d) to afford the glycoconjugated TEMPO-adduct (2d) in 45 5% yield, which was based on 1d. These results indicated that the reaction has the potential to become an easy and also safe strategy, which provided various functionalized alkoxylamines. Received 20 November 2002/Revised Version: 5 December 2002/ Accepted: 7 December 2002 Correspondence to Naoya Sugimoto     

Synthesis and field screening of chiral monounsaturated epoxides as lepidopteran sex attractants and sex pheromone components

Enantiomerically enriched forms of (Z)-6-cis-9,10-epoxymonoenes and (Z)-9-cis-6,7-epoxymonoenes of chain lengths C_17–20 were synthesized by Sharpless asymmetric epoxidation of allylic alcohol intermediates, followed by tosylation or halogenation and chain extension. The resulting monounsaturated epoxides were field tested as sex attractants for lepidopteran species.Euchlaena madusaria Walker males were attracted to blends of the enantiomers of (Z)-6- cis- 9,10-epoxynonadecene 6Z-cis-9,10-epoxy-19:H; IUPAC name [2,3(Z)]-2-pentyl-3-(2-dodecenyI)oxirane in combination with 6Z,9Z-19: H. The response was antagonized by 9Z-cis-6,7-epoxy-19: H. 6Z,9Z-19: H was tentatively identified in pheromone gland extracts.Xanthotype sospeta Drury male moths were attracted to lures containing 6Z-9S,10R-epoxy-19: H; the response was antagonized by the opposite enantiomer.Pal-this angulalis Hübner males were attracted to 9Z-6S,7R-epoxy-19:H; the opposite enantiomer was antagonistic. 6Z,9Z-19:H and 9Z-cis-6,7-epoxy-19:H and 9Z-cis-6,7-epoxy-19:H were tentatively identified in pheromone gland extracts fromAnacamptodes humaria Guenée females. In field trails, 9Z-6R,7S-epoxy-19:H proved to be the attractive enantiomer, and the response was potentiated by 6Z,9Z-19:H. Mechanisms by which unique chemical communication channels are maintained by each species are discussed.1 Issued as NRCC #32455.     

Chemo-enzymatic synthesis of amino acid-based surfactants

The application of lipases to the synthesis of amino acid-based surfactants was investigated. Low yields (2–9%) were obtained in the acylation of free amino acids, such as l-serine and l-lysine, as well as their ethyl esters and amides with fatty acids, owing in part to low miscibility of the reactants. When the N-carbobenzyloxy (Cbz)-l-amino acids were used in an effort to improve miscibility of the amino acid derivatives with the acyl donor, a dramatic improvement was observed for N-Cbz-l-serine (92% yield) but not for N _α-Cbz- or N _ζ-Cbz-l-lysine (7 and 2% yield, respectively). As an alternative, and efficient synthesis of N _ζ-acyl-l-lysines was developed, based on the regiospecific chemical acylation of copper(II) lysinate. In pursuit of a general route to amino acid-fatty acid surfactants, the utility of a polyol linker was investigated. Thus, the glycerol ester of N _α′ N _ζ-di-Cbz-l-lysine was prepared and evaluated as a substrate for acylation. As expected, this and other glycer-1-yl esters of N-protected amino acids were excellent substrates for lipase-catalyzed acylation. Their reaction with myristic acid in the presence of Novozyme resulted in the regioselective acylation of the primary hydroxyl group of the glycerol moiety to afford the corresponding 1-O-(N-Cbz-l-aminoacyl)-3-O-myris-toylglycerols with conversions of 50–90%. These were readily deprotected to give a range of 1-O-(aminoacyl)-3-O-myristoyl-glycerols with overall yields of 27–71%.     

Highly diastereoselective synthesis of novel polymers via tandem Diels–Alder–ene reactions

Cis -9,10-dihydro-9,10-ethanoanthracene-11-12-dicarboxylic acid anhydride (1) was converted into its amic acid derivative by reaction with L -leucine. The cyclization reaction was carried out in situ using triethylamine to give the succinic imide-acid derivative (2). Compound (2) was converted to the acid chloride (3) by reaction with thionyl chloride. The reaction of acid chloride (3) with isoeugenol (4) was carried out in chloroform and a novel optically active isoeugenol ester derivative (5) was obtained in high yield. 4-Phenyl-1,2,4-triazoline-3,5-dione (PhTD) (6) was allowed to react with compound (5). The reaction is very fast and gives only one diastereoisomer of (7) via Diels–Alder and ene pathways in quantitative yield. Compound (7) was characterized by ¹H NMR, IR, specific rotation and elemental analysis, and was used as a model for the polymerization reactions. The polymerization reactions of compound (5) with bis-triazolinediones (8), (9) were performed in N,N-dimethylacetamide (DMAc) at room temperature. The reactions are exothermic and fast, and give novel optically active polymers. Some physical properties and structural characterizations of these new polymers have been studied, and are reported. © 1999 Society of Chemical Industry     

An efficient synthesis of muscalure from jojoba oil or oleyl alcohol

A four-step synthesis of (Z)-9-tricosene (muscalure), a component of the pheromone of the housefly, from jojoba oil (or three-step from oleyl alcohol) by 3-carbon (or 5-carbon) unit elongation was developed in overall high yield. The sequence of reactions and the purity of the products could be easily followed, with relatively good accuracy, by NMR technique.     

Novel heterocyclic synthesis and investigation on radiation‐grafted low‐density polyethylene with 2‐N‐vinylpyrrolidone

Radiation‐induced graft polymerization of low‐density polyethylene with N‐vinylpyrrolidone, LDPE‐g‐PNVP, was used as a starting material for the synthesis of polyfunctionally substituted heterocyclic products. Thus, LDPE‐g‐PNVP reacts with ylidenemalononitrile derivatives to give the Michael addition products. In multistep reaction, LDPE‐g‐PNVP reacts with N,N‐dimethylformamide dimethyl acetal (DMFDMA), hydrazine hydrate and malononitrile, respectively, to give a hydropyrrolopyridazine derivative. The latter could also be prepared via the reaction of LDPE‐g‐PNVP with DMFDMA, followed by treating with cyanoacetohydrazide. Also, LDPE‐g‐PNVP reacts with malononitrile to give an adduct product, dimer malononitrile derivative 13. The latter reacts with sulfur element to afford the thiophene derivative. Furthermore, this adduct reacts with hydrazine hydrate to isolate the original starting material, LDPE‐g‐PNVP, and aminopyridine derivative. The resulted films were characterized by infrared (IR) spectroscopy, ¹H nuclear magnetic resonance (¹H‐NMR) mass spectroscopy, elemental analysis, swelling behavior, and electron scanning microscope. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2963–2970, 1999     

Large-scale synthesis of methyl cis-9, trans-11-octadecadienoate from methyl ricinoleate

The conjugated linoleic acid methyl cis-9,trans-11-octadecadienoate has been prepared on a large scale from methyl ricinoleate. Methyl ricinoleate was purified from castor esters by a partition method. It was converted to the mesylate, which was reacted with a base (1,8-diazabicyclo[5,4,0]-undec-7-ene) to give a product that contained 66% of the desired ester. Two urea crystallizations produced a product containing 83% methyl cis-9,trans-11-octadecadienoate, the identity of which was confirmed by gas chromatography linked to mass spectrometry and by Fourier transform infrared spectroscopy. The remaining impurities were methyl cis-9,cis-11- and cis-9-,trans-12-octadecadienoate.     

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.     

Nitriles in heterocyclic synthesis. Part III: New sulpha drugs related to cyanopyridine derivatives

4-Hydroxyacetophenone (1) was reacted with cinnamonitrile derivatives (2–6) to give 3-cyano-4-(substituted phenyl)-6-(p-hydroxyphenyl)-pyridines (7–11). Interaction of compounds 7–9 with 4-substituted heterocyclo-benzenesulphonyl diazoniura chloride gave the corresponding 3-cyano-4-(sub-stituted phenyl)-6-(3′-azobenzene sulphonamido-4′-hydroxyphenyl) pyridines (12–29). The corresponding iron (III) copper (II) and mercury (II) chelates were also prepared in a 1:2 metal-to-ligand ratio. All the synthesized compounds were characterized on the basis of microanalysis, IR and ¹H-NMR spectrometry.     

An efficient and novel method for the synthesis of cardiolipin and its analogs

A novel synthetic method has been developed for cardiolipin and its analog via a chlorophosphoramidite coupling reaction followed by oxidation. The reagent, N,N-diisopropylmethylphosphoramidic chloride, couples effectively with 1,2-O-dimyristoyl-sn-glycerol in the presence of an amidite activator to form a phosphoamidite intermediate, which then reacts with 2-O-benzylglycerol in the presence of a basic catalyst followed by in situ oxidation to give the corresponding protected cardiolipin. Deprotection of the protecting groups provides tetramyristoyl cardiolipin in good overall yield of 60%. The synthetic method is applicable to large-scale synthesis of cardiolipin and various analogs with or without unsaturation for liposomal drug delivery. Presented at the 94th AOCS Annual Meeting & Expo, Kansas City, Missouri, May 4–7, 2003.     

Palladium nanoparticles as reusable catalyst for the synthesis of N-aryl sulfonamides under mild reaction conditions

An efficient palladium nanoparticles-catalyzed N-arylation of sulfonamides and sulfonyl azides is described. This procedure serves as an active protocol for intermolecular C–N bond formation using Pd(OAc)₂ in PEG-400 under air. Aryl bromides and triflates react at 35°C, while aryl chlorides require heating to 50°C and give the desired products only in low yields. This reaction proceeds smoothly in acceptable yields using low catalyst loading.     

Carboxymethylcellulose synthesis in organic media containing ethanol and/or acetone

A study of the carboxymethylation of wood pulp cellulose and cotton linters cellulose in different organic media, namely, ethanol, acetone, and ethanol-acetone mixtures, is performed. Previously, the ethanol-acetone 1 : 1 (w/w) mixture used as reaction medium was found to give a higher degree of substitution (DS) than the pure solvents separately. In the present work, the kinetic investigation of cellulose carboxymethylation was carried out in ethanol-acetone 3 : 7 (w/w) mixture, as well as in acetone as reaction media, and the same synergistic effect of the solvents mixture was observed. The data suggested a pseudo-first-order kinetic behavior satisfactorily described by the following equation: ln(1.11 − DS) = −kt. The two reaction steps observed are related to the transformations of less ordered regions with higher reaction rate and more ordered regions with smaller reaction rates, respectively. A possible explanation for this behaviour is given, taking into account the different structural changes of cellulose crystallinity and accessibility produced by ethanol-acetone 3 : 7 (w/w) mixture, ethanol, and acetone, as revealed by X-ray diffraction and calorimetry determinations. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 67: 481–486, 1998     

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.

     

Stereoselective Synthesis and Binding Properties of Novel Concave‐Shaped Indolizino[3,4‐b]quinolines

Novel all‐cis‐configurated indolizino[3,4‐b]quinoline receptors 3, 4 were prepared via diastereoselective Lewis acid‐catalyzed cyclization of N‐arylimines 6, 7 as the key step. In order to obtain the indolizino[3,4‐b]quinoline derivative 21 without a gem‐dimethyl group at C‐7, an N‐arylimine precursor 18 bearing a vinyldisilane terminus was prepared in 8 steps from L‐prolinol 15 . In contrast to the known β‐effect of silyl groups cyclization of 18 proceeded via an α‐carbenium ion species to give the diastereomeric products 19, 20, which were desilylated to 21, 22 . The association constants for receptors 2 — 4 and 21 decreased in the order 21 > 2 > 4 > 3 for both acetic acid and N‐Z‐phenylalanine as substrates.