Amino Acid Derivatives,V [1]: Synthesis and Antiviral Evaluation of α-Amino Acid Esters Bearing an α-<Emphasis Type="SmallCaps">d</Emphasis>-Mannofuranoside Side Chain

Summary. d-Mannose was treated with dry acetone in the presence of conc. H₂SO₄ to afford 2,3:5,6-di-O-isopropylidene-α-d-mannofuranoside. Treating the latter with ethyl chloroacetate gave carboethoxymethyl 2,3:5,6-di-O-isopropylidene-α-d-mannofuranoside, which was hydrolyzed with N₂H₄ · H₂O to afford the acid hydrazide derivative. Treating of the acid hydrazide with acylated amino acides, via the azide-coupling method afforded the corresponding O-glycopeptides. Reaction of the glycopeptide methyl esters with N₂H₄ · H₂O afforded the corresponding hydrazides, which were coupled with the amino acid methyl esters to afford the dipeptides. Deprotection was carried out by using 70% AcOH. The prepared O-glycopeptides were tested for antiviral activity against hepatitis B virus and showed moderate activities.     

Amino Acid Derivatives, V [1]: Synthesis and Antiviral Evaluation of α-Amino Acid Esters Bearing an α-d -Mannofuranoside Side Chain

d-Mannose was treated with dry acetone in the presence of conc. H₂SO₄ to afford 2,3:5,6-di-O-isopropylidene-α-d-mannofuranoside. Treating the latter with ethyl chloroacetate gave carboethoxymethyl 2,3:5,6-di-O-isopropylidene-α-d-mannofuranoside, which was hydrolyzed with N₂H₄ · H₂O to afford the acid hydrazide derivative. Treating of the acid hydrazide with acylated amino acides, via the azide-coupling method afforded the corresponding O-glycopeptides. Reaction of the glycopeptide methyl esters with N₂H₄ · H₂O afforded the corresponding hydrazides, which were coupled with the amino acid methyl esters to afford the dipeptides. Deprotection was carried out by using 70% AcOH. The prepared O-glycopeptides were tested for antiviral activity against hepatitis B virus and showed moderate activities.     

Diarylmethyl ethers and Pd salts or complexes: a perfect combination for the protection and deprotection of alcohols

Primary and secondary alcohols are easily protected as diphenylmethyl (DPM) or bis(methoxyphenyl)methyl (BMPM) ethers in good yield using PdCl₂(CH₃CN)₂ as catalyst in dichloroethane at 60 or 20 °C, respectively. These conditions are compatible with other functional and protecting groups such as halides, esters, acetal, benzyl, para-methoxybenzyl, benzyloxycarbonyl, and tert-butyldiphenylsilyl. Good selectivity was observed in favor of primary over secondary alcohols. Deprotection of diphenylmethyl or bis(4-methoxyphenyl)methyl ethers was efficiently achieved at room temperature using PdCl₂(CH₃CN)₂ in dichloroethane in the presence of 10 equiv of ethanol.     

Solvent effects of pyridine on the NMR spectra of carboxylic acids. I—study of the acrylic,trans-crotonic and 3-butenoic acids

Proton magnetic resonance spectral parameters of acrylic, trans-crotonic and 3-butenoic acids, their methyl esters and the corresponding alcohols (COOH substituted by CH₂OH) have been measured for 5% (w/v) solutions in carbon tetrachloride and in pyridine-d₅ at 33·5 °C. The total solvent effect of pyridine on the shifts of the skeleton protons of the acid was found to consist of three different effects independently measured from the reference samples.     

Some approaches to the synthesis of fluorine-containing alcohols and esters

Among F-containing alcohols only trifluoroethanol, the so-called ‘telomer alcohols’ [H(CF₂CF₂)_nCH₂OH], and certain esters of 2-(F-alkyl)ethanols and 3-(F-alkyl)propanols, have achieved commercial importance. Their utilization has been limited by lack of suitable methods of synthesis and by their high cost. Yet F-containing alcohols and their esters have unique properties, and comprise a versatile class of compounds. It is to be noted that completely fluorinated esters have recently become available.F-substituted alcohols must be made by special, less well-known methods. Routes based on tetrafluoroethylene (TFE) as starting material are of current interest. F-alkyl iodides (R_FI) are made in two steps from TFE. Reaction of R_FI with ethylene gives 2-(F-alkyl)-1-ethanes, and under suitable conditions, higher telomers in high yield. Displacement of iodine of R_FCH₂CH₂I by an acyloxy group gives an ester, such as acrylate or fumarate of the F-substituted alcohol. Several methods have been discovered for this process, most recently by reaction with N-methylformamide or N,N-dimethylformamide and water. Free radical addition of R_FI to vinyl acetate and subsequent reduction provided 2-(F-alkyl)ethanols in excellent yield. Similar steps using allyl acetate gave both 3-(F-alkyl)-1-propanols and 3-(F-alkyl)-2-propanols; the latter compound also was formed by hydrolysis of the initial adduct. These various methods will be outlined and some recent results in a study of O-alkylation will be presented.Support by the Central Research Group, Ciba-Geigy Corp., Ardsley, N.Y. is gratefully acknowledged.     

Preparation and Structural Characterization of [CpRu(1,10-phenanthroline)(CH3CN)][X] and Precursor Complexes (X=PF6, BArF,TRISPHAT-N)

Cationic [Ru(η⁵-C₅H₅)(CH₃CN)₃]⁺ complex, tris(acetonitrile)(cyclopentadienyl)ruthenium(II), gives rise to a very rich organometallic chemistry. Combined with diimine ligands, and 1,10-phenanthroline in particular, this system efficiently catalyzes diazo decomposition processes to generate metal-carbenes which undergo a series of original transformations in the presence of Lewis basic substrates. Herein, syntheses and characterizations of [CpRu(Phen)(L)] complexes with (large) lipophilic non-coordinating (PF₆⁻ and BAr_F⁻) and coordinating TRISPHAT-N⁻ anions are reported. Complex [CpRu(η⁶-naphthalene)][BAr_F] ( [1][BAr_F] ) is readily accessible, in high yield, by direct counterion exchange between [1][PF₆] and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBAr_F) salts. Ligand exchange of [1][BAr_F] in acetonitrile generated stable [Ru(η⁵-C₅H₅)(CH₃CN)₃][BAr_F] ( [2][BAr_F] ) complex in high yield. Then, the desired [CpRu(Phen)(CH₃CN)] ( [3] ) complexes were obtained from either the [1] or [2] complex in the presence of the 1,10-phenanthroline as ligand. For characterization and comparison purposes, the anionic hemilabile ligand TRISPHAT−N (TTN) was introduced on the ruthenium center, from the complex [3][PF₆] , to quantitatively generate the desired complex [CpRu(Phen)(TTN)] ( [4] ) by displacement of the remaining acetonitrile ligand and of the PF₆⁻ anion. Solid state structures of complexes [1][BAr_F] , [2][BAr_F] , [3][BAr_F] , [3][PF₆] and [4] were determined by X-ray diffraction studies and are discussed herein.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. X. synthesis of 5-substituted ethyl or methyl 4-isoxazolecarboxylates and methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with hydroxylamine hydrochloride in methanol solution afforded in high yields the relative esters of 5-substituted 4-isoxazolecarboxylic acids II . These esters were hydrolyzed generally with concentrated hydrochloric acid-acetic acid mixtures to the corresponding carboxylic acids in satisfactory yields. Ethyl or methyl esters II isomerized with sodium ethoxide or methoxide, respectively, to the corresponding esters or hemiesters of 2-cyano-3-oxoalkanoic acids generally in excellent to satisfactory yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with hydroxylamine hydrochloride afforded in moderate yield methyl 4-(2,2-dimethyl-1-oxopropyl)-5-isoxazolecarboxylate, which was converted by acid hydrolysis as above to 4-t-butyl-4-hydroxyfuro[3,4-d]isoxazol-6-(4H)-one.     

Studies on sulfinatodehalogenation. XX. Sodium dithionite-initiated addition of per- and polyfluoroalkyl iodides to cyclic enol ethers and chemical conversions of the products

Per- and polyfluoroalkyl iodides [R_FI, R_F=Cl(CF₂)₄, 1a ; Cl(CF₂)₆, 1b ; Cl(CF₂)₈, 1c ; n-C₆F₁₃, 1d ; n-C₈F₁₇, 1e ] reacted with cyclic enol ethers such as 2,3-dihydrofuran (2) and 3,4-dihydro-2H-pyran (3) in aqueous acetonitrile in the presence of sodium dithionite and sodium bicarbonate at room temperature (10–15°C) to give the corresponding 2-(F-alkyl) hemiacetals in high yields. The adducts were oxidized with Ce(NH₄)₂(NO₃)₆ in acetonitrile or reduced with LiAlH₄ in ether to form the corresponding 2-(F-alkyl)lactones or diols respectively in good yields. In the presence of p-toluenesulfonic acid, the adducts were refluxed in benzene and CH₃CN to produce the corresponding 2,3-dihydro-4-(F-alkyl) furan and 3,4-dihydro-5-(F-alkyl)-2H-pyran. This is a new and effective method for preparing these useful organofluorine compounds.     

Alternating copolymerization of 1- and 2-vinylnaphthalene with methyl methacrylate by using diethylaluminum chloride

The alternating copolymerization of 1- and 2-vinylnaphthalene (1-VNap and 2-VNap) with methyl methacrylate (MMA) by using diethylaluminum chloride (Et₂AlCl) in toluene at 0°C has been studied. No polymerization could occur without Et₂AlCl, and alternating copolymers were obtained only when an equimolar amount of Et₂AlCl with MMA was supplied. Through ¹H-NMR analyses on both dyad and triad of alternating deuterated 1- and 2-α-d-VNap–MMA copolymers, each configuration could be described successfully by a single parameter, coisotacticity σ, whose value was estimated as 0.41 for the former and 0.56 for the latter copolymer, respectively. A rather low coisotacticity of copoly(1-VNap–MMA) was explained in the terms of steric effect (peri effect) of 1-VNap monomer.     

Detailed studies on the reduction of aliphatic 3-, 4-, 6-, and 13-oximino esters: Synthesis of novel isomeric amino esters,oximino alcohols,and amino alcohols

The preparation of novel 3-, 4-, 6-, and 13-amino-tetradecanoic acid methyl esters (2a–d) obtained by the reduction of 3-, 4-, 6-, and 13-oximino-tetradecanoic acid methyl esters (1a–d), was investigated. Oximino esters were reduced to afford the corresponding amino esters using NaBH₄–ZrCl₄ reducing system with good yields (58–82%). However, the reduction of oximino esters with LiAlH₄ and BH₃. Tetrahydrofuran gave the corresponding novel 3-, 4-, 6-, and 13-oximino alcohols (3a–d), and 3-, 4-, 6-, and 13-amino alcohols (4a–d) respectively with good chemical yields.     

Polymerization of Methyl Methacrylate with Bis(Cyclopentadienyl)Titanium Dichloride in a Water-Methanol Mixture: Formation of Tetrahydrofuran-Insoluble Polymer

Abstract

Methyl methacrylate (MMA) was found to be effectively polymerized with bis(cyclopentadienyl)titanium dichloride (CP₂TiCl₂) in a water-methanol mixture (1:1, v/v). The polymerization proceeded heterogeneously because the resulting poly(MMA) was insoluble in the system. The rate (R _p) of the heterogenous polymerization was apparently expressed by R _p = k[Cp₂TiCl₂]²[MMA]^2˙5 (at 40°C). The resulting poly(MMA) was observed to consist of tetrahydrofuran (THF)-soluble and insoluble parts. In contrast with the usual radical poly(MMA), the THF-insoluble part was soluble in benzene, toluene, and chloroform but insoluble in polar solvents such as ethyl acetate, acetone, acetonitrile, dimethylformamide, and dimethylsulfoxide. The polymerization was found to be profoundly accelerated by irradiation with a fluorescent room lamp (15 W). The results of copolymerization of MMA and acrylonitrile indicated that the present polymerization proceeds through a radical mechanism.     

Reactions of metallocenes during intercalation into the layered TiSe2 lattice

The intercalation of metallocenes (Cp₂Co, Cp₂Fe, and Cp₂Ni, where Cp is η⁵-C₅H₅) from the gas phase into the TiSe₂ lattice and of cobaltocene from solutions in acetonitrile, carbon tetrachloride, and chloroform into TiSe₂ was studied. The insertion of metallocenes from the gas phase into the TiSe₂ lattice gives rise to the TiSe₂(Cp₂M)_0.3 compounds (M = Co or Fe) having the same stoichiometry. The reactions with the use of acetonitrile as the solvent for metallocenes, which facilitates the insertion, afford not only the intercalation complex but also the reaction product of metallocene and acetonitrile, viz., (η ⁵-C₅H₅)Co(η⁴-C₅H₅CH₂CN) (1). In the reactions of cobaltocene with chloroform or carbon tetrachloride in the presence of titanium diselenide, only the addition product, viz., (η ⁵-C₅H₅)Co(η₄-C₅H₅CCl₃) (2), was isolated. The structures of complexes 1 and 2 were studied by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 876–880, May, 2007.     

DBU-CH3I,a Potential Substitute for CH2N2 in the Preparation of Methyl Esters and Methyl Aryl Ethers: Studies with Assorted Acids

DBU-CH₃I has been poised to be a substitute for diazomethane in the preparation of methyl esters from carboxylic acids. The reactions can be carried out in commercial untreated acetone and acetonitrile, which have been exemplified with several methyl esters, otherwise it is difficult to prepare. Bis-esterification using diiodomethane can also be achieved in a similar fashion. Sufficiently acidic phenols are also conveniently O-methylated by the method.     

The influence of molecular interactions on polymerization—IV: Copolymerization of 2-naphthyl methacrylate and methyl methacrylate in solvents with different dielectric constants

The copolymerization of 2-naphthyl methacrylate (2-NM) with methyl methacrylate (MMA) initiated by 2,2′-azoisobutyronitrile in carbon tetrachloride, chloroform, benzene, acetone and acetonitrile was investigated. The reactivity ratios determined by the methods of Fineman-Ross and Kelen-Tüdo&#x030B;s are: in carbon tetrachloride—r_2-NM = 2.46 ± 0.25, r_MMA = 0.61 ± 0.06; chloroform—r_2-NM = 2.71 ± 0.30, r_MMA = 0.60 ± 0.06; benzene—r_2-NM = 2.62 ± 0.44, r_MMA = 0.63 ± 0.11; acetone—r_2-NM = 4.13 ± 0.45, r_MMA = 0.60 ± 0.06 and acetonitrile—r_2-NM = 3.70 ± 0.30, r_MMA = 0.62 ± 0.05.The dependence of the reactivity ratios on the solvent is explained on the basis of formation of complexes between the electron-donating naphthalene rings and the electron-accepting methacrylic double bonds, as indicated by NMR studies.     

Star poly(methyl methacrylate) with end‐functionalized arm chains by ruthenium‐catalyzed living radical polymerization

Star polymers with end‐functionalized arm chains (surface‐functionalized star polymers) were synthesized by the in situ linking reaction between ethylene glycol dimethacrylate (linking agent) and an α‐end‐functionalized linear living poly(methyl methacrylate) in RuCl₂(PPh₃)₃‐catalyzed living radical polymerization; the terminal on the surface functionalities included amides, alcohols, amines, and esters. The star polymers were obtained in high yields (75–90%) with initiating systems consisting of a functionalized 2‐chloro‐2‐phenylacetate or ‐acetamide [F? C(O)CHPhCl; F = nPrNH? , HOCH₂CH₂O? , Me₂NCH₂CH₂O? , or EtO? ; initiator] and n‐Bu₃N (additive). The yield was lower with a functionalized 2‐bromoisobutyrate [Me₂NCH₂CH₂OC(O)CMe₂Br] initiator or with Al(Oi‐Pr)₃ as an additive. Multi‐angle laser light scattering analysis showed that the star polymers had arm numbers of 10–100, radii of gyration of 6–23 nm, and weight‐average molecular weights of 1.3 × 10⁵ to 3.0 × 10⁶, which could be controlled by the molar ratio of the linking agent to the linear living polymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1972–1982, 2002     

Polymer-mounted N3P(MeNCH2CH2)3N: a green, efficient and recyclable catalyst for room-temperature transesterifications and amidations of unactivated esters

Merrifield resin-supported N₃P(MeNCH₂CH₂)₃N shows excellent activity in the transesterification of higher esters such as glyceryl tribenzoate to methyl esters. The catalyst was successfully cycled 20 times (albeit with an increase in reaction time) without compromising yield up to the 20th cycle. The catalyst also showed good performance in amidation reactions of unactivated esters with amino alcohols.     

SYNTHESIS OF ABA TYPE TRIBLOCK COPOLYMERS BY RADICAL POLYMERIZATION WITH 1,4-BIS(p-TERTBUTYLPHENYLSELENOMETHYL) BENZENE AS A PHOTOINIFERTER

1,4-Bis(p-tert-butylphenylselenomethyl)benzene was used as a bifunctional photoiniferter for the polymerization of methyl methacrylate (MMA). Both the polymer yields and the number average of molecular weights ([Mbar]_n) of polymers increased with the polymerization time and the [Mbar]_n linearly increased with polymer yield. The addition of MMA to the poly(MMA) with irradiation increased the [Mbar]_n of the polymer. Photoirradiation of telechelic polystyrene having phenylseleno groups at both ends as polymeric photoiniferter in the presence of MMA or p-chloromethylstyrene afforded effectively corresponding to the ABA type triblock copolymers. On the other hand, photopolymerization of p-methylstyrene with ABA type triblock copolymer of styrene and p-chloromethylstyrene as polymeric photoiniferter afforded to multiblock copolymer of styrene and p-substituted styrenes.     

Stereoselective synthesis of tetrahydropyran new derivatives underlain by α-allyl ketones

Decarboxylation of α-allyl-substituted acetoacetic esters afforded α-allyl ketones that were reduced with L-selectride [LiBH(s-Bu)₃] in alcohols RCH(OH)CH₂CH₂CH=C(Me)CH₂R'. The latter reacted with methyl 4-hydroxy-3-formylbenzoate and methyl orthoformate in the presence of p-toluenesulfonic acid to provide trans-tetrahydropyrano[3,2-с][1]benzopyran. In reaction of the E-isomer of alcohol Me₂CHCH(OH) CH₂CH₂CH=C(Me)CH₂CH₂Ph with CF₃SO₃H a stereoselective cyclization occurred with the formation of 2,6-disubstituted tetrahydropyran; Prins reaction with 4-bromobenzaldehyde and salicylaldehyde in the presence of boron trifluoride etherate also proceeded stereoselectively giving a substituted tetrahydropyrano-[3,2-c][1]-benzopyran.     

Telomerization of propylene with methyl dichloroacetate

Conclusions The telomerization of propylene with methyl dichloroacetate includes chain transfer via the C-H and C-Cl bonds, and leads to the formation of four series of telomers, the methyl esters of chloro-substituted acids of type X[CH(CH₃)CH₂]_nCClYCO₂CH₃ (X, Y=H, Cl), and also of the telomeric esters of the higher alcohols and dichloroacetic acid.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2150–2152, September, 1977.     

Free radical polymerization of methyl methacrylate initiated by the diphosphine Mo(0) complexes

The polymerization of methyl methacrylate MMA catalyzed by [Mo(CO)₄L₂] [L₂ = diphenylphosphinomethane (dppm), diphenylphosphinoethane (dppe) or diphenylphosphinopropane (dppp)] has been studied. The activity of these single‐component catalysts depends on the length of the (CH₂)_n bridge of diphosphine ligand. Thus, the dppm derivative displays higher activity than dppe or dppp ligands. These complexes, as free radical initiators, afforded the methyl methacrylate polymerization in chlorinated solvents. The mechanism of the polymerization was discussed and a radical mechanism was proposed. Copyright © 2006 John Wiley & Sons, Ltd.