Oxidation of Unsaturated Ethers with the System Aluminum Tri-tert-butylate-tert-Butyl Hydroperoxide

The system aluminum tri-tert-butylate-tert-butyl hydroperoxide oxidizes alkyl allyl and aryl allyl ethers by the radical mechanism at room temperature. In the process, either the substrate skeleton is preserved and the carbonyl and hydroperoxy groups are introduced, or the carbon-carbon and carbon-oxygen bonds in the allyl moiety are cleaved. In allyl benzyl ether the reaction centers are the methylene groups of the benzyl and allyl fragments.     

The electronic effects of substituents at the acyl carbon in the gas-phase elimination kinetics of tert-butyl α-substituted acetates

The gas-phase eliminations of several tert-butyl esters, in a static system and in vessels seasoned with allyl bromide, have been studied in the temperature range of 171.5–280.1°C and the pressure range of 23–98 torr. The rate coefficients for the homogeneous unimolecular elimination of these esters are given by the following Arrhenius equations: for tert-butyl pivalate, log k₁(s^?1) = (13.44 ± 0.30) ? (169.1 ± 3.1) kJ · mol^?1 (2.303RT)^?1; for tert-butyl trichloroacetate, log k₁(s^?1) = (12.41 ± 0.08) ? (141.1 ± 0.7) kJ · mol^?1 (2.303RT)^?1; and for tert-butyl cyanoacetate log k₁(s^?1) = (11.31 ± 0.44) ? (137.8 ± 4.1) kJ · mol^?1 (2.303RT)^?1. The data of this work together with those reported in the literature yield a good linear relationship when plotting log k/k₀ vs. σ* values (ρ* = 0.635, correlation coefficient r = 0.972, and intercept = 0.048 at 250°C). The positive ρ* value suggests that the movement of negative charge to the acyl carbon in the transition state is rate determining. The present results along with previous investigations ratify the generalization that electron-withdrawing substituents at the acyl side of ethyl, isopropyl, and tert-butyl esters enhance the elimination rates, while electron-releasing groups tend to reduce them. The negative nature of the acyl carbon and the polarity in the transition state increases slightly from primary to tertiary esters.     

Synthesis and biological activity of alkylidene-substituted cephems and penams

The condensation of tert-butyl esters of 3-methyl-7-oxoceph-3-em-4-carboxylic and 6-oxopenicillanic acids with a series of 2-oxoalkylidene(triphenyl)phosphoranes gave tert-butyl esters of new cephalosporin and penicillin analogs with an alkylidene substituent in the β-lactam ring. Most of these products were oxidized by meta-chloroperbenzoic acid to the corresponding sulfones. The cephemes and penams synthesized including the oxidized products displayed high cytotoxicity relative to cancer cells in vitro. Some of the alkylidene-substituted cephems as the free acids, similar to Tazobactam, inhibit the catalytic activity of Enterobacter cloacae penicillinase.     

Chemoselective hydrolysis of tert-butyl esters in acetonitrile using molecular iodine as a mild and efficient catalyst

A simple, mild and efficient method for the hydrolysis of tert-butyl esters using molecular iodine as a catalyst is described. Acid labile protecting groups, such as N-Boc, OBn, OAc and double bonds, are compatible under the reaction conditions.     

Generation and Reactions of Lithiated tert-Butyl and 2,6-Di(tert-butyl)-4-methylphenyl Cyclopropanecarboxylates

tert-Butyl and 2,6-di(tert-butyl)-4-methylphenyl (BHT) cyclopropanecarboxylates ( 4 , 6 , 24 , 25 ) are lithiated with LiN(i-Pr)₂ and t-BuLi, respectively. Reactions with alkyl halides, aldehydes, acyl chlorides, and heteroelectrophiles give α-substituted BHT esters which can be cleaved (t-BuOK/H₂O/THF) to the corresponding carboxylic acids or reduced (LiAlH₄/THF) to the cyclopropanemethanols.     

Functionally Substituted Amides and Esters of 3,4,4-Trichloro-3-butenoic Acid

Substituted amides and esters of 3,4,4-trichloro-3-butenoic acid were prepared by reactions of its chloride with appropriate amines and alcohols. Treatment of 3,4,4-trichloro-3-butenomorpholide and tert-butyl 3,4,4-trichloro-3-butenoate results in nucleophilic substitution of the internal chlorine atom with the morpholine residue, accompanied by prototropic allyl rearrangement.     

Oxidation of Substituted 1,5-Hexadien-3-ols with Various Oxidants

Substituted 1,5-hexadien-3-ols were synthesized by the [2,3]-Wittig rearrangement of unsymmetrical bis-allyl ethers, as well as by reactions of 1-(2-alkenyl)-2-chloromethyloxiranes with Mg/THF. The products were oxidized with pyridinium chlorochromate (PCC), zinc chlorochromate (ZCC), tert-butyl hydroperoxide in the presence of OsO₄, and tert-butyl hydroperoxide alone. The oxidation of substituted 1,5-hexadien-3-ols with PCC and ZCC gave the corresponding carbonyl compounds. In the reaction with tert-butyl hydroperoxide catalyzed by OsO₄ the internal double bond in the substrate was regioselectively converted into epoxy group, whereas allylic oxidation was prevented.     

Synthesis of Glycopeptides,Partial Structures of Biological Recognition Components [New Synthetic Methods (67)]

Glycopeptides are partial structures of the connecting regions of glycoproteins and, like these, always contain glycosidic bonds between the carbohydrate and peptide parts. Glycoproteins are not only widely distributed but are also decisive factors in post-translational biological selectivity, especially in biological recognition. Targeted syntheses of glycopeptides require stereoselective formation of the glycosidic bonds between the carbohydrate and the peptide parts and protective group methods that enable selective deblocking of only one functional group in these polyfunctional molecules. These heavy demands have been met by the well-established use of benzylic protective groups, which can be removed by hydrogenolysis, combined with the use of base-labile 2-phosphonioethoxycarbonyl (Peoc) or 9-fluorenylmethoxycarbonyl (Fmoc) protective groups or of bromoethyl esters, which can be removed under neutral conditions. The acidolysis of tert-butyloxycarbonyl (Boc) groups and of tert-butyl esters has also been successfully used, although, under acidic conditions, anomerization or rupture of the glycosidic bonds may occur, especially when nucleophiles are present. The stable, two-stage 2-(pyridyl)ethoxycarbonyl (Pyoc) protective groups allow a more reliable synthesis of complex glycopeptides since they can be removed, after modifications, under mild conditions. Particularly suitable for the synthesis of sensitive glycopeptides are the stable allyl protective groups. They can be removed from the complex glycopeptides in a highly selective and effective manner by means of noble-metal catalysts under practically neutral conditions. These methods have been employed to synthesize glycopeptides corresponding to partial structures of interesting glycoproteins. Deprotected glyopeptides representing tumor-associated antigen structures can be coupled to bovine serum albumin, which serves as a biological carrier molecule, without the necessity of using an artificial coupling component (spacer).     

Indium(III) chloride-catalyzed oxidative cleavage of carbon-carbon multiple bonds by tert-butyl hydroperoxide in water—a safer alternative to ozonolysis

An efficient and general method for the oxidative cleavage of alkenes and alkynes using tert-butyl hydroperoxide and indium(III) chloride as catalyst in water to give the corresponding carboxylic acids or ketones has been achieved. The reaction conditions are compatible with sensitive moieties such as peptide bonds, tert-butyl carboxylic esters and N-Boc-protected tryptophan. The catalyst could be recycled.     

Structure and properties of bis{[2-(4-<Emphasis Type="Italic">tert</Emphasis>-butyl)phen]ethyl}phosphine sulfide

Previously unknown bis[2-(4-tert-butyl)phen]ethylphosphine sulfide is obtained with a high yield from 4-tert-butyl styrene, red phosphorus, and elemental sulfur. Using single crystal XRD, multinuclear NMR, IR, and UV spectroscopy, it is found that the phosphorus atom is four-coordinated in the bis[2-(4-tert-butyl)phen]ethylphosphine sulfide molecule (regardless of the phase state of the compound: crystal, solution). By the example of phosphorylation of bis[2-(4-tert-butyl)phen]ethylphosphine sulfide acetylene in the KOH-DMSO system it is shown that the reaction proceeds by double addition with the participation of phosphorus-centered nucleophiles.     

In situ study of the interaction between <Emphasis Type="Italic">tert</Emphasis>-butyl chloride and aluminum activated with liquid In-Ga eutectic

The interaction between tert-butyl chloride and activated aluminum was studied by attenuated total reflectance Fourier transform infrared spectroscopy near room temperature (18–25°C). A long induction period of ∼240–260 min was observed. The ionic aluminum chloride complexes [Al _n Cl_3n+1]⁻ (n = 1, 2) and the molecular species AlCl₃ were identified at the activated aluminum/tert-butyl chloride interface during the reaction. The formation of the ion in the AlCl₄⁻ ion in the liquid medium and the presence of the same ion and a molecular AlCl₃-tert-butyl chloride complex in the resinous products of the reaction were confirmed by ²⁷Al NMR spectroscopy. The reaction products were analyzed qualitatively by GC/MS. The reactivities of activated aluminum and anhydrous aluminum chloride toward tert-butyl chloride under the same conditions were compared. A distinctive feature of the interaction activated aluminum and tert-butyl chloride is the dominant formation of the AlCl₄⁻ ion. By contrast, the interaction between aluminum chloride and tert-butyl chloride yields the polynuclear ion Al₂Cl₇⁻ and, likely, Al₃Cl₁₀⁻.     

Liquid-phase oxidation of sulfides by an aluminum (and titanium) <Emphasis Type="Italic">tert</Emphasis>-butoxide—<Emphasis Type="Italic">tert</Emphasis>-butyl hydroperoxide system

A system aluminum (and titanium) tert-butoxide—tert-butyl hydroperoxide (1 : 2) under mild conditions (20 °C, 1 h) oxidizes aliphatic and alkylaromatic sulfides and diphenyl sulfide to the corresponding sulfones in yields close to 100%. The oxidation is induced by electron-excited dioxygen formed upon thermal decomposition of intermediate metal-containing peroxy trioxides (ozonides). The latter are formed as a result of the reversible reaction of aluminum or titanium tert-butoxides with tert-butyl hydroperoxide followed by the interaction of di-tert-butoxy-tert-butylperoxyaluminum and tri-tert-butoxy-tert-butylperoxytitanium that formed with another Bu^tOOH molecule. Aluminum-containing peroxide (Bu^tO)₂AlOOBu^t oxidizes sulfides to sulfoxides.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1663–1668, August, 2004.     

A fast and practical synthesis of tert-butyl esters from 2-tert-butoxypyridine using boron trifluoride·diethyl etherate under mild conditions

A practical direct preparation of tert-butyl esters from 2-tert-butoxypyridine has been developed. This system features the use of boron trifluoride·diethyl etherate in toluene solvent to rapidly achieve the reaction at room temperature. Using this reaction protocol, a variety of tert-butyl esters were synthesized from several different carboxylic acids at high yields. This practical procedure provides a promising and effective approach to the protection of carboxylic acids with a tert-butyl group.     

Synthesis and cytotoxic activity of derivatives of the <Emphasis Type="Italic">tert</Emphasis>-butyl ester of 7<Emphasis Type="Italic">Z</Emphasis>-acetylmethylene-3-methyl-3-cephem-4-carboxylic acid

The condensation of the acetylmethylene group in the tert-butyl esters of 7Z-acetylmethylene-3-methyl-3-cephem-4-carboxylic acid and 7Z-acetylmethylene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid and in 7Z-acetylmethylene-3-methylene-1,1-dioxo-3-cephem with arylmethoxyamines and O-alkylation of the tert-butyl ester of 7Z-(2-hydroxyimino)propylidene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid using substituted benzyl bromides as well as pyridylmethyl chlorides gave arylmethoxyimino and pyridylmethoxyimino derivatives of these compounds in the syn and anti isomeric forms. The Vilsmaier reagent was used to introduce the N,N-dimethylaminomethylene group at C-2 of the cephem system in the tert-butyl esters of 7Z-[2-(arylmethoxyimino)propylidene]-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid. Subsequent transformation of the N,N-dimethylaminomethylene cephems using hydroxylamine led to 3Z-[2-(anti-arylmethoxyimino)propylidene]-tert-butoxycarbonylmethyl-4-(5-methyl-4-isoxazolylsulfonyl)- azetidin-2-ones. Condensation of the acetyl group in the tert-butyl ester of 7Z-acetylmethylene- 3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid with 4-bromophenylhydrazine gave a cephem with a 2-(4-bromophenylhydrazono)propylidene group at C-7. Acylation of the tert-butyl ester of 7Z-(2-hydroxyimino)propylidene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid by 2-bromobenzoyl chloride gave a cephem with a 2-(2-bromo-benzoyloxyimino)propylidene group at C-7. Biological screening of these products towards to malignant and normal cells in vitro showed that their antitumor activity and cytotoxic selectivity towards to malignant and normal cells depend on the structure and configuration of the arylmethoxyimino and pyridylmethoxyimino groups in the 7-alkylidene substituent as well as on the presence or absence of N,N-dimethylaminomethylene and carboxyl groups, respectively, at C-2 and C-4 of the cephem system.     

New reagent for the introduction of Boc protecting group to amines: Boc-OASUD

A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.     

ESR study of the thermal decomposition of di-tert-butoxy-tert-butyl alumotrioxide formed in the reaction of tri-tert-butoxyaluminum with tert-butyl hydroperoxide

Tri-tert-butoxyaluminum reacts with tert-butyl hydroperoxide to produce di-tert-butoxy-tert-butyl alumotrioxide, which decomposes heterolytically to form singlet dioxygen and homolytically with the O—O bond cleavage. The Bu^tOO^·, (Bu^tO)₂AlOO^·, Bu^tO^·, and (Bu^tO)₂AlO^· radicals were identified by ESR using spin traps. These findings confirm the formation of aluminum-containing trioxide. The above radicals initiate alkylarene oxidation by the tri-tert-butoxyaluminum—tert-butyl hydroperoxide system. The carbon-centered and alkylperoxy radicals originated from the oxidized substrates were identified.     

Nitrogen–Carbon Bond Formation by Reactions of a Titanium–Potassium Dinitrogen Complex with Carbon Dioxide,tert-Butyl Isocyanate,and Phenylallene

Nitrogen–carbon bond-forming reactions at coordinated dinitrogen in a bifunctional titanium–potassium system are reported. A titanium atrane complex with a tris(aryloxide)methyl ligand ( 1 ) was treated with two equivalents of potassium naphthalenide under N₂ atmosphere to generate a bifunctional complex ( 2 ) in which N₂ binds end-on to two titanium centers and side-on to three potassium cations. Dinitrogen complex 2 reacted with carbon dioxide, tert-butyl isocyanate, and phenylallene, forming nitrogen–carbon bonds and affording diverse N-functionalized products. The reaction of 2 with CO₂ followed by addition of Me₃SiCl resulted in the formation of the starting complex 1 with concomitant release of silylated carboxyl hydrazines while the reaction with two equivalents of tert-butyl isocyanate proceeded by insertion into the Ti−N bonds. Treatment of 2 with phenylallene afforded vinyl-substituted hydrazido complexes.     

Catalytic hydrophosphorylation of semicarbazones, thiosemicarbazones, carbonohydrazones, and oxalyldihydrazones

Reaction of diethyl phosphite with semicarbazones, thiosemicarbazones, carbonohydrazones, and oxalyldihydrazones of aliphatic and carbocyclic ketones catalyzed by [tetra(tert-butyl)phthalocyanine]aluminum chloride resulted in hydrophosphorylation of the C=N bonds of hydrazones under study.     

Cationic polymerization with boron halides. IV. Elucidation and control of initiation and termination by the help of model experiments

The proposition that BCl₃-coinitiated olefin (isobutylene, styrene) polymerizations terminate by chlorination has been corroborated by model experiments. Key experiments showed that under simulated polymerization conditions neither tert-butyl chloride nor 2-chloro-2,4,4-trimethylpentane reacts with BCl₃; that H₂O/BCl₃ + 2,4,4-trimethyl-1-pentene (TMP) produce 2-chloro-2,4,4-trimethylpentane; and that H₂O/BCl₃ + isobutylene gives rise to tert-butyl chloride. Extended model studies demonstrated that certain alkyl and benzyl chlorides produce carbenium ions in the presence of BCl₃ and that TMP can readily be alkenylated by using 1-substituted allyl chlorides in conjunction with BCl₃. These experiments led to the discovery that olefin polymerizations may be initiated by suitable allyl or benzyl chlorides and BCl₃. Accordingly, polymerizations of isobutylene have been carried out with RCl/BCl₃, where R is allyl or benzyl. These experiments suggest that both controlled initiation and termination, i.e., initiation by alkenylation and termination by chlorination, can be achieved with the allyl chloride/BCl₃ initiator system opening new avenues toward the synthesis of asymmetric telechelic polymers.     

Preparation of functional polymers by living anionic polymerization: Polymerization of allyl methacrylate

The anionic polymerization of allyl methacrylate was carried out in tetrahydrofuran, both in the presence and in the absence of LiCl, with a variety of initiators, at various temperatures. It was found that (1,1-diphenylhexyl)lithium and the living oligomers of methyl methacrylate and tert-butyl methacrylate are suitable initiators for the anionic polymerization of this monomer. The temperature should be below −30°C, even in the presence of LiCl, for the living polymerization to occur. When the polymerization proceeded at −60°C, in the presence of LiCl, with (1,1-diphenylhexyl)-lithium as initiator, the number-average molecular weight of the polymer was directly proportional to the monomer conversion and monodisperse poly(allyl methacrylate)s with high molecular weights were obtained. ¹H-NMR and FT-IR indicated that the α CC double bond of the monomer was selectively polymerized and that the allyl group remained unreacted. The prepared poly(allyl methacrylate) is a functional polymer since it contains a reactive CC double bond on each repeating unit. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2901–2906, 1997