Asymmetric synthesis of α-mercapto-β-amino acid derivatives: application to the synthesis of polysubstituted thiomorpholines

Tandem conjugate addition of homochiral lithium N-benzyl-N-(α-methyl-p-methoxybenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS^tBu proceeds with high diastereoselectivity to give a homochiral anti-α-tert-butylthio-β-amino ester. Stepwise deprotection gives the corresponding free α-tert-butylthio-β-amino acid without epimerisation. Tandem conjugate addition of homochiral lithium N-allyl-N-(α-methylbenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS^tBu followed by conversion of the S-tert-butyl group to a disulphide, and reduction with Lalancette’s reagent generates polysubstituted thiomorpholine derivatives.     

Rational enhancement of the energy barrier of bis(tetrapyrrole) dysprosium SMMs via replacing atom of porphyrin core

With the coordination geometry of Dy^III being relatively fixed, oxygen and sulfur atoms were used to replace one porphyrin pyrrole nitrogen atom of sandwich complex [(Bu)₄N][Dy^III(Pc)(TBPP)] [Pc = dianion of phthalocyanine, TBPP = 5,10,15,20-tetrakis[(4-tert-butyl)phenyl]porphyrin]. The energy barrier of the compounds was enhanced three times, with the order of Dy^III(Pc)(STBPP) > Dy^III(Pc)(OTBPP) > [(Bu)₄N][Dy^III(Pc)(TBPP)] [STBPP = monoanion of 5,10,15,20-(4-tert-butyl)phenyl-21-thiaporphyrin, OTBPP = monoanion of 5,10,15,20-(4-tert-butyl)phenyl-21-oxaporphyrin]. Theoretical calculations offer reasonable explanations of such a significant enhancement. The energy barrier of 194 K for Dy^III(Pc)(STBPP) represents the highest one among all the bis(tetrapyrrole) dysprosium SMMs, providing a strategy to rationally enhance the anisotropy and energy barrier via atom replacement.     

Di-tert-butyl dicarbonate: a versatile carboxylating reagent

Carbon nucleophiles generated by a non-nucleophilic base (LDA) were effectively trapped with di-tert-butyl dicarbonate (Boc-anhydride) to provide the corresponding tert-butyl aryl acetates, di-tert-butyl aryl malonates, unsymmetrical aryl malonates and tert-butyl benzoates in high yields. This reaction represents another useful way to prepare a variety of tert-butyl carboxylates and highlights the synthetic utility of di-tert-butyl dicarbonate as a versatile carboxylating reagent.     

New synthesis of tert-butyl peroxycarboxylates

tert-Butyl peroxyacetate, tert-butyl peroxybutyrate, tert-butyl phenylperoxyacetate, and tert-butyl peroxyundecanoate were obtained in nearly quantitative yields by the esterification of the corresponding carboxylic acids with tert-butyl hydroperoxide in the presence of trifluoroacetic anhydride and pyridine in nonaqueous medium at 0–5°C. No tert-butyl peroxytrifluoroacetate was formed as a by-product during the process. A possible reaction mechanism is discussed.     

Cyclic peptides containing a δ-sugar amino acid—synthesis and evaluation as artificial receptors

An Fmoc-protected δ-sugar amino acid, prepared by oxidation of a glucosamine derivative, was coupled to three different tripeptide tert-butyl esters (H-Tyr-Tyr-Tyr-O^tBu, H-Tyr-Glu(OBzl)-Tyr-O^tBu and H-Tyr-Arg(Mtr)-Tyr-O^tBu) and the resulting sugar amino acid/amino acid hybrids were transformed into dimers that were subsequently cyclized to give three C₂-symmetric macrocycles. The macrocycles were deprotected and their binding properties towards p-nitrophenyl glycosides, nucleotides, and purines were examined. Of the ligands screened, only some of the purines showed weak, but significant, binding.     

An efficient synthesis of tert-butyl ethers/esters of alcohols/amino acids using methyl tert-butyl ether

A facile synthesis of a wide variety of tert-butyl ethers and tert-butyl ester derivatives under mild conditions is described. Alcohols etherified with tert-butyl methyl ether as tert-butyl source and solvent, in the presence of sulfuric acid. Many amino acid tert-butyl esters have been synthesized by this procedure. The reaction is simple, inexpensive, easily scaled up, and proceeds without observable racemization. A green method was developed for the deprotection of this group using Amberlite resin IR 120-H as catalyst.     

Regioisomer-Free C4h β-Tetrakis(tert-butyl)metallo-phthalocyanines: Regioselective Synthesis and Spectral Investigations

Metal β-tetrakis(tert-butyl)phthalocyanines are the most commonly used phthalocyanines due to their high solubility, stability, and accessibility. They are commonly used as a mixture of four regioisomers, which arise due to the tert-butyl substituent on the β-position, and to the best of our knowledge, their regioselective synthesis has yet to be reported. Herein, the C_4h-selective synthesis of β-tetrakis(tert-butyl)metallophthalocyanines is disclosed. Using tetramerization of α-trialkylsilyl phthalonitriles with metal salts following acid-mediated desilylation, the desired metallophthalocyanines were obtained in good yields. Upon investigation of regioisomer-free zinc β-tetrakis(tert-butyl)phthalocyanine using spectroscopy, the C_4h single isomer described here was found to be distinct in the solid state to zinc β-tetrakis(tert-butyl)phthalocyanine obtained by a conventional method.     

Kinetics and mechanism of the liquid-phase oxidation of tert-butyl phenylacetate

The oxidation of tert-butyl phenylacetate in ortho-dichlorobenzene at 140°C occurs with short chains. The primary nonperoxide reaction products (tert-butyl α-hydroxyphenylacetate, tert-butyl α-oxophenylacetate, and benzaldehyde) are formed by the decomposition of a hydroperoxide (tert-butyl α-hydroperoxyphenylacetate) and (or) by the recombination of peroxy radicals with and without chain termination. Benzaldehyde and tert-butyl α-hydroxyphenylacetate undergo radical chain oxidation in a reaction medium to result in benzoic acid and tert-butyl α-oxophenylacetate. Homolytic hydroperoxide decomposition is responsible for process autoacceleration and results in benzaldehyde, which is also formed from hydroperoxide by a nonradical mechanism, probably, via a dioxetane intermediate. Both of the reactions are catalyzed by benzoic acid. Benzoic acid has no effect on hydroperoxide conversion into tert-butyl α-oxophenylacetate, which most likely occurs as a result of hydroperoxide decomposition induced by peroxy radicals. The rate constants of the main steps of the process and kinetic parameters have been calculated by solving an inverse kinetic problem.     

Synthesis oftert-butyl substituted polymethine 1-benzothiopyrylium dyestuffs

A series of polymethine thiopyrylium dyestuffs of symmetrical and unsymmetrical structure, containing one to fourtert-butyl groups, has been synthesized from 6-tert-butyl-2-(p-tert-butylphenyl)-4-methyl-, 4,6-di(tert-butyl)-2-methyl-, and 6-tert-butyl-2,4-dimethyl-1-benzothiopyrylium perchlorates.     

Kinetics of proton transfer from tetra(4-nitro-5-tert-butyl)phthalocyanine to nitrogen-containing bases in benzene

The acid-basic interaction between tetra(4-nitro-5-tert-butyl)phthalocyanine and pyridine, 2-methylpyridine, morpholine, piperidine, n-butylamine, diethylamine, and triethylamine in benzene is studied. It is found that the intermolecular transfer of protons of NH groups from tetra(4-nitro-5-tert-butyl)phthalocyanine to morpholine and diethylamine is characterized by unusually low values of the reaction constant rates. The effect of the structure of tetra(4-nitro-5-tert-butyl)phthalocyanine and tetra(3-nitro-5-tert-butyl)phthalocyanine, and of the nature of the base on the kinetic parameters of acid-base interaction is demonstrated. A structure is proposed for complexes with the transfer of displaced phthalocyanines’ protons. It is found that they undergo decomposition over time.     

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 of N,N′-di(tert-butyl)bispidin-9-ones

Condensation of 1,3,5-tri(tert-butyl)-1,3,5-triazacyclohexane with acetone gave 3,7-di(tert-butyl)-1,5-bis[(tert-butylamino)methyl]bispidin-9-one. Reactions with ethyl methyl ketone and other ketones of the formula RCH₂COCH₃ yielded 5-R-3,7-di(tert-butyl)-1-[(tert-butylamino)methyl]bispidin-9-ones, while reactions with diethyl ketone and other symmetrical ketones of the formula RCH₂COCH₂R afforded 1,5-R-3,7-di(tert-butyl)bispidin-9-ones.     

Organocatalytic conjugate addition of α-nitroacetates to β,γ-unsaturated α-keto esters and subsequent decarboxylation: synthesis of optically active δ-nitro-α-keto esters

Organocatalytic asymmetric conjugate addition of tert-butyl nitroacetates to β,γ-unsaturated α-keto esters has been developed. The subsequent in situ hydrolysis-decarboxylation of the adducts provided 5-nitro-2-oxopentanoates. A pyrrolidine-based thiourea-tertiary amine was identified as the best catalyst. A number of γ-aryl, γ-alkyl, and γ-heteroaryl β,γ-unsaturated α-keto esters and α-substituted tert-butyl nitroacetates were examined in the transformation. Generally 5-nitro-2-oxopentanoates were obtained in good yields (up to 97%) and enantioselectivities (up to 94% ee). The products were readily transformed to chiral proline derivatives by catalytic hydrogenation.     

Boron trichloride as an efficient and selective agent for deprotection of tert-butyl aryl sulfonamides

A fast, mild and selective method for deprotection of tert-butyl aryl sulfonamides utilizing BCl₃ as deprotection reagent has been developed. A variety of tert-butyl aryl sulfonamides used under these conditions gave the corresponding primary sulfonamides in high yields. The method does not cleave methoxy groups and prevents incorporation of tert-butyl groups onto electron-rich aromatic rings.     

Synthesis of polypeptide/inorganic hybrid block copolymers

Polypeptide/inorganic hybrid copolymers were obtained by a four-step synthetic approach combining (i) atom transfer polymerization of tert-butyl acrylate, (ii) chemical modification of the bromo end groups of ATRP-polymers into primary amino group using Gabriel reaction, (iii) ring opening polymerization of N_ε-trifluoroacetyl-l-lysine or γ-benzyl-l-glutamate N-carboxyanhydrides followed by (iv) the transamidification reaction using a large excess of (3-aminopropyl)trimethoxysilane to substitute the tert-butyl groups of the poly(tert-butyl acrylate) block. Products were characterized using ¹H NMR, FT-IR, DSC and MALDI-TOF MS. These techniques proved that polymerization of tert-butyl acrylate was controlled whatever the molecular weight targeted and that bromide was quantitatively converted to amino end group by a original method leading to the synthesis of copolymers in the presence of N-carboxyanhydrides as monomers. Amphiphilic polypeptide/inorganic hybrid copolymers were then achieved.     

Kinetics of heat-induced and photochemical transformations of quinonimines and their derivatives

Heat-induced transformations of N-[2,6-diisopropylphenyl]-3,5-di(tert-butyl)-, N-[2,6-diethylphenyl]-3,5-di(tert-butyl)-, and N-[2-methyl-6-ethylphenyl]-3,5-di(tert-butyl)-o-benzoquinonimines in nonane follow the first-order rate equation, whereas that of N-[2,5-di(tert-butyl)phenyl]-3,5-di(tert-butyl-o-benzoquinonimine obey the second-order rate equation. Kinetic parameters of these reactions have been determined. 4aH-Phenoxazine derivatives of quinonimines are intermediates of the heat-induced transformations following the first-order kinetics; under the irradiation with 405 nm light they undergo the ring opening to give the starting compounds with quantum yield close to unity.     

Synthesis of a ferrocenyl uracil PNA monomer for insertion into PNA sequences

The deprotection of the tert-butyl group of a ferrocenyl uracil Peptide Nucleic Acid (PNA) monomer, Fmoc-aeg(R)-O^tBu (1) was achieved using a two step synthesis involving hydrolysis in basic conditions to give first the zwitterion of ⁺NH₃-aeg(R)-O⁻ (7). Compound 7 was reacted in situ with N-(9-fluorenylmethoxycarbonyloxy)succinimide to obtain the expected compound Fmoc-aeg(R)-OH (2) (Abbreviations: Aeg = (2-aminoethyl)-glycine; Fmoc = 9-fluorenylmethoxycarbonyl; O^tBu = tert-butyl; R = 5-(N-ferroce-nylmethylbenzamido)uracyl).     

Tandem mass spectrometry study of C-phenyl-N-tert-butyl nitrone spin adducts from in vitro rat liver microsomal metabolism of bromotrichloromethane and carbon tetrachloride

Electron ionization and thermospray were used in conjunction with tandem mass spectrometry methods to identify trichloromethyl/C-phenyl-N-tert-butyl nitrone (PBN) spin adducts produced in rat liver microsomal dispersions that had been treated with reduced nicotinamide adenine dinucleotide phosphate (NADPH)-generating system and BrCCl₃ (or CCl₄). In the identification of PBN spin adducts, a scan of precursors of m / z 57 was utilized to confirm the presence of PBN spin adducts, because PBN spin adducts produce m / z 57 from tert-butyl as a characteristic fragment. Use of deuterated PBN (PBN-d₉ deuterated at tert-butyl; PBN-d ₁₄ deuterated at both phenyl and tert-butyl) improved the recognition of PBN adducts in mixtures by precursor ion scans, because m / z 66 (which corresponds to the deuterated tert-butyl group) is characteristic and, unlike m / z 57, it is not a common fragment for any other compounds. Two new PBN spin adducts that were not detected before by electron paramagnetic resonance or mass spectrometry were identified by these methods for the first time.     

(Liquid + liquid) equilibria of methanol + ethylbenzene + isooctane + methy <Emphasis Type="Italic">tert</Emphasis>-butyl ether quaternary system at <Emphasis Type="Italic">T</Emphasis> = 303.15 K

Tie line data of {methanol + methyl tert-butyl ether + isooctane} ternary systems were obtained at T = 303.15 K, while data for {methanol + ethylbenzene + isooctane} were taken from literature. The ternary system {methanol + methyl tert-butyl ether + ethylbenzene} and {methyl tert-butyl ether + ethylbenzene + isooctane} were completely miscible. A quaternary system {methanol + ethylbenzene + isooctane + methyl tert-butyl ether} was also studied at the same temperature. In order to obtain equilibium data of the quaternary system, four quaternary sectional planes with several methyl tert-butyl ether/methanol ratios were studied. The effect of the addition of methyl tert-butyl ether on the liquid-liquid equilibrium data of {methanol + ethylbenzene + isooctane} ternary system has been investigate at the same temperature. The distribution curves for ternary and quaternary system was analysed. For the quaternary system {methanol + ethylbenzene + isooctane + methyl tert-butyl ether}, experimental data demonstrated that the distribution coefficient of ethylbenzene between the hydrocarbon and methanol phase on a methyl tert-butyl ether–free basis slightly increases with the increase of methyl tert-butyl ether/methanol ratio. Ternary experimental results were correlated with the UNIQUAC and NRTL equation. The NRTL equation is more accurate than the UNIQUAC equation for the ternary systems studied here. The equilibrium data of three ternary systems were used for determining interactions parameters for the UNIQUAC equation. The UNIQUAC equation fitted to the experimental data appeared to be more accurate than the UNIFAC method for the same quaternary system.