Di-tert-butyl Azodicarboxylate Research Articles

Thermal decomposition mechanism and hazard assessment of di-tert-butyl azodicarboxylate (DBAD)

Thermal decomposition mechanism and hazard assessment of di-tert-butyl azodicarboxylate (DBAD)

Photocatalytic Methane Conversion: Insight into the Mechanism of C(sp 3 )–H Bond Activation

Photocatalytic Methane Conversion: Insight into the Mechanism of C(sp ³ )–H Bond Activation

Concise Synthesis of (S)-7-Hydroxy-5-aza-8a-epi-d-swainsonine from a d-Erythrose Derivative

AbstractA five-step synthesis of (S)-7-hydroxy-5-aza-8a-epi-d-swainsonine [(3S,4S,4aS,5S,6R)-octahydropyrrolo[1,2-b]pyridazine-3,4,5,6-tetraol] was accessed in good overall yield from readily available d-erythrosyl benzylidene acetal buta-1,3-diene. The key step of the reaction sequence is a full stereoselective Diels–Alder cycloaddition between­ the diene and dienophile: diethyl azodicarboxylate (DEAD) or di-tert-butyl azodicarboxylate (DBAD). The cycloadducts were further transformed into the title 5-aza-indolizidine. Optimized procedures were obtained for the synthesis of intermediates and products.

Asymmetric Synthesis of γ-Amino-Functionalised Vinyl Sulfones: De Novo Preparation of Cysteine Protease Inhibitors

AbstractThe enantioselective azo-based α-amination of an aldehyde followed by a Horner–Wadsworth–Emmons-based vinyl sulfone formation is reported. The thus obtained optically active N,N′-diprotected trans-(phenylsulfonyl)vinyl hydrazine products were then converted into the corresponding N-functionalised trans-(phenylsulfonyl)vinyl amines. Specifically, reaction of 4-phenylbutanal with di-tert-butyl azodicarboxylate (DBAD) in the presence of l- or d-proline, followed by addition of diethyl [(phenylsulfonyl)methyl]phosphonate, gave either enantiomer of di-tert-butyl trans-1-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]hydrazine-1,2-dicarboxylate. The enantiomeric excesses of the (+)- and (–)-enantiomers prepared in this manner were in the range 86–89%. The conversion of these γ-hydrazino vinyl sulfones into the corresponding γ-amino-substituted compounds was achieved following a Boc deprotection, Zn reduction, N-functionalisation sequence. This three-step sequence was reasonably efficient (approx. 50%) and no erosion of enantiopurity was found to have taken place. The compounds accessed via this process include both enantiomers of tert-butyl trans-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]carbamate and epimeric dipeptide mimetics including 4-methyl-N-{(S)-1-oxo-3-phenyl-1-[((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino]propan-2-yl}piperazine-1-carboxamide (also known as K777).

N-Hydroxyphthalimide catalyzed hydrazination of polyethylene glycol

In this work, N-hydroxyphthalimide (NHPI) was used as catalyst to cleave CH bonds in polyethylene glycol (PEG) backbones to generate carbon free radicals that reacted with the NN bonds of di-tert-butyl azodicarboxylate (DBAD) to form CN grafts (PEG-g-DBAD). Subsequently, the tert-butoxycarbonyl (-Boc) groups of PEG-g-DBAD were removed by treating with trifluoroacetic acid (TFA) to obtain hydrazino functionalized PEG (PEG-g-NHNH2). The structure of functionalized PEG was confirmed by Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance spectroscopy (1H NMR), elemental analysis and size exclusion chromatography (SEC). Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) were applied to investigate thermal stability and crystallization properties of the functionalized PEG. The synthesized PEG-g-NHNH2 could be used to toughen epoxy resin (EP). The results of mechanical testing and SEM images indicated that the compatibility between PEG backbones and EP has been improved due to the existing of hydrazino groups. The grafted hydrazine groups could also react with 2-bromoisobutyryl bromide (BIBB) to obtain PEG-g-BIBB which initiated the polymerization of (methyl) methacrylate (MMA) by ARGET-ATRP. Thus, we presented a methodology with high efficiency for hydrazination of PEG under mild condition, and the functionalized PEG might have many potential applications.

Decarboxylative hydrazination of unactivated carboxylic acids by cerium photocatalysis.

We report the cerium photocatalyzed radical decarboxylative hydrazination of carboxylic acids with di-tert-butylazodicarboxylate (DBAD). The operationally simple protocol provides rapid access to synthetically useful hydrazine derivatives and overcomes current scope limitations in the photoredox-catalyzed decarboxylation of carboxylic acids.

Direct Amination of Polyethylene by Metal-Free Reaction

Using recently developed alkane C–H amination chemistry, a mild postmodification of polyethylene (PE) to form C–N grafts without using a metal catalyst is reported. This method applies N-hydroxyphthalimide (NHPI) as an organic catalyst to cleave C–H bonds to generate a carbon radical that reacts with the N═N of dialkyl azodicarboxylates to form a hydrazine unit. The amination of linear PE was successfully conducted with bis(2,2,2-trichloroethyl)azodicarboxylate (BTCEAD) and di-tert-butyl azodicarboxylate (DBAD) in the presence of NHPI in tetrachloroethane at 110 °C. Both BTCEAD and DBAD units have been introduced into PE chains. By optimizing the conditions, like time and feed ratio, the number of grafted BTCEAD units can reach about 10 per 100 ethylene units. Moreover, the DBAD units of PE may be transformed into hydrazine units by treating with trifluoroacetic acid (TFA). The PE modified by BTCEAD and DBAD grafts was blended with poly(methyl methacrylate) (PMMA) and the compatibility was greatly improve...

Mechanism of Copper/Azodicarboxylate-Catalyzed Aerobic Alcohol Oxidation: Evidence for Uncooperative Catalysis.

Cooperative catalysis between Cu(II) and redox-active organic cocatalysts is a key feature of important chemical and enzymatic aerobic oxidation reactions, such as alcohol oxidation mediated by Cu/TEMPO and galactose oxidase. Nearly 20 years ago, Markó and co-workers reported that azodicarboxylates, such as di-tert-butyl azodicarboxylate (DBAD), are effective redox-active cocatalysts in Cu-catalyzed aerobic alcohol oxidation reactions [Markó, I. E., et al. Science 1996, 274, 2044], but the nature of the cooperativity between Cu and azodicarboxylates is not well understood. Here, we report a mechanistic study of Cu/DBAD-catalyzed aerobic alcohol oxidation. In situ infrared spectroscopic studies reveal a burst of product formation prior to steady-state catalysis, and gas-uptake measurements show that no O2 is consumed during the burst. Kinetic studies reveal that the anaerobic burst and steady-state turnover have different rate laws. The steady-state rate does not depend on [O2] or [DBAD]. These results, together with other EPR and in situ IR spectroscopic and kinetic isotope effect studies, reveal that the steady-state mechanism consists of two interdependent catalytic cycles that operate in sequence: a fast Cu(II)/DBAD pathway, in which DBAD serves as the oxidant, and a slow Cu(II)-only pathway, in which Cu(II) is the oxidant. This study provides significant insight into the redox cooperativity, or lack thereof, between Cu and redox-active organic cocatalysts in aerobic oxidation reactions.

ChemInform Abstract: Organocatalytic Asymmetric α‐Amination of Unprotected 3‐Aryl and 3‐Aliphatic Substituted Oxindoles Using Di‐tert‐butyl Azodicarboxylate.

The bifunctional quinine-derived thiourea catalyst 14 was found to catalyze the direct amination of unprotected 3-aryl and aliphatic substituted oxindoles with di-tert-butyl azodicarboxylate (DBAD) to construct a tetrasubstituted stereogenic carbon center at the C-3 position of oxindoles in good to excellent yield and enantioselectivity.

Synthesis of oleophilic electron-rich phenylhydrazines

Phenylhydrazines 1 substituted with two or three long-chain alkyl, alkoxy or alkylsulfanyl groups were successfully prepared by acid-induced removal of the Boc group in hydrazides 2. The reaction is carried out with 5 equivalents of TfOH in CF3CH2OH/CH2Cl2 at −40 °C for 1.5 min. Under these conditions, the deprotected hydrazine 1 is fully protonated, which increases its stability in the reaction medium. The hydrazines were isolated in 60–86% yields and purities >90%. The hydrazides 2 were obtained in 43–71% yields from aryl bromides 5, which were lithiated with t-BuLi and subsequently reacted with di-tert-butyl azodicarboxylate (DTBAD).

Organocatalytic Asymmetric α‐Amination of Unprotected 3‐Aryl and 3‐Aliphatic Substituted Oxindoles using Di‐tert‐butyl Azodicarboxylate

AbstractThe bifunctional quinine‐derived thiourea catalyst 14 was found to catalyze the direct amination of unprotected 3‐aryl and aliphatic substituted oxindoles with di‐tert‐butyl azodicarboxylate (DBAD) to construct a tetrasubstituted stereogenic carbon center at the C‐3 position of oxindoles in good to excellent yield and enantioselectivity.

ChemInform Abstract: Diastereoselective Electrophilic Amination of Ketone Enolates in 2- Substituted 2-Acyl-1,3-dithiane 1-Oxides.

Abstract Enolate anions derived from 2-substituted 2-acyl-1,3-dithiane 1-oxides react readily with the nitrogen electrophile di- tert -butyl azodicarboxylate (DBAD) to give α-aminoketones with good diastereoselectivity and in reasonable yields; in some cases diastereoselectivity appears sufficiently high that the minor isomer cannot be detected by 400 MHz 1 H NMR spectroscopy.

One-Pot Synthesis of N-Arylpyrazoles from Aryl Halides

A facile one-pot synthesis of functionalized pyrazoles from aryllithium or arylmagnesium compounds, di-tert-butylazodicarboxylate (DBAD) as hydrazine equivalent and 1,3-dicarbonyl compounds or equivalents thereof is reported affording the desired pyrazoles in good yields.

Redox‐Switchable Phase Tags – Facile Mitsunobu Reactions using Ferrocenyl‐Tagged Triphenylphosphine

AbstractThe use of redox‐switched phase tags in ferrocenyl‐substituted triphenylphosphine combined with DBAD (di‐tert‐butyl azodicarboxylate) allows high yield (>90 %) Mitsunobu transformations without the need for the chromatographic purification of the products. The redox‐switchable phosphine can be easily synthesized in two steps from 4‐bromoaniline, ferrocene and chlorodiphenylphosphine. It is separated from the reaction mixture by oxidation with iron(III) chloride and can be recycled efficiently by reductive treatment.

An Exception to the Normal Mitsunobu Reaction with Phenols: The Formation of Hydrazones from Salicylaldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient synthesis of orthogonally protected anti-2,3-diamino acids

An asymmetric synthesis of anti-2,3-diamino acids is reported. The enolates of N, N-dibenzylated β 3-amino esters were treated with di- tert-butyl azodicarboxylate (DBAD) to afford their N′, N″-di-Boc-2-hydrazino derivatives with excellent anti diastereoisomeric ratio. Final Boc removal and reductive cleavage of the hydrazino bond led to the expected 2,3-diamino esters having only one free amino group. In comparison with other asymmetric C-2 amination procedures, this method does not need the use of expensive chiral reagents and/or chiral auxiliaries, while leads to products which can be orthogonally protected.

An exception to the normal Mitsunobu reaction with phenols; the formation of hydrazones from salicylaldehydes

The reaction of 2-hydroxybenzaldehydes with alkanols in the presence of triphenylphosphine and di- tert-butyl azodicarboxylate (DBAD), under the Mitsunobu reaction conditions, gives rise to the formation of hydrazones as the major products rather than the expected alkyl aryl ethers.

Efficient, copper-catalyzed, aerobic oxidation of primary alcohols.

An additive is the key to success: Catalytic amounts of N-methylimidazole are crucial for the aerobic oxidation of primary aliphatic alcohols in the presence of CuCl, 1,10-phenanthroline (phen), and di-tert-butyl azodicarboxylate (DBAD). This reaction, under neutral conditions, yields the aldehydes quantitatively and selectively without overoxidation to the carboxylic acids.

Synthesis, NMR, and X-ray Crystallographic Analysis of C-Hydrazino-C-Carboxycarboranes: Versatile Ligands for the Preparation of BNCT and BNCS Agents and 99mTc Radiopharmaceuticals

Protected hydrazine derivatives of ortho-, meta-, and para-carboranes were synthesized in good to excellent yields by reacting the mono-lithio salts of the respective carboranes with di-tert-butyl azodicarboxylate (DBAD). Subsequent deprotonation of the remaining carborane CH group, followed by the addition of CO(2)(g), resulted in the formation of bifunctional C-hydrazino-C-carboxycarboranes in good to excellent overall yields. Crystal structures of the monosubstituted ortho-carborane, 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,2-dicarba-closo-dodecaborane (8) [a = 21.213(6) A, b = 10.498(3) A, c = 9.866(2) A, alpha = gamma = 90 degrees, beta = 90.529(4) degrees ] and the bifunctional para-carborane 1-[(N,N'((tert-butyloxy)carbonyl)hydrazino)]-1,12-dicarba-closo-dodecaborane-12-carboxylic acid (3) [a = 12.744(10) A, b = 12.875(9) A, c = 14.767(9) A, alpha = beta = gamma = 90 degrees ] were obtained. Intermolecular hydrogen bonding was a dominant packing feature in both structures. The reported compounds represent a unique class of bifunctional carboranes that can be used in peptidomimetic research and as synthons to prepare novel radiopharmaceuticals and boron neutron capture therapy/boron neutron capture synovectomy (BNCT/BNCS) agents.

Diastereoselective electrophilic amination of ketone enolates in 2-substituted 2-acyl-1,3-dithiane 1-oxides

Enolate anions derived from 2-substituted 2-acyl-1,3-dithiane 1-oxides react readily with the nitrogen electrophile di- tert-butyl azodicarboxylate (DBAD) to give α-aminoketones with good diastereoselectivity and in reasonable yields; in some cases diastereoselectivity appears sufficiently high that the minor isomer cannot be detected by 400 MHz 1H NMR spectroscopy.