Diethyl azodicarboxylate formation

The mechanistic pathway" " can be divided into three steps 1. formation of the activating agent from triphenylphosphine and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) 2. activation of the substrate alcohol 1 3. a bimolecular nucleophilic substitution (Sn2) at the activated carbon center. 

Mercaptans have been oxidized with diethyl azodicarboxylate and triphenylphosphine. It is suggested that the formation of a charge-transfer complex (57) may be a key step in the reaction. 

Acyclic ADC compounds, which are more correctly named as derivatives of diazene, are generally prepared from hydrazine derivatives. For example, diethyl azodicarboxylate (Chemical Abstracts name diethyl diazene-1,2-dicarboxylate)5 is prepared from hydrazine by treatment with ethyl chloro-formate followed by oxidation with chlorine in benzene-water.6 Other oxidants which have been used include JV-bromosuccinimide,7 nitric acid,8 inorganic nitrates,9 potassium dichromate,10 silver carbonate on celite,11 and phenyl iodosotrifluoroacetate.12 The hydrazine derivative may also be... 

The reactivity of compound 113 toward reactive linear and cyclic dienophiles was reported in a study directed to find a model systems for the proposed [4+2] cycloaddition in the biosynthesis of the natural products brevianamides, paraherquamides, and marcfortines. With DMAD and diethyl azodicarboxylate the formation of 114 and 115 was almost quantitative after 48 h at 80 °C (Cbz = Carbobenzyloxygroup). When relatively unreactive dienophiles such as cyclopentene and cyclohexene were used, harsh reaction conditions and/or a Lewis acid catalyst are necessary for the formation of 116a and 116b (Scheme 16). In contrast, the analogous intramolecular reaction carried out on compound 117 takes place within a few hours at room temperature, even in the absence of a Lewis acid catalyst, to give 118 in 42% yield (Scheme 16) <2000T6345>. 

Treatment of the cyclic ketene aminal 267 with diethyl azodicarboxylate results in formation of the reduced ring system 268 (Equation 52), probably via an initial aza-ene reaction, followed by fragmentation and ring closure <2002T7791>. 

Azo compounds are reactive dienophiles. Indeed, one of the very first Diels-Alder reactions was the addition of diethyl azodicarboxylate to cyclopentadiene (equation 134)128 129. Other early examples of the reaction are the formation of tetrahydropyridazines from indazolone 252 and phthalazinedione 253 (equations 135 and 136)130. 

As l,2,4-triazole-3,5-dione (PTAD) is a stronger dienophile than acetylenic esters, more facile formation of the Diels-Alder cycloadducts was expected. But because it cannot behave as a diene in a reaction with alkynes such as diethyl azodicarboxylate, the formation of dihydrooxadia-zines is excluded. In spite of these characteristics, no Diels-Alder adducts were obtained in the reaction of l-phenyl-4-vinylpyrazole with PTAD in acetone at -80°C and 2,2-dimethyl-4(l-phenylpyrazol-4-yl)-8-phenyl-l,6,8-triaza-3-oxabicyclo[4.3.0]nona-7,9-dione 277 was obtained as a major product. The isolation of the tetrahydrooxadiazine 277 indicates that the 1,4-dipole 278 was formed and trapped with acetone. 

The Diels-Alder addition of diethyl azodicarboxylate to the thiazole (187) leads to the formation of the tetrahydro derivative (188) (Equation (28)) <89SUL23>. 

Macrolactonization can also be achieved by the Mitsunobu reaction [44] with inversion of the configuration of the alcohol. The reaction principle and mechanism are demonstrated in Scheme 24. Addition of triphenylphosphine to diethyl azodicarboxylate (DEAD, 73) forms a quaternary phosphonium salt 74, which is protonated by hydroxy acid 11, followed by phosphorus transfer from nitrogen to oxygen yielding the alkoxyphosphonium salt 76 and diethyl hydrazinedicarboxy-late 75. Then, an intramolecular Sn2 displacement of the important intermediate 76 results in the formation of the lactone 15 and triphenylphosphine oxide. 

As adenosine antagonists, a great number of 8-substituted xanthines with varying substitution patterns in the 1- and 3-position have been prepared. As starting materials, l,3-dialkyl-5,6-di-aminouracils are used, which are transformed to the 1,3,8-trisubstituted xanthines by one of three methods. The first consists of condensing diaminouracil with an aldehyde to form the imine which is oxidatively cyclized by treatment with diethyl azodicarboxylate (DEAD) in a modification of a reported general procedureto give the appropriate xanthine derivative, e.g. formation of 10. 

The system of PhsP-diethyl azodicarboxylate-hydroxy compound-LiBr allows the formation of alkyl bromides under mild conditions (equation An 5N2-type displacement of an intermediate alkoxy-... 

In total syntheses of 3-lactam antibiotics, the formation of 2-azetidinones is crucial. In a biomimetic synthesis, the N—C4 bond is best closed by the open chain hydroxamate (equation 48), because, depending on the different pATa values of the three potentially ionizable positions, only the ring-forming amide is ionized. 3-halohydroxamates are cyclized by base treatment, whereas 3-hydroxyhydroxamates cyclize via the Mitsunobu reaction (diethyl azodicarboxylate, PhsP). More highly substituted precursors yield isomeric 3-lactams after rearrangement. ... 

The anomeric mixture of C-nucleoside 519 was obtained by C—C bond formation between two subunits the aldehydo-sagat derivative 36 and 2-haloimidazolo[4,5-d]pyrimidine in the presence of butyllithium. The produced acyclo C-nucleoside 518 was cyclized with diethyl azodicarboxylate and triphenylphosphine to 519 [95JAP(K)95/118268] (Scheme 140). 

A new reagent for activating carboxylic acids for amide formation is the phosphonate (396). The azomethine imine (397), obtained from diphenyl-keten and diethyl azodicarboxylate, forms the 1,3-cyclo-adduct (398) with... 

The formation of a 7-pyrone (203) from the reaction of 5-ethoxyoxazoles (199) with diphenylcyclopropenone constitutes an example of a retro-homo-Diels-Alder reaction.353 364 In no case were adducts of the types 200 or 202 isolated. But, nevertheless, stable adducts (204, R = H or Me) have been isolated from the oxazoles (199, R = H or Me) and diethyl azodicarboxylate in 65-66% yield, whereas 199 (R = Me) gives adduct 205... 

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