Diethyl azodicarboxylate, in the

The Mitsunobu reaction was also applied to the synthesis of [ 1,2,4]triaz-ino[4,5-n]indoles (84AG517). Thus, reaction of the 2-acylindoles 127 with sodium borohydride in methanol or with lithium aluminium hydride in tetrahydrofuran gave the corresponding alcohols 128. Their cyclization with diethyl azodicarboxylate in the presence of triphenyl-phosphine gave the triazinoindoles 129. Acid treatment of the latter afforded 130 (Scheme 30). 

Cyclization of 1 -amino-8-(2-hydroxyalkyl)-4-oxoquinoline-3-carboxyl-ates (130) on the action of diethyl azodicarboxylate in the presence of triphenylphosphine afforded 7-oxopyrido[3,2,l-jy]cinnoline-8-carboxylates (131) (92EUP470578). 

Aromatic compounds add to DEAD (diethyl azodicarboxylate), in the presence of InCl3-Si02 and microwave irradiation, to give the A-aryldiamino compound [ ArNCCOaEO-NHCOaEt]. ... 

A different chemical method for the preparation of 5-thioaldopyranosides was chosen by Hashimoto and coworkers [40] (Scheme 9.2). They converted per-O-benzylated methyl (3-d-glucopyranoside 33 into the open-chain mixed acetal 34, which, in turn, was treated with the Mitsunobu system triphenylphosphine and diethyl azodicarboxylate in the presence of benzoic acid to yield protected 5-thio-L-idopyranosides 35. 

Mitsunobu, O., Yamada, M., Mukaiyama, T. Preparation of esters of phosphoric acid by the reaction of trivalent phosphorus compounds with diethyl azodicarboxylate in the presence of alcohols. Bull. Chem. Soc. Jpn. 1967,40, 935-939. 

Isocyanides. Ugi et at.3 investigated the synthesis of isocyanides (2) by dehydration of N-monosubstituted formamides (1) with triphenylphosphine-diethyl azodicarboxylate. In the 11 cases investigated, no isocyanide could be obtained in six of them. In the... 

A soln. of ethyl tetraethylphosphorodi imidite in tetrahydrofuran added dropwise at room temp, to benzoic acid and diethyl azodicarboxylate in the same solvent, stirred 9 hrs., and coned. -> ethyl benzoate. Y 90.7%. F. e. s. O. Mitsunobu and M. Eguchi, Bull. Chem. Soc. Japan 44, 3427 (1971). 

The conversion of an alcohol to an amine can be achieved in a one-pot reaction the alcohol 1 is treated with hydrazoic azid (HN3), excess triphenylphosphine and diethyl azodicarboxylate (DEAD). The initial Mitsunobu product, the azide 14, further reacts with excess triphenylphosphine to give an iminophosphorane 15. Subsequent hydrolytic cleavage of 15 yields the amine—e.g. as hydrochloride 16 ... 

A solution of phenylaminomethylenemalonate (1485) in THF was added to a solution of triphenylphosphine and diethyl azodicarboxylate in THF at -20°C. The reaction mixture was warmed to room temperature, diluted with water, and extracted with ethyl acetate to give methylenemalonate (1486) in 75-99% yields (87USP4636506). 

In a 1-1., three-necked, round-bottomed flask equipped with a constant-pressure dropping funnel, a mechanical stirrer, and a reflux condenser is placed 174 g. (1.0 mole) of ethyl azodicarbox-ylate in 150 ml. of ether. Freshly prepared cyclopentadiene (70 g., 1.06 moles) is added dropwise over a 1-hour period to the stirred ethereal solution of diethyl azodicarboxylate. During the addition a gentle reflux is maintained by external cooling with an ice-water bath as needed. When the addition is complete, the reaction mixture is allowed to stand for 4 hours, or less if the yellow color of the azodicarboxylic acid ester disappears. I he dropping funnel and condenser are replaced by a glass stoj)pcr and a short distillation head, respectively. The ether and unreactcd diene are distilled off on a steam bath and the... 

OH - —NTfCHj. Primary or secondary alcohols are converted to protected secondary amines by this triflamide under Mitsunobu conditions (triphenylphos-phine, diethyl azodicarboxylate) in 70-86% yield. The reaction proceeds with inversion, and is useful for preparation of optically active secondary amines. 

The acetate ofthis alcohol is used in a Diels-Alder reaction with the interesting dienophile DEAD (diethyl azodicarboxylate—in orange). 

Va represented one stereochemically satisfactory example of the possibilities (71). The reaction of gelsemine with diethyl azodicarboxylate rendered the first of these untenable, but the structure VI (position of ether link again unspecified), advanced in lieu of Va or Vb (75) was in turn invalidated by the discovery that the molecule contains a vinyl side chain. 

Dichlorocarbene addition to azodicarboxylate esters, Phenyl(bromodichloro-mcthyl)mercury reacts with diethyl azodicarboxylate to give phenylmercuric bromide (98% yield) and a product (87% yield) which was found not to be the expected di-aziridine( I), but to have the structure (2). The same product is obtained by decarboxylation of CCIjCOONa in the presence of diethyl azodicarboxylate in refluxing 1,2-dimethoxyethane (69% yield). 

Both saturated and benzylic alcohols are dehydrogenated by refluxing with diethyl azodicarboxylate in benzene for 10 h. The azodicarboxylate is converted into hydrazodicarboxylate, while the alcohols give ketones in 51-87% yields [977. ... 

This method is unusually mild, using neutral conditions and low temperatures (20 °C and less). It tolerates a number of functional groups in the components (e.g. acetals, esters, alkenes, etc.)- The alcohol, the carboxylic acid and triphenylphosphine are treated dropwise in an inert solvent (dichloromethane, THF, ether) with diethyl azodicarboxylate (DEAD). The ester is formed rapidly. However, tedious chromatography is frequently required to remove the by-products, triphenylphosphane oxide and hydrazo ester. The main value of the reaction lies in the clean inversion of configuration at a secondary carbinol center and in its selectivity towards primary hydroxy groups (vide infra). Inversions are usually performed with benzoic or p-nitrobenzoic acid. The benzoates are purified and saponified with aqueous base to furnish the inverted alcohols in overall yields of ca. 50%. Elimination is the main side reaction. Thus, from (44) 75% of the desired Sn2 product (45) is formed, along with 25% of the elimination product (46) (equation 19). The mechanism of the reaction has been clarified to the point that betaine (47) is the pri-... 

The synthesis of 2,2-difluoro 3-amino-deoxystatine (74) is shown in Scheme 4. The key reaction is the stereospecific intramolecular Mitsunobu reaction (75). Condensation of the sodium carboxylate 7 with p-methoxyaniline gave the amide 8. Intramolecular cyclization with triphenylphosphine and diethyl azodicarboxylate afforded the P-lactam 9. Basic hydrolysis of the P-lactam ring gave the sodium salt of the protected difluoro 3-amino-deoxystatine 10. This proved useful in the preparation of peptide XII. 

Another well-known process that utilizes a nucleophilic phosphane is the Mit-sunobu reaction, that is, the reaction between an acidic partner and an alcohol, typically facilitated by an azodicarboxylate and a phosphane. Two options are possible, anchoring of the electrophilic part to the solid support, dealt with in the next section, or anchoring of the nucleophilic phosphane. Georg et al. used polystyrene-bound triphenylphosphane and DEAD (diethyl azodicarboxylate) in their synthesis of aryl ethers [31]. Alcohols were reacted successfully with electron-rich and electron-deficient phenols, giving the desired products in good yield and purity. More recently, Wilhite and coworkers disclosed an efficient protocol for the synthesis of pyridine ethers using ADDP [l,l -(azodicarbonyl)dipiperidine] and polymer-supported triphenylphosphane (Scheme 6.9) [32], Both methods eliminate purification problems caused by triphenylphosphane oxide, but chromatography is still needed. 

The cross-conjugated thione (20 X = S), prepared from the corresponding ketone (20 X = O) with phosphorus pentasulfide, participates in a diene-transmissive Diels-Alder reaction with diethyl azodicarboxylate <90BCJ284>. The 3,4-dihydro-2//-l,2,3-thiadiazine (21) so formed is isolable (see Section 6.13.7.2.2) and on prolonged heating with diethyl azodicarboxylate undergoes further cycloaddition to yield the pyridazino[3,4-e]-l,2,3-thiadiazine derivative (23) in 74% yield (Scheme... 

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