Azodicarboxylic acid esters diethyl azodicarboxylate

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... 

Diethyl azodicarboxylate Formic acid, azodi-, diethyl ester (8) Diazenedicarboxylic acid, diethyl ester (9) (1972-28-7)... 

ETHYL AZODICARBOXYLATE (Formic acid, azobis-, diethyl ester)... 

An interesting alternative in using diols, but starting from 3,4-dihydroxythiophene-2,5-dicarboxylic acid diethyl ester (the same intermediate as used in the Gogte pathway above), was developed independently by the groups of Reynolds [25] and Bauerle [26], who utilized the Mitsunobu reaction with azodicarboxylic acid ester-phosphane as the etherification agent. 

Kauhaluoma and Samanta used miinchnone as the key intermediate to obtain a triazole core (Scheme 9.41). Starting with Ameba resin 351, 3.84 equiv of amino acid ester 352 and 25 equiv of NaBHaCN were employed for the reductive alkylation in 1% acetic acid in DMF at room temperature for 12 h. Resin 353 was treated with 10 equiv of carboxylic acid chloride 354 in the presence of 12 equiv of A,A-diisopropylethylamine in DCM at room temperature for 12h to form amide 355, which was treated with 5% KOH in dioxane H20 (3 1) for 4h to give the corresponding carboxylic acid. Resin 356 was treated with 23.5 equiv of acetic acid anhydride, 3 equiv of DEAD (diethyl azodicarboxylate) 357, and 3 equiv of 4-phenyl-4/f-l,2,4-triazoline-3,5-dione 358 in DCM at room temperature for 5-10 h, giving the miinchnone intermediate 359, which reacted with compound 357 or 358 to form resin 360. Treatment of this with 30% TFA in DCM at room temperature for 1.5 h resulted in cleavage from the resin, producing 361. 

Cydization of P-hydroxy-a-amino esters under Mitsunobu reaction conditions is an alternative approach to aziridine-2-carboxylic esters [6b, 13-16], In this case the P-hydroxy group is activated by a phosphorus reagent. Treatment of Boc-a-Me-D-Ser-OMe 13 (Scheme 3.5) with triphenylphosphine and diethyl azodicarboxylate (DEAD), for example, gave a-methyl aziridinecarboxylic acid methyl ester 14 in 85% yield [15]. In addition to PPh3/DEAD [13b, 15], several other reagent combi-... 

We were not able to obtain any cycloadduct from unactivated 2-azadienes 139 and esters of acetylenedicarboxylic acid. However, we found that 139 did cycloadd to typical electron-poor dienophiles such as esters of azodicarboxylic acid and tetracyanoethylene (Scheme 62). Thus, diethyl and diisopropyl azodicarboxylates underwent a concerted [4 + 2] cycloaddition with 139 to afford in a stereoselective manner triazines 278 in 85-90% yield (86CC1179). The minor reaction-rate variations observed with the solvent polarity excluded zwitterionic intermediates on the other hand, AS was calculated to be 48.1 cal K 1 mol-1 in CC14, a value which is in the range of a concerted [4 + 2] cycloaddition. Azadienes 139 again reacted at room temperature with the cyclic azo derivative 4-phenyl-1,2,4-triazoline-3,5-dione, leading stereoselectively to bicyclic derivatives 279... 

When esterification is achieved under the Mitsunobu conditions (diethyl azodicarboxylate, Ph3P), only esters at positions 6 and 6 are produced, and isolation of the 6-monoester, which is formed faster is possible. Thus diesters can be efficiently prepared.97 99 In this type of reaction, when the carboxylic acid is... 

One of the most widely used procedures for dehydrative coupling and cyclization reactions is the Mitsunobu reaction in which the components are treated with triphenylphosphine and diethyl azodicarboxylate (DEAD, EtOaC—N=N—COiEt). The overall equation for reaction of an alcohol 67 with an acid 68 to form the ester 69 is as shown and the active species is the zwitterionic... 

The Mitsunobu esterification of carboxylic acids with alcohols in the presence of Ph3P and DEAD (diethyl azodicarboxylate) occurs under neutral conditions and provides the corresponding esters in high yields. 

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-... 

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. 

In the Mitsunobu reaction, a chiral 2° alcohol and a carboxylic acid are converted to an ester with clean inversion at the electrophilic C. The reaction requires PI13P and Et02CN=NC02Et (diethyl azodicarboxylate, DEAD). It is usually carried out by adding DEAD slowly to a mixture of the alcohol, PI13P, and the nucleophile in its protonated form. 

---