Diethyl azodicarboxylate preparation

To prepare fervenulin 4-oxides 12 or toxoflavine 4-oxides 146, it is convenient to use the reaction of l,3-dimethyl-2,4-dioxopyrimidin-6-yl hydrazone 147 or N-(3-methyl-2,4-dioxopyiimidin-6-yl) iV-methylhydrazone 148 with potassium nitrate in acetic acid [75CPB1885,76CPB338,76JCS(CC)658,82JHC1309,93CPB362]. Diethyl azodicarboxylate can be used instead of potassium nitrate [76JCS(P1 )713]. 

Unsymmetrical disulfides can be prepared by treatment of a thiol RSH with diethyl azodicarboxylate (EtOOCN=NCOOEt) to give an adduct, to which another thiol R SH is then added, producing the disulfide RSSR. ... 

A variety of reagents can function as the electrophile E+ in the general mechanism. The most useful synthetic procedures for preparation of halides are based on the halogens, positive halogens sources, and diethyl azodicarboxylate. A 1 1 adduct formed from triphenylphosphine and bromine converts alcohols to bromides.15 The alcohol displaces bromide ion from the pentavalent adduct, giving an alkoxyphosphonium intermediate. The phosphonium ion intermediate then undergoes nucleophilic attack by bromide ion, forming triphenylphosphine oxide. 

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 3-methyl- and 3-phenyl-l,2,3-oxadiazolinium salts 96 and 97 are capable of oxidizing thiols to disulfides <1995MI817>. New dihydro-1,2,3-benzoxadiazoles, prepared by the reaction of 1,2-benzoquinones with diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) in the presence of triphenylphosphine (Section 5.03.9.4), have been shown to undergo catalytic hydrogenolysis to give phenols (Equation 12) <20050L5139>. 

Diethyl azelate, 45, 31 Diethyl azodicarboxylate, reaction with cyclopentadiene, 49,1 Diethylbenzene as solvent for decomposition of diphenyIiodonium-2-carboxylate in preparation of... 

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... 

A wide variety of species can function as the electrophile E+ in the general mechanism. The most useful synthetic procedures for preparation of halides are based on the halogens, positive halogen sources, and diethyl azodicarboxylate. 

A variety of 2,4-oxazolidinedione moieties have been prepared as precursors to A-acyliminium ions. These, in turn, have been used in synthetic approaches to 13-aza-16-oxasteroids, interesting and novel heterocycles, " and natural products such as ( )-p-conhydrine, 294b, ( )-6>-methylpaUidinine, 297, 4-oxa-2-aza-podophyllotoxin, 299, and morphine, 302. Introduction of the 2,4-oxazolidinedione can be achieved by conventional alkylation. However, it is normally introduced through Mitsunobu chemistry using diisopropyl azodicar-boxylate or diethyl azodicarboxylate. " The former reagent is favored by... 

Hydrogenated derivatives of this system have been prepared from acyclic enyne precursors (Scheme 75) by ringclosing metathesis, followed by [4-1-2] cycloaddition of the resulting diene with diethyl azodicarboxylate <2003S2017>. 

N-Alkyl amides or imides can also be prepared starting from alcohols by treatment of the latter with equimolar amounts of the amide or imide, Ph3P, and diethyl azodicarboxylate (EtOOCN=NCOOEt) at room temperature (the Mitsunobu reaction, see p. 396).925... 

Much work has been done on configuration and conformation, e.g. of 2-methoxy-2-oxo-4,5-diphenyl-l,3,2-dioxaphospholanes with 170 and lsO labelled reagents (81CC245). A large number of 2-dimethylamino-l,3,2-dioxaphospholanes or 3-methoxy-2-methyl-l,3,2,-oxazaphospholanes are mentioned in a recent publication, in which spiro compounds of the general structure (108) were prepared by addition to diethyl azodicarboxylate (equation (69)) (80PS(8)147>. 

A compound formulated as 5-methyl-1,4-dihydro-1,2,4-triazin-3(2//)-one (696) was obtained by sodium hydroxide treatment of compound (697). Reacting (697) with thallium ethoxide led to the isolation of diethyl 5-methyl-3-oxo-l,2,3,4-tetrahydro-l,2,4-triazine-1,6-dicarboxylate (698) (70JOC3792). Since compound (697) is formed by reaction of aminocrotonic ester with diethyl azodicarboxylate, these reactions can also be treated as [3 + 3] atom component preparations. 

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... 

Methods for the conversion of derivatives of morphine into their N-nor-com-pounds, using vinyl chloroformate,149 trichloroethyl chloroformate,150 and phenyl chloroformate,151 have been patented. Norneopine has been prepared from neopine and diethyl azodicarboxylate and by the hydrolysis of 7V-nitrosonor-neopine.152 The conversion of N-nor-bases into N-alkyl-compounds by the reduction of amides has been covered by a further patent.153... 

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. 

Fig. 2.33. Mitsunobu inversion a typical substrate, the reagents, and products (possible preparation of the substrate Figure 2.27). "DEAD" stands for diethyl-azodicarboxylate.

---