Azodicarboxylates preparation

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

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]. 

Preparation of 7-(N,N -Dicarbobenzyloxyhydrazino)-6-Demethyttetracydine A 1.0 g portion of O-demethyltetracycline was dissolved in a mixture of 9.6 ml of tetrahydrofuran and 10.4 ml of methanesulfonic acid at -10°C. The mixture was allowed to warm to 0°C. A solution of 0.86 g of dibenzyl azodicarboxylate in 0.5 ml of tetrahydrofuran was added dropwise and the mixture was stirred for 2 hours while the temperature was maintained at 0°C. The reaction mixture was added to ether. The product was filtered off, washed with ether and then dried. The 7-(N,N -dicarbobenzyloxyhydrazino)-6-demethyltetracycline was identified by paper chromatography. 

All attempts to prepare other [2 + 4] cycloadducts of sulfoxides 115 with dienophiles such as maleic anhydride, ethyl azodicarboxylate, etc., have failed60. A method for preparing ordinary alkyl-substituted thiirene oxides (e.g. 18 R1 = R2 = alkyl) is still lacking. 

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>. 

This class of compound is represented by 2,3-disubstituted-l,2,3-benzoxadiazoles and new caged structures. 2,3-Disubstituted-l,2,3-benzoxadiazoles 128 were prepared in high yield when the Huisgen zwitterion, formed between dialkyl azodicarboxylates 127 and triphenylphosphine, was reacted with 3-methoxy 4,6-disubstituted-l,2-benzoqui-nones 126 (Equation 23 Table 6) <20050L5139>. 

Di-r-butyl azodicarboxylate, BocN=NBoc (1). Preparation.1 Supplier Fluka. 

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. 

In common with other azodicarboxylic acid derivatives, the uses of 4-phenyl-l,2,4-triazoline-3,5-dione are many. It undergoes a Diels-Alder reaction with most dienes11-14 and is, in fact, the most reactive dienophile so far reported.15 16 As with the formation of all Diels-Alder adducts the reaction is reversible, and in the case of the adduct with 3-j3-acetoxy-17-cyano-5,14,16-androstatriene, the reverse reaction can be made to proceed under especially mild conditions.14 An instance has also been reported of the dione photochemically catalyzing other retro Diels-Alder reactions.17 Along with the proven use of azodicarboxylic ester,18-18 the dione should be potentially important in the preparation of strained ring compounds. 

Scheme 6.81 Transformation of one adduct prepared from the 64-catalyzed asymmetric addition of a-substituted P-keto esters to di-tert-butyl azodicarboxylate (a-hydrazination) into the corresponding oxazolidinone amino acid derivative.

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

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>. 

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