Trichloroethyl Azodicarboxylate

Chemical Abstracts Nomenclature (Collective Index Number) (Registry Number) 

Benzyl isocyanide (8) Benzene, (isocyanomethyl)- (9) (10340-91-7) 5-Benzylaminotetrazole IW-Tetrazole, 5-(benzylamino)- (8) 1//-Tetra-zol-5-amine, W-(phenylinethyl)- (9) (14832-58-7) 

2-TRICHLOROETHYL) AZODICARBOXYLATE [Diazenedicarboxylic acid, bis(2,2,2-trichloroethyl) ester] 

Submitted by R DANtEL Little and Manuel G Venegas Checked by Sandy Banks and Orville L Chapman 

A Bisi2,2,2-trichloroethyl) hydrazodicarboxylate. In a 500-mL, three-necked flask equipped with mechanical stirrer, thermometer, and 250-mL and 125-mL dropping funnels (Note 1) is placed a solution of 13.34 g (0.23 mol) of 64% hydrazine hydrate (Note 2) in 60 mL of 95% ethanol The reaction flask is cooled in an ice bath and 96 g (0.46 mol) ol 2,2,2-trichloroeihyl chloroforraate (Note 3) is added dropwise so that 

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Table 5.8 summarizes the glycals that had been converted into 2-aminoglycosides so far. In general, photolytic ds/trans isomerization of trans-azodicarboxylates is necessary to accomplish good yields of the initial cycloadducts [335-337]. However, bis-trichloroethyl azodicarboxylate also reacts under thermal conditions and also gives a more reactive cycloaddition product [338,339]. 

Electron-rich aromatic compounds, such as phenol, anisole and A,./V-dimethylaniline, add to bis(2-trichloroethyl) azodicarboxylate under the influence of lithium perchlorate, boron trifluoride etherate or zinc chloride to yield para-substituted products 74, which are transformed into the anilines 75 by means of zinc and acetic acid86. Triflic acid (trifluoromethanesulphonic acid) catalyses the reactions of phenyl azide with benzene, toluene, chlorobenzene and naphthalene, to give TV-arylanilines (equation 34)87. 

Silylated primary allylic amines, e.g. CH2=CHCH2N(SiMe3)2, are produced from allylic chlorides and the mixed reagent AgI/LiN(SiMe3)2205. The formation of allylic amines from olefins by the ene reaction is shown in equation 77. The ene adducts 205 from bis(2,2,2-trichloroethyl) azodicarboxylate are converted into 206 by zinc dust in acetone/acetic acid206. 

B. Bis(2,2,2-trichloroethyl) azodicarboxylate Caution Large amounts of nitrogen oxides are evolved during the oxidation with fuming nitric acid. Therefore, operations should be conducted in an efficient fume hood. 

The synthesis of BENZYL ISOCYANIDE from benzaldehyde via reductive amination with 5-aminotetrazole followed by oxidation of the resultant amine with sodium hypobromite provides a general method for the synthesis of isocyanides. The preparation of BIS(2,2,2-TRICHLOROETHYL) AZODICARBOXYLATE makes available an alternative to dimethyl azodicarboxylate that is not only more reactive in Diels-Alder reactions but whose ester groups can be removed under neutral conditions. 

A. 1 -(2-Acetyl-4,6-dimethoxyphenyl)-1,2-hydra2inedicarboxy ic acid bis(2,2,2-trichloroethyl) ester. A 2-L, round-bottomed flask, equipped with a magnetic stirrer, thermometer, and an ice bath is charged with 3,5-dimethoxyacetophenone (20.00 g, 111.0 mmol) (Note 1) and dichloromethane (CH2CI2, 555 mL) (Note 1). At 0-5°C, under nitrogen, trifluoromethanesultonic acid (980 pL, 11.1 mmol) (Note 1) is added in one portion. To the resulting yellow solution, bis(2,2,2-trichloroethyl) azodicarboxylate... 

Bis(2,2,2-trichloroethyl) azodicarboxylate was purchased from Aldrich Chemical Company, Inc. It can also be prepared as described in reference 2. 

Acetyl-4,6-dimethoxyphenyl)-l, 2-hydrazinedicarboxylic acid bis(2,2,2-trichloroethyl) ester 1,2-Hydrazinedicarboxyiic acid, l-(2-acetyl-4,6-dimethoxyphenyl)-, bis(2,2,2-lrichloroethy ) ester (13) (154876-13-8) Trifluoromethanesulfonic acid Methanesulfonic acid, trifluoro- (8,9) (1493-13-6) Bis(2,2,2-trichloroethyl) azodicarboxylate Diazenedicarboxylic acid, bis(2,2,2-trichloroethyl) ester (9) (38857-88-4)... 

We know of no instances of explosions with t-butyl azodicarboxylate [Org. Synth., Coll. Vol. V. 1973, 1601 or bis(2,2,2-trichloroethyl) azodicarboxylate [Org. Synth., Coll. Vol. VI11990, 56], which would be expected to be less prone to explosion than the methyl or ethyl azodicarboxylates because of their higher molecular weights. Nevertheless, for safety they too should be prepared and handled behind good shielding and, if they are to be kept for a long time, stored in a shock-stable solvent as described above. 

DIELS-ALDER DIENOPHILES Bis(2,2,2-trichloroethyl) azodicarboxylate. 1-Bromo-2-chlorocyclopropene. Chromium carbene complexes. (R)-Ethyl p-tolysulfinyl-methylenepropionate.l (S)-a-Hydroxy-p,p-dimethylpropyl vinyl iketone. (IR)-m-3-Hydroxy isobomyl ndopentyl ether. Oxa-zolidones, chiral. Phdnylselenenyl ben-zenesulfonate. 

Catalysis of reactions of triorganotin phenoxides with diethyl azodicarboxylate, bis(trichloroethyl) azodicarboxylate and diethyl acetylenedicarboxylate... 

Both 1,4-dimethoxy- and 1,4-di-/-butyloxy-1,3-butadiene give moderate yields of diethyl 3,6-dialkoxy-l,2,3,6-tetrahydropyridazine-l,2-dicarboxylates by [4 + 2] cycloaddition with diethyl azo-dicarboxylate. The butadienes are formed as mixtures of geometrical isomers, and at least for the t-butyloxy case, it was shown that the (Z,Z) isomer did not react under the conditions used <82JOC5083, 83JOC3096>. 2-Cyanobutadiene, produced in situ from 3-cyano-2,5-dihydrothiophene dioxide, reacts with diethyl azodicarboxylate to give diethyl 4-cyano-l,2,3,6-tetrahydropyridazine-l,2-dicar-boxylate in 95% yield <88T6451>. Bis(trichloroethyl) azodicarboxylate undergoes cycloaddition with... 

The [4+2] cycloaddition reaction of furanoid and pyranoid glycals with azodicarboxylates allows the introduction of a nitrogen atom at C-2 of a carbohydrate, and the adducts thus obtained can be converted to structurally complex 2-amino saccharides under mild conditions. Towards this end, dibenzyl and bis(2,2,2-trichloroethyl) azodicarboxylates were used as dienes since they allow the free amines to be generated in a single operation under mild conditions later in the synthetic sequence. 

TABLE m AMINATION OF GLYCALS WITH BIS(2,2.2-TRICHLOROETHYL) AZODICARBOXYLATE... 

In general, on water reactions of nonpolar hquid substrates are the most efficient. However, reactions in which one of the components is sohd can also be effectively carried out on water if adequate mixing is provided. The ene reaction of cyclohexene with bis(trichloroethyl) azodicarboxylate (45) was shown to proceed at a much faster rate on water than in the absence of solvent or when carried out in nonpolar solvent (Fig. 11.13). ... 

Figure 11.13 Ene reaction of cydohexene with bis(trichloroethyl) azodicarboxylate.

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