Tetrazol-5-enes

4-Tetrazol-5-enes (Anhydro-5-alkyl-l,2,3,4-tetrazolium Hydroxides) (296) 

The salts (294)197 with malononitrile and triethylamine in boiling acetonitrile yield the new class of meso-ionic heterocycles212 in which the exocyclic carbanionoid residue is a biscyanomethylene group. The diphenyl derivative (296, R1 = R2 = Ph) has a dipole moment of 9.54 D in benzene solution.108 

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Some other highly efficient cycloaddition reactions have been used for polymer end-group modification and polymer-polymer conjugation. These include an additive-free version of the hetero Diels-Alder (HDA) reaction or the nitrile-imine-mediated tetrazole-ene cycloaddition (NITEC), the latter only requiring photoirradiation. Both techniques meet the criteria to be considered bioorthogonal reactions and can be performed under mild reaction conditions. As such, these reactions should also be applicable for the preparation of bioconjugates. 

There are many well-studied photochemical reactions that are clean, high yielding, relatively fast, and require no chemical catalysts. A number of these have been examined for SCNP formation, including the photochemically triggered Diels-Alder reaction between 2,5-dimethylbenzophenone and maleimide, the photo-dimerization of coumarin, the photodimerization of anthracene, and the photo-induced nitrile imine mediated tetrazole-ene cycloaddition. ... 

Chemical Name (6R-trans)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)thio] methyl)-8-oxo-7-([(1-H-tetrazol-1 -yl)acetyl] amino)-5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid sodium salt... 

CN [6R-[6a,7p(/J )]]-7-[(hydroxyphenylacetyl)amino]-3-[[(l-methyl-l//-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid... 

Ceforanide Ceforanide, (6R, 7R)-7[2-(a-amino-o-tolyl)acetamido]-3-[[[l-carboxymethyl-17/-tetrazol-5-yl]-thio]methyl]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (32.1.2.27), is also structurally related to cefamandole, differing in that the acylating acid was o-aminomethylphenylacetic acid, and also in the presence of a carboxyl group in the methyl substituent of the tetrazol ring. It is also synthesized by methods analogous to the synthesis of cefamandole [124-128]. 

N1 - 5-THIA-l-AZABICYCLO(4.2.0)QCT-2-ENE-2-CARBOXYLXC ACID, 7-<2-(<CYAN0METHYL)THX0)ACETAMID0)-6-OXO"3-1I IH-TETRAZOL-S-YLTHIOIMETHYL)-, SODXUM SALT... 

OXA-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID, 7-(2-CARBOXY-2-(p-HYDROXYPHENYL)ACETAMIDO)-7-METHOXY-3-(((1-METHYL-1H-TETRAZOL-5-... 

Moxalactam disodium is a drug entity which was discovered at Shionogi and Company, Limited, Osaka, Japan, and codeveloped with Eli Lilly and Company. The drug is marketed under the trade names of MOXAM and LAMOXAM . The chemical entity is the disodium salt of (6R,7R)-7-[[carboxy(4-hydroxy-phenyl)-acetyl]amino]-7-methoxy-3-[[l-methyl-lH-tetrazole-5-yl)thio]-methyl]-8-oxo-5-oxa-l-azabi cyclo[4.2.0]oct-2-ene-2-carboxyli c acid. 

To a solution of 1 equivalent (eq.) of lH-tetrazole-1-acetic acid and 1 eq. of triethylamine in 20 ml of tetrahydrofuran cooled to -20°C was added 1 eq. of pivaloyl chloride. After thirty-minute stirring of the mixture 20 ml of a chloroform solution containing 1 eq. of and 1 eq. of triethylamine was poured into the solution cooled at -10°C during a period of 30 minutes. The resulting mixed solution was stirred for 30 minutes at the same temperature, for 1 hour in an ice-water mixture and for 3 hours at room temperature. Removal of a solvent from the reaction mixture afforded an oily residue, which was dissolved into 15 ml of 10% sodium bicarbonate aqueous solution. The resulting aqueous layer was adjusted to pH 1.0-2.0 with 10% hydrochloric acid, washed with ether and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and concentrated under reduced pressure leaving a residue which was triturated with ethyl acetate to obtain 3-acetoxymethyl-8-oxo-7-(2-tetrazol-l-acetylamino)-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

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