Sodium azide tetrazoles

Although SiCh 57 has been employed, e.g., in the presence of sodium azide to convert ketones into tetrazoles (Section 5.3), to condense cyclopentanone in high yields into 1.2.3.4.5.6-tris(trimethylene)benzene (Section 9.2), or used for the condensation of amino acids to polyamides (Chapter 14) with formation of Si02, enol-trimethylsilyl ethers 107 a of ketones such as cyclohexanone are cleanly converted by SiCh 57 in the presence of Hg(OAc)2 into the trichlorosilylenol ether 116, which adds benzaldehyde in the presence of the asymmetric catalyst 117 to give... 

Nitrilium salts, e.g., 66, prepared from the alkylation of nitriles, react with sodium azide to yield 1,5-disubstituted tetrazoles, e.g., 67 (Scheme 7).121 The Schmidt reaction,122 a versatile method for the preparation of 1,5-disubstituted tetrazoles from ketones and hydrazoic acid, can now be regarded as a special case of azide addition to nitrilium salts.123... 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

Compound 145 on lithiation <1999SM(102)987> and subsequent reaction with carbon dioxide afforded compound 146. Sandmeyer reaction of 2-bromodi thieno[3,2-A2, 3 -with copper(l)cyanide in hot iV-methyl pyrrolidine (NMP) gave the corresponding nitrile 148 which was then converted to the tetrazole 149 with a mixture of sodium azide and ammonium chloride in NMP in low overall yield (Scheme 14) <2001JMC1625>. 

Dichlorooxadiazolo[3,4-3]pyrazine 181 forms the tricyclic tetrazole derivative 182 on reaction with sodium azide (Equation 44). The 7-azido group readily undergoes nucleophilic substitution <1997CHE977>. 

Nucleophilic substitution of the chloropyridazine 166 with sodium azide in DMF is followed by cyclization to give the fused tetrazole 167 (Equation 41) <1997JHC39>. 

Aryl and vinyl nitriles have been prepared very efficiently from the corresponding bromides by palladium-catalyzed reactions under microwaves. This energy source has been employed for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions with sodium azide (Scheme 9.66). The direct transformation of aryl halides to the aryl tetrazoles in a one pot procedure could be accomplished both in solution and on a solid support [115], The reactions were complete in a few minutes, a reaction time considerably shorter than those previously reported for the thermal reactions. The cydoadditions were performed with sodium azide and ammonium chloride in DMF and, although no explosion occurred in the development of this work, the authors point out the necessity of taking adequate precautions against this eventuality. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

The conversion of acyl isothiocyanates 47 with sodium azide leads to thiol-functionalized tetrazole derivatives such as 48 (Scheme 9) <1995PJC1022>. The reaction of 48 with chloro acetonitrile leads to an intermediate 49 that reacts in... 

Ring closure to the 5//-tetrazolo[5,l-t][l,3]oxazine skeleton has been reported by Hoornaert and co-workers <1996T8813>. These authors treated variously substituted 2,4-dichloro[l,4]oxazin-2-ones 133 with sodium azide. The fused tetrazoles 135 obtained were formed via the formation of their azide valence bond isomer intermediate 134. A similar approach proved to be suitable for the benzologues of these compounds. Thus, the benzoxazinone compounds 136 gave the tricyclic ring-closed tetrazoles 137. Both reactions yielding 135 and 137 proceeded in high yields (80-90%). 

The tetramethylammonium triazine-olate 55 was treated with sodium azide, whereupon nucleophilic exchange of the trinitromethyl substituent took place to give the azide intermediate 56, which spontaneously underwent valence bond isomerization to the fused tetrazole 57. 

A subsequent report outlined the synthesis of a diastereomer of tetrazole 58 that used similar methodology <1997TL4655>. Treatment of nitrile mesylate 60 with sodium azide affords D-talonotetrazole 62, presumably by intramolecular [1,3] dipolar cycloaddition of a 4-azido-4-deoxy-D-talonitrile intermediate 61. Acid hydrolysis affords the deprotected tetrazole 63 (Scheme 5). 

The reaction of the -C(Hal)=N-function with azide ion or hydrazoic acid is known to give the tetrazole system. As part of a mechanistic study of the one-pot synthesis of an azadibenzoporphyrine in 84% isolated yield from reaction of a 1-bromobenzopyrromethene hydrobromide 74 with sodium azide at 140 °C, 74 was treated with azide at lower temperature (60 °C) in an attempt to isolate the proposed azide mechanistic intermediate 75 however, the fused tetrazole 76 was isolated in 47% yield (identified by X-ray analysis) (Equation 4) <1999MI530>. Upon heating a dimethyl formamide (DMF) solution of tetrazole 76 to 140°C for 1 h, the desired porphyrin was indeed obtained in 14% yield, consistent with the temperature-dependent equilibrium between tetrazole and azide that has been observed with some fused tetrazoles. 

The reaction of sodium azide with N-aryl chloroimines, obtained from benzanilides and thionyl chloride, to form 1,5-disubstituted tetrazoles is catalysed by tetra-n-butyl-ammonium bromide (Scheme 5.26, Table 5.40) [18] in variable yields, but generally <85%. 5-Butyl-2,3-diphenyltetrazolium salts have also been used as catalysts [18, 19]. 1,5-Disubstituted tetrazoles are also obtained from a one-pot sequential reaction of carbodimides with sodium azide and an aroyl chloride in the presence of tetra-n-butylammonium chloride [20]. 5-Chlorotetrazoles are obtained from the catalysed reaction of aryldichloroisocyanides with sodium azide (Scheme 5.26) [21],... 

The high nitrogen content and the endothermic nature of the tetrazole ring lends itself to the synthesis of energetic materials. Compounds such as -H tetrazole and 5-aminotetrazole can be used as nucleophiles to incorporate the tetrazole ring into other molecules. 5-Aminotetrazole is synthesized from the reaction of dicyandiamide with sodium azide in hydrochloric acid. 

The tetrazole procedure that has been proved to be of value in the thiazolo[3,2-6][l,2,4]triazole series (see Section VIII) has also been applied in this field. V-Acylated 2-aminothiadiazoles 193 on treatment with phosphorus pentachloride (120°C) and subsequently with sodium azide (aqueous acetone) yield tetrazoles 194. Thermolysis in tetraline (160-180°C) gives the heterocycles 195 in moderate yields [85IJC(B)908 WFA953]. 

Excerpt 4F is taken from an article written by Demko and Sharpless. (Barry Sharpless was a co-recipient of the Nobel Prize in Chemistry in 2001 for his work on chirally catalyzed oxidation reactions.) In this article, the authors propose a way to synthesize aromatic tetrazoles from nitriles in water, using only sodium azide and a zinc salt. Water, despite its obvious advantages (i.e., safe and inexpensive), rarely succeeds as a solvent in organic synthesis. Thus, a synthesis that uses water successfully is an important scientific accomplishment. 

We report here a safer and exceptionally efficient process for transforming nitriles 1 into tetrazoles 2 in water the only other reagents are sodium azide and a zinc salt (eq 1). 

Very wordy In their article titled Preparation of 5-Substituted IH-Tetrazoles from Nitriles in Water, Demko and Sharpless propose a way to synthesize IH-tetrazoles using nitriles and sodium azide in water. 

Concise IH-tetrazoles have been prepared using nitriles and sodium azide in water. ... 

The addition of sodium azide to nitriles to give IH-tetrazoles is shown to proceed readily in water with zinc salts as catalysts. The scope of the reaction is quite broad a variety of aromatic nitriles, activated and unactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. 

Kadaba (14) reported the first example of an intermolecular cycloaddition of sodium azide with a vinyl azide (60) to give the tetrazole 62 in 25% yield (Scheme 9.14). 

The microwave-assisted preparation of aryl tetrazoles 179 was reported using the intermolecular 1,3-dipolar cycloaddition of aryl nitriles 178 with sodium azide (38) (Scheme 9.38). 

The presence of the propionamide fragment in the stmcture of the anti-inflammatory agent broperamole (125-1) is reminiscent of the heterocycle-based NSAID propionic acids. The activity of this agent may trace back to the acid that would result on hydrolysis of the amide. Tetrazoles are virtually always prepared by reaction of a nitrile with hydrazoic acid or, more commonly, sodium azide in the presence of acid in a reaction very analogous to a 1,3-dipolar cycloaddition. A more recent (and safer) version of the reaction noted later (see losartan, 77-4) uses tributyltin azide. In the case at hand, reaction of the anion of mefa-bromobenzonitrile (125-1) with sodium azide and an acid affords the tetrazole (125-2). Condensation of the anion from that intermediate with ethyl acrylate leads to the product from Michael addition saponiflcation gives the corresponding carboxylic acid (125-3). This is then converted to the acid chloride reaction with piperidine affords broperamole (125-4) [136]. 

Synthesis The cyclization of ethyl isocyanate with sodium azide by means of AICI3 in refluxing THF gives 1 -ethyl-1,4-dihydro-5H-tetrazol-5-one, which is alkylated with 1-chloro-2-bromo-ethane in the presence of Na2CC>3 and Kl in refluxing 4-methyl-2-pentanone to afford 1-ethyl-4-(2-chloroethyl)1,4-dihydro-5H-tetrazol-5-one i (Janssen (Janssen), 1978 Janssens et al., 1986 Hopkins, 1981 Kleemann et al., 1999). 

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