Heterocycles sodium azide

In an earlier study the authors proposed a [3.2.0] bicyclic sulfonium salt 8 as the reactive intermediate in the trimethylsilyl iodide mediated ring contraction of 4-methoxythiephane <1996T5989>. Enantiomerically pure thio-lane derivatives were synthesized via a ring contraction of a seven-membered sulfur heterocycle by nucleophilic transannular substitution <2000TA1389>. The thiepane derivative 15, derived from d-sorbitol, was converted into the dimesyl derivative 16 following deprotection under acidic conditions. Treatment of 16 with sodium azide in DMSO at 120°C yielded the corresponding thiolane as a mixture of two diastereoisomers, 17a and 17b, in a 5 1 ratio (see Scheme 1). 

Boyer and Gunasekaren reported the synthesis of the furazan-based heterocycle NOTO (44), which contains 50 % by mass of nitrogen and is a liquid at room temperature. The flve-step synthesis of NOTO (44) starts from the diazotization of 4,4 -diamino-3,3 -azoxyfurazan (DAAF) (27), followed by reaction with sodium azide to form the diazide (42). Heating the diazide (42) as a solution in acetonitrile induces cyclization to the triazole (43) and this is followed by reduction and oxidation of the remaining azide group to complete the synthesis of NOTO (44). 

The reaction of aminoguanidine bicarbonate (84) with sodium nitrite in the presence of excess acetic acid produces 1,3-ditetrazolyltriazine (89), another nitrogen-rich heterocycle (C2H3N11 = 85 % N) which readily forms explosive metal salts. The reaction of aminoguanidine bicarbonate (84) with sodium nitrite in the presence of mineral acid yields guanyl azide (90), of which, the perchlorate and picrate salts are primary explosives. Guanyl azide (90) reacts with sodium hydroxide to form sodium azide, whereas reaction with weak base or acid forms 5-aminotetrazole. ... 

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]. 

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]. 

It has been shown also that both thiocarbamoylimidazoles 147 and 148 can react with sodium azide. These compounds were successfully used to prepare heterocycle-peptide conjugates as peptidomimetics. A-Terminal aminothiatriazole modified amino acids have been synthesized using two methods (Scheme 35). To prepare monosubstituted aminothiatriazoles 151 the amino acid derivatives were converted into the thiocarbamoyl imidazoles of type 147 that can react with azide ion to form the thiatriazole ring. On the other hand, for the synthesis of disubstituted amino acid derivatives of 1,2,3,4-thiatriazoles 153 and 155 the activation of the thiocarbonyl group via a salt of type 148 was required. The reaction conditions and the yields of thiatriazoles 151, 153, and 154 prepared by this approach are shown in Scheme 35. 

Searching for other 6-membered "diazido malonyl N-heterocycles" we have selected the pyridazine derivative 25 and diazido barbituric acids 32 as model systems, since they are available easily and in large quantities. Compound 25 is obtained in the usual way by chlorination of 23 with sulfuryl chloride and exchange of the halogen atoms with sodium azide. 

Azido-1,3,4-thiadiazoles (87) can be prepared by reaction of hydra-zinothiadiazoles (86) with nitrous acid, and by reaction of halogeno-thiadiazoles with sodium azide. Like similar heterocyclic azides - they may exist as true azides (87) or as tetrazolothiadiazoles (88). Kanaoka prefers the bicyclic formulation when R = Ph, but Bacchetti et al. have shown that in the solid state the compound... 

Additions of hydrazoic acid to carbon-sulphur double bonds may conceivably be of the general type outlined in equation (88) but do not constitute a synthetic route to azides. Recent corrections to the earlier literature relating to this field are, however, noteworthy. It was originally suggested that thiocarbamoyl azides " (193) were obtained from organic isothiocyanates and hydrazoic acid. The spectroscopic studies of Lieber and co-workers " have now established that the products are in fact thiatriazoles (194). The reactions of sodium azide with isothiocyanates , and carbon disulphide , which were also previously considered to furnish organic azides, have now been shown to produce the heterocyclic compounds 195 and 196 respectively. 

The reaction of sodium azide with chloromethyl heterocycles (8) derived from morpholine, thiazine, piperazine and piperidine gave the corresponding ring-expanded compounds (11) along with the normally substituted compounds (10) via the postulated aziridinium intermediate (9) (Scheme 2) (94JCS(P1)2565). 

The use of acetic anhydride as the solvent facilitates432 intermolecu-lar iodide displacements at C-5 of 156. Acylation of the heterocyclic base occurred at N-l (as indicated by infrared spectroscopy) during the reaction, and this inhibited occurrence of intramolecular displacement. The electron-withdrawing effect of the acyl group presumably diminishes the nucleophilicity at N-3. N-Formyl-2, 3 -0-iso-propylidene-5 -0-p-tolylsulfonyladenosine also reacts intermolecu-larly with lithium chloride or sodium azide in methyl sulfoxide to give 5 -chloro and 5 -azido derivatives.432... 

We now return to the attempts to solvolyze primary S-coupled TTF salts. Reasoning that the solvolysis might be triggered in an Sn2 manner with more powerful nucleophiles, the salt 2a was treated with sodium azide [20]. Although TTF was produced, this did not result from a simple substitution reaction, as the other product was the Z-alkene 69. This can be rationalized as resulting from attack by azide at the peripheral alkene bond followed by fragmentation of the heterocycle however it is not clear why only the Z-isomer is detected. No other product was isolated from this reaction, but, to rationalize the formation of TTF, the thio-ketenedithioacetal 70 was proposed as an intermediate. Fragmentation of the azide adduct could occur by either of two possible pathways, as shown in Scheme 12. 

This may be attributed to the spatial proximity of the azide and alkyne substituents enforced by the bulky side chain. After successfully synthesizing amino acid derived fused triazoles 6a-g, 8a, and 8b, we decided to extend the scope of this methodology by varying the alkyl, as well as the acyl components, which may furnish other triazole-fused heterocycles. Accordingly, compound la was treated with chloromethane sulfonyl chloride in the presence of triethylamine to furnish chlorosulfonamide derivative 7c in moderate yield (60%). Compound 7c was then treated with an excess amount of sodium azide in DMF at 100 °C. 

Many examples of 4- or 5-acetyl-1,2,3-triazoIes have been prepared and a number of methods developed. For example, the addition of phenyl azide to acetylphenylacetylene (Eq. 14) gives an excellent yield, and both isomeric products are obtained. The reaction of sodium azide with /3-acetylstyrylsulfones proceeds in good yield (Eq. 15). The diacetyl phenylhydrazone 5.1-12 is smoothly converted to a 1,2,3-triazole under novel conditions that deserve further exploration (Eq. 16). The heterocyclic azide 5.1-13 reacts with 2,4-pentanedione under basic conditions (. 17). The treatment of the amides 5.1-14 with a Grignard reagent produces... 

From these examples, the versatility of 1,3-cycloaddition reactions in the synthesis of 1,2,3-triazoles is apparent. Other strategies, however, are available. Greif and coworkers developed perfluoroalkyl-substituted p-chlorovinylaldehydes as new building blocks for a number of fluorinated heterocyclic systems such as thiazoles, pyridines, pyrazoles, and benzimidazoles. Reaction of the chlorovinylaldehydes with sodium azide leads to the formation of moderate to good yields of 4-perfluor-... 

The number of five-membered heterocycles with four hetero atoms is limited to those with nitrogen atoms. Thus, the tetrazole acyclonucleo-sides were formed from sugars N,N -diphenylformazanes by the action of AT-bromosuccinimide or lead tetraacetate [133,134]. The synthesis of the tetra-O-benzoyl-D-lyxononitrile and its conversion to (o-lyxo-tetritol-l-yl)-tetrazole derivatives upon reaction with sodium azide was reported [133, 134]. A pseudo C-nucleoside including a tetrazole ring was achieved by conversion of 3- 0-benzyl- 1,2-O-isopropylidene-D-ribo-pentodialdehydo-1,4-furanose to the respective nitrile and then reaction with sodiiun azide [86]. 

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