NaN3 synthesis

Scheme 4.22 Stockman two-directional tandem synthesis sequence (2005). (a) 1 /4NaBH4, H2O (95%), (b) CH3SO2CI, Et3N (100%) (c) NaN3 (d) [3 -1-2] (e) [1,4]-H (f) thermal cyclization (52%, 4 steps).

The synthesis of a,a-disubstituted amino acids is a difficult task and continues to attract attention. An efficient route that utilizes the ring-opening of an epoxide with azide has been reported <06TL9268>. Treatment of the sulfoxide substituted epoxide 23 with NaN3 provides intermediate azido aldehyde 24. This aldehyde was not isolated but oxidized to the acid and then the azide reduced to provide the a,a-disubstituted amino acid 25. The regioselectivity of this reaction was impressive with only one product reported. 

Synthesis of another triazole derivative was described by Clerica et al. [53]. This synthetic strategy involved reaction of an isothiazole derivative (e.g., compound 48) with an equimolecular quantity of NaN3 in a variety of solvents, e.g., different alcohols, THF, etc. Acetonitrile was used to produce compound 49 in a 30% yield, Scheme 8. 

Fig. 5. System of three microreactors (Fig. 1) and two separators (Fig. 4) for continuous synthesis of carbamates from NaN3 and organic chlorides (Sahoo et al. 2007)...

The cyclobutanone (255) reacted with acid to furnish the keto-acid (259). Upon esterification, ketalization and reduction, (259) was converted to the alcohol (260). Mesylation of the alcohol (260) and then treatment of the mesylate with NaN3 in DMSO provided the azide (261). The azide (261) was then transformed to the urethane (262) by reduction and ethyl chloroformate reaction. The urethane (262) was deketalized by acid, nitrosated by N204—NaOAc and decomposed by NaOEt—EtOH to give the ketone (263) 89). The ketone (263) served as a starting material for the synthesis of veatchine (264)90). 

This methodology provides a general synthesis of L-amino acids in 92-96% ee and in chemical yields of about 40-60%. Thus reaction of 3 (X = Br) with NaN3 under phase-transfer conditions provides 6, which is homologated to the 1-chloro-2-azidoboronate 7. This product is oxidized by sodium chlorite directly to an azido carboxylic acid (8). Hydrogenation of 8 provides L-amino acids (9). 

Sha et al. (45) reported an intramolecular cycloaddition of an alkyl azide with an enone in an approach to a cephalotaxine analogue (Scheme 9.45). Treatment of the bromide 205 with NaN3 in refluxing methanol enabled the isolation of compounds 213 and 214 in 24 and 63% yields, respectively. The azide intermediate 206 underwent 1,3-dipolar cycloaddition to produce the unstable triazoline 207. On thermolysis of 207 coupled with rearrangement and extrusion of nitrogen, compounds 213 and 214 were formed. The lactam 214 was subsequently converted to the tert-butoxycarbonyl (t-Boc)-protected sprrocyclic amine 215. The exocyclic double bond in compound 215 was cleaved by ozonolysis to give the spirocyclic ketone 216, which was used for the synthesis of the cephalotaxine analogue 217. 

When the enone 218, possessing a methyl group at the C(2) position, was treated with NaN3 in DMF, aziridine 219 was isolated as the only product (46) (Scheme 9.46). This reaction was adopted for the total synthesis of ( )-desamyl-perhydrohistrionicotoxin (224) from the azido enone 220. 

Cha and co-workers (54) described an enantioselective total synthesis of (—)-slaframine (269) based on an intramolecular cycloaddition of an azide (Scheme 9.54). On reaction with NaN3 in DMF at 60 °C followed by intramolecular... 

In 1984, a facile synthesis of pyrrolo[3,4-/ ]indole (5) as a stable indole-2,3-quinodimethane analogue using an intramolecular azide-alkene cycloaddition-cycloreversion strategy was reported (Scheme 9.2) (3). Treatment of bromo compound 3 with NaN3 in aqueous tetrahydrofuran (THF) produced the triazoline 4 via an intramolecular 1,3-dipolar cycloaddition of an intermediate azide. Treatment of the triazoline 4 with p-toluenesul fonic acid (p-TSA) effected 1,3-dipolar cycloreversion of 4 to give pyrroloindole 5 in 82% yield along with diethyl diazomalonate. 

Combustion synthesis of metal nitrides from a solid nitrogen source was first investigated by Petrov in 1975.32 He used barium azide (Ba2N6) powder for the synthesis of TiN and Mg3N2. Holt, in 1983,33 reported the synthesis of TiN by using sodium azide (NaN3)as the solid nitrogen source. 

A method has been reported for the solid-phase synthesis of tetrazolo[5,1 -tf]phthalazine derivatives 501 based on the cyclization of resin-bound chlorophthalazines 500 with NaN3 in l-methyl-2-pyrrolidinone (NMP) at 120°C (Scheme 63) <2005TL3107>. 

Table 30 Synthesis of tetrazoles from ketones and SiCI4-NaN3 via geminal diazide 520 <1995TL7337>...

Disubstituted tetrazoles 751 are most often prepared by the cyclization of imidoyl azides 750. The traditional method for generation of imidoyl azides 750 consists of treating the appropriate imidoyl chlorides 749 with HN3 or NaN3 (Scheme 323) numerous other methods for the synthesis of imidoyl azides and their cyclization to tetrazoles have also been reported . 

In a subsequent paper, Diamantis et al.2536 have reported the synthesis of compounds of type [Ru(H edta)L ] [L = CO, NO etc. (n = 1) and L = RCN (n = 2)] by reaction of [Ru(Hedta)OH2] with the appropriate ligand in the presence of H2/Pt. The compounds were characterized by a range of spectroscopic techniques which indicate that the ligands L are accommodated in equatorial positions. For L = N2, the anions [Ru(edta)N2]2- and [ Ru(edta) 2N2]4 were isolated. The corresponding Na2[Ru(pdta)N2] 2H20 (H4pdta = propylenediaminetetraacetic acid) has been prepared from [Ru(Hptda)(OH2)] H2O and NaN3,2537... 

The synthesis of the triazolo-pyridine-fused 1,3-diazocine 20a was achieved starting from 56a, which by de-O-benzoylation followed by reaction with NaN3 in DMF afforded the triazolo-pyridine 57. The latter by treatment with a mixture of acetone and 2,2-dimethoxypropane in the presence of acid afforded the O-isopropylidene derivative 60. The Mitsunobu reaction led to the diazocine 19a, which, as mentioned in Section 14.05.2.5 (Scheme 2), afforded 20a in 19% overall yield (Scheme 11) <2005JME6454>. 

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