Azides, sodium, with aldehydes

Figure 5.35 ABH reacts with aldehyde-containing compounds through its hydrazide end to form hydrazone linkages. Glycoconjugates may be labeled by this reaction after oxidation with sodium periodate to form aldehyde groups. Subsequent photoactivation with UV light causes transformation of the phenyl azide to a nitrene. The nitrene undergoes rapid ring expansion to a dehydroazepine that can couple to nucleophiles, such as amines.

The synthesis of 4,5-disubstituted triazoles shown in Scheme 208, carried out on a polymer support with microwave assistance, is based on a similar principle. In the first step, sulfinate 1248 is converted to sulfone 1249. Condensation with aldehydes provides vinyl sulfones 1250. Cyclocondensation of sulfones 1250 with sodium azide generates corresponding triazoline intermediates that eliminate sulfinate 1248 to provide triazoles 1251 in moderate to good yield <2006OL3283>. 

A general synthesis of functionalized 1,2,3-triazolyl acylsilanes (160) was based on the intermolecular cycloaddition of azides 159 with the alkynyl acylsilane 158 (Scheme 9.32) (32). The resulting triazolyl acylsilanes (160) were smoothly converted into their corresponding aldehydes 161 upon treatment with sodium hydroxide in ethanol. 

The 3-carboxamides were dehydrated to the 3-nitriles.711,255,284 The 3-nitrile group of 4-oxo-4//-pyrido[l,2-a]pyrimidines was transformed with sodium azide to a tetrazolyl group.155 The 3-carbazoyl group was acylated at N-2,138 and in the 6,7,8,9-tetrahydro series, it was transformed to a —CONHN=CH—NMe2 group284 or condensed with aldehydes.266... 

SODIUM, AZOTURE de (French) (26628-22-8) see sodium azide. SODIUM-2-BENZOTHIAZOLE-THIOATE (2492-26-4) C,HsNS2Na Combustible liquid (flash point >212°F/>100°C). Incompatible with strong oxidizers such as calcium hypochlorite strong bases, amines, amides, and inorganic hydroxides alcohols, aldehydes, mineral acids and acid fumes (releases heat). Concentrated aqueous solutions are corrosive. On small fires, use dry chemical powder (such as Purple-K-Powder), foam, water spray, or CO2 extinguishers. 

Compounds other than carbonyls could be activated by L-Pro. Thus, nitroalkanes react with aldehydes in a Henry-type reaction facilitated by L-Pro. After elimination of the catalyst and a water molecule, the resulting nitroalkene can react with several nucleophiles such as sodium azide, p-ketoesters or sulfur ylides. ... 

A majority of reaction sequences rely on the use of nucleophilic (metalated) variants of 1. However, the electrophilic character of the sterically congested methine carbon has been successfully exploited via displacement reactions with sodium azide.Ogata and Shimizu have also reported that 1 undergoes nucleophilic attack by 1,2,4-tiiazole in the presence of potassium carbonate to provide l-[bis(trimethylsilyl)methyl]-1,2,4-triazole (3) (eq 2). Subsequent introduction of TBAF results in desilylation of 3 to afford an a-sUyl carbanion intermediate that provides 1-vinyl-1,2,4-triazole products upon condensations with aldehydes or ketones (eq 3). While high yields of the alkene products are generally obtained, mixtures of 7Z-isomers are observed in all cases. 

Using a similar system, Johnson et al. have been able to effect the overall result of the Wittig reaction but using sulphur ylides. Thus, an alkylphenyl sulphoxide was converted into the sulphoximine with sodium azide, the imine group was methylated with formic acid-formaldehyde, and the N-methylimine was converted into the ylide (157) with n-butyl-lithium in THF. The ylide reacted with aldehydes or ketones by adding to the carbonyl group to produce the hydroxy sulphoximine (158). The sulphur group could... 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Acetaldehyde can be isolated and identified by the characteristic melting points of the crystalline compounds formed with hydrazines, semicarbazides, etc these derivatives of aldehydes can be separated by paper and column chromatography (104,113). Acetaldehyde has been separated quantitatively from other carbonyl compounds on an ion-exchange resin in the bisulfite form the aldehyde is then eluted from the column with a solution of sodium chloride (114). In larger quantities, acetaldehyde may be isolated by passing the vapor into ether, then saturating with dry ammonia acetaldehyde—ammonia crystallizes from the solution. Reactions with bisulfite, hydrazines, oximes, semicarb azides, and 5,5-dimethyl-1,3-cyclohexanedione [126-81 -8] (dimedone) have also been used to isolate acetaldehyde from various solutions. 

The Schmidt reaction of ketones works best with aliphatic and alicyclic ketones alkyl aryl ketones and diaryl ketones are considerably less reactive. The reaction is only seldom applied to aldehydes as starting materials. The hydrazoic acid used as reagent is usually prepared in situ by treatment of sodium azide with sulfuric acid. Hydrazoic acid is highly toxic, and can detonate upon contact with hot laboratory equipment. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

Sodium hydrogen telluride, (NaTeH), prepared in situ from the reaction of tellurium powder with an aqueous ethanol solution of sodium borohydride, is an effective reducing reagent for many functionalities, such as azide, sulfoxide, disulfide, activated C=C bonds, nitroxide, and so forth. Water is a convenient solvent for these transformations.28 A variety of functional groups including aldehydes, ketones, olefins, nitroxides, and azides are also reduced by sodium hypophosphite buffer solution.29... 

A way to introduce the primary amino group directly onto the selenophene ring is via the azido compound, obtained by nucleophilic substitution of the bromo derivative with sodium azide. Useful transformations of the azido group are shown in Scheme 12.117 The amino aldehyde (109) is a suitable starting material for the preparation of selenolo[3,2-b]pyridine (110) by the Friedlander reaction.138 Not only can the azido be reduced to an amino... 

Tandem nucleophilic substitution-[2+3] cycloaddition reaction of 4-bromo- and 4-toluenesulfonyloxy aldehydes 77 with sodium azide in DMF at 50 °C affords excellent yields (>80%) of substituted pyrrolo[.2.3.4]oxatriazoles 78 (Scheme 8) <2002HAC307>. 

Diazocycloalkanones with five- to twelve-membered rings can be synthesized by the present procedure in good yields (Table I).4 Diazo transfer with deformylation can also be used for the preparation of bicyclic a-diazo ketones.10,11 A related procedure involving reaction of the sodium salt of an a-(hydroxy methylene)-ketone with p-toluenesulfonyl azide in ethanol has been applied to the synthesis of diazoalkyl ketones, a-diazo aldehydes, and a-diazo carboxylic esters.12... 

The synthesis of valsartan (2) by Novartis/Ciba-Geigy chemists is highlighted in Scheme 9.5. Biphenylbenzyl bromide 18 is converted to biphenyl acetate 19 in the presence of sodium acetate in acetic acid. Hydrolysis of 19 followed by Swern oxidation delivered the biphenyl aldehyde 20, which underwent reductive amination with (L)-valine methyl ester (21) to give biphenyl amino acid 22. Acylation of 22 with penta-noyl chloride (23) afforded biphenyl nitrile 24, which is reacted with tributyltin azide to form the tetrazole followed by ester hydrolysis and acidihcation to provide valsartan (2). [See Biihlmayer et al. (1994, 1995).]... 

For the synthesis of amino acids, the reaction of an a-haloalkyl boronic ester 4 with sodium azide and a phase-transfer catalyst in dichloromethane/water requires a large excess of azide in order to form the a-azidoalkyl boronic ester 5 with only 1-2% epimer34. With the exception of R1 = benzyl, where epimerization of 4 is relatively rapid, bromoalkyl boronic esters are preferred. Chloroalkyl boronic esters react so slowly that the azide and dichloromethane may generate hazardously explosive diazidomethane65,66. Chain extension of 5 to 6 proceeds normally. Sodium chlorite, which is known to oxidize aldehydes to carboxylic acids67-69, also oxidizes a-chloroalkyl boronic esters to carboxylic acids34. The azido acid is hydrogenated to the amino acid. 

---