Hydrogenation, catalytic azides

Formation and Reduction of Azides Azide ion ( N3) is an excellent nucleophile that displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The products are alkyl azides (RN3), which have no tendency to react further. Azides are easily reduced to primary amines, either by LiAlH4 or by catalytic hydrogenation. Alkyl azides can be explosive, so they are reduced without purification. 

Alkyl azides prepared by nucleophilic substitution by azide ion in primary or secondary alkyl halides are reduced to primary alkylamines by lithium aluminum hydride or by catalytic hydrogenation... 

In HMPA, highly fluorinated azides are prepared Catalytic hydrogenation of these compcMnds leads to the corresponding amines [89] (equation 77)... 

Treatment of 8-azidomethylperhydropyrido[l,2-c]pyrimidin-l-one 157 with methyl triflate and catalytic hydrogenation of the azide group led to the formation of tricyclic guanidine derivative 158 (01JA8851). Hydroxy group of 149 was protected with methoxymethyl chloride, and the p-methoxybenzyl protecting group (PMB) was eliminated by treatment with DDQ. 

A better method for preparing primary amines is to use the azide synthesis, in which azjde ion, N3, is used for SN2 reaction with a primary or secondary alkyl halide to give an alkyl azide, RN3. Because alkyl azides are not nucleophilic, overalkylation can t occur. Subsequent reduction of the alkyl azide, either by catalytic hydrogenation over a palladium catalyst or by reaction with LiAlK4. then leads to the desired primary amine. Although the method works well, low-molecular-weight alkyl azides are explosive and must be handled carefully. 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

Puacz et al. (1995) developed a catalytic method, based on the iodine-azide reaction, for the determination of hydrogen sulfide in human whole blood. The method involves the generation of hydrogen sulfide in an evolution-absorption apparatus. In addition, the method allows for the determination of sulfide in blood without interference from other sulfur compounds in blood. A detection limit of 4 g/dm3 and a percent recovery of 98-102% were achieved. Although the accuracy and precision of the catalytic method are comparable to those of the ion-selective electrode method, the catalytic method is simpler, faster, and would be advantageous in serial analysis. 

See Other CATALYTIC NITRO REDUCTION PROCESSES, HYDROGENATION INCIDENTS, ORGANIC AZIDES... 

Catalytic transfer hydrogenations for the reduction of carbon-carbon double bonds are illustrated in Scheme 4.18. Reductions of azide functionalities to amines with lipases suspended in organic media under microwave conditions have also been reported [206]. 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

Thus, reaction of tetrahydrofuroic acid (40-1) with triphenylphosphoryl azide leads to isocyanate (40-2). Treatment of this intermediate with benzyl alcohol then affords the corresponding carbamate (40-3). Catalytic hydrogenation removes the benzyloxy group, leading to the free primary amine. That product is then resolved by way of its camphorsulfonyl salt to afford (40-5). Reaction of this intermediate with desamino chloroadenosine (40-6) affords tecadenoson (40-7) [42]. 

Catalytic hydrogenation or LiAlH4 reduction of amides, azides or nitriles produces amines (see Section 5.7.23). 

Amides, azides and nitriles are reduced to amines by catalytic hydrogenation (H2/Pd—C or H2/Pt—C) as well as metal hydride reduction (LiAlH4). They are less reactive towards the metal hydride reduction, and cannot be reduced by NaBITj. Unlike the LiAlIU reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlIU reduction of amides, azides and nitriles yields amines. Acid is not used in the work-up step, since amines are basic. Thus, hydrolytic work-up is employed to afford amines. When the nitrile group is reduced, an NH2 and an extra CH2 are introduced into the molecule. 

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