Vanillin Amine

Substances suitable for the estimation acetanilide, sucrose, glucose, cinnamic acid, diphenyl amine, salicylic acid, vanillin, />"bromoacetanilide, toluene p-sul phonamide. 

Vanillin reacts with primary amines in weakly basic media to form fluorescent or colored Schiff s bases whereby colored phenolates are also produced at the same time. 

Reductive amination of vanillin with ammonia leads to benzylamine 94. Acylation of that compound with (Z)-9-octadecenoyl chloride affords the analgesic olvanil (95) [23]. 

Aromatic aldehydes react in basic as well acidic medium. Thus vanillin and primary amines yield Schiff s bases (cf. vanillin-potassium hydroxide reagent in Volume 1 a). Colored phenolates are formed at the same time. As would be expected secondary amines, indole derivatives and lysergic acid derivatives do not react. 

Aryl alcohol oxidase from the ligninolytic fungus Pleurotus eryngii had a strong preference for benzylic and allylic alcohols, showing activity on phenyl-substituted benzyl, cinnamyl, naphthyl and 2,4-hexadien-l-ol [103,104]. Another aryl alcohol oxidase, vanillyl alcohol oxidase (VAO) from the ascomycete Penicillium simplicissimum catalyzed the oxidation of vanillyl alcohol and the demethylation of 4-(methoxymethyl)phenol to vanillin and 4-hydro-xybenzaldehyde. In addition, VAO also catalyzed deamination of vanillyl amine to vanillin, and hydroxylation and dehydrogenation of 4-alkylphenols. For the oxidation of 4-alkylphenol, the ratio between the alcohol and alkene product depended on the length and bulkiness of the alkyl side-chain [105,106]. 4-Ethylphenol and 4-propylphenol, were mainly converted to (R)-l-(4 -hydroxyphenyl) alcohols, whereas medium-chain 4-alkylphenols such as 4-butylphenol were converted to l-(4 -hydroxyphenyl)alkenes. 

Vanillylamine [(4-hydroxy-3-methoxy-phenyl)methylamine] is the substrate of choice for the formation of vanillin with the help of amine oxidase. It can be obtained by cleavage of capsaicin (N-[(4-hydroxy-3-methoxy-phenyl)methyl]-8-methyl-6-nonenamide) isolated from pepper and capsicum [83]. As natural vanillin extracted from beans of Vanilla planifolia is rare and extremely expensive, this pathway for the production of natural vanillin is regarded to have a great potential. The vanillin obtained by the process can be labelled as natural if the cleavage of capsaicin is performed enzymatically. 

As VAO is able to perform an oxidative deamination of capsaicin-derived vanillyl amine, vanillin can be produced by the pathway described in the previous subsection. Van den Heuvel et al. [83] pointed out this biocatalytic route of synthesis in 2001 using penicillin G acylase to obtain vanillyl alcohol from natural capsaicin (Scheme 22.6). As the vanillin obtained can be labelled as natural. 

Scheme 22.6 Oxidative deamination of capsaicin-derived vanillyl amine and formation of vanillin [83] VAO vanillyl alcohol oxidase...

Amines containing APIs have also been known to react with other formulation components such as flavoring agents and even enteric coating constituents. An example of the reaction of a primary amine with a flavoring agent is illustrated in Figure 48 (83). In this example, the API was formulated in a ready-to-use liquid, oil-based formulation, and vanillin was one of the... 

The installation of the amine functionality at C5 is accomplished by mesylation of 41 followed by azide displacement to give 44 (71% yield over four steps). The P-aminopropanamide 13 is then introduced directly to the lactone under 2-hydroxypyridine catalysis to give the penultimate intermediate 45. Reduction of the azide and isolation as the hemifumarate salt provides aliskiren hemifiimarate (l).37 Based on the information disclosed to date, the synthesis of aliskiren is accomplished with an overall yield of 14% from iso vanillin 14 with a longest linear sequence of 15 steps. Given the complexity of aliskiren, this is a remarkably efficient process, and it should be noted that this analysis likely only establishes a lower limit of efficiency, as further optimization of the route on a manufacturing scale is expected. 

Yoshida et al. (1997) achieved the production of vanillin by oxidation of vanillylamine using amine oxidase (AO) from Aspergillus niger and monoamine oxidase (MAO) from Escherichia coli. Enzyme kinetic studies have revealed that AO is... 

Yoshida, A., Takenaka, Y., Tamaki, H., Frebort, I., Adachi, O. and Kumagai, H. (1997) Vanillin formation by microbial amine oxidases from vanillylamine. Journal of Fermentation and Bioengineering 84(6), 603-605. 

DL-Dopa may be first prepared from vanilline and glycine which is then converted to the DL-N-acetyl-3-methoxy-4-acetoxy phenylalanine. The resulting product is then resolved by means of a-phe-nyl-ethyl amine which upon hydrolysis with aqueous HBr forms levodopa. 

Poly(hydroxystyrene-co-methyl methacrylate) [poly(HS-co-MMA)] can be modified to add amino groups onto the side chain of the polymer. The amine-modified polymer can react with two classes of active compounds the first class is aldehydes such as vanillin, p-hydroxybenzaldehyde, P-chlorobenzaldehyde and anisaldehyde, and the second class is phenolic esters such as p-hydroxymethylbenzoate, 2,4-dihydroxymethyl benzoate and methyl salicylate. 

The chemical modification of CS biopolymers via reductive amination, to yield alkylated CS derivatives, and further quaternisation result in very efficient antibacterial materials the degree of activity is correlated to the length of the alkyl chain and bacterial strain. The most active CS derivatives are more selective at killing bacteria than the quaternary ammonium disinfectants, cetylpyridinium chloride and benzalkonium chloride, and AMP. Vanillin can be used as a crosslinker of CS nsing this approach, functionalised antimicrobial polymers based on CS, vanillin. Tween 60 and so on may be easily prepared. Imino-CS biopolymer films, prepared by the acid condensation of the amino groups of CS with various aldehydes, can be used as functional biodynamic materials. 

Some of the innumerable reagents used in TEC are based on reactions with more or less well-established mechanism. Eor example, sodium iodobismuthate (Dragendorff reagent) is widely used among others for alkaloids and quaternary ammonium compounds, 4-dimethylaminobenzaldehyde for primary amines and amino acids, 2,4-dinitrophenylhydrazine for aldehydes and ketones, ninhydrin for amino acids and some antibiotics, fluorescamine for primary and secondary amines, phosphomolybdic acid for lipids, various steroids, and other compounds, chlorine vapor followed by Kl/starch for amines and amides. More complex is the mechanism of the reactions with some other reagents, containing high concentrations of sulfuric acid, vanillin/sulfuric acid, phosphoric acid, aluminum chloride, antimony(III)... 

STRATEGY AND ANSWER Albuterol has the following functional groups 1° alcohol, 2° alcohol, phenol, and 2° amine. Vanillin has aldehyde, ether, and phenol functional groups. See Chapter 2 for a review of how to classify alcohol and amine functional groups as 1°, 2°, or 3°. 

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