Piperidine aromatic amides

Most pyridines are reduced to the corresponding piperidines, but certain substituents, notably 2-amino and 2-hydroxy, tend to arrest the hydrogenation at the tetrahydro stage (55,56 7). Wenkert et ai. (llS) noted that in hydrogenation of any aromatic system capable of unmasking a stable, vinylogous amide unit, absorption may cease at this stage. An example is reduction of 3-acetylpyridine (I) to 2, a compound that resisted further attempts at reduction (31). 

Most C,H-acidic compounds can be condensed with aldehydes or ketones to yield alkenes. Some of these reactions have also been realized on insoluble supports, with either the C,H-acidic (nucleophilic) reactant or the electrophilic reactant linked to the support. Some illustrative examples are listed in Table 5.6. Polystyrene-bound malonic esters or amides, cyanoacetamides, nitroacetic ester [95], and 3-oxo esters undergo Knoevenagel condensation with aromatic or aliphatic aldehydes. Catalytic amounts of piperidine and heating are generally required, although reactive substrates can react at room temperature. 

The spirane ring is formed by treating amides derived from 16 with formamide and reducing the product.(20,56) In the solid state the 4-NPh moiety adopts an equatorial rather than an axial conformation in relation to the piperidine ring,(57) akin to the solid and probable solute state conformation of fentanyl, for which there is X-ray<58) and H-nmr evidence (see 20). The activities of the spiranes 19 also provide evidence that anilido phenyl is a- rather than /3-oriented in active conformations of fentanyl derivatives (21). This aromatic feature is confined to the /3-orientation in the bicyclo analogs 22, neither of... 

Kamochi and Kudo have reported the use of the Sml2/THF-H20 system to reduce aromatic carboxylic acids to alcohols (Scheme 50). Furthermore, aromatic esters amides and nitriles were similarly reduced by this system in good yield [104]. As indicated above, reduction of carboxylic acids to primary alcohols is also effective with Sml2 in a THF-H20-NaOH mixture [105]. In contrast, without water these substrates remain unchanged. With the Sml2/THF-H20 system, pyridine was rapidly reduced to piperidine in similar reactions with pyridine derivatives bearing chloro, amino and cyano substituents, these functionalities were partly eliminated to afford pyridine or piperidine [107]. 

Reductions. Aromatic carboxylic acids, esters, and amides are reduced to ArCH20H and nitriles to ArCH2NH2 by the Sml2-H20 system. Pyridine derivatives are completely reduced to afford piperidines in aqueous THF. With MeOH as a proton source the labile 2-aminonitroalkanes are converted to the diamines." ... 

The amides are characteristically straight-chain, usually unsaturated compounds, and many incorporate an aromatic group (frequently 3, 4 -methylenedioxyphenyl) at the terminus remote from the amide function. Amides with and without a distal aromatic group are frequently produced by the same plant. Isobutylamine, pyrrolidine and piperidine predominate as the amine components of the Piper amides, although other amide classes, e.g., -pentyl or isopentylamides may be occasionally encountered [6]. In the case of at least one Piper species, P. guineense, attention has been drawn to the existence, which is intuitively predictable, of geographic variations in the relative proportions of amide constituents found in a species [7]. 

The amino amides 195 were obtained from isatoic or 6-iodoisatoic anhydrides and the esters of amino acids. They were converted by the action of aromatic aldehydes or acetone into derivatives of dihydro-4-quinazolone 196 (ethanol, piperidine, boiling for 1 h, or cone, hydrochloric acid, boiling for 6 h [117] toluene, toluene sulfonic acid, boiling for 0.5 h, [118]). 

Nitroso-piperidine—Nitro-toluene—Azo-benzene, introduction of hydroxyl groups — Toluene-sulphone-amides— Saccharine—p-Nitro-o-toluene-sulphone - amide—Oxida -tion of aromatic oxy-carboxylic acids.76-78... 

Optically active aromatic isocyanates have been synthesized and polymerized. " Poly-(S)-145 prepared by polymerization using the lithium amide of piperidine showed a very large levorotation ([ajses -1969° to -2014°), which was only... 

Piper alkaloids a group of alkaloids occurring in various species of Piper, especially black pepper Piper nigrum). Structurally, P.a. consist of an aromatic carboxylic acid with an unsaturated side chain (e.g. piperic acid, sinapic acid) in amide linkage with a basic component, usually piperidine. The chief representative is Piperine (see). 

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