Piperidine derivatives

Piperidine Derivatives. Dehydrogenation of both l-methyl-3-(2-hydroxy-ethyl)- and -(3-hydroxypropyl)-piperidines (351) with mercuric ion and edta 

spectra of several alkylpiperidines have been reported, the eflFects of A -methyl and C-methyl groups on adjacent ring protons being discussed in detail.  

The reduction of cyclic nitroxides by sodium sulphide in DMF gives fair yields of cyclic amines, e.g. (356). These reactions, which have induction 

Casy and McErlane have reported synthetic and stereochemical studies on the l,2-dimethyl-4-phenylpiperidin-4-ols (357), and on the 3-methyl-4-phenylpiperidines (358). By comparison of the i.r. spectra of [ N]- and 

Some dinitroxide radicals, e.g. (360), have been made which fulfil the 

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Reduced pyrido[4,3-c]pyridazines are obtained from piperidine derivatives such as (371) with hydra2dne e.g. 79AF1835), whilst another related synthesis coupled the enamine (372) with phenacyl bromide semicarbazone to give (373) (74JAP(K)7488897). 

Delourme-Houd found that on conversion to quaternary derivatives the capacity of sparteine to intensify and prolong the hypertensive action of adrenaline was increased. Pratesi and Aitieri have investigated the sparteine-like activity of piperidine derivatives of the type, CjHioN. CHj. CHjX where X is NH, NMcj, NEtj, NMePh or a second... 

These substances differ structurally from niquidine (VI) by the substitution in the latter of a propylidene chain at C. Ainley and King having already found that d- and Z-dihydroquinicinols (VIII) which are y-substituted piperidine derivatives, were inactive, it appeared from these two sets of results that the strongly basic centre should not be separated by more than two carbon atoms frorn the point of attachment to the quinoline nucleus. King and Work therefore prepared a series of... 

Draw or build a molecular model of what you would expect to the most stable conformation of the piperidine derivative In which the hydro- gen bonded to nitrogen has been replaced by methyl. ... 

Bohlmann et al. (118-121) observed that an infrared absorption band between 2700-2800 cm is characteristic of a piperidine derivative possessing at least two axial carbon-hydrogen bonds in antiperiplanar position to the free-electron pair on the nitrogen atom. The possibility of forming an enamine by dehydrogenation can be determined by this test. Compounds which do not fulfill this condition cannot usually be dehydrogenated (50, 122,123). Thus, for example, yohimbine can be dehydrogenated by mercuric acetate,whereas reserpine or pseudoyohimbine do not react (124). The quinolizidine (125) enamines (Scheme 4), l-azabicyclo(4,3,0)-nonane, l-azabicyclo(5,3,0)decane, l-azabicyclo(5,4,0)undecane, and l-azabicyclo(5,5,0)dodecane have been prepared in this manner (112,126). 

Chiral and nonracemic A-cyanomethyloxazolidines in diastereoselective synthesis, particularly of pyrrolidine and piperidine derivatives 99CSR383. 

Diastereoselective synthesis, particularly of piperidine derivatives using chiral and nonracemic A-cyanomethyloxazolidines 99CSR383. 

Dehydrogenation of piperidine derivative 329 with Hg(II)-EDTA reagent afforded a mixture of perhydropyrido[l,2-n]pyrimidin-2-one 330 and pyrido[],2-c][],2,5]oxadiazine 331 (99ZN(B)632). 

Reaction of the chiral piperidine derivative 602 with the activated alkyne 603 afforded the corresponding oxazoloquinoline derivative 604 (98H747) (Scheme 102). 

Under the circumstance of catalytic hydrogenation of piperidine derivatives 190 in MeOH over Pd/C catalyst afforded an isomeric mixture of perhydropyrido[l,2-c]pyrimidines 174-177 (98TL7021, 00JA5017). The main product was 174 (66%). 

An 1 5 epimeric mixture of piperidine derivatives 191 was cyclized under Mitsunobu condition to afford a mixture of l-iminoperhydropyrido[l,2-c] pyrimidines 153 and 192 (00TL1849). 

Other examples were tested and the results are summarized in Table 5.7 [24]. The reactions always proceeded smoothly to afford the corresponding piperidine derivatives in high yields with high enantiomeric excess. In addition, reverse enantio-... 

The precise structure of the zirconium catalyst was examined by NMR analysis. When Zr(Ot-Bu)4 (1 equiv), 8b (2 equiv), and NMI (3 equiv.) were combined in benzene-dg at 23 °C, two independent species which were assigned to a new zirconium catalyst and free 8b were observed. Although the signals of free 8b were still observed when Zr(Ot-Bu)4 (1 equiv), 8b (1 equiv), and NMI (3 equiv.) were stirred at 23 °C, only the signals assigned to the new zirconium catalyst were detected when the mixture was stirred at 80 °C for 2.5 h. These results indicated the formation of 9b as the new zirconium catalyst. The structure was also supported by an experiment in which Zr(Ot-Bu)4 (0.2 equiv), 8a (0.2 equiv), NMI (0.6 equiv), and MS 3 A were combined in benzene and the mixture was stirred for 2.5 h at 80 °C (formation of 9a). Imine Id (1 equiv.) and 7a (1.2 equiv.) were then added to the catalyst solution, and the mixture was stirred for 48 h at 23 °C. After the same work-up procedures as described above, the desired piperidine derivative was obtained in >98% yield with 89% ee, values comparable with those... 

A somewhat more complex scheme is required for the preparation of benzimidazolones in which one of the nitrogen atoms is substituted by a 4-pi peridyl group. The sequence starts with aromatic nucleophilic substitution on dichlorobenzene by protected amino-piperidine derivative to give Reduction of the... 

A representative example is the cyclic enamide 1, containing an optically active A-camphanoyl substituent as a chiral auxiliary82. Treatment of 1 at — 78 C with hydrogen chloride and then a Lewis acid leads to the chiral A -acyliminium intermediate that is alkylated with high stereoselectivity to provide optically active piperidine derivatives. 

In the intramolecular amidoalkylation of certain (Z)-allylsilanes, piperidine derivatives (n = 2) are formed less stereoselectively than the corresponding pyrrolidines (n = 1). The complete regiocontrol is induced by the /3-effect of the silicon atom. 

Amidoalkylation of silyl enol ethers with /V-acyliiiiiiiium ions containing camphanoyl-derived acyl functions (see Appendix) as the chiral auxiliary leads to optically active 2-substituted piperidine derivatives with moderate to high diastereoselectivity, depending on the chiral auxiliary and the cnol ether82 99. The auxiliary is removed by hydrolysis with base or acid. 

Substituted Piperidine Derivatives by Amidoalkylation of Silyl I nnl Ethers General Procedure82 ... 

Alkylations of 6-methoxycarbonyl six-membered cyclic (V-acyliminium ions show a strong preference for the formation of m-products. This is explained by the A0-3 strain between the substituent and the (V-mcthoxycarbonyl group of the iminium ion, forcing the substituent into an axial position. Stereoelectronically preferred axial attack by the nucleophile then leads to the 2,6-d.v-disubstituted piperidine derivatives. 

Reduction of aromatic rings with lithium or calcium " in amines (instead of ammonia—called Benkeser reduction) proceeds further and cyclohexenes are obtained. It is thus possible to reduce a benzene ring, by proper choice of reagent, so that one, two, or all three double bonds are reduced. Lithium triethylborohy-dride (LiBEtsH) has also been used, to reduce pyridine derivatives to piperidine derivatives." ... 

The ZwKKER reaction involving Co salts is frequently used for the detection of barbituric acid derivatives [31-35], but some purine, pyridine and piperidine derivatives and heterocyclic sulfonamides also yield colored derivatives. The Zwkker reaction is particularly sensitive when it is possible to form a tetrahedral complex [Co(Barb)2 Xj] (X = donor ligand, e.g. amine) [4]. 

The N-alkylation of a range of 2-benzoyl-3-alkylaziridines 98 with rert-butyl bromoacetate followed by Wittig olefination gave directly piperidine derivatives 99 <95JCS(P1)2739>. 

Radical cyclization of dihydropyridones 108 provided piperidine derivatives 109 containing a trifluoromethyl group at the bridgehead position adjacent to nitrogen <96JOC(61)8826>. 

The enantioselectivity is due to the retention of the chiral sparteine in the lithiated reagent. The adducts have been used to synthesize a number of pyrrolidine and piperidine derivatives. 

I. 1-cyclohexyl piperidine derivatives Anticholinesterase activity and antagonist ability to acetylcholine. Biochem Pharmacol 23 1263-1281, 1974. 

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