2- piperidines, from

Piperidyl (from piperidine) Quinolyl (from quinoline) Isoquinolyl... 

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). 

In the generation of 3,5-dibenzylpyridine from piperidine and benzalde-hyde, the formation of enamine and dienamine intermediates must also be involved (191-193). 

The formation of bicyclic imines (263,264) from piperidine enamines and y-bromopropyl amines may appear at first sight to be a simple extension of the reactions of enamines with alkyl halides. However, evidence has been found that the products are formed by an initial enamine exchange, followed by an intramolecular enamine alkylation. Thus y-bromodiethylamino-propane does not react with piperidinocyclohexene under conditions suitable for the corresponding primary amine. Furthermore, the enamine of cyclopentanone, but not that of cyclohexanone, requires a secondary rather than primary y-bromopropylamine, presumably because of the less favorable imine to enamine conversion in this instance. 

The reactions of enamines with aldehydes (329,350) are noteworthy in that they provide a route to the monobenzylidene derivatives of five- to seven-membered eyclic ketones as well as a method for the formation of other a, 9-unsaturated carbonyl compounds, in fair to good yields. The condensation of benzaldehyde with enamines is also involved in the formation of 3,5-dibenzylpyridine from piperidine and benzaldehyde (191-193). 

The preparations of over two hundred tetrahydro- and octahydro-pyrido[4,3-d]pyrimidines from piperidines or from purely aliphatic starting materials are described in the patent literature. Fully aromatic examples of the system have been prepared from pyridines and pyrimidines. 

Another class of configurationally stable a-mctallo amines is derived from the N-tert-butoxy-carbonyl-protected piperidines 32 and 3516, l7. Addition of the lithiated piperidines to aldehydes leads to mixtures of the anti- and. yin-diastereoiners. Although the diastereoselectivity is low, the diastereomers can be readily separated by chromatography since the. vyn-isomer is often in a cyclized form 34. The stereochemistry of the products obtained from piperidines 32 are consistent with an equatorial a-lithiation followed by addition to the aldehyde with retention of configuration. However, with piperidine 35 selective axial lithiation is observed. 

These compounds are made by allowing the salt made from piperidine and sodium hydride to react with CS2 and then with an acetylated glycosyl bromide.56... 

Three syntheses of homopumiliotoxin alkaloids are compared below, and one more reaction leading to homo-pumiliotoxin-related compounds was mentioned in Section 12.01.9.3.7. The strategies involved for the ring-closure procedures leading to the quinolizidine system involved the formation of a- or 7-bonds from piperidine precursors and are summarized in Scheme 97. 

Early workers noted that electrochemical oxidation of N,N-dimethyl-amides in acetic acid gives the a-acetoxy compound [101]. Oxidation in acetic acid of amides derived from piperidine and pyrroUdine proceeds differently to yield a mixture of stereoisomers of the a,P-diacetoxy and p-acetoxy-a-hydroxy compounds [125]. 

Alkaloids with the piperidine nucleus, such as pelletierine (Punica grana-tum), lobelanine Lobelia inflata) and piperine Piper nigrum), have a typical biosynthesis pathway. It starts with L-lysine and continues via cadaverine (biogenic amine), A -piperideine and A -piperidinium cations and lobelanine, to be synthesized as lobeline. Piperine is synthesized from A -piperideine via piperidine (Figure 49). For the transformation from A -piperideine to A -piperideine cation, the residue from acetyl-CoA is needed, together with SAM activity in the transformation to lobelanine. Piperine is synthesized from piperidine through the formation of amide. 

Meperidine hydrochloride (l-methyl-4-carbethoxy-4-phenylpiperidine), also known as Demerol, is an important narcotic and analgesic. It is not made from piperidine, but rather by ring-closure reactions of appropriate precursors,... 

Quinuclidine ring formation starting from piperidine derivatives is carried out usually by (a) intramolecular alkylation or acylation or (b) intramolecular Dieckmann condensation. 

Comparison of the synthetic methods for the preparation of quinuclidine derivative starting from piperidines and tribromo-alkanes and dibromoalkylamines shows that in some cases Prelog s scheme gives better results, while in others intramolecular alkylation, acylation, or Dieckmann cyclization are more useful. For example, the best yield (37%) of 2-methylquinuclidine (12)23 and the only known 3,5-disubstituted quinuclidine, 3,5-dimethylquinuclidine,120 (58) were synthesized by Prelog s method. 

Perhydropyrido[2,l-c][l,4]oxazine-l,4-diones 299, 301, and 303 were obtained from piperidine derivatives 298, 300, and 302 stirring in MeOH saturated with HC1 gas overnight, but stereoisomer 304 gave only tarry material (07EJ03028). 

Phenylpiperidine reacts with fuming nitric acid (d 1.5) at -10°C to produce about 90% l-(2,4-dinitrophenyl)piperidine. Mononitration can be achieved by using nitric acid in acetic anhydride at RT, which gives the 4-nitrophenyl product in quantitative yield with no ortho product to be seen. The 4-nitrophenyl product is nitrated by concentrated nitric acid (d 1.42) to give the 2,4-dinitropheny 1 compound, but the 2-nitrophenyl isomer (prepared from piperidine and 2-nitrochlorobenzene) is unaffected even by fuming nitric acid (32JCS1376). 

On the other hand, some evidence for the longer life-time of the intermediate formed with amines may be inferred from the formation of small amounts of (116a) from piperidine and /J-chloroacrylonitrile, in addition to the main substitution product. (116a) is also the sole substitution product with aniline (R1=Ph, R2 = H) but no such products were reported for reactions with oxygen or sulphur nucleophiles. For formation of (116a) the initially-formed carbanion should be long-lived enough as to attack another j8-chloroacrylonitrile molecule (Scotti and Frazza, 1964). 

Alkylation of enamines prepared from aldehydes was studied by Elkik,210 Opitz and Mildenberg,211 and Williamson 212 and alkylation of enamines prepared from ketones by Stork et al.75 These investigators demonstrated that the ease of alkylation depends on the basicity of the enamine in question. Enamines prepared from the more basic pyrrolidine are alkylated more readily than those obtained from morpholine. Better yields of the enamines (44) from pyrrolidine are obtained, in contrast to the preparations (45) from piperidine (which are bases about as strong as pyrrolidine) this may result from the stabilizing influence of the exocyclic double bond in the polarized form of the pyrrolidine derivative. 

Derivatives of triazole have been obtained by Fusco et al,280 from phenyl azide and 1-morpholinocyclohexene. Their decomposition leads to cyclopentanecarboxylic acid by elimination of nitrogen and ring contraction.281 The dienamine obtained from piperidine and... 

Enediamines 35,103 and 104, derived from piperidine, react readily with acids to form the amidinium salts 105-107. The perchlorate salts are particularly easy to prepare since they crystallize in analytically pure form on titration of the parent compound with 0.1 N perchloric acid in acetic acid (equation 36)84. Secondary 1,1-enediamines 8 and 53 give amidinium salts almost quantitatively on treatment with hydrochloric acid in methanol29,85. The evidence for formation of amidinium salts has been provided by the... 

Although controlled substitution with molecular fluorine is difficult to attain, noteworthy is the recent success in perfluorinating both saturated and unsaturated heterocycles by electrolysis in anhydrous hydrogen fluoride. Cf. T. C. Simmons and F. W. Hoffmann, J. Am. Chem. Soc. 79, 3429 (1957), for the preparation of undecafluoropiperidine (from piperidine). The latter compound can be converted into pentafluoropyridine by passing it over an iron contact at 600° [R. E. Banks, A. E. Ginsberg, and R. N. Haszeldine, J. Chem. Soc. p. 1740 (1961)]. 

Secondary amines can be converted into sulfenamides by reaction of the lithium dialkylamides with disulfldes. Perchlorylamines (3ti) have been prepared in good yields from piperidine and other secondary amines by reaction with chlorine(vn) oxide. ... 

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