Piperidides

D, J Sturzebecher and WBode 1991. Geometry of Binding of the N-Alpha-Tosylated Piperidides of weffl-Amidino-Phenylalanine, Para Amidino-Phenylalanine and para-Guanidino-Phenylalanine to Thrombin and Trypsin - X-ray Crystal Structures of Their Trypsin Complexes and Modeling of their Thrombin Complexes. FEBS Letters 287 133-138. 

With some special diazirines interconversion with diazoalkanes was observed on illumination (79AHC(24)63), e.g. with diazirinecarboxylic acid piperidide (194), spirodiazirine (195) and the tetracyclic ketodiazirine (196) (78CC442). 

Most heterocyclic anions may be considered to be derived by loss of a proton from a parent compound, which is therefore the conjugate acid. Such anions have at least one unshared pair of electrons at the anionic site. They are named by appending the suffix -ide , with elision of a terminal e (lUPAC recommendation RC-83.1.1), as in (190)-(193). The site may be specified by a locant placed immediately before the suffix, and so chosen as to be as low as possible consistent with the numbering of the skeleton of the parent compound. The locant may be omitted in order to designate an equilibrating mixture of positionally isomeric anions, which is what one usually obtains in practice. The anion of piperidine is often informally referred to as piperidide . 

This tertiary ester was developed to reduce aspartimide and piperidide formation during the Fmoc-based peptide synthesis by increasing the steric bulk around the carboxyl carbon. A twofold improvement was achieved over the the standard Fbutyl ester. The Mpe ester is prepared from the acid chloride and the alcohol and can be cleaved under conditions similar to those used for the r-butyl ester. ... 

Whereas only one dehydrobenzene, benzyne, has been detected, two pyridynes are possible. Thus, the scheme we can write ab initio for the action of a nucleophile on the isomeric monosubstituted derivatives of pyridine involving 2,3- (26) and/or 3,4-pyridyne (31) is more complicated than that for the analogous reaction of the corresponding benzene derivative. The validity of this scheme can be checked using data available in the hterature on reactions of halogenopyridines with potassium amide and hthium piperidide involving pyridynes. 

The reactions of various halogenopyridines with lithium piperidide and piperidine have been studied by Kauffmann and Boettcher. ... 

By treating 3-bromo- (27, X = Br) or 3-chloropyridine (27, X = Cl) with lithium piperidide (2.2 equivalents) and piperidine (2.8 equivalents) in boiling ether, mixtures of 3- (29, Y = NC5H10) and 4-piper-idinopyridine (34, Y = NC5H10) were obtained in 85-90% total yield. In both reactions the ratio of the 3- to 4-piperidino compounds was 48 52. Support for the hetaryne mechanism as the sole pathway for these reactions comes from the fact that increasing the amounts of lithium piperidide and piperidine to 5 and 10 equivalents, respectively, scarcely changed the composition of the reaction products. If addition-elimination had occurred concomitantly with reaction via the hetaryne, more of the 3-piperidino compound would have been formed, since the reconversion of the hthium intermediate 30 into 27 by piperidine would be accelerated by the enhancement of the concentration of this substance. 

None of the 3-halogenopyridines yield 2-piperidinopyridine. This substance was obtained as the only product from the reaction of 2-fluoropyridine (24, X = F) with lithium piperidide under the same conditions in 97% yield. Finally, it was found that 4-chloropyridine (32, X = Cl) was converted in 95% total yield into a mixture of 0.4% of 3-piperidino- (29, Y = NC5H10) and 99.6% of 4-piperidino-pyridine (34, Y = NCsHio)- Thus, in contrast to the amination with potassium amide, 4-chloropyridine reacts with lithium piperidide almost exclusively via the addition product 33 (X = Cl, Y = NC5H10). 

Those reactions of halogenopyridines with potassium amide and lithium piperidide which proceed via 3,4-pyridyne form the 3- and 4-substituted pyridine derivatives in ratios of 1 2 and 1 1, respectively (see Section II, A, 1). It appears that the ring nitrogen atom has an orienting effect on these additions, but the quantitative divergence of the addition of ammonia and piperidine is not understood at present. 

The four 3-halogenoquinolines were allowed to react with lithium piperidide and piperidine (molar ratio 1 2.2 2.8) in boiling ether. The chloro, bromo, and iodo compound gave, in 45—60% total yield, mixtures of 3- and 4-piperidinoquinoline of the same composition... 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

No crystalline hydrochlorides eould be obtained from either santalene. tt-Santalene forms a liquid dihydrochloride of optical rotation -n 6°, when dry hydrochloric acid is passed through its ethereal solution. It also forms a crystalline nitrosochloride melting with decomposition at 122°, and a nitrol-piperidide melting at 108° to 109°. /3-santalene forms corresponding compounds, the dihydrochloride having a rotatory power -H 8°. It forms, however, two isomeric nitrosochlorides, CigHj NOCl. They may be separated by fractional crystallisation from alcohol. One melts at 106°, the other at 152°. The corresponding nitrol-piperidides melt at 105° and 101° respectively. 

The piperidide 30 a of o-aminohippuric acid cyclizes to the benzodiazepinedionc 31 a in refluxing acetic acid.209 Similarly, the free acids 30b-e210 and their ethyl esters 30f—I211 undergo ring closure on heating. The reaction has been extended to hydrazine derivatives 30m-q.212... 

Difluorobiphenyl has been prepared from 4,4 -biphenyl-bis-diazonium piperidide (by diazotizing benzidine and coupling with piperidine) and concentrated hydrofluoric acid 1 by the action of sodium on -fluorobromobenzene in ether 2 from benzidine by tetrazotization and decomposing the biphenyl-bis-diazonium salt with concentrated hydrofluoric acid 3 by the above method in the presence of ferric chloride 4 and by the prolonged contact of the vapors of fluorobenzene with a red-hot wire.5 The method described here is the most satisfactory for... 

Zur asymmetrischen Reduktion von Diaryl-ketonen mit (S)-Lithium-2-methyl-piperidid zu optisch akti-ven Alkoholen mit im wesentlichcn (/ )-(Configuration (Umsatz —50%) s. Lit.1. 

Nitro-phenyl)- -athylester 694 4-(2-Oxo-propyl)- -methylester 629 Pcntafluor- 599, 616 Pentafluor-amino- 616 Pentafluor-4-chlor- 616 Pentafluor-methoxy- 616 Pentamethoxy- -aziridid 234 -phenylester 192, 601 -piperidid 240... 

Phenyl- -methylester 193, 198 Phenyl- -2-phenyl-athylester 189 Phenyl- -piperidid 240 Trichlor-148, 618, 674 Trideutero- -O-D 150 Trifluor- 147... 

The same reaction sequence performed in methanol affords a mixture of diastereo-mers of the phosphorylated phosphinic ester 48b, of which one pure isomer can be isolated32 . In the presence of piperidine, reductive elimination of nitrogen 28,29) from 45 to give bis(diphenylphosphoryI)methane competes with the prevailing formation of the phosphinic piperidide 48c32). Expected trapping of 47 by [2 + 2]-cycloaddition with benzaldehyde fails to occur in place of 1,2k5-oxaphosphetanes, products are obtained which arise mainly by way of the benzoyl radical32,33). 

Recently, a series of cycloadducts possessing unusual flipping modes have been isolated from the 1,3-dipolar cycloaddition of 3,4,5,6-tetrahydropyridine IV -oxide to piperidides of cinnamic acid and para-substituted cinnamic acids (791). 

The bromomethoxy compound 115 undergoes lithiation by attack at hydrogen when treated with BuLi, rather than transmetallation of the bromine atom (Equation 10). Reaction with propanal then gives a mixture of 116 and 117, suggesting that both mono- and di-lithiation have occurred <1998T6485>. Lithium tetramethyl piperidide was less satisfactory than BuLi, and gave low yields after reaction with propanal. Neither the parent compound 64 nor the 8-methoxy derivative reacted with BuLi. 

Lithium derivatives of dialkylamines react with aryl methyl ethers in refluxing THF by substitution to afford TV-aryldialkylamines (equation 10). Similarly, lithium piperidide and veratrole give 7V-(2-methoxyphenyl)piperidine (15)40. 

The conversion of symmetrical into unsymmetrical thioureas is exemplified by the formation of Af-cyclohexyl-Af -phenylthiourea when yV,iV-diphenyl thiourea is heated with cyclohexylamine and triethylamine in acetonitrile367. Carbonylation of lithium piperidide in the presence of tellurium generates the lithium carbamotellurate 307, which is trapped as the 7V-ethyl carbamotellurate 308 by ethyl bromide368. 

LHMDs, lithium hexamethyldisilylamide LTMP, lithium 2,2,6,6-tetramethyl-piperidide. 

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