Pyrrolidine derivatives

Nitrogen-containing Rings.—Pyrrolidine Derivatives. A study of the quaterniza-tion of some N-substituted 2-phenyl pyrrolidines (280) has shown that the cis irons product ratio does not vary appreciably with the N-substituent, but does alter significantly with the incoming electrophile.  

Cyclization of de-unsaturated nitroso-compounds, e.g. (282), by the action of iodine gives rise to pyrrolidino-nitroxide radicals, e.g. (283).  

An aminomercuration reaction on w-amino-ethylene derivatives (284), which has been shown to proceed via a /ra 5-addition mechanism, gives rise to different types of heterocycles (285), especially pyrrolidine derivatives, e.g. (286) - (287). 

In aqueous solutions of the acetylenic amino-alcohols (288) nucleophilic attack of the nitrogen on the triple bond, followed by treatment with hydri-odic acid, gives the pyrrolidinium iodides (289).  

The preparation and e.s.r. spectra of the nitroxide radicals (290)—(292) have been reported,  

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When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

Aldehydes take part in the cycloaddition to give the methylenetetrahydrofuran 178 by the co-catalysis of Pd and Sn compounds[115]. A similar product 180 is obtained by the reaction of the allyl acetate 179, which has a tributyltin group instead of a TMS group, with aldehydesfl 16]. The pyrrolidine derivative 182 is formed by the addition of the tosylimine 181 to 154[117]. 

Carbonylation of the tetrasubstituted bispropargyiic amine 23 using PdCP and thiourea under mild conditions affords the carboxylated pyrrolidine derivatives 24a and b in good yields. Thiourea is regarded as effective for the oxidative carbonylation of alkynes, but no oxidative carbonylation was observed in this case[21]. 

Synthesis of the densely functionalized heterocyclic system of antitumor antibiotics azinomycins AandB, azirino [l,2-<2]pyrrolidine derivatives 98SL1031. 

Diastereoselective synthesis of pyrrolidine derivatives using chiral and non-racemic A-cyanomethyloxazolidines 99CSR383. 

Treatment of the pyrrolidine derivative 130 with sodium hydride followed by A-methyl piperazine afforded pyrrolidino[l,2-a]quinolinone 4-carboxy-late 131 (93JPR397) (Scheme 25). 

Reaction of the chloro-substituted propargyl acetate 132 with aniline gave the pyrrolidine derivative 133 that was cyclized through treatment with... 

Cyclization of the thiazolidine methylidinemalonate 684 with PPA gave thiazoloquinoline 3-carboxylate which upon hydrolysis afforded 685 and reaction with A-methylpiperazine or a pyrrolidine derivative gave 686 as antibacterial agent (82EP58392, 85USP4550104) (Scheme 116). 

Alkylation of these as their sodium salts with the ubiquitous N-C2-chloroethyl)dimethylamine affords the desired antihistamines. There are thus obtained, respectively, mephenhydramine (23a) chlorphenoxamine (23b), and mebrophenhydramine (23c)Alkylation of the tertiary alcohol, 22b, with the pyrrolidine derivative, 24, affords meclastine (25). In much the same vein, reaction of 2-acetylpyridine with phenyImagnesium bromide gives the tertiary alcohol, 27. Alkylation in the usual way leads to the potent antihistamine, doxylamine (28). " ... 

Finally, it should be mentioned that the allylation of 2,4-disubstituted pyrrolidine derivatives proceeds with reasonable diastereosclectivity for the trans-compound 2,4-rra .v-l, but with low selectivity for the m-isomer 2,4-m-l131. 

Mass spectra of pyrrolidine derivatives of methyl or ethyl esters The molecular ions are intense with characteristic fragment ions at m/zs 70, 98, and 113. The position of the double bond can be determined by locating two peaks that differ by 12 mass units. A relatively intense peak should be observed 26 m/z units higher than the lower mass peak. The double bond lies between the two peaks that are separated by 26 Daltons. 

Pyrrolidine derivative of monounsaturated methyl or ethyl ester for determining the double bond position. 

Benzodiazepin-2-ones are converted efficiently into the 3-amino derivatives by reaction with triisopropylbenzenesulfonyl (trisyl) azide followed by reduction <96TL6685>. Imines from these amines undergo thermal or lithium catalysed cycloaddition to dipolarophiles to yield 3-spiro-pyrrolidine derivatives <96T13455>. Thus, treatment of the imine 50 (R = naphthyl) with LiBr/DBU in the presence of methyl acrylate affords 51 in high yield. 

Tertiary amines and quaternary ammonium compounds [25-27] Pyrrolidine derivatives [28]... 

Pyrrolidines have been prepared by 1,3-dipolar cycloaddition of N-(benzyli-dene)trimethylsilylamine/TMSOf 20 and methyl acrylate, N-methylmaleimide, or dimethyl maleate [35]. More recently, methyl trans-3-cyanociruiamate 1479 was reacted with N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether 1480 and trifluoroacetic acid in CH2CI2 at 0°C and 24°C to afford, via 1481, the pyrrolidine derivative 1482 in high yield and MeOSiMe3 13a [35a] (Scheme 9.20). Several... 

Parker, Raphael, and Wilkinson have investigated a synthetic approach to tropinone (124), which they call the acetylenic route (78). Reaction of hexa-1,5-diyne-l,6-dicarboxylate (145) with methylamine yields the pyrrolidine derivative (146), which by catalytic hydrogenation affords the diester 147 (79,50). 

Pyrrolidine derivatives Catalytic hydrogenolysis of the N-OH bond producing pyrrolidine was performed in the presence of Ra-Ni (Scheme 4.136).528... 

Under similar conditions, reactions between pyrrolidine derivatives 632 and MTAD proceed much more slowly and less cleanly with formation of a polymeric material. When the reaction is stopped before 50% conversion is reached, starting compound 632 is isolated as the main component (c. 40%) and compound 637 as a minor product (10-14%). Mechanistically, the most difficult problem lies in the fact that a reduction step has to be involved and no particular reduction agent is present. A proposed mechanism is shown in Scheme 103. The pathway includes a Cannizzaro-type hydride transfer between dipole 633 and product 634 (keto tautomer), resulting in the formation of the iminium derivative 635, which might be responsible for the polymeric material, and hydroxy derivative 636, the direct precursor of the final products 637. The low experimental yield of 637 could be explained by this mechanism <2003EJ01438>. 

A wide variety of other photocyclizations have been reported, but only a few of these have any general application. The unsaturated amine 366 undergoes cyclization in cyclohexane to give the 7-azabicyclo[4.3.0]nonan-2-one 367.303 The formation of pyrrolidine derivatives by photocyclization has also been observed in JV-alkyl-2-allylanilines,304 and imidazoles have been obtained by irradiation of 2-amino-1-dialkylaminoanthraquinones.30 5... 

React at room temperature for 1 hour to remove the trityl-protecting group, yielding the N-H pyrrolidine derivative of C60-... 

Figure 15.5 A trityl-protected pyrrolidine derivative of Cgg can be prepared by the reaction of N-trityl-oxazolidinone with a fullerene. Deprotection of the trityl group using methanesulfonic acid gives the secondary amine, which can be used in further conjugation reactions.

Similar to the fullerene modifications using either glycine/formaldehyde derivatives or oxazolidinone compounds, Maggini and Scorrano (1993) found that aziridines could yield similar pyrrolidine derivatives. Heating aziridine compounds in toluene was found to result in ring... 

Figure 15.7 The reaction of aziridine derivatives with fullerenes also can give pyrrolidine derivatives useful for...

Figure 15.17 An amino-PEG-pyrrolidine derivative of carbon nanotubes can be used to couple metal chelating groups, such as DTPA. Subsequent coordination of mIn results in an indium chelate that can be used for imaging applications.

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

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