1.3- Dimethyl-42-pyrroline, synthesis

Rolgamidine (14) is a dihydropyrrole derivative which has antidiarrheal activity It can be synthesized by alkylation of trans 2,5-dimethyl-3 pyrroline (12) with methyl bromoacefate to give 13 An amide-ester exchange reaction with guanidine hydrochloride completes the synthesis of rolgamidine (14) [3]... 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

A new synthesis of pyrrolizidine, which is based on the reaction of bis-tertiary glycols with co-chloronitriles, was reported by Meyers and Libano.28 The method involves three steps (a) condensation of 2,5-dimethyl-2,5-hexanediol (48) with 4-chlorobutyronitrile in the presence of sulfuric acid to give a derivative of A 1-pyrroline (49), (6) reduction of 49 with sodium borohydride to give the corresponding pyrrolidine (50), and (c) intramolecular cyclization of the pyrrolidine in the presence of alkali to give the pyrrolizidine derivative 51. The three-step synthesis was performed without isolation of the intermediate products. 

In a paper published along with that of Stevens and Wentland20 and in agreement with these authors, Keely and Tahk23 reported the independent synthesis of dl-mesembrine, also from I-methyl-3-(3,4-dimethoxyphenyl)-2-pyrroline and methyl vinyl ketone. In their work the cyclopropyl derivative 3b was prepared from the reaction of the anion of 3,4-dimethoxyphenylacetonitrile (lc) with ethylene dibromide in dimethyl sulfoxide and its sodium salt as solvent and base. Reduction with ethereal diisobutylaluminum hydride gave the aldehyde, which was condensed with excess methylamine in benzene-ether solution with calcium oxide as the dehydrating agent. 

Snider reported synthesis of ficuseptine (169) and juliprosine (172) containing 2,3-dihydro-l//-indolizinium alkaloids via biomimetic intramolecular Chihibabin pyridine synthesis." Two molecules of aldehyde 167 and one molecule of 4-aminobutanal dimethyl acetal 168 in acetic acid at 95 °C gave 169 in 52% yield. Meanwhile, two molecules of aldehyde 170 and one molecule of 1-pyrroline 171 in acetic acid at room temperature gave 172 in 72% yield. 

Scharm, S., Bruban, V., Pompermayer, K., Feldman, J., Pfeiffer, J Renard, P Scalbert, E Bousquet, P and Ehrhardt, J.-D. (2001) Synthesis and biological evaluation of pyrrolinic isosteres of rilmenidine. Discovery of cis-/ trans-dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3 H-pyrrol-2-yl)-amine... 

Kamibayashi M, Oowada S, Kameda H et al (2006) Synthesis and characterization of a practically better DEPMPO-type spin trap, 5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-l-pyrroline N-oxide (CYPMPO). Free Radio Res 40 1166-1172... 

There are few reports in the literature for the synthesis of 3-pyrrolin-2-ones so a simple method for the preparation of substituted 4-phenyl derivatives from phenylpropiolic ester, dimethyl sulphoxonium methylide and amines is welcome (Scheme 64). T-Azaspiroannelation has been described by Bryson and Wilson, ... 

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