Pyrroline structure

The ultraviolet spectra were also used for determination of the pyrroline structure (1,158-160). They exhibit a bathochromic shift to 225-235 m, caused by the auxochromic action of the nitrogen-free electron pair which is in conjugation with n electrons of the enamine double bond (161,162). 

In the case of class-II inhibitors, the acyl-enzyme undergoes either normal deacylation (Fig. 5.3, Pathway c) or a chemical re-arrangement in which the enamine tautomerizes to an imine, generating an acyl-enzyme with a A -pyrroline structure (Fig. 5.3, Pathway b). This second acyl-enzyme intermediate hydrolyzes at a much slower rate, and the decreased tum°ver cacis t0 transient inhibition of the enzyme [22] [50]. 

In 1955, Guthrie and co-workers (131) erroneously assigned pyrroline structure 87 to the crystalline compound obtained by treating aminoacetal 86 with sulfuric acid (Scheme 14). The structure assignment was revised by Battersby and Yeowell (69) to 35, who named it isopavine, since the structure had already been proposed but eliminated for the isomeric compound pavine (34) (95,97). The Battersby structure was conclusively confirmed through a study of the chem-... 

If the internal nucleophile is an alkenic group, then 5,6-dihydropyridine (Scheme 18) " or 1-pyrroline (Scheme 19) rings are produced. In a recent development of the latter process, the diol (44) follows the same sequence to yield the carbenium ion (45 R = Bn). However, this now cyclizes onto the aromatic group originating from the nitrile component and produces the tetrahydrobenz indole (46) in good yield, with the conventional pyrroline structure (47) now being only a minor product. Compound (46), present as a tautomeric mixture, was rapidly autoxidized to (48 Scheme 20). A further unusual variant of this process is the production of small quantities of the 3-azabicyclo[3.3.0]octanes (49) and (50) from Ritter reaction of l-vinylbicyclo(2.1.1]hexane (equation 32). ... 

Although the A -pyrroline structure CCI had generally been accepted to represent myosmine, the location of the double bond in the pyrroline ring had never been rigidly demonstrated. A study of the infrared... 

A single-crystal X-ray diffraction study has shown that sola-maladine possesses the pyrroline structure (14) rather than the... 

The piperideine derivatives have not been studied as extensively as the analogous pyrrolines (151,152). The imino structure has been established, for example, for the alkaloid y-coniceine (146) (46). The great influence of conjugation on the structure is seen with l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline (47), possessing an enamine structure, whereas the analogous 1-methyl derivative (48) possesses an imine structure according to infrared spectra (152,153). 

Tertiary pyrrolines (49, = 1) and piperideines (49, = 2) (if R = H and the enamine can exist in the monomeric form or if R = aryl) evidently possess an endocyclic -double bond (79,155,156). The stretching frequency of the double bond can be lowered to 1620-1635 cm by conjugation with an aromatic substituent. The double bond of an analogous compound with aliphatic substituents in position 2 may occupy either the endo or the exo position. Lukes and co-workers (157) have shown that the majority of the five-membered-ring compounds, traditionally formulated with the double bond in a position, possess the structure of 2-alkylidene derivatives (50) with an exocyclic double bond, infrared absorption at 1627 cm . Only the 1,2-dimethyl derivative (51) is actually a J -pyrroline, absorbing at 1632 cm . For comparison, l,3,3-trimethyl-2-methylene pyrrolidine (52) with an unambiguous exocyclic double bond has been prepared (54). 

Physicochemical investigations of enamines and their salts have shown that the addition of a proton occurs almost exclusively at the /3-carbon atom of the enamine grouping. This means that salts of pyrrolines (82), piperideines (83), and enamines of 1-azabicycloalkanes (84) possess immon-ium structures. 

Although pyrrole appears to be both an amine and a conjugated diene, its chemical properties are not consistent with either of these structural features. Unlike most other amines, pyrrole is not basic—the pKa of the pyrrolin-ium ion is 0.4 unlike most other conjugated dienes, pyrrole undergoes electrophilic substitution reactions rather than additions. The reason for both these properties, as noted previously in Section 15.5, is that pyrrole has six 77 electrons and is aromatic. Each of the four carbons contributes one... 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

FIGU RE 10.1 The structure of DMPO. The diamagnetic compound 5,5-dimethyl-l-pyrroline-iV-oxide reacts with an unstable radical R to form a relatively stable radical adduct. 

Ultrasound irradiation of mixtures of amines RNH2 (R = PI1CH2, Ph or Ar) and methyl pyruvate results in the 3-pyrrolin-2-ones 322377. The silver tetrafluoroborate-catalysed cyclization of the allenic amines 323 leads either to a pyrroline 324 or tetrahydropyridine 325, depending on the structure of the amine. The former is formed from 323 (R = H), the latter from 323 (R = Me)378. 

Thermal rearrangement of 0-acyl Af-hydroxycarbamates carrying a cyclopropane substituent was reported (equation 255). When subject to flash vacuum thermolysis at 500 °C the carbamate 573 generates the Af-acyl imine 574 that rearranges to pyrroline 577 in 21-37% yield. The formation of a biradical intermediate 575 or a polar zwitterionic structure 576 was proposed. 

Pyrrolidine alkaloids have a pyrrolidine (C4N skeleton) nucleus. The structural a of these alkaloids is L-ornithine (in plants) and L-arginine (in animals). The pyrro-line skeleton is synthesized after /3 (putrescine) and

Schiff base reaction forms which is A-methyl-A -pyrrolinium cation. Subsequently, A (hygrine) is formed. Typical pyrroline alkaloids are (-)- and (-1-)- hygrines (Figure 56). 

Tropane alkaloids have a tropane (C4N skeleton -f) nucleus. Structurally, these alkaloids synthesize as postcursors of pyrrolines (Figure 57). a, /3,

tropane alkaloids (e.g., atropine, hyoscyamine, cocaine, tropinone, tropine, littorine and cuscohy-grine) have a strong biological activity, especially as neurotransmitters. 

The attachment of the pyrrole ring at C-8 was confirmed by noting that the shift of the aromatic H in the H-NMR spectrum moved from 8 5.93 to 6.38 in the acetylated product. This showed that the free proton is ortho to the phenolic OH at C-5 and that the pyrrole must therefore be at C-8. Further proof of the structure of vochysine was obtained when it was synthesized from 5,4 -di-hydroxy-7-methoxyflavan and an alcoholic solution of pyrroline. 

The gross structural features, presence of a tetramic acid and E-decenoyl side chain, could be inferred from NMR studies. Methanolysis (HCl/MeOH) of 47 and pentane extraction of the quenched reaction mixture gave two compounds that were determined to be the methyl esters of decenoic acid and N-(2-decenoyl)leucine. The nature of the 3-acyl tetramic acid was deduced from the identification of 48 and 49 in the aqueous portion of the methanolysis reaction mixture following treatment with trifluoroacetic acid anhydride. The unusual C-C bond fragmentation under acidic conditions, and the structure of the antibiotic was confirmed by synthesis of racemic 47 [86]. The configuration at the lone chiral centre was established as R by chiral GC. The carbon NMR spectrum of 47 indicated an equilibrium between three tautomers in which the A2-pyrrolin-4-one form is preferred (60%) and the two internal tautomers (50, 51) make equal contributions (20% each). 

Polymerization (76MI11100) of the maleimide isomer 5-(l-adamantyloxy)-2//-pyrrol-2-one (11) allows incorporation (Scheme 6) of the 4-pyrrolin-2-one ring system into a polymeric framework. In analogy with model compounds, polymers and copolymers containing the structural unit (12) undergo photochemical rearrangement to the isocyanate structure (13). Thermolysis, on the other hand, produces poly(maleimides) (14). 

The polymeric pyrrolic autoxidation products probably result from the oxidized monomeric systems, which are analogous in structure to those isolated from photooxidation and peroxide oxidation reactions. Thus, for example, analysis of the products of the autoxidation of 1-methylpyrrole (Scheme 47) would suggest that 1 -methyl-A3-pyrrolin-2-one (153) is initially formed from a radical reaction of the pyrrole with triplet oxygen. This reaction sequence should be compared with that proposed for the oxidation of pyrroles with hydrogen peroxide (Scheme 50), which yields (181), (182) and (183) as the major isolable products. The acid-catalyzed reaction of a pyrrole with its oxidation product e.g. 153) also results in the formation of polymeric material and the formation of pyrrole black is probably a combination of oxidation and acid-catalyzed polymerization processes. 

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