Phenanthridines preparation

Over the years, many spiropyran structures have been prepared. The pyran component consists of benzopyran or naphthopyran and the heterocyclic part consists of indoline, benzothiazoline, benzoxazoline, benzoselen-azoline, phenanthridine, acridine, quinoline, benzopyran, naphthopyran, xanthene, benzodithiole, benzoxathiole, and saturated heterocyclic rings such as pyrolidine and thiazolidine. 

Reductive cyclization of 2-formyl-2 -nitrobiaryl compounds gives phenanthridine derivatives.136 The Stille coupling of nitroarylstannanes with 2-bromobenzaldehyde are used for the preparation of the requisite 2-formyl-2 -nitrobiaryls. Subsequent treatment of biphenyl derivatives with zinc dust in acetic acid gives the phenanthridine derivatives as shown in Eq. 10.80.137... 

Oxidative photocyclization of benzylideneaniline appears to proceed efficiently only in the presence of strong acid. The phenanthridine 31, however, has been prepared by irradiation of the imine 3228 few other examples of the photocyclization of arylimines have been reported.29 Strong acid is also required for successful photocyclization of azobenzenes to benzo-[c]cinnolines. Here, protonation is claimed to lower the reactive n, n excited state below the level of the unreactive n, it state. 2-Phenylazopyridine,... 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

Intramolecular cyclization of 2-lithiobenzyl-2-halophenyl amines, ethers, and thioethers—Synthesis of phenanthridine, dibenzopyran, and dibenzothiopyran derivatives Having demonstrated the efficiency of this methodology for the preparation of indole derivatives, we prepared the 2-fluoro-phenyl ether and thioether 22 a, b to study their potential as substrates that could afford oxygen and sulfur heterocycles. However, treatment of 22 a, b with fBuLi afforded, after... 

The intermediacy of aryne intermediates generated by dehydrohalogenation of the corresponding aryl bromide is useful in preparing polycyclic isoquinolines with the phenanthridine skeleton <99T5195, 990L985>. 

Mol. wt. 181-233, m.p. 124°. The reagent is prepared by reduction of phenanthridine with lithium aluminum hydride in refluxing ether (75% yield).1... 

Hydroxy-8,9-methylenedioxyphenanthridine, [10]. The method developed by Kessar et al. [11] for phenanthridines and related compounds was applied to the synthesis [10] of 3-hydroxy-8,9-methylenedioxyphenanthridine (22) (Scheme 5). Thus, the benzylidene aniline 23, prepared from 6-chloropiperonal and 3-benzyloxyaniline, was reduced to the secondary amine 24. Treatment of 24 with excess lithium diisopropylamide furnished, on work-up, the benzyl ethers 25 (22%) and 26 (6%) respectively. Catalytic debenzylation of the former generated 22. 

Badger and Sasse have described the preparation of 2-, 3-, and 8-bromophenanthridine by the cyclization of the appropriate bromo-formamidobiphenyl with polyphosphoric acid.25 In the case of 2-bromo-2 -formamidobiphenyl a higher concentration of phosphorus pentoxide in the acid was necessary to effect ring closure, and a simple steric effect was invoked.26 Nevertheless, the Morgan-Walls reaction has been used to obtain several overcrowded compounds in which unfavorable steric factors operate. Following the original report of the preparation of the 1,10-dimethylphenanthridine (5a) by this procedure,27 several other examples have been described, notably the synthesis of the related phenanthridine (5b),28 the l,2-(6)29 and 9,10-benzophenanthridines (7),30 and the 1,2 9,10-dibenzophenanthridine (8).29... 

Recently, several syntheses of phenanthridines have been described in which the biphenyl bond is formed by photochemical coupling. The chief advantage of this method is that relatively simple intermediates are required on the other hand, since dilute solutions must be employed to minimize dimerization of the reactant, the technique is usually convenient only for the preparation of relatively small amounts of material. 

In the simplest case, the conversion of benzylideneaniline to phenanthridine, ring closure occurs satisfactorily in sulfuric acid,151 and both 6-methyl- and 3,6-dimethylphenanthridine have been prepared in the same way, albeit in low yield, from the appropriate acetophenone anil.152 However, Mallory and Woods153 have shown that no phenanthridine is formed when benzylideneaniline is irradiated in either cyclohexane, benzene, or ethanol at 30°-40°, and have ascribed this to the short half-life (ca. 1 second at room temperature154, 155) of the cis isomer [although a successful cyclization has been reported in the case of the dimethylamino derivative (112b)156]. 

Several pyrolytic methods of preparation have been reported. The thermal decomposition of 1-benzylbenzotriazole in the presence of copper at 350-400° gives phenanthridine in low yield,189 together with some jV-benzylaniline.190 The pyrolysis of 11-phenyldibenzo-thiazepine (166) (R1 = R2 = H) in diethyl phthalate in the presence of copper bronze provides 6-phenylphenanthridine in 94% yield,191... 

Phenanthridine is known to undergo direct amination readily with hydride extrusion (the Chichibabin reaction) and further examples have been reported.22 More interesting is the preparation of 6-aminophenanthridine in high yield by the action of the sodium salt of N,N-dimethylhydrazine on phenanthridine in benzene. The adduct (224) (R = Me) loses dimethylamine on heating leaving the sodium salt of the 6-amino compound (225).318... 

Aminative replacement in compounds other than those bearing halogen atoms are uncommon, but 6-aminophenanthridine is easily prepared by heating 6-phenoxyphenanthridine with urea296 and 6-anilinophenanthridine has been obtained by the action of aniline on the 6-phenoxy compound.268 The formation of 6-anilinophenanthridine from phenanthridine iV-oxide and phenyl isocyanate probably proceeds via an initial 1,3-dipolar addition, followed by nucleophilic substitution and decarboxylation (Scheme 4).309... 

Synthetic and degradative use has been made in several instances of the easy decarboxylation of phenanthridine-6-carboxylio acids.30, 80, 324 The corresponding iV-oxide is decarboxylated by heating in aqueous sulfuric acid.77 Phenanthridine-3,8-dicarboxylic acids are more resistant to decarboxylation, which can be achieved (in poor yield) by heating with copper powder in quinoline.194 The usual carboxyl derivative inter con versions (esterification, amide formation, ester and amide hydrolyses, etc.) proceed normally with both phenanthridine-6-carboxylic acid and its A-oxide,77, 232, 352 although an unsuccessful attempt to prepare 6-acetylphenanthridine from the acid with methyllithium has been reported.232... 

Among more recent examples of cyclization through a nitro group the reaction of preparation of phenanthridine might be referred to (Muth, Ellers and Folmer [20]) ... 

The oxidation of chars prepared from nitrogen-containing precursors has been investigated. Chars produced from the nitrogen-containing compounds acridine and phenanthridine were oxidized at atmospheric pressure at temperatures of 773-873 K. The relative rates of nitrogen and carbon release and the formation of NO have been determined in relation to char nitrogen content and precursor type. 

By suitable substitution the enaminones can often serve as precursors for heterocycles and preparation of indoles, carbazoles, quinolines, acridines and phenaNthridines can be achieved easily. However, this part of enaminone chemistry can lead to surprising and unexpected reactions if the multifunctional properties of the enaminones are ignored, e.g. ring contraction, ring expansion and other rearrangements are observed. In some cases jft-ketoenamines react as the ene-component in cycloaddition. Enaminones are even suitable synthones for building aromatic rings. 

Preparation of A,-(5-ethyl-6-oxo-5,6-dihydro-phenanthridin-9-yl)-2,2,2-trifluoro-acetamide... 

The phenanthridine skeleton is synthesized by photocyclization of the enamides prepared from cyclohexanonimines and benzoyl chlorides (17,18). The benzo[c]phenanthridine skeletons are formed from the enamides prepared from 2-tetralonimines and benzoyl chlorides (19,20). More conveniently, the skeletons of protoberberine alkaloids are readily synthesized from the enamides prepared by simple acylation of 1 -methyl-3,4-dihy-droisoquinolines with benzoyl chlorides (21-24). This berbine synthesis is one of the most typical examples of the application of enamide photocyclization to alkaloid synthesis and can be further extended to the facile synthesis of the skeletons of the yohimbine group of indole alkaloids (25,26). 

The alkaloid contents in a single alkaloid cell from M. cordata roots of three different thicknesses (age 1-2 years) were determined as follows. The liquid from various numbers of alkaloid cells (Table II) was removed uniformly and collected in the microtrap. The liquid in the capillary and connection tubes was washed into the microtrap to make a certain definite volume for analysis. Quantitative analysis of each alkaloid was carried by preparing a calibration graph (4). Figure 3 shows the HPLC chromatogram of alkaloids from the alkaloid cells. The content of each alkaloid per single alkaloid cell in tissues from three different thickness of roots and its ratio are shown in Table II. The liquid in colorless cells contained only a minute amount of protopine and allocryptopine (Fig. 3). The thicker the roots, the more alkaloids were contained in a single alkaloid cell. In any thickness of root, the content of protopine-type alkaloids exceeded that of benzo[c]phenanthridine-type alkaloids. The ratio of the former to the latter was almost steady over 5 mm of root thickness (86-87%). The ratio of alkaloids in methanol extracts of the same fresh samples (thickness 5 mm) was determined by HPLC (Table III). The ratio of protopine-type alkaloids in the methanol extracts ( 80%) was less than that in the liquid from the alkaloid cells ( 87%). This was because the liquid in alkaloid cells near the cambium were picked up more than that in center cells (pith). Thus, intracellular components scattered in different places are analyzed qualitatively and quantitatively in situ by HC. 

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