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The Bischler-Napieralski Reaction

Tryptamine cyclization can also be conducted at the amide oxidation level, which is an example of Bischler-Napieralski reaction. The usual reagent is POCI3, which generates a chloroiminium ion intermediate. The immediate products of cycUzatiOTi are iminium ions, which are typically then reduced. [Pg.101]

Bischler-Napieralski cyclization of N -formyl and A/ -acetyltryptamine has been carried out with microwave heating the reactant and POCI3 adsorbed on silica [363]. [Pg.101]

As with the PictetASpengler reaction, the Bischler-Napieralski cyclization has been used in alkaloid synthesis. For example, a synthesis of yohimbine and related alkaloids began with enantiomerically pure amide [364], [Pg.102]

Other examples of alkaloids recently synthesized by Bischler-Napieraski cycli-zations include (-)-vincamine [365], [Pg.102]


Formally analogous to the foregoing Grignard additions are the intramolecular condensations of amides with aromatic systems, found in the Bischler-Napieralski reaction 101), which is of particular interest in isoquinoline and indole alkaloid syntheses (102). Condensations of amidines with reactive methylene compounds also led to enamines (103-106). [Pg.324]

The Bischler-Napieralski reaction involves the cyclization of phenethyl amides 1 in the presence of dehydrating agents such as P2O5 or POCI3 to afford 3,4-dihydroisoquinoline products 2. This reaction is one of the most commonly employed and versatile methods for the synthesis of the isoquinoline ring system, which is found in a large number of alkaloid natural products. The Bischler-Napieralski reaction is also frequently used for the conversion of N-acyl tryptamine derivatives 3 into p-carbolines 4 (eq 2). [Pg.376]

Despite the synthetic utility of this transformation, nearly eighty years elapsed between the discovery of the Bischler-Napieralski reaction and the first detailed studies of its mechanism. " Early mechanistic proposals regarding the Bischler-Napieralski reaction involved protonation of the amide oxygen by traces of acid present in P2O5 or POCI3 followed by electrophilic aromatic substitution to provide intermediate 5, which upon dehydration would afford the observed product 2. However, this proposed mechanism fails to account for the formation of several side products that are observed under these conditions vide infra), and is no longer favored. [Pg.376]

A common modification of the Bischler-Napieralski reaction involves reduction of the dihydroisoquinoline product 2 to provide a tetrahydroisoquinoline derivative 19. A variety of different reducing agents have been employed, with NaBHi used with the greatest frequency. In many cases the reduction is carried out on the crude product of the Bischler-Napieralski reaction purification of the dihydroisoquinoline prior to reduction is usually not necessary. [Pg.378]

An interesting synthesis of quinolizidines was achieved using a vinylogous variation of the Bischler-Napieralski reaction. Angelastro and coworkers reported that treatment of amide 26 with PPSE (polyphosphoric acid trimethylsilyl ester) followed by reductive... [Pg.379]

The adaptation of the Bischler-Napieralski reaction to solid-phase synthesis has been described independently by two different groups. Meutermans reported the transformation of Merrifield resin-bound phenylalanine derivatives 32 to dihydroisoquinolines 33 in the presence of POCI3. The products 34 were liberated from the support using mixtures of HF/p-cresol. In contrast, Kunzer conducted solid-phase Bischler-Napieralski reactions on a 2-hydroxyethyl polystyrene support using the aromatic ring of the substrate 35 as a point of attachment to the resin. The cyclized products 36 were cleaved from the support by reaction with i-butylamine or n-pentylamine to afford 37. [Pg.380]

One important variation of the Bischler-Napieralski reaction is the Pictet-Gams modification, in which p-hydroxy or -alkoxy phenethylamides 38 are converted to isoquinolines 39. This transformation is covered in detail in section 9.12 of this text. [Pg.381]

The Bischler-Napieralski reaction is one of the most widely used methods for the construction of dihydro- and tetrahydroisoquinoline units in the synthesis of alkaloid natural products. A few representative examples of the Bischler-Napieralski reaction in complex alkaloid syntheses are shown below. [Pg.382]

Wender and Aube have independently described the use of the Bischler-Napieralski reaction in the synthesis of Yohimban alkaloids. Aube s approach involved the cyclization of indole 50 followed by reduction of the resulting dihydroisoquinoline... [Pg.382]

The Bischler-Napieralski reaction was employed by Bonjoch in the synthesis of melinonine-E and strychnoxanthine. The preparation of polycyclic compound 57 was achieved in 53% yield by treating 56 with POCI3 followed by reduction of the dihydroisoquinoline with NaBIii. [Pg.383]

Application of the Bischler-Napieralski reaction to amides of tryptophan has been investigated. The cyclodehydration of acetyltrypto-phan under conventional conditions proved unsuccessful. Attempted ring closure of acetyltryptophan or its ethyl ester was accompanied by decarboxylation and aromatization, yielding... [Pg.111]

A synthetic approach to the same tetracyclic y-carboline nucleus (235) is the consecutive Fischer indole and Bischler-Napieralski ring closure of o-acetamidoacetophenone methylphenyUiydrazone (234). The Bischler-Napieralski reaction has also been used in the synthesis of 3,4-benz-j8-carbolines (236) and 3,4-benz-3-carbolines, e.g. 237... [Pg.136]

For the synthesis of quinolines and isoquinolines the classical approaches are the Skraup and the Bischler-Napieralski reactions. The reaction of substituted anilines with different carbonyl compounds in acid medium has been reported to be accelerated under microwave irradiation to give differently substituted quinolines and dihydro quinolines [137]. Although the yields are much better and the conditions are milder than under conventional heating, the acidity of the medium may prevent the preparation of acid-sensitive compounds. Thus, alternative approaches have been investigated. Substituted anilines and alkyl vinyl ketones reacted under microwave irradiation on the surface of sihca gel doped with InCU without solvent [137] to furnish good yields of quinohnes 213 (Scheme 77). [Pg.252]

The Bischler-Napieralski reaction has been described to proceed imder microwave irradiation to give very good yields of dihydroisoquinolines [140] and other polycyclic compounds (see below) in the presence of POCI3 and P2O5 (classical conditions) in toluene (10 cycles of 60 s each using a dedicated microwave reactor). [Pg.253]

Among the many applications of cyclodehydration to the formation of heterocyclic systems is the Bischler-Napieralski reaction. In this reaction, amides of the type 35 are cyclized with phosphorous oxychloride ... [Pg.721]

The Bischler-Napieralski reaction is one of the traditional methods for isoquinoline synthesis, and has been applied to the preparation of fused quinolizidine systems. One simple example is the transformation of compound 246 into a 9 1 mixture of diastereomers 247 and 248 by treatment with phosphorus oxychloride followed by sodium borohydride reduction of a nonisolated iminium salt resulting from the cyclization (Scheme 49) <2000BMC2113>. [Pg.37]

The first two reported syntheses of manzamine C utilized the two most common approaches to the /J-carboline ring system—the Pictet-Spengler reaction [13,14] and the Bischler-Napieralski reaction [15]. These two reactions are illustrated in Fig. 3. [Pg.108]

One of the earliest syntheses of lavendamycin methyl ester, however, did not employ either the Pictet-Spengler or the Bischler-Napieralski reactions for construction of the /J-carboline ring system. Instead, a palladium-promoted ring closure of aryl pyridine 36 (Fig. 12) was used to prepare /1-carboline 37 by Boger and coworkers [35]. Unfortunately, stoichiometric palladium was found to be necessary, in this case 1.5 equivalents of the tetrakis(triphenylphosphine)palladium(0) being used. Friedlander condensation with aldehyde 38 in the presence of benzyltrimethylammonium hydrox-... [Pg.114]

Bischler, A. Napieralski, B. Ber. Dtsch. Chem. Ges. 1893, 26, 1903. Augustus Bis-chler (1865—1957) was born in South Russia. He studied in Zurich with Arthur Hantzsch. He discovered the Bischler-Napieralski reaction while studying alkaloids at Basel Chemical Works, Switzerland with his coworker, B. Napieralski. [Pg.58]

For the preparation of 3,4-dihydro-/3-carbolines the Bischler-Napieralski reaction is widely used (510R74). Since this reaction requires rather drastic conditions, A-acetyl tryptophan and its analogs yielded l-methyl-/8-carboline (harman) rather than l-methyl-3,3-dihydro-j8-carboline-3-carboxylic acid derivatives owing to accompanying decarboxylation and aromatization (41JCS153 50JA2962). [Pg.56]

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophihc process and only works well for electron-rich rings. [Pg.521]

The 3,4-dihydrobenzo[h]furo[2,3-c]pyridine system (49) has been synthesized by applying the Bischler-Napieralski reaction to amide (48) (78JHC481). [Pg.978]

What is the mechanism of the Bischler-Napieralski reaction of step b ... [Pg.4]


See other pages where The Bischler-Napieralski Reaction is mentioned: [Pg.378]    [Pg.379]    [Pg.380]    [Pg.381]    [Pg.457]    [Pg.465]    [Pg.107]    [Pg.197]    [Pg.23]    [Pg.112]    [Pg.102]    [Pg.218]    [Pg.335]    [Pg.247]    [Pg.72]    [Pg.224]    [Pg.978]    [Pg.271]    [Pg.978]    [Pg.61]    [Pg.72]   


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