Benzamides metallation

A rational extension of ortho-tolyl benzamide metalation [68], part of the broadly encompassing lateral metalation protocol [69] that can be DoM-connected, is the DreM equivalent, 154 —> 155 (Scheme 41), which provides a general regioselective route to 9-phenanthrols (156, 157, 158) [70] and may be extended to diaryl nitriles, hydroxylamine ethers, and hy-drazones 160, which provide the corresponding 9-amino derivatives 161 of similar generality 162-165 (Scheme 42), as may also be applied in natural product synthesis [71]. Further opportunities for DoM-cross-coupling and reduction/oxidation chemistry (159) have also been demonstrated [70a]. 

Acid anhydride-diol reaction, 65 Acid anhydride-epoxy reaction, 85 Acid binders, 155, 157 Acid catalysis, of PET, 548-549 Acid-catalyzed hydrolysis of nylon-6, 567-568 of nylon-6,6, 568 Acid chloride, poly(p-benzamide) synthesis from, 188-189 Acid chloride-alcohol reaction, 75-77 Acid chloride-alkali metal diphenol salt interfacial reactions, 77 Acid chloride polymerization, of polyamides, 155-157 Acid chloride-terminated polyesters, reaction with hydroxy-terminated polyethers, 89 Acid-etch tests, 245 Acid number, 94 Acidolysis, 74 of nylon-6,6, 568... 

Similarly, reactions which are substantially enhanced by the use of PTC can be carried out even with reduced use of PTC with substantial enhanced rates of reaction as has been demonstrated by Sivakumar and Pandit (2000) in the case of conversion of benzamide to benzonitrile. In the case of A-alkylation of diphenylamine with benzyl bromide, in the presence of KOH as the anion source and PEG methyl ether as the PTC, some improvement in the rate has been observed. (Cains et al., 1998). Metal catalysed hydrogenations, such as those based on Ni, Pd/C, and Ru/C also benefit from ultra-sound. 

Birch reduction of the chiral benzamide 5 generates the amide enolate 6 (Scheme 4). This enolate has been characterized by NMR spectroscopy and by an extensive examination of the effects of changes in alkali metal, solvent, reaction... 

Systematic studies by Iwao on diethyl and diisopropyl amides 447 in reactions with benzamides to give products 448 are significant also in that optimum conditions for metalation (LiTMP/DME/-78°C/5-15 min.) on the recommended diisopropyl amide were established (Scheme 134) (83TL2649). The application of 448 in the synthesis of natural products is delineated in Section VIII. 

Bacteriochlorins, 851 Barbituric acid metal complexes, 798 Barium alkoxides synthesis, 336 Barium complexes phthalocyanines, 863 porphyrins, 820 Becium homblei copper accumulation, 964 Benzaldehyde, 2-amino-self-condensation aza macrocycles from, 900 Benzamide, o-mercapto-metal complexes, 655 Benzamide oximes metal complexes, 274 Benzamidine, /V, V -diphenyl-metal complexes. 275 Benzene, 1,2-diamino-reactions with dicarbonyl compounds aza macrocycles from, 902 Benzene, 4 methylthionitroso-metal complexes, 804 Benzenedithiolates metal complexes, 605... 

The concept of in situ liberation of carbon monoxide would be even more attractive if a metal-free material could serve as the carbon monoxide source. In the ideal carbonylation method, the organic solvent itself could be exploited for controlled generation of carbon monoxide. In 2002, Wan et al. addressed this issue and developed a microwave-promoted carbamoylation process based on the commonly used solvent dimethylformamide (DMF) as the carbon monoxide precursor75. Firstly, it was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of a nucleophilic catalyst, imidazole (Scheme 2.34). Secondly, tertiary benzamides other than dimethylamides were synthesised by addition of 3 equiv of an external amine (Scheme 2.34). 

Mills, Taylor and Snieckus103 describe a methodology based on the preferre o metallation of benzamides (equation 40). In this case the trimethylsilyl group is use to block one of the ortho positions, directing the electrophile to the other. 

Generally, the direct metallation of unactivated alkyl groups is not a synthetically useful reaction. However, under certain circumstances unactivated a-silylcarbanion formation has been reported. Treatment of orf/zo-silylated benzamides 149 with LDA gave an a-silyl carbanion 150, stabilized by a complex-induced proximity effect, which then underwent... 

Intermolecular additions of the O-H bonds of phenols and alcohols and the N-H bonds of sulfonamides and benzamide to alkenes catalysed by 1 mol% of triflic acid have been reported as tools for the synthesis of cyclic ethers and amines. This study contributed to defining the relationship between these reactions and those catalysed by metal triflates.36... 

Non-enolizable amides, for example N,N-dialkyl pivalamides [212], benzamides, thiobenzamides [213], or phosphinamides (Ph2P(0)NR2[214]), can be lithiated a to the amino group by treatment with sBuLi[54, 213, 215] or tBuLi[216], without further additives, in THF at -78 °C. N,N-Dimethylbenzamides can be attacked at the carbonyl group by these organolithium reagents to yield ketones [217] or alcohols, but with sterically more demanding amides metalation is usually faster than addition. 

As shown by the last reaction in Scheme 5.23, the metalation of benzamides is complicated by several potential side reactions (Scheme 5.24). Thus, benzamides can also undergo ortho-metalation [181, 217-222] or metalation at benzylic positions [223-225], Ortho-metalation seems to be promoted by additives such as TMEDA, and benzylic metalation can be performed selectively with lithium amide bases [217,224], which are often not sufficiently basic to mediate ortho- or a-amino metalation. If deprotonation of the CH-N group succeeds, the resulting product might also undergo cydization by intramolecular attack at the arene [214, 216] (see also Ref. [226] and Scheme 5.27) instead of reacting intermolecularly with an electrophile. That this cydization occurs, despite the loss of aromatidty, shows how reactive these intermediates are. 

Ach, D. Reboul, V. Metzner, P. Atroposelec-tivity of reactions of benzylic metalated thio-benzamides and thionaphthamides. Ear. J. 

Anthraquinone synthesis.1 The original anthraquinone synthesis (10, 75) from benzamides and benzaldehydes involving a tandem orf/io-lithiation can be improved by use of an ort/to-bromobenzaldehyde as the second component. In this version, the second lithiation involves halogen-metal exchange, which results in higher yields. In the example cited here, the yield was only 15% in the absence of the bromine substituent on the aldehyde. 

The use of transition-metal arene complexes to facilitate nucleophilic aromatic substitution features in a route to derivatives of thiosalicylic acid and hence to thioxanthone. The cyclopentadienyl iron complex of 2-chlorobenzoic acid is converted into the benzamide prior to displacement of the chloride by thiophenoxide. Photolytic decom-plexation followed by directed remote metallation of the diaryl sulfide yielded the heterocycle (Scheme 207) <2000SL975>. 

The anti-tumour properties of cryptopleurine (33) continue to stimulate synthetic work in this area, and two new syntheses have been reported this year. Snieckus and co-workers25 have described a short, efficient synthesis of the alkaloid, utilizing a benzamide-directed metallation reaction (Scheme 6). In the other synthesis,26 the piperidine derivative (35), prepared by a nitrone cycloaddition reaction, is cyclized... 

The reaction of ort/zo-metallated tertiary benzamides with epoxides affords a mixture of anti and syn alcohols which on lactonisation gives the dihydroisocoumarin as a single diastereomer. Using (5)-(+)-propylene oxide it was possible to synthesise the fungal metabolite (5)-(+)-mellein 29 <06SL873>. 

MetaUation of benzamides. The ort/io-metallation of tertiary amides (10, 75 11, 367-368) permits a novel epoxy cyclialkylation route to benzofuranes and -pyranes. Examples ... 

As a result of this and Eq. 2.4, Hammett constants directly influence the complex formation eqnilibria, although to varying extents depending on whether this is first-order or second-order, the latter due to aromatic substitution next to different donor sites (P (phosphines), N (benzamides, pyridines or pyrazininm ions), S (thiophenolates) or O (phenolates, benzoates, combinations like salicylate derivates) or combinations thereof (see case c. above) (salen derivatives or those of hippnric acid, both linked to metal by N -t- O)). 

Now benzamide forms similar metallic salts and these salts when treated with alkyl halides yieXd alkyl amine derivatives of benzoic acid. 

Hofmann Reaction.—The metallic salts of benzamide are also involved in the Hofmann reaction (p. 148), by which an acid amide is converted into a primary amine. 

There are interesting transition metal-catalyzed-reactions that lead to aryl amides. The use of POCI3 and DMF, with a palladium catalyst, converts aryl iodides to benzamides. A palladium-catalyzed reaction of aryl hahdes and for-mamide leads to benzamide derivatives. Carbonylation is another method that generates amides. When an aryl iodide was treated with a secondary amine and Mo(CO)e, in the presence of 3 equivalents of DBU, 10% Pd(OAc)2, with micro-wave irradiation at 100°C, the corresponding benzamide was obtained. 

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