Condensations potassium tert-butoxide

The first synthesis of a 3//-3-benzazepine, e.g. 65 (R1 = R2 = Me), was achieved by the condensation of phthalaldehyde with a bis[(alkoxycarbonyl)methyl]methylamine.24"25 With sodium methoxide as the base, A%V-bis[(methoxycarbonyl)methyl]pheiiylaniine condenses with the dialdehyde in a similar manner to give dimethyl 3-phenyl-3//-3-benzazepine-2,4-dicar-boxy late (65, Rl — Ph R2 — Me).99 However, replacement of methoxide by potassium tert-butoxide results in formation of 3-phenyl-3//-3-benzazepine-2,4-dicarboxylic acid (65, R1 = Ph R2 = H).25... 

The propargylic alcohol 102, prepared by condensation between 100 and the lithium acetylide 101, was efficiently reduced to the hydrocarbon 103, which on treatment with potassium tert-butoxide was isomerized to the benzannulated enyne-allene 104 (Scheme 20.22) [62], At room temperature, the formation of 104 was detected. In refluxing toluene, the Schmittel cyclization occurs readily to generate the biradical 105, which then undergoes intramolecular radical-radical coupling to give 106 and, after a prototropic rearrangement, the llJ-f-benzo[fo]fluorene 107. Several other HJ-f-benzo[fo]fluorenes were likewise synthesized from cyclic aromatic ketones. 

The aniline nitrogen is then converted to the para-toluenesulfonamide (4-3). Reaction of this intermediate with ethyl co-chlorobutyrate in the presence of potassium carbonate then gives the alkylation product (4-4). Potassium tert-butoxide-catalyzed Claisen condensation of this diester leads to azepinone (4-5) as a mixture of methyl and ethyl esters resulting from alternate cyclization routes. A strong acid leads to the transient keto-acid, which then decarboxylates the toluensulfonyl group is lost under reaction conditions as well as affording the benzazepinone (4-6). This last intermediate is then acylated with the benzoyl chloride (4-7) to afford amide (4-8). 

This reaction involves the condensation of an aldehyde or ketone with an a-halo ester in the presence of a basic condensing agent (sodium ethoxide, sodamide, finely divided sodium or potassium tert.-butoxide) to give a glycidio (or ap-epoxy) ester. Thus acetophenone and ethyl chloroacetate yield phenyl-methylglycidic ester (I) ... 

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a little reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl sucoinate in the presence of potassium tert.-butoxide to give a 94 per cent, yield of (3-carbethoxy-YY-diphenylvinylacetic acid (I) is the potassium salt ... 

B. Ethyl 4-hydroxy[1-13C]benzoate. A 100-mL, single-necked, round-bottomed flask equipped with a magnetic stirring bar, pressure-equalizing addition funnel and a reflux condenser beyond the dropping funnel (Note 10) is charged with 20 mL of tert-butyl alcohol (t-BuOH) (Note 11), 1.01 g (10.5 mmol, 1.05 equiv) of 4H-pyran-4-one (Note 12), and 1.61 g (10.0 mmol, 1 equiv) of diethyl [2-13C]malonate. The condenser is sealed with a silica gel drying tube, and the stirred solution is put in an oil bath at 105°C. A solution of 0.22 g (2.0 mmol, 0.2 equiv) of potassium tert-butoxide (Note 13)... 

The present procedure affords 4-hydroxy[1-13C]benzoic acid from ethyl [2-13C]acetate in three steps with 72% overall yield. It is based on an observation of Woodward17 that ethyl 4-hydroxy benzoate is formed by base-catalyzed condensation of 4H-pyran-4-one with diethyl malonate. The submitters studied several solvent-base combinations for this reaction and found that tert-butyl alcohol/potassium tert-butoxide gave the highest yields. When a stoichiometric amount of the base is used, an excess of 4H-pyran-4-one has to be used.4b This can be avoided by the use of substoichio-metric amounts as given in the procedure. 

The use of ethyl [2-13C]acetoacetate instead of diethyl [2-t3CJmafonafe in the condensation reaction with 4H-pyran-4-one afforded ethyl 4-hydroxy[1 -13C]benzoate in 87% yield. In this case, 1.1 equiv of 4H-pyran-4-one and 1.1 equiv of potassium tert-butoxide were optimal. The addition of catalytic amounts of the base was not satisfactory. Ethyl [2-13C]acetoacetate was prepared from ethyl (2-13C]acetate as described for diethyl [2-13C]matonate.16 The maximum yield for this reaction on a 10-mmol scale was only 70% after distillation. 4H-Pyran-4-one reacted with nitromethane and potassium tert-butoxide (each 1.1 equiv) to afford 4-nitrophenol in 75% yield after purification by flash chromatography. This gives easy access to 4-nitro[4-13C]phenol. With 2,4-pentanedione, the condensation with 4H-pyran-4-one under the same reaction conditions gave 4-hydroxyacetophenone in 45-50% yield after purification. 

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