Strongly basic conditions

The Claisen condensation is initiated by deprotonation of an ester molecule by sodium ethanolate to give a carbanion that is stabilized, mostly by resonance, as an enolate. This carbanion makes a nucleophilic attack at the partially positively charged carbon atom of the e.ster group, leading to the formation of a C-C bond and the elimination ofan ethanolate ion, This Claisen condensation only proceeds in strongly basic conditions with a pH of about 14. 

Oxindoles can be prepared from Af,p-acylphenylhydrazines by a reaction which is analogous to the Fischer cyclization. This is known as the Brunner reaction. The reaction is typically conducted under strongly basic conditions. For example, heating Af-phenylcyclopentanecarbonylhydrazide with CaO gives a 70% yield of spiro-cyclopentane oxindole[l]. 

It looks as though all that is needed is to prepare the acetylenic anion then alkylate it with methyl iodide (Section 9 6) There is a complication however The carbonyl group m the starting alkyne will neither tolerate the strongly basic conditions required for anion formation nor survive m a solution containing carbanions Acetyhde ions add to carbonyl... 

Itaconic acid (1) is isomeric with citraconic [498-23-7] (2) and mesaconic [498-24-8] (3) acids. Under acidic, neutral, or mildly basic conditions and at moderate temperatures, itaconic acid is stable. At elevated temperatures or under strongly basic conditions, the isomers are interconvertible. 

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

In the preparation of hydroperoxides from hydrogen peroxide, dialkyl peroxides usually form as by-products from the alkylation of the hydroperoxide in the reaction mixture. The reactivity of the substrate (olefin or RX) with hydrogen peroxide is the principal restriction in the process. If elevated temperatures or strongly acidic or strongly basic conditions are required, extensive decomposition of the hydrogen peroxide and the hydroperoxide can occur. 

Benzyltriethylammonium chloride [56-37-1] is the most widely used catalyst under strongly basic conditions. Methyltrioctylammonium chloride [5137-55-3] (Ahquat 336, Adogen 464) is probably the least expensive catalyst. Others of high activity and moderate price are tetra- -butylammonium chloride [1112-67-0] bromide [1643-19-2] hydrogen sulfate [32503-27-8], tetra- -butylphosphonium chloride [2304-30-5], and other phosphonium salts of a similar number of C atoms. Many other onium salts can also be utilized. 

Acylation of pyridazinones and related compounds in the presence of weakly basic catalysts such as pyridine or sodium acetate produces IV-acylated products, while O-acylated products are obtained under strongly basic conditions. However, the reaction between 6-chloropyridazin-3(2//)-one with chlorocarbonates and that of maleic hydrazide with unsaturated acid chlorides or chloromethylsulfonyl chloride gives preferentially N-substituted products. 

Me2S04, 2 N NaOH, MeOH, H2O, reflux, 30 min, 85% yield.In this case the hemiacetal of phthaldehyde is alkylated with methyl sulfate this use is probably restricted to cases that are stable to the strongly basic conditions. 

The most common conditions employed in the Madelung process are sodium/potassium alkoxide or sodium amide at elevated temperature (200-400 C). The Madelung reaction could be effected at lower temperature when -BuLi or LDA are employed as bases/ The useful scope of the synthesis is, therefore, limited to molecules which can survive strongly basic conditions. The process has been successfully applied to indoles bearing alkyl substituents. ... 

Dihydro-2/7- 74 and -4//-l,2-oxazines and thiazines 75 are interrelated by prototropy, being enamines and imines, respectively. In the case of oxazines, the imine form 75 is favored, and there are several well established examples of this system, including the parent heterocycle 75 (X = O) [84MI2]. No tautomeric equilibrium between the 2H and 4H forms has been observed under normal conditions in solution or in the solid state. However, the formation of intermediate 2H isomers 77 was proposed both for the conversion of 3-phenyl-5,6-dihydro-4//-l,2-oxazine 76 (R = Ph, r = R = H) into 2-phenylpyrrole(89TL3471) under strong basic conditions and for thermal decomposition of cyclopentene-fused 1,2-oxazine 76... 

Compound 15 is prepared in two steps acid-catalyzed condensation of the pyrimidinediamine with ethyl aceloacelale provides ester 14, which cyclizes under strongly basic conditions. The pyrimidodiazepinone 15 undergoes ring contraction to 7-isopropenyl-7//-purin-8(9//)-one (16) on prolonged heating under basic conditions.297... 

Because of the strongly basic conditions needed for Wittig reactions with now-stabilized ylides, one-pot reactions have not been carried out [57]. Ley s recent report of a TPAP-Wittig oxidation performed in a sequential one-pot manner is thus a promising alternative [58]. The reaction is fast and straightforward the... 

In this way cyclohexanones with two or three contiguous stereogenic centers are obtained under mild conditions, as compared to the Diels-Alder conditions or the strongly basic conditions of the lithium enolate MIMIRC reaction. 

Bunnett (1991) expresses doubts that the aryldiazene can be formed at all under these strongly basic conditions, after Huang and Kosower (1968) showed that phenyldiazene is destroyed in water at pH 13.8 (25 °C) with a half-life of <10s, doubtless via C6H5-N2. In addition, Broxton s proposal (Scheme 8-53) does not provide a satisfying explanation of why the ortho halogen has such a strong effect in favor of the carbanion mechanism. 

Oxime carbamates are generally stable in aqueous solutions at pH 4-6. Their chemical degradation (hydrolysis) in water depends strongly on pH. Strongly basic conditions... 

Stable in an acidic to neutral aqueous solution. Unstable in strongly basic conditions Stable in most organic solvents... 

In an attempt to hydrolyze PSPDM completely to head-to-head poly(methacrylic acid), higher temperature, and more strongly basic conditions were employed. PSPDM was heated at 125 C for four days in 5M NaOH. Like the 0.1M NaOH experiments, the imide was hydrolyzed to the amic acid and no further. The amide of the ring opened imide (V) is extremely resistant to basic hydrolysis. 

Methods such as the pyrolysis of (106), that do not require strongly basic conditions, have been used to generate arynes in bulk for preparative purposes, and another, even better, method is oxidation of l-aminobenzotriazole (107) with lead tetraacetate ... 

Since the suggested conversion process does not include a thermally promoted bond-scission step, the question arises of how the addition of hydrogen results in the bond breaking necessary for significant reduction in molecular weight. We have already noted that the nucleophilic action of the basic methanol system was sufficient to cleave diphenyl ether, and a similar route is available in the basic i-PrOH and C0/H20 systems. On the other hand, we showed in control experiments that strongly basic conditions alone were not sufficient for significant conversion of coal. 

Nitroethylene is extremely reactive and sensitive to strong basic conditions, but various ketone and ester enolates undergo alkylation with nitroethylene at low temperature (Eq. 4.5165 and Table 4.1). 

In the context of preparing benzothienyloxy phenylpropanamines as inhibitors of serotonin and norepinephrine uptake, a group from Eli Lilly and Company has developed a two-step synthesis of benzo[fo]thiophenes (Scheme 6.193) [354]. Thus, a 2-mercapto-3-phenylpropenoic acid derivative was cyclized with iodine in 1,2-dimethoxyethane at 120 °C to give 5-fluoro-4-methoxybenzothiophene-2-carboxylic acid in 67% yield. Decarboxylation under strongly basic conditions involving 1,8-di-azabicyclo[5.4.0]undec-7-ene (DBU) as base in N,N-dimethylacetamide (DMA) as... 

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