Sodium methoxide Reagents

Prepare sodium methoxide reagent as follows To 20-0 g of freshly cut sodium in a flask fitted with a reflux condenser, add, in portions down the condenser, sufficient anhydrous methanol to dissolve all the sodium, warming and refluxing if necessary. Transfer to a 500-ml graduated flask, washing in with anhydrous methanol, and dilute to volume with anhydrous methanol. Chill, centrifuge from any carbonate impurity and store in a suitable container to exclude moisture and carbon dioxide. Adjust to 40 g Na per litre (1-74N) by titration with standard acid. Prepare a new standard curve for each fresh batch of the reagent. 

Transfer a 5-ml aliquot to a flask and add exactly 10 ml of the sodium methoxide reagent. Mix well, allow to stand for fifteen minutes and determine the extinction at 600 m// using matched, stoppered cells with, in the comparison cell, a mixture of one volume of benzene and two volumes of the sodium methoxide reagent. (Readings in the blue at 450 m/< and in the green at 510 m// should also be made to check the presence of extraneous yellow and red colours when the samples are read.) Prepare a curve by plotting extinction against //g dicophane. 

Methyl-3,4-dinitropyrrole (170) undergoes some interesting reactions with nucleophilic reagents. With methanolic sodium methoxide it yields a product (171) which on treatment with trifluoroacetic acid gives the 2-methoxypyrrole (172) 78CC564). 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

It may be unsafe to carry this discussion further until more data are available. Knowledge of the activation parameters would be especially desirable in several respects. Reactivity orders involving different reagents or substrates may be markedly dependent on temperature. Thus, in Table IV both 2- and 4-chloroquinolines appear to be about equally reactive toward sodium methoxide at 86,5°. However, the activation energies differ by 3 kcal/mole (see Section VII), and the relative rates are reversed below and above that temperature. Clearly, such relative rates affect the rs-/ ro- ratios. 

Scheme 9.6 Synthesis of methyl heptaglucoside 1. The letters indicate intermediates used in the synthetic sequence displayed at the bottom of the scheme. The numbers describe reaction conditions or reagents (1) IV-iodosuccinimide, trifluoroacetic acid (2) removal of benzylidine (3) acetylation (4) removal of t-butyldimethylsilyl (5) sodium methoxide/methanol.

Better results can be obtained by generating the boronate species with the aid of sodium methoxide. In this case, satisfactory transmetalation occurs on treatment with Cul. Thus, the functionalized copper reagent 55 can be alkynylated with 1-bromo-l-hexyne at —40 °C, furnishing the enyne 56 in 75% yield (Scheme 2.15) [32]. 

The methanol-triethylamine reagent is superior to the previously used methanolic sodium methoxide, and the crude 2-methoxycyclooctanone oxime thus obtained can be used for the Beckmann fission reaction without further purification. However, it is easily purified by distillation, b.p. 101° (0.7 mm.). 

Like the corresponding methylpyridines, 2- and 4-methylquinolines can be deprotonated by a base, such as sodium methoxide, forming resonance-stabilized anions (Scheme 3.9). The latter are useful in synthesis, providing nucleophilic reagents that allow extension of quinoline side chains through reactions with appropriate electrophiles. Activation of the 2-methyl group can also be achieved by the use of acetic anhydride (the same type of process occurs with 2-methylpyridine, Section 2.7.1, Worked Problem 2.3). 

Sodium methoxide in methanol, often with chloroform as cosolvent, has customarily been the basic reagent employed. Less frequently, particularly with water-soluble esters, sodium or potassium hydroxide in aqueous solution has been used. Generally, an excess of the basic reagent is taken, except where the possibility of epoxide migration arises (see p. 127). In the latter situation, only a limited excess of reagent is used, at low temperature, or, alternatively, the... 

Similar to the conversion of 267 to 270, the N-methyl ammonium salt 271 is converted into 272 upon treatment with active methylene reagents in the presence of sodium methoxide (77CPB535). 

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