Sodium methoxide

Most alkoxides are highly basic. These moisture-sensitive substances are corrosive and caustic. Skin contact can cause irritation. However, highly exothermic water-reactive compounds such as potassium tert-butoxide, are strongly corrosive and can cause bums. 

It is used as a catalyst and finds application in many organic syntheses. 

White crystalline powder hygroscopic melts at 257°C (494°F) (decomposes) powder density 0.50 g/mL soluble in tetrahydrofuran and ferf-butanol [20% at 20°C (68°F)], low solubility in hexane, benzene, and ether. 

The addition of potassium terf-butoxide to the solvent dimethyl sulfoxide can cause ignition of the latter (Bretherick 1995). 

It is used as a catalyst for treatment of edible fats and oils, as an intermediate in many synthetic reactions, to prepare sodium cellulosate and as a reagent in chemical analysis. 

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Williamson s lethod, more particularly lor hydroxy- and thloT (mercapto) compounds. The substance is treated either directly with sodium or (more usually) with a solution of sodium methoxide in methanol, to give the sodium derivative. The latter is then boiled with methvl iodide. 

In general the method is more satisfactory with esters of aromatic acids than with esters of aliphatic acids. Esters of alcohols other than methyl and ethyl are best treated by first converting them into methyl esters thus Heat together under reflux i ml. of the higher ester, 5 ml. of methanol and 0-2 g. of sodium methoxide. [In place of the sodium methoxide, it suffices to add o i g. of metallic sodium to the methanol.] After refluxing, distil off the excess of methanol (b.p, 65 ). The residue is then heated under reflux with benzylamine as described above. 

The reaction (which is essentially the direct aminolysis of esters with benzylamine) proceeds readily when R is methyl or ethyl. Esters of higher alcohols should preferably be subjected to a preliminary methano-lysis by treatment with sodium methoxide in methanol ... 

The hydrazides are often crystalline and then serve as useful derivatives. Esters of higher alcohols should be converted first to the methyl esters by boiling with sodium methoxide in methanol (see under AT-benzylamides). 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

RCH=N—ONa and R R C=N—ONa) which may be filtered off and washed with methanol to remove traces of sodium methoxide. It should be kept moist with methanol the sodium derivative, if allowed to dry, may become very explosive. Also, upon contact with a trace of water, it is liable to decompose with explosive violence. The sodium derivative may be dissolved by successively adding small quantities to cold water with continual stirring. 

Perbenzoic acid. Treatment of a cold sodium methoxide solution with a solution of pure benzoyl peroxide in chloroform affords methyl benzoate and a solution of the sodium salt of perbenzoic acid ... 

The m.p. is not always a safe criterion of purity. Benzoyl peroxide may be analysed as follows -. Dissolve about 0-6 g., accurately weighed, of benzoyl peroxide in Is ml. of chloroform in a 350 ml. conical flask. Cool to — 5°, and add 25 ml. of 0- IN sodium methoxide solution at once with cooling and shaking. After 5 minutes at — 5°, add 100 ml. of iced water, 5 ml. of 10 per cent, sulphuric acid, and 2 g. of potassium iodide in 20 ml. of 10 per cent, sulphuric acid in the order mentioned with vigorous stirring. Titrate the liberated iodine with standard 0-lN sodium thiosulphate solution. 

By increasing the molar proportion of the monocarboxylic acid, the yield of (II) is improved. Thus electrolysis of a mixture of decanoic acid (n-decoic acid capric acid) (V) (2 mols) and methyl hydrogen adipate (VI) (1 mol) in anhydrous methanol in the presence of a little sodium methoxide gives, after hydrolysis of the esters formed, n-octadecane (VII), tetradecanoic or myristic acid (VIH) and sebacic acid (IX) ... 

Ninhydrin (also named 1 2 3-triketoindane or 1 2 3-triketohydrindene hydrate) is prepared most simply from the inexpensive phthahc anhydride (I). The latter is condensed with acetic anhydride In the presence of potassium acetate to give phthalylacetlc acid (II) reaction of the latter with sodium methoxide in methanol yields 1 3-indanedionecarboxyhc acid, which is decomposed upon warming with dilute hydrochloric or sulphuric acid to indane-1 3-dione (or 1 3-diketohydrindene) (HI). Selenium dioxide oxidation of (III) afibrds indane-1 2 3-trione hydrate (ninhydrin) (IV). 

Indane-1 3-dione (1 3-diketohydrindene). Method A. To a solution of sodium methoxide, prepared from 6 1 g. of sodium and 200 ml. of anhydrous methanol, add 15 g. of phthalylacetic acid and allow to stand for 1 hour at room temperature collect the yellow precipitate by suction filtration. Mix the yellow solid with 150 ml. of 10 per cent, sulphuric acid, heat on a steam bath until no more carbon dioxide is evolved (15-20 minutes), filter the hot solution and allow to cool. Collect the yellow crystals by filtration at the pump, wash with a httle water and dry at 100°. The yield of crude 1 3-indanedione, m.p. 125-126°, is 7 g. RecrystaUise from hght petroleum, b.p. 80-100°, and thus obtain the pure product, m.p. 129-130°. 

Phenylethylbarbituric acid (also termed luminal and phenobarbitone) may be prepared by condensing ethyl phenyletUylmalonate with urea in the presence of sodium methoxide ... 

It is conveniently prepared in the laboratory by the interaction of sulphanil-amide and guanidine (from guanidine nitrate and sodium methoxide solution) the resulting guanidine salt of sulphanilamlde decomposes upon heating at 150-160° into sulphaguanidine and ammonia ... 

What product would you get from dus and sodium methoxide in methanol ... 

Cis-olefins or cis./rjns-dienes can be obtained from alkynes in similar reaction sequences. The alkyne is first hydroborated and then treated with alkaline iodine. If the other substituents on boron are alkyl groups, a cis-olefin is formed (G. Zweifel, 1967). If they are cir-alkenyls, a cis, trans-diene results. The reactions are thought to be iodine-assisted migrations of the cis-alkenyl group followed by (rans-deiodoboronation (G. Zweifel, 1968). Trans, trans-dienes are made from haloalkynes and alkynes. These compounds are added one after the other to thexylborane. The alkenyl(l-haloalkenyl)thexylboranes are converted with sodium methoxide into trans, trans-dienes (E. Negishi, 1973). The thexyl group does not migrate. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

A solution of sodium methoxide (25% w, 115 ml, 532 mmol) in methanol (187 ml) was cooled to — 8 "C under nitrogen. A solution of 2,4,5-trimethoxy-benzaldehyde (25 g, 128 mmol) and methyl azidoacetate (59 g, 513 mmol) in a 1 2 mixture of methanol-THF (50 ml 4- 100ml) was added dropwisc to the sodium methoxide solution with stirring at — 8°C over a period of 45 min. The solution was stirred and kept below 5°C for 2 h. The mixture was then poured onto ice (1 kg) and stirred. The precipitate which resulted was collected by filtration, washed with water and dried over CaCl in a vacuum desiccator. The dried precipitate was dissolved in EtOAc (600 ml) and dried over Na2S04. 

Charge diagrams suggest that the 2-amino-5-halothiazoles are less sensitive to nucleophilic attack on 5-position than their thiazole counterpart. Recent kinetic data on this reactivity however, show, that this expectation is not fulfilled (67) the ratio fc.. bron.c.-2-am.noih.azoie/ -biomoth.azoie O"" (reaction with sodium methoxide) emphasizes the very unusual amino activation to nucleophilic substitution. The reason of this activation could lie in the protomeric equilibrium, the reactive species being either under protomeric form 2 or 3 (General Introduction to Protomeric Thiazoles). The reactivity of halothiazoles should, however, be reinvestigated under the point of view of the mechanism (1690). 

The reaction of MeO /MeOH with 2-Cl-5(4)-X-thiazoles (122) follows a second-order kinetic law, first order with respect to each reactant (Scheme 62) (297, 301). A remark can be made about the reactivity of the dichloro derivatives it has been pointed out that for reactions with sodium methoxide, the sequence 5>2>4 was observed for monochlorothiazole compounds (302), For 2.5-dichlorothiazole, on the contrary, the experimental data show that the 2-methoxy dehalogenation is always favored. This fact has been related to the different activation due to a substituent effect, less important from position 2 to 5 than from... 

The conjugate bases listed m Table 1 7 that are anions are commonly encountered as their sodium or potassium salts Thus sodium methoxide (NaOCH3) for example is a source of methoxide ion (CH30 ) which is the conjugate base of methanol... 

Similarly sodium methoxide (NaOCHj) is a suitable base and is used m methyl alco hoi Potassium hydroxide m ethyl alcohol is another base-solvent combination often employed m the dehydrohalogenation of alkyl halides Potassium tert butoxide [K0C(CH3)3] is the preferred base when the alkyl halide is primary it is used m either tert butyl alcohol or dimethyl sulfoxide as solvent... 

Use curved arrows to track electron movement in the dehydro halogenation of tert butyl chloride by sodium methoxide by the E2 mechanism J... 

Increasing rate of reaction with sodium methoxide m methanol (50°C)... 

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

The most common types of aryl halides m nucleophilic aromatic substitutions are those that bear o ox p nitro substituents Among other classes of reactive aryl halides a few merit special consideration One class includes highly fluormated aromatic compounds such as hexafluorobenzene which undergoes substitution of one of its fluorines on reac tion with nucleophiles such as sodium methoxide... 

Write equations describing the addition-elimination mechanism for the reaction of hexafluorobenzene with sodium methoxide clearly showing the structure of the rate determining intermediate j... 

Halides derived from certain heterocyclic aromatic compounds are often quite reac tive toward nucleophiles 2 Chloropyridme for example reacts with sodium methoxide some 230 million times faster than chlorobenzene at 50°C... 

Pentafluoro 6 nitrobenzene reacts readily with sodium methoxide m methanol at room temperature to yield two major products each having the molecular formula C7H3F4NO3 Suggest reasonable structures for these two compounds... 

A careful study of the reaction of 2 4 6 trinitroanisole with sodium methoxide revealed that two different Meisenheimer complexes were present Suggest reasonable structures for these two complexes... 

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