Hydroxide, potassium reaction with alkyl halides

Potassium hydroxide, KOH Reacts with alkyl halides to yield alkenes by an elimination reaction (Sections 7.1 and 11.11). 

Under microwave irradiation several azaheterocycles (i.e. pyrrole, imidazole, indole and carbazole) can react remarkably fast with alkyl halides to give, exclusively, N-al-kyl derivatives (Eqs. 32 and 33) [45, 46]. Such reactions have been performed simply by mixing an azaheterocycle compound with 50% excess alkyl halide and a catalytic amount of TBAB. The reactants were absorbed either on a mixture of potassium carbonate and potassium hydroxide or on potassium carbonate alone and then irradiated in a domestic microwave oven for 30 s-10 min. 

The monopotassium salt (103) and the dipotassium salt (105) can be prepared in quantitative yield from (101) and potassium hydroxide. Reaction of (105) in DMF with alkyl halides gives dialkylation products (106a) from benzyl bromide, (106b) from methyl iodide, (106c) from allyl bromide, and (106d) from 1-butyl bromide in low yield. 

Whereas nucleophilic substitution occurs on heating with water, aqueous potassium carbonate, silver oxide or sodium acetate, elimination reactions occur on heating an alkyl halide with ethanolic potassium hydroxide. Both unimolecular (El) and bimolecular (E2) pathways occur, the former with tertiary and the latter with primary and secondary halides. The reactions of alkyl halides with oxygen nucleophiles are summarized in Scheme 2.3. 

The reaction of j>, S alkyl and benzyl cyanodithioimido-carbonate (1 5) with potassium hydroxide in an acetone medium afforded the -potassium S-alkyl and benzyl cy-anothioimidocarbonates (6-10). The reaction of the potassium salts with alkyl, allyl or benzyl halides furnished the titled thiolcarbamates (11-29). 

The primary amines unite with alkyl halides to form salts of secondary and tertiary amines and of the quarternary ammonium bases, the reactions being analogous to those already described in connection with the aliphatic amines. Like the latter they are converted into isocyanides when warmed with potassium hydroxide and an alcoholic solution of chloroform. 

Nitroalkanes can be alkylated in a single step with hydroxide as abase phase transfer conditions (see p. 585) keep the HO and the electrophile apart, preventing alcohol formation. The reaction below on the left works despite the quaternary carbon atom in the product. The reaction on the right gives a cyclic nitroalkane now there really is no aiternative the base and electrophile must cohabit in the reaction mixture, so a weaker base such as potassium carbonate must be used—hydroxide or amines are no good here because they would undergo substitution reactions with the halide. 

The two most common elimination reactions arc dehydroUalogenalion—the loss of HX from an alkyl halide—and dehydration—(he loss of water from an alcohol. Dehydrohalogenation usually occurs by reaction of an alkyl halide with strong base such as potassium hydroxide. For example, bromocvclohexane yields cyclohexene when treated with KOH in ethanol solution. 

N-Substituted amides and lactams can be rapidly N-alkylated under solid-liquid PTC conditions by use of microwave irradiation. The reactions were performed simply by mixing an amide with 50% excess of an alkyl halide and a catalytic amount of TBAB. These mixtures were absorbed on a mixture of potassium carbonate and potassium hydroxide [41] and then irradiated in an open vessel in a domestic micro-wave oven for 55-150 s (Eq. 28). 

The general feature of alkylation reactions at a carbon atom is that they can be achieved under sonication using solid bases even in apolar solvents. The advantage is that side reactions are generally minimised. Deprotonation occurs readily on a benzylic position in the presence of aqueous sodium hydroxide, as shown with indene (Eq. 3.21) [117]. A quantitative yield of the alkylated product can be obtained using sonication in the presence of a PTC. It was suggested that alkylation of cyclopentadiene or indene by secondary or tertiary alkyl halides in the presence of potassium hydroxide and Ali-quat occurred via a SET process [118]. 

The Gabriel synthesis of amines uses potassium phthalimide (prepared from the reaction of phthalimide with potassium hydroxide). The structure and preparation of potassium phthalimide is shown in Figure 13-13. The extensive conjugation (resonance) makes the ion very stable. An example of the Gabriel synthesis is in Figure 13-14. (The N2H4 reactant is hydrazine.) The Gabriel synthesis employs an 8, 2 mechanism, so it works best on primary alkyl halides and less well on secondary alkyl halides. It doesn t work on tertiary alkyl halides or aryl halides. 

A mixture of an azaheterocyclic compound (5.0 mmol), alkyl halide (7.5 mmol), tetrabutylammonium bromide - TBAB (0.17 g, 0.50 mmol), and potassium carbonate (2.8 g, 20 mmol) or mixture of potassium carbonate (2.8 g, 20 mmol) and potassium hydroxide (1.1 g, 20 mmol) was heated in a domestic microwave oven in an open Erlenmeyer flask for an appropriate time. After being cooled down, the reaction mixture was extracted with methylene chloride or THF (2x25 mL). Then the extract was dried with MgSCL, filtered, and the solvent was evaporated to dryness. Liquid compounds were purified on Kugelrohr distillation apparatus, while solid compounds were purified by means of flash chromatography to afford desired 77-alkyl derivatives of azalieterocycle compound, yield 58-95%. 

An alternative reagent equivalent for the amide anion synthon is the potassium salt of phthalimide which can only react with one molecular proportion of alkyl halide. The resulting JV-alkylphthalimide is then cleaved to the primary amine (the Gabriel synthesis). The preliminary preparation of potassium phthalimide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75% ethanol) may be avoided in some cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The cleavage of the JV-substituted phthalimide is best effected by reaction with hydrazine hydrate and then heating the reaction mixture with hydrochloric acid. The insoluble phthalylhydrazide is filtered off, leaving the amine hydrochloride in solution from which the amine may be liberated and isolated in the appropriate manner. 

Reaction with ethanolic potassium hydroxide. Boil 0.5 ml of the compound with 4 ml of 0.5 m ethanolic potassium hydroxide under reflux for 15 minutes. Most alkyl halides and benzyl halides give a crystalline precipitate of the potassium halide. Dilute with 5 ml of water, acidify with dilute nitric acid and test with silver nitrate solution. 

Alkyl vinyl tellurium compunds were obtained when tellurium was reacted with acetylene in the presence of an alkyl halide in a system consisting of potassium hydroxide, tin(II) chloride, water, and hexamethylphosphoric triamide2,3. Divinyl tellurium (53-60% yield) and dialkyl telluriums (4-12% yield) were also formed in these reactions. 

Several variations of this reaction are possible. The halo acid is boiled with a solution of sodium in absolute alcohol as in the formation of y-bu-tyrolactone (67%), or the dry sodium salt of a halo acid is heated under vacuum as in the preparation of 8-valerolactone (30%). The corresponding esters are sometimes refluxed with alcoholic potassium hydroxide or decomposed thermally at 15 180° whereby a molecule of an alkyl halide is eliminated. The latter process is valuable in making a-alkyl-y-lac-tones of higher-molecular-weight acids since the y-bromo esters are available by the free-radical addition of a-bromo esters to 1-olefins. 

As mentioned above (Section 4.07.1.3.2) imidazoles are readily alkylated in neutral or basic medium following either an 5e2 or an 5e2cB mechanism. The method of choice now commonly involves alkylation of the heterocycle in basic medium (Scheme 17) since these conditions do not suffer from side reactions which produce the imidazolium species. Thus, the reaction of an imidazole with an alkyl halide (or related compound) is carried out in the presence of the oxide or hydroxide of an alkali metal or alkaline earth element, with sodium ethoxide or sodamide, in solvents such as ethanol, dioxane, acetone or liquid ammonia. The use of sodium in liquid ammonia gives excellent yields (>70%) in many instances. Other workers have obtained high yields of A-alkylimidazoles by heating the potassium imidazolate with an alkyl halide either in a sealed tube or under reflux in xylene, benzene or toluene. 

The reverse of this reaction also takes place for, when an alkyl halide, especially the iodide, is heated with alcoholic potassium hydroxide, or is passed over heated potassium hydroxide, hydrogen iodide is lost, and ethylene is obtained, as follows ... 

Sulphonic Acids to Hydroxyl Compounds.—(4) Reactions with alkalies by fusion. In the aliphatic series the most important synthetic reaction for the formation of hydroxyl derivatives is the treatment of the alkyl halides with silver hydroxide, which reaction we have said does not occur in the benzene series when the substitution is in the ring and not in the side chain. The most important method for preparing ring-hydroxyl compounds is by the fusion of a sulphonic acid or its salt with alkalies, potassium or sodium hydroxide, a reaction which does not occur with the aliphatic sulphonic acids. 

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