Chlorides, alkyl hydrolysis

Caibamates ate formed from an amine with a wide variety of reagents, of which the chloroformate is the most common amides are formed from the acid chloride. -Alkyl caibamates are cleaved by acid-catalyzed hydrolysis A/-alkylamides are cleaved by acidic or basic hydrolysis at teflux. conditions that cleave peptide bonds. 

Aqueous solutions of methyl isothiocyanate are slowly oxidized in air to give 2,4-dimethyl-1,2,4-thiadiazoline-3,5-thione (71) <82AHC(32)285>. When mixtures of alkylisothiocyanates and alkyl-isocyanates are chlorinated, 3-oxathiadiazolium salts (198) are formed via an intermediate iminochloromethylsulfenyl chloride (199). Hydrolysis of these salts yields 2,4-dialkyl-1,2,4-thia-diazolidin-3,5-diones (200) (Scheme 45) <80USP4183816>. 

The dithiane-derived anion can be generated by the action of Bu"Li in THF at -78 C or with complex bases NaNH2-RONa at room temperature. Lithiated dithiane can also be prepared in situ by sonica-tion of n-butyl chloride with lithium in the presence of dithiane. Dithioacetals or ketals are resistant to acidic or basic hydrolysis. Regeneration of the carbonyl group from the dithioketal sometimes presents difficulties but can be carried out by hydrolysis in polar solvents (acetone, alcohols, acetonitrile) in the presence of metallic ions such as Hg, Cu, Ag, Ti or Tl. Alternatively, alkylative hydrolysis... 

The formation of ethers can also occur with cyclization and the synthesis of heterocyclic phosphorus compounds (Scheme 37). The reaction between the benzodioxaphosph(V)ole 241 and a Grignard reagent (R = alkyl or aryl) followed by a treatment of the product 242 with base affords the dihydrobenzodioxaphosph(V)orin 243 also available from catechol and bis(chloromethyl)phosphinic chloride. The hydrolysis of243 and cyclization of... 

Iminic derivatives of (4R,55)-l,5-dimethyl-4-phenyhmidazolidin-2-one have been dia-stereoselectively alkylated with activated alkyl halides or electrophilic olefins either under phase transfer catalysis (PTC) conditions or in the presence of the phosphazene base BEMP at —20°C in the presence of lithium chloride (LiCl). Hydrolysis of the alkylated imino imides gave (5)-a-amino acids with recovery of the imidazolidinone chiral auxihary [18]. 

A dithiane synthesis can convert an aldehyde to a ketone. The aldehyde is first converted to its dithiane derivative, which is deprotonated and alkylated. A mercuric chloride-assisted hydrolysis gives the ketone. Show how this technique might be used to convert benzaldehyde to benzyl phenyl ketone. 

Hydrolysis of primary alkyl halides with aqueous alkali follows S 2 mechanism. For example, methyl chloride undergoes hydrolysis with sodium hydroxide following second order kinetics. 

Among the various carboxylic acid derivatives, acyl chlorides are especially useful because they are readily converted to acid anhydrides, esters, and amides by nucleophilic acyl substitution (Table 19.1). Yields are high and the reaction rates are much greater than the corresponding rates of alkyl halides with the same nucleophiles. Benzoyl chloride, for example, is about 1,000 times more reactive than benzyl chloride toward hydrolysis at 25°C. 

In our system, the acid chloride as the acylating agent was not applicable due to the basic conditions of the proposed transformation and the internal free nitrogen of the piperidyl moiety. However, the trioxifene acylation was adapted by preparing the phenyl ester of 5. Therefore, the required phenyl 4-[2-(l-piperidinyl)ethoxy]benzoate (9) was prepared by alkylating methyl 4-hydroxybenzoate with 2-(l-piperidinyl)ethyl chloride (6). Hydrolysis of the methyl ester provided the carboxylic acid that was converted to the acid chloride (8) using SOCI2 in a mixture of 1,2-dichloroethane and toluene. Acid chloride 8 was then reacted with sodium phenolate to provide 9 as a stable crystalline solid in 64% overall yield from the carboxylic acid. 

Alkyl Isoquinolines. Coal tar contains small amounts of l-methylisoquinoline [1721-93-3] 3-methylisoquinoline [1125-80-0] and 1,3-dimetliylisoquinoline [1721-94-4J. The 1- and 3-methyl groups are more reactive than others in the isoquinoline nucleus and readily oxidize with selenium dioxide to form the corresponding isoquinoline aldehydes (174). These compounds can also be obtained by the hydrolysis of the dihalomethyl group. The 1- and 3-methyhsoquinolines condense with benzaldehyde in the presence of zinc chloride or acetic anhydride to produce 1- and 3-styryhsoquinolines. Radicals formed by decarboxylation of carboxyUc acids react to produce 1-aIkyhsoquinolines. 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

Aiyl benzoates, stable to alkylation conditions using K2C03/Me2S04, are cleaved by more basic hydrolysis (KOH). They are stable to anhydrous hydrogen chloride, but are cleaved by hydrochloric acid ... 

Monoesterification of a symmetrical dihydroxy aromatic compound can be effected by reaction with polymer-bound benzoyl chloride (Pyr, benzene, reflux, 15 h) to give a polymer-bound benzoate, which can be alkylated with diazomethane to form, after basic hydrolysis (0.5 M NaOH, dioxane, H2O, 25°, 20 h, or 60°, 3 h), a monomethyl ether. ... 

The 2-methylthioethyl ester is prepared from a carboxylic acid and methylthioethyl alcohol or methylthioethyl chloride (MeSCH2CH20H, TsOH, benzene, reflux, 55 h, 55% yield MeSCH2CH2Cl, Et3N, 65°, 12 h, 50-70% yield). It is cleaved by oxidation [H2O2, (NH4)6Mo7024, acetone, 25°, 2 h, 80-95% yield pH 10-11, 25°, 12-24 h, 85-95% yield] and by alkylation followed by hydrolysis (Mel, 70-95% yield pH 10, 5-10 min, 70-95% yield). ... 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

In their original communication on the alkylation and acylation of enamines, Stork et al. (3) had reported that the pyrrolidine enamine of cyclohexanone underwent monoacylation with acid chlorides. For example, the acylation with benzoyl chloride led to monobenzoylcyclohexanone. However, Hunig and Lendle (33) found that treatment of the morpholine enamine of cyclopentanone with 2 moles of propionyl chloride followed by acid hydrolysis gave the enol ester (56), which was proposed to have arisen from the intermediate (55). 

Acylation of the enamine (113) with a,/9-unsaturated acid chlorides has been shown (57) to give bicyclo(3.3.1)nonan-2,9-diones. Acryloyl ehloride on reaction with the enamine (113) and subsequent hydrolysis gave bicyelo-(3.3.1)nonan-2,9-dione (123). Mechanistic studies suggest that C alkylation by the olefin precedes acylation (87). 

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