Alcohols halogen-atom substituted

This compound is heated with caustic potash solution, yielding beta-hydroxy-coumarin. From this body, coumarin is obtained by substituting a halogen atom for the OH group, and then reducing the product in alcoholic solution with zinc-dust. 

A dihallde will not do as it would be unreactive towards substitution and we already have three halogen atoms in (3). The answer Is to use the aldehyde (4) -chloral - in acid solution. One addition gives the alcohol (5) which dehydrates and reacts again via a carbonium ion. In practice (5) need not be Isolated. 

The enhanced reactivity of 5-halogeno-l,2,4-thiadiazoles over 3-halogeno-l,2,4-thiadiazoles has been mentioned before (see Section 5.08.7.1). Nucleophilic substitution at this center is a common route to other 1,2,4-thiadiazoles, including 5-hydroxy, alkoxy, mercapto, alkylthio, amino, sulfonamido, hydrazino, hydroxylamino, and azido derivatives. Halogens in the 3-position of 1,2,4-thiadiazoles are inert toward most nucleophilic reagents, but displacement of the 3-halogen atom can be achieved by reaction with sodium alkoxide in the appropriate alcohol <1996CHEC-II(4)307>. 

Alcohols undergo nucleophilic substitution at the 8+ carbon atom when reacted with halogenating agents. 

Remarks on 1 and 2.—These two reactions are special cases of a general change, namely, the substitution of an alcoholic hydroxyl group by a halogen atom. This substitution can be carried out in two ways first, as in the preparation of ethyl bromide, 1, by acting on alcohols with hydrogen halides, e.g. 

When a halogen acid, such as HCl, HBr, or HI, reacts with an alcohol, the halogen atom is substituted for the OH group of the alcohol. This is shown in Figure 2.7(A). The reverse reaction takes place when an alkyl halide reacts with OH in a basic solution. See Figure 2.7(B). 

Alcohols may be prepared (1) by hydration of alkenes (1) in presence of an acid and (11) by hydroboratlon-oxidatlon reaction (2) from carbonyl compounds by (1) catalytic reduction and (11) the action of Grignard reagents. Phenols may be prepared by (1) substitution of (1) halogen atom In haloarenes and (11) sulphonic acid group In aiyl sulphonic acids, by -OH group (2) by hydrolysis of diazonium salts and (3) industrially from cumene. 

In alkaline media, 3-halogeno compounds appear to be less stable 3-chloro-5-phenyl-l,2,4-thiadiazole is decomposed completely by 1 Jf-alcoholic potassium hydroxide and by hydrazine.178 Nucleophilic substitution of the 3-halogen atom by alkoxy groups can be achieved, however, by means of sodium alkoxide in the appropriate alcohol 3-methoxy-, 3-benzyloxy-, and 3-(2 -hydroxyethoxy)-5-phenyl-l,2,4-thiadiazole are obtainable by this route in good yield.178... 

Table 10-4 shows that substitution by electron-withdrawing halogen atoms enhances the acidity of alcohols. For example, 2-chloroethanol is more acidic than ethanol because the electron-withdrawing chlorine atom helps to stabilize the 2-chloroethoxide ion. 

Lithium hydride can be substituted for most of the lithium aluminum hydride. Aryl halogen atoms have been successfully removed in certain cases by magnesium and methanol, sodium and amyl alcohol, and nickel-aluminum alloy in aqueous alkali. ... 

A variety of bases have been used to effect dehydrohalogenation of halo acids and halo esters. a-Bromo esters or a-bromo acyl halides give a,/3 lefinic acids with alcoholic potassium hydroxide. Yields are poor with the higher-molecular-weigbt a-bromo acids other products are those formed by substitution of the halogen atom by the basic anions. 

Preparation of diazoketones and their rearrangements during hydrolysis (method 271) and alcoholysis (method 295) are discussed elsewhere. Ammonolysis of diazoketones leads to amides of acids containing one more carbon atom than the original acyl halide. Halogen atoms may be present in a remote position on an aliphatic chain. The reaction is carried out by heating the diazoketone in alcohol or dioxane solution with aqueous ammonia in the presence of silver oxide or silver nitrate catalysts. Substituted acetanilides are formed when aniline is used in place of ammonia. ... 

The Mitsunobu procedure, which uses diethyl azodicarboxylate (DEAD) or diisopropyl azodi-carboxylate (DIAD) to react with PPh3 and alcohols providing configuration-inversed substitution products via alkoxytriphenylphosphonium ion intermediates (O Scheme 28), presents another route for introducing halogen atoms into carbohydrates [48]. 

The replacement of an alcoholic hydroxyl group by a halogen atom is one of the most common reactions carried out in organic chemistry. The usual reagents for effecting the transformation include halogen acids, thionyl chloride, and phosphorus halides. The reaction is of particular theoretical interest since experiments with optically active alcohols suggest still another substitution process. It has been called an internal nucleophilic substitution reaction (S i).20... 

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