Halo acids reaction

This reaction is of synthetic value in that a halo acids are reactive sub strates m nucleophilic substitution reactions... 

Nucleophilic substitution by ammonia on a halo acids (Section 19 16) The a halo acids obtained by halogenation of car boxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reac tive substrates in nucleophilic substitu tion processes A standard method for the preparation of a ammo acids is dis placement of halide from a halo acids by nucleophilic substitution using excess aqueous ammonia... 

The a halo acid is normally prepared by the Hell-Volhard-Zehnsky reaction (see Sec tion 19 16)... 

Alkenyl haUdes have also been used for halo alkylation reactions in the presence of protic acids (49). 

Substitution Reactions. Reaction with nitrous acid in dilute aqueous solutions yields the corresponding hydroxy acid or in solution containing a hydrohahc acid, the corresponding a-halo acid, with inversion in many cases. 

Bromination of the substituted butyric acid, 26, by the Hell-Volhardt-Zelinsky procedure affords the a-halo acid bromide (27). Reaction of this with urea affords directly bromisovalum (28). 

Although alcohols are oxidized by tetra-n-butylammonium persulphate when the reaction is conducted in dichloromethane, tetrahydropyranyl ethers have been produced (>90%) when attempts to oxidize the alcohol are conducted in tetrahydro-pyran (see Chapter 10) [ 19], Tetrahydrofuranyl ethers have been prepared by an analogous method [20,21 ]. Base-mediated elimination of halo acids from P-halo alcohols under phase-transfer catalysed conditions produce oxiranes in high yield (70-85%). The reaction has particular use in the synthesis of epihalohydrins from p,y-dihalo alcohols [22],... 

The second method of intramolecular cyclization to 2,5-DKPs involves formation of the Ni—Ce bond. This reaction entails acylation of glycinamide with an a-halo acid halide, followed by ring closure under basic conditions. ... 

The Hell-Volhard Zelinsky reaction is a method for forming a-halo acid. 

This is a synthetically useful procedure because the a-halo acids are useful starting materials for other reactions. For example, the addition of hydroxide ion leads to the replacement of the halogen with an -OH group. The reaction with ammonia replaces the halogen with -NH2. The reaction with cyanide ion, CN , converts the halide to a nitrile. Figure 12-33 illustrates this reaction. 

One of the more important uses of thioureas has been in the preparation of 2-imino-4-thiazolidinones, first reported by Meyer135 and Andreasch,136 138 via reaction with a-halo acids or esters. This reaction has been covered by Brown139 in a review on 4-thiazolidinones which appeared in 19(51, and, therefore, will not be discussed in detail here. The corresponding reaction between a-halo acids or esters and scleno-ureas to produce 2-iminoselenazolidin-4-ones is also known and has been reviewed.77-78 Akerblom140 has attempted to clear up some of the confusion in the literature on whether 3-alkyl-2-iminothiazolidin-4-ones (63) or 2-alkylamino-2-thiazolin-4-ones (64) are formed from 1-alkyl-thioureas and chloroacetic acid. She found that the reaction in water... 

The ring may be cleaved hydrogenolytically. Halo acids afford 4-halobutanols or 1,4-dihalobutanes, depending on the reaction conditions. Acid chlorides in the presence of zinc chloride afford esters of 4-chlorobutanol, and LAH and aluminum chloride give butanol. Reaction with carbon monoxide and nickel tetracarbonyl affords adipic acid. 

Preparation. The general preparation of u-hydroxy acids is by the hydrolysis of an a-halo acid or by Ihe acid hydrolysis of the cyanohydrins of an aldehyde or a ketone. 0-Hydroxy acids may be made by catalytic reduction of 0-keut esters followed by hydrolysis. 0-Hydroxy acids can also he prepared by ihe ReformaCsky reaction y-Hydroxy acids are seldom obtained in the free slate because of ihe case wilh which they form... 

Many of the types of reactions that are useful for the preparation of amino acids have been discussed previously in connection with separate syntheses of carboxylic acids (Chapter 18) and amino compounds (Chapter 23). Examples include the SN2 displacement of halogen from a-halo acids by ammonia,... 

Heinrikson et al. (161) have extended the study of the reaction at pH 5.5 to a series of halo acids, investigating the effect of chain length, d and l antipodes, and the position of the halogen substituent. All of the alkylated products showed enzymic activities of less than 0.5%. A summary of the rates of reaction of the various compounds with both His 12 and 119 and free histidine are shown in Table VII. All of the reagents react more rapidly with the protein than with free histidine. 

In all photochemical cases, UV light is required for hydrogen production and in most cases the reactions occur in strongly acidic solutions. Sulfuric, phosphoric, perchloric and nitric acids are the preferred media, although halo acids have occasionally been employed. 

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