Acid chlorides nucleophilic substitution reactions

Acetyl chloride must always be stored under anhydrous conditions, because it readily reacts with moisture and becomes hydrolysed to acetic acid. On the other hand, if one wanted to convert ethyl chloride into ethanol, this nucleophilic substitution reaction would require hydroxide, with its negative charge a better nucleophile than water, and an elevated temperature (see Section 6.3.2). It is clear, therefore, that the carbonyl group is responsible for the increased reactivity, and we must implicate... 

In the initial step, the first BOC-protected amino acid is bound to the polymer, e.g. polystyrene in which a proportion of the phenyl rings have chloromethyl substitution. Attachment to these residues is through the carboxyl via an ester linkage. This involves a simple nucleophilic substitution reaction, with the carboxylate as nucleophile and chloride as leaving group (see Section 6.3.2). After each stage, the insoluble polymer-product combination is washed free of impurities. 

Esters are formed in nucleophilic substitution reactions in which the nucleophile is a carboxylate anion. The anions of carboxylic acids are relatively weak nucleophiles towards sp3-hybridized carbon. Swain s nucleophilic constant, n, for acetate ion is 2.7183, slightly smaller than that for chloride. Thus acetate is selectively alkylated by alkyl halides in aqueous solution, e.g. 

C is correct. Inorganic add chlorides react with carboxylic acids by nucleophilic substitution to form acyl clorides you should memorize this reaction. 

Most reactions in two-phase systems occur in a liquid phase following the transfer of a reactant across an interface these are commonly known as extractive reactions. If the transfer is facilitated by a catalyst, it is known as phase-transfer catalysis [2]. Unusually, reactions may actually occur at an interface (interfacial reactions) examples include solvolysis and nucleophilic substitution reactions of aliphatic acid chlorides [3 ] and the extraction of cupric ion from aqueous solution using oxime ligands insoluble in water [4], see Section 5.2.1.3(ii). 

The combination of addition and elimination reactions has the overall effect of substituting one nucleophile for another in this case, substituting an alcohol for water. The rate of these nucleophilic substitution reactions is determined by the ease with which the elimination step occurs. As a rule, the best leaving groups in nucleophilic substitutions reactions are weak bases. The most reactive of the carboxylic acid derivatives are the acyl chlorides because the leaving group is a chloride ion, which is a very weak base (ATb KT20). 

Nucleophilic substitutions reactions are those reactions in which the substitution of one nucleophile for another is involved. Alkyl halides, carboxylic acids, and carboxylic acid derivatives undergo nucleophilic substitution. However, the mechanisms involved for alkyl halides are quite different from those involved for carboxylic acids and their derivatives. The reaction of a methoxide ion with ethanoyl chloride is a nucleophilic substitution reaction (Following fig.). In it one nucleophile (the methoxide ion) substitutes another nucleophile Cl. ... 

Acid chlorides can be converted to acid anhydrides, esters, or amides. These reactions are possible because acid chlorides are the most reactive of the four carboxylic acid derivatives. Nucleophilic substitutions of the other acid derivatives are more limited because they are less reactive. For example, acid anhydrides can be used to synthesise esters and amides, but cannot be used to synthesise acid chlorides. 

Sulfonic acids, like sulfuric acid, are much stronger acids than carboxylic acids. However, their chemical behavior resembles that of carboxylic acids in many other respects. Sulfonic acids form the same type of derivatives, sulfonyl chlorides, esters, amides, and so on, as do carboxylic acids. These derivatives are intercon-verted by nucleophilic substitution reactions that resemble those of carboxylic acid derivatives. 

The preparation of tosylate and other sulfonate esters for use as leaving groups in nucleophilic substitution reactions (see Section 8.9) employs the reaction of a sulfonyl chloride (an acid chloride of a sulfonic acid) with an alcohol. Another example is shown in the following equation. Note the similarity of this reaction to the reaction of an acyl chloride with an alcohol to form an ester. 

These reactions are used to make anhydrides, carboxylic acids, esters, and amides, but not acid chlorides, from other acyl compounds. Acid chlorides are the most reactive acyl compounds (they have the best leaving group), so they are not easily formed as a product of nucleophilic substitution reactions. They can only be prepared from carboxylic acids using special reagents, as discussed in Section 22.10A. 

Although somewhat less reactive than acid chlorides, anhydrides nonetheless readily react with most nucleophiles to form substitution products. Nucleophilic substitution reactions of anhydrides are no different than the reactions of other carboxylic acid derivatives, even though anhydrides contain two carbonyl groups. Nucleophilic attack occurs at one carbonyl group, while the second carbonyl becomes part of the leaving group. 

Although alkyl chlorides (RCH2CI) and acid chlorides (RCOCI) both undergo nucleophilic substitution reactions, acid chlorides are much more reactive. Suggest reasons for this difference in reactivity. 

It is interesting to note that zeolite KY, which is most effective in promoting the benzylation mentioned above, has both moderately acidic and moderately basic sites. This suggests that the nucleophilic substitution reaction can be induced most efficiently by the cooperative function of weakly acidic and weakly basic sites alcohol and benzyl chloride molecules are located accessible to each other on the acidic and basic sites where the nucleophilicity of the OH group of the alcohol is enhanced by a basic site, and benzyl chloride is activated concertedly by an acidic site (Fig. 1). 

Like other acid derivatives, acid chlorides typically undergo nucleophilic substitution. Chlorine is expelled as chloride ion or hydrogen chloride, and its place is taken by some other basic group. Because of the carbonyl group these reactions take place much more rapidly than the corresponding nucleophilic substitution reactions of the alkyl halides. Acid chlorides are the most reactive of the derivatives of carboxylic acids. 

Scheme 16).3 Tetrahydrophthalimide (37) contains an acidic imino hydrogen atom and forms a sodium salt the latter undergoes a nucleophilic substitution reaction with trichloromethanesulfenyl chloride (34), yielding captan (35) (Scheme 16). 

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... 

Hence the larger the n value, the stronger the nucleophile, and the smaller the [nucl]50o/o. As already pointed out earlier, the [nucl]50o/o values given in Table 2 show that in uncontaminated freshwaters, hydrolysis is by far the most important nucleophilic substitution reaction. Furthermore, since the hydrolysis of a carbon-halogen bond is generally not catalyzed by acids, one can assume that the hydrolysis rate of aliphatic halides will be independent of pH at typical ambient conditions (i.e., pH < 10). In this context it is also important to note that no catalysis of the hydrolysis of alkyl halides by solid surfaces has been observed (El-Amamy and Mill, 1984 Haag and Mill, 1988). In salty or contaminated waters, reactions of organic chemicals with nucleophiles other than water or j hydroxide ion may be important. Zafiriou (1975), for example, has demonstrated j that in seawater ([Cl ] 0.5 M), a major sink for naturally produced methyl j iodide is transformation to methyl chloride j... 

Nucleophilic substitution reactions involving molten salts are well known. A number of esamples of molten pyridinium hydrochloride (mp 144 °C) being used in chemical synthesis, dating back to the 1940s, are known. Pyridinium chloride can act as both an acid and as a nucleophilic source of chloride. These properties are exploited in the dealkylation reactions of aromatic ethers [85]. An example involving the reaction of 2-methoxynaphthalene is given in Scheme 5.2-51 and a mechanistic explanation is given in Scheme 5.2-52. 

The nucleophilic hydroxyl oxygen of the carboxylic anion, generated by deprotonatlon of the carboxylic acid, undergoes a nucleophilic substitution reaction with the alkyl chloride formed In the previous step (with anchimeric assistance of the SMe group) to give the ester product. 

Epoxides are very susceptible to nucleophilic substitution reactions, especially when activated by Lewis acids. Linder these circumstances, the alkyl chloride is the less reactive group. Alkenes are weak nucleophiles. 

An activation energy of this magnitude would lead to an unobservably slow reaction at normal temperature. There is an abundance of evidence that carbocations can be intermediates in nucleophilic substitution reactions. Carbocation formation in solution is feasible because of the solvation of the ions that are produced. One of the earliest pieces of evidence for the existence of carbocation intermediates was the observation that triphenylmethyl chloride (trityl chloride) gave conducting solutions when dissolved in liquid sulfur dioxide, a polar non-nucleophilic solvent. Trityl chloride also reacted with Lewis acids, such as aluminum chloride, to give colored salt-like solids. 

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