HYDROLYSIS OF NITRILE

 

The hydrolysis of nitriles, which are organic molecules containing a cyano group, leads to carboxylic acid formation. These hydrolysis reactions can take place in either acidic or basic solutions.

 

The mechanism for these reactions involves the formation of an amide followed by hydrolysis of the amide to the acid. The mechanism follows these steps:

1.      The nitrogen atom of the nitrile group is protonated.

 

2..      The carbocation generated in Step 1 attracts a water molecule

.

 

3.      The oxonium ion loses a proton to the nitrogen atom, forming an enol.

 

4.      The enol tautomerizes to the more stable keto form.

 

5.      The amide is protonated by the acid, forming a carbocation.

 

6.      A water molecule is attracted to the carbocation.

 

7.      The oxonium ion loses a proton.

 

8.      The amine group is protonated.

 

9.      An electron pair on one of the oxygens displaces the ammonium group from the molecule.

http://www.cliffsnotes.com/study_guide/Preparation-of-Carboxylic-Acids.topicArticleId-23297,articleId-23284.html

Hydrolysis of nitriles with aqueous acid to give carboxylic acids

Description: Addition of water and acid to a nitrile leads to formation of a carboxylic acid.
Notes:

• This reaction is referred to as “acidic hydrolysis”.
• The reaction is generally used with water as solvent, so an excess of water is present. The acid used is often written as “H3O(+)”

Examples:
 


Notes: Note that example 4 is a cyanohydrin, so this produces an “alpha hydroxy carboxylic acid”

Mechanism:

Protonation of the nitrile nitrogen by acid (Step 1, arrows A and B) makes the nitrile carbon a better electrophile. Attack at the carbon by water (Step 2, arrows C and D) followed by proton transfer (Step 3, arrows E and F) gives a species that is in resonance with a protonated amide (arrows G and H). Addition of water to the protonated amide (Step 4, arrows I and J) followed by proton transfer (Step 5, arrows K and L) result in formation of NH3(+) which is an excellent leaving group. Expulsion of NH3 through 1,2-addition (Step 6, arrows M and N) followed by deprotonation (Step 7, arrows O and P) give the carboxylic acid.

 

 http://masterorganicchemistry.com/reaction-guide/hydrolysis-of-nitriles-with-aqueous-acid-to-give-carboxylic-acids/

Nitrile Hydrolysis in Basic Conditions

 

http://chemistry.boisestate.edu/people/richardbanks/organic/nitrilehydrolysisbasicReview.htm

Aliphatic nitriles are prepared by treatment of alkyl halides with sodium cyanide in a solvent that will dissolve both reactants. In dimethyl sulfoxide (DMSO), reaction occurs rapidly and exothermically at room temperature. The resulting nitrile is then hydrolysed to the acid by boiling with aqueous alkali or acid.

 

 

LACTONE

In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule. It is characterized by a closed ring consisting of two or more carbon atoms and a single oxygen atom, with a ketone group =O in one of the carbons adjacent to the other oxygen.

Synthesis

Many methods in ester synthesis can also be applied to that of lactones. In one industrial synthesis of oxandrolone the key lactone-forming step is an organic reduction - esterification

In halolactonization, an alkene is attacked by a halogen via electrophilic addition with the cationic intermediate captured intramolecularly by an adjacent carboxylic acid (See also iodolactamization), for example in this iodolactonization:

Specific methods include Yamaguchi esterification and nucleophilic abstraction.

A recent study has isolated β-lactones from bromination of 2,3-dimethylmaleate and/or 2,3-dimethylfumarate disodium salts, under ambient and aqueous conditions. The carboxylate groups of the maleate and fumarate moieties exhibit neighbouring group effects and alpha-lactones are proposed in the detailed mechanism

Reactions

The most stable structure for lactones are the 5-membered γ-lactones and 6-membered δ-lactones because, as in all organic cycles, 5 and 6 membered rings minimize the strain of bond angles. γ-lactones are so stable that, in the presence of dilute acids at room temperature, 4-hydroxy acids (R-CH(OH)-(CH₂)₂-COOH) immediately undergo spontaneous esterification and cyclisation to the lactone. β-lactones do exist, but can only be made by special methods. α-lactones can be detected as transient species in mass spectrometry experiments.^[6]

The reactions of lactones are similar to those of esters, as exemplified by gamma-lactone in the following sections:

Hydrolysis

Heating a lactone with a base (sodium hydroxide) will hydrolyse the lactone to its parent compound, the straight chained bifunctional compound. Like straight-chained esters, the hydrolysis-condensation reaction of lactones is a reversible reaction, with an equilibrium. However, the equilibrium constant of the hydrolysis reaction of the lactone is lower than that of the straight-chained ester i.e. the products (hydroxyacids) are less favored in the case of the lactones. This is because although the enthalpies of the hydrolysis of esters and lactones are about the same, the entropy of the hydrolysis of lactones is less than the entropy of straight-chained esters. Straight-chained esters give two products upon hydrolysis, making the entropy change more favorable than in the case of lactones which give only a single product.

Reduction

Lactones can be reduced to diols using lithium aluminium hydride in dry ether. The reduction reaction will first break the ester bond of the lactone, and then reduce the carboxylic acid group (-COOH) to the alcohol group (-OH). For instance, gamma-lactones will be reduced to butan-1,4-diol, (CH₂(OH)-(CH₂)₂-CH₂(OH).

Aminolysis

Lactones also react with ethanolic ammonia, which will first break the ester bond and then react with the acidic -COOH group, because of the basic properties of ammonia, to form a difunctional group, i.e. alcohol and amide. Gamma-lactones will react to yield CH₂(OH)-(CH₂)₂-CO-NH₂.

Michael reaction

Sesquiterpene lactones, found in many plants, can react with other molecules via a Michael reaction.

http://en.wikipedia.org/wiki/Lactone

Examples

Artemisinin, a new, highly-effective anti-malarial compound, is a sesquiterpene lactone found in Chinese wormwood. Lactucin, desoxylactucin, lactucopicrin, lactucin-15-oxalate, lactucopicrin-15-oxalate are some of the most prominent found in lettuce and spinach, giving most of the bitter taste to these crops.

One eudesmanolide, 3-oxo-5αH,8βH-eudesma-1,4(15),7(11)-trien-8,12-olide, can work with vernolic acid and other compounds in plants to reduce inflammation

http://en.wikipedia.org/wiki/Sesquiterpene_lactone

 

LACTONE

In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule. It is characterized by a closed ring consisting of two or more carbon atoms and a single oxygen atom, with a ketone group =O in one of the carbons adjacent to the other oxygen.

Synthesis

Many methods in ester synthesis can also be applied to that of lactones. In one industrial synthesis of oxandrolone the key lactone-forming step is an organic reduction - esterification

In halolactonization, an alkene is attacked by a halogen via electrophilic addition with the cationic intermediate captured intramolecularly by an adjacent carboxylic acid (See also iodolactamization), for example in this iodolactonization:^[4]

Specific methods include Yamaguchi esterification and nucleophilic abstraction.

A recent study has isolated β-lactones from bromination of 2,3-dimethylmaleate and/or 2,3-dimethylfumarate disodium salts, under ambient and aqueous conditions. The carboxylate groups of the maleate and fumarate moieties exhibit neighbouring group effects and alpha-lactones are proposed in the detailed mechanism

Reactions

The most stable structure for lactones are the 5-membered γ-lactones and 6-membered δ-lactones because, as in all organic cycles, 5 and 6 membered rings minimize the strain of bond angles. γ-lactones are so stable that, in the presence of dilute acids at room temperature, 4-hydroxy acids (R-CH(OH)-(CH₂)₂-COOH) immediately undergo spontaneous esterification and cyclisation to the lactone. β-lactones do exist, but can only be made by special methods. α-lactones can be detected as transient species in mass spectrometry experiments.^[6]

The reactions of lactones are similar to those of esters, as exemplified by gamma-lactone in the following sections:

Hydrolysis

Heating a lactone with a base (sodium hydroxide) will hydrolyse the lactone to its parent compound, the straight chained bifunctional compound. Like straight-chained esters, the hydrolysis-condensation reaction of lactones is a reversible reaction, with an equilibrium. However, the equilibrium constant of the hydrolysis reaction of the lactone is lower than that of the straight-chained ester i.e. the products (hydroxyacids) are less favored in the case of the lactones. This is because although the enthalpies of the hydrolysis of esters and lactones are about the same, the entropy of the hydrolysis of lactones is less than the entropy of straight-chained esters. Straight-chained esters give two products upon hydrolysis, making the entropy change more favorable than in the case of lactones which give only a single product.

Reduction

Lactones can be reduced to diols using lithium aluminium hydride in dry ether. The reduction reaction will first break the ester bond of the lactone, and then reduce the carboxylic acid group (-COOH) to the alcohol group (-OH). For instance, gamma-lactones will be reduced to butan-1,4-diol, (CH₂(OH)-(CH₂)₂-CH₂(OH).

Aminolysis

Lactones also react with ethanolic ammonia, which will first break the ester bond and then react with the acidic -COOH group, because of the basic properties of ammonia, to form a difunctional group, i.e. alcohol and amide. Gamma-lactones will react to yield CH₂(OH)-(CH₂)₂-CO-NH₂.

Michael reaction

Sesquiterpene lactones, found in many plants, can react with other molecules via a Michael reaction.

http://en.wikipedia.org/wiki/Lactone

Examples

Artemisinin, a new, highly-effective anti-malarial compound, is a sesquiterpene lactone found in Chinese wormwood. Lactucin, desoxylactucin, lactucopicrin, lactucin-15-oxalate, lactucopicrin-15-oxalate are some of the most prominent found in lettuce and spinach, giving most of the bitter taste to these crops.

One eudesmanolide, 3-oxo-5αH,8βH-eudesma-1,4(15),7(11)-trien-8,12-olide, can work with vernolic acid and other compounds in plants to reduce inflammation

http://en.wikipedia.org/wiki/Sesquiterpene_lactone

 

Synthesis of lactones and related compounds

Related: