Amine

Amine Introduction Amines are derivatives of ammonia in which one or more hydrogen atoms have been replaced by alkyl Group. Amines are organic compounds and a type of functionl group that contain nitrogen as the key atom. Structurally amines resemble ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups. As displayed in the images below, primary amines arise when one of the three hydrogen atoms in ammonia is replaced by an organic substituent. Secondary amines have two organic substituents bound to nitrogen together with one hydrogen. In tertiary amines all the three hydrogen atoms are replaced by organic substituents.

Similarly, an organic compound with multiple amino groups is called a diamine, triamine, tetraamine and so forth. Nitrogen can take three or four bonds. When nitrogen takes four bonds, it has a positive charge. Nitrogen also carries a lone pair of electron. General characteristics of amines are 1. They act as nucleophile as a lone pair of electron attacks a positive charge. 2. When nitrogen forms forth bond, it becomes positively charged.

3. Amines are Lewis bases as they are capable of donating electron pair. 4. Donation of electron pair tends to stabilize carbocation in the same molecule. Basicity of Amine Amines are basic in nature. It is because they posses a lone pair of electron on nitrogen. They are weak bases. Electron withdrawing substituent reduces the basicity while electron donating group increases its basicity. The reduction in basicity is also possible due to presence of bulky functional group which reduces the ability of amine to donate lone pair (because of steric hindrance). The decreasing order of basicity is with electron donating group is 20 > 10 > NH3 An amine group attached to aromatic ring further reduces its basicity and aromatic amines are weaker base than corresponding aliphatic amines. The cause of this low basicity is delocalization of electron pair around aromatic ring. An electron withdrawing group from benzene further weakens aromatic ring basicity. Physical Properties of Amines Hydrogen bonding significantly influences the properties of primary and secondary amines as well as the protonated derivatives of all amines. Thus the boiling point of amines is higher than those for the corresponding phosphines but generally lower than the corresponding alcohols. Methyl-, dimethyl-, trimethyl-, and ethylamine are gases under standard conditions, while diethylamine and triethylamine are liquids. Most other common alkyl amines are liquids; high molecular weight amines are, of course, solids. Most aliphatic amines display some solubility in water, reflecting their ability to form hydrogen bonds. Solubility decreases with the increase in the number of carbon atoms, especially when the carbon atom number is greater than six. Aliphatic amines display significant solubility in organic solvents, especially polar organic solvents. Primary amines react with ketones such as acetone, and most amines are incompatible with chloroform and carbon tetrachloride. Tertiary amines of the type NHRR' and NRR'R" are chiral: the nitrogen atom bears four distinct substituents counting the lone pair.

Condensation with ketones Amine reacts with aldehyde or ketone by nucleophilic addition. If the amine is primary the initial addition product undergoes dehydration to form compound containing carbon-nitrogen double bond.It is called imine.

Aldehyde and ketone react with secondary amine to form compound called enamines. The general reaction is as follows.

Excess of acid should be avoided as amine will initially be protonated. The protonated amine becomes poor nucleophile due to positive charge and will not proceed further. The imine product exists as a tautomer with its corresponding enamine.

Wolff-Kishner Reduction The Wolff-Kishner reduction is a chemical reaction that fully reduces a ketone (or aldehyde) to an alkane.

The ketone or aldehyde can be reduced by treating aldehyde or ketone with hot acid in presence of amalgamated zinc. Some aldehyde or ketone do not respond to this process of reduction and in such cases Wolf- Kishner reduction is used. The reaction takes place in strongly basic medium and can be used for those compounds which are sensitive to acid.The first step in the reaction is formation of hydrazone.

Hydrazone is formed using the same mechanism which was used for preparation of imine. The only difference is the use of hydrazine in place of amine. The step is nucleophilic addition. A strong base is then added. The strong base brings tautomerization to a derivative with the structure – CH – N = NH. The derivative then undergoes the base catalyzed elimination of a molecule of nitrogen.

The reaction produces nitrogen gas as by product. The solvent used has high boiling point so that high temperature of the reaction can be achieved. Alkylation Addition of an alkyl group to amine is called alkylation. Amines can be alkyled by various methods. However generally alkylation is carried by alkyle halides. The reaction is nucleophilic addition reaction and amine acts as nucleophile.

The reaction between ammonia and alkyl halide is a continuous reaction as it is clear from the above shown set of reactions. However once the reaction has started, the product amine competes with the starting material in the later stages of alkylation, and some higher alkylated products are also formed. Even 3ºamines may be alkylated to form quaternary (4º) ammonium salts when tetra alkyl ammonium salts are desired.

The quaternary ammonium salt is an excellent leaving group in comparison to amino group -NH2 . Quaternary ammonium salts are the product of final stage of alkylation of nitrogen. They have general formula R4N+X-. These salts are used to prepare quaternary ammonium hydroxide. The quaternary ammonium hydroxide is prepared by treating silver oxide with quaternary alkyl halide.

The aqueous solution of quaternary ammonium hydroxide is strongly alkaline and is comparable with sodium or potassium hydroxide.

Hofmann Elimination Reaction The quaternary ammonium hydroxides decompose by strong heating giving water, a tertiary amine and an alkene. This reaction is called Hofmann elimination reaction. This reaction is quite analogous to dehydrohalogenation of alkyl halide. The reaction follows an E2 mechanism requiring a strong base.

The E2 mechanism produces a major product and a minor product. The major product is least branched alkene and minor product is more highly branched alkene. Diazotization of Amine Production of diazonium ion using amine is called diazotization of amine. Diazonium ion structure is R – N+ N: Diazonium ion is used in synthesis of various diazonium salts. Aliphatic diazonium salts are very unstable and break down to yield a complicated mixture of organic product and nitrogen gas. Primary aryl-amine can also be used to produce arenediazonium salts which are more stable than aliphatic diazonium salt. These salts are stable below 50C. The complete process follows various stages of reactions. First stage is the production of nitrous acid which is very weak and unstable acid. It is generally prepared in situ by treating sodium nitrite with a strong acid.

Nitrous acid reacts with all classes of amine. The product obtained depends upon type of amine whether primary, secondary, tertiary, aliphatic, or aromatic.

In the second stage nitrosonium ion is produced by protonation of nitrous acid by a strong acid. Nitrous acid is a weak acid. A strong acid can dehydrate nitrous acid.

In the next stage nitrosonium ion reacts with nitrogen of primary amine to form an unstable N-Nitroso-ammonium ion.

N-nitroso-ammonium ion loses a proton to form an N-nitrosoamine.

N-nitrosoamine tautomerizes with diazohydroxide.

In the last stage dizohydroxide loses water in presence of acid and form diazonium ion.

It may be noted that 20 amine cannot form diazonium ion. Diazonium ion is very useful and can be easily substituted by variety of other functional groups. The reaction with other functional group is very simple. Addition of reagent is done by mixing the reagent with functional group and warming the mixture. Replacement occurs with the evolution of nitrogen.

It may be noted that aliphatic diazonium salts cannot be used as these salts decompose even below 50 C. Hence all the substitution in the above set of reaction has aromatic diazonium salt. Amides Amides are derivatives of carboxylic acid in which hydroxyl group is replaced by ammonia or amine group. Amides can be classified depending upon number of hydrogen atoms present on the nitrogen of amino group. Amides are the most stable of all the carbonyl functional groups. Amides are commonly formed from the reaction of acid chloride with an amine.

Primary amides are amides which have no substituent on the nitrogen. Primary amides are named by replacing the ‘-ic’ in the corresponding acid with amide. Acitamide is formed when –OH group in the acid is replaced. Substituent on the amide is prefaced by N- ,e.g. if one H in acetaamide is replaced by ethyl group it is called N-ethylacacetamide.

Amides can be a weak base or weak acid. Amines are more basic than amide as amines have electron withdrawing properties of the carbonyl group. Amides form intermolecular hydrogen bonding. Amides are easily hydrolyzed by strong acid or base.

∃- Lactams Cyclic amides are called lactams. Shape of ring is indicated by Greek letters. ∃-lactam has quadrilateral shape (-lactam has a pentagon shape ∗-lactam has hexagonal shape)

Amides are most stable of and least reactive of all the derivatives of carboxylic acid. However ∃-lactam are highly reactive. Nucleophile easily reacts with ∃-lactam. The Hofmann Rearrangements Primary amides react with solution of bromine or chlorine in sodium hydroxide to yield amines. The reaction is known as Hofmann rearrangement or Hofmann degradation.

From the equation it is clear that carbonyl carbon atom of amide and ‘R’ group of amide gets attached to nitrogen of amine. Primary amine prepared by this method is not mixed with 20 or 30 amine. Reaction occurs in multiple steps. Step 1: It is the halogenation of amide. N-haloamide is isolated and treated with base.

Step 2: It is abstraction of hydrogen ion by hydroxide ion. The presence of electron withdrawing bromine increases the acidity of amide.

Step 3: It involves the separation of halide ion which leaves behind an electron deficient nitrogen atom.

Step 4 In the step shown below actual rearrangement occurs. It is estimated that step three and step four take place simultaneously. The alkyl group gets detached it self from carbonyl carbon and gets bonded to nitrogen. The attachment of ‘R’ to nitrogen helps to push halide ion out of the molecule.

Step 5: The isocyanate (R—N=C=O) is hydrolyzed to form an amine and carbonate ion.

In the rearrangement, the alkyl group migrates to electron deficient nitrogen even though it loses electron to bromide ion (step 3 & 4) while migration takes place.

The advantage of production of amines by Hofmann rearrangement is that it is possible to produce primary, secondary, tertiary amine. This is not possible by other method as other method rely on SN2 mechanism by which tertiary amine cannot be produced. Phosphoric acid Phosphoric acid is very important compound because it is present in ATP in the form of triphosphate. ATP finds its presence in the process of photosynthesis of plant.

Phosphoric acid gets dehydrated and forms phosphoric anhydride. It also forms ester on treating with alcohols.

Ester is formed at the site of terminal phosphorus while formation of anhydride takes place at central hydroxyl group. ________________________________________________________________________