Amines

Preparation Of Amines



When RX = MeI, the sequence is called exhaustive methylation.



Alkylation of Imides; Gabriel Synthesis of 1^o Amines






Reduction of N-Containing Compounds

1. Nitro Compounds




2. Nitriles



Nucleophilic Displacements

1. Carbylamine Reactions of 1^o Amines


Nucleophilic RNH₂ attacks electrophilic intermediate [:CCl₂].




2. Hinsberg Reaction





Ring Reactions of Aromatic Amines

NH₂, - NHR and -NR₂ strongly activate the benzene ring toward electrophilic substitution.



1. Halogenation

For monohalogenation, NH₂ is first acetylated, because



is only moderately activating







2. Sulfonation





3. Nitration

To prevent oxidation by HNO₃ and meta substitution of C₆H₅NH₃⁺, amines are first acetylated.




Benzoylation (Schotten Baumann Reaction)






Hofmann Mustard Oil Reaction

Primary amines when warmed with alcoholic carbon disulphide followed by heating with excess of mercuric chloride form isothiocyanates having pungent smell similar to mustard oil.



C₆H₅NH₂ + S = C = S C₆H₅NCO + 2HCl + HgS




Reaction of Quaternary Ammonium Salts:

Hofmann Elimination
When a quatenary ammonium hydroxide is heated strongly (125^o or higher) composes to yield water, a tertiary amine and an alkene. This reaction, called the Hoffmann elimination. The

formation of quaternary ammonium salts followed by an elimination of the kind just described and identification of the alkene and tertiary amine formed was once used in the

determination of the structure of complicated amines.







Reaction of Primary Arylamines with Nitrous Acid
Primary arylamines react with nitrous acid to give arenediazonium salt. These salts are for more stable than aliphatic diazonium salts, they do not decompose at an appreciable rate is

solution when the temperature of the reaction mixture is kept below 5^oC





Synthesis using daizonium salts

Diazonium salts are highly useful intermediate in the synthesis of aromatic compounds, because the diazonium group can be replaced by any one of number of other atoms or groups.

Including -F, -Cl, -Br, -I, -CN, -OH, and -H

Diazonium salts are prepared by diazotizing primary aromatic amines. Primary arylamines can be synthesized through reduction of nitro compounds that are readily available through

direct nitration reactions.




Note: If copper powder and hydrogen halide are used in place of cuprous halide than reaction is called Gatterman reaction



Reaction of secondary Amines with Nitrous acid

Secondary amines both aryl and alkyl react with nitrous acid to yield N-nitrosoamines. N-nitrosoamines usually separate from the reaction mixture as oily yellow liquid.




N-nitrosoamines are very powerful carcinogens



Reaction of Tertiary amines with Nitrous acid

When a tertiary aliphatic amines is mixed with nitrous acid, an equilibrium is established among the tertiary amine, its salt, and an N-Nitrosoammonium compound.




Tertiary arylamines react with nitrous acid to form o-nitrosoaromatic compound. Nitrosation takes place almost exclusively at the para position if it is open and if not, at the

orthoposition. The reaction is another example of electrophilic aromatic substitution.




Separation of a Mixture of Amines

Hinsberg's Method

Three amines + quaternary salt Three amines distilled leaving quaternary salt unchanged.
Mixture of three amines + benzene sulphonyl chloride (C₆H₅SO₂Cl)
(Hinsberg's reagent)



Primary amine:

RNH₂+ C₆H₅SO₂Cl C₆H₅- SO₂ - NH - R + HCl

(N-alkyl benzene sulphonamides)

(Dissolve in NaOH due to acidic H-attached to Nitrogen)




Secondary amine:




Tertiary amine

Tertiary amines does not react with Hinsberg's reagent. After reacting with NaOH the Aqueous layer and the second layer [Secondary and Tertiary) can be separated by ether.

Aqueous layer Hydrolysed with conc. HCl gives primary amine. The ether layer is distilled and tertiary amine is distilled over. Residue hydrolysed with conc. HCl to recover secondary

amine.



Hofmann's Method:

The mixture of amines is treated with diethyloxalate which forms a solid oxamide with primary amine, a liquid oxime ester with secondary amine. The tertiary amine does not react.






Acidic strength of (I) benzoic acid and ring substituted benzoic acid (ii) Phenol and ring substituted phenol.





Note
(1) (a) if Z is (-I) group, acidic strength increases

(b) If z is (+I) group acidic strength decreases

(c) If z is (+m) group acidic strength decreases

(d) If z is (-m) group acidic strength increases


2. If +m/-m group is present at meta position, acidic strength will not be affected by m- effect.


3. Ortho Effect: If a group is present at ortho position of -COOH group in benzoic acid, it repels -COOH group, and disturb the co planarity of -COOH group with ring, hence

acidic strength increases.


4. If z is OH, a strong intramolecular H-bonding is observed, after loss of H and acidic strength increases much more than due to ortho effect.



Basic Strength of Amines

Type (1) Aliphatic amines - 2^o>1^o>3^o>NH₃

2. Aromatic - C₆H₅NH₂ weaker than all aliphatic due to delocalization of lone pair of electrons.

3. Aromatic non nuclear - C₆H₅CH₂NH₂ ( more than aniline but less than aliphatic amines) due to (-I) effect of C₆H₅


4. Amides




Less basic than any of above



5. Urea



More than simple amide but less than 1,2,3 amine



6. N - substituted amine

(a)

Rapid decrease due to amide structure


(b) N - substituted with C₆H₅CO group

decreases


(c) N - substituted with R group in Aniline only



Stearic inhibition of resonance by close proximity (approach) of Hydrogen of alkyl group with ortho hydrogen, resonance diminishes due to which basic strength increases.



Type (2) Nuclear Substituted Aniline
Rule (+I) Increase basic strength

(-I) Decrease

(+m) Increaes

(-m) decrease



decreases



O - substituted alkyl group repel H of NH₂ group diminished protonation at N-atom basic strength decrease
.
(i)


C₆H₅ NH₂ > m > p > o



(ii)


C₆H₅NH₂ > p > m > o




(iii)




(+m strong) p>m > aniline (+ I weak)

n - Phenylated aniline




Basicity And Nucleophilicity

Nucleophile and basicity both involve the availability of electron pair and the ease with which they are donated



Basicity:
The basicity involves electron pair donation to hydrogen atom (electron deficient) only



Nuelophilicity:

Nucleophilicity involves electron pair donation to carbon atoms only. Basicity is little affected by steric influences where as nucleophilicity may be markedly affected.


Note:
Nucleophilicity is a kinetic property whereas basicity is a thermodynamic property.

The rates of S_N1 reactions are independent on the identity of the nucleophile, since it does not appear in the rate determining step however S_N2 reactions are dependent upon the

identity of nucleophile as it appears in the rate determining step.


Nucleophilic reactivity

1. A nucleophile with a negative charge is always a more powerful nucleophile than its conjugated acid (assuming the latter is also a nucleophile)

Thus is more stronger nucleophile than H₂O

is more stronger nucelophile etc.



2. In comparing nucleophiles whose attacking atom is within the same row (period) of the periodic table, nucleophilicity is roughly in order of basicity. So on approximate order of

nucleophilicity is

and



3. Going down the group in periodic table, nucleophilicity increases, though basicity decreases

Example : I^- > Br^- > Cl^- > F^- (nucleophilicity)

RS^- > RO^- or (Ar)₃P > Ar₃N

HS^- > HO^- or PH₃ > NH₃