Chapter 29: Nitrogen Containing Compounds PDF

1361 60 Nitrogen Containing Compounds Chapter E3 29 Nitrogen Containing Compounds C 2 H 5 I  KONO Ethy l iodide Pot. nitrite ID The important nitrogen containing organic compounds are alkyl nitrites (RONO), nitro-alkanes (RNO2), aromatic nitro compounds (ArNO2), alkyl cyanides (RCN), alkyl iso cyan...

1361 60 Nitrogen Containing Compounds Chapter E3 29 Nitrogen Containing Compounds C 2 H 5 I  KONO Ethy l iodide Pot. nitrite ID The important nitrogen containing organic compounds are alkyl nitrites (RONO), nitro-alkanes (RNO2), aromatic nitro compounds (ArNO2), alkyl cyanides (RCN), alkyl iso cyanides (RNC), amines (– NH2), aryl diazonium salts (ArN2Cl), amides (– CONH2) and oximes (>C = N OH). D YG Nitrous acid exists in two tautomeric forms. O O H O  N  O ⇌ H  N Nitrite form Nitro form Corresponding to these two forms, nitrous acid gives two types of derivatives, i.e., alkyl nitrites and nitro alkanes. O O R O  N  O ; R  N Alky l nitrite Nitro alkane ST U It is important to note that nitro alkanes are better regarded as nitro derivatives of alkanes, while alkyl nitrites are regarded as alkyl esters of nitrous acid. (1) Alkyl nitrites : The most important alkyl nitrite is ethyl nitrite. Ethyl nitrite (C2H5ONO) (i) General methods of preparation : It is prepared (a) By adding concentrated HCl or H2SO4 to aqueous solution of sodium nitrite and ethyl alcohol at very low temperature (0°C). NaNO 2  HCl NaCl  HNO 2 C 2 H 5 OH  HNO 2 C 2 H 5 ONO  H 2 O Ethy l nitrite (b) From Ethyl iodide Ethy l nitrite (c) By the action of N 2 O 3 on ethyl alcohol. 2C2 H 5 OH  N 2 O3 2C2 H 5 ONO  H 2 O (ii) Physical properties U Alkyl nitrites and nitro alkanes C 2 H 5 ONO  KI (a) At ordinary temperature it is a gas which can be liquified on cooling to a colourless liquid, (boiling point 17°C) having characteristic smell of apples. (b) It is insoluble in water but soluble in alcohol and ether. (iii) Chemical properties (a) Hydrolysis : It is hydrolysed by aqueous alkalies or acids into ethyl alcohol. NaOH C 2 H 5 ONO  H 2 O    C 2 H 5 OH  HNO 2 (b) Reduction : Sn C2 H 5 ONO  6 H   C2 H 5 OH  NH 3  H 2 O HCl Small amount of hydroxylamine is also formed. C2 H5 ONO  4 H C2 H5 OH  NH 2 OH (iv) Uses (a) Ethyl nitrite dialates the blood vessels and thus accelerates pulse rate and lowers blood pressure, so it is used as a medicine for the treatment of asthma and heart diseases (angina pectoris). (b) Its 4% alcoholic solution (known as sweet spirit of nitre) is used in medicine as a diuretic. (c) Since it is easily hydrolysed to form nitrous acids, it is used as a source of nitrous acid in organic synthesis. 1362 Nitrogen Containing Compounds  Isoamyl nitrite is used as an antispasmodic in angina pectoris and as a restorative in cardiac failure.  1° and 2° - Nitro alkanes are known to exist as tautomeric mixture of nitro-form and aci-form. Primary nitro alkane R CHNO 2 ; R R Secondary nitro alkane R R C  NO 2 Tertiary nitro alkane (iv) Chemical properties (a) Reduction : Nitro alkanes are reduced to corresponding primary amines with Sn and HCl or Fe and HCl or catalytic hydrogenation using nickel as catalyst. RNO 2  6 H RNH 2  2 H 2 O (ii) General methods of preparation (a) By heating an alkyl halide with aqueous alcoholic solution of silver nitrite C 2 H 5 Br  AgNO 2 C 2 H 5 NO 2  AgBr Zn  NH 4 Cl R – NO 2  4 H   R  NHOH  H 2 O (b) Hydrolysis : Primary nitro alkanes on hydrolysis form hydroxylamine and carboxylic acid. HCl or 80 % H 2 SO 4 RCH 2 NO 2  H 2 O   RCOOH  NH 2 OH secondary nitro ketones. ID Some quantity of alkyl nitrite is also formed in this reaction. It can be removed by fractional distillation since alkyl nitrites have much lower boiling points as compared to nitro alkanes. However, when reduced with a neutral reducing agent (Zinc dust + NH4Cl), nitro alkanes form substituted hydroxylamines. E3 RCH 2 NO 2 ; (aci- form) (nitro - form) 60 (i) Classification : They are classified as primary, secondary and tertiary depending on the nature of carbon atom to which nitro groups is linked. CH 2  N  OH  O CH 3  N  O  O (2) Nitro alkanes or Nitroparaffins : Nitro alkanes are regarded as nitro derivatives of hydrocarbons. (b) By the direct nitration of paraffins (Vapour phase nitration) 400 C hydrolysis form Ketone U (c) Action of nitrous acid : Nitrous acid reacts with primary, secondary and tertiary nitro alkanes differently.  H 2O R  CH 2  O  NOH    R  C  NOH (c) By the action of sodium nitrite on -halo carboxylic acids D YG on HCl 2 R 2 CHNO 2   2 R 2 CO  N 2 O  H 2 O CH 3 CH 3  HONO 2 (fuming )   CH 3 CH 2 NO 2  H 2 O With higher alkanes, a mixture of different nitro alkanes is formed which can be separated by fractional distillation. alkanes | Nitrous acid | NO 2 NO 2 Nitrolic acid Primary 2 CH 2 ClOOH  CH 2 NO 2 COOH NaNO  – Chloro acetic acid  NaCl NaOH    R  C  NONa α – Nitro acetic acid | heat   CH 3 NO 2  CO 2 NO 2 Red coloured sodium salt Nitro methane (d) By the hydrolysis of –nitro alkene with water or acid or alkali (Recent method) CH 3 | CH 3  –  H 2O R 2 C H  HON  O   R 2 C  NO  Blue colour | U 2 - Methy l,1- nitro propene ST (e) Tertiary nitro alkanes are obtained by the oxidation of t-alkyl amines with KMnO4. KMnO 4 R 3 CNH 2   R 3 CNO 2  H 2 O (iii) Physical properties (a) Nitro alkanes are colourless, pleasant smelling liquids. (b) These are sparingly soluble in water but readily soluble in organic solvents. (c) Their boiling points are much higher than isomeric alkyl nitrites due to polar nature. (d) Again due to polar nature, nitro alkanes are excellent solvents for polar and ionic compounds. | NO 2 NaOH NO 2 Secondary | H or OH CH 3  C  CH NO 2  HOH    CH 3  C  O  CH 3 NO 2 O H2 Acetone Nitro methane Ether or Pseudo nitrol Tertiary nitro alkanes do not react with nitrous acid. (d) Thermal decomposition :. 300 C R.CH 2.CH 2 NO 2   R.CH  CH 2  HNO 2 moderately On rapid heating nitro alkanes decompose with great violence. heat, Rapidly CH 3 NO 2   1 3 N 2  CO 2  H 2 2 2 (e) Halogenation : Primary and secondary nitro alkanes are readily halogenated in the -position by treatment with chlorine or bromine. Cl 2 CH 3  NO 2   NaOH CCl 3 NO 2 Chloropicr in or nitro chloroform (insecticide) Nitrogen Containing Compounds CH 3 and thus can be abstracted by strong alkalies like aq. NaOH. Therefore, 1° and 2° nitroalkanes dissolve in aq. NaOH to form salts. For examples. CH 3 | | Cl 2  NaOH CH 3 – C H – NO 2  CH 3 – C – NO 2 | 2  Nitropropa ne Cl    O NaOH    Na  C H 2 – N O– I CH 3  N (f) Condensation with aldehyde : CH 3 CHO  CH 3 NO 2 CH 3 CH (OH )CH 2 NO 2 (g) Reaction with grignard reagent : The aci-form of nitroalkane reacts with Grignard reagent forming alkane.   OH  CH 3 MgI CH 4  RCH  N O Methane OMgI O  The nitrogen of –NO2 carrying a positive charge exerts a powerful – I effect and thus activates the hydrogen atom of the -carbon. Thus the important reactions of nitroalkanes are those which involve hydrogen atom of primary and secondary nitroalkanes (tertiary nitroalkanes have no -hydrogen atom and hence do not undergo such type of reactions). Thus 1° and 2° nitroalkanes are acidic mainly due to following two reasons, (a) Strong electron withdrawing effect of the – NO2 group. (b) Resonance stabilisation of the carbanion (I) formed after the removal of proton. The aci-form of nitroalkanes is relatively more acidic because it produces relatively more conjugate base. (v) Uses : Nitro alkanes are used, (a) As solvents for polar substances such as cellulose acetate, synthetic rubber etc. (b) As an explosive. (c) For the preparation  Acidic character :The -hydrogen atom of hydroxylamines, chloropicrin etc. primary and secondary nitroalkanes are weakly acidic Table : 29.1 Distinction between Ethyl nitrite and Nitro ethane Ethyl nitrite (C2H5ONO) amines, Nitro ethane (C2H5NO2) (Nitro alkane, RNO2) U (Alkyl nitrite, RONO) of ID Test  ONa O 60 (nitro alcohol)  O  H 2C  N O E3  -Hy droxy nitropropa ne RCH  N 1363 Low, 17°C Much higher, 115°C Reduction with metal and acid (Sn/HCl) or with LiAlH4. Action of NaOH (alkalies). Gives alcohol + hydroxyl amine or NH3. C2 H 5 ONO  4 H C2 H 5 OH  NH 2 OH Gives corresponding primary amine. C2 H 5 NO 2  6 H C2 H 5 NH 2  2 H 2 O RONO  6 H ROH  NH 3  H 2 O RNO 2  6 H RNH 2  2 H 2 O Readily hydrolysed to give corresponding alcohol and sodium nitrite (decomposition). Not decomposed, i.e., alcohols are not produced. But it may form soluble sodium salt, because in presence of alkali the nitro form changes into aci form, which dissolves in alkalies to form sodium salt. D YG Boiling point C2 H 5 ONO  NaOH C2 H 5 OH  NaNO 2 RONO  NaOH ROH  NaNO 2 U CH 3  CH  N No action with nitrous acid. ST Action of HNO2 (NaNO2+ HCl) Aromatic Nitro Compounds Aromatic nitro compounds are the derivatives of aromatic hydrocarbons in which one or more hydrogen atom (s) of the benzene nucleus has been replaced by nitro (– NO2) group. (1) Preparation OH NaOH   CH 3  CH  N O ONa O Primary nitro alkanes forms nitrolic acid, which dissolve in alkali to give red solution. Secondary nitro alkane yields pseudo-nitrol, which dissolves in alkali to give blue solution. Tertiary nitro alkanes does not react with nitrous acid. (i) Nitration (Direct method) : The number of – NO2 groups introduced in benzene nucleus depends upon the nature and concentration of the nitrating agent, temperature of nitration and nature of the compound to be nitrated. (a) The nature of the nitrating agent : For example, NO2 NO2 Fuming HNO3 +conc. H2SO4 conc. HNO3 +conc. H2SO4 100° C 100°C O2N Syn-Trinitro benzene NO2 Benzen e NO2 mDinitrobenzene 1364 Nitrogen Containing Compounds (ii) They are either pale yellow liquids or solids having distinct smells. For example, nitro benzene (oil of Mirabane) is a pale yellow liquid having a smell of bitter almonds. (3) Chemical properties NO2 NO2 NO2 HNO3 + H2SO4 60°C Benzen e m-Dinitro benzene Nitrobenzene N+ NO2 OH OH OH NO2 No reaction dil. HNO3 H2SO4 Phenol NO2 2, 4, 6Trinitrophenol oNitrophenol NO2 pNitrophenol U ST (ii) Indirect method : The aromatic nitro compounds which can not be prepared by direct method may be prepared from the corresponding amino compound. N2BF4 NO2 pNitroaniline (2) Physical properties Resonance hybrid of nitrobenzene (ii) Displacement of the – NO2 group : Although – NO2 group of nitrobenzene cannot be replaced by other groups, but if a second – NO2 group is present on the benzene ring of nitrobenzene in the o- or p- position, it can be replaced by a nucleophile. For example, NO2 Nu + aq. KOH, NH3 or C2H5OK NO2 NO2 NO2 pDinitrobenzene (Where, Nu = OH, NH2 or OC2H5 ) (iii) Reduction : Aromatic nitro compounds can be reduced to a variety of product as shown below in the case of nitrobenzene. C 6 H 5 NO 2 C 6 H 5 NO C 6 H 5 NHOH C 6 H 5 NH 2 Nitrobenze ne Nitrosoben zene NO2 pDinitroanilin e (i) Aromatic nitro compounds are insoluble in water but soluble in organic solvents. Pheny lhy droxy lamine Aniline The nature of the final product depends mainly on the nature (acidic, basic or neutral) of the reduction medium and the nature of the reducing agent. (a) Reduction in acidic medium NO2 + 6H NO2 + + NaNO2 Cu, heat NaNO2 HBF4 + + On the other hand, nitration of aromatic compounds having electron withdrawing groups like – NO2, – SO3 H requires powerful nitrating agent (like fuming HNO3 + conc. H2SO4) and a high temperature. NH2 + + Resonating structures of nitrobenzene NO2 conc. HNO conc.3 N+ OH D YG O2N + N+ U dil. HNO3 conc. HNO3 H2SO4 N+ ID (c) Nature of the compound to be nitrated : Presence of electron-releasing group like –OH, –NH2, – CH3, –OR, etc., in the nucleus facilitates nitration. Thus aromatic compounds bearing these groups (i.e. phenol, aniline, toluene, etc.) can be nitrated readily as compared to benzene. Thus benzene is not affected by dilute HNO3 while phenol, aniline and toluene forms the corresponding ortho- and para-nitro compounds. N+ E3 HNO3 + H2SO4 100°C (i) Resonance in nitrobenzene imparts a partial double bond character to the bond between carbon of benzene nucleus and nitrogen of the – NO2 group with the result the – NO2 group is firmly bonded to the ring and therefore cannot be replaced other groups, i.e., it is   – very inert. –O O O O– O– O– O– O– O– O – 60 (b) Temperature of nitration : For example, Nitrobenzen e Sn + HCl NH2 + 2H2O Aniline Reduction of dinitrobenzene with ammonium sulphide reduces only one – NO2 group (selective reduction) Nitrogen Containing Compounds NO2 NO2 (NH4)2S or Na2S NO2 NO2 NO2 NH2 m-Dinitro benzene m-Nitroaniline Zn dust  NH 4 Cl C 6 H 5 NO 2  2 H  C 6 H 5 NO C 6 H 5 NHOH Phenylhy droxy lamine (c) Reduction in alkaline medium :  C 6 H 5 NO  2[ H ] C 6 H 5 NO 2    Nitroso benzene     C 6 H 5  N O  H 2O Nitrobenze ne || C 6 H 5 NHOH  C6 H 5  N Pheny l hy droxy lamine Azoxy benzene Azoxybenzene on further azobenzene and hydrazobenzene. reduction yields C 6 H 5 – N O  C 6 H 5 – N  C 6 H 5 – N H 2[ H ] | || C6 H 5  N C6 H 5  N C6 H 5  NH Azobenzene Hy drazoben zene Azoxy benzene Although nitrobenzene, itself undergoes electrophilic substitution under drastic conditions, nitrobenzene having activating groups like alkyl, – OR, – NH2 etc. undergoes these reactions relatively more readily. CH3 CH3 NO2 2[ H ] || m-Nitrobenzene sulphonic acid 60 Nitrosoben zene (intermediate) SO3H Nitrobenze ne HNO3 H2SO4 HNO3 H2SO4 oNitrotoluene NO2 ne U ST (a) (b) Cl mChloronitrobenzene NO2 NO2 conc. HNO3 conc. H2SO4 NO2 Nitrobenze ne Sym-trinitrobenzene (TNB) is preferentially prepared from easily obtainable TNT rather than the direct nitration of benzene which even under drastic conditions of nitration gives poor yields. CH3 COOH NO2 NO2 NO2 O2N O2N O2N Na2Cr2O7 H2SO4 Sodalime (–CO2) OH NO2 NO2 NO2 1, 3, 5TrinitroBenzene (TNB)is inert (v) Nucleophilic Substitution : Benzene (TNT ) 2, 4, 6-Trinitro benzoic acid to nucleophiles, but the presence of – NO2 group in the benzene ring activates the latter in o- and p-positions to nucleophiles. NO2 NO2 NO2 OH KOH fuse Nitro benzene + oNitrophenol OH p- AlCl3 Nitrobenze ne NO2 2, 4, 6Trinitrotoluene (TNT) p-Aminophenol  Alkaline medium of electrolytic reduction gives all the mono- and di-nuclear reduction products mentioned above in point (c). (iv) Electrophilic substitution : Since – NO2 group is deactivating and m-directing, electrophilic substitution (halogenation, nitration and sulphonation) in simple aromatic nitro compounds (e.g. nitrobenzene) is very difficult as compared to that in benzene. Hence vigorous reaction conditions are used for such reaction and the new group enters the m-position. NO2 NO2 + Cl2 2, 4Dinitrotoluene U D YG electrolyti rearrangeme c nt reduction in presence of conc. H2SO4 Phenylhydroxylami Nitrobenzene NO2 NO2 O2N ID (d) Electrolytic reduction :  Weakly acidic medium of electrolytic reduction gives aniline.  Strongly acidic medium gives phenylhydroxylamine which rearranges to pNH2 aminophenol. NO2 NHOH CH3 E3 ( H 2 O ) 100°C + H2SO4 (fuming) (c) (b) Reduction in neutral medium : Nitrobenze ne 1365 m-Dinitrobenzene Nitrophenol (vi) Effect of the – NO2 group on other nuclear substituents (a) Effect on nuclear halogen : The nuclear halogen is ordinarily inert, but if it carries one or more electron-withdrawing groups (like – NO2) in o- or pposition, the halogen atom becomes active for nucleophilic substitutions and hence can be easily replaced by nucleophiles KOH , NH 3 , NaOC 2 H 5 . 1366 Nitrogen Containing Compounds Cl Nu NO2 NO2 + KOH, NH3 or C2H5ONa (4) Uses NO2 2, 4Dinitrochlorobenzene (i) On account of their high polarity, aromatic nitro compounds are used as solvents. (Where, Nu = OH, NH2, OC2H5) (b) Effect on phenolic –OH group : The acidity of the phenolic hydroxyl group is markedly increased by the presence of – NO2 group in o- and p-position. The decreasing order of the nitrophenols follows following order of (iv) Nitro benzene is used in the preparation of shoe polish and scenting of cheap soaps. OH O2N (iii) These are used for the synthesis of aromatic amino compounds. NO2 E3 OH acidity (ii) Nitro compounds like TNT, picric acid, TNB etc. are widely used as explosives. 60 NO2 NO2 Cyanides and Isocyanides Hydrogen cyanide tautomeric mixture. NO2 NO2 2, 4, 6-Trinitro phenal 2, 4-Dinitrophenol known to exist as a  C H–CN⇌ HN OH Hence, it forms two types of alkyl derivatives which are known as alkyl cyanides and alkyl isocyanides. ID OH is R–N  C R–C  N Alky l Cy anide NO2 Alkylisocyanide U (1) Alkyl Cyanides o- and p-Nitrophenols Phenol D YG Increased acidity of o- and p-nitrophenols is because of the fact that the presence of electronwithdrawing – NO2 group in o-and p-position (s) to phenolic –OH group stabilises the phenoxide ions (recall that acidic nature of phenols is explained by resonance stabilisation of the phenoxide ion) to a greater extent. – O–N=O O– O– O (a) From alkyl halides : The disadvantage of this method is that a mixture of nitrile and isonitrile is formed. RX  KCN (orNaCN ) Alky l halide OH Acetamide NO2 NO2 + PCl5 + POCl3+HCl NO2 NO2 2, 4-Dinitrophenol 2, 4-Dinitrochlorobenzene RNC Isonitrile (Minor pro duct) 2 P2 O5   RCN  H 2O Methyl cyanide Industrially, alkyl cyanides are prepared by passing a mixture of carboxylic acid and ammonia over alumina at 500°C. Al 2 O3 RCOOH  NH 3 RCOONH 4    Ammonium salt – H 2O Al 2 O3 RCONH 2    RCN Amide – H 2O Alkylcyanide (c) From Grignard reagent RMgX  ClCN RCN  Mg Grignard reagent Alky l cy anide CH 3 MgBr  ClCN Methy l magnesium Cy anogen chloride bromide Cl  P2O5 CH 3 CONH 2   CH 3 CN  H 2 O Acid Due to increased acidity of nitrophenols, the latter react with phosphorus pentachloride to give good yields of the corresponding chloro derivative, while phenol itself when treated with PCl5 gives poor yield of chlorobenzene. RCN Nitrile (Major product) (b) From acid amides : RCONH Extra stabilisation of pnitrophenate ion due to –NO2 group ST Phenoxide ion (no –NO2 group) + O – N – O– U – + (i) Methods of preparation X Cl CH 3 CN  Mg Methy lcy anide Br Cl (d) From primary amines : Primary amines are dehydrogenated at high temperature to form alkyl cyanides. This is also a commercial method. Nitrogen Containing Compounds R Cu or Ni RCH 2 NH 2   RCN  2H 2 500 C Primary amine |  R  C  OH  Mg H 2O Cu or Ni CH 3 CH 2 NH 2   CH 3 CN  2H 2 500 C | R  Methyl cyanide Tertiary alcohol (e) From oximes : (d) Alcohololysis : | P2 O5 R  C  NOH   R  CN  H 2 O  H 2O Alky l cy anide (ii) Physical properties (a) Alkyl cyanides are neutral substance with pleasant odour, similar to bitter almonds. (b) Lower members containing upto 15 carbon atoms are liquids, while higher members are solids. (c) They are soluble in water. The solubility decreases with the increase in number of carbon atoms in the molecule. (d) They are soluble in organic solvents. HCN H 2O   RCOOH  NH 3 H Acid CH 3 CN  CH 3 CONH 2 CH 3 Cl  Methy l chloride Acetamide D YG H Acetic acid (b) Reduction : When reduced with hydrogen in presence of Pt or Ni, or LiAlH4 (Lithium aluminium hydride) or sodium and alcohol, alkyl cyanides yield primary amines.   RCH 2 NH 2 4H Primary amine U However, when a solution of alkyl cyanides in ether is reduced with stannous chloride and hydrochloric acid and then steam distilled, an aldehyde is formed (Stephen's reaction). SnCl 2 HCl H 2O R  C  N   RCH  NH.HCl   RCHO  NH 4 Cl ST Imine hy drochloride Aldehy de (c) Reaction with Grignard reagent : With grignard's reagent, an alkyl cyanide forms a ketone which further reacts to form a tertiary alcohol. R RCN Cy anide (Nitrile) Minor pro duct CH 3 NC  CH 3 CN Methy l isocy anide (Main product) | Ketone R | R – C  O  R MgX R  C  OMgX | R  RNC  3 KCl  3 H 2 O Isocy anide (c) From N-alkyl formamides : O || POCl 3   R  N  C  H 2O R  NH  C  H  N alky l formamide Py ridine Isocy anide (ii) Physical properties (a) Alkyl isocyanides are colourless, unpleasant smelling liquids. (b) They are insoluble in water but freely soluble in organic solvents. (c) Isonitriles are much more poisonous than isomeric cyanides. (iii) Chemical properties (a) Hydrolysis :  H RN  C  2 H 2 O   RNH 2  HCOOH Primary amine Formic acid Ni (b) Reduction : R  N   C  4 H  RNHCH 3 o R 2 H 2O    R  C  O  NH 3  Mg RNH 2  CHCl 3  3 KOH Primary amine Chloroform Alky l isocy anide | R  C  N  R ' MgX R  C  NMgX | AgCN  (b) From primary amines (Carbylamine reaction) : H 2O   CH 3 COOH  NH 3 R RNC Isocy anide (Isonitrile) Main product U H [2 H ] (i) Methods of preparation ID 2 Amide H 2O RCN (iv) Uses : Alkyl cyanides are important intermediates in the organic synthesis of a large number of compounds like acids, amides, esters, amines etc. Alky l halide H 2O RCN   RCONH Alkylcyanide Ester R  X  AgCN (a) Hydrolysis Methy l cy anide H 2O   RCOO R   NH 4 Cl (a) From alkyl halides : (iii) Chemical properties H imido ester (2) Alkyl Isocyanides (e) They are poisonous but less poisonous than Alky l cy anide    N H2   ||   RCN  R OH  HCl  R  C  O R  Cl  Alky l Alcohol   cy anide     60 H Aldoxime OH X E3 Ethylamine 1367 Alkyl isocyanide OH X 300 C secondary amine (c) Action of heat : When heated for sometime at 250°C, a small amount of isonitrile changes into isomeric nitrile. heat RNC   RCN 1368 Nitrogen Containing Compounds (d) Addition reaction : Alkyl isocyanide give addition reactions due to presence of unshared electron pair on carbon atom.   R : N ::: C : or R  N  C Amines are regarded as derivatives of ammonia in which one, two or all three hydrogen atoms are replaced by alkyl or aryl group. NH3 The following are some of the addition reactions shown by alkyl isocyanides. (Halogen) RNCX 2 Alky l iminocarbo ny l halide RNC  S RNCS Alky l isothiocy a nate –3H + 3R RNH2 R2NH R3N (Primary) (Secondary ) (Tertiar y) Amines are classified as primary, secondary or tertiary depending on the number of alkyl groups attached to nitrogen atom. ; RNC  HgO RNCO  Hg Alky l isocy anate (iv) Uses : Due to their unpleasant smell, alkyl isocyanides are used in detection of very minute leakage. Carbylamine reaction is used as a test for the detection of primary amino group.  Methyl isocyanate (MIC)gas was responsible for Bhopal gas tragedy in Dec. 1984. The characteristic groups in primary, secondary Ethyl cyanide Ethyl isocyanide D YG Test Smell Strong but pleasant Extremely unpleasant Dipole More ( 4D) Less ( 3D) B.P. 98°C(i.e. High) 78°C (i.e. low) Solubilit Soluble Insoluble moment y in water. Hydrolys Gives propionic acid Give ethyl amine (1° is (Acid, in general) amine, in general) Same as above No action U with acids Hydrolys with ST is (amino) (imino) Reductio Gives propylamine (1° Gives n amine, in general) amine (2° amine, in Gives s propionaldehyde reaction (Aldehyde, in general) Heating No effect (250°C) Amines | (tert  nitrogen) In addition to above amines, tetra-alkyl derivatives similar to ammonium salts also exist which are called quaternary ammonium compounds. NH 4 I ; ; R 4 NI Quaternary ammonium iodide (CH 3 ) 4 NI or Tetramethyl ammonium iodide  R   |     R  N|  R  X   R   Tetra - alky l am m onium salt (1) Simple and mixed amines : Secondary and tertiary amines may be classified as simple or mixed amines according as all the alkyl or aryl groups attached to the nitrogen atom are same or different. For example, Simple amines : (CH 3 ) 2 NH ; (CH 3 CH 2 )3 N Dimethy lamine Triethy lamine Mixed amines : C 2 H 5  N H ; C 6 H 5  N H | | CH 3 CH 3 Ethy lmethylamine Methy laniline The aliphatic amines have pyramidal shape with one electron pair. In amines, N undergoes sp3 hybridisation. (2) General methods of preparation alkalies Stephen' N U  Being less polar, isocyanides are not attacked by OH– ions. Table : 29.2 Comparison of Alkyl Cyanides and Alkyl Isocyanides | | and tertiary amines are: – NH 2 ; – NH ; ID  Cyanides have more polar character than isocyanides. Hence cyanides have high boiling points and are more soluble in water. However, both isomers are more polar than alkylhalides, hence their boiling points are higher than the corresponding alkyl halides. 60 –2H + 2R E3 RNC  X 2 –H +R ethylmethyl Does not occur formed cyanide of amines (a) Hofmann's method :The mixture of amines (1°, 2° and 3°) is formed by the alkylation of ammonia with alkyl halides. general) Ethyl (i) Methods yielding mixture (Primary, secondary and tertiary) is CH 3 I  Methy liodide CH 3 I NH 3 CH 3 NH 2  (CH 3 )2 NH Methy lamine (1) Dimethy lamine (2) CH 3 I CH 3 I   (CH 3 )3 N   (CH 3 )4 NI Trimethylamine (3) Tetramethyl ammonium iodide Nitrogen Containing Compounds The primary amine may be obtained in a good yield by using a large excess of ammonia. The process is also termed as ammonolysis of alkyl halides. It is a nucleophilic substitution reaction. Amide Pri- amine This is the most convenient method for preparing primary amines. carbon atom less than amide. Al 2 O 3 CH 3 OH  NH 3    CH 3 NH 2 350 C (f) Gabriel phthalimide synthesis : This method CH 3 OH Primary amine may be obtained in a good yield by using a excess of ammonia.  Phthalimide is reacted with KOH to form potassium phthalimide.  The potassium salt is treated with an alkyl (ii) Methods yielding primary amines halide. (a) Reduction of nitro compounds  The product N-alkyl phthalimide is put to hydrolysis with hydrochloric acid when primary amine E3 Sn HCl or R  NO 2  6[H ]    RNH 2  2 H 2 O Zn HCl or Ni or LiAlH 4 is formed. C 2 H 5  NO 2  6[H] C 2 H 5 NH 2  2 H 2 O CO (b) Reduction of nitriles (Mendius reaction) R  C  N  4[H] R  CH 2 NH 2 ID Phthalimi de Ethy lamine SOCl 2 KCN R  OH    R  Cl   D YG LiAlH 4 or R  CN    RCH 2 NH 2 Na  C 2 H 5 OH Primary amine This sequence gives an amine containing one more carbon atom than alcohol. LiAlH 4   RCH 2 NH 2 LiAlH 4 CH 3 CONH 2    CH 3 CH 2 NH 2 Ethylamine U Acetamide (d) By reduction of oximes : The start can be made from an aldehyde or ketone. ST H 2 NOH LiAlH 4 RCHO   RCH  NOH   RCH 2 NH 2 Aldehyde R R Oxime C  O  H 2 NOH Ketone R R orH 2 Ni Primary amine C  NOH Oxime LiAlH 4    R R CH  NH 2 Primary amine (e) Hofmann's bromamide reaction or degradation (Laboratory method) : By this method the amide (– CONH2) group is converted into primary amino (– NH2) group. CO NC2H5 HOH HCl COOH C2H5NH2+ CO COOH Phthalic acid When hydrolysis is difficult, the N-alkyl phthalimide can be treated with hydrazine to give the required amine. CO (c) By reduction of amides with LiAlH4 2 C2H5X Potassium phthalimide N-Ethyl phthalimide Alky l chloride NK CO U The start can be made from alcohol or alkyl halide. RCONH CO KOH NH –H 2O CO CH 3 C  N  4[H ] CH 3  CH 2 NH 2 Alky l nitrile involves the following three steps. 60 (CH 3 )2 NH (CH 3 )3 N CH 3 OH Alcohol R  CO  NH 2  Br2  4 KOH R  NH 2  2 KBr  K2CO3  2 H 2O This method gives an amine containing one (b) Ammonolysis of alcohols : Methy l cy anide 1369 CO NH2 heat NR + | NH2 Hydrazine CO –NH | + RNH2 CO –NH Nitrogen Containing Compounds 1369 (g) By decarboxylation of -amino acids Ba (OH )2 R C HC OOH    RCH 2 NH 2 | heat NH 2 | heat Methy l amine NH 2  - amino acetic acid (Gly cine) (h) By means of a Grignard reagent and chloramine : RMgX  ClNH 2 RNH 2  MgXCl (i) By hydrolysis of Isocyanides or Isocyanates H OH ( HCl ) R  N  C  2 H 2 O   R  NH 2  HCOOH Alky l amine H OH O || heat (NaN 3  H 2 SO 4 N 3 H  NaHSO 4 ) H CH 3  NC  2 HOH   CH 3  NH 2  HCOOH E3 (k) By Ritter reaction : It is a good method for preparing primary amines having -tertiary alkyl group. methy l isonitile H OH CH 3  N  C  O  2 KOH CH 3  NH 2  K 2 CO 3 H OH (CH 3 )3 C  OH  H 2 SO 4  HCN (CH 3 )3 C  NH 2 Methy l isocy anate Tert- buty l alcohol R  NCO  2 KOH R  NH 2  K 2 CO 3 Conc. H 2 SO 4 R  COOH  N 3 H    R  NH 2  N 2  CO 2 Hy drazoic acid Alky l amine D YG RCON 3 R  N  C  O  N 2 Alky l isocy anate R  N  C  O  H 2 O R  NH 2  CO 2 Alky l amine U The overall reaction which proceeds by the elimination of nitrogen from acyl azide followed by acidic or alkaline hydrolysis to yield primary amine containing one carbonless, is called Curtius Degradation. The method uses acid chloride to prepare primary amine through acyl azide. O O O || || || 2 3 R  C  OH   R  C  Cl   R  C N3 ST SOCl NaN Acy lchloride Acy lazide O ||  N2 R  C  N 3  R  N  C  O  R  NH 2  Na 2 CO 3 N=N=N heat –   C || || O O –N2 + N–N  N R C N  C || O (l) Reductive amination of aldehydes and ketones : O || Ni ,150 C R  C  H  NH 3  H 2   R  CH 2  NH 2  H 2 O Aldehy de 300 atm Primary amine H H  | |  ( H 2 O )  NH ]  R  C  O  H 2 HN [R  C Imine   2   RCH 2  NH 2   Ni H CH 3 O || Intramolecu alkyl lar shift | Ni ,150 C R  C  CH 3  NH 3  H 2    R  CH  NH 2 300 atm Ketone This reaction probably takes place through the formation of an imine (Schiff's base). The primary amine can also be converted into sec. or tert. amines by the following steps H 2 Ni R  CHO  RNH 2    RCH 2 NH R Sec. amine RNH 2  2 H 2C  O  2 HCOOH RN (CH 3 )2  2 H 2 O  2CO 2 Tert.- amine (m) By reduction of azide with NaBH4 NaBH 4 R  X  NaN 3 RN 3   RNH 2 Alky l halide (1or2 ) Sodium azide Alky l azide H 2O 1amine (n) By Leuckart reaction : Aldehydes or ketones react with ammonium formate or with formamide to give formyl derivative of primary amine.  R  H 2O OH   CHO  R 3 CNH   R 3 C  NH 2  HCOO   Pri- amine  2 NaOH The mechanism of curtius rearrangement is very similar to Hofmann degradation. R   H HCN  H 2 O  R3 C    R 3 C N  CH  R 3 C  OH  Tert-carboniumion  U In this reaction the acyl azide (R – CON3) and alkyl isocyanate (R – NCO) are formed as an intermediate. R – COOH  N 3 H RCON 3  H 2 O Acy lazide Tert buty lamine (1amine) ID Alky l isocy anate (j) By Schmidt reaction : Acy lazide NaN  H SO (conc.) 3 4 2  RNH 2  N 2  CO 2 R  C  OH  Alky l isocy anide Acid Schmidt reaction converts R – COOH to R–NH2, which is a modification of curtius degradation. In this reaction a carboxylic acid is warmed with sodium azide (Na+N3–) and conc. H2SO4. The carboxylic acid is directly converted to the primary amine without the necessity of isolating alkyl azide. 60 Ba(OH )2 CH 2  COOH   CH 3 NH 2 R–N=C=O 1370 Nitrogen Containing Compounds (d) Hydrolysis of dialkyl cyanamide O || 2H 2 O  CO 2  NH 3 O ||  C  O  2 HCONH 2  CHNH  C  H  CO 2  NH 3 Formamide These formyl derivatives are readily hydrolysed by acid to yield primary amine. O R R ||  H CHNH  C  H  HOH   R R CHNH 2  H 2 O  CO 2 This is called Leuckart reaction, i.e., R R  R R 450 C, 20 atm D YG (iii) Methods yielding secondary amines (a) Reaction of primary amines with alkyl halides   R  NH 2  R  X  R2 NH  HX  R2 N H 2 X dialky l ammonium salt R2 NH  Secondary amine H 2 O  NaX (b) Reduction of isonitriles : Pt R  NC  4 [H ]  RNHCH 3 Alky l isonitrile U Sec. amine Secondary amine formed by this method always possesses one –CH3 group linked directly to nitrogen. ST (c) Reaction of p-nitroso-dialkyl aniline with strong alkali solution : NH2 RX heat Anilin e NR2 NR2 NaOH 2 OH + R2NH Sec. p-Nitroso-dialkyl aniline LiAlH 4 R  CONH R   4[H ]   RCH 2 NH R  H 2 O N - Alky l acid amide Sec.amine (a) Reaction of alkylhalides with ammonia  3 RX  NH 3 R 3 N  3 HX   R3 N H X Trialky l ammonium salt  R 3 N H X  NaOH R 3 N  NaX  H 2 O (b) Reduction of N, N-disubstituted amides : The carbonyl group is converted into – CH2 group. RCON R 2 N , N -disubstitu ted amide LiAlH 4    RCH 2 NR 2  H 2 O 4[H ] ter. amine (c) Decomposition of tetra-ammonium hydroxides : The tetra-alkyl ammonium hydroxides are formed when corresponding halides are treated with moist silver oxide.    R4 N I  AgOH R4 N O H  AgI The hydroxides thus formed on heating decompose into tertiary amines. Tetramethyl ammonium hydroxide gives methyl alcohol as one of the products while all other tetra-alkyl ammonium hydroxides give an olefin and water besides tertiary amines. (R)4 NOH (R)3 N  olefin  H 2 O Dialkyl aniline ON The product is referred to as Mannich base and the reaction is called Mannich Reaction. (CH 3 )4 NOH (CH 3 )3 N  CH 3 OH HNO OH H ON Alkyl -amino ketones are formed by the action of ketone with formaldehyde and NH3 (or primary or secondary amines). U Cobalt catalyst CH 2  CH 2  NH 3    CH 3 CH 2 NH 2 R2 N H 2 X  NaOH (e) Reduction of N-substituted amides : Reduction of N-substituted amides with LiAlH4 yields secondary amines. (iv) Methods yielding tertiary amines  On commercial scale, ethylamine is obtained by heating a mixture of ethylene and ammonia at 450°C under 20 atmospheric pressure in presence of cobalt catalyst.  Dialky l amine ID CHNH 2  H 2 O  CO 2 Primary amine  OH Which can be reduced to alkyl amines. Ketone Ethylene  H or R 2 N  CN  2 HOH   R 2 NH  CO 2  NH 3  heat CH 3 COCH 3  HCHO  RNH 2   CH 3 COCH 2 CH 2 NHR 180  200 C C  O  HCOONH 4   Amm.formate   CaN  CN   2 NaOH 2 RX   Na N  CN    R N  CN 2 2  Calcium  Sodium Dialky l  cy anamide cy anamide cy anamide   60 Amm.formate E3  C  O  2 HCOONH 4  CHNH – C – H p-Nitroso amine phenol This is one of the best method for preparing pure secondary amines. (3) Separation of mixture of amines : When the mixture consists of salts of primary, secondary and tertiary amines along with quaternary salt, it is first distilled with KOH solution. The mixture of three amines distils over leaving behind non-volatile quaternary salt. Nitrogen Containing Compounds   C6 H 5 SO 2 Cl  HNHR C6 H 5 SO 2 NHR  RNH 2.HI or RN H 3  I  K O H RNH 2  KI  H 2 O Primary amine Primary amine (Volatile), Distillate    N - Alky l benzene sulphonami de NaOH    C 6 H 5 SO 2 N ( Na )R  R 2 NH.HI or R 2 N H 2  I  K O H R 2 NH  KI  H 2 O  1371  R 3 N.HI or R 3 N H  I  K O H R 3 N  KI  H 2 O  R 4 N I (non-volatile tetra-alkyl ammonium salt) Soluble salt The secondary amine forms N,N-dialkyl benzene sulphonamide which does not form any salt with NaOH and remains as insoluble in alkali solution. C6 H 5 SO 2 Cl  HNR 2 C6 H 5 SO 2 NR 2 Sec. amine has no reaction with KOH, however remains as residue. can be separated by fractional distillation. This method is used satisfactorily in industry. (Insoluble in water, soluble in ether) Tertiary amine does not react. The above alkaline mixture of the amines is extracted with ether. Two distinct layers are formed. Lower layer, the aqueous layer consists of sodium salt of N-alkyl benzene sulphonamide (primary amine) and upper layer, the ether layer consists of N,N-dialkyl benzene sulphonamide (secondary amine) and tertiary amine. Two layers are separated. The upper layer is fractionally distilled. One fraction obtained is tertiary amine and the other fraction is treated with concentrated HCl to recover secondary amine hydrochloride which gives free secondary amine on distillation with NaOH. C6 H5 SO 2 NR 2  HCl  H 2O C6 H5 SO 2.OH  R2 NH.HCl U ID (ii) Hofmann's method : The mixture of three amines is treated with diethyl oxalate. The primary amine forms a solid oxamide, a secondary amine gives a liquid oxamic ester while tertiary amine does not react. CO OC 2 H 5 H NHR  2 C 2 H 5 OH |    C ONHR | CO OC 2 H 5 H NHR CONHR Primary Diethy l oxalate 60 (i) Fractional distillation : The boiling points of primary, secondary and tertiary amines are quite different, i.e., the boiling point of C2H5NH2 is 17°C, (C2H5)2NH is 56°C and (C2 H5 )3 N is 95°C and thus, these NaOH    No reaction E3 This mixture is separated into primary, secondary and tertiary amines by the application of following methods. Dialky l oxamide (Solid) D YG amine  C 2 H 5 OH COOC 2 H 5  HNR 2    CONR 2 | COOC 2 H 5 Diethy l oxalate | Secondary amine COOC 2 H 5 Dialky l oxamic ester (liquid) Primary amine is recovered when solid oxamide is heated with caustic potash solution and collected as distillate on distilling the reaction mixture. CO NHR |  Sec. amine The aqueous layer is acidified and hydrolysed with dilute HCl. The hydrochloride formed is then distilled with NaOH when primary amine distils over. C 6 H 5 SO 2 N ( Na)R  HCl C 6 H 5 SO 2 NHR  NaCl Sulphonami de of primary amine C6 H 5 SO 2 NHR  HCl  H 2 O C6 H 5 SO 2.OH  RNH 2.HCl Primary amine hy drochloride H OK COOK |  2 RNH 2 H OK COOK Primary amine Pot.oxalat e (Distillate) U CO NHR R2 NH.HCl  NaOH R2 NH  NaCl  H 2 O ST The liquid (mixture of oxamic ester+ tertiary amine) is subjected to fractional distillation when tertiary amine distils over. The remaining liquid is distilled with KOH to recover secondary amine. CONR 2 HOK COOK |  R 2 NH  |  C 2 H 5 OH Secondary COOK COOC 2 H 5 HOK amine Po t. o x alate (iii) Hinsberg's method : It involves the treatment of the mixture with benzene sulphonyl chloride, i.e., Hinsberg's reagent (C6H5SO2Cl). The solution is then made alkaline with aqueous alkali to form sodium or potassium salt of monoalkyl benzene sulphonamide (soluble in water). RNH 2.HCl  NaOH RNH 2  NaCl  H 2 O (4) Physical properties (i) Lower amines are gases or low boiling point liquids and possess a characteristic ammonia like smell (fishy odour). Higher members are solids. (ii) The boiling points rise gradually with increase of molecular mass. Amines are polar compounds like NH3 and have comparatively higher boiling points than non-polar compounds of similar molecular masses. This is due to the presence of intermolecular hydrogen bonding. H H H | | | H – N :   H – N :   H – N :    | R | | R R Hy drogen bonding in amines 1372 Nitrogen Containing Compounds (iii) Amines are soluble in water. This is due to hydrogen bonding between amine and water molecules. Amines are also soluble in benzene and ether. H H | |     H – O :   H – N :   H – O :   H – N :    | | | | H R H R But anilinium ion is less resonance stabilized than + + aniline. NH3 NH3 Hy drogen bonding b etween amine and water molecules No other resonating structure possible However, any group which when present on benzene ring has electron withdrawing effect (– NO2, – CN, – SO3H, – COOH – Cl, C6H5, etc.) decreases basicity of aniline (Nitroaniline is less basic than aniline as nitro group is electron withdrawing group (– I group) and aniline is more basic than diphenyl amine), while a group which has electron repelling effect (– NH2, – OR, R –, etc.) increases basicity of aniline. Toluidine is more basic than aniline as – CH3 group is electron repelling group (+ I group). ID Except the amines containing tertiary butyl group, all lower aliphatic amines are stronger bases than ammonia because of + I (inductive) effect. The alkyl groups, which are electron releasing groups, increase the electron density around the nitrogen thereby increasing the availability of the lone pair of electrons to proton or Lewis acids and making the amine more basic (larger Kb). Thus, it is expected that the basic nature of amines should be in the order tertiary > secondary > primary, but the observed order in the case of lower members is found to be as secondary > primary > tertiary. This anomalous behaviour of tertiary amines is due to steric factors, i.e., crowding of alkyl groups cover nitrogen atom from all sides and thus makes the approach and bonding by a proton relatively difficult which results the maximum steric strain in tertiary amines. The electrons are there but the path is blocked, resulting the reduced in its basicity. Thus, electron density is less on N atom due to which aniline or other aromatic amines are less basic than aliphatic amines. E3 (5) Chemical properties : The main reactions of amines are due to the presence of a lone pair of electrons on nitrogen atom. Amines are electrophilic reagents as the lone pair of electrons can be donated to electron seeking reagents, (i.e., electrophiles). 60 Solubility decreases with increase of molecular mass. D YG U Further greater the value of Kb or lower the value of pKb, stronger will be the base. The basic character of some amines have the following order, (i) The order of basic nature of various amines has been found to vary with nature of alkyl groups. Alkyl group C2H5 –  C6 H 5 NHCH 3  C6 H 5 NH 2 NH 3  C6 H 5 NHC 2 H 5  C6 H 5 NHCH 3  C6 H 5 NH 2  C6 H 5 NHC 6 H 5 In Toluidines –p-isomer > m- > o- R2NH > RNH2 > NH3 > R3N Chloroanilines–p-isomer>m-> o- RNH2 > NH3 > R2NH > NH3 > RNH2 > R2NH > R3N (ii) Basic nature of aromatic amines : In aniline or other aromatic amines, the lone pair present on nitrogen atom is delocalized with benzene ring by resonance. +NH 2 Phenylene diamines –p-isomer > m- > oNitroanilines–m-isomer > p- > o- ST (CH3)3C – :NH2 C6 H 5 N(C 2 H 5 )2  C6 H 5 NHC 2 H 5  C6 H 5 N(CH 3 )2 R2NH > RNH2 > R3N > NH3 (CH3)2CH – R3N N-alkylated anilines are stronger bases than aniline because of steric effect. Ethyl group being bigger than methyl has more steric effect, so N-ethyl aniline is stronger base than N-methyl aniline. Thus, basic character is, Relative strength U CH3 – R2 NH  RNH 2  C6 H 5 CH 2 NH 2  NH 3  C6 H 5 NH 2 +NH 2 +NH 2 – – –  Aniline is less basic than ammonia. The phenyl group exerts –I (inductive) effect, i.e., it withdraws electrons. This results to the lower availability of electrons on nitrogen for protonation.  Ethylamine and acetamide both contain an amino group but acetamide does not show basic nature. This is because lone pair of electrons on nitrogen is delocalised by resonance with the carbonyl group which makes it less availableNot foravailable protonation. due to –  N–H || + N–H | | H H Resonance hybrid delocalization – O |    CH 3 – C  N H 2  CH 3  C  N H 2 O Nitrogen Containing Compounds 1373 Tertiary amines do not react since they do not have replaceable hydrogen on nitrogen.  The compounds with least 's' character (sp3hybridized) is most basic and with more ‘s’ character (sp-hybridized) is least basic. Examples in decreasing order of basicity are,  2 RNH 2  2 Na  2[RNH ]– Na   H 2  2 R 2 NH  2 Na  2[R 2 N ]– Na   H 2  (sp ) CH 3CH 2CH 2 NH 2  H2C  CHCH 2 NH 2  HC  CCH 2 NH 2 2o amine X2 X2 RNH 2   RNHX   RNX 2 (CH 3 )2 NH  CH 3 NH 2  C6 H 5 NHCH 3  C6 H 5 NH 2 CH 3 CH 2 NH 2  HO(CH 2 )3 NH 2  HO(CH 2 )2 NH 2 D YG  2 R – NH 2  H 2 SO 4 (R N H 3 )2 SO 4– Alky lammonium sulphate (iv) Nature of aqueous solution : Solutions of amines are alkaline in nature.  RNH 2  HOH ⇌ R N H 3 OH – ⇌ [RNH 3 ]  OH –  R2 NH  HOH ⇌ R2 N H 2OH – ⇌ [R2 NH 2 ]  OH –  U R3 N  HOH ⇌ R3 N HOH – ⇌ [R3 NH ]  OH – ST The aqueous solutions of amines behaves like NH4OH and give ferric hydroxide precipitate with ferric chloride and blue solution with copper sulphate. 3 RNH 3OH  FeCl 3 Fe(OH )3  3 RNH 3Cl    RX RX RX RNH 2   RNH R    R – N R 2   (R – N R 3 )X – Pri.amine  HX Tert. amine Quaternary salt (vi) Reaction with acetyl chloride (Acylation) RNH 2  Pri. amine – HCl ClOCCH 3   RNHOCCH 3 N - Alky lacetamide – HCl R2 NH  ClOCCH 3  R2 NOCCH 3 Sec. amine Dialky l amine NaOH Halo -dialky l amine (ix) Reaction with Grignard reagent CH 3 CH 4  RNH  Mg  I I R2 NH  CH 3 – Mg – I CH 4  R2 N – Mg – I (x) Carbylamine reaction : This reaction is shown by only primary amines. This is a test of primary amines and is used to distinguish primary amines from secondary and tertiary amines. RNH 2  CHCl 3  3 KOH RNC (Alc.) Alky l isocy anide (carby lamine)  3 KCl  3 H 2 O Isocyanides are bad smelling compounds and can be easily detected. (xi) Reaction with nitrous acid (a) Primary amines form alcohols with nitrous acid (NaNO2+ HCl). Nitrogen is eliminated. RNH 2  HONO ROH  N 2  H 2 O Pri. amine Alcohol Methyl amine is an exception to this reaction, i.e., CH 3 NH 2  2 HONO CH 3 – O – N  O  N 2  2 H 2 O Methy l nitrite 2CH 3 NH 2  2 HONO CH 3 – O – CH 3  2 N 2  3 H 2 O Dimethy l ether (b) Secondary amines form nitrosoamines which are water insoluble yellow oily liquids. R 2 NH  HONO R 2 NNO  H 2 O (v) Reaction with alkyl halides (Alkylation) Sec.a mine Dihalo -alky l amine X2 R 2 NH   R 2 NX U (iii) Salt formation : Amines being basic in nature, combine with mineral acids to form salts.  NaOH ID CH 3 CH 2 NH 2  C6 H 5 CONH 2  CH 3 CONH 2 Alky lammonium chloride NaOH RNH 2  Mg  Electron withdrawing inductive effect of the –OH group decreases the electron density on nitrogen. This effect diminishes with distance from the amino group.  HX Alkylamine E3  Electron withdrawing (C6H5 –) groups decrease electron density on nitrogen atom and thereby decreasing basicity.  Sod.sa lt (viii) Action of halogens (CH 3 )2 NH  CH 3 NH 2  NH 3  C6 H 5 NH 2 R  NH 2  HCl R N H 3 C l Sod. salt  60 (sp ) (vii) Action of sodium 1o amine H  CH – N   CHC H  CH – C  N  CH 3 N 2 3 3 3 2 (sp 3 ) Therefore, all these above reactions are used to distinguish between 1 o , 2 o and 3 o -amines. N , N - Dialkyl acetamide Sec. amine Dialky l nitrosoami ne Nitrosoamine on warming with phenol and conc. H2SO4 give a brown or red colour which soon changes to blue green. The colour changes to red on dilution and further changes to blue or violet with alkali. This colour change is referred to Liebermann's nitroso reaction and is used for the test of secondary amines. 1374 Nitrogen Containing Compounds (c) Tertiary amines react nitrous acid to form nitrite salts which are soluble in water. These salts on heating give alcohols and nitrosoamines. R3 N  Tert.amine heat HONO [R3 NH ] NO 2–   R – OH  R2 N –N  O Alcohol Trialkyl ammoniumnitrite (xv) Ring substitution in aromatic amines : Aniline is more reactive than benzene. The presence of amino group activates the aromatic ring and directs the incoming group preferably to ortho and para positions. Nitrosoamine (a) Halogenation NH2 This reaction (nitrous acid test) is used to make distinction between primary, secondary and tertiary amines. (xii) Reaction with carbon di sulphide : This Hofmann’s mustard oil reaction is used as a test for primary amines. heat NR 2 SH S C  S R 2 NH   S  C 2  HgS  2HCl Black ppt. 2   No reaction HgCl Dialky l dithiocarb amic acid ID (xiii) Oxidation : All the three types of amines undergo oxidation. The product depends upon the nature of oxidising agent, class of amine and the nature of the alkyl group. However, if monosubstituted derivative is desired, aniline is first acetylated with acetic anhydride and then halogenation is carried out. After halogenation, the acetyl group is removed by hydrolysis and only monosubstituted halogen derivative is obtained. E3 RNC  S It may be noted that – NH2 group directs the attacking group at o- and p-positions and therefore, both o- and p-derivatives are obtained. NH2 NHCOCH3 NHCOCH3 U (a) Oxidation of primary amines H 2O [O ] RCH 2 NH 2   RCH  NH   RCHO  NH 3 Pri. amine KMnO 4 Aldimine Aldehy de H 2O [O ] R 2 CHNH 2   R 2 C  NH   R 2 CO  NH 3 D YG KMnO 4 + 3HBr Br 2, 4, 6-Tri Bromoaniline (white This reaction is used as a test ppt.) for aniline. Alky ldithiocarb amic acid Alky lisothiocy a nate (Mustard oil smell) Br 60 RNH 2  S  C 1 Br + 3Br2 NHR HgCl 2   SH S C S NH2 Ketimine Ketone Br (CH3CO)2O –CH3COOH Br2 Acetanili de Aniline pBromoacetanilid e (minor) (b) Oxidation of secondary amines [O ] R 2 NH   R 2 N – NR 2 Sec. amine KMnO 4 Tetra -alky l hydrazine [O ] ; R 2 NH   H 2 SO 5 (c) Oxidation of tertiary amines : Tertiary amines are not oxidised by potassium permanganate but are oxidised by Caro's acid or Fenton's reagent to amine oxides. U R 3 N  [O] [R 3 N O] Tert. amine Amine oxide (xiv) Reaction with other electrophilic reagents ST Aldehyde Schiff's base O O || || Carbony l chloride Dialky l urea (Sy mmetrical) 2 RNH 2  Cl – C – Cl RNH – C – NHR  2 HCl O || RNHH  O  C  N – R  RNH – C – HN R  Isocy anate Dialky l urea (Unsy mmetrical) S || RNHH  S  C  N – R  RNH – C – NH R  Isothiocy anate NH2 NH2 Br H2O, H+, CH3COOH + – + o-Bromoaniline (minor) Br p-Bromoacetanilide (major) Br p-Bromoaniline (major) Acetylation deactivates the ring and controls the reaction to monosubstitution stage only because acetyl RNH 2  O  CH R  RN  CH R  Pri. amine NHCOCH3 R 2 NOH Dialkyl hydroxylamine Dialky l thiourea group is electron withdrawing group and therefore, the electron pair of N-atom is withdrawn towards the carbonyl group. (b) Nitration : Aromatic amines cannot be nitrated directly because they are readily oxidized. This is because, HNO3 is a strong oxidising agent and results in partial oxidation of the ring to form a black mass. Therefore, to solve this problem, nitration is carried out by protecting the –NH2 group by acetylation. The acetylation deactivates the ring and therefore, controls the reaction. Nitrogen Containing Compounds The hydrolysis of nitroacetanilides removes the protecting acyl group and gives back amines. NHCOCH3 || HNO3, H2SO4 288 K Acetyl chloride Aniline Acetanilide NHCOCH3 oNitroacetanilide NH2 NH2 – CH COOH H23O, H+ NO2 (6) Uses pNitroaniline (major) pNitroacetanilid e (c) Sulphonation (i) Ethylamine is used in solvent extraction processes in petroleum refining and as a stabiliser for rubber latex. NH3+ HSO4– + H2SO4 (ii) The quaternary ammonium salts derived from long chain aliphatic tertiary amines are widely used as detergents. ID NH2 Heat 453-473 K (iii) Aliphatic amines of low molecular mass are Anilinium hydrogen sulphate used as solvents. U Aniline Zwitter ion structure (II) E3 o-Nitroaniline (minor) Sulphanilic acid (I) (structure II) which has acidic and basic groups in the same molecule. Such ions are called Zwitter ions or inner salts. + NO2 SO3– The sulphanilic acid exists as a dipolar ion NO2 + SO3H NHCOCH3 NO2 O + Cl – C – CH3 NH3+ 60 NH2 NH2 1375 Table : 29.3 Distinction between primary, secondary and tertiary amines Test Primary amine Tertiary amine Bad smelling carbylamine (Isocyanide) is formed. No action. No action. Action of CS2 and HgCl2. (Mustard oil test) Alkyl isothiocyanate is No action. No action Action of nitrous acid. Alcohol is formed with evolution of nitrogen. Forms nitrosoamine which Forms nitrite in cold gives green colour with phenol and conc. H2SO4 (Liebermann's test). which on heating gives nitrosoa- mine which D YG Action of CHCl3 and Secondary amine formed which has pungent smell like mustard oil. U alcoholic KOH. (Carbylamine test) responds to Liebermann's test. Acetyl derivative is formed. Acetyl derivative is formed. No action. Action of reagent. Monoalkyl sulphonamide is Dialkyl No action. formed which is soluble in KOH. formed which is insoluble in KOH. 3 molecules (moles) of CH3I 2 moles of CH3I to form One mole of CH3I to to form quaternary salt with one mole of primary amine. quaternary salt with one mole of secondary amine. form quaternary salt with one mole of tertiary amine. ST Action of acetyl chloride. Hinsberg's Action of methyl iodide.  Aniline does not form alcohol with nitrous acid but it forms benzene diazonium chloride which shows dye test. sulphonamide is Aniline Aniline was first prepared by Unverdorben (1826) by dry distillation of indigo. In the laboratory, 1376 Nitrogen Containing Compounds it can be prepared by the reduction of nitrobenzene with tin and hydrochloric acid. 2 CH 3 CH 2 NH 2   CH 3 CH 2 OH Sn , HCl C 6 H 5 NO 2  6 H   C 6 H 5 NH 2  2 H 2 O Nitrobenze ne (2) Conversion of ethylamine to methylamine (Descent) HNO Aniline Ethy lamine Ethanol [O ]   CH 3 CHO K 2 Cr 2 O7 H 2 SO 4 Acetaldehyde [O ] 2   CH 3 COOH   CH 3 COCl SOCl with NH 3 Br2   CH 3 CONH 2   CH 3 NH 2 From double salt, aniline is obtained by treating with conc. caustic soda solution. (C6 H5 NH 3 )2 SnCl 6  8 NaOH 2C6 H5 NH 2 HNO 2 7 C2 H 5 NH 2    C2 H 5 OH 2 2   K Cr O Ethy lamine Ca (OH )2 7 CH 3 CHO 2 2   CH 3 COOH   (CH 3 COO )2 Ca H 2 SO 4 Acetaldehyde Acetic acid  CH 3 COCH 3 (4) Conversion of propionic acid to SOCl 2 NH 3 (i) CH 3 CH 2 COOH    CH 3 CH 2 COCl   Propionic aicd ID D YG Properties Aniline when freshly prepared is a colourless oily liquid (b.p. 184°C). It has a characteristic unpleasant odour and is not poisonous in nature. It is heavier than water and is only slightly soluble. It is soluble in alcohol, ether and benzene. Its colour changes to dark brown on standing. It shows all the characteristic reactions discussed earlier. U Uses : (1) It is used in the preparation of diazonium compounds which are used in dye industry. (2) Anils (Schiff's bases from aniline) are used as antioxidants in rubber industry. ST (3) It is used for the manufacture of its some derivatives such as acetamide, sulphanilic acid and sulpha drugs, etc. (4) It is used as an accelerator in vulcanizing rubber. Some important conversions (1) Conversion of methylamine to ethylamine (Ascent) Methy l iodide Ethy lamine N3H 4 5 CH 3 CH 2 CH 2OH  (ii) CH 3 CH 2 COOH  LiAlH PBr Ether Propionic acid n - Propy l alcohol KCN CH 3 CH 2CH 2 Br   CH 3 CH 2CH 2CN Propyl bromide Propyl cyanide Na C2 H 5 OH    CH 3 CH 2 CH 2 CH 2 NH 2 o r LiAlH 4 (5) Conversion diaminobutane of n-Butylamine ethylene to 1,4- Br2 NaCN CH 2  CH 2   CH 2 Br.CH 2 Br    Ethy lene CCl 4 Ethy lene bromide LiAlH 4 NCCH 2CH 2 CN   NH 2 CH 2CH 2 CH 2 CH 2 NH 2 Ethy lene cy anide 1,4 - Diaminobut ane Diazonium salts The diazonium salts have the general formula ArN 2 X – , where X– may be an anion like Cl–, Br– etc. and the group N 2 ( N  N  ) is called diazonium ion group. (1) Nomenclature : The diazonium salts are named by adding the word diazonium to the name of the parent aromatic compound to which they are related followed by the name of the anion. For example, N+  NCl– Cl   CH 3 CN  CH 3 CH 2 NH 2 KOH Propionami de Benzenediazonium chloride HNO 2 PI3 CH 3 NH 2    CH 3 OH   CH 3 I Methy l alcohol Br2 CH 3 CH 2 CONH 2   CH 3 CH 2 NH 2 H 2 SO 4 (conc.) 200 C 2C 6 H 5 Cl  2 NH 3  Cu 2 O   2C 6 H 5 NH 2  Cu 2 Cl 2  H 2 O Methy lamine Propiony l chloride or C 2 H 5 COOH  C 2 H 5 NH 2 U Aniline is also obtained on a large scale by the action of amine on chlorobenzene at 200°C under 300400 atm pressure in presence of cuprous catalyst. 300  400 atm Acetone (i) Ethylamine, (ii) n-Butylamine. NH2 Na2CO3 Calcium acetate heat E3 On a commercial scale, aniline is obtained by reducing nitrobenzene with iron filings and hydrochloric acid. H 2 SO 4 Ethy l alcohol K Cr O 6 NaCl  Na2 SnO 3  5 H 2O Fe3/HCl 30% Methylamine (3) Conversion of ethylamine to acetone Double salt NH3+Cl– KOH Acetamide 2C6 H 5 NH 2  SnCl 4  2 HCl (C 6 H 5 NH 3 )2 SnCl 6 NO2 Acety lchloride 60 Aniline produced combines H 2 SnCl 6 (SnCl 4  2 HCl) to form a double salt. Acetic acid N+  NCl– CH3 p-Toluenediazonium chloride HO LiAlH 4 NaCN Methy l cy anide Ethy lamine N+  NCl– o-chlorobenzenediazonium chloride N+  NBr– mHydroxybenzenediazonium bromide Nitrogen Containing Compounds 1377 The diazonium salt may contain other anions also such as NO 3– , HSO 4– , BF4 etc. This reaction is called Sandmeyer reaction. N+  NHSO4– When the diazonium salt solution is warmed with copper powder and the corresponding halogen acid, the respective halogen is introduced. The reaction is a modified form of Sandmeyer reaction and is known as Gattermann reaction. p-Nitrobenzenediazonium hydrogen sulphate (2) Preparation of diazonium salts : NaNO 2  HCl NaCl  HONO NH2 N2+Cl– NaNO2 HCl, 273 K The reaction of + NaCl + H2O Benzene diazonium chloride aromatic converting Cl Cu HCl + N2 (d) Replacement by iodo (–I) group primary amine to diazonium salt is called diazotisation. E3 Aniline N2+Cl– 60 O2N N2+Cl– I Heat + KI (3) Physical properties of diazonium salts Iodobenzene ID (i) Diazonium salts are generally colourless, crystalline solids. (ii) These are readily soluble in water but less soluble in alcohol. (e) Replacement by – F group N2+Cl– U (iii) They are unstable and explode in dry state. Therefore, they are generally used in solution state. D YG (iv) Their aqueous solutions are neutral to litmus and conduct electricity due to the presence of ions. (4) Chemical properties of diazonium salts (i) Substitution reaction : In substitution or replacement reactions, nitrogen of diazonium salts is lost as N2 and different groups are introduced in its place. N2+BF4– + HBF4 Fluoroboric acid Benzene Fluorobenzen diazonium e fluoroborate This reaction is called Balz Schiemann reaction. (f) Replacement by Cyano (– CN) group N2+Cl– CN CuCN U OH + H2O Warm + N2 Cyanobenzen e The nitriles can be hydrolysed to acids. + N2 + HCl CN Phenol ST Benzene diazonium chloride COOH Hydroly sis (b) Replacement by hydrogen Benzoic acid N2+Cl– This method of preparing carboxylic acids is more useful than carbonation of Grignard reagents. + N2 + H3PO3+ HCl + H3PO2 + H2O Hypophosphoric acid Benzene diazonium chloride N2+BF4– HBF (c) Replacement by–Cl group N2 (g) Replacement by – NO2 group N2+Cl– Benzen e 4 +Cl– F Heat (a) Replacement by –OH group N2+Cl– + N2 + KCl NaNO2 Cu NO2 + NaBF4 + N2 Cl Diazonium fluoro borate Cu2Cl2 + N2 Chlorobenzen e Nitrobenzene 1378 Nitrogen Containing Compounds (h) Replacement by thio (–SH) group N2+Cl– SH OH– 273-278 K + KSH Na+O3–S Methyl orange + N2 + KCl (ii) Coupling reactions : The diazonium ion acts as an electrophile because there is positive charge on terminal nitrogen. It can react with nucleophilic aromatic compounds (Ar–H) activated by electron donating groups (– OH and – NH2), which as strong nucleophiles react with aromatic diazonium salts. Therefore, benzene diazonium chloride couples with electron rich aromatic compounds like phenols and anilines to give azo compounds. The azo compounds contain –N = N– bond and the reaction is called coupling reaction. N+  NCl– + OH 60 Thiophenol  Diazonium salts are highly useful intermediates in the synthesis of large variety of aromatic compounds. These can be used to prepare many classes of organic compounds especially aryl halides in pure state. For example,. 1, 2, 3-tribromo benzene is not formed in the pure state by direct bromination of benzene. However, it can be prepared by the following sequence of NH reaction starting NH2from p-nitroaniline 2 through the formation of diazonium salts as : Br Br Br2 E3 Potassium hydro sulphide NO2 p-Nitroaniline ID Br Base (pH  9273-278 10) K N=N U OH p-Hydroxyazobenzene (yellow) N+  NCl– + D YG NH2 H+(pH  4.5) K 273-278 N=N CH3 U H+(pH  4.5) K 273-278 N N=N CH3 N,N-dimethyl-paminoagobenzene (orange ) ST Coupling occurs para to hydroxy or amino group. All azo compounds are strongly coloured and are used as dyes. Methyl orange is an important dye obtained by coupling the diazonium salt of sulphanilic acid with N, N-dimethylaniline. Na+O3–S NH2 NaNO2, HCl 273-278 K Sod. Salt of sulphanilic acid Na+O3–S Na+O3–S Br Br Br N  N Cl + H N  NCl N(CH3)2 N, NDimethylaniline Br Diazotisati on N2+Cl– NH2 Br Br N CH3 Sn, HCl NO2 CH3 N+  NCl– + Br CuBr Br Br Br Br Br NO2 NH2 p-Aminoazobenzene (orange) Diazotisati on NO2 N2+Cl– Phenol N(CH3)2 N=N Br H3PO2 1, 2, 3-Tribromo benzene (5) Uses of diazonium salts (i) For the manufacture of azo dyes. (ii) For the industrial preparation of important organic compounds like m-bromotoluene, mbromophenol, etc. (iii) For the preparation of a variety of useful halogen substituted arenes.