Nitro compounds.pdf

Nitro compounds They are compounds containing one or more nitro groups attached to alkyl or aryl groups. 1/2 O O O R N R N R...

Nitro compounds They are compounds containing one or more nitro groups attached to alkyl or aryl groups. 1/2 O O O R N R N R N 1/2 O O O resonance structure resonance hybrid Nomenclature: They are named as substituted alkane or arene. CH3CH2CH2NO2 O2NCH2CH2CH2CH2CH2NO2 1-nitropropane 1,5-dinitropentane NO2 NO2 NO2 NO2 O 2N NO2 NO2 1,3,5-trinitrobenzene 1,2,3-trinitrobenzene nitrobenzene or sym.trinitrobenzene or vicinal trinitrobenzene NO2 NO2 NO2 1,2,4-trinitrobenzene or asym-trinitrobenzene Preparation: I. Direct nitration: Aliphatic nitro compounds were prepared by heating with conc. nitric acid at 500oC and it gives a mixture of products. 500oC CH3CH2CH3 Conc. HNO3 CH3CH2CH2NO2 CH3CHCH3 CH3CH2NO2 CH3NO2 NO2 1 Also, sodium nitrite or silver nitrate was used in the synthesis of aliphatic nitro compounds. RX AgNO3 RNO2 OR NaNO2 H2C COOH NaNO2 H2C COOH CH3NO2 - CO2 Cl O2N Unstable Ter Meer reaction: While the introduction of a nitro group on aromatic compound was achieved by using one of the nitrating reagents which are: 1- Mixed acids eg. c.HNO3/c.H2SO4. (nitrating mixture) is the most commonly used. 2- Fuming nitric acid which is c.HNO3 saturated with NO2 gas. 3- Nitric acid in organic solvent eg. HNO3/CH3COOH. 4- Acyl nitrates, these are also called "ortho-nitrating agents" O O eg. CH3C O NO2 C6H5 C O NO2 or (acetylnitrate) (benzoyl nitrate). 5- Nitronium salts eg. N+O2F–/BF3 or N+O2–ClO4– (nitronium fluoride) (nitronium perchlorate) The choice of nitrating agent is according to reactant and product desired. i.e. if the ring is more electron rich  nitration reaction will be easy and we use a mild reagent and so if less electron rich (electron deficient) it requires stronger reagent. 2 1. Direct nitration of benzene: (EAS) NO2 NO2 c.HNO3/ c.HNO3/ + c.H2SO4 c.H2SO4 NO2 m.dinitrobenzene fuming HNO3/H2SO4 NO2 100oC 5 days. O2N NO2 Since the nitro group decreases the electron density on the ring  requires stronger reagent for further nitration. 2. Nitration of substituted benzene: OCH3 OCH3 OCH3 O2N c.HNO3/ + + c.H2 SO4 anisole NO2 minor major OCH3 OCH3 O NO2 + CH3 C O NO2 (obtained from HNO3/Ac2O) pure o-isomer Mech: O O O CH3 C O C CH3 + HNO3 CH3 C O NO2 + CH3COOH acetyl nitrate 3  H 3C O H3C O H 3C H 3C C O: H 3C O H3C C + C + O O O O O NO2 NO2 O 2N "six membered ring" O CH3 C O - H 3C H3C O O NO2 H + - H+ NO2 This is through "six center rearrangement". The o-nitrating agent reacts with the lone pair of heteroatom attached to benzene ring. 3. Nitration of phenol and aniline: Nitration of phenol and aniline gives a mixture of mono- di- and trinitro products as they are highly reactive. OH OH O2N NO2 c.HNO3/c.H2SO4 Picric acid NO2 Protection of OH and NH2 groups is carried out before nitration by acylation reactions using acetyl chloride or acetic anhydride. 4  O OH O C CH3 c.HNO3/c.H2SO4 + CH3COCl or Ac2O phenylacetate (ester) O- Na + OH O COCH3 H+ NaOH (hydrolysis) NO2 NO2 NO2 The acetate group is bulky  gives p-isomer only and it is less reactive than OH  prevent polynitration. O NH2 NH C CH3 NHCOCH3 CH3COCl or Ac2O c.HNO3/c.H2SO4 acetanilide NO2 p-nitroacetanilide 70% H2SO4 NH2 NH2.H2SO4 NaOH NO2 NO2 5  O O NH C CH3 NH C CH3 NH2 NO2 + NO2 HNO3/Ac2O H /H2O (acetylnitrate) Oleum NHCOCH3 NHCOCH3 NO2 c.HNO3/c.H2SO4 acid hydrolysis SO3H SO3H If nitration of aniline in strong acidic medium protonation of NH 2 group occur to give anilinium ion which is electron withdrawing group therefore m-directing. This is called “m-nitration”. + - + - NH2 NH3HSO4 NH3HSO4 NH2 c.HNO3 c.HNO3 NaOH c.H2SO4 c.H2SO4 NO2 NO2 anilinium bisulphate In case of reactive compounds like phenol, nitrosation followed by oxidation may be used. Since nitrosonium ion is a weak electrophile  it reacts with reactive rings only as phenol and only in p-position. OH OH OH HNO3 eg.5 + HNO2/H2 SO4 oxidation NO NO2 P-nitrosophenol + - H2O + - HO NO + H2 SO4 H O NO NO + HSO4 H nitrosonium ion (weak electrophile) 6 II. Indirect method from amines: 1. By oxidation: NH2 O NO2 CF3 C O O H/CH2Cl 2 one step oxidation peroxy trifluoroacetic acid N O NO2 H2SO5 dil. HNO3/H2O2 Caro's acid nitrosobenzene nitrobenzene 2. From diazonium salt: + - NH2 N N BF4 NO2. NaNO2/HBF4 or HCl NaNO2/Cu/ or. + N2 0 - 5oC HNO2/Cu/ Reactions of aliphatic nitro compounds: 1- Reduction: [H] [H] [H] R NO2 R N R NHOH R NH2 O nitro nitroso N-alkyl hydroxylamine amine Nitro compounds are reduced to the corresponding primary amines by using : - Catalytic reduction - Metal in acidic medium - Lithium aluminium hydride H2 / Ni or Zn / H R NO2 R NH2 or LiAlH4 They are also reduced into the corresponding hydroxylamine derivatives via reaction with metal in neutral medium. 7  Zn / NH4Cl R NO2 R NHOH N-alkyl hydroxylamine 2- Condensation with carbonyl compounds: Nitroalkanes condense with aldehydes and ketones in presence of base. This is occurred because nitroalkanes have active methylene group that loses its acidic proton to produce carbanion which is stabilized by resonance. O O R C N R C N H H O O NaOH CHO CH3NO2 CH - H2O HC NO2 nitrostyrene Mechanism: O O OH H H2C N CH2 H2C N NO2 O O O O C CH H CH2 O2N H - H2O OH CH CH HC NO2 CH H O2N 8  3- Mannich reaction: It includes the reaction of primary or secondary amine with formaldehyde and compound containing active methylene group. CH3NH2 HCHO CH3NO2 CH3NHCH2CH2NO2 Mechanism: H3C O H3C O H3C OH -H +H NH C N CH2 N CH2 H H H3C H3C H3C +H H H3C H3C - H2O H3C O H N CH2 N CH2 N CH2 H3C H3C H3C O H3C H2C N N CH2CH2NO2 O H3C Reactions of aromatic nitrocompounds: 1. Reactions of benzene ring. 2. Reactions of nitro group. I. Reactions of benzene ring: 1) Electrophilic aromatic substitution: EAS NO2 group is electron withdrawing, deactivating, m-orienting group towards electrophilic aromatic substitution reactions. 9  NO2 NO2 c.HNO3/c.H2SO4 NO2 NO2 Oleum SO3H NO2 Cl 2/AlCl 3 Cl F.C. alkylation or F.C. acylation Fails No Reaction 2) Nucleophilic aromatic substitution: SNAr Nitro group activates the ring toward nucleophilic substitution by – I and –R effect. It is o,p-orienting and the reaction mechanism proceeds by SNAr involving “Meisenhiemer intermediate” which is stabilized by the nitro group. There are three types of substitution reactions 1. Substitution of hydride o- and p- to NO2 group. 2. Substitution of halide if o- or p- to nitro group. 3. Substitution of NO2 group if more than one nitro o- or p- to each other. 10 1. Substitution of hydride: NO2 NO2 NO2 OH Fusion KOH + air major OH NO2 NO2 NH2 NaNH2/liq NH3 + major NH2 minor Here o-isomer is major due to – I and –R effect of NO2 group while p- isomer is due to –R only. NO2 NO2 NO2 OH NaOH + K3[Fe(CN) 6] NO2 NO2 NO2 OH major minor Potassium ferricyanide is an oxidizing agent  help in removal of hydride. NO2 NO2 NaOH K3[Fe(CN) 6] O2N NO2 O2N NO2 OH Picric acid 2. Substitution of halogen: Halogens are easily substituted if in o- or p- positions to NO2 group. 11  Cl OH NaHCO3/130oC or KOH NO2 NO2 CN KCN NO2 OCH3 - + CH3 ONa NO2 NH2 alc. NH3 NO2 Reactivity toward SNAr reaction "replacement of Chloride" Cl Cl Cl Cl Cl O 2N NO2 O 2N NO2 NO2 NO2 NO2 NO2 NO2 3. Substitution of nitro group: If the ring has two nitro groups o- or p- to each other, substitution of one of them occur by the nucleophile. 12  NO2 OH NO2 NO2 NaOH + NaNO2 o - or p-dinitro benzene NH2 NO2 alc. NH3 + HNO2 100oC OCH3 -+ NO2 CH3ONa/ + NaNO2 SH NO2 NaHS + NaNO2 mechanism: NO2 HO NO2 O NO2 - + HO O HO NO2 N - + N slow O - O OH HO NO2 NO2 HO O NO2 NO2 + N - NO2 O II. Reactions of nitro group: 1) Reduction of nitro group: a) Catalytic reduction. b) Chemical reduction. NO2 N O NHOH NH2 [H] [H] [H] nitro nitroso N-phenyl hydroxylamine 13 a) Catalytic reduction: NO2 NH2 H2/Ni or Pt or Pd b) Chemical reduction: The reduction product depends on the: 1- Strength of the reducing agent. 2- pH of the medium. In acidic medium: NO2 NH2... Fe or Sn or Zn/ HCl or SnCl2/HCl In neutral medium: NO2 NHOH. Zn/NH4Cl + ZnCl2 + NH3 + H2O N-phenyl hydroxylamine 14 In alkaline medium: NO2 O NaOH/CH3OH N N Azoxybenzene SnCl2/NaOH NH2 SnCl2/NaOH Zn/HCl N N Azobenzene Zn/NaOH Zn/NaOH NH NH Hydrazobenzene CHO CHO SnCl 2/HCl NO2 NH2 We use SnCl2 in acidic medium for reduction of nitro compounds containing formyl group. However, if there is more than one nitro group selective reduction of one of them could be carried out by using (NH4)2S or Na2S. NO2 NH2 (NH4) 2S Na2S NO2 50oC NO2 15 2) Benzidine rearrangement: "Intramolecular rearrangements" /HCl or H2SO4 NH NH H2N NH2 Hydrazobenzene 4,4'-diaminobiphenyl + + H2 N NH2 2H + NH NH Protonation H - 2H + H2N NH2 H2N NH2 + + H 3) Rearrangement of N-phenyl hydroxylamine: It occurs in acidic medium and the product depends on the conditions. NHOH NH2 aqueous H2SO4.. P-aminophenol Nu : H2O OH NH2 P-chloroaniline..HCl - Nu : Cl Cl NH2 H2SO4/CH3OH.. - Nu : OCH3 P-anisidine OCH3 H2SO4/CH3CH2OH NH2.. - Nu : OC2H5 P-phenitidine OCH2CH3 mechanism: 16 III. Condensation with aldehydes: The three nitro groups activate CH3 group so the hydrogens become acidic and react with aldehydic group in alkaline medium. 17 18