Aromatic Halogen Compounds PDF

Aromatic halogen compounds Halogen compounds can be obtained from three types of reactions: a- addition reactions b-substitution reactions c-side-chain substitution reactions [A] addition reactions: These compounds can be obtained by the addition of h...

Aromatic halogen compounds Halogen compounds can be obtained from three types of reactions: a- addition reactions b-substitution reactions c-side-chain substitution reactions [A] addition reactions: These compounds can be obtained by the addition of halogens ( Cl2, Br2) to benzene in presence of indirect sun light and absence of the catalyst. Cl Cl Cl 3 Cl2 gamexan hv Cl Cl ( hexachloro benzene) Cl [B] Substitution reactions products: 1-Halogens ( Cl2, Br2) react with benzene or alkyl benzene in presence of a catalyst such as ( low FeCl3 and in absence of sun light to give substitution products in benzene ring. temperature) Cl2 Cl + HCl FeCl3 chloro benzene CH3 Cl2 CH3 CH3 + FeCl3 Cl Cl o-chloro toluene p-chloro toluene The extend of halogenation depends on the amount of halogen used Iodine compounds: Iodination can be carried out in the presence of an oxidizing agent e.g., nitric acid mercuric oxide, ect.. the yield of the iodo-compound is usually very good. 2 C6H6 + I2 (HNO3) 2 C6H5-I +H2O  2-Sandmayer reaction: Replacement of diazonium group by -Cl or -Br is carried out by mixing the solution of freshly prepared diazonium salt with cuprous chloride or cuprous bromide ArN2X + CuX ArX + N2 ( X= Cl or Br). Gattermann reaction: Sandmayer reaction can be carried out by modification, in which the copper powder and hydrogen halide are used in place of cuprous halide. Replacement of the diazonium group by iodide does not require the use of a cuprous halide or copper, the diazonium salt and potassium iodide are simply mixed together and allowed to react. Cu / HCl Ar-Cl chloro benzene Cu /HBr ArN2 X Ar-Br bromo benzene KI Ar-I if Ar = C6 H5 - iodo benzene Replacement of the diazonium salt by fluoride -F can be carried out by using fluoroboric acid ( HBF4). C6H5N2Cl + BF4- C6H5-F fluoro benzene. Properties of Aryl halides: The aryl halides differ from alkyl halides, this is due to the resonance in aryl halides which leads to give the C-X bond some of the double bond character ( i.e. this bond become difficult to be broken ).  X X X X X hybrid structure This also explain why the halogen atom in aryl halides can not be replaced by nucleophiles except under very drastic reaction conditions.- However, the presence of certain groups at certain positions of the ring markedly activates the halogen of aryl halides towards displacement. 1- with aqueous NaOH: Chlorobenzene is converted into phenol by aqueous NaOH only at temp. over 300 C. The presence of a nitro group ortho or para to the chlorine increases its reactivity so, p-chloro benzene is converted into p-chloro phenol by treatment with aqueous NaOH at 160 C.Phenol is obtained from 2,4-dichlorobenzene by treatment with hot aq. NaOH and from 2,4,6-trichlorobenzene by simple treatment with water.  Cl OH aq. NaOH, 300C Cl OH Cl OH aq. NaOH, 160 C 2,4-dichlorobenzene o-dihydroxybenzene ( catechol) Cl OH H2 O, warm Cl Cl HO OH 2,4,6-trichlorobenzene 2,4,6-trihydroxybenzene 2-with aqueous NH3: Chlorobenzene reacts with ammonia in presence of a catalyst such as CuO at 200C and under pressure to give aniline. 2 NH3, CuO, 200C 2 Cl 2 NH2 + CuCl + H 2O Bromobenzene reacts with KNH2 in liquid ammonia to produce aniline. Br KNH2 NH2 liq. NH3 The mechanism of this reaction involves elemination-addition reaction through the formation of an intermediate called benzyne as follow:  Br + NH3 + Br H NH2 benzyne NH2 NH2 NH2 NH2 + NH3 The benzyne intermediate can be trapped through its reaction with diene under Diels- Alder reaction, for example it reacts with furan to form Diels-Alder adduct as follow: + O benzyne O 3-with cuprous cyanide: They react with CuCN to form aryl cyanides which on hydrolysis give the corresponding acids. Cl CN CO 2H CuCN hydrolysis Chloro benzene phenyl cyanide benzoic acid 4-Wurtz- Wittig reaction: Heating of aryl halides with alkyl halides in presence of metallic sodium give alkyl benzenes [ see the preparation of alkyl benzene ]. C6H5-Br + CH3Br + 2Na C6H5-CH3 + 2NaBr bromo benzene methyl bromide toluene 5-formation of Grignard’s reagent: Aryl halides react with Mg in presence of water free ether as a solvent to give aryl magnesium halides where the reactivity of halogen in this reaction are in the following order I2  Br2  Cl2. C6H5-I + Mg/ether C6H5-MgI iodo benzene phenyl magnesium iodide Preparation of DDT. Cl Cl H2 SO 4 2 Cl + CCl 3 CHO Cl C CH conc. Cl chlorobenzene chloral Cl [ c ] Side- chain substitution compounds: This type of halogenated compounds can be prepared by 1-Halogenation: This type of halogenation ( chlorination and bromination ) favour the high temperature and light. Chlorination of toluene is carried out stepwise to give mono, di, and trihalo derivatives. CH3 CH2Cl CHCl 2 CCl 3 Cl2 Cl2 Cl2 hv hv hv benzylchloride benzalchloride benzotrichloride Halogenation of alkyl benzene proceeds in this order 3  2 1carbon atom. 2-Chloromethylation: Benzene reacts with formaldehyde and HCl in the presence of ZnCl2 as Lewis acid catalyst and in methylene chloride as a solvent to give benzyl chloride. C6H6 + CH2O /HCl C6H5CH2Cl benzyl chloride Mechanism: the mechanism of the reaction is similar to Fridel-Craft alkylation reaction. ( suggest the mechanism ). Chemical properties: The halogen in the side-chain undergoes the same reactions as those of aliphatic alkyl halides. C6H5CH2Cl + aq. NaOH C6H5CH2OH benzyl alcohol C6H5CHCl2 + aq. NaOH C6H5CHO benzal chloride benzaldehyde C6H5CCl3 + aq. NaOH C6H5CO2H benzotrichloride benzoic acid C6H5CH2Cl + alc. NH3 C6H5CH2NH2 benzyl amine C6H5CH2Cl + KCN C6H5CH2CN C6H5CH2CO2H Phenylacetic acid  ALIPHATIC AMINES Aliphatic amines can be considered as derivatives from ammonia by replacing hydrogen atoms by the alkyl groups and they classified into primary, secondary and tertiary amines. Aliphatic amines can be considered as derivatives of ammonia (NH3), R-NH2 R2NH R3N primary amines secondary amines tertiary amines Nomenclature: Aliphatic amines are named according to the alkyl groups attached to the nitrogen by adding the word amine CH3-NH2 CH3NHCH3 ( CH3)3N methyl amine dimethyl amine trimethyl amine Methods of preparations: 1- Ammonolysis of alkyl NH3 NH3 a)- R X R NH3X R NH2 + NH4X NH3 NH3 CH3Cl CH3NH3Cl CH3NH2 + NH4Cl methyl chloride methyl amine RX + HX b)- R NH2 R2NH CH3Cl CH3 NH2 ( CH3 )2NH + HCl R2NH R-X c)- R3N + HX CH3Cl ( CH3 )3N + HCl (CH3)2NH trimethyl amine 2-Catalytic reduction of alkyl cyanides: H2/Ni R-C N RCH 2NH2 alkyl cyanide H2 / Ni CH3CN CH3CH2NH2 methyl cyanide ethyl amine 3-Hofmann degradation reaction: Action of bromine and sodium hydroxide on amides ( -CONH2 ) O C NH2 + Br2 + NaOH R NH2 +Na2CO3 + NaBr + H2O R CH3CONH 2 + Br2 +NaOH CH3-NH2 + Na2CO3 + NaBr +H2O acetamide methyl amine 4- Gabriel phthalimide synthesis : O O O KOH R-X NH NK N-R O O O phthalimide pot.phthalimide HCl/H2O NaOH/H2O CO2H CO2Na + RNH 3Cl R-NH2 + CO2H CO2Na phthalic acid sod.phthalate 5-Reductive amination: Aldehydes and ketones can be reduced by H2/Ni in presence of ammonia to give primary amines: H H H2/Ni C O + NH3 R C NH R CH2NH2 R aldehyde imine 1o amine H2/Ni CH3CHO + NH3 CH3CH=NH CH3CH2NH2 ethyl amine  R` R` R` H2/Ni R C O + NH3 R C NH R C NH2 CH3 CH3 CH3 H2/Ni CH3 C O + NH3 CH3 C NH CH3 C NH2 acetone isopropyl amine Physical properties of amines: Like ammonia , amines are polar compounds and except ter.amines they can form intramolecular hydrogen bonding. H H H R N H N H N R R H H-bonding Therefore amines have higher boiling points than non-polar compounds of the same molecular weight, but they have lower boiling points than alcohols. Chemical reactions of amines: 1- Basicity: Aliphatic amines more basic than ammonia due to the presence of alkyl groups which have donating properties i.e increase the electron density on nitrogen atom and hence increase the basicity, therefore we expect than tertiary amines more basic than secondary amines and the later more basic than primary amines. They react rapidly with mineral acids to give the corresponding salts. CH3CH2NH2 + HCl → CH3CH2NH3+Cl- ethyl amine ethyl amine hydrochloride 2- Alkylation: Amines can be alkylated in presence of alkyl halides to give the quaternary ammonium salts as the final stage of alkylation.  H R R RX RX RX R NH2 R-N-R R-N-R R-N-R X R ( see preparation of amines ). 4-Acylation: Action of acetyl chloride or acetic anhydride on amines. CH3NH2 + CH3COCl CH3NHCOCH3 + HCl methyl amine acetyl chloride N-acetyl methyl amine 3-Reaction with nitrous acid: This reaction used for differentiation between primary, secondary and tertiary amines: a-Primary amines react with nitrous acid with evolution of nitrogen gas to give alcohols. R-NH2 + HNO2 R-OH + N2 + H2O CH3CH2-NH2 + HNO2 CH3CH2OH + N2 + H2O ethyl amine ethanol b- Secondary amines give N-nitroso dialkyl amine: H N O HONO R-N-R` R R` + H2O N N O ( NaNO2/ HCl) CH3NHCH 3 CH3 N CH3 + H2O N-nitrosodimethyl amine c-Tertiary amines does not react with nitrous acid.  Aromatic amines Aromatic amines contain an amino group ( NH2 ) which can be attached directly to benzene nucleus as in case of aniline C6H5-NH2 or attached to the side chain as in case of benzyl amine C6H5CH2NH2.The latter amine is very similar to those of aliphatic amines in their preparations and reactions. Benzyl amine C6H5CH2NH2 Preparation: 1-Reduction of phenyl cyanide. C6H5-CN + C2H5-OH / Na C6H5-CH2-NH2 2-Heating of benzyl chloride with ammonia under pressure. C6H5-CH2-Cl + NH3 C6H5-CH2-NH2 3-Hofmann degradation of phenyl acetamide C6H5-CH2CO-NH2 + Br2 / KOH C6H5-CH2-NH2 4-Reaction with nitrous acid forms benzyl alcohol. C6H5-CH2-NH2 + HNO2 C6H5-CH2-OH+N2+H2O Chemical properties: Benzyl amine in its reactions is similar to the reactions of aliphatic amines. Aryl amines Ar-NH2 Methods of preparation: 1-Reduction of nitro compounds C6H5-NO2 + H2/Ni C6H5-NH2 nitro benzene 2-potassium hydroxide on benzamide (Hofmann degradation): C6H5-CONH2 + Br2/ KOH C6H5-NH2 Mechanism of Hofmann degradation(Hofmann rearrangement)  O O Br / KOH Ar Ar C NHBr C NH2 (HOBr ) O O OH Ar C NHBr Ar C N Br -H + O Ar C N Br Ar N C O isocyanate H2O OH Ar NH C Ar-NH2 Ar N C O -CO2 O isocyanate Also aryl amines can be obtained from carboxylic acids or their derivatives through Curtius rearrangement: PCl5 NaN3 CO2H COCl CON3 O H2O C N N N N C O NH2 phenylisocyanate Lossen Rearrangement: Action of a base on the ester of hydroxamic acid which gives amines through the formation of isocyanate as an intermediate: B Ph CONHOCOR Ph C N OCOR Ph N C O -H + O H2O Ph NH2 + CO2  3-Ammonolysis of halo benzene. C6H5-Cl + 2NH3/ Cu2O / P C6H5-NH2 chloro benzene 4-Action of NH3 on phenol. C6H5-OH + NH3/ ZnCl2 / P , C6H5-NH2 5-From sulphonic acid C6H5-SO3Na + NaNH2, fusion C6H5-NH2 + Na2SO3 sod.benzenesulphonate sodamide Properties of Aromatic amines: Primary aromatic amines are liquid compounds and have characteristic odour and they become darkens when they expose to air due to the oxidation. 1-Basicity: The basicity of aniline is less than of aliphatic amines due to the fact that the unshared electron pair on nitrogen atom are less available owing to their introducing with - cloud of the benzene ring. NH2 NH2 NH2 NH2 NH2 hybrid structure The basicity increases by introducing an electron releasing group And decreases by introducing an electron withdrawing group.  NH2 NH2 NH2 OCH3 H NO2 p-anisidine aniline p-nitroaniline The methoxyl group OCH3 has +M effect so it increases the electron density on the amino group NH2, therefore the basicity increases while the nitro group NO2 has -I and -M effect so it decreases the electron density on the amino group therefore the basicity decreases. Aniline reacts with mineral acids such as HCl to give aniline hydrochloride C6H5-NH2 + HCl C6H5-NH3+Cl- 2-Alkylation: Aniline reacts with alkyl halides giving secondary and tertiary amines. CH3 CH3Cl CH3Cl NH2 NH Cl N(CH3)2Cl NaOH NaOH N(CH3)2 NHCH3 N-methyl aniline N,N-dimethyl aniline Hofmann- Martius rearrangement: Alkyl aniline also its quaternary salts in their hydrochloride salts under high temperature, the alkyl groups migrate to the para position and when the p-position is occupied they migrate to the ortho position. + - N(CH3)3 Cl N(CH3)2 HCl NHCH3HCl NH2.HCl CH3 H3C CH3 CH3 CH3 CH3  3-Acylation: Aniline reacts with acetyl chloride or acetic anhydride in presence of a base such as sodium hydroxide to give acetanilide and this reaction known as Schotten-Baumann reaction C6H5-NH2 + CH3COCl / NaOH C6H5-NHCOCH3 + HCl acetanilide C6H5-NH2 + (CH3CO)2O / NaOH C6H5-NHCOCH3 +CH3CO2H p-Toluidine can be also acylated by acetic anhydride to give p-aceto-toluidine. NH2 NHCOCH3 (CH3CO)2O + CH3CO2H CH3 CH3 p-toluidine p- aceto-toluidine Secondary aromatic amines such as N-methylaniline can be also acylated to gine N-acetyl methylaniline but tertiary amines can not be acylated. NHCH3 H3C NCOCH3 (CH3CO)2O + CH3CO2H N-methylaniline N-acetyl methylaniline ( CH3CO)2O C6H5 N (CH3 )2 no reaction dimethylaniline Also it reacts with benzoyl chloride under the same reaction conditions to give benzanilide. C6H5-NH2 + C6H5COCl / NaOH C6H5-NHCOC5H5 + HCl Benzanilide 4- Reaction with arylsulphonyl chlorides: NH2 H NSO2 C6H5 C6H5SO2Cl +HCl benzene sulphonylchloride aniline N-phenylbenzenesulphonamide base C6H5NH2 C6H5NH SO2 CH3 H3C SO2Cl N-phenyl-p-tolunesulphonamide 5-Reaction with nitrous acid: ( diff. between 1, 2, 3 aromatic amines). A-ِprimary amines: Primary aromatic amines react with nitrous acid to give diazonium salts which are stable in contrast with aliphatic amines which decompose in solution to give alcohols. The stability of these salts attributed to presence of benzene ring which stabilized these salts by resonance. C6H5-NH2 + NaNO2 / HCl C6H5-N2Cl + 2H2O benzene diazonium chloride + + - + - + - N N N N N N N N + + + B- secondary amines: give N- nitroso amines. NO NaNO2 / HCl NHCH3 NCH3 + H2O N-methyl aniline N-methyl -N-nitroso aniline C-tertiary amines: give p- nitroso derivatives. NaNO2 / HCl N(CH3)2 ON N(CH3)2 N,N-dimethyl aniline p-nitroso-N,N-dimethyl aniline 5-Condensation with aldehydes and ketones: aniline condenses with aldehydes and ketones giving Schiff bases. C6H5-NH2 + C6H5-CHO C6H5-N=CHC6H5 + H2O benzaldehyde benzal aniline [B] Reactions involving the aromatic nucleus: 7-Oxidation: Aniline can be oxidized by sodium hybochlrite to give p-amino phenol. NaOCl NH2 HO NH2 p-hydroxy aniline or p- amino phenol 8-Bromination: Treatment of aniline with bromine solution gives 2,4,6-tribromo aniline. NH2 NH2 3 Br2 Br Br Br The formation of tribromide is due to the amino group ( NH2 ) which activates the o- and p- positions. In order to introduce one bromine atom, the activating effect of the amino group must be lowered by acylation.  NH2 NHCOCH 3 NHCOCH 3 NHCOCH 3 CH3COCl Br2 Br + acetanilide Br NaOH NaOH NH2 NH2 Br Br 9-Nitration: Nitration of aniline can not be carried out using nitric acid alone due to its ease of oxidation, therefore the nitration of aniline can be carried out in concentrated sulfuric acid giving m- nitro aniline due to the formation of NH3+ which is m- directing group. NH2 NH3.HSO 4 NH3.HSO 4 NH2 H.HSO 4 HNO3 NaOH NO2 NO2 In order to prepare o- and p- nitroaniline, the acylation of aniline must be carried out firstly. NH2 NHCOCH 3 NHCOCH 3 NHCOCH 3 CH3COCl HNO 3 NO2 + acetanilide NO2 70%H2SO4 70 % H2SO 4 NH2 NH2 NO2 NO2 10-Sulphonation: Heating of aniline with concentrated sulfuric acid at 180 C gives sulphanilic acid. NH2 NH2 H2 SO 4 + H2 O 180 C SO 3 H Hinsberg method for differentiation between primary, secondary and tertiary aromatic amines: Aniline, methylaniline and dimethyaniline react with p-toluene sulphonylchloride (Tos-Cl); aniline forms sulphonamide which soluble in KOH solution while methylaniline forms sulphonamine insoluble in KOH solution but dimethylaniline does not react with Tos-Cl. - + NH2 NHSO2 Tos N SO2Tos K Tos-Cl KOH soluble NO2 NHCH3 H3C NSO2 Tos Tos-Cl KOH insoluble (no NH ) N(CH3)2 Tos-Cl no reaction  Diazonium Salts Diazonium salts are important materials in preparation of various organic compounds. They are difficult to be isolated in solid form therefore they are prepared in solution. Preparations: Treatment of an aromatic amine with sodium nitrite/ HCl ( nitrous acid ) on cold. Ar-NH2 + NaNO2/ HCl Ar-N2+ Cl- for example NaNO2 / HCl NH2 N N Cl benzene diazonium chloride Chemical reactions: ( a ): Replacement reactions: 1-Replacement by hydroxyl group: when benzene diazonium chloride is boiled in water it gives phenol. C6H5-N2Cl + H2O boil C6H5-OH + N2 + HCl 2-Replacement by hydrogen: heating of the diazonium salt with methanol or with H3PO2 afforded benzene. C6H5-N2Cl + CH3OH boil C6H6 + N2 + HCl + CH2O 3-Replacement by halogen: i- Sandmayer’s reaction: Replacement of diazonium group by -Cl or -Br is carried out by mixing the solution of freshly prepared diazonium salt with cuprous chloride or cuprous bromide ArN2X + CuX ArX + N2 ( X= Cl or Br). ii-Gattermann reaction: Sandmeyer reaction can be carried out by modification, in which the copper powder and hydrogen halide are used in place of cuprous halide. Replacement of the diazonium group by iodide does not require the use of a cuprous halide or copper, the diazonium salt and potassium iodide are simply mixed together and allowed to react.  Cu / HCl Ar-Cl chloro benzene Cu /HBr ArN2 X Ar-Br bromo benzene KI Ar-I if Ar = C6 H5 - iodo benzene Replacement of the diazonium salt by fluoride F- can be carried out by using fluoroboric acid ( HBF4). C6H5N2Cl + BF4- C6H5-F fluoro benzene 4-Replacing by nitro group: They react with sodium nitrite inpresence of copper to give nitrobenzene. C6H5-N2Cl + NaNO2/Cu C6H5-NO2 nitrobenzene 5- Replacing by cyano group: This reaction is carried out using cuprous cyanide in presence of potassium cyanide and powder cupper. C6H5-N2Cl + K3Cu(CN)6 C6H5-CN phenyl cyanide This phenyl cyanide on hydrolysis gives corresponding acid. C6H5-CN + 2H2O/ base C6H5-CO2H + NH3 Benzoic acid 6- Replacing by an aryl group ( Gomberg reaction): N2Cl NaOH biphenyl This reaction proceeds through free radical mechanism: C6H5-N2Cl + OH- C6H5 -N= N-OH C6H5 -N= N-OH C6H5. + N2 + OH. C6H5. + C6H6 C6H5¯ C6H5 + H2O ( b ) Coupling reactions: The diazonium salt ion C6H5N2- is a weak electrophile, therefore it attacks the activated benzene ring gives rise to highly colored compounds known as Azo-dye. Coupling takes place at the p- position , when this p- position is blocked, the coupling takes place at the o- position.  NaOH N N Cl + OH N=N ONa benzene diazonium chloride p- hydroxy azo benzene NaOH N N Cl + NH2 N=N NH2 benzene diazonium chloride p- amino azo benzene N=N OH ONa N N Cl + NaOH benzene diazonium chloride  ALCOHOLS Alcohols are compounds which contain one hydroxyl group called monohydric alcohols, while those of two hydroxyl groups called dihydric alcohold. Alcohols of three hydroxyl groups called trihydric alcohols. Monohydric alcohols : The monohydric alcohols have a general formula R-OH where R is an alkyl group , these alcohols have a general molecular formula Cn H2n+2 O and the are divided into three classes: a- Primary alcohols R-CH2-OH b- Secondary alcohols (R)2-CH-OH c- Tertiary alcohols (R)3-C-OH Nomenclature of alcohols 1-IUPAC system: alcohols have a name derived from the corresponding alkane by changing " e " of " ane " to " ol" and alcohols of more than two carbon atoms must be numbered starting from carbon atom which is nearest to the hydroxyl group, where the alcohol take the number of carbon atom in which the hydroxyl group is attached to it. 2-Alkyl system: in which the word alcohol is coupled with the name of alkyl group. 3-Carbinol system: where the simplest alcohol ( CH3OH ) called carbinol and the other alcohols can be considered as a derivatives from carbinol  CH3OH CH 3CH2OH CH 3CH2CH2OH methnaol ethanol n-propanol( 1-propanol) methyl alc. ethyl alcohol n-propyl alcohol carbinol methyl carbinol ethyl carbinol CH3 CH3 CHCH 3 CH3 C CH3 CH3CH2CH2CH2OH OH OH n-butanol(1-butanol) isopropanol(2-propanol) ter.butanol isopropyl alcohol ter.butyl alcohol n-butyl alcohol dimethyl carbinol n-propyl carbinol trimethyl carbinol CH3-CH-CH2-CH3 CH3-CH-CH2-OH OH CH3 sec.butanol( 2-butanol) iso-butanol sec.butyl alcohol iso-butyl alcohol ethyl methyl carbinol isopropyl carninol Methods of preparation 1-Hydrolysis of alkyl halides with aqueous alkali ( NaOH, KOH ) : R-X + NaOH R-OH + NaX e.g.: CH3CH2Cl + NaOH CH3CH2OH + NaCl ethyl chloride ethanol 2-Indirect hydration of olefins: H.OH CH3CH CH2 + H.HSO 4 CH3 CH CH3 propene HSO4 CH3 CH CH3 + H2SO4 OH isopropanol 3-Reduction of carbonyl compounds with lithium aluminum hydride (LiAlH 4) or H2 in presence of a catalyst; where aldehydes give primary alcohols , ketones give secondary alcohols while the reduction of the fatty acids ,esters, acid anhydride and acid chlorides give primary alcohols. a-reduction of aldehydes: LiAlH4 R C O R CH2OH H e.g.: CH3 LiAlH4 C O CH3CH2OH H acetaldehyde ethanol b-reduction of ketones LiAlH4 R C O R C R` R` OH LiAlH4 e.g.: CH3 C O CH3C CH3 CH3 OH acetone isopropyl alcohol  c- reduction of fatty acids: LiAlH4 R C O R CH2OH + H2O OH LiAlH4 e.g.: CH3 C O CH3CH2OH + H2O OH acetic acide d-reduction of acid chloride: LiAlH4 R C O R CH2OH + HCl Cl LiAlH4 e.g.: CH3 C O CH3CH2OH + HCl Cl acetyl chloride e- reduction of acid anhydride: R-CO O = LiAlH4 2 RCH2OH R-CO acid anhydride CH3-CO O + LiAlH4 2CH3CH2OH CH3CO acetic acid 4- Action of Grignard'reagenrs on: a- formaldehyde gives primary alcohols: H.OH OH RMgX + C O R-CH2OMgX R-CH2OH +Mg X H H.OH CH CH OH +Mg OH CH3MgI + CH2O CH3CH2OMgI 3 2 I methyl mag.iodide ethanol aldehydes rather than formaldehyde give secondary alcohols -c H H OH H.OH RMgX + R` C O R-COMgX R-C-R` + Mg H R` OH X H H H.OH CH3MgI + CH3CH2CHO CH3 CH2COMgI CH3 CH2CCH3 propionaldehyde CH3 OH sec.butanol c- ketones give tertiary alcohols: R OH OH H.OH RMgX + R` C O R-COMgX R-C-R` +Mg X R R` R CH3 CH3 H.OH CH3MgI + CH3CCH3 CH3 COMgI CH3CCH3 acetone O CH3 OH ter.butanol e-ethylene oxide gives primary alcohol : Ag2O RMgX H.OH CH2 CH2 CH2 CH2 RCH 2CH2OMgX O R-CH2CH2OH + Mg X OH H2O CH3MgBr + CH2 CH2 CH3CH2CH2OMgBr O ethylene oxide CH3CH2CH2OH + Mg Br OH n-propanol 5-Alkaline hydrolysis of esters give alcohols and fatty acids ( their salts): H2O RCOOR' R'OH + RCOONa NaOH NaOH CH3CO2C2H5 C2H5OH + CH3CO2Na H2O ethylacetate ethanol sod. acetate 6-Action of nitrous acid on primary amines: R-CH2NH2 + HONO R-CH2OH + N2 + H2O 10 amine nitrous acid CH3CH2NH2 + HNO2 CH3CH2OH +N 2 +H2O ethanol ethyl amine  Properties of alcohols Isomerism in alcohols: 1- Position isomerism which depends on the position of the functional group in the molecule. e.g.: CH3CH2CH2CH2OH CH3CH2CHCH 3 OH 1-butanol 2-butanol 2- Chain isomerism, which depends on the shape of carbon chain( straight or branched ). e.g.: CH3CH2CH2CH2OH CH3CH-CH 2OH CH3 n-butanol iso-butanol 3-Optical isomerism, present in alcohols which contain asymmetrical carbon atom, where the molecule in this case has two isomers called " enantiomers" which they are optical active ( i.e. rotate the plane of polarized light in spectrometer).e.g.: sec-butanol can has this configuration in the space: CH3 CH3CH2CH2CH2OH CH3 CH CH2OH n-butanol iso-butanol Hydrogen Bonding: The relative low volatility of alcohol is due to the association of the molecules in the liquid state, through the hydrogen bond, these hydrogen bonds could be broken by the action of heat and this explain the high boiling points of alcohols. R H etc. R R O O H O R O H H hydrogen bonding Chemical properties of alcohols: 1-Reaction with alkali metals such as Na, and K; form salts which are called alkoxides with liberation of H2: R--OH + Na R-ONa + 1/2 H2 CH3CH2OH + Na CH3CH2ONa + 1/2 H2 ethanol sodium ethoxide 2-Action of hydrogen halides ( HX) give alkyl halides (R-X) : ROH + HX RX + H2O HBr CH3CHCH3 CH3CHCH3 + H2O OH Br iso-propanol iso-propyl bromide 3-Action of phosphorouspentachloride (PCl5) or thionyl chloride ( SOCl2) give alkyl chlorides: CH3CH2OH + PCl5 CH3CH2Cl + POCl3 + HCl ethanol ethyl chloride CH3OH + SOCl2 CH3Cl + SO2 + HCl methanol methyl chloride 4-Dehydration by the action of heated alumna( Al2O3) or concentrated sulfuric acid give olefins -H2O CH3CH2OH + H.HSO 4 CH3CH2.HSO4 ethyl hydrogen sulfate o 140 C 170oC C2H5OH CH3CH2OCH 2CH3 CH2 CH2 + H2SO 4 diethyl ether ethylene The formation of ether proceeds according to Williamson continuos etherification method, where the heating of ethylhydrogen sulfate at 140C in presence of an excess of alcohol led to the formation of ether according to the following mechanism. H -H2O HOCH 2CH3 CH3CH2OH CH3CH2OH2 CH3CH2 -H CH3CH2-O-CH2CH3 CH3CH2-O-CH2CH3 H HSO4 dietyl ether if there is no adjacent -C-H , the dehydration takes place with rearrangement  CH3 CH3 CH3 H -H2O CH3-C-CH2OH CH3-C-CH2OH2 CH3-C-CH2 CH3 CH3 CH3 2,2-dimethyl-1-propanol rearrangement -H CH3-C-CH2 CH3 CH3-C CHCH 3 CH3 CH3 2-methyl-2-butene Also dehydration of 2,3-dimethyl-butanol can be represented as follow: CH3 H CH3 H -H2O CH3 C C CH3 CH3 C C CH3 H+ CH3 OH CH3 secondary carbonium ion ( less stable ) CH3 H E1 CH3 C C CH3 CH2 C CH CH3 + B-elimination CH3 CH3 CH3 ter- carbonium ion ( minor ) CH3 CH3 ( more stable ) CH3 C C CH3 ( major ) 5-Esterification: Fisher method: by the reaction of alcohol with organic acid in presence of )a dehydrating agent such as hydrochloric acid in gaseous state or conc. sulfuric acid:  H2SO4 R-CO2H + R`OH RCO2R` + H2O H2SO4 CH3CO2H + CH3OH CH3CO2CH3 + H2O methanol conc. methyl acetate Mechanism: OH R`OH OH H R-C OH R-C OH R-C OH O O-R` OH O H H -H2O -H R-C OH2 R-C R-C -OR` OR` OR` O b-reaction with acid chloride: - O R-C-Cl + HOR` R-C-OR` + HCl O e.g.: CH3COCl + C2H5OH CH3CO2C2H5 +HCl acetyl chloride ethyl acetate c- Reaction of alcohol with acid anhydrides: (RCO)2O + R'OH RCOOR' + RCOOH acid anhydride alcohol ester acid (CH3CO)2O + C2H5OH CH3COOC2H5 + CH3COOH acetic anhydride ethanol ethyl acetate acetic acid 6- Dehyrogenation: Dehydrogenation is carried out by passing the vapor of alcohol over heated copper ( 350C) : a- Primary alcohols give aldehydes:  Cu /350o e.g.: CH3CH2OH CH3CHO +H2 acetaldehyde b-Secondary alcohols give ketones: OH O Cu /350o CH3-CH-CH3 CH3C-CH3 + H2 acetone isopropanol c-Tertiary alcohols give olefins: OH Cu /350o CH3-C-CH3 CH3-C CH2 ter.butanolCH3 isobutene CH3 7- Oxidation: Oxidation with potassium permanganate or potassium dichromate: a) 10 alc. ( O) ( O) aldehyde acid (O) (O) R CH2 OH R CHO R CO2H KMnO 4 KMnO 4 (O) b) sec. alc. ketones (O) R CH R' R C R' OH O c) ter. alcohols resist the oxidation under this conditions 8- Haloform reaction: Alcohols which have CH3 CH OH group in the presence of halogen ( X2 ) and NaOH give Haloform: 3 I2 NaOH I2 CH 3CH 2OH CH 3CHO CI 3 CHO oxidation substitution iodal ethanol acetaldehyde CHI 3 + HCOONa chloroform sod.formate Differentiation between primary, secondary and tertiary alcohols: Oxidation ( as mentioned before ) Dehyrogenation ( as mentioned before ) Victor- Mayer's method: a- Primary alcohol: AgNO3 R CH2OH + PC l 5 R CH2Cl HONO NaOH R C NO 2 red colour (NaNO2/HCl) N OH b) Secondary alcohols: AgNO 3 R CH R' + PCl5 R CH R' R CHNO 2 OH Cl R' R' HONO NaOH R C NO 2 blue colour (NaNO2/HCl) N O c) Tertiary alcohols: R" R" R" PCl5 AgNO3 HNO2 R C R' R C R' R C R' OH Cl NO2 HNO2 no reaction  Dihydric Alcohol e.g. Ethylene glycol CH2(OH) - CH2(OH) Methods of preparation: 1- Hydrolysis of vic-dihalides CH2 CH2 + NaOH CH2 CH2 Cl Cl OH OH ethylene chloride 2-By passing ethylene into cold dilute alkaline permanganate (O) CH2 CH2 CH2 CH2 KMnO 4 OH OH Chemical reactions: 1- Glycols condense with aldehydes or ketones to give cyclic acetals or cyclic ketals O CH3 CH2 OH CH3 CH2 + O C C CH2 OH CH3 CH2 CH3 O 2-With hydrochloric acid (HCl): The products depends on the reaction's temperature. CH2 Cl HCl CH2 OH HCl CH2 Cl CH2 OH 160o CH2 OH 200o CH2 Cl 2-Oxidation with nitric acid gives glycollic and oxalic acids: with nitric acid, ethylene glycol can be oxidized finally to oxalic acid through different oxidative steps: CHO ( O ) C O2H CH2 OH (O) CH2 OH glycollic CH2 OH CH2 OH acid (O) (O) CHO (O) C O2H (O) C O2H CHO C O2H CHO glyoxal oxalic glyoxalic acid acid Trihydric Alcohols e.g. Glycerol ( propane-1,2,3-triol ) CH2(OH)CH(OH)CH2(OH) Glycerol occurs in almost all animal and vegetable oils and fats as the glyceryl ester of palmitic, stearic and oleic acids. Preparations: 1- Glycerol is prepared for industrial uses by the hydrolysis of fats and oils with water under pressure at 220 C CH2 O-CO-R CH2 OH NaOH CH O-CO-R + 3 H2O CH OH + 3 RCO 2Na CH2 O-CO-R CH2 OH triglyceride glycerol soap 2- From propene: Cl2/400oC HOCl CH3 CH CH2 Cl-CH2-CH CH2 soda lime CH2 CH CH2 CH2 CH CH2 hyd. -HCl Cl O Cl Cl OH CH2 CH CH2 OH OH OH 3- From acrolein: H2O2 CH2 CH CHO H2/Pt CH2 CH CH2 CH2 CH CHO OH OH OH OH OH Chemical reactions: 1-Action of conc. H2SO4 gives acrolein. CH2 OH CH2 OH CHO CHO conc. -H2O CH OH CH CH CH H2SO4 H2SO4 CH2 OH CH2 OH CH2 OH CH2 2-Action of HI. CH2 OH CH2 I CH2 CH2 3HI -I2 HI HI CH OH CH I CH CH CH2 OH CH2 I CH2I CH3 CH3 CH CH3 allyl iodide I isopropyl iodide 3- Conversion to citric acid: CH2 OH CH2 Cl CH2 Cl CH2 Cl 2HCl (O) HCN CH OH CH OH C O CH (OH)CN CH2 OH CH2 Cl CH2 Cl CH2 Cl CH2 CN CH2 CO2H hyd. 2 KCN CH (OH)CN CH (OH)CO2H CH2 CN CH2 CO2H citria acid 4-Nitration: CH2 OH CH2 O NO2 conc. CH OH CH O NO2 HNO 3 /H2S O 4 CH2 OH CH2 O NO2 glyceryl trinitrate 5-Oxidation: With dilute nitric acid , it gives glyceric acid. CH2 OH CO2H dilute CH OH CH OH HNO 3 CH2 OH CH2 OH glyceric acid  Aromatic Alcohols Aromatic alcohols are hydroxy compounds in which the hydroxyl groups are attached to a side chain of benzene ring, for example benzyl alcohol C6H5CH2OH which can be considered as a phenyl derivative of methanol, therefore it resembles aliphatic alcohols in its preparations and its chemical reactions. Benzyl alcohol C6H5CH2OH Methods of preparations: 1-In industry: it can be prepared by the alkaline hydrolysis of benzyl chloride with sodium bicarbonate solution. CH2Cl CH2OH Na2CO3 solution 2-From Canizzaro’s reaction: CHO CO2Na NaOH CH2OH 2 + 3-By reduction of benzaldehyde with sodium amalgam. CHO CH2OH Na /Hg 4-From Grignard’s reagent: by the action of phenylmagnesium iodide on formaldehyde. MgI 1) CH2 O CH2OH 2)H2O Chemical reactions: Na C6H5CH2ONa + H2 HCl or C6H5CH2Cl PCl5 CH3COCl or C6H5CH2OCOCH3 C6H5CH2OH (CH3CO)2O benzylacetate [O] O C6H5CHO C6H5CO2H HNO3 HI / P C6H5CH3 conc. H2SO4 C6H5CH2OCH2C6H5 - H2O dibenzyl ether  Phenols Phenols characterized by the presence of one or more hydroxyl group ( OH ) are directly attached to the benzene nucleus. They are classified as monohydric, dihydric, trihydric or polyhydric phenols according to the number of the hydroxyl groups which are attached to benzene nucleus. OH OH OH OH OH CH3 CH3 NO2 CH3 Phenol p-nitrophenol o-methylphenol m-methylphenol p-methylphenol ( o-cresol ) ( m-cresol ) ( p-cresol ) OH OH OH OH OH OH OH OH Catechol resorcinol quinol alph naphthol beta naphthol Methods of preparations 1-Fusion of sodiumbenzenesulphonate with sodium hydroxide gives sodium phenoxide which can be easily hydrolyzed to give phenol. SO3Na ONa OH NaOH HCl fusion This method is important in conversion of benzene to phenol.  2-From diazonium salts: by boiling it in water. N2Cl OH H2O + N2 + HCl boil 3- From Grignard’s reagent: Br MgBr OMgBr OH Mg O H2O ether 4- Hydrolysis of aromatic halogen compounds : by heating with alkali such as NaOH at high temperature and pressure in presence of a catalyst such as copper. Cl OH ONa NaOH H2CO3 P Physical properties: Simplest phenols are liquid compounds , phenol itself is solid in low temperature but in relatively high temperature become liquid, it characterized by characteristic odor and is partially soluble in water.  Chemical Properties of Phenols Phenols are acidic in nature and the greater acidity of phenols rather than aliphatic alcohols is due to the delocalization of the lone pair of electrons on the oxygen atom with the π electrons cloud of benzene ring. Such delocalization creates a partial positive charge on the oxygen atom, therefore it facilitate the removal of H as H+. OH OH OH OH OH Beside the above reason, the acidity of phenols can be also attributed to the fact that the phenoxide ion is more stabilized by the resonance than phenol molecule. O O O O O Hybrid structure The presence of OH group in phenol increase the electron delocalization on the benzene ring by +R effect, i.e activates the benzene ring towards the electrophiles which will attack the ring on o- and p- positions. The chemical reactions of phenol may be divided into: 1- Reactions involving the O-H bond. 2- Reactions involving the C-O bond. 3- Reactions involving the aromatic ring.  [A] Reactions involving the O-H bond. 1-Formation of metallic salts: due to the acidity of phenol as mentioned before, phenols soluble in aqueous alkali solutions to give phenoxides. ONa OH NaOH sodium phenoxide The acidity of phenols can be increased by introducing of an electron attracting group especially in o- and p- positions as the nitro group ( NO2 ) which has –R effect i.e this group will increases the positive charge on the oxygen atom of the hydroxyl group i.e facilitate its removal as H+. OH OH OH OH N N N N O O O O O O O O While in case of p- cresol the acidity is less than that of phenol due to the + I effect of methyl group in p- position. H3C OH p- cresol  2-Methylation with diazomethane: it gives anisole. CH2N2 OH OCH3 anisole 4- Formation of ester: Schotten-Baumann reaction. Reaction of phenol with acid chloride or anhydrides in presence of a base such as NaOH gives ester. CH3COCl OH OCOCH3 or (CH3CO)2O phenylacetate C6H5COCl OH OCOC6H5 NaOH phenylbenzoate 5-Formation of ethers: phenol reacts with alkyl halides in presence of a base such as NaOH to give phenyl alkyl ether. CH3Cl OH OCH3 NaOH phenylmethyl ether ( anisole ) 6-Formation of thiophenol: phenols react with phosphorus pentasulphide P2S5 to give thiophenol. P2S5 OH SH  [B] Reactions of C- O bond: Due to the resonance, oxygen atom has a partial positive charge and therefore the C-O bond has a double bond character, therefore the tendency of OH group to be replaced by a halogen atom through the action of PCl5 or HX as in aliphatic alcohols is so difficult. However, the replacement of the hydroxyl group ( OH ) by halogens or by an amino group ( NH2 ) must be carried out under drastic conditions. 1-placement of ( OH ) group by amino group. When phenol is heated with NH3 under pressure and in presence of a catalyst such as ZnCl2 it gives aniline. NH3 OH NH2 + H2O ZnCl2 / 2-Replacement by hydrogen: reduction. By passing the vapor of phenol over zinc it will be reduced to benzene. OH + H2O Zn /  [C] Reaction of the aromatic ring: 1-Reimer-Tiemann reaction: Phenol reacts with chloroform CHCl3 in presence of NaOH to give salicylaldehyde. OH OH CHCl3 CHO NaOH The Mechanism of reaction: OH CHCl3 CCl2 carbene - H2O O O O H H CCl2 CCl2 OH O O CHCl2 CHCl2 CHO hydrolysis 2-Kolb’s reaction: Heating of sodium phenoxide with carbon dioxide at high temperature and pressure gives salicylic acid. ONa OCOONa OH OH COONa CO2H CO2 HCl p/  Mechanism of the reaction: O O O O H H C O COONa OH OH CO2Na HCl CO2H [ D ] Substitution by electrophilic reagents: The high electron density on benzene ring in phenol ( due to the delocalization of lone pair of electrons from oxygen atom to the  electrons of benzene ring ) result in the rapid substitution by electrophiles compared with benzene i.e benzene ring in case of phenol is more reactive than benzene towards electrophiles. 1-Halogenation: Phenol reacts with bromine solution rapidly to give a white precipitate from 2,4,6- tribromophenol. OH OH 3 Br2 Br Br Br But if the bromination is carried out in anhydrous carbon disulphide CS2 it gives a mixture from o- and p-bromophenol. OH OH OH Br2 Br + Br  b- Sulphonation: Phenol can be easily sulphonated by concentrated H2SO4 to give a mixture from o- and p- phenolsulphonic acid. OH OH OH conc. SO3H + H2SO4 SO3H Nitration: I ) In dilute nitric acid , phenol can be nitrated by the action of dilute HNO3 to give a mixture from o- and p- nitrophenol. OH OH OH dilute NO2 + HNO3 NO2 ii) In concentrated nitric acid, phenol is nitrated to give 2,4,6-trinitrophenol ( picric acid ). OH OH conc. HNO3 NO2 NO2 2,4,6-trinitrophenol NO2 ( picric acid )  d- Nitrosation: Phenol reacts with nitrous acid to give p- nitrosophenol. OH CH2OH (NaNO2/HCl) HNO2 NO e- Coupling reactions: Diazonium salts couple with phenol in alkaline medium at the para position, but if the para position is occupied, the coupling occurs in ortho position giving a red dye. OH N2Cl N N OH NaOH p-hydroxyazobenzene f-Hydroxymethylation: Phenol condenses with formaldehyde at low temperature to give p-hydroxybenzyl alcohol as a major product and a small amount from o-hydroxybenzyl alcohol. OH OH OH CH2O CH2OH + NaOH CH2OH  ALDEHYDES AND KETONES Aldehydes are compounds which have general formula R-CHO and ketones have a formula R-CO-R'. Aldehydes and ketones have a general molecular formula CnH2n+2O. Both aldehydes and ketones have a carbonyl group( C=O ) therefore they are called carbonyl compounds, in aldehydes ,the carbonyl group is attached to at least one hydrogen atom ( -CHO ) while in ketones the carbonyl group is attached to two alkyl groups. Nomenclature: 1-Common name: Aldehydes have a name derived from the corresponding acids by replacing word aldehyde instead of " ic " of an acid, while ketones named as dialkyl ketone. 2-IUPAC system: Aldehydes named from corresponding alkane by changing "e" of ane to "al" while ketones take a name derived from the corresponding alkane by changing "e" of ane to "one" and ketones of five chain carbon atoms and more must be numbered starting from carbon atom which is nearest to the carbonyl group. CH3CHO CH3CH2CHO CH3CH(CH3)CHO acetaldehyde propionaldehyde isobutyraldehyde ethanal propanal 2-methyl propanal CH3COCH3 CH3CH2COCH3 CH3CH2COCH2CH3 dimethyl ketone ethyl methyl ketone diethyl ketone propanone butanone 3- pentanone Isomerism in aldehydes and ketones: i- Position isomerism: CH3CH2COCH2CH3 CH3CH2CH2COCH3 3-pentanone 2-pentanone ii-Chain isomerism: CH3CH2CH2CHO CH3CH CHO CH3 n-butyraldehyde isobutyraldehyde PTRPARATION OF ALDEHYDES AND KETONES 1-Oxidation of alcohols: a- Primary alcohols are oxidized by acidic pot.dichromate K2Cr2O7 to aldehydes and the latter can undergo further oxidation to the corresponding acids ( see reactions of aldehydes). (O) (O) R-CH2OH R-CHO R-CO2H 1o alcohol aldehyde acide (O) (O) e.g.: CH3CH2OH CH3CHO CH3CO2H ethanol acetaldehyde acetic acid b-Secondary alcohols by oxidation give ketones: (O) e.g.: CH3-CH-CH3 CH3-C-CH3 OH O isopropanol acetone O (O) e.g.: CH3CHCH 2CH3 CH3C-CH2CH3 OH butanone sec.butanol 2- Dehydrogenation of alcohols by passing their vapor over heated copper ( as mentioned before ). a-primary alcohols give aldehydes  Cu / 500oC R-CH2OH R-CHO + H2 b- secondary alcohols give ketones H R-C-R` R-C-R` + H2 Cu /350 C OH O CH3CHCH2CH2CH3 CH3COCH2CH2CH3 Cu /350 C OH 2-pentanol n-propylmethylketone 3-Ozonolysis of olefins: ( Alkenes): a-symmetrical and straight alkenes give aldehydes: H 1) O3 CH3CH= CHCH 3 2 CH3-C=O 2) H2O/ Zn 2-butene acetaldehyde b-symmetrical and branched chain alkenes give ketones: CH3 1) O3 CH3 CH3-C=C CH3 2 CH3 C=O 2) H2O/Zn CH3 2,3-dimethyl-2-butene acetone 4-Hydration of acetylene's in presence of sulfuric acid and mercuric sulfate as catalyst: a-acetylene gives acetaldehyde b-other acetylene's give ketones; ( see reactions of acetylene's). 5-Hydrolysis of gem-dihalides by action of a base: a- if the dihalogen atoms are terminal, the products will be aldehydes:  H2O OH -H2O e.g.: CH3CHCl 2 CH3CH CH3CHO NaOH OH acetaldehyde ethylidene chloride b- if the halogen atom are not terminal ;the products will be ketones: H2O O CH3CCl2CH3 CH3 C CH3 NaOH 2,2-dichloropropane acetone 6- Dry distillation of calcium salts: a- calcium formate gives formaldehyde HCOO Ca CH2O + CaCO 3 HCOO b-calcium formate + another calcium salt give aldehyde rather than formaldehyde: HCOO OOC-CH 3 Ca + Ca 2 CH3CHO HCOO OOC-CH 3 ca.formate ca.acetate acetaldehyde c-calcium salt gives ketones: CH3COO Ca CH3COCH3 + CaCO3 CH3COO ca.acetate acetone 7-Action of Grignard's reagent on: a-formate esters give aldehydes. This aldehyde can be under further reaction with Grignard reagent giving secondary alcohols. OC 2H5 OC 2H5 - C H OMgI 2 5 H C O + CH3MgI H C OMgI ethyl formate CH3 H CH3 1) CH3MgI CH3 C O +CH 3MgI H C OH 2) H2O CH3 acetaldehyde iso-propanol b-esters rather than formate give ketones and these ketones can be react with excess Grignard's reagent giving tertiary alcohols: OC 2H5 OC 2H5 - C H OMgI 2 5 CH3 C O + CH3MgI CH3 C OMgI ethyl acetate CH3 CH3 CH3 1) CH3MgI CH3 C O +CH 3MgI CH3 C OH 2) H2O CH3 acetone ter.butanol 8-Rosenmund reduction: Aldehydes can be prepared by the reduction of acid chlorides with hydrogen in presence of palladium as a catalyst:  O H H2 /Pd R C Cl R C=O + HCl CH3COCl CH3CHO + HCl H2 /Pd acetyl chloride acetaldehyde Physical properties: Aldehydes and ketones are polar compounds due to they contain a carbonyl group which is polar, hence they have higher boiling points than non-polar compounds of comparable molecular weight. They can not form H-bonding ,therefore they have lower boiling points than alcohols. Formaldehyde is a gas , and is handled as an aqueous solution which called" formalin" or as a solid polymer called paraformaldehyde. [A] ADDITION REACTIONS 1- Addition of Grignard's reagent ( see preparation of alcohols ). a- formaldehyde gives primary alcohols b-other aldehydes give secondary alcohols c-ketones give ter- alcohols. 2-Addition of hydrogen cyanides: give cyanohydrin: HCN 2 H2O C=O C OH C COOH+ NH 3 CN OH cyanohydrine hydroxy acid  HCN 2 H2O CH3C=O CH3CH-CN CH3CH-CO 2H H OH OH acetaldehyde acetald.cyanohydrine lactic acid HCN CH3 CH3C=O CH3C-CN acetone cyanohydrine CH3 OH 3- Addition of alcohols: in presence of an acid or a base they give hemiacetal and acetals: OC2H5 OC2H5 C2H5OH C2H5OH CH3C=O H C CH3 H C CH3 H H H OC2H5 OH hemiacetal acetal 4-Addition of hydrogen: a-addition of hydrogen in presence of a catalyst such as Pt or Ni reduce aldehydes to primary alcohols and ketones to secondary alcohols ( see preparation of alcohols ). b- Clemmensen reduction: ketones can be reduced by zinc amalgam (Hg/Zn) in presence of an acid to give alkanes: Zn/Hg/HCl C=O CH2 + H2O Zn/Hg/HCl CH3COCH 3 CH3CH2CH3 + H2O acetone propane 5- Addition of ammonia: Aldehydes except formaldehyde react with ammonia to give aminohydrin:  H NH3 R C=O R CH NH2 OH aminohydrin NH3 CH3CHO CH3CHNH 2 OH acetald.aminohydrin [B] CONDENSATION REACTIONS 1-With hydroxylamine: (NH2OH): Aldehydes and ketones react with hydroxylamine with elimination of water molecule to give oxime: C=O + H2N-OH C=N-OH + H2O oxime CH3-C=O + H2N-OH CH3-C=N-OH + H2O CH3 CH3 2-With hydrazine:( NH2NH2): Aldehydes and ketones react with hydrazine to give the corresponding hydrazones: C=O + H2N-NH2 C=N-NH2 + H2O hydrazone CH3CHO + NH2NH2 CH3CH=N-NH2 + H2O acetald. hydrazone CH3-C=O + NH2NH2 CH3-C=N-NH2 + H2O CH3 CH3 acetone hydrazone 3-With semicarbazide( NH2NHCONH2): They react with semicarbazide to give semicarbazones:  CH3-C=O + H2N-NH-CONH 2 - H2O CH3-C=N-NH-CONH 2 CH3 CH3 acetone semicarbazide 4-With thiosemicarbazide( NH2NHCSNH2): Reaction of aldehydes and ketones with thiosemcarbazide give thiosemicarbazones: S C=O + H2N-NH-CSNH2 - H2O C N.NH-C-NH2 H S H S - H2O CH3-C O + H2N-NH C NH2 CH3 C N-NH C NH2 S C=O + H2N-NH-CSNH2 - H2O C N.NH-C-NH2 H H S S - H2O CH3-C O + H2N-NH C NH2 CH3 C N-NH C NH2 5-Aldol condensation: Aldehydes and ketones which have at least one - hydrogen atom undergo self addition reaction to give hydroxy aldehyde or ketones which lose water molecule to give ,- unsaturated aldehyde or ketone in presence of sodium hydroxide. H NaOH - H2O 2CH -C O CH CH CH CHO CH3 CH CH CH3 3 3 2 OH B-hydroxybutyraldehyde crotonaldehyde CH3 CH3 NaOH -H2O CH C CHCOCH CH3 C CH2COCH3 3 3 OH mesityl oxide Mechanism: H H OH H C C O CH2CHO NaOH H -H H H H CH3C=O + CH2CHO CH3 C CH2CHO O - H2O CH3 CH CH2CHO CH3 CH CHCHO OH [C] SUBSTITUTIONJ REACTIONS 1-Haloform reaction: Aldehydes or ketones which contain CH3CO group in presence of halogen (X2) and sodium hydroxide give Haloform compounds, 3I2 NaOH CH3 C CH3 CI3 C CH3 CHI3 + CH3CO2Na O O iodoform sod.salt 2-Substitution in carbonyl group takes place, when these compounds are treated with phosphorous pentachloride (PCl5):giving gem-dichlorides: + PCl5 Cl C=O C + POCl3 Cl H e.g.: CH3 C=O + PCl5 CH3CHCl2 + PO Cl3 [D] Cannizzaro's reaction : ( special reaction for aldehydes): Aldehydes without -C-H atoms ( as formaldehyde and trimethyl acetaldehyde) when boiled with alkali it will oxidized to the corresponding acid and the other molecule is reduced to alcohol.  2 CH2O + NaOH CH3OH + HCO2Na methanol sod.formate CH3 CH3 CH3 NaOH 2 CH3-C CHO CH3-C CH2OH + CH3-C CO2Na CH3 CH3 CH3 trimethyl acetaldehyde Mechanism: H H H H C=O H OH H C=O H C O H C=O H C O OH O H H -H HCO2Na + CH3OH +H Identification of aldehydes and ketones 1-Aldehydes are oxidized by Tollen's reagent ( ammoniac silver nitrate) to the corresponding acid and silver ion( Ag+) will be reduced to silver metal (Ag) which forms a mirror. R-CHO + Ag(NH3)2+ R-COO- + Ag 2-Aldehydes also reduce Fehling reagent ,where the blue color is discharged with formation of a reddish brown precipitate from Cu2O. 3-Aldehydes with Schiff's reagent give pink color.  Aromatic Aldehydes Aromatic Aldehydes contain an aldehydic group ( CHO ) which can be attached directly to the benzene ring as in case of benzaldehyde C6H5CHO or attached to the side chain as in case of phenyl acetaldehyde C6H5CH2 CHO. The latter type of compounds resemble those of aliphatic aldehydes in their preparations and reactions. But the first type which the aldehydic group is attached to the benzene ring differ than from aliphatic aldehydes and we will study benzaldehys as an example of these aldehydes. Benzaldehyde C6H5CHO Preparation of benzaldehyde: 1- Oxidation of benzyl chloride with lead nitrate. CH2Cl CHO Pb(NO3)2 + 2NO + PbClOH (O) 2-Oxidation of toluene with manganese dioxide. CH3 CHO MnO2 + MnSO4 + H2O H2SO4 3-Hydrolysis of benzal chloride with lime water. CHCl2 CHO Ca(OH)2 H2O  4-Gattermann-Koch reaction: Benzaldehyde can be produced by the action of a mixture from CO/HCl and anhydrous AlCl3 on benzene under pressure. CO + HCl HCOCl 1) HCOCl / AlCl3 CHO 2) H2O 5-Rosenmund reduction: Reduction of benzoyl chloride by hydrogen over palladium as a catalyst. H2 / Pd COCl CHO + HCl 6-Distillation of calcium salts: Heating a mixture from calcium formate with calcium benzoate gives benzaldehyde. (C6H5CO2)2Ca + ( HCO2 )2Ca 2C6H5CHO + 2 CaCO3 7- Stephen’s method: Reduction of aryl cyanides by SnCl2 in presence of HCl followed by acid hydrolysis: CN C H NH CHO SnCl2 / HCl + H3O +NH3 Chemical properties of benzaldehyde: Benzaldehyde possesses all the properties of aliphatic aldehydes. [A] Addition reactions: Addition of reagents occurs at the partially polarized carbonyl group. 1-Benzaldehyde reacts with Grignard’s reagent to give secondary alcohols. + H H R MgX C6H5 C O C6H5 C OMgX + R H2O H C6H5 C OH + MgXOH R 2-Clemmensen reduction:] Benzaldehyde can be reduced by zinc amalgam in presence of hydrochloric acid to give toluene. Zn /Hg / HCl C6H5 CHO C6H5CH3 + H2O 3-Addition of bisulphite: Addition involves nucleophilic attack of sulphide ion on carbonyl group followed by the addition of hydrogen ion to negative oxygen. - + H H SO3H Na - + C6H5 C O C6H5 C O H + - SO3 H C6H5 C OH - + SO3 Na 5-Addition of hdrogen cyanide: Aldehes add HCN to gine cyanohdrin derivatives which can hydrolyzed to hydroxy acids.  CN + HCN - H C6H5 C O C6H5 C O H H CN CO2H 2H2O C6H5 C OH C6H5 C OH H H benzaldehyde phenylglycolic acid cyanohydrin [B] Condensation reactions: 1-Benzaldehyde like aliphatic aldehydes condenses with hydrazine, phenylhydrazine, hydroxylamine, Semicarbazide and thiosemicarbazide. H H2NNH2 C NNH2 hydrazone H C6H5NHNH2 C NNHC6H5 H H H2NOH C NOH oxime C O H H2NNHCONH2 C NNHCONH2 semicarbazide H semicarbazone H2NNHCSNH2 C NNHCSNH2 thio semicarbazide thiosemicarbazone 2-Condensation of Aldol type:- a-Benzaldehyde condenses with acetaldehyde in the presence of sodium hydroxide to give cinnamaldehyde, this type of condensation known as Claisen-Schmidt condensation. H H H CH3CHO C O C C CHO NaOH / - H2O b-with acetone: Benzaldehyde condenses with acetone under the same reaction condition to give benzal acetone. H H H CH3COCH3 C O C C COCH3 NaOH / - H2O c-with acetophenone: Benzaldehyde condenses with acetophenone under the same reaction condition to give benzal acetophenone. H H H CH3COC6H5 C O C C COC6H5 NaOH / - H2O [ C] Substitution reactions: Benzaldehyde undergoes substitution reactions in the carbonyl group as the with aliphatic aldehydes. Thus it reacts for example with PCl5 to give benzal chloride. H H PCl5 Cl + POCl3 C O C Cl [D] Oxidation: Benzaldehyde is rapidly oxidized by air to give benzoic acid. H OH [O] C O C O [ E ] Reactions in which benzaldehyde differ from aliphatic aldehydes: 1-Perkin condensation: When benzaldehyde is heated with acetic anhydride in presence of sodium acetate, the condensation takes place giving Cinnamic acid. H H H (CH3CO)2O O C C CO2H C CH3CO2Na cinnamic acid Mechanism of the reaction: CH3CO2Na CH3COOCOCH3 CH2COOCOCH3 + CH3CO2H H -H H CH2COOCOCH3 C O C CH2COOCOCH3 O H H - H2O C CH2COOCOCH3 H OH H hydrolysis C CHCOOCOCH3 C CHCOOH 2-Cannizaro reaction: When benzaldehyde is warmed with sodium hydroxide it gives benzyl alcohol and sodium benzoate. CHO CH2OH CO2Na NaOH 2 + 3-Benzoin condensation: When benzaldehyde is boiled with alcoholic potassium cyanide solution it gives benzoin which can be oxidized by concentrated nitric acid to benzil. KCN [O] 2C6H5 CHO C6H5 CH CO C6H5 HNO3 OH benzoin C6H5 CO CO C6H5 benzil Mechanism of reaction: CN CN C6H5 CH CN C H C6H5 C O C6H5 OH O CN H CN H C6H5 CH O -H+ C6H5 C C6H5 C6H5 C C Ph C +H+ O OH OH O _ -CN C6H5 C CH C6H5 O OH Substitution reactions in benzene ring : Aldehyde group is an electron attracting group which orient the electrophiles to m- position, therefore benzaldehyde undergoes electrophilic substitution reactions giving m- derivatives. For example, nitration of benzaldehyde gives m-nitro benzaldehyde and it is carried out with concentrated H2SO4 / HNO3 at low temperature while if the nitration is carried out at relatively high temperature, benzaldehyde can be oxidized by conc. Nitric acid to benzoic acid. CHO CHO H2SO4 m-nitrobenzaldehyde HNO3 NO2 ( How can you convert m-nitro benzaldehyde to m-chloro benzaldehyde? ) Aromatic Ketones Aromatic ketones contain a carbonyl group C= O and these ketones can be contain an alkyl group and aryl group attached to the carbonyl group as in case4 of acetophenone C6H5- CO-CH3 or two aryl groups as in case of benzophenone C6H5-CO-C6H5. Acetophenone C6H5-CO-CH3 Preparation: 1- By didtillation of calcium acetate and calcium benzoate. ( C6H5CO2)2Ca +( CH3CO2 )2Ca C6H5COCH3 + 2CaCO3 2-Acetylation of benzene through Fridel-Craft’s reaction. CH3COCl or (CH3CO)2O COCH3 AlCl3  Chemical properties of acetophenone: 1-Condensation reactions: As mentioned in aldehydes, acetophenone condenses with hydrazine, phenylhydrazine, hydroxylamine, Semicarbazide and thiosemicarbazide to give the condensation products. CH3 H2NNH2 C NNH2 hydrazone CH3 C6H5NHNH2 C NNHC6H5 CH3 CH3 C O H2NOH C NOH oxime CH3 H2NNHCONH2 C NNHCONH2 semicarbazide semicarbazone CH3 H2NNHCSNH2 C NNHCSNH2 thio semicarbazide thiosemicarbazone 2-Haloform reaction: Acetophenone contains CH3CO group. Therefore it reacts with halogens in presence of sodium hydroxide to give the haloform and sodium benzoate. 3I2 NaOH C6H5COCH3 C6H5COCI3 CHI3 + C6H5CO2Na H2O 3-duction: The products of reduction depends on the reducing agents: i-reduction by zinc amalgam ( Clemmensen reduction ) gives ethyl benzene. Zn /Hg / HCl C6H5COCH3 C6H5CH2CH3 + H2O ii- reduction by LiAlH4, it gives methyl phenyl carbinol.  LiAlH4 C6H5COCH3 C6H5CHCH3 OH 4-Claisen-Schmidt condensation: Acetophenone has active methyl group so it condenses with aldehydes in the presence of sodium hydroxide to give Chalcones. C6H5CHO C6H5COCH3 C6H5COCH CHC6H5 NaOH benzal acetophenone 5-Acetophenone condenses with ethylbenzoate in presence of sodium ethoxide to give dibenzoyl methane. C6H5CO2C2H5 C6H5-CO-CH3 C6H5CO-CH2-COC6H5 NaOC2H5 (Explain the mechanism of the reaction?) 6-Acetophenone reacts with bromine in glacial acetic acid or in dry ether as a solvent to form φ-bromoacetophenone. COCH3 Br COCH2Br 2 Et2O Bezophenone C6H5COC6H5 Methods of preparation: 1- By distillation of calcium salts:  ( C6H5CO2 )2Ca C6H5COC6H5 + CaCO3 calcium benzoate 2-By using Fridel-Craft’s reaction: Reaction of benzene with benzoyl chloride in presence of anhydrous AlCl3 gives benzophenone. C6H5COCl CO + HCl AlCl3 Chemical properties: 1-Benzophenone can be reduced by zinc in alcoholic KOH to give benzhydrol. Zn /KOH C6H5-CO-C6H5