Aromatic Alcohols Aromatic alcohols are compounds containing a hydroxyl group in a side- chain, and may be regarded as aryl derivatives of the aliphatic alcohols Preparation 1-By hydrolyzing benzyl chloride with aqueous sodium hydroxide CH2Cl NaOH CH2OH NaCl 2-By reducing benzaldehyde with zinc and hydrochloric acid e, H CHO CH2OH By means of the cannizaro reaction 2 CHO NaOH CH2OH COONa 90 % It may also be prepared by means of a crossed Cannizzaro reaction Ar-CHO + HCHO Ar-CH2OH The reactions of benzyl alcohol are similar to those of the primary aliphatic alcohols; e.g., on oxidation, it forms benzaldehyde and finally benzoic acid [O] [O] CH2OH CHO COOH Benzyl alcohol may be catalytically (palladium) reduced to toluene: Pd/C CH2OH H2 CH3 H2O Aromatic aldehydes Aromatic aldehydes fall into two groups: those in which the aldehyde group is directly all to the nucleus, and those in which it is attached to the side- chain. The former group comprise the aromatic aldehydes; the latter, which behave as aliphatic aldehydes, are best regarded aryl-substituted aliphatic aldehydes 1- Benzaldehyde (benzenecarbonal) It is also known as oil of bitter almonds, since it is found in glucoside amygdalin, which occurs in bitter almonds Preparation CHCl2 CHO H O+ 1- 3 + 2 HCl (76%) Hydrolysis with aq acid Benzylidene chloride H O CH2Cl CH O N CHO O 2- Pb(NO3)2, + HNO2 CO2 Benzyl chloride CH3 CH(OCOCH3)2 CHO + 3- CrO3 H + 2 CH3COOH (CH3CO)2O Toluene Benzylidene acetate (40-50%) Hydrolysis with dilute H2SO4 or HCl 4- Gattermann-Koch aldehyde synthesis: CHO AlCl + CO + HCl 3 + HCl Cu2Cl2 Mechanism .. CO + HCl + AlCl3 CH O CH O + AlCl4 Formyl cation 5- Gattermann aldehyde synthesis CHO AlCl HCl 3 + HCN + + NH3 Mechanism AlCl HCl + HCN 3 NH CHCl (imidoformyl chloride) CH NH AlCl + NH CHCl 3 + HCl Aryl imine H2O CHO + NH3 Benzaldehyde and aromatic aldehydes in general resembles aliphatic aldehydes in the following reactions: (i) It gives the Schiff’s reaction. (ii) It is readily oxidised, i.e., it is a strong reducing agent; e.g., it reduces ammoniacal silver nitrate, itself being oxidised to benzoic acid when exposed to air. (iii) Benzaldehyde forms a bisulphite compound, and may be prepared via this compound: OH CHO CH SO Na 3 + NaHSO3 (iv) Benzaldehyde forms a cyanohydrin (mandelonitrile) OH CHO CH CN + HCN Cyanohydrin (mandelonitrile) CHO NHNH2 HC N NH + Benzaldehyde Phenyl hydrazine Phenylhydrazone CHO HC N N CH + NH2NH2 Benzaldehyde Hydrazine Benzylideneazine Benzaldehyde reacts with hydroxylamine to give benzaldoxime which exists in two geometrical isomeric forms. H OH H CHO C N C N OH + NH2OH + Benzaldoxime (syn-form) Benzaldoxime (anti-form) Benzaldehyde and other aromatic aldehydes differs from aliphatic aldehydes in the following ways: (i) It does not reduce Fehling’s solution. (ii) It does not readily polymerise; e.g., it does not resinify with sodium hydroxide (Aldol reaction no alpha hydrogen), (iii) but undergoes the Cannizzaro reaction because it is not having an alpha- hydrogen atom (The reaction is limited to aldehydes lacking alpha hydrogen centers. Under ideal conditions the reaction produces only 50% of the alcohol and the carboxylic acid. CHO CH2OH COONa 2 + NaOH + (iii) Reduction of benzaldehyde with zinc/HCl or sodium amalgam gives hydrobenzoin as well as benzyl alcohol. H OH OH .. C O . HC C H 2 Zn/HCl H+ Hydrobenzoin With aliphatic aldehydes it gives only the alcohol (vi) When benzaldehyde chlorinated , benzoyl chloride is produced (no alpha-hydrogen is present H O C O C Cl + Cl2 + HCl In aliphatic aldehydes, halogenation occur at alpha hydrogen Condensation reactions of benzaldehyde 1- Claisen reaction benzaldehyde, in the presence of dilute alkali, condense with aliphatic aldehydes or ketones containing α-hydrogen CHO CH CHCHO NaOH + CH3CHO + H2O Cinnamaldehyde CHO CH CHCOCH3 NaOH + CH3COCH3 + H2O Benzylideneacetone (65-78%) CHO CH CHCOCH3 NaOH + CH3COCH3 + H2O Benzylideneacetone (65-78%) CHO CH CHCOCH CH Dibenzylideneacetone CHO CH NaOH CHCO + CH3CO + H2O (Benzylideneacetophenone, Chalcone) (phenyl styryl ketone) (85%) CH CHCO CH2 CH2CO Pt/EtOAc + H 2 Zn/HOAc (Benzylideneacetophenone, Chalcone) Benzylacetophenone (81-95%) (phenyl styryl ketone) (85%) 2- Perkin reaction When benzaldehyde (or any other aromatic aldehyde) is heated with the anhydride of an aliphatic acid (containing two α-hydrogen atoms) in the presence of its salt, condensation takes place to form a β-arylacrylic acid Perkin reaction does not usually take place with aliphatic aldehydes. CHO CH CHCOOH CH3COONa + (CH3CO)2O Cinnamic acid arylacrylic acid Mechanism CH COOCOCH 3 3 + CH3COO CH2COOCOCH3 + CH3COOH O OH H O - H O CH COOCOCH 2 2 C + 2 3 C CH2COOCOCH3 H H C CHCOOCOCH H3O C CHCOOH 3 + CH3COOH H H 3- Benzoin condensation The benzoin condensation is a reaction between two aromatic aldehydes, particularly benzaldehyde. The reaction is catalyzed by a nucleophile such as the cyanide anion. The reaction product is benzoin as the parent compound (aliphatic aldehydes do not undergo the benzoin condensation) HO CHO CH CO 2 KCN EtOH/H2O Benzoin (83%) Mechanism O O OH C + CN C CN C.. CN H H CHO OH O O OH C C C C CN H CN H O OH C C + CN H OH O C C HO C C OH H O OH O H Reduction C C C C H H Benzoin Deoxybenzoin (desoxybenzoin) Derivatives of Benzaldehyde Phenolic aldehydes (Hydroxyaldehydes): Gattermann’s aldehyde synthesis (prep. of p-hydroxybenzaldehyde OH OH AlCl + HCN + HCl 3 + HCl OH CH NH ClCH NH H2O + NH3 Imidoformyl chloride CHO Reimer-Tiemann reaction (for prep. of o and p-hydroxybenzaldehyde) OH OH CHO NaOH + CHCl3 60oC Mechanism : CHCl3 + OH H2O + CCl3 Cl + : CCl2 Dichlorocarbene O O O H H CCl2 C Cl + : CCl2 Cl Dichlorocarbene (Electrophilic reagent) O O O H H H OH C Cl C Cl C .. OH OH O OH H H C C O H O Salicylaldehyde (o-hydroxybenzaldehyde) Preparation OSO2 OSO2 OH CH3 CHO CHO + MnO2 H H2SO4 o-Methylphenyl benzenesulphonate Properties OH OH OH CH2OH CHO COOH Reduction Oxidation o-Hydroxybenzyl alcohol Salicylaldehyde o-Hydroxybenzoic acid oxidation with alkaline H2O2 OH OH Catechol m-Hydroxybenzaldehyde CHO CHO CHO (i) Sn-HCl H2O (ii) NaNO2- HCl boil (51-56%) NO2 OH N2 Cl Vanillin OH OH OCH3 OCH3 CHCl3 NaOH CHO Guaiacol Vanillin Aromatic Ketones Aromatic ketones may be either alkaryl ketones or diaryl ketones Acetophenone (methyl phenyl ketone, acetylbenzene) Preparation: (1) From calcium or iron salt of benzoic acid: COO COCH3 2 Ca + (CH3COO)2Ca + 2 CaCO3 2 Calcium benzoate Calcium acetate acetophenone (2) Friedel-Crafts acylation of benzene: COCH3 AlCl3 + CH3COCl + HCl (50%) acetophenone (3) Oxidation of ethylbenzene CH2CH3 COCH3 (O) 126oC acetophenone Ethylbenzene Chemical reactions:- (1) Reduction:- OH COCH3 HC CH3 Na/EtOH acetophenone Phenylmethylmethanol COCH3 H2C CH3 Zn/HCl Or LiAlH4 acetophenone ethylbenzene (2) Oxidation:- O COOH COCH3 C COOH KMnO4 KMnO4 acetophenone Phenylglyoxylic acid Benzoic acid (benzoyl formic acid) COCH3 COCHO + SeO2 + Se + H2O + H2O (72-96%) Phenylglyoxal CO2OH COCH3 OCOCH3 (63%) Phenyl acetate (3) Halogenation COCH COCH Br 3 2 Br2 + HBr (64-66%) Ether at 0oC Phenacyl bromide Acetophenone forms an oxime, phenylhydrazone and cyanohydrin The acetyl group is m-orienting, and so when acetophenone undergoes substitution, the main product is the m-derivative. Condensation reaction of acetophenone - Acetophenone condenses with acetic anhydride in the presence of BF3 to form benzoylacetone. COCH3 COCH COCH CHO 2 C3H CHCOOH BF3 + (CH3CO)2O + CH3COOH (83%) CH3COONa + (CH3CO)2O Benzoylacetone Cinnamic acid arylacrylic acid Acetophenone condenses with ethyl benzoate in the presence of sodium ethoxide COOC H COCH3 2 5 COCH2CO C H ONa + 2 5 (62-71%) ethylbenzoate dibenzoylmethane + C2H5OH Acetophenone undergoes the Mannich reaction:- COCH3 COCH2CH2N(CH3)2. HCl + HCHO + (CH3)2NH. HCl (60%) Benzophenone (diphenyl ketone) O Preparation C (1) By heating of Calcium benzoate COO CO Ca + CaCO3 (30%) 2 (2) By Friedel-Crafts condensation between benzoyl chloride and benzene COCl CO (1) AlCl + 3 + HCl (80%) (2) AlCl3 2 + COCl2 + 2 HCl Carbonyl chloride CO Chemical reactions Benzophenone forms an oxime, but does not form a cyanohydrin or bisulphate addition compound 1- Reduction: OH Zn, CH COOH HC Zn, KOH C 3 C C OH O OH Benzhydrol (diphenylcarbinol) (90%) Benzopinacol (90%) CO CH2 LiAlH4/AlCl3 diphenylmethane 2- Fusion with KOH CO COOK KOH + H2O.