Polynuclear Hydrocarbons PDF

UNIT-IV Polynuclear hydrocarbons Polynuclear hydrocarbons 1. Polycyclic aromatic hydrocarbons are hydrocarbons—organic compounds containing only carbon and hydrogen—that are composed of multiple aromatic rings. The simplest suc...

UNIT-IV Polynuclear hydrocarbons Polynuclear hydrocarbons 1. Polycyclic aromatic hydrocarbons are hydrocarbons—organic compounds containing only carbon and hydrogen—that are composed of multiple aromatic rings. The simplest such chemicals are Naphthalene, having two aromatic rings, and the three-ring compounds Phenanthrene, Anthracene, Diphenylmethane, Triphenylmethane 2. Polynuclear aromatic hydrocarbons are aromatic organic compounds which contain more than one atom. This class of compounds contains polycyclic aromatic compounds and other aromatic compounds containing more than one atom. The term polynuclear refers to many+nuclei. Naphthalene Anthracene Phenanthrene H2 H C C Diphenylmethane Triphenylmethane 1  Classification of Polynuclear hydrocarbons Polynuclear Hydrocarbons Benzenoid Non- Benzenoid eg. Azulene Isolated Fused rings eg. H2 C Diphenylmethane H Linear Angular C eg. eg. Triphenylmethane Naphthalene Phenanthrene Anthracene 2 4.1. Naphthalene 1. Naphthalene is an organic compound with formula C10H8. It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor as an aromatic hydrocarbon 2. Naphthalene is an aromatic hydrocarbon found in coal tar or crude oil. Naphthalene is used in the manufacture of plastics, resins, fuels, and dyes. It is also used as a fumigant insecticide that works by turning directly from a solid into a toxic vapor. This process is called sublimation. 4.1.1. Structure: Naphthalene's structure consists of a fused pair of benzene rings 8 1 7 2 6 3 5 4 4.1.2. Resonance Structure: Conjugated double bonds in a molecule means alternate single and double bonds. These enables the electrons to be delocalized over the whole system and so be shared by many atoms. I II III Hybrid nucleus of Napthalene 3 4.1. 3. Synthesis/ Preparation of Naphthalene 1) From - 4 – Phenyl – 1- butene: This preparation involves the reaction occurs on 4 – Phenyl – 1- butene, which is passed over red hot copper oxide (CuO) to form naphthalene Selenium CuO Se Cyclization H2 dehydrogenation 4- phenyl - 1- butene 1,2-Dihydro Naphthalene naphthalene (But-3-enyl-benzene) II I 2) Haworth synthesis for Naphthalene O O AlCl3 Zn-Hg/HCl O R HO Clemmensen R HO reduction R Substituted O O O benzene Succinic anhydride I II R= CH3 dehydrolysis conc. -H2O H2SO4 Cyclization Se ,  Zn-Hg/HCl R 2 H2 Clemensen R R Dehydrogenation reduction O V IV III Substituted alkyl Naphalene 4 3) From – benzylidene – propenoic acid (4- phenyl – 3- butanoic acid) Keto - enol form conc. H2SO4 Isomerization -H2O OH Rearrangment O dehydrolysis O OH -Benzylidene- Cyclization 2H-Naphthalen-1-one Naphthalen-1-ol 3-propenpoic acid II I Zn -ZnO Naphthalene III 4) From Petroleum o Cu , 650 C Peteroleum Distillation (Petroleum is a mixture of a very large number of different hydrocarbons the most commonly found molecules Naphthalene are alkanes) 5 5) Synthesis of - alkyl naphthalene O O AlCl3 O COOH Benzene O 4-Oxo-4-phenyl-butyric acid Succinic I anhydride Clemmensen Zn - Hg/ HCl reduction conc. H2SO4 H2O COOH O dehydrolysis 3,4-Dihydro-2H-naphthalen-1-one Cyclization 4-Phenyl-butyric acid II III Grignard reagent RMgX addition H2O H2SO4 Se H2O H2 dehydrolysis R OH dehydrogenation R R IV V VI R= CH3, C2H5 Alkyl Napthalene 6 4.1. 4. Reactions of Naphthalene 1) Oxidation reaction O Chromium oxide CrO3 AcOH Acetic acid O 1, 4- Naphthoquinone Ozone CHO O3 H2O, Zn CHO Benzene-1,2-dicarbaldehyde O Oxygen Naphthalene molecule O2 O V2O5 Vanadium oxide O Pthalic anhydride COOH KmnO4 H COOH Phthalic acid 7 2) Reduction reaction Na EtOH 1,4-Dihydro-naphthalene Na Isoamyl alcohol (isopentyl Naphthalene alcohol) 1,2,3,4-Tetrahydro-naphthalene H2 Ni / Pt Decahydro-naphthalene (Decalene) 8 3) Electrophilic Aromatic Substitution reaction: Electrophilic Aromatic Substitution reactions take place in Naphthalene at 1 – Position Question: Why Electrophilic Aromatic Substitution reaction take place in Naphthalene at 1 – Position Ans: 8 1 7 2 6 3 5 4 i) Attack at C- 1 Position Electrophilic group H E H E E Naphthalene I II H H E E III IV 9 ii) Attack at C- 2 Position Electrophilic group H H E E E Naphthalene I II Justification: 1. According to fries rule, the most stable arrangement of a Polynuclear compound is that form which has the maximum number of rings in the benzenoid condition 2. At C- 1 position, contributing 4 resonance structure or canonical form, while at C- 2 position, contributing only 2 resonance structure 3. Attack at the C- 1 position is much more stable than attach at C- 2 position. Therefore Electrophilic Aromatic Substitution reactions take place in naphthalene at 1 – position 10 Electrophilic Aromatic Substitution reaction with Naphthalene 3.1) Nitration reaction NO2 Conc. H2SO4 Conc. HNO3 Naphthalene 1-Nitro-naphthalene 3.2) Sulfonation reaction SO3H Conc. H2SO4 o 80 C Naphthalene Naphthalene-1-sulfonic acid Conc. H2SO4 SO3H o 160 C Naphthalene-2-sulfonic acid 11 3.3) Halogenation reaction i) Chlorination Cl Cl2 HCl FeCl3 (biproduct) Naphthalene 1-Chloro-naphthalene (Product) ii) Bromination Br Br2 HBr CCl4 (biproduct) Naphthalene No catalyst require like FeBr3 1-Bromo-naphthalene (Product) 12 3.4) Fridel Craft’s reaction i) Alkylation CH3 CH3Cl HCl AlCl3 (biproduct) Naphthalene 1-Methyl-naphthalene (Product) ii) Acylation O C CH3 Acetyl chloride CH3COCl HCl AlCl3 , CS2 (biproduct) (non polar solvent) Naphthalene 1-Naphthalen-1-yl-ethanone (Product) O CH3COCl C CH3 HCl AlCl3 , Nitro benzene (biproduct) ( polar solvent) 1-Naphthalen-2-yl-ethanone 13 4) Addition of Chlorine to Naphthalene Cl Chlorine Cl2 Naphthalene Cl 1,4-Dichloro-1,4-dihydro-naphthalene Cl Cl Excess Cl2 Cl Cl 1,2,3,4-Tetrachloro-naphthalene 5) Carboxylation Br MgBr Br2 Mg FeBr3, AlCl3 Naphthalene 1-Bromo-naphthalene CO2 COOMg COOH H2O H Naphthalene-1-carboxylic acid 14 4.1.5. Medicinal use of Naphthalene: 1. Naphthalene is use in the synthesis of Propranolol drug as antihypertensive agent OH H N O 2. Naphthalene is use in the synthesis of Tolnaftate drug as antifungal agent S N O 3. Naphthalene is use in the synthesis of menadione drug, as supplement for vitamin K O O 15 4. Naphthalene is use in the synthesis of Napthazoline drug, as vasoconstriction for rhinitis & sinusitis (allergic inflammation) H N N 5. Naphthalene is use in the synthesis of Naproxen drug, as antiinflammatory agent OH OH O H3CO Other Uses of Naphthalene 1. Naphthalene is use as a moth-repellent 2. Naphthalene is use as insecticide 3. Naphthalene is also used for increasing illuminating power of coal gas 4. Napthol is used in the manufacturing of pthalic anhydride compound, which is an intermediate for insectides 5. Naphthalene is useful for preparation of dyes 16 4.6. Naphthalene Derivative There are some naphthalene derivatives as follows NO2 NH2 OH OH 1- Napthylamine Naphthalen-2-ol 1-Nitro-naphthalene Naphthalen-1-ol 4.6.1. Naphthalene Derivative Preparation 4.6.1. 1. Preparation of 1 – Napthylamine NH2 4.6.1.1. Synthesis/ Preparation of 1- Napthylamine NO2 NH2 Conc. HNO3 Zn/ HCl Conc. H2SO4 Reduction Nitration Naphthalene 1-Nitro-naphthalene 1 - Napthylamine 17 4.6.1.2. Reactions of 1- Napthylamine NH2 N N Cl Br NaNO2 CuBr,  HCl N2 Diazotization reaction Sandmeyer 1-Bromo Napthalene reaction 1 - Napthylamine naphthalene diazotisation salt 4.6.2. 2- Napthol (α- Napthol) OH 4.6.2. 1. Synthesis/ Preparation of 1- Napthol (α- Napthol) SO3H OH Conc. H2SO4 NaOH o o 80 C 300 C Naphthalene Naphthalene 1- Napthol -sulfonic acid 18 4.6.2. 2. Reactions of 1- Napthol (α- Napthol i) Methoxylation OCH3 OH Methanol CH3OH Conc. H2SO4 H2O 1-Methoxy-naphthalene 1- Napthol ii) Bucher reaction NH2 OH NH3 NH4HSO3 Ammonium bisulfite 1- Napthyl amine 1- Napthol H2O 4.6.3. 2- Napthol (β- Napthol) OH 19 4.6.3. 1. Synthesis/ Preparation of 2- Napthol (β- Napthol) SO3H Conc. H2SO4 o 180 C Naphthalene o NaOH Naphthalene 2-sulfonic acid 160 C OH 2- Napthol 4.6.3. 2. Reactions of 2- Napthol (β- Napthol) i) Methoxylation Methanol OH OCH3 CH3OH Conc. H2SO4 H2O 2- Napthol 2-Methoxy-naphthalene ii) Bucher reaction OH NH3 NH2 NH4HSO3 Ammonium 2- Napthol bisulfite 2- Napthyl amine H2O 20 4.2. Anthracene Structure: 1 9 8 8 9 1 7 7 2 2 OR 3 3 6 6 5 10 4 4 10 5 1. Anthracene is a tricyclic aromatic hydrocarbon or polycyclic aromatic hydrocarbon (PAH) of formula C14H10 2. It is consisting of three fused benzene rings. It is a component of coal tar. 3. Anthracene is used in the production of the red dye alizarin and other dyes 4.2.1. Resonance: I II III IV 21 4.2.2. Synthesis/ Preparation of Anthracene 1) Fridel Craft’s alkylation reaction: Benzyl chloride reacts with itself to form 9, 10 – dihydro – anthracene, which readily loses two hydrogen atoms to yield anthracene attachment Cyclization CH2Cl AlCl3 ClH2C 2 HCl EAS Benzyl Benzyl 9, 10- dihydro-anthracene chloride chloride I Se dehydrogenation H2 Anthracene 22 2) From Anthraquinone O Distillation o Zn , 150 C H2 Reduction Anthracene O reaction Anthraquinone 3) Elbes reaction: The conversions of a diaryl ketone, containing a methyl or methylene group at ortho to the carbonyl function is known elbes reaction O Pyrolysis (Heat) H2O CH3 Intermolecular Anthracene O - methyl - o- benzophenone reaction 23 4) Haworth synthesis for Anthracene O H COOH H AlCl3 O attach Attachment O O Benzene Pthalic anhydride 2-Benzoyl-benzoic acid I Cyclization H2SO4 H2O O Zn(Hg) HCl Clemmensen 9,10-Dihydro-anthracene reduction O III Anthraquinone dehydrogenation Pd, CO2 II H2 Anthracene IV 24 5) Diel’s Alder reaction Attachment O O H2C CH cycloaddition CH H2C O O Naphthoquinone Buta-1,3-diene 1,4,4a,9a-Tetrahydro-anthraquinone I AcOH CrO3 (acetic acid) (chromium trioxide) O Zn / HCl Clemmensen reduction 9,10 - dihydro-anthracene O Anthraquinone III II dehydrogenation Se H2 Anthracene IV 25 4.2. 3. Reactions of Anthracene 1) Oxidation O K2Cr2O7 H dil. HNO3 Anthracene O 4a,9a-Dihydro-anthraquinone 2) Addition O2 (Oxygen) Molecule O O2 O Oxygen Anthracene molecule Anthracne epoxide 3) Reduction Na ethanol/ isopropanol Anthracene 9, 10 -dihydro-anthracene 26 4) Electrophilic Aromatic Substitution reaction Electrophilic Aromatic Substitution reaction takes place at C – 9 positions in anthracene 8 9 1 7 2 3 6 5 10 4 i) Attack at C – 1 position H E E Electrophilic group I Anthracene H E II 27 ii) Attack at C – 2 position H E E Electrophilic group Anthracene iii) Attack at C – 9 position H E E Electrophilic group Anthracene Most stable Carbocation 1. At C – 1 & C – 2 attack anthracene system retained and gets less stable product 2. At C – 9 position, forms more stable carbocation intermediate 3. Attack at 9th position in anthracene, which is more susceptibility at C – 9 is preferable. Hence electrophilic aromatic substitution is observed at C – 9 position 28 4. 1) Nitration NO2 HNO3 H2SO4 Anthracene 9-Nitro-anthracene 4. 2) Sulphonation SO3H H2SO4 Anthracene Anthracene-1-sulfonic acid 4.3) Halogenation i) Chlorination Cl Cl2 HCl CCl4 Anthracene 9-Chloro-anthracene 29 ii) Bromination Br Br2 HBr acetic acid Anthracene 9-Bromo-anthracene 4.4) Fridel Craft’s reaction i) Alkylation CH3 CH3Cl HCl AlCl3 Anthracene 9-Methyl-anthracene ii) Acylation O C CH3 Acetyl chloride CH3COCl HCl AlCl3 Anthracene 1-Anthracen-9-yl-ethanone 30 5) Diel’s Alder reaction O Cycloaddition Reaction O  O Anthracene Furan-2,5-dione O O O Endo - Anthracene - Maleic acid 4.2. 4. Medicinal uses of Anthracene 1. Anthracene is use in the synthesis of Anthraquinone (Laxative drug) 2. Anthracene derivatives act as good anti-cancerous drugs and they are carcinogenic to many living beings. 3. Anthracene is use in the synthesis of Anthracycline anticancer antibiotics are Structurally they are glycoside & contain a sugar portion & a non sugar organic portion. Example, Doxorubicin, Daunorubicin 31 1) Doxorubicin O OH O OH OH H3C O O OH O CH3 H2N O 2) Daunorubicin O OH O OH O OH O CH3 H2N O HO Other uses: 1. Anthraquinone is used in the manufacture of alizarin and several dyes 2. It is also used in wood preservatives, insecticides, and coating materials 32 4.5. Anthracene Derivatives O O OH OH O O 9, 10 - Anthraquinone Alizarine 33 4.5.1 Anthracene Derivative Preparation 4.5. 1.1. Preparation of 9, 10 - Anthraquinone O O AlCl3 O HOOC O Benzene Pthalicanhydride H2O H2SO4 O O 9, 10 - Anthraquinone 34 4.5.1.2. Reactions of 9, 10 – Anthraquinone O Zn ,  Dostillation Anthracene O Sn/HCl O 9, 10 - Anthraquinone AcOH Zn / NaOH OH 10H-Anthracen-9-one OH Anthracene-9,10-diol 35 4.5.2.1. Preparation of Alizarine O O SO3H SO3H Oleum , H2SO4 o 160 C O O 9, 10 - Anthraquinone 9,10-Dioxo-9,10-dihydro-anthracene-1,2-disulfonic acid  2 NaOH O OH OH O Alizarine 4.5.2.2. Reactions of Alizarine O OH O OH OH OH H2SO4 HNO3 O Nitration O NO2 Alizarine 1,2-Dihydroxy-4-nitro-anthraquinone 36 4.3. Phenanthrene Structure: 6 1 5 10 9 4 1 6 8 14 2 10 3 2 13 OR 5 7 9 7 11 3 4 11 8 12 12 14 Phenanthrene 13 Phenanthrene 1. Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings. The name 'phenanthrene' is a composite of phenyl and anthracene. 2. Phenanthrene is used to make dyes, plastics and pesticides, explosives and drugs. It has also been used to make bile acids, cholesterol and steroids 37 4.3.1. Resonance Phenanthrene II III I V IV Resonance energy 1. Naphthalene: 61 Kcal mol-1 2. Anthracene: 84 Kcal mol-1 3. Phenanthrene: 92 Kcal mol-1 38 4.3.2. Preparation of Phenanthrene: 1) Haworth synthesis of Phenanthrene O O COOH AlCl3 O Naphthalene O I Succinic anhydride Clemmensen Zn - Hg / HCl reduction COOH Conc. H2SO4 O H H2O Cyclization II 3,4-Dihydro-2H-phenanthren-1-one III Clemmensen Zn - Hg / HCl reduction Se 2 H2 dehydrogenation Phenanthrene 1,2,3,4-Tetrahydro-phenanthrene VI V 39 2) Preparation of 2 – alkyl phenanthrene O R O R COOH AlCl3 O H2O O I Naphthalene Substituted Clemmensen Zn - Hg/HCl succinic reduction anhydride R R COOH H2SO4 ,  O H2O Cyclization II III Clemmensen Zn - Hg/HCl reduction R R Se 3H dehydrogenation V IV 2 - alkyl Phenanthrene 40 3) Preparation of 1- alkyl phenanthrene Grignard reagent R RMgX OMgX O Grignard addition I 3,4-Dihydro-2H-phenanthren -1-one H2O H R H2SO4 ,  OH R H2O dehydrolysis II III Se dehydrogenation R H2 Substituted alkyl Phenanthrene IV 41 4) Pschorr synthesis for Phenanthrene C - C attachment O COOH CH2COONa C H acetic anhydride AC2O NO2 H2O NO2 dehydrolysis sodium 2-Nitro-benzaldehyde acetate 3-(2-Nitro-phenyl)-2-phenyl-acrylic acid I Zn - Hg / HCl reduction COOH COOH NaNO2 H2SO4 N2 NH2 Diazotisation II III Cu coupling reaction N2 Phenanthrene IV 42 5) Bardhan – Sengupta Phenanthrene synthesis Vanadium pentoxide V2O5 ,  HO H2O dehydrolysis 2-Phenethyl-cyclohexanol I Cyclization 1,2,3,4,4a,9,10,10a-Octahydro-phenanthrene dehydrogenation Se 3 H2 II Phenanthrene 43 4.3.3. Reactions of Phenanthrene 1) Oxidation reaction i) Addition of Potassium Dichromate molecule O O Potassium dichromate K2Cr2O7 / NaCr2O7 H Oxidation Phenanthrene-9,10-dione Phenanthrene ii) Addition of Oxygen molecule Oxygen molecule CHO O2 CHO H2O Phenanthrene Biphenyl-2,2'-dicarbaldehyde 44 iii) Addition of hydrogen peroxide molecule Hydrogen peroxide COOH 2 H2O2 COOH ACoH acetic acid Oxidation reaction Biphenyl-2,2'-dicarboxylic acid Phenanthrene 2) Reduction reaction Hyderogenation Na,  isopropyl alcohol / ethanol 4a,9,10,10a-Tetrahydro- Phenanthrene phenanthrene 45 3) Electrophilic aromatic substitution reaction 6 1 5 10 9 4 1 6 8 14 2 10 3 2 13 OR 5 7 9 7 11 3 4 11 8 12 12 14 Phenanthrene 13 Phenanthrene i) Attack at C – 1 position E H E Electrophilic I group Phenanthrene E H II 46 ii) Attack at C – 2 position E E H Electrophilic I group Phenanthrene iii) Attack at C – 9 position H E E Electrophilic I group Phenanthrene 1. At C – 1 & C – 2 attack phenanthrene system retained and gets less stable product 2. At C – 9 position, forms more stable carbocation intermediate 3. Attack at 9th position in phenanthrene, which is more susceptibility at C – 9 is preferable. Hence electrophilic aromatic substitution is observed at C – 9 position 47 1) Nitration NO2 10 9 1 6 8 14 HNO3 2 13 5 7 H2SO4 3 4 12 11 9-Nitro-phenanthrene Phenanthrene 2) Sulfonation conc. H2SO4 HO3S Phenanthrene Phenanthrene-2-sulfonic acid 3) Halogenation i) Chlorination Cl chlorine molecule Cl2 HCl FeCl3 Phenanthrene 9-Chloro-phenanthrene 48 ii) Bromination Br bromine molecule Br2 HBr FeBr3 9-Bromo-phenanthrene Phenanthrene 4) Fridel Craft’s reaction i) Alkylation CH3 CH3Cl HCl AlCl3 9-Methyl-phenanthrene Phenanthrene ii) Acylation O acetyl chloride C CH3 O Cl C CH3 HCl AlCl3 Phenanthrene 49 6) Addition of Bromine molecule Bromine molecule Br Br2 Addition reaction Br Phenanthrene 9,10-Dibromo-9,10-dihydro-phenanthrene 7) Benzilic acid rearrangement O COOH NaOH OH H O Phenanthrene-9,10-dione 9-Hydroxy-9H-fluorene-9-carboxylic acid (Diketone) 50 4.3.4. Medicinal uses of Phenanthrene 1. Many steroid moiety contain phenanthrene nucleus and steroids are mainly useful to reduce inflammation (antiinflammatory) & treatment of asthma, hormone disorder, skin disorder, autoimmune disorder & some kinds of cancer disorder 2. Phenanthrene nucleus is present in sex hormones such as Estrogen, Progesterone and Testosterone & Bile salts Estrogen Progesterone Testosterone 3. Steroid is used as oral contraceptives & antiinflammatory agents (Norethisterone; oral contraceptives) (Prednisone; antiinflammatory) 51 4. Phenanthrene is useful in the synthesis of Steroids, as dexamethasone, It is used in the treatment of many conditions, including rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease (Dexamethasone) 5. Narcotic opiate drug such as Morphine & Codeine drug contains phenthrene moiety. These two drugs are used to treat acute & chronic pain, coughing, and diarrhea. It is frequently used for pain from myocardial infarction and during labor (Morphine) (Codeine) 52 6. Phenanthrene nucleus is present in Cardiac Glycosides, which is used in the treatments for congestive heart failure and cardiac arrhythmias 7. Phenanthrene is used to make dyes, plastics and pesticides, explosives 53 4.3.5. Phenanthrene Derivatives H HO O H H O N O H H H H HO Steroid Phenanthraquinone Morphine (Phenanthrene-9,10-dione) 54 4.3.5. 1. Phenanthrene Derivative Preparation 4.3.5. 1. 1. Preparation of Phenanthraquinone O K2Cr2O7 , H2SO4 O Oxidation Phenanthraquinone Phenanthrene 4.3.5. 1.2. Reaction of Phenanthraquinone NO2 O O HNO3 O O H2SO4 2-Nitro-phenanthrene-9,10-dione Phenanthraquinone 55 4.4. Diphenyl methane Diphenylmethane is an organic compound with the formula (C6H5)2CH2 2). The compound consists of methane wherein two hydrogen atoms are replaced by two phenyl groups Structure: H C H 4.4.1. Resonance: H H C C H H I II 56 4.4.2. Preparation of Diphenyl methane 1) From Benzyl chloride & Benzene: Benzene is react with benzyl chloride in presence of aluminum amalgam along with heat to form diphenyl methane H2 ClH2C C Al (Hg) ,  HCl Benzene Benzyl chloride Diphenyl methane 2) From Benzophenone O Clemmensen reduction H2 C C Zn- Hg / HCl or AlH4 Alumimium hydride Benzophenone Diphenyl methane (Diphenyl-methanone) 3) From Phenyl magnesium bromide & Benzyl chloride H2 MgBr ClH2C C  MgBrCl Phenyl magnesium Benzyl chloride bromide Diphenyl methane 57 4.4.3. Reaction of Diphenyl methane 1) Oxidation reaction O H2 C C KMnO4 Oxidation Benzophenone Diphenyl methane 2) Cyclization H2 C o 400 C H2 Cyclization 9H-Fluorene Diphenyl methane 3) Nitration reaction H2 H2 C C HNO3 H2SO4 NO2 4 - Nitro - diphenyl methane Diphenyl methane (1-Benzyl-4-nitro-benzene) 58 4) Sulphonation reaction H2 H2 C C H2SO4 SO3H Diphenyl methane - 4- sulfonic acid Diphenyl methane (4-Benzyl-benzenesulfonic acid) 5) Halogenation reaction H2 H2 C C X2 - HX X X2 = Cl2, Br2 X = Cl, Br 4.4.4. Medicinal Uses 1. Diphenyl methane has antioxidant activity 2. It is useful in the synthesis of steroid drugs 3. It also useful in the synthesis of paracetmol or acetaminophen drug (treatment of fever & pain) 4. Diphenyl methane is use in the synthesis of benzophenone & Benzhydrol. These two compounds are act as intermediate for drug synthesis Other uses 1. Diphenylmethane is use for the preparation of dyes 2. It is used in the preparation of a polymerization initiator, diphenyl methyl potassium 59 4.4.5. Diphenyl methane Derivatives OH O C C H Benzhydrol Benzophenone (Diphenyl-methanol) (Diphenyl-methanone) 4.4.5. 1. Diphenyl methane Derivative Preparation 4.4.5. 1.1. Preparation of Benzhydrol O H2 C C KMnO4 Oxidation Diphenyl methane Benzophenone reduction NaBH4 , H2O reaction OH C H Benzhydrol 60 4.4.5. 1.2. Reactions of Benzhydrol OH OH Nitration C C 2 HNO3 H H 2 H2SO4 O2N NO2 Benzhydrol C2H5OH  H2SO4 OC2H5 esterification C H 61 4.5. Triphenyl methane 1. Triphenylmethane is the hydrocarbon 2.Triphenylmethane is the basic skeleton of many synthetic dyes called triarylmethane dyes, many of them are pH indicators, and some display fluorescence. 3. A trityl group in organic chemistry is a triphenylmethyl group Ph3C, e.g. triphenylmethyl chloride (trityl chloride) and the triphenylmethyl radical Structure CH 4.5.1. Resonance CH CH CH I II III 62 4.5.2. Preparation of Triphenyl methane 1) From Fridel crafts reaction: Triphenylmethane can be synthesized by Friedel-Crafts reaction from benzene and chloroform with aluminium chloride catalyst Electrophilic Aromatic Substitution Cl ALCl3 ,  3 Cl C H 3 HCl Cl H Benzene Chloroform (Trichloro-methane) Triphenyl methane 2) From Benzaldehyde & Benzene O Condensation H C ZnCl2 ,  2 H2O H Benzaldehyde Benzene Triphenyl methane 63 3) From benzene & Carbon tetrachloride : Benzene may react with carbon tetrachloride using the same catalyst to obtain the trityl chloride-aluminium chloride adduct, which is hydrolyzed with dilute acid and to form triphenyl methane EAS C AlCl3 3 CCl4 Cl 3 HCl AlCl3 carbon Benzene teterachloride I HCl C AlCl4 H Aluminium tetrachloride II (biproduct) Triphenyl methane (product) 64 4.4.3. Reaction of Triphenyl methane 1) Oxidation reaction KMnO4 H OH Triphenyl methane Triphenyl-methanol 2) Reaction with sodium metal C Na H H Na 65 3) Nitration reaction NO2 EAS 3 HNO3 H H 3 H2SO4 NO2 O2N 4) Sulfonation reaction SO3H EAS 3 H2SO4 H H SO3H HO3S Triphenyl methane 66 5) Halogenation reaction X 3 X2 H H EAS X X X2 = Cl2, Br2 X = Cl, Br 5.5.4. Medicinal uses 1. Triphenyl methane is useful in the synthesis of Clotrimazole (antifungal agent) 2. It is used in the preparation of Gentian (antiseptic) 3. It also used in the preparation of Imiramin blue (antidepressant & anticancer agent) Other uses 1. Triphenyl methane is useful in the synthesis of rosaniline & paraosaniline (organic compound) 2. It is use in the manufacturing of textile products & dye 67 5.4.5. Triphenyl methane Derivatives Triphenyl methane Derivatives mainly as Clotrimazole, Gentian violet & Imiramin blue 1. Clotrimazole: antifungal agent 2) Gentian violet: (methyl violet 10B or hexamethyl pararosaniline chloride) : antiseptic dye used to treat fungal infections of the skin 3) Imiramin blue: A novel analogue of antidepressant & anticancer agent 68 4.4.5. Triphenyl methane derivative preparation 5.4.5.1. Preparation of Clotrimazole Cl 2 Cl2 Cl HCl I Substitution reaction Triphenyl methane Substitution reaction H N triethylamine Cl  N HCl 1H-Imidazole N N Clotrimazole II 69 5.4.5.2. Reactions of Clotrimazole H3C alkylation Cl CH4 N uv light N HCl N N Clotrimazole amination NH3 H2N HCl N N 70