MScCH-07 Vardhman Mahaveer Open University, Kota Synthetic Organic Chemistry MScCH-07 Vardhman Mahaveer Open University, Kota Synthetic Organic Chemistry Course Development Committee Chair Person Prof. Ashok Sharma Vice-Chancellor Vardhman Mahaveer Open University, Kota Coordinator and Members Coordinator SANDEEP HOODA Assistant Professor of Zoology School of Science & Technology Vardhman Mahaveer Open University, Kota Prof L.R. Gurjar Dr. Arvind Pareek Director Academic Director Regional Centre-Bharatpur VMOU Kota VMOU Kota Dr. Anuradha Dubey Dr. Sunil kumar Jangir Deputy Director,SOST Convener Chemistry VMOU Kota VMOU Kota Prof. P.S. Verma (Retd.) Prof. Pahup Singh (Retd.) Department of Chemistry Department of Chemistry University of Raj, Jaipur University of Raj, Jaipur Prof. P.D. Sharma (Retd.) Prof. Ashu Rani Department of Chemistry Department of Chemistry University of Raj, Jaipur University of Kota, Kota Dr. R.L. Pilaliya, (Retd.) Dr. Sapna Sharma Department of Chemistry, Govt. College Department of Chemistry Bikaner JECRC,university Jaipur Dr. Sanjay Kumar Sharma Dr. Sushil Kumar Sharma Department of Chemistry Department of Chemistry JECRC,university Jaipur University of Kota, Kota Editing and Course Writing Editor Prof. P.S. Verma (Retd.) Dr. Sushil Kumar Sharma Department of Chemistry Assistant Professor, Department of Pure University of Raj, Jaipur and Applied Chemistry University of Kota, Kota Writers: Dr. Shobhana Sharma 1,2,3,6 Dr.Sushil Kr. Sharma 4 ,8,11,14, Assistant Professor, Assistant Professor, Department of Chemistry Department of Pure and S.S.Jain Subodh Applied Chemistry P.G.College,Jaipur University of Kota, Kota Mr. Ankit Sharma 5.7,12 Dr.Girja Shankar Tailor 9,10 Assistant Professor, Assistant Professor, Department of Pure and Department of Chemistry Applied Chemistry Poddar University of Kota, Kota International College, Mansarovar, Jaipur Dr. Poonam Khandelwal 13,15,17,18 Dr. Neetu Kumari 19,20 Assistant Professor, Assistant Professor, Department of Chemistry Department of Chemistry Mohan lal Sukhadia Mohan lal Sukhadia University, University, Udaipur Udaipur Academic and Administrative Management Prof. Ashok Sharma Prof. L.R. Gurjar Vice-Chancellor Director (Academic) Vardhman Mahaveer Open University, Kota Vardhman Mahaveer Open University, Kota Prof. Karan Singh Dr. Subodh Kumar Director (MP&D) Additional Director (MP&D) Vardhman Mahaveer Open University, Kota Vardhman Mahaveer Open University, Kota ISBN : All Right reserved. No part of this Book may be reproduced in any form by mimeograph or any other means without permission in writing from V.M. Open University, Kota. Printed and Published on behalf of the Registrar, V.M. Open University, Kota. Printed by : MScCH-07 Vardhman Mahaveer Open University, Kota Index Unit No. Unit Name Page No. Unit -1 Organometallic Reagents-I 1 Unit -2 Organometallic Reagents-II 17 Unit -3 Oxidation 35 Unit -4 Oxidation of – OH group 53 Unit -5 Oxidation of Carbonyl And Carboxylic Groups 69 Unit -6 Reduction 98 Unit -7 Reduction of Carbonyl and Carboxylic Group 106 Unit -8 Reduction of Nitrogen containing group 146 Unit -9 Metallocene : Introduction, Synthesis and Chemical 159 reactions of Ferrocene Unit -10 Nonbenzenoid Aromatic Compounds: -General 173 consideration, Monocyclic aromatic anions, Synthesis and reactions of Tropone and Tropolone Unit -11 Polycyclic Aromatic Compounds General consideration, 188 synthesis and reactions of phenanthrene Unit -12 Disconnection Approach 205 Unit -13 Disconnections of C-X Group 226 Unit -14 Protecting Groups I 249 Unit -15 Protecting Group II 621 Unit -16 One Group C - C Disconnection Alcohols and Carbonyl 275 Compounds Unit -17 Two Group C-C Disconnections 298 Unit -18 Ring Synthesis 319 Unit -19 Synthesis of Some Complex Molecules I 345 Unit -20 Synthesis of Some Complex Molecules II 360 MScCH-07 Vardhman Mahaveer Open University, Kota Preface The present book entitled “Synthetic Organic Chemistry” has been designed so as to cover the unit-wise syllabus of MScCH-07 course for M.Sc. Chemistry (Final) students of Vardhman Mahaveer Open University, Kota. The basic principles and theory have been explained in simple, concise and lucid manner. Adequate examples, diagrammes , photographs and self-learning exercises have also been included to enable the students to grasp the subject easily. The unit writers have consulted various standard books and internet as their reference on the subject and they are thankful to the authors of these reference books. ---------------- Unit - 1 Organometallic Reagents-I Structure of unit: 1.0 Principle of organolithium compounds 1.1 Preparations of organolithium compounds 1.1.1 Oxidative- Addition reaction 1.1.2 Metal-metal exchange (Transmetallation) 1.1.3 Carbanion-halide exchange 1.1.4 Metal hydrogen exchange reactions (Metallation) 1.1.5 Metal hydride addition to alkenes 1.1.6 Halogen –metal exchange or inversion 1.1.7 By reduction of sulphides 1.2 Properties of organolithium compounds 1.2.1 Addition reaction with aldehydes and ketones 1.2.2 Addition reaction with ketenes and isocyanates 1.2.3 Addition reaction with immines, nitriles and isonitriles 1.2.4 Addition with CO2 and CS2 1.2.5 Nucleophilic substitution reactions at sp2 hybrid carbon 1.2.6 Nucleophilic substitution reactions at saturated atoms 1.3 Applications of organolithium compounds 1.4 Principle of organomagnesium halides 1.5 Preparations of organomagnesium halides 1.5.1 Oxidative- addition reaction 1.5.2 Carbanion-halide exchange 1.5.3 By vinyl halide 1.5.3 Metallation 1.5.4 By alkynes 1.6 Properties of organomagnesium halides 1.6.1 Reaction with compounds having acidic hydrogens 1.6.2 Addition with aldehydes and ketones 1 1.6.3 Addition with ketene and isocyanates 1.6.4 Addition reaction with imines and nitriles 1.6.5 Addition with CO2 and CS2 1.6.6 Nucleophilic substitution reactions at sp2 hybrid carbon 1.6.7 Nucleophilic substitution reactions at saturated atoms 1.7 Applications of organomagnesium halides 1.8 Summary 1.9 Review Questions 1.10 References and Suggested Readings 1.0 Principle of organolithium compounds Organolithium compounds are often schematically depicted as monomeric species with one lithium atom and a carbanionic group [MeLi or nBuLi] . But actually the structure of these compounds are much more complicated e.g- n-alkyl lithium are found to be hexameric in solvent.The simplest Li-R bond represents lithium atom as electron deficient and explains its tendency for polymerization like other electron deficient molecules. Infrared studies show that the strong tendency of methyl lithium to associate which persists in vapour phase also. Raman bands in diethyl ether solutions of methyl lithium indicates cluster mode of tetrameric units. Fig.1 Structure of (LiC2H5)4 with tetrahedral geometry NMR studies also indicate that methyl lithium retains the tetrameric solid state structure in solution. The structures of (Li-R)4 units i.e tetrameric depicted by X- 2 ray techniques . These comprises of four lithium atoms at the corners of a tetrahedron and the alkyl groups are located at each face of the tetrahedron. 1.1 Preparations of organolithium compounds The following methods can be adopted to prepare various organolithium compounds: 1.1.1 Oxidative- Addition reaction It is an important method for the preparation of simplest organolithium reagents. The most important alkyl lithium reagent is butyl lithium. This method involves the oxidation of a metal M by the addition of a group R-X. Et2O 1.1.2R -X + 2Li R-Li + LiX Metal-metal exchange -20 °C (Transmetallation) This route depends on the difference in the free energies of the formation of the two species Li-R and Mg-R2. 2Li + Mg-R2 2Li-R + Mg 1.1.3 Carbanion-halide exchange This reaction involve the interchange of the carbanion (alkyl/ aryl) and halide groups present on two different metals. MXn + M'Rm MX R + MR X n-a a m-a a (X = halogen, R = alkyl / aryl , M' = Li) ether Li -R + Mg-X2 Mg(R )X + LiX 1.1.4 Metal hydrogen exchange reactions (Metallation) Due to strong polarisation (Mδ+- C δ-) of the alkali metal carbon bond, the carbon atom bound to an alkali metal should be a strong base which is capable of abstracting protons from more acidic hydrocarbons. MR' + RH MR + R'H ( R = alkyl / aryl , M = Li) 3 LiC2H5 + Ph3CH LiCPh3 + C2H6 1.1.5 Metal hydride addition to alkenes This route involves insertion of an alkene in a metal hydrogen bond which lead the formation of metal –carbon bond. M-H + C=C M-C-C-H Pressure LiAlH4 + 4CH =CH Li[Al(CH CH ) 2 2 100°C 2 3 4 1.1.6 Halogen –metal exchange or inversion or Lithiation The halogen metal exchange is useful for converting aryl and alkenyl halides to the corresponding lithium compounds by the use of of butyl lithium.Driving force of this reaction is the greater stability of sp2 carbanion than the sp3 carbanion. ϴ + BuLi + BuBr ϴLi OCH3 Br OCH3 More stable carbanion due to OCH3 1.1.7 By reduction of sulphides Alkyllithium can be prepared by the reduction of sulphides. This method is generally useful for the preparation of α- lithioether and silanes. For this reaction LDMAN (Dilithium dimethyl aminonaphthalene) is used as a reducing agent S-C H Li 6 5 LDMAN O O 1.2 Properties of organolithium compounds Organolithium compounds possess ionic structure Li+R- due to small size of Li cation it possess greater polarizing power and provide special properties to its compounds.Organolithium derivatives are appreciably covalent and soluble in hydrocarbon or non polar solvents. 4 Organolithium derivatives are extremely reactive (super Grignard reagent). Organolithium compounds are oxygen and moisture sensitive and show Lewis acidic character. Butyllithium deprotonate protons which are more acidic than butane. (Lithiation). Position of lithiation is determined by the relative acidity of the available hydrogen and directing effect of substitutent groups. Benzyl and allylic hydrogens are relatively more reactive towards lithiation due to resonance stabilization of resulting anion.