Module IV: Chemistry of Functional Groups – I (9 hrs) Halogen Compounds: Preparation of alkyl halides from alkanes and alkenes - Wurtz reaction and 1 2 Fittig’s reaction - Mechanism of SN and SN reactions of alkyl halides – Effect of substrate and stereochemistry. Alcohols: Preparation from Grignard reagent - Preparation of ethanol from molasses - Wash, rectified spirit, absolute alcohol, denatured spirit, proof spirit and power alcohol (mention only) – Comparison of acidity of ethanol, isopropyl alcohol and tert-butyl alcohol - Haloform reaction and iodoform test - Luca’s test - Chemistry of methanol poisoning – Harmful effects of ethanol in the human body. Phenols: Preparation from chlorobenzene – Comparison of acidity of phenol, p-nitrophenol and pmethoxyphenol – Preparation and uses of phenolphthalein. Ethers: Preparation by Williamson’s synthesis – Acidic cleavage - Crown ethers (mention only). Preparation of alkyl halides from alkanes Alkanes (the most basic of all organic compounds) undergo very few reactions. One of these reactions is halogenation, or the substitution of single hydrogen on the alkane for a single halogen to form a haloalkane. When methane (CH4) and chlorine (Cl2) are mixed together in the presence of ultra violet irradiation, product is formed, chloromethane (CH3Cl). The reaction proceeds through the radical chain mechanism. The radical chain mechanism is characterized by three steps: initiation, propagation and termination. Initiation requires an input of energy but after that the reaction is self-sustaining. The first propagation step uses up one of the products from initiation, and the second propagation step makes another one, thus the cycle can continue until indefinitely. Step 1: Initiation: Initiation breaks the bond between the chlorine molecule (Cl2). For this step to occur energy must be put in, this step is not energetically favorable. After this step, the reaction can occur continuously (as long as reactants provide) without input of more energy. Step 2: Propagation: The next two steps in the mechanism are called propagation steps. In the first propagation step, chlorine radical combines with a hydrogen on the methane. This gives hydrochloric acid (HCl, the inorganic product of this reaction) and the methyl radical. In the second propagation step more of the chlorine starting material (Cl2) is used, one of the chlorine atoms becomes a radical and the other combines with the methyl radical. Step 3: Termination: In the termination steps, all the remaining radicals combine (in all possible manners) to form more product (CH3Cl), more reactant (Cl2) and even combinations of the two methyl radicals to form a side product of ethane (CH3CH3). However, the reaction doesn't stop there, and all the hydrogens in the methane can in turn be replaced by chlorine atoms. Substitution reactions happen in which hydrogen atoms in the methane are replaced one at a time by chlorine atoms. You end up with a mixture of chloromethane, dichloromethane, trichloromethane and tetrachloromethane. Precisely because of this reason large scale synthesis of alkyl halides never utilises this method from alkanes. When alkanes larger than ethane are halogenated, isomeric products are formed. Thus chlorination of propane gives 45% 1-chloropropane and 55% 2-chloropropane. If it is bromination (light-induced at 25 ºC), 2-bromopropane accounts 97% of the mono-bromo product. These results suggest strongly that 2º-hydrogens are inherently more reactive than 1º hydrogens, the reason being the higher stability of secondary free radical over the primary. Preparation of alkyl halides from alkenes Hydrogen halide addition to an alkene: Halogen halides add across carbon‐carbon double bonds. These additions follow Markovnikov's rule, which states that the positive part of a reagent (a hydrogen atom, for example) adds to the carbon of the double bond that already has more hydrogen atoms attached to it. The negative part adds to the other carbon of the double bond. Such an arrangement leads to the formation of the more stable carbocation over other less‐stable intermediates. Benzylic and allylic sites (which are resonance stabilised) are exceptionally reactive in free radical halogenation reactions. The brominating reagent, N-bromosuccinimide (NBS), has proven useful for achieving allylic or benzylic substitution. Wurtz reaction is an organic reaction used to couple two alkyl halides to form an alkane using sodium metal. The mechanism begins with a single electron transfer (SET) from sodium metal to the alkyl halide, which dissociates to form an alkyl radical and sodium halide salt. Another molecule of sodium performs another SET to the alkyl radical to form a nucleophilic carbanion. The carbanion then attacks another molecule of alkyl halide in a nucleophilic substitution reaction (SN2) to form the final coupled product and another molecule of sodium halide salt. Limitations: One can prepare higher alkanes with even number of carbon atoms only, by this method If two different alkyl halides are treated with sodium metal in presence of dry ether then mixture of three different products is obtained. Fittig reaction is an extension to the Wurtz reaction wherein two aryl halides couple using sodium metal. If a mixture of aryl halide and alkyl halide is coupled together in presence of sodium metal, its called Wurtz–Fittig reaction. 1 SN mechanism or dissociative mechanism 1 1 SN indicates a substitution, nucleophilic, unimolecular reaction. In an SN there is loss of the leaving group generates an intermediate carbocation which is then undergoes a rapid reaction with the 1 nucleophile. In an SN reaction, the rate determining step is the loss of the leaving group to form the intermediate carbocation. The more stable the carbocation is, the easier it is to form, and the faster 1 the SN reaction will be. The C-X bond breaks first, before the nucleophile approaches. This results in the formation of a carbocation. because the central carbon has only three bonds, it bears a formal charge of +1. Recall that a carbocation should be pictured as sp2 hybridized, with trigonal planar geometry. Perpendicular to the plane formed by the three sp2 hybrid orbitals is an empty, unhybridized p orbital. In the second step of this two-step reaction, the nucleophile attacks the empty, 'electron hungry' p orbital of the carbocation to form a new bond and return the carbon to tetrahedral geometry. 1 In the model SN reaction shown above, the leaving group dissociates completely from the vicinity of the reaction before the nucleophile begins its attack. Because the leaving group is no longer in the picture, the nucleophile is free to attack from either side of the planar, sp2-hybridized carbocation electrophile. This means that about half the time the product has the same stereochemical configuration as the starting material (retention of configuration), and about half the time the stereochemistry has been inverted. In other words, racemization has occurred at the carbon center. 1 Influence of the solvent in an SN reaction: A polar protic solvent is highly positively charged, it can speed up the rate of the unimolecular substitution reaction because the large dipole moment of the solvent helps to stabilize the inermediate. Since the carbocation is unstable, anything that can stabilize this even a little will speed up the reaction. And also the highly positive and highly negative parts interact with the substrate to lower the energy of the transition state. 1 1 Influence of the substrate in an SN reaction: In the SN reaction, the big barrier is carbocation stability. 1 Since the first step of the SN reaction is loss of a leaving group to give a carbocation, the rate of the reaction will be proportional to the stability of the carbocation. Carbocation stability increases with increasing substitution of the carbon (tertiary > secondary >> primary) as well as with resonance. 2 SN mechanism The reaction takes place in a single step, and bond-forming and bond-breaking occur simultaneously. 2 2 This is called an 'SN ' mechanism. In the term SN , S stands for 'substitution', the subscript N stands for 'nucleophilic', and the number 2 refers to the fact that this is a bimolecular reaction: the overall rate depends on a step in which two separate molecules (the nucleophile and the electrophile) collide. The nucleophile, being an electron-rich species, must attack the electrophilic carbon from the back side relative to the location of the leaving group. Approach from the front side simply doesn't work: the leaving group - which is also an electron-rich group - blocks the way. The result of this backside attack is that the stereochemical configuration at the central carbon inverts as the reaction proceeds. In a sense, the molecule is turned inside out. At the transition state, the electrophilic carbon and the three 'R' substituents all lie on the same plane. 2 2 Influence of the solvent in an SN reaction: The rate of an SN reaction is significantly influenced by the solvent in which the reaction takes place. The use of protic solvents (those, such as water or alcohols, with hydrogen-bond donating capability) decreases the strength of the nucleophile, because of strong hydrogen-bond interactions between solvent protons and the reactive lone pairs on the 2 2 nucleophile. A less powerful nucleophile in turn means a slower SN reaction. SN reactions are faster in polar aprotic solvents: those that lack hydrogen-bond donating capability. 2 2 Influence of the substrate in an SN reaction: In the SN reaction, the big barrier is steric hindrance. 2 Since the SN proceeds through a backside attack, the reaction will only proceed if the empty orbital is accessible. The more groups that are present around the vicinity of the leaving group, the slower the reaction will be. That’s why the rate of reaction proceeds from primary (fastest) > secondary >> tertiary (slowest) Preparation of Alcohols from Grignard reagent Alkyl Magnesium halides are called Grignard reagents (RMgX).