Organic Halide (Part 1 & 2) PDF

Organic Halides Dr. Sham Wali Qurban Organic Chemistry Second Stage  Introduction Alkyl halides are also known as haloalkanes. Alkyl halides are compounds in which one or more hydrogen atoms in an alkane have been replaced by halogen atoms (fluorine, chlorine...

Organic Halides Dr. Sham Wali Qurban Organic Chemistry Second Stage  Introduction Alkyl halides are also known as haloalkanes. Alkyl halides are compounds in which one or more hydrogen atoms in an alkane have been replaced by halogen atoms (fluorine, chlorine, bromine or iodine). Halogen atoms are more electronegative than carbon atoms, and so the C-Hal bond is polarized. General Properties CH3Cl, CH3Br, CH3F and CH3CH2Cl are gases at room temperature. Other alkyl halides up to C18 are colourless liquids. Those beyond C18 are colourless solids. Alkyl halides are insoluble in water but soluble in organic solvents. The insolubility in water is due to their inability to form hydrogen bonds with water. Alkyl bromides and iodides are denser than water. Alkyl chlorides and fluorides are lighter than water. Dipole moment Boiling point and melting point Two types of intermolecular forces influence the boiling points of Alkyl Halides: The London force is the strongest intermolecular attraction in alkyl halides. London forces are surface attractions, resulting from coordinated temporary dipoles. Molecules with larger surface areas have larger London attractions, resulting in higher boiling points. Dipole-dipole attractions (arising from the polar C-X bond) also affect the boiling points, but to a smaller extent. Molecules with higher molecular weights generally have higher boiling points because they are heavier (and therefore slower moving), and they have greater surface.  Alkyl halides have higher bp’s and mp’s than alkanes having the same number of carbons CH3CH and CH3CH2Br bp = -89 °C bp = 39 °C Bp’s and mp’s increase as the size of R increases CH3CH2Cl CH3CH2CH2Cl Larger surface area mp=-136 °C mp=-123 °C higher mp and bp bp = 12 °C bp = 47°C Bp’s and mp’s increase as the size of X increases CH3CH2Cl CH3CH2Br More polarizable mp=-136°C mp=-119°C halogen, higher mp bp = 12°C bp=39°C and bp F > Cl > Br >I Classification of alkyl halides: Based on the Hybridization of Carbon Alkyl halide simply has a halogen atom bonded to one of the sp3 hybrid carbon atoms of an alkyl group. Vinyl halide has a halogen atom bonded to one of the sp2 hybrid carbon atoms of an alkene. Aryl halide has a halogen atom bonded to one of the sp2 hybrid carbon atoms of an aromatic ring Benzylic halides the halogen group is joined to a benzylic carbon atom that has undergone sp3 hybridization and is then joined to an aromatic ring. Classification of alkyl halides: Based on the number of halogen atoms: The classification depends primarily on whether the structure contains one, two, or more halogen atoms. The categories include: 1. MonoHaloalkane : the alkanes having one halogen atom. 2. DiHaloalkane: the alkanes having Two halogen atom. 3. TriHaloalkane: the alkanes having three halogen atom. Classification of alkyl halides: Based on the Position of the Halogen atom Along the Chain of Carbon Atom: 1. Primary alkyl halide 2. Secondary alkyl halides 3. Tertiary alkyl halides Dihalides A geminal dihalide (Latin, geminus, “twin”) has the two halogen atoms bonded to the same carbon atom. A vicinal dihalide (Latin, vicinus, “neighboring”) has the two halo- gens bonded to adjacent carbon atoms. Nomenclature of Alkyl Halides According to IUPAC, alkyl halides are treated as alkanes with a halogen (Halo-) substituent. The halogen prefixes are Fluoro-, Chloro-, Bromo- and Iodo-. Examples: CH2X2 type are called methylene halides. (CH2Cl2 is methylene chloride). CHX3 type compounds are called haloforms. (CHI3 is iodoform). CX4 type compounds are called carbon tetrahalides. (CF4 is carbon tetrafluoride). In addition to systematic names, IUPAC nomenclature also recognizes common names for many halogenated organic compounds, as seen in the following examples: The letter “n” stands for “normal” and indicates that the carbon atoms of the alkyl substituent are arranged in a linear chain (not branched) with the halogen connected to the end of the chain Example: Uses of Organohalides Solvents industrial and household solvents. carbon tetrachloride (CCl4) used for dry cleaning, spot removing. methylene chloride (CH2Cl2) is used to dissolve the caffeine from coffee beans to produce decaffeinated coffee. Reagents: Alkyl halides are used as the starting materials for the synthesis of many compounds. Alkyl halides are used in nucleophilic reactions, elimination reactions, formation of organometallics,.and etc. Refrigerants: Freons (ChloroFluoroCarbon) Pesticides: DDT(Dichloro Diphenyl- Trichloroethane), Aldrin, Chlordan  Herbicides: Kills broad leaf weeds but allow narrow leaf plants to grow unharmed and in greater yield, 2,4 dichlorophenoxyacetic acid. Not all halogenated compounds are toxic. In fact, many organohalides have clinical applications. Some organohalides have even been used in the food industry. Consider, for example, It is several hundred times sweeter than sugar and is sold as an artificial, low-calorie sweetener under the trade name Splenda. Preparation of Alkyl Halides 1. Halogenation of Alkanes: Alkanes react with Cl2 or Br2 in the presence of UV light or at high temperature (400°C) to give alkyl halides along with polyhalogen derivatives. This method is not used in the laboratory because of the difficulty of separating the products. Sometimes if there can be control over the selectivity of halogenation this is a useful route. 2. Allylic Bromination The bromination of cyclohexene produces a high yield of 3- bromocyclohexene. An allylic hydrogen has been substituted for a bromine. The bromine atom abstracts an allylic hydrogen because the allylic radical is resonance stabilized. The radical then reacts with a bromine molecule to continue the chain.  A common reagent for these allylic brominations is N- bromosuccinamide (NBS) because it continually generates small amounts of Br2 through reaction with HBr. 3. Addition of Halogen Acids to Alkenes Halogen acids (HCl, HBr, HI) add to alkenes to yield alkyl halides. The mode of addition follows Markovnikov rule, except for the addition of HBr in the presence of organic peroxides (R-O-O-R). 4. Action of Halogen Acids on Alcohols Alcohols react with HBr or HI to produce alkyl bromides or alkyl iodides. Alkyl chlorides are produced by the action of dry HCl in the presence of zinc chloride catalyst. 5. Action of Thionyl chloride on alcohols. Alcohols react with thionyl chloride (SOCl2) in the presence of pyridine to produce alkyl chlorides. Pyridine (C5H5N) absorbs hydrogen chloride as it is formed. 6. Halogen Exchange reaction This reaction is particularly suitable for preparing alkyl iodides. The alkyl bromide or chloride is heated with a concentrated solution of sodium iodide in acetone. Alkyl fluorides are also prepared by treating an alkyl chloride or bromide with inorganic fluorides. Chemical Properties of Organic Halogen Compounds There are three main classes of reactions for the organic halogen compounds Although nucleophilicity and basicity are interrelated, they are fundamentally different. Substitution, Nucleophilic, Bimolecular: The SN2 Reaction The nucleophile attacks the carbon bearing the leaving group from the back side. The orbital that contains the electron pair of the nucleophile begins to overlap with an empty(antibonding) orbital of the carbon bearing the leaving group. The bond between the nucleophile and the carbon atom is forming, and the bond between the carbon atom and the leaving group is breaking. The formation of the bond between the nucleophile and the carbon atom provides most of the energy necessary to break the bond between the carbon atom and the leaving group. Consider the reaction of hydroxide ion with methyl iodide, to yield methanol. The rate law for a reaction often gives clues to the mechanism for a reaction. Kinetic information tells us that the rate is doubled when the [CH3I] is doubled, and also doubled when the [HO-] is doubled. Rate = k [CH3I] [HO-] Second-order kinetics We can conclude that: the reaction is second order the reaction is bimolecular The reaction is said to be concerted, taking place in a single step with the new bond forming as the old bond is breaking. The transition state is a point of highest energy (not an intermediate). The mechanism requires a collision between the hydroxide ion and methyl iodide. Both species are present in the transition state, and the frequency of collisions is proportional to the concentrations of the reactants. SN2 = substitution, nucleophilic, bimolecular. Bimolecular means that the transitions state of the R.D.S. involves the collision of two molecules. (Bimolecular reactions generally have 2nd order overall rate equations). Stereochemistry of the SN2 Reaction A nucleophile donates its electron density into (attacks) the small back lobe of the sp3 hybridized C-X bond, since the leaving group itself blocks attack from any other direction. This is called back side attack. Factors that Affect the Rate of the SN2 Reaction 1. The structure of the substrate 2. The concentration and reactivity of the nucleophile 3. The effect of the solvent 4. The nature of the leaving group Transition State 1. The Structure of the Substrate In the SN2 reaction, the rate of the reaction is slowed by bulky groups near the reaction center due to steric hindrance. crowding in the T.S. raises the activation energy and slows the reaction. 2. The Effect of the Concentration and Strength of the Nucleophile. How do we determine nucleophilic strength? By measuring the rates of substitution reactions Rates of SN2 Reaction of Various Nucleophiles with Iodomethane in Methanol: Nucleophilicity depends on a variety of factors: concentration of charge, solvent, polarizability and the nature of the substituents. Best Nucleophiles: have high concentration of negative charge are highly polarizable are less solvated are not too hindered Increasing negative charge increases nucleophilicity Species with a negative charge are stronger nucleophiles than analogous species without a negative charge Bases are always stronger nucleophiles than their conjugate acids  Nucleophilicity decreases to the right in the periodic table (this correlates with basicity). (The more electronegative elements hold on more tightly to their non bonding electrons) Nucleophilicity increases as you go down a row in the periodic table (this does not correlate with basicity!!) Increase in polarizability and size More polarizable atoms can form bonds at greater distances, which gives rise to stronger bonding in the T.S. 3. The Effect of Solvent on the Rate of Reaction Protic Solvents that can donate hydrogen bonds (-OH or –NH) that may slow SN2 reactions by associating with reactants Polar aprotic solvents (no NH, OH, SH) form weaker interactions with substrate and permit faster reaction Anions are freer to react because they are unencumbered by solvent molecules. Rates of SN2 reactions are greatly enhanced in polar aprotic solvents 4. The Nature of the Leaving Group Good leaving groups are weak bases. The same factors that make a species a weak base also make it a good leaving group. The Reversibility of an SN2 Reaction Many different kinds of nucleophiles can react with alkyl halides, and a wide variety of organic compounds can be synthesized by means of SN2 reactions: The reverse reaction cannot occur because hydroxide ion is a terrible leaving group! The reaction is only reversible if the two possible leaving groups have similar leaving group abilities (ie. they have similar basicities) Example of reversible SN2 reaction: Substitution, Nucleophilic, Unimolecular: The SN1 Reaction: This type of mechanism involves two steps. The first step is the reversible ionization of the alkyl halide. This step provides a carbocation as an intermediate. In the second step this carbocation is attacked by the nucleophile to give the product. The rate was found to depend only on the concentration of t- butyl bromide. Rate = k[(CH3)3C-Br] The rate is first order overall – unimolecular. The SN1 reaction is a two step process, with the first being a slow ionization reaction generating a carbocation. The second is the quick nucleophilic attack by the nucleophile on the carbocation. (In some case, like when water or alcohol is the nucleophile, a quick loss of a proton gives the final product).  SN1 Energy Diagram because this step has the higher- energy transition state and also because this step has the larger Ea. The rate- determining step is the step with the larger Ea Factors that Affect the Rate of the SN1 Reaction 1. The structure of the substrate 2. The effect of the solvent 3. The nature of the leaving group 1. The Structure of the Substrate 2. The effect of the solvent The R.D.S. of an SN1 reaction involves the formation of 2 ions, therefore polar solvents (which stabilize ions) enhance SN1 reactivities. Protic solvents are especially useful since the hydrogen bonding stabilizes the anionic leaving group after ionization. Dielectric Constant Dielectric constant (ε) is a measure of a solvents’ polarity. Ionization requires the stabilization of both positive and negative charges, solvents with higher ε have faster rates for SN1 reactions. 3. The Nature of the Leaving Group In the R.D.S. for an SN1 reaction, the bond to the leaving group is breaking, therefore a highly polarizable leaving group helps stabilize the T.S. through partial bonding as it leaves (like for SN2 case). The leaving group should be stable after it has left with the bonding electrons, and also be a weak base. The leaving group starts to take on partial negative charge as the cation starts to form. Good leaving groups are essential for both SN1 and SN2 reactions. Elimination Reactions (E) An elimination is the loss of two atoms or groups from a molecule, which will typically result in the formation of a new  bond. there are two mechanisms of elimination (E2 and E1). E2 mechanism — bimolecular elimination E1 mechanism — unimolecular elimination  The E2 and E1 mechanisms differ in the timing of bond cleavage and bond formation, analogous to the SN2and SN1 mechanisms. E2 and SN2 reactions have some features in common, as do E1 and SN1 reactions. Reactions of Organometalic Compounds (Reduction) The alkali metals (Li, Na, K etc.) and the alkaline earth metals (Mg and Ca, together with Zn) are good reducing agents. 1. Reduction with alkaline earth metals 2. Reduction with alkali metals a) Reduction by Zinc metal and acids or by metal hydrides b) Reduction by sodium metal (coupling reaction) c) Reduction using lithium dialkyl cuprate (Gilman reagent)