6-1 Physical Properties of Haloalkanes CHAPTER 6 ot the b Properties and Reactions of Haloalkanes: Bimolecular Nucleophilic o Substitution The C-X bond is polarized 6S0eonoese6aaae' ctronegative that carbon,carbor The Polar Character of the C-X Bond " 芳-…-天 specles attack the hal c22orewron ronn r and nteract more 6-2 Nucleophilic Substitution Carbaecanresctwthnucteophleatthereletophic 1
1 CHAPTER 6 Properties and Reactions of Haloalkanes: Bimolecular Nucleophilic Substitution 6-1 Physical Properties of Haloalkanes The bond strength of C-X decreases as the size of X increases. A halogen uses a p orbital to overlap an sp2 orbital on a carbon atom. As the size of the halogen p orbital increases (F < Cl < Br < I), the percentage overlap with the smaller sp2 carbon orbital is less and the bond strength decreases. The C-X bond is polarized. Because halogens are more electronegative that carbon, carbonhalogen bonds are polarized. The halogen atom possesses a partial negative (δ-) and the carbon atom a partial positive (δ+) charge. The electrophilic δ+ carbon atom is subject to attack by anions and other nucleophilic species. Cations and other electron-deficient species attack the halogen atom. Haloalkanes have higher boiling points than the corresponding alkanes. Boiling points of haloalkanes are higher than those of the parent alkanes mainly due to dipole-dipole interactions between the haloalkane molecules: As the size of the halogen increases there are also larger London forces between the haloalkane molecules. Larger atoms are more polarizable and interact more strongly through London forces. 6-2 Nucleophilic Substitution Haloalkanes can react with nucleophiles at their electrophilic carbon atom. The mucleophile can be charged, as in :OH- or neutral, as in :NH3. In nucleophilic substitution of haloalkanes, the nucleophile replaces the halogen atom. 6-2 Nucleophilic Substitution Nucleophiles attack electrophillic centers. Nucleophilic substitution of a haloalkane can be described by two general equations: In both cases, the leaving group is the halide anion, X- . In describing reactions, the organic starting material is called the substrate of the reaction. Here, the substrate is being attacked by a nucleophile
Nuceophililc substitution exhibits considerable xn(KH)displaces crto produce c Rxn 2:OCH,'displaces C to produce an ether. Rxn5:thioether. hteds5aebeotac2tona5a392eRsh urved arrows depict the movement of electrons H H-6-H+i-:、H-0-H+:0 heoe9enheae.arotee eaaie2cewneeHamoecenspsalbene B4ACeiboklteneeophicSutstion Ck 2
2 Nucleophililc substitution exhibits considerable diversity. Rxn 1: OH- (KOH) displaces Cl- to produce an alcohol. Rxn 2: OCH3 - displaces Cl- to produce an ether. Rxn 3: I- displaces Cl- to produce a different haloalkane. Rxn 4: CN- (NaCN) displaces Cl- to form a new C-C bond. Rxn 5: The S analog of Rxn 2 forming a thioether. Rxn 6: Neutral :NH3 produces a cationic ammonium salt Rxn 7: Neutral :PH3 produces a cationic phosphonium salt. Halides can serve as nucleophiles and as leaving groups in nucleophilic substitution reactions. These reactions are reversible. Strong bases, such as HO- and CH3O- , however do not serve as good leaving groups. Substitution reactions involving these species are not reversible. Reaction Mechanisms Involving Polar Functional Groups: Using “Electron-Pushing” Arrows 6-3 Curved arrows depict the movement of electrons. The oxygen lone pair of electrons ends up being shared between the oxygen and the hydrogen. The bonding pair electrons in the HCl molecule ends up as a lone pair on the chloride ion. Mechanisms in organic chemistry are described by curved “electron pushing” arrows. Notice that in the 1st and 3rd examples, the destination of the moving electrons is a carbon atom with a filled outer shell. In these nucleophilic substitution and addition reactions, room must be made in the outer shell of the carbon atom to put the incoming electrons. A Closer Look at the Nucleophilic Substitution Mechanism: Kinetics 6-4 Consider the reaction between chloromethane and sodium hydroxide: This experimental data showing the reactants, products, and reaction conditions, gives no information on how the chemical reaction occurred or how fast it occurred. By measuring the rate product formation beginning with several different sets of reactant concentrations, a rate equation or rate law can be determined
6-4 A Close ook at the Mechanism:Kinetics cleophilic Substitution -oaeCgesoweaiwreo Theeacnof chloromethane with sodum hydroxideis ules int cting in a sing one of the ecular nucleophilic substitution reactions are abbreviated In the case of betwe Rate=k[CH,CI][HO:]mol aeoonsieppholesgbstutionisa oeceStem6ntehalaterggoans52 52 substitution is a one step process This is an example of a concerted reaction. tion is si n the 一0 24o-340 6-5Frone r Backside Altack? The S.2 action &apg8i69ntoaoceea88ecoat2bcateC mecular mdeand C5ueesS3aotesereochemistyataisimverteg e is observed as a product.All Sv2 proceec ●我w● 3
3 A Closer Look at the Nucleophilic Substitution Mechanism: Kinetics 6-4 The reaction of chloromethane with sodium hydroxide is bimolecular. The rate of a reaction can be measured by observing the appearance of one of the products, or by the disappearance of one of the reactants. In the case of reaction between chloromethane and hydroxide ion: doubling the hydroxide concentration (keeping the chloromethane concentration fixed) doubles the reaction rate. doubling the chloromethane concentration (keeping the hydroxide concentration fixed) also doubles the reaction. These observations are consistent with a second-order process whose rate law is: Rate = k[CH3Cl][HO- ] mol L-1 s-1. All of the nucleophilic substitution reactions show earlier follow this rate law (with different values of k). The mechanism consistent with a second order rate law involves the interaction of both reactants in a single step (a collision). Two molecules interacting in a single step is call a bimolecular process. Bimolecular nucleophilic substitution reactions are abbreviated SN2. Bimolecular nucleophilic substitution is a concerted, on-step process. A SN2 substitution is a one step process. The bond formation between the nucleophile and the carbon atom occurs at the same time that the bond between the carbon atom and the electrophile is breaking. This is an example of a concerted reaction. There are two distinct stereochemical alternatives for an SN2 concerted reaction: frontside displacement and backside displacement: In SN2 nucleophilic substitution reactions, the transition state of the reaction is simply the geometric arrangement of reactants and products as they pass through the point of highest energy in the single-step process. Frontside or Backside Attack? Stereochemistry of the SN2 Reaction 6-5 The SN2 reaction is stereospecific. When (S)-2-bromobutane reacts with iodide ion, there are two possible theoretical products: Frontside displacement: the stereochemistry at C2 is retained. The product is (S)-2-iodobutane. Backside displacement: the stereochemistry at C2 is inverted. The product is (R)-2-iodobutane. Only (R)-2-iodobutane is observed as a product. All SN2 proceed with inversion of configuration. A process in which each stereoisomer of the starting material is transformed into a specific stereoisomer of product is called stereospecific. The same reaction shown with Spartan molecular models and with electrostatic potential maps is:
6-6 Consequences of Inversion in S.2 Reactions g8meatesizeapecicenantiomerbyusng (5)- changed to H (S)-2Octanethll HeRagtoeo2.ea5enio0ioa62temocoa0ee8r nomet8etanaeR8oteto2ateerg3 as2cy9waoemhrteqecanw NC一H +B Note that in the first case a meso product is formed 6-7 Structure and S,2 Reactivity:The Leaving Group Sg592dlearnngroupsthatcanbedspecadbynuceophe inroupability is a measure of the ease of aby品cag2gesambecmeado (best)B F(worst) 4
4 Halfway through the course of an SN2 reaction, the sp3 hybridization of the carbon atom has changed to the planar sp2 hybridization (transition state). As the reaction proceeds to completion the carbon atom returns to the tetrahedral sp3 hybridization. The transition state of the SN2 reaction can be described in an orbital picture. 6-6 Consequences of Inversion in SN2 Reactions We can synthesize a specific enantiomer by using SN2 reactions. When (R)-2-Bromooctane is reacted with HS- , only (S)-2- octanethiol is obtained: If we had started with the S enantiomer of 2-bromooctane, only the R enantiomer of 2-octanethiol would have been produced. In order to retain the R configuration of the starting 2- bromooctane, a sequence of two SN2 reactions is used: The double inversion sequence of two SN2 processes results in a net retention of configuration. When a substrate contains more than one stereocenter, inversion takes place only at the stereocenter being attacked by the nucleophile. Note that in the first case a meso product is formed. 6-7 Structure and SN2 Reactivity: The Leaving Group The rates of SN2 reactions depend upon: •Nature of the leaving group. •Reactivity of the nucleophile •Structure of the alkyl portion of the substrate. Leaving-group ability is a measure of the ease of displacement. The leaving group ability of a leaving group can be correlated to its ability to accommodate a negative charge. For halogens, iodide is a good leaving group, while fluoride is a poor leaving group in SN2 reactions. SN2 reactions of fluoroalkanes are rarely observed. Leaving-Group Ability (best) I- > Br- > Cl- > F- (worst) Other good leaving groups that can be displaced by nucleophiles in SN2 reactions are:
Weak bases are good lcaving groups. 6-8 Structure andS2 Reactivity:The Nucleophile ohilicity of the nucleophile depends upon: ote the sequence:1>Br Ch>F i charge increase ydecreaeto the right in the Consider these experiments: +HN: CHCHNH++-a CHOH+:: Cm+5一i+n GH:+hg一CH+:-na CHCH+4一CHCH,,+smtm CHG:+HN:一CHNH+G:e C,Ce◆5：一H,HH+0sww Conclusion:Nucleophilicity correlates with basidty Sce9eie0aetorgtacrosthepenodcable, Should basicity and nucleophilicity be correlated? tion impedes nucleophilicity. Nudeophilicity is a kinetic phenomenon c亦+t 5
5 Weak bases are good leaving groups. Leaving group ability is inversely related to base strength. Weak bases are best able to accommodate negative charge and are the best leaving groups. (Weak bases are the conjugate bases of strong acids.) Note the sequence: I- > Br- > Cl- > F- 6-8 Structure and SN2 Reactivity: The Nucleophile Nucleophilicity of the nucleophile depends upon: •Charge •Basicity •Solvent •Polarizability •Nature of substituents Increasing negative charge increases nucliophilicity. Consider these experiments: Conclusion: Comparing nucleophiles having the same reactive atom, the species with the negative charge is the more powerful nucleophile. A base is always more nucleophilic than its conjugate acid. Nucleophilicity decreases to the right in the periodic table. Consider these experiments: Conclusion: Nucleophilicity correlates with basicity. As we proceed from left to right across the periodic table, nucleophilicity decreases. (best) H2N- > HO- > NH3 > F- > H2O (worst nucleophile) Should basicity and nucleophilicity be correlated? Basicity is a thermodynamic property: K A + H O AH + HO K = equilibrium constant 2 − − ←⎯⎯⎯⎯→ Nucleophilicity is a kinetic phenomenon: k Nu + R-X Nu-R + X k = rate constant − − ⎯⎯→ Despite this difference in definition, there is a good correlation between nucleophilicy and basicity in the cases of charged versus neutral nucleophiles along a row in the periodic table. Solvation impedes nucleophilicity. Consider these experiments: Conclusion: Nucleophilicity increases in the progression down a column of the periodic table which is opposite the trend predicted by the basicity of the nucleophiles tested