Vollhardt Capítulo 6 (Haloalcanos)
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charge on the nucleophile has spread partly onto the leaving group. As the reaction comes to completion, the leaving group evolves to a fully charged anion. In the electrostatic potential map of the transition state, this process is refl ected in the attenuated red color around the two halogen nuclei, compared with the full red visible in the starting and ending halide ions. Note that in the reaction schemes preceding the electrostatic potential renditions, we use the mechanistic color scheme of green for the leaving group, and not red. In other respects, the colors match, as you would expect. } } @ C Br BrI \u2212 I H S R H3C CH3CH2 C +I H CH3 CH2CH3 C H CH3 CH2CH3 \u2021 \u3b4 \u2212 \u3b4 \u2212 Stereochemistry of the Backside Displacement Mechanism for SN2 Reactions Backside displacement(Chiral and optically active) (Chiral and optically active; configuration inverted) Br \u2212 MECHANISM MODEL BUILDING Exercise 6-11 Draw representations of the hypothetical frontside and backside displacement mechanisms for the SN2 reaction of sodium iodide with 2-bromobutane (Table 6-3). Use arrows like those shown in Figures 6-2 and 6-3 to represent electron-pair movement. ANIM ATION ANIMATED MECHANISM: Nucleophilic substitution (SN2) 3157T_ch06_215-250.indd Page 226 4/18/09 7:52:25 AM user-s1723157T_ch06_215-250.indd Page 226 4/18/09 7:52:25 AM user-s172 /Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE036-/Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:V Admin Callout Há inversão da configuração do carbono quiral, que passa de (R) para (S), uma vez que única substituição que ocorre de verdade é que acontece por trás. Admin Highlight C h a p t e r 6 227 \u2021 \u2021 I I IBr Br Br The stereochemistry of displacement at a primary carbon is more diffi cult to observe directly, because a primary carbon atom is attached to two hydrogens in addition to the leaving group: It is not a stereocenter. This obstacle may be overcome by replacing one of the two hydrogen atoms by deuterium, the hydrogen isotope with mass 5 2. The result is a stereocenter at the primary carbon and a chiral molecule. This strategy has been employed to confi rm that SN2 displacement at a primary carbon atom does indeed occur with inversion of confi guration, as the example below illustrates. S-1-Chloro-1-deuteriobutane (Chiral and optically active) Stereochemistry of SN2 Displacement at a Primary Carbon Atom R-1-Azido-1-deuteriobutane (Chiral and optically active; configuration inverted) i \u2211 [ CH D ClO CH3CH2CH2 70% i \u2211 [ N3 H D CO CH2CH2CH3 A \u201cprimary stereocenter\u201d NaN3, CH3OH, H2O SN2 displacement with 100% inversion The nucleophile, azide ion (N3 2), gives rise to stereospecifi c backside displacement of chloride, giving the azidoalkane product with the inverted confi guration at the chiral carbon. 6 - 5 F r o n t s i d e o r B a c k s i d e A t t a c k ? Exercise 6-12 Write the products of the following SN2 reactions: (a) (R)-3-chloroheptane 1 Na 12SH; (b) (S)-2- bromooctane 1 N(CH3)3; (c) (3R,4R)-4-iodo-3-methyloctane 1 K 12SeCH3. Exercise 6-13 Write the structures of the products of the SN2 reactions of cyanide ion with (a) meso-2,4- dibromopentane (double SN2 reaction); (b) trans-1-iodo-4-methylcyclohexane. 3157T_ch06_215-250.indd Page 227 4/18/09 7:52:29 AM user-s1723157T_ch06_215-250.indd Page 227 4/18/09 7:52:29 AM user-s172 /Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE036-/Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:V 228 C h a p t e r 6 P r o p e r t i e s a n d R e a c t i o n s o f H a l o a l k a n e s 6-6 Consequences of Inversion in SN2 Reactions What are the consequences of the inversion of stereochemistry in the SN2 reaction? Because the reaction is stereospecifi c, we can design ways to use displacement reactions to synthesize a desired stereoisomer. } } @ C C Nu:\u2212 + Nu\u3b4 \u2212 \u3b4 \u2212 X X CNu + X\u2212 \u2021 Reaction coordinate E Figure 6-5 Potential energy diagram for an SN2 reaction. The process takes place in a single step, with a single transition state. ANIM ATION ANIMATED MECHANISM: Nucleophilic substitution (SN2) \u2021 R\u2032\u2032 R R\u2032 C C Nu XXX Nu sp2 hybridization at carbon Nu \u3b4 \u2212 \u3b4 \u2212 R\u2032\u2032 R\u2032 R \u2212 \u2212 C R\u2032\u2032 R R\u2032 Figure 6-4 Orbital description of backside attack in the SN2 reac- tion. The process is reminiscent of the inversion of an umbrella ex- posed to gusty winds. The transition state of the SN2 reaction can be described in an orbital picture The transition state for the SN2 reaction can be described in orbital terms, as shown in Figure 6-4. As the nucleophile approaches the back lobe of the sp3 hybrid orbital used by carbon to bind the halogen atom, the rest of the molecule becomes planar at the transition state by changing the hybridization at carbon to sp2. As the reaction proceeds to products, the inversion motion is completed and the carbon returns to the tetrahedral sp3 confi guration. A depiction of the course of the reaction using a potential energy \u2013 reaction coordinate diagram is shown in Figure 6-5. A former president experiences inversion of confi guration. 3157T_ch06_215-250.indd Page 228 4/18/09 7:52:34 AM user-s1723157T_ch06_215-250.indd Page 228 4/18/09 7:52:34 AM user-s172 /Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:Vollhardt/FREE036-/Users/user-s172/Desktop/Tempwork/Don'tDelete_Job/FREE036:V Admin Highlight Admin Callout O Estado de transição é, obviamente, o estado de mais alta energia. C h a p t e r 6 229 We can synthesize a speci\ufb01 c enantiomer by using SN2 reactions Consider the conversion of 2-bromooctane into 2-octanethiol in its reaction with hydrogen sulfi de ion, HS2. If we were to start with optically pure R bromide, we would obtain only S thiol and none of its R enantiomer. } ~ O O 0 0 D HS \ufffd C CH3(CH2)4CH2 CH3 CH3 H CH2(CH2)4CH3 H Br HS Inversion of Configuration of an Optically Pure Compound by SN2 Reaction (R)-2-Bromooctane ([ ] \ufffd \ufffd34.6) (S)-2-Octanethiol ([ ] \ufffd \ufffd36.4) G C \ufffd\ufffd \ufffd \ufffd Br \ufffd But what if we wanted to convert (R)-2-bromooctane into the R thiol? One tech- nique uses a sequence of two SN2 reactions, each resulting in inversion of confi guration at the stereocenter. For example, an SN2 reaction with iodide would fi rst generate (S)-2- iodooctane. We would then use this haloalkane with an inverted confi guration as the substrate in a second displacement, now with HS2 ion, to furnish the R thiol. This double inversion sequence of two SN2 processes gives us the result we desire, a net retention of confi guration. } ~ O O 0 0 DC CH3(CH2)4CH2 CH3 CH3 H CH2(CH2)4CH3 H II \ufffd \ufffdBr\ufffd First inversion of configuration Second inversion of configuration HS\ufffd \ufffdI\ufffd Using Double Inversion to Give Net Retention of Configuration (R)-2-Bromooctane ([ ] \ufffd \ufffd34.6) (S)-2-Iodooctane ([ ] \ufffd \ufffd46.3) (R)-2-Octanethiol ([ ] \ufffd \ufffd36.4) G } O0 C CH3(CH2)4CH2 CH3 H SHGC \ufffd \ufffd\ufffd Br 6 - 6 C o n s e q u e n c e s o f I n v e r s i o n i n S N 2 R e a c t i o n s Color code for priorities (see Section 5-3) Highest: red Second highest: blue Third highest: green Lowest: black Exercise 6-14 As we saw for carvone (Chapter 5, Problem 43), enantiomers can sometimes be distinguished by odor and fl avor. 3-Octanol and some of its derivatives are examples: The dextrorotatory compounds are found in natural peppermint oil, whereas their (2) counterparts contribute to the essence of lavender. Show how you would synthesize optically pure samples of each enantiomer of 3-octyl acetate, starting with (S)-3-iodooctane. (The conversion of acetates into alcohols will be shown in Section 8-5.) O 3-Octyl acetate OCCH3 CH3CH2CHCH2CH2CH2CH2CH3 A B Exercise 6-15 MODEL BUILDING Working with the Concepts: Stereochemical Consequences of SN2 Displacement Treatment of (S)-2-iodooctane with NaI in solution causes the optical activity of the starting organic compound to disappear. Explain.