Basic Organic Chemistry C/CHE 11022 PDF

C/CHE 11022 Basic Organic Chemistry Dr. Dinusha Udukala  https://www.youtube.com/watch?v=TnY1S5IdVqI&t =457s  The SN1 Reaction Tertiary alkyl halides react rapidly in protic solvents by a mechanism that involves departure of the leaving group prior to addition of the n...

C/CHE 11022 Basic Organic Chemistry Dr. Dinusha Udukala  https://www.youtube.com/watch?v=TnY1S5IdVqI&t =457s  The SN1 Reaction Tertiary alkyl halides react rapidly in protic solvents by a mechanism that involves departure of the leaving group prior to addition of the nucleophile Called an SN1 reaction – occurs in two distinct steps while SN2 occurs with both events in same step If nucleophile is present in reasonable concentration (or it is the solvent), then ionization is the slowest step 3  SN1 Energy Diagram Step through highest energy point is rate- k1 k-1 k2 limiting (k1 in forward direction) V = k[RX] Rate-determining step is formation of carbocation The rate depends upon the concentration of only the alkyl halide-not the nucleophile. v 4  Rate-Limiting Step The overall rate of a reaction is controlled by the rate of the slowest step The rate depends on the concentration of the species and the rate constant of the step The highest energy transition state point on the diagram is that for the rate determining step (which is not always the highest barrier) This is the not the greatest difference but the absolute highest point 5  Stereochemistry of SN1 Reaction The planar intermediate leads to loss of chirality o A free carbocation is achiral Product is racemic or has some inversion 6 Delocalized Carbocations Delocalization of cationic charge enhances stability Primary allyl is more stable than primary alkyl Primary benzyl is more stable than allyl 7  Characteristics of the SN1 Reaction Tertiary alkyl halide is most reactive by this mechanism o Controlled by stability of carbocation 8  Allylic and Benzylic Halides Allylic and benzylic intermediates stabilized by delocalization of charge o Primary allylic and benzylic are also more reactive in the SN2 mechanism 9  Rearrangement in SN1 reactions  Hydride shift: H- on adjacent carbon bonds with C+. Br H H CH3 C C CH3 CH3 C C CH3 H CH3 H CH3 H H CH3 C C CH3 CH3 C C CH3 H CH3 H CH3 H H Nuc CH3 C C CH3 Nuc CH3 C C CH3 H CH3 H CH3  Rearrangement in SN1 reactions  Methyl shift: CH3- moves from adjacent carbon if no H’s are available. Br CH3 CH3 CH3 C C CH3 CH3 C C CH3 H CH3 H CH3 CH3 CH3 CH3 C C CH3 CH3 C C CH3 H CH3 H CH3 CH3 CH3 Nuc CH3 C C CH3 Nuc CH3 C C CH3 H CH3 H CH3  Effect of Leaving Group on SN1 Critically dependent on leaving group o Reactivity: the larger halide ions are better leaving groups In acid, OH of an alcohol is protonated and leaving group is H2O, which is still less reactive than halide p-Toluensulfonate (TosO-) is excellent leaving group 12  Nucleophiles in SN1 Since nucleophilic addition occurs after formation of carbocation, reaction rate is not affected by nature or concentration of nucleophile 13  https://www.youtube.com/watch?v=JmcVgE2WKB E  SN2 and SN1 SN2 SN1 CH3X > 1º > 2º 3º > 2º Strong nucleophile Weak nucleophile Polar aprotic solvent Polar protic solvent. Rate = k[alkyl Rate = k[alkyl halide] halide][Nuc] Inversion at chiral carbon Racemization No rearrangements Rearranged products  Alkyl Halides: Elimination Elimination is an alternative pathway to substitution Opposite of addition Generates an alkene Can compete with substitution and decrease yield, especially for SN1 processes 16  Zaitsev’s Rule for Elimination Reactions (1875) In the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates 17  Mechanisms of Elimination Reactions Ingold nomenclature: E – “elimination” E1: X- leaves first to generate a carbocation o a base abstracts a proton from the carbocation E2: Concerted transfer of a proton to a base and departure of leaving group 18  The E2 Reaction Mechanism A proton is transferred to base as leaving group begins to depart Transition state combines leaving of X and transfer of H Product alkene forms stereo specifically E2 reactions occur when a 2° or 3° alkyl halide is treated with a strong base such as OH-, OR-, NH2-, H-, etc. 19  E2 Reaction Kinetics All strong bases, like OH-, are good nucleophiles. In 2° and 3° alkyl halides the α-carbon in the alkyl halide is hindered. In such cases, a strong base will ‘abstract’ (remove) a hydrogen ion (H+) from a β-carbon, before it hits the α-carbon. Thus strong bases cause elimination (E2) in 2° and 3° alkyl halides and cause substitution (SN2) in unhindered methyl° and 1° alkyl halides.  E2 Reaction Kinetics One step – rate law has base and alkyl halide Transition state bears no resemblance to reactant or product V=k[R-X][B] Reaction goes faster with stronger base, better leaving group 21  Geometry of Elimination – E2 Antiperiplanar allows orbital overlap and minimizes steric interactions 22  E2 Stereochemistry Overlap of the developing  orbital in the transition state requires periplanar geometry, anti arrangement Allows orbital overlap 23  Summary of the E2 Reaction E2 reaction is a B-elimination reaction of alkyl halides that is promoted by strong bases. The following list summarizes the key points about this reaction: l. The rates of E2 reactions are second order overall: first order in base and first order in the alkyl halide. 2. E2 reactions normally occur with anti stereochemistry. 3. The E2 reaction is faster with better leaving groups-that is, those that give the weakest bases as products. 4. The rates of E2 reactions show substantial primary deuterium isotope effects at the B hydrogen atoms. 5. When an alkyl halide has more than one type of B-hydrogen, more than one alkene product can be formed; the most stable alkenes (the alkenes with the greatest numbers of alkyl substituents at their double bonds) are formed in greatest amount. 6. E2 reactions compete with SN2 reactions. Elimination is favored by alkyl substitution in the alkyl halide at the a- or B-carbon atoms, by alkyl substituents at the a-carbon of the base. and bv stronger bases  The E1 Reaction Competes with SN1 and E2 at 3° centers V = k [RX] The E1 and SN1 reactions have the same conditions so a mixture of products will be obtained. 25  Stereochemistry of E1 Reactions E1 is not stereospecific and there is no requirement for alignment Product has Zaitsev orientation because step that controls product is loss of proton after formation of carbocation 26  Comparing E1 and E2 Strong base is needed for E2 but not for E1 E2 is stereospecifc, E1 is not E1 gives Zaitsev orientation 27  E2 or E1 Mechanism E2 E1  Tertiary > Secondary  Tertiary > Secondary  Strong base required  Base strength unimportant (usually weak)  Solvent polarity not  Good ionizing solvent important.  Rate = k[alkylhalide][base]  Rate = k[alkyl halide]  Zaitsev product  Zaitsev product  Coplanar leaving groups  No required geometry (usually anti)  No rearrangements  Rearranged products  Substitution or Elimination Strength of the nucleophile determines order: Strong nucleophiles or bases promote bimolecular reactions. Primary halide usually undergo SN2. Tertiary halide result a mixture of SN1, E1 or E2. They cannot undergo SN2. High temperature favors elimination Bulky bases favor elimination and also form the least stable alkene. .  Summary of the SN1 and El Reactions Let's summarize the important characteristics of the SNl and El reactions. l. Tertiary and secondary alkyl halides undergo solvolysis reactions by the SN1 and El mechanisms; tertiary alkyl halides are more reactive. 2. If an alkyl halide has B-hydrogens, elimination products formed by the El reaction accompany substitution products formed by the SN1 mechanism. 3. Both SNl and E1 reactions of a given alkyl halide share the same rate-limiting step: ionization of the alkyl halide to form a carbocation. 4. The SNl and El reactions are first order in the alkyl halide. 5. SNl and El reactions differ in their product-determining steps. The product-determining step in the SNl reaction is reaction of a nucleophile with the carbocation intermediate, and in the El reaction, loss of a B-proton from the carbocation intermediate. 6. Carbocation rearrangements occur when the initially formed carbocation intermediate can rearrange to a m-ore stable carbocation. 7. The best leaving groups are those that give the weakest bases as products. 8. The reactions are accelerated by polar, protic, donor solvents. 9. SNI reactions of chiral alkyl halides give largely racemized products, but some inversion of configuration is also observed.  When asked to predict how a given alkyl halide will react, you must first answer three major questions. l. Is the alkyl halide primary, secondary, or tertiary? If primary or secondary, is there a significant amount of alkyl substitution at the B- carbon? 2. Is a Lewis base present? If so, is it a good nucleophile, a strong Bronsted base, or both? Most strong Bronsted bases, such as ethoxide, are good nucleophiles; but some excellent nucleophiles, such as iodide ion, are relatively weak Bronsted bases. 3. What is the solvent? The practical choices are limited for the most part to polar protic solvents, polar aprotic solvents, or mixtures of both. Once these questions have been answered, a satisfactory prediction in most cases can be obtained from Table 9.7