Orgo II Test 2

Ch 8 Nucleophilic substitution reactions

-illustrate the transition state for an S_N2 reaction

-Draw a complete mechanism for an S_N1 reaction

-understand that S_N1 reactions result in both inversion and retention of configuration (raceamic mixture) at the electrophilic carbon. S_N2 gives inversion of configuration.

-be able to recognize the nucleophile, electrophile, and leaving group in an S_N1 or S_N2 reaction

-understand that in most cases anything that makes something a stronger base also makes it a more powerful nucleophile.

-know periodic trends for nucleophilicity

-Resonance effects on nucleophile strength

- For electrophiles know that less hindered electrophiles will react faster in S_N2 reactions

-understand the properties that make a good leaving group

- be able to identify which carbocation is more stable

-effect of electron withdrawing groups/electron (inductive/resonance)donating groups on carbocation stability

- how the presence of a heteroatom can stabilize a nearby carbocation by resonance effects.

Nucleophilic Carbonyl Additions

you should be confident in your ability to:

·       Recognize aldehyde and ketone groups in organic biomolecules

·       Draw/explain the bonding picture for aldehyde and ketone groups

·       Explain why the carbonyl carbon in an aldehyde or ketone is electrophilic

·       Draw complete curved arrow mechanisms for the following reaction types:

o   formation of a hemiacetal/hemiketal

o   collapse of a hemiacetal/hemiketal to revert to an aldehyde/ketone

o   formation and hydrolysis of an acetal/ketal

o   formation and hydrolysis of an N-glycosidic bond

o   formation and hydrolysis of an imine

o   transimination

·       Explain how the carbocation intermediates in glycosidic bond formation and hydrolysis reactions are stabilized by resonance

·       Explain the stereochemical considerations of a nucleophilic addition to an aldehyde/ketone, especially in the context of glycosidic bond formation. Be able to identify the re and si faces of an aldehyde, ketone, or imine.

·       In addition to these fundamental skills, you should develop your confidence in working with end-of-chapter problems involving more challenging, multi-step biochemical reactions.

Ch 11: Acyl Substitution Reactions

you should be able to:

·       Recognize and draw examples of carboxylic acid derivative functional groups:

o   carboxylic acids/carboxylates

o   acyl phosphates (both acyl monophosphate and acyl-AMP)

o   thioesters

o   esters

o   amides

o   acid chlorides

o   carboxylic acid anhydrides

·       Know the meaning of the terms 'acyl', 'acetyl', 'formyl', 'lactone', and 'lactam'.

·       You need not memorize the structure of coenzyme A, but you should recognize that it contains a key thiol group and often forms thioester linkages, particularly in fatty acid metabolism.

·       Understand what happens in a nucleophilic acyl substitution (also called acyl transfer reaction), and be able to draw mechanistic arrows for a generalized example.

·       Know the trends in relative reactivity for the carboxylic acid derivatives:

o   in a biological context (acyl phosphates and thioesters as activated acyl groups)

o   in a laboratory context (acid chlorides and carboxylic acid anhydrides as activated acyl groups)

·       Recognize and understand the most important types of nucleophilic acyl substitution reactions in biology:

o   How a carboxylate group, which is unreactive to nucleophilic acyl substitution reactions, is activated in the cell by ATP-dependent phosphorylation to either acyl monophosphate or acyl-AMP.

o   Conversion of an acyl phosphate to a thioester, a (carboxylic) ester, or an amide.

o   Transthioesterification, esterification, and transesterification reactions.

o   Conversion of a thioester or ester to an amide

o   Hydrolysis of a thioester, a (carboxylic) ester, or an amide to a carboxylate.

·       Understand the energetics of the above reactions:

o   Carboxylate to acyl phosphate is 'uphill' energetically, paid for by coupling to hydrolysis of one ATP

o   Other conversions above are 'downhill': it is unlikely, for example, to see a direct conversion of an amide to an ester. (Notable exception: the lactam (cyclic amide) group in penicillin is very reactive due to ring strain, and forms an ester with an active site serine residue in the target protein)

·       You need not memorize all of the details of peptide bond formation on the ribosome, but you should be able to follow the description in section 7 and recognize the nucleophilic acyl substitution reactions that are occuring.

·       Be able to draw complete mechanisms for the following lab reactions:

o   acid-catalyzed esterification of a carboxylic acid

o   saponification (base-catalyzed hydrolysis of an ester), application to soap-making

o   base-catalyzed transesterification, application to biodiesel production

·       Understand how acid chlorides and carboxylic acid anhydrides serve as activated acyl groups in laboratory synthesis. Be able to describe how an amide to ester conversion could be carried out in the laboratory.

·       Understand how polyesters and polyamides are formed. Given the structure of a polymer be able to identify monomer(s), and vice-versa.

·       Be able to recognize, predict products of, and draw mechanisms for the Gabriel synthesis of primary amines, using either hydroxide ion or hydrazine to release the amine product.

Alpha-carbon chemistry

·       Understand what is meant by 'alpha and beta positions' relative to a carbonyl group.

·       Understand how an enzyme can increase the acidity of an alpha-proton through the active site micro-environment

·       Understand the 3D bonding arrangement of an enolate ion

·       Be able to recognize and draw reasonable mechanisms for the following reaction types:

o   tautomerizations: keto-enol, imine-enamine

o   racemization/epimerization

o   carbonyl isomerization (changing position of a carbonyl group)

o   alkene isomerization (changing position of an alkene relative to carbonyl)

o   aldol addition, retro-aldol cleavage (both enolate intermediate and enamine intermediate mechanisms)

·       Be able to draw a mechanism for a laboratory alkylation reaction at the a-carbon of a ketone or aldehyde. Understand the difference between kinetic and thermodynamic control of this reaction type, and be able to predict the regiochemical outcome of the reaction based on reaction conditions.