In a basic solution, why are ketones more reactive than ethers? I know you said that ethers cannot be deprotonated by bases because they do not have an -OH bond, but neither does the ketone. (Most ketones have more acidic alpha-hydrogens. Also, a base can add to the C=O group. - GS).

In the lecture notes, it says, “Reactivity with nucleophiles is decreased by the stabilizing conjugation, which depends on the electron donating ability of X.” This confuses me because I thought that weak bases were good leaving groups and, therefore, more reactive to nucleophilic substitution? That is correct. (Weak bases usually hold an electron pair better, so stabilization of the carbonyl group decreases, and, therefore, reactivity increases. It is another part of the explanation of the basicity trend. - GS). So does that mean that strong acids are bad leaving groups and are more reactive to nucleophilic substitution because they want to donate their electrons?

Can you explain the main difference between an enol and an enolate? (Enol is a conjugate acid to enolate. - GS).

During class when you were talking about Histones and the ability of the amines in them to form spikes, what did you want us to know for that? I understand if there’s a spike in the wound structure of the protein and DNA that it won’t unravel easily but what else is there to know about the importance of Histones and how they relate to the chemistry we are learning now? (Just know that the amino-groups of histones can act as nucleophiles in the nucleophilic acyl substitution with a thioester AcetylCoa. You do not need to know anything from biochemistry for the exam. - GS).

I know we went over the mechanism of alkylation of amines in class but could you explain it again? (It is SN2 with amine as a nucleophile: http://ochem.orgfree.com/sn2.html - GS). Could you also explain how alkylation of amines is different from acylation of amines? (Acylation of amines proceeds by the nucleophilic acyl substitution that will be discussed in unit 10. - GS).

Why are aldehydes more reactive than ketones? (Less steric hindrance, less stabilization of the partial positive charge of the carbonyl group, and the possibility to oxidize the aldehyde proton - GS).

Substitution is more favorable right because it restores aromaticity? (Yes, for the second step of aromatic electrophilic substitution. - GS).

What does it mean when there is anoic at the end of a word like butanoic or propanoic? (It means “carboxylic acid”, for instance propanoic acid is CH3CH2COOH - GS).

Does acylation of an amine create an amide? (Yes. - GS).

What does cyclic mean? (It means, that some atoms are connected by chemical bonds to at least one chain that has no ends. - GS).

Going off of the previous questions, to be a H bond donor do you need more than one Hydrogen? (One H is sufficient as long as it is acidic enough - GS ) And to be a H bond acceptor do you only need one pair of lone electrons? (Yes, if it is by O, N. or F - GS)

What is the correlation between s character and basicity in amines? (The increased s-character of the orbital holding the electron pair, decreases its energy, and, therefore, decreases basicity. - GS).

How do we determine basicity between different amines? (Conjugation of the electron pair on nitrogen reduces basicity of the amine. - GS).

I know you touched on this at the end of class, but i am still confused. When trying to determine whether or not hydrogen bonds will form between a molecule and water we look for lone pairs, correct?? (Yes. - GS). What about when trying to determine if a molecule will form hydrogen bonds with itself?? (It happens when the molecule contains a both H-bond donor, and a H-bond acceptor. - GS).

What is the difference between alkylation and acylation of amines? Could you please go through an example of each? (Alkylation is introduction of an alkyl group to the amine’s nitrogen. Example - preparation of lecithin from methyl iodide. Acylation is introduction of an acyl group to the amine’s nitrogen. Example - synthesis of acetaminophen from para-aminophenol. - GS).

In Gabriel Synthesis, what deactivates the lone electron pair? (Resonance conjugation with two C=O groups - GS).

Is there a way to predict the major product of an electrophilic substitution reaction for aromatic compounds without doing all of the steps in the reaction mechanism? (Yes. Determine if the existing substituent is ortho-para- or meta-director. - GS).

What is n in 4n+2? I understand that it is an integer but what number does it represent? Principal Quantum number? (No, it comes from the mathematical definition of an odd number of orbitals (2n+1). - GS). It is still not clear. (Each orbitals holds 2 electron, so the number of electrons = 2X(2n+1) - 4n+2. - GS).

Can a substituent be an electron donor and acceptor? (Yes. - GS). If it can, does the electron donor effects always override the acceptor effects? (No. Resonance effects override the inductive effects for activators or deactivators, except for F with its huge inductive effect. - GS).

How do you determine the order of reactivity when comparing cyclodienes, cis-dienes, and trans-dienes? (By their ability to produce the reactive (in the Diels-Alder reaction) s-cis conformation. - GS).

Can you please review how to determine if a compound is aromatic or not depending on the number of conjugated electrons?  I understand how to count the number of conjugated electrons but am unsure of how that relates to aromaticity. Thanks (An aromatic system must contain 4n+2 electrons (n=0,1,2,....) in a cyclic conjugation (uninterrupted by sp3-hybridized atoms. - GS).

Why is having a donor in the Meta position so unfavorable? (Since the sigma-complex has the formal positive charge distributed between ortho- and para-positions, the groups at those positions have the strongest effect on the reaction, so the donor speeds up ortho- and para-substitution much more than meta-substitution. - GS).

How do you identify a “pure acceptor?” How are these different than regular acceptors? (They have no electron-donating effects. - GS).

What does resonance have to do with the weak influence of the donor in the meta position? (Since the sigma-complex has the formal positive charge distributed between ortho- and para-positions, the groups at those positions have the strongest effect on the reaction. - GS).

To clarify- if you have an incoming substituents in the metha or ortho position, there is a strong influence and if you have an incoming substituent in the ortho position there is little influence? (No. Since the sigma-complex has the formal positive charge distributed between ortho- and para-positions, the groups at those positions have the strongest effect on the reaction.The incoming substituent has almost no influence, because it attaches to an sp3-carbon with no formal charge - GS).

How do you determine whether a compound will go through the SN1 reactions slower or faster?? (More stable intermediate carbocation, higher concentration of the substrate, and a better leaving group will all make the reaction faster. - GS).

Just to clarify something with more substituents is more stable than something with less? (That is true for C=C bonds and carbocations. There are other examples. - GS).

So far we learned about ortho and para positions but do compounds ever go to the meta position and if so when does that happen? (Electrophiles always enter the meta-position,, but preferably - when the existing group has no donating effects. - GS). Also can you go over why meta isn’t as favorable as ortho or para please, I’m still confused why it isn’t? (The sigma-complex has the positive charge distributed over the ortho- and para-positions, so it is stabilized better by ortho- and para- electron-donating substituents, which makes the ortho- and para-orientation preferred. Ortho- and para-substituents with no electron-donating effects are are having trouble withdrawing electrons from the positively-charged ortho- and para-positions, which makes ortho- and para-orientation unfavorable, so the meta-substitution is preferred. - GS).  

How do you tell if something has a resonance electron withdrawing effect? (There is a X=O bond or empty d-orbital (like in Cl, Br, and I) in conjugation with the benzene ring - GS).

Can you go over another example of the pi-complex and sigma-complex mechanisms? I don’t really know the distinction between the two quite yet. Thanks!! (They are steps of the same mechanism of aromatic electrophilic substitution: http://ochem.orgfree.com/SEAr.html  - GS).

How do we know if lone pairs participate in regards to aromatic and antiaromatic compounds? (It participates if it can be perpendicular to the plane of the ring and, therefore, align with the pi-system. It will always happen if that space is not already occupied by a p-orbital of the pi-system. - GS).

How do we know if a carbon is allylic? (If it is next to C=C, which is not a part of an aromatic ring. If it is, the carbon is benzylic. - GS).

For clarification does the acidity dictate the aromaticity of the molecule? (No. - GS). Is a more acidic compound automatically aromatic if it follow Huckel’s rules? (No. Aromaticity increases stability of the conjugate base, which increases acidity of the conjugate acid - GS).

So when a molecule is twisted it can not be either aromatic or anti-aromatic?(Correct - GS). No matter the number of electrons? (Correct - GS) Would a non-aromatic molecule be more stable than an anti-aromatic molecule? (Correct - GS)

I understand that hydroboration followed by oxidation is used when we need to perform hydration of a double bond against markovnikov’s rule, however, at what point is the markovnikov’s rule broken? According to markovnikov, the halogen of the hydrogen halide attaches to the carbon of alkene bearing the fewer number of hydrogen and greater number of carbons, so does this mean the rule is broken when the conditions are changed as to where it attaches? (That was the original rule formulation of Markovnikov’s himself. Now, we understand the rule broader: instead of halogen, it can be any negative part of the reagent. The rule usually works if addition proceeds through a carbocation, which is not the case for hydroboration. - GS).

Does the SP3 bond break when its fragments are rotated? (There are no sp3 bonds. - GS). Also, can you please give an explanation on this concept. Thanks!  (Sigma-bonds do not break, because the bond-forming orbitals (may involve sp3-orbitals), overlap in only one area. Pi-bonds break, because the bond-forming p-orbitals overlap in two areas, which have to disconnect during the rotation.. - GS).

When selecting R or S configuration, I know that we 1. Rank substituents by highest priority (highest atomic mass) 2. Find out which way priority is decreasing 3. If priority is decreasing clockwise, then R configuration… If priority is decreasing counterclockwise, then S configuration 4. Change R configuration to S configuration, or vice-versa, if lowest priority group is pointing to the front….. I understand all of this, however, I always get confused when the lowest priority group is neither pointing towards you or away from you…. Do we still flip the configuration if the lowest priority group is in the plane of the paper? (Flip the lowest in priority group, which is in the plane of paper with the group behind paper, determine configuration as usual, and flip your answer. - GS).   Or do we instead have to rotate the molecule in our minds in order to get the lowest priority facing away, and then go ahead and figure out the configuration?  Spasibo.  (This will also work.  Choose either method, depending on your individual strengths. - GS).  Your advice to flip the lowest priority, which is in the plane of paper, with the group behind the paper, determine configuration, and flip the answer sounds much better.  That really cleared things up.  Thank you!!

Are all H atoms abstracted from beta carbons only? (No. It is true for E1 and E2 reactions - GS). What other conditions are necessary for H abstraction? (Besides of E1 and E2, it is also free radical abstraction, and some other reaction conditions outside of the scope of this course. - GS).

Actually, please explain the entire concept of Solvent Effects on Nucleophilicity. Please be specific on what we need to know. Thanks. (As opposed to protic solvents, aprotic solvents selectively solvate cations, leaving anions “untamed”. This reverses the nucleophilicity trend of anions in groups, such is from F to I - GS).

Please explain further what polar aprotic solvents are? (There are polar solvents with no protons acidic enough to create hydrogen bonds - GS).

Are nonpolar solvents aprotic? (Yes. - GS). What is the connection if there is any? (Protons acidic enough for hydrogen bonds, create polarity, but there are other sources of polarity - GS).

Please explain why diluting a system of Sn1 and Sn2 will favor Sn1 and why concentrating the same system will favor Sn2. (Because the reaction rate of SN1 is proportional to the total concentration, while the reaction rate of SN2 is proportional to the square of the total concentration. - GS).

Can you explain how you know which reaction will be more efficient in an E2 reaction? (Usually by Zaitsev rule in the anti-fashion, unless the alternative regio- and stereo-pathways have lower transition states. - GS).

Why are some bonds only partially formed? (Because it corresponds to the lowest energy of the system when the atomic nuclei are in the process of moving from one intermediate to the next one on the reaction pathway. - GS).

Is it true for majority of reactions that you can’t obstruct a Hydrogen from an alpha Carbon and it has to be beta? (Yes, beta-abstraction is preferred over alpha-abstraction - GS).

How do you determine the major product? I have been going over questions from the database and just when I think I’m doing it right I get the question wrong. Could you please clarify on that. (The major product is either lowest in energy (for equilibrium conditions), or the fastest forming product - GS).

Could we please go over what exactly a carbocation is?  It comes up a lot in class and I just wanted to make sure I know what it exactly is.  Thank you! (It is a particle with a carbon with the formal charge +1 - GS).

Could you please explain how to tell the strength of an acid from looking at its structure? (For neutral acids, remove H+ and evaluate stability of the remaining anion (= conjugate base), taking into consideration electronegativity of atoms holding the negative charge, and number of resonance structures. - GS).

Could you just remind us the difference between the molecular geometry versus the shape? (For molecular geometry, you consider both bonds and lone electron pairs. Next, you remove the lone pairs, do not move any atoms, and that will be the shape. - GS).

Could you explain how to determine the hybridization state of a molecule? (Hybridization state of ATOMS is determined by the geometry around them, which leads to different participation of p-orbitals in the formation of sigma-bonds. - GS).

I was wondering if you can have two sigma bonds or if you can only have multiple pi bonds? (There can not be more than one sigma-bond or more than two pi-bonds between the same pair of atoms because of the space conflict. - GS).  

What is the difference between reducing esters with LiAlH4 or NaBH4? (The first one reduces esters, the second one - does not. - GS).

What is thermodynamic control? (Directing a reaction towards the most stable product. - GS).

Why does having a destabilized nucleophile in an SN2 reaction decrease the free energy of activation? (Because the transition state retains its energy, so the activation barrier is lower. - GS).

How does a polar, protic solvent reduce the free energy of activation and stabilize an intermediate in an SN1 reaction? (By solvation of the very polar transition state - GS). And, why does a stabilized intermediate reduce the energy barrier? (Because the less polar starting compound is not stabilized as efficiently as the transition state - GS).

Can you just briefly explain what a meso compound is? Is it just a compound that hasn't been distinguished between cis and trans?(No. It is an achiral compound with chiral centers. - GS).

Dr. Sereda, I was looking over some of the previous year’s quizzes and in the preparation of 5-methyl-2-hexyne from propyne, what would be the nucleophile? Would it be the same as the alkylating agent? Thanks. (The nucleophile is deprotonated alkyne, which attacks the alkylating agent and kicks out the leaving group from it. Overall, it results in the introduction of the alkyl group to the alkyne. - GS).

How do you know, when looking at a Newman projection, if it is staggered or eclipsed? (Eclipsed conformations have three dihedrals of 0o, staggered conformations have none. - GS).

How do you prove that the Beckmann’s rearrangement pathway where the leaving group and alkyl migration occur simultaneously is prefered over a pathway with a nitrenium ion intermediate? (For the simultaneous pathway, the group in the anti-position with respect to the oxime hydroxyl will migrate. If the nitrenium ion forms, both group will have a good chance to migrate. - GS).