When looking for a compound that is the most reactive with a nucleophile do you always choose the molecule that is the least electronegative?(No. Electronegativity refers to an atom rather than to a molecule. - GS) Would it be correct if I had said: the most reactive compound with a nucleophile is the molecule that contains  the least electronegative atom because this reaction will lead to the best leaving group? (No. Most electronegative atom makes the weakest base if you compare elements of the same period with the same charge. - GS).

Dr. Sereda, out of the choices A. I-, B. H2O, C. Cl-, D. CH3OH, and E. F-, which would be the LEAST reactive with bromoethane? (Choices B, D, and E are bad for the reaction. One of them can be made worse than another depending on solvent and concentration. Nucleophilicity of F- will benefit from an aprotic solvent, water and methanol - from using them as solvents. - GS).

Do inductie acceptors, resonance acceptors, resonance donors, hyperconjugative donors, and hyperconjugative acceptors all proceed preferentialyl to the meta-position? If not, which ones don’t and what do they proceed to? (You need to look at the existing substituent, not the incoming one. - GS).

For a compound to absorb UV-Light at the longest wavelength and highest intensity, would it always be in regards to the length of the conjugated chain; thus the longest chain of conjugation= the best compound to absorb UV-light at the longest wavelength and the highest intensity? (Yes, but for comparison, it must be a linear (non-cyclic) conjugation. For example, graphene has a huge number of conjugated benzene rings, but stays colorless. - GS).

Is sp hybridized, in general, less stable than say sp2 or sp3? I know that the sp has a shorter bond length than sp3 and that the bonds involved in sp are stronger than the sp3 but I am not 100% sure how that relates to stability. I was thinking that the single bonds are more stable because they have less energy in the bonds and thus sp3 will generally be more stable than sp, is that right? (I would not directly relate energy to the hybridization model, except for the orbital holding a lone electron pair. - GS).

I cant seem to remember what “poly” means? I know that the -diene means 2 double bonds, -ene means a single double bond; cis means on  the same side of a double whereas trans means across/opposite sides of the double bond. Thanks. (“Poly-” means “polymer”. - GS).

Hello Dr. Sereda, I have a quick question about multiple substituents on benzene rings. If you have two substituents that are donors, how you can tell which is the more activating donors group? (The resonance donor wins - GS). For instance, if you had a OH and a methyl group in the para positions to each other, (OH-group will determine orientation - GS).  how would you know where the incoming substituent would attach? (ortho-position with respect to the OH-group - GS).

How do you know when a substituent will hyperconjugate? How can you tell if it is a donor or an acceptor? (Hyperconjugation is essential for alkyl substituents (donors) and polyfluoroalkyl substituents (acceptors). For our substituents, hyperconjugation is usually muted by other effects and should not be considered. - GS).

How can you tell what a free radical is? (It is an orbital occupied by a single electron, which is denoted by a dot on organic structures.. - GS)

Can we go over why halogens are ortho, para-directing but a deactivating group again? (F is so electronegative that it overrides even the resonance donating effect of its lone electron pairs. For Cl, Br, and I, the lone electron pairs are taking too much space, which makes their overlap with the pi-system of the benzene ring less efficient, so the donating resonance effect is outcompeted by the inductive withdrawing effect. Also, empty d-orbitals of Cl, Br, and I account for additional resonance withdrawing effect. -GS).

If a substituent is a good electron donor, does that mean that the benzene ring is more reactive and willing to accept another substituent? (Yes, but only toward the SEAr reaction - GS). I think I am getting the para-ortho/ meta-directing groups mixed up with what a good activating and deactivating group is. How are these related? (Substituents are meta-directors only if have no electrondonating effects at all. All other substituents a o-,p-directors. Activating substituents are overall donors and deactivating substituents are overall acceptors. The resonance effect takes precedence over the hyperconjugative effect, which takes precedence over the inductive effect except for halogens, which are deactivating substituents. To avoid the most common mistake, consider the existing substituent, not the incoming one. - GS)

Could we go over what makes a good activating/deactivating group again? I still don’t understand the concept. (Donating electrons activates the ring toward an electrophile, withdrawing electrons does the opposite. - GS).

Why is the overlap of p orbitals in molecules with cyclic arrays of 4n pi electrons a destabilizing effect? (The highest occupied molecular orbital has higher energy and has same energy as the lowest unoccupied molecular orbital. - GS).

I read that a 1,4 addition more favorable than a 1,2 addition, but I don’t understand why? Wouldn’t the carbocation formed in a 1,4 addition be less stable than a 1,2 addition? Or is it because the carbocation is stabilized by resonance? (1,2-addition is faster, but 1,4-addition gives a more stable product. - GS),

What forces cyclooctatetraene into it’s tub-shaped structure? I understand the consequences of the tub shape in relation to it’s ability for p orbital overlap, but I don’t understand what forces it to be tub-shaped? (Mostly avoiding anti-aromaticity. - GS).

Do you have any tips on how to distinguish aromatic, antiaromatic, and nonaromatic?  (Use Huckel rule. - GS).

What is the significance of a sigma complex? (It is formed at the rate-limiting step of aromatic electrophilic substitution and where the electrophile is bonded by a sigma-bond. . - GS).

Dr. Sereda, I am still a bit confused on the counting of electrons on aromatic and antiaromic species. When a triangle, square, or hexagon has a + sign somewhere on the molecule, does that not contribute to counting of electrons? (It does contribute, because electrons carry a negative charge. - GS). Furthermore, does a - symbol count as two electrons? (No. It means that the structure has one more electron, than its neutral analogue. For instance, cyclopentadienyl-cation with 4 electrons has one less electron, than its neutral analogue - free radical with 5 electrons. Cyclopentadienyl-anion with 6 electrons has one more electron, than its neutral analogue - free radical with 5 electrons. - GS).

Is it true that for Huckel’s rule, if you solve for n and obtain a fraction, that it does not work? (No. The rule still works. It means that the system is not aromatic or it is antiaromatic. If you want to challenge the rule, make the system non-planar, or break the continuous conjugation by sp3 atoms, or introduce a bunch of additional cycles (polycyclic system). - GS).

Dr. Sereda, I am mostly understanding Huckel’s rule, however, I am unsure of what integer to plug in. I understand that it can be 0, 1, 2, 3, etc.. but how do you know when to plug in 0 for n, versus when to plug in 1 or 2? (If N is number of electrons, the integer n can be found from the equation: N=4n+2 or n=(N-2)/4  - GS).

Dr. Sereda, what causes a compound to absorb UV-light at the highest and longest intensity? (Generally speaking, the “transition moment”, which is related to the overlap of wavefunctions of the ground and excited states, determines intensity of absorption. For linear conjugated polyenes - it is simply the number of C=C bonds in continuous conjugation. - GS).

Does the “starting material” for polymerization always have to contain the prefix “poly?” (Never. The polymer has the prefix “poly”. - GS).

What’s a Frost circle? (It is a polygon-circle diagram that gives energies of pi-orbitals of a cyclic system by Huckel model without performing quantum chemistry computations. - GS).

When a molecule has adjacent double bonds, does that make it conjugated? (Yes, if they are not connected to the same carbon. - GS).

When looking at conjugation, does it matter if the adjacent bond is double or triple. Does it matter that instead of another double bond it is a triple bond? (No. Triple bonds will also conjugate. - GS).

Why would Methylene Chloride be a better solvent than Hexane? Both are immiscible with water, but hexane (dielectric constant= 1.9) is less polar than methylene chloride (dielectric constant 8.9). The compound is only slightly polar, so wouldn’t you want the slightly polar solvent (hexane) since “like dissolves like?” (A more polar solvent will be better to dissolve a slightly polar substance due to stronger dipole-dipole interaction. The rule “like dissolves like” is a good starting point for people who know nothing about chemistry. You do not belong to that group anymore. - GS).

I am having trouble figuring out how one would even figure out what is the best choice to extract a slightly polar compound. Would it be the most electronegative or something that is completely unsoluble in water like an alkane? I dont understand. (Most polar solvent immiscible with water. - GS).

How does a protic solution affect the leaving group ability and the nucleophilicity? (It decreases nucleophilicity (comparing with aprotic solvents) by stronger solvation and does not significantly affects quality of the leaving  group) - GS).

Is the compound with Iodine in it always the most reactive if its an option? (No - GS). Could you explain why it isn’t please (Besides of the leaving group, there are other factors of reactivity. For instance, primary iodides will not react under SN1 conditions. - GS).

Could you give us a basic definition of what the dielectric constant tells us? (It tells us by how much electrostatic energy is decreased in the solvent and is a measure of the solvent’s polarity. - GS).  I looked up definitions online and I did not understand. Does a greater dielectric constant mean it will enhance the extraction from a slightly nonpolar substance (It will increase extraction of a polar compound due to decreasing its electrostatic energy, therefore, stabilization, therefore, higher solubility. - GS).

What is the difference between a “bulky base” and a “non-bulky base? (Size, causing steric hindrance - GS)

Why is an alcohol more acidic than an ether? I don’t understand how the Hydrogen attached to the Oxygen plays a role. (Oxygen is more electronegative, than carbon, which makes the conjugate base stable and weaker. - GS).

Why is propanol a bad leaving group? (It is a good leaving group, because its protonated form is a strong acid - GS).

For the Regioselectivity of E2, how do you know which one is the minor product and which is the major product? (More stable emerging C=C bond leads to the major product - GS).

For chain termination, is the only thing that is happening is that 2 separate molecules form a bond? (Chain termination is any reaction consuming reactive free radicals - GS).

In a question asking to rank ions/molecules (F-, Br- Cl-, OH-, I- H2O) in order of increasing nucleophilicity, where would H2O rank? (About the weakest, close to fluoride - GS). Also, which would the the best leaving group? Would it be I-? (Yes - GS).

So when charge increases there is an increase in Nu and basicity?  (Yes - GS).

When do you use "mercaptan" in nomenclature? (It is not used in the systematic nomenclature. However, the SH-group is referred to as “mercapto”, if it is not the highest in priority group. - GS).

Is the preferred Sn2 and E2 solvent a polar “aprotic” solvent? (Both. Aprotic solvents increase both nucleophilicity and basicity - GS). Does this mean that there are no O-H or N-H bonds? (Yes - GS).

You stated about that Sn2 reactions are not the only ones affected by steric hindrance-so what other types of reactions are affected and will we need to know them now or later? (Regioselectivity of hydroboration, ant-character of E2 - GS).

Are you going to over examples of these? (We did. Markovnikov rule, Zaitsev rule, staggered and eclipsed conformations - GS).

Before you get too carried away, what is regioselectivity? (Preference to react with one part of the molecule as opposed to another, such as addition or elimination. - GS).

For an E1 mechanism, will both cis- and trans- isomers be produced? (Yes, with a preference of the more stable trans-isomer - GS).

What are alkoxides? (Conjugate bases of alcohols - GS).

Can you go over Regioselectivity of E2? (Anti-fashion shown on U.CAN - GS).

Are alcohols stronger acid than ethers because in alcohols oxygen is bonded with hydrogen? (Yes. - GS).

Is I- a better leaving group than OH- because it’s cheating with its size, or is it just a better leaving group in general? (Because it is a much weaker base. - GS).

How do you determine what the best leaving group is? (The weakest base. - GS).

How does pKa relate to the reactivity of a nucleophile? (No connection. - GS). Would the highest pKa mean that that specific nucleophile has the highest reactivity? (No. - GS).

Is steric hindrance only applied to SN2 reactions? (No. - GS).

I have a question regarding the radical halogention of alkanes; in the chain propagation portion when R’ + Cl2 = RCl + Cl’, why doesn’t the R’simply attach to the extra Cl^- from chain initiation? (It does, but slowly because of very low concentration. - GS). In chain initiation, Cl2 = 2 Cl. In the first part of chain propagation, one Cl is used but there is no mention of what happens to the other. (Same thing. Both atoms are identical. - GS). In other words, is the second part of chain propagation (R’ + Cl2 = RCl + Cl) used to initiation the breaking of a Cl2 bond and continue the reaction? (It does break the Cl-Cl bond, but it is called propagation rather than initiation. - GS). So if there is no irradiation by light or heat, will the Cl2 bond not break and propagation won’t occur? (Light or temperature are not needed for propagation because of the highly energetic carbon-centered free radical. - GS). But on your powerpoint, you stated for initiation to occur, it requires light or heat. I don’t understand how propagation can then occur

without the initial breaking of the Cl2? (It can not. Propagation must be preceded by initiation. - GS).

Does the “2” in SN2 denote that there is two species involved in the reaction? Is one of these the nucleophile? (Yes to both. - GS). Just to be clear, for an SN2 reaction there would be (for example) a methyl iodide molecule and a nucleophile? (Yes. - GS).  Or would there be a methyl iodide molecule, an ethoxide ion, AND a nucleophile? (No. Methoxide is a nucleophile. - GS).

A compound is more acidic when the bond between two molecules is weaker? (No. It is more acidic when the conjugate base is more stable and the acid is less stable. - GS).  Is a primary compound  less acidic than secondary and a secondary compound  less acidic than tertiary? (No. It depends on a specific acid-base pair. - GS). So basically if its attached with a triple bond its more acidic than if it were attached with a double bond and so on? (If you mean hydrogen attached to a carbon connected with a multiple bond - yes. - GS).

How would you know if a reaction is faster than another? Does it have to do with stability, Such as that the reaction would be slower if the molecule is very stable (mainly when a compound is branched)? Or is it only related to primary, secondary, and tertiary; where primary is the fastest and tertiary is the slowest? (Lower energy difference  between a starting compound (intermediate) and the transition state  (activation energy) at the rate-limiting step makes the reaction sequence faster. - GS).

Boiling points increase as the attractive forces between molecules increase, so would that basically mean that the boiling point increases when the electronegativity difference  between two compounds is higher/increased?  (No. Electronegativity refers to atoms rather than to compounds. - GS).

What characteristics identify a compound as being highly soluble in water, besides being a nonpolar substance? (Nonpolar substances have very low solubility in water. Polarity and ability to form hydrogen bonds increase solubility in water., Sometimes it is not enough, and a weak crystal lattice needed. - GS).

Can you go over how to determine boiling point just by looking at a molecule? (You can not do it, but can compare it for different structures. Stronger intermolecular interactions (usually H-bonding > polarity > surface area) correspond to higher boiling points. - GS).

What does the structure of cyclohexyl mercaptan look like? (Cyclohexanol, but with sulfur instead of oxygen - GS). And benzenthiol? (Cyclohexyl mercaptan, but with three C=C bonds in the ring - GS).

What is steric hinderance? (Parts of molecules bump into each other due to the repulsive interaction between occupied orbitals. It slows down some chemicals reactions and affects shapes of molecules that tend to avoid such interactions. - GS). And how does it apply to Sn1 and Sn2 reactions? (As opposed to SN1 reactions, SN2 reactions are very sensitive to steric repulsion. - GS).

So basically apply Zaitsev’s rule  only to dehydration reactions? (No. To any elimination. - GS). Also, would the Markovnik rule be used to identify which carbon a halogen should be attached to? In specific does it mean that a halogen attaches to the carbon with the least hydrogens? (Correct. This rule applies to addition. Compare with Zaitsev’s rule. “Zaitsev” is a derivative from the Russian word for “Jack rabbit” or "Hare", which can run away or eliminate. “Markovnikov” is a derivative from the Russian word for “Carrot”, which adds good nutrients. Just a way to remember to which reactions those two rules apply. - GS). That’s a very helpful/interesting way to remember which is which. Thanks. :)

Can we spend time discussing what racemates are? (1:1 mixture of opposite enantiomers. - GS).

How can you tell when a chirality center loses/switches its configuration? (If at any point of the reaction path this carbon has a planar geometry, configuration is lost. In the SN2 mechanism (see U.CAN), it is inverted. In all other cases, it is kept. Excellent question. Failure to answer it has led to the Thalidomide tragedy. - GS.

How do meso compounds and optical rotation relate? (No optical rotation like for any other achiral compounds. - GS).

When you count the hydrogens in elimination, would you also count the hydrogens attached to the carbon, say if the carbon was on the 3rd or 4th in a hexane chain? (We count hydrogens bound to the carbon next to the carbon, which has the leaving group (Br) - GS).

Whats the difference between hydrobromination and bromination? (Hydrobromination adds hydrogen and bromine to the double bond. Electrophilic bromination adds two bromines to the double bond. - GS).

Are alkynes sp hybridized, or sp3? (For carbons connected with a triple bond, we use the sp model, for tetrahedral carbons of alkynes - sp3 model - GS)

would tetrahedral and trigonal bipyramidal both have the same hybridization of sp3? (No. Only tetrahedral. Bipyramidal involves d-orbitals - GS).

Would you consider sigma bond to be more stable since it is a stronger bond and has less energy than the pi bond? (Yes. - GS).

When is markovnikov's rule against and when is it by? (Addition through an alkyl cation goes by Markovnikov. Other cases must by considered depending on their mechanisms - GS).

Why is HPClBrCH3+ chiral? It looks like the C is attached to 3 of the same H? would the chiral center actually be Br assuming that it is attached to a Cl, a CH3, a P, and a H? (It is chiral because of a chiral phosphorous, not chiral carbon. - GS).