hello everybody my name is Iman welcome back to my YouTube channel today we're continuing chapter 9 for mcount organic chemistry in the first part we covered some Basics about Esters amides and anhydrides today we move into the second object objective where we're going to cover reactivity principles now in nucleophilic substitution reactions we know the reactivity of the carbonal is determined by its substituents and hydrides are going to be the most reactive followed by Esters which are essentially tied with carboxilic acids and then finally amides now this can be explained by the structure of these molecules so if we look at the structure of these three molecules we said anhydrides are the most reactive then Esters and then amides are the least reactive and hydrides all right with their resonance stabilization and three electron withdrawing atoms they're going to be the most electrophilic Esters by comparison they they lack one elect El electron withdrawing carbonal oxygen and they are then slightly less reactive sorry I got so excited saying electron withdrawing that I had a little bit of a tongue twister moment and then finally amides we said least reactive in comparison to these three amides they have an electron donating amino group and so they are the least reactive towards nucleophiles now in talking about these three molecules there's a couple of important things for us to cover to really understand these molecules and their comparisons relatively their relative reactivity comparisons and the first thing that we want to do is talk about steric hindrance all right steric hindrance is always worth keeping in mind when you're considering reactivity and it describes when a reaction does not preed due to the size of the substituents and so a good example of this is when we learned about sn2 reactions in organic chemistry and also in this series we noticed that they're not going to occur with tertiary carbons sn2 reactions do not happen with tertiary carbons this effect is can be used to our advantage for specific synthesis protocols if we needed to and knowing that right but the reason essentially why sn2 reactions don't occur with tertiary carbons is because of steric effects all right and so steric effects are a good thing to keep in mind when you are discussing reactivity steric hindrance is something is usually one or the main reason why certain reactions do not occur we we also learned that considering steric hindrance you can take advantage of that to prevent certain byproducts of a reaction or favor one product over the other when we talked about protecting groups like acetals we said that you can use it to increase steric hindrance in an area where you don't want things to react or otherwise decrease the reactivity of a particular portion of a molecule now some else we could talk about is electronic effects and there are several electronic effects that must be considered in organic chemistry on the MCAT and you guess that all of them come into play when you're considering carboxilic acid derivatives so we can start with induction induction refers to the distribution of charge across Sigma bonds electrons they're attracted to B to atoms that are more electronegative and that generates a dipole across that Sigma Bond the less electronegative atom obviously acquires a slightly positive charge and the more electronegative atom acquires a slightly negative charge all right this effect is relatively weak but it gets and it gets weaker as one moves away you know further from that group in a molecule you know this effect right when we talk about carbonal groups all right there's a dipole moment where the carbon gets a partially positive charge associated with it and the oxygen a slightly negative charge associated with this all right this effect is responsible for that dipole character of the carbonal group that we've been talking about for nearly the past 3 to four chapters now in addition to that all right this also explains thinking about induction also explains the overall relative reactivity of of anhydrides Esters and amides towards nucleophilic attack anhydrides have two electron withdrawing groups which leaves a significant partial positive charge on that electrophilic carbon and this effect is less with amides all right this effect is smaller in amides because nitrogen is a less electronegative atom than oxygen and so the dipole is not as strong something else under this category of electronic effects that we need to talk about is resonance and conjugation they also affect the reactivity of a molecule conjugation refers to the presence of alternating single and multiple bonds this setup implies that all atoms involved in these bonds are either going to be SP2 or SP hybridized and therefore have unhybridized P orbitals and then when those P orbitals align they can delocalize Pi electrons through resonance forming clouds of electron density above and below the plane of the molecule all right so conjugation induction both electronic effects to keep in mind when you are trying to reason through why anhydrides are more reactive followed by estr and then amines now resonance is also another thing to keep in mind electrons experience resonance through the unhybridized P orbitals increasing stability and so conjugated carbonal compounds are going to be more reactive because they can stabilize their transition States and then as a last point to talk about for reactivity principles that's um important especially for cyclic molecules is strain in cyclic derivatives we talked about lacms and lactones there cylic amides and Esters respectively and one thing to keep in mind is that increased strain in a molecule can make it more reactive so things like betal lactams are prone to hydrolysis because they have significant ring strain and ring strain is due to torsional strain from eclipsing interactions and angle strain from compressing bonds uh compressing Bond angles below a certain threshold around 10 9° all right so for reactivity principles we we discussed steric hindrance induction conjugation resonance and cyclic um uh strain and cyclic derivatives as all things to consider when we talk about the reactivity the relative reactivity of anhydrides Esters and amides all right and that is our second objective we just completed our second objective with that we move into our last and final objective which is nucleophilic AAL substitution reactions now when you took oam 1 and 2 you probably encountered a ton of reactions all right for this chapter for this category of you know for this topic carboxilic acid derivatives for the previous couple chapters we talked about but something you've noticed is that in the MCAT there's only a handful of reactions that you're going to get potentially tested on and so we're going to discuss those reactions as they pertain to carboxilic acid d uh derivatives all right and the first thing that we want to talk about is anhydride cleavage all right we said that anhydrides are the most reactive towards nucleophiles followed by estos and then amines and so in this first category we're going to talk about anhydride cleavage and we're going to talk about three things we're going to talk about anhydrides being cleaved using amines and hydrides being cleaved using um alcohols and anhydrides being cleaved using water and so this first reaction we see here all right cleavage reactions and we say anhydride cleavage here because um our anhydride is going to be that one anhydride molecule is going to be split into two molecules now in this first reaction ammonia acts as has the nucleophile one and one of the carbonal carbons as acts as the electrophile so this is symmetrical all right so it doesn't matter which carbon here this carbon is going to be our electrophilic carbon that our ammonia is going to um attack all right so our ammonia acts as the nucleophile this is our electrophilic carbon all right and then ammonia attacks it adds itself to that carbon we break that double bond it dumps its electrons on the oxygen now now our oxygen has a negative charge associated with it all right our oxygen has a negative charge this nucleophile that attacked and added itself to the anhydride molecule has a positive charge now this oxygen right here has two lone pairs one of these lone pairs is going to snatch the hydrogen all right from the nucleophilic group that just attached all right and then after that happens our um El or our electron group on this oxygen is going to reform a double bond and then we're going to break this Bond completely all right and as a result what you get is a carboxilic acid and an amide all right so this is nucleophilic ACL substitution going from anhydride to an amide and a carboxilic acid as end products now something else that can happen is that alcohols can also act as nucleophiles towards anhydrites so here we see an alcohol doing the same thing it's going to attack our electrophilic carbon here attach itself we break this double bond it dumps its electrons on the oxygen this oxygen in the anhydride with lone pairs is going to snatch a hydrogen from our nucleophilic group that just attached and then we're going to reform our double bond and break away this portion of the molecule and what we get at the end is an Esther and a carboxilic acid so in this new nucleophilic ACL substitution we go from an anhydride to an Esther and a carboxilic acid as the end products lastly anhydrides can also be reverted to carboxilic acids by exposing them to water like we see in this reaction again pretty much the same protocol except now we have water all right and that means that our end products are going to be two carboxilic acid molecules so for this nucleophilic ACL substitution tion reaction we go from anhydride to two carboxilic acid molecules the next reaction that we want to talk about is transesterfication now alcohols they can act as nucleophiles and they can displace the estery group on an Esther and this process is called transesterification so in this reaction One Esther is simply transformed to another like we see in this reaction so we go from this oxygen having a methyl group group to having now an ethyl group all right so transesterification different alcohol chains are swapped into and out of the esterifying group position all right and then last but not least to end this chapter we're going to talk about the hydrolysis of amides amides can be hydrolized under highly acidic conditions through nucleophilic substitution the acidic conditions allow the carbonal oxygen to become proteinated at making the molecule more susceptible to a nucleophilic attack by a water molecule all right and then the product of this reaction at the end is a carboxilic acid and ammonia and as you notice this water attacks it adds itself here all right then we reform a double bond kick out this um amine group all right and then lose a hydrogen up here to form our end products of carboxilic acid and amine all right so this is how we go from an amide all the way to carboxilic acid with ammonia as a byproduct all right now hydrolysis can also occur if conditions are basic enough this reaction is very similar to the this acid catalyze reaction mechanism that you see except that the carbonal oxygen is not protonated and the nucleophile is going to be a hydroxide ion instead all right with that we have covered everything we need to know in this chapter we talked about reactivity principles in this video we talked about how you should consider steric hindrance induction conjugation resonance and ring strain as possible explanations for why certain groups may be more reactive than others and we use that as a basis to understand why anhydrites are more reactive than Esters which are more reactive than amides and then we covered a couple of nucleophilic AAL substitution reactions that we need to know for the mcap we saw how anhydrites can be cleaved by the addition of a nucleophile and that nucleophile can be ammonia or an amine it could be alcohol or water and we learned what each of those scenarios for n different nucleophiles what it results in at the end all right so for anhydrides being cleaved by ammonia or amine the results is an amide and a carboxilic acid with an alcohol nucleophile you get an ester and carboxilic acid and with water you get two carboxilic acids then we learned about transesterification which is exchanging one esterifying group for another on an Esther and then we talked about hydrolysis of amides all right with that we end this chapter in the next video we're going to do a practice problem set together let me know if you have any questions comments concerns down below other than that good luck happy studying and have a beautiful beautiful day future doctors