The Big Daddy Flowchart (Determining Mechanisms)

Here is the best flowchart you’ll ever learn in your life. Seriously.

Professors rarely tell you which mechanisms to use. Instead, they’ll give you a set of reagents and ask you to figure it out yourself. This flowchart basically explains that entire process. Let’s go! 

Determining Mechanisms

When do you use this flowchart? Whenever you have a nucleophile and a GOOD leaving group. 

Concept: Overview of the flowchart. 

3m
Video Transcript

So, guys, we have a big problem. I've taught you guys all about SN1, SN2, E1, E2 and I taught you about all the different conditions that are favored for each one. And in some cases, it's kind of obvious what mechanism we would use. But there are a lot of cases where it's going to be kind of blurry and you're going to be wondering is it going to be SN2, is it going to be E2.
I remember having this problem as a private tutor back many years ago when I just used to do private tutoring and trying to put myself and my thinking into my student's head and trying to tell them, “Guys, it's just this. It's just obviously the nucleophile, whatever.” And what I realized is that it wasn't getting through. I needed some method or some way to just give my brain to someone else so that they would be able to see what kind of mechanism we're using because many times – sometimes we're going to have to ask ourselves up to four different questions to determine what mechanism to use.
That is when I decided to make a solution and lo and behold I'm going to introduce you guys to one of the best parts of this whole chapter which is this awesome Johnny-patented flow chart called the Big Daddy flow chart. And it's just going to change your life. So are you guys excited? Ready to get going?
Like I said, this is such a great flow chart. I've even had students that have already taken their MCAT in med school tell me, “Johnny, the Big Daddy flow chart still saves my life.” So I'm like wow, it must be pretty good.
So now I've just hyped it up a crazy amount. Hopefully, you guys like it. Let's go ahead and get started.
As you guys can see it's very complicated. It's very big. But it's actually pretty easy to use. The way that we're going to use this is like a series of questions that you ask yourself. We're just going to ask ourselves, self, is this whatever and then you say yes or no and then you keep going down the flow chart until you get to the mechanism that you need.
All right? So what's the most important question? It's actually the same question that we were asking when I was teaching you about the mechanisms at the beginning which is what kind of nucleophile do I have. Is it strong or is it weak? The way we determine that is by looking at negatively charged or neutral. So actually, it's the same question that we always start off with.
So if it's negative charged, what that means is that we're going to go down the left part of the pathway. If it's neutral, then we're going to go down the right part of the pathway. How about if it's positive? That's a trick question. Positive charges are not nucleophiles, those are electrophiles. So it could never be positive. But it could either be negative or it could be neutral. 

In general, the left side of the flowchart predicts SN2 /E2 mechanisms, and the right side predicts SN1/E1 mechanisms, but there are exceptions.

Concept: How to predict SN2 and E2 mechanisms. 

10m
Video Transcript

So let's go ahead and go down the negative part first because that's actually the more complicated one. Let's just get it over with.
The second question that I ask myself once I've determined that it's negative – oh, by the way, I'm sorry. There's something I forgot to tell you guys. There's going to be some negative nucleophiles that don't look negative at the beginning and that's because they're attached to a spectator ion. Do you guys remember what spectator ions are? They're just ions that dissociate in solution and don't participate in the reaction.
So spectator ions, there's actually four of them. They're in the first column of the periodic table. And there's four that you should be aware of. We have lithium. Lithium dissociates into Li+. We have sodium. We have potassium. And then finally we have cesium, which doesn't always show up, but sometimes it does. These are the four cations that are going to dissociate from our nucleophiles and make them negatively charged.
So for example, if I gave you – I'm just going to tell you this is a really common mistake that's made. If I gave you the nucleophile NaOH, guess what's going to happen, a lot of students are going to say that's neutral, but obviously, that's not neutral. You have to dissociate the Na first and what you're going to get afterwards is OH-. That is negatively charged so we'd go down the left-hand side. Do you guys see how to use that?
So watch out for these spectators. They're there to make your life just a little bit more complicated.
Now let's go to the second question. The second question I ask myself is okay, I know that I have a nucleophile that's negatively charged. I know it's strong. But is it a bulky base. For this question, we're just going to memorize three bulky bases. These are just three bulky bases that I've seen professors use. There really isn't a very long list of them. Really if you just memorize this list of three, you're set.
All it is is tert-butoxide, which is this one, LDA and LiTMP. These are the three bulky bases that you could find. And what you might even notice is that your professor might not use all three. A lot of times professors will have like a pet base that they really like and they'll just stick with it the whole semester. So for example, some professors love LDA. They just LDA everywhere. Some professors love tert-butoxide. Tert-butoxide everywhere. It just depends on which professor you get.
So I would just say just know them just in case. Also, in case you ever want to look up the stuff online or do some more reading in your book, you want to know what the other ones are even though your professor might not use it very often. Cool.
So those are the three that we say are bulky. If they're bulky, what did we say about nucleophiles? If I have a very bulky nucleophile, is that going to be a good base of a bad base? That's going to be a really good base. Remember that I said bulk increases basicity. That means that automatically right away, we know what the mechanism is. We know that it's going to be a really strong base, so it's going to be E2. Isn't that easy? We're just going to say, oh, this is E2 right away.
Now, notice that it has a word Hofmann next to it, don't worry about that yet. We haven't gotten there yet. This flow chart not only works for this topic, but it works later on as well. So we're going to get there in a little bit.
That would be if we said yes that it is bulky. Now but what if it's no. What if, for example, OH- is that one of the three bulky bases? No, it's not. So that means I keep going to now the next question. The next question is question three. So you can see we've already asked ourselves two questions, we're onto the third one. The third one is what type of leaving group do I have.
Remember that leaving group could be a few different things. Usually, that's going to be an alkyl halide, but that could also be a sulfonate ester. And then we also said water, but – yeah, water too. Sure. So it could also be water. But water doesn't happen quite as much. So I'm just going to put here.
So those are like our three main leaving groups. Now the way that we have to think about these leaving groups is we want to separate them into two categories. There's the leaving groups that have a good back side. That means they're really accessible. It's easy to do a back side attack. Then we have the nucleophiles that have a bad back side.
If you had to think about the types of nucleophiles that have a really good back side what would you think? What would you say? Very available. Very down for back side attack. That would be methyl and primary, right? Because they have no steric bulk back there. So it turns out that methyl and primary are always going to pretty much give us the same mechanism because they have a good – I'm just going to write it here – good back side.
So we get an SN2 reaction. Everything that went along with SN2, you think of it, that's going to be for methyl and for primary. Easy, right?
But now we think about the secondary and tertiaries. The secondary and the tertiaries, which are right here and here are the ones with bad back sides. They aren't as good – in fact, tertiaries impossible. Secondary can happen, but it's kind of bad in some cases. So for secondary and tertiary, we're going to have to ask ourselves another question. So this brings us to the fourth question. Let's start off with secondary first.
Now for secondary what I want to ask myself is this nucleophile that's negatively charged, it's not bulky, what I want to know is is it going to be a better nucleophile, is it going to be better at donating electrons, or is it going to be a better base, meaning that it's better at pulling off protons.
For this part, all I want you to do it memorize the good bases. Why? Because it turns out that there's probably 20 different nucleophiles that your professor could use. Lots of different ones. He could basically put anything with a negative charge on it and say that's a nucleophile. For you, as a student, that could get very confusing trying to memorize every single nucleophile and what it does. Instead of memorizing every single nucleophile, let's just memorize the ones that are good bases because that's a much shorter list and then what that means is that anything that's not on my base list, I'm going to automatically assume is better as a nucleophile – being a nucleophile.
So what are these bases that are strong bases? The bases are one – oxides. That means any molecule that I have OR-. So that's the first one. The second one is called an alkynide. An alkynide is just a triple bond with a negative charge at one side. That negative charge has to be directly on the C. That's also a very, very strong base. It's not very stable. Then we have two bases that are very similar, which is NH2- and H-. these are both going to be small, very strong bases because they're not very stable in solution at all. And then finally we have one more thing that's not really a base, but it favors basic reactions and that's heat. It turns out that heat is going to favor elimination for a variety of reasons.
So these five things are things that I want you guys to memorize as favoring an E2 mechanism on a secondary alkyl halide. If you have one of those five things or even more than one of those five things, then for sure it's going to be E2.
Now, what's this word next to it Zaitsev? Again, don't worry about that. We're not going to get to that until the next topic or until a few topics from now. But for right now you should just know that it's E2.
So now what if I gave you a nucleophile that you really don't know what it is. For example, if I gave you something that looks like this, N double bond N double bond N positive negative. So what if I gave you a nucleophile that looks like that? Oh, I'm sorry, this is supposed to be a negative 2. So then after you – just so you know, this is actually called N3-. If you added up all the formal charges, it would be negative at the end. And I gave you N3- on a secondary alkyl halide. So my question to you is what would the nucleophile be, I mean what would the mechanism be?
I would just ask myself is N3- on my base list. Is it an oxide? No. Is it an alkynide? No. No, no, no. There's no heat. So that means it must be in my nucleophile category that it's not a good base and that's going to be SN2 and that's going to apply for a lot of different nucleophiles. So also, for example, SH-. SH- not on this list, right? So that means it must be a better nucleophile and it's going to do SN2. Do you guys get the point?
So basically I'm just going to go with whatever those bases are, that's E2. If it's not on that list, it's going to prefer SN2. Are you guys cool with that? Awesome.
So now let's go to tertiary. So for tertiary, oops, sorry. So for tertiary, we get a similar problem where we need figure out if it's a nucleophile or a base.
So now for the base list it's actually going to be the same as the other list, so the same five compounds, except that now I'm going to add OH- to the mix. So OH- was actually not on my list before because my list before as strong bases, it only had oxides. OH- is not an oxide because it doesn't have an R group attached to the O. That's a hydroxyl, it's not – it's hydroxide, it's not an oxide. But now I'm going to treat the hydroxide as one of the strong bases, so it's actually going to be those five things I told you plus OH- are going to favor E2. 

Concept: How to predict SN1 and E1 mechanisms. 

7m
Video Transcript

Then what I want to do finally is I'm not going to do this last pathway. I'm going to save that one for the end. We're done with the negative one for now. Now I want to go to the neutral pathway and then finish up with this last little stick.
So let's go to the neutral pathway now. I know that was a mouthful, but now I have to do the neutral pathway.
What if we have something like instead of OH-, how about if we just have water? Water is neutral, right? So now my second question is – actually this pathway's a lot easier. All I'm going to ask myself is what type of leaving group do I have because if this is a neutral, then that's going to prefer what kind of mechanisms? That's going to prefer – it's going to be mechanisms that aren't bimolecular, that don't have the nucleophile attacking at the beginning. So this is going to favor SN1 and E1 mechanisms because it's going to be waiting around for a carbocation to be generated. Remember that first step.
So then I just have to ask myself two things. I just have to ask – or one thing actually, for the second question. I'm going to say what type of leaving group do I have. Do I have a leaving group that can make a good carbocation in the first step or do I have a leaving group that wouldn't make a great carbocation in the first step? So it turns out that if your leaving group doesn't make a good carbocation in the first step, that will be what type of alkyl halide? Well, remember that primaries and methyls are really bad at making carbocations. I'm going to say here, bad carbocation.
The two mechanisms that are good at making carbocations because there's a lot of R groups, so it's going to stabilize it. Remember that I said R groups stabilize carbocations would be secondary and tertiary. So these would be good carbocations.
The mechanism's really just going to determine on which side you land. If you're on the bad side, that means that you have water. Water or whatever neutral nucleophile can't do shit really. It's just stuck there. It's not very strong and then it's waiting for the first step. The rate determining step to happen to make the carbocation. But then methyls and primaries make terrible carbocations, so guess what happens, nothing happens. So what happens is that the end result is just no reaction because you have a bad nucleophile and you have a bad leaving group, so it's just the combination is just bad. So overall you get nothing happening.
But what if you have a good leaving group? How about if you have one that's going to be actually make a good molecule that could make a carbocation like secondary and tertiary? Then that's where you're going to favor SN1 and E1 because now you have that good carbocation that you can make. The neutral nucleophile can attack it and the reason you get SN1 and E1 is because, guess what, they compete with each other. So whenever you get an SN1 mechanism, you're also going to get E1 competing at the same time because the environment that favors SN1 is also favored for E1. Are you guys getting that? So we can never really separate the two.
Now there is one thing that we could do to make it favor one over the other and that is heat. I'm just going to put here heat can favor E1. That's true. For example, if I ran it with these conditions where I had a neutral nucleophile, a tertiary alkyl halide and then I jack up the heat to like 50 degrees Celsius then that can favor E1 over SN1 but you're still going to get a mixture of products. It's just you're going to get a little bit more E1. Cool.
Now I want to talk about this last direction which was how about if I am – I'm sorry about that again. How about if I'm in the tertiary position and I want to – and I don't have a good base. Basically, I have a base that isn't good at pulling off protons.
What that means is that this nucleophile wants to do an SN2 because it's not good at pulling off protons. So let's say something like I-. I- is a molecule that is not very basic at all. It's a pretty good nucleophile, but it's terrible base. It was very bad at pulling off protons. So it's not on my list. It's not on my list of five. It's not OH-. So that means that it wants to do an SN2, but it can't because the back side is totally clogged up. Instead, it's going to have to wait around for a carbocation to be generated just like a weak nucleophile would have had to do in SN1 and E1, so you wind up getting SN1 and E1 from this situation.
So I'm explaining the logic so that you guys will understand where this flow chart is coming from, but guess what, the coolest thing about this flow chart is that you don't actually need to understand it. I know that's kind of blasphemy for me to say that you don't need to understand it, but in the end of the day, you guys just want to do really well on your test, right? That's why we have Clutch. I want to be Clutch for you guys.
I just want you guys to memorize this flow chart. If you can understand it, awesome, even better. But in the event that maybe your test is in two days or whatever, I don't need you know every single detail about why this, why that. I just need you to memorize what are the good bases, what are the different pathways for primary, secondary, tertiary. If you know that – how do I tell if something's neutral or negative. If you know those things, guess what, you could go into your test not knowing much about why this flow chart exists and still get every single mechanism right. That's because you memorized the flow chart and you know how to use it.
What that means is that for the rest of all the practice problems you do for this course, the ones that I give you, the ones that you have to do online, the ones that you have to do in your book, whatever you do, make sure you have this flow chart next to you and you start using it to determine what mechanism you're using.
Because guess what, on your test your professor isn't going to be so nice and tell you draw all the products for the E2 reaction. No. Guess what. They're going to let you figure that out on your own because you're supposed to know what mechanism it is. How? Well, you're supposed to be a genius, but in the case that you aren't a genius, you can just use this flow chart and it's going to work out pretty well for you.
So I hope that that made sense. I do expect you guys to all try to memorize this at some point, but the best way is just through practice. Use it like an open-book test and do all your practice problems with this flow chart in front of you and eventually you'll have it memorized.
All right guys so that's the end of that topic. Let's go ahead and move on. 

Cumulative Practice

Use the Big Daddy Flowchart to solve the following questions. 

Problem: Predict the mechanism for the following reaction. 

5m

Problem: Predict the mechanism for the following reaction. 

2m

Problem: Predict the mechanism for the following reaction.

5m

Problem: Determine the mechanism and predict the product(s) of the following reaction. 

6m

Problem: Predict the mechanism for the following reaction

7m

Problem: Predict the mechanism for the following reaction.

5m

The Big Daddy Flowchart (Determining Mechanisms) Additional Practice Problems

The following reaction below is probably

 

A) an SN1-type reaction involving the protonated alcohol as the substrate.

B) an SN2 -type reaction involving the protonated alcohol as the substrate.

C) an E1 -type reaction involving the protonated alcohol as the substrate.

D) an E2 -type reaction involving the protonated alcohol as the substrate.

E) an epoxidation reaction.

Watch Solution

 Supply a structural formula for the major organic product(s) when the product(s) is(are) not given; if no reaction occurs, write N.R. IMPORTANT: If the major product is a mixture of stereoisomers, give a structural formula for each of the stereoisomers in the mixture.

Watch Solution

Supply a structural formula for the major organic product(s) when the product(s) is(are) not given; if no reaction occurs, write N.R. If the major product is a mixture of stereoisomers (such as a pair of enantiomers or a pair of diastereomers), give a structural formula for each of the stereoisomers in the mixture. 

Watch Solution

Supply a structural formula for the major organic product(s) when the product(s) is(are) not given; if no reaction occurs, write N.R. If the major product is a mixture of stereoisomers (such as a pair of enantiomers or a pair of diastereomers), give a structural formula for each of the stereoisomers in the mixture. 

Watch Solution

True/False. Identify the statements as either True or False. 

 

Reduction of an alkyne to an alkene with sodium metal in liquid ammonia is a partial radical mechanism.

In polar protic solvents a selenide anion (Se-2) is a stronger nucleophile as compared to a sulfide anion (S-2).

The leaving group and the departing hydrogen in an E2 elimination reaction has to be on the same side.

Halogens have lower priority as compared to alkenes in IUPAC naming system.

The rate of a SN1 reaction increases with increasing carbocation stability.

Sodium hydroxide is a strong base and can be used to deprotonate terminal alkynes in a 100% yield.

Carbocations form tight ion-pairs with halide anion.

In SN2 reactions the rate-determining step involves two molecules.

Iodine is a better leaving group than fluorine because iodine is more polarizable than fluorine. 

Vinylic carbocations can undergo carbocation rearrangement.

Watch Solution

For each reaction, mark all of the statements below that correctly describe the reaction. 

Watch Solution

Answer each of the following questions dealing with the given alkyl halides

a) Which compound cannot undergo an E1 reaction?

 

b) Which compound will undergo an E1 reaction to form a tetrasubstituted alkene, but undergoes an E2 reaction to form a trisubstituted alkene?

 

 

 

c) Which compounds cannot undergo an SN2 substitution?

 

 

d) Which compound will form a nitrile, R–CN, with S configuration on treatment with KI followed by NaCN (both in polar aprotic solvent)?

 

 

e) Which compound will form a nitrile with S configuration on treatment with NaCN in polar aprotic solvent? 

 

 

Watch Solution

Answer each of the following questions dealing with the given alkyl halides

a) Which compound will undergo E1 most readily? 

 

 

 

b) Which compound will undergo E2 most readily?

 

 

 

c) Which compounds would form a trisubstituted alkene as the major E1 and E2 product?

 

 

 

d) Which compound(s) cannot undergo elmination at all?

 

 

 

Watch Solution

Determine the major product formed for the following reactions. 

Watch Solution

Identify whether the following substrate favor SN2, SN1, both or neither: 

Watch Solution

Identify whether the following substrate favor SN2, SN1, both or neither: 

Watch Solution

Identify whether the following substrate favor SN2, SN1, both or neither: 

Watch Solution

Identify whether the following substrate favor SN2, SN1, both or neither: 

Watch Solution

Identify whether the following substrate favor SN2, SN1, both or neither: 

Watch Solution

Identify whether the following substrate favors SN2, SN1, both or neither: 

Watch Solution

Consider the compounds below and answer the following questions.

a) Which of the compounds below will most readily react via SN1? 

 

 

b) Which of the compounds below will not significantly undergo SN2 reaction? 

 

 

c) True/False: Reacting compound I with CH 3CH2ONa will favor SN2 reaction. 

 

 

d) Which of the compounds below will react with KCN to form a product with R-configuration? 

 

 

e) Which of the compounds below will react via SN2 most readily?

 

 

 

Watch Solution

Provide likely product or starting material and circle the correct answers to the questions that follow each problem.

Watch Solution

Provide likely product or starting material and circle the correct answers to the questions that follow each problem.

Watch Solution

Provide likely product or starting material and circle the correct answers to the questions that follow each problem.

Watch Solution

Predict the product(s).

 

Watch Solution

Pick the true statement regarding the mechanism of the reaction shown below (alkyl sulfonate esters and alkyl halides behave similarly).

A) It is an E1 reaction.

B) It is an E2 reaction. 

C) It is an SN2 reaction. 

D) It is an SN1 reaction. 

E) It is either an E1 or SN1 reaction.

Watch Solution

Identify the mechanistic pathways, respectively, for the products in the reaction below.

a) E1, SN1

b) E1, SN2

c) E2, SN1

d) E2, SN2

Watch Solution

The mechanism of the following reaction is

a) SN1

b) SN2

c) E1

d) E2

Watch Solution

The following transformation takes place with what kind of mechanism?

a. E2

b. SN2

c. SN1only

d. SN1+ E1

e. Bridged ion intermediate

Watch Solution