[toadesque]

We just started doing this and it's REALLY confusing me. I spent a lot of time learning preparation for alkynes, reductions, hydroborations, etc and now it's like I have to apply all that for the synthesis problems and I'm not getting it. I don't understand how when given a target molecule and the starting materials (acetylene and a haloalkane) how you know which steps to do in order to eventually get to the target molecule.

Example, if you have a target molecule of cis-3-Hexene and have starting materials of Acetylene and Bromoethane.

How do you know that you are supposed to do it in 5 steps like this?

1. NaNH2 ----> 2. CH3CH2Br


1-Butyne


3. NaNH2 ----> 4. CH3CH2Br


3-Hexyne


5. H2 ----> Lindlar catalyst

target molecule: cis-3-Hexene


Have an exam on Thurs, I seem to understand everything but this

[stewie griffin]

I'm not sure I understand what's going on in your reactions. Could you please write out the reactions in full with starting materials and products.

[nj_bartel]

It's generally a good idea to work backward from the products, if you don't immediately see a viable synthesis route from the starting material.  For example, you have your product, cis-3-hexene.  What reaction do you know that leads to the production of cis alkenes?  Catalytic reduction with Lindlar's catalyst.  So what would be your reactant that you reduce to yield that product?  An alkyne.  As you work backward like this, keep your starting material in mind so you can consciously make an effort to go in that direction.

[toadesque]

Ok for a problem like this:



EVERY reagent I pick is always the wrong one. I don't understand this at all, I just can't get my head around how you are supposed to know which one to use. Even while looking at my notes I don't pick the right ones. This is killing me.

Like this is my thought process. For a) it looks like you're going from an alkane to an alkyne. So I thought it would appropriate to treat with:

 2 NaNH2    NH3 (l)
               -------->  

But it's not right, I don't even know how they came up with the answer given.

[nj_bartel]

Ok, so for a, your product is an alkyne that has the carbon skeleton extended by 2 carbons from the starting material.  So how do we know to make alkynes?  By double elimination of a vicinal dihalide using sodium amide in liquid ammonia.  So our previous reactant was reagent A in the link.  How do we form vicinal dihalides?  By reaction of an alkene with a halide, usually bromine.  So our previous reacant was reagent B in the link.  Looking at our starting material, we can see that this reagent is just starting material that has undergone an SN2 reaction at the carbon attached to the halide to extend the carbon chain by 2 carbons and adding a double bond.  This can be accomplished by reaction of vinyl magnesium bromide (a grignard reagent) with our starting material.

http://img4.imageshack.us/img4/4543/ochemsynthesis.jpg

[sjb]

Ok, so for a, your product is an alkyne that has the carbon skeleton extended by 2 carbons from the starting material.  So how do we know to make alkynes?  By double elimination of a vicinal dihalide using sodium amide in liquid ammonia.  So our previous reactant was reagent A in the link.  How do we form vicinal dihalides?  By reaction of an alkene with a halide, usually bromine.  So our previous reacant was reagent B in the link.  Looking at our starting material, we can see that this reagent is just starting material that has undergone an SN2 reaction at the carbon attached to the halide to extend the carbon chain by 2 carbons and adding a double bond.  This can be accomplished by reaction of vinyl magnesium bromide (a grignard reagent) with our starting material.

http://img4.imageshack.us/img4/4543/ochemsynthesis.jpg

Whilst this is all right, and I have no problem with it, is the problem not just wanting to use the reagents in the picture?

[stewie griffin]

For reaction A you need to slow down and pay attention to all of the details. For example, the product has 2 more carbons than the starting material. So even if you could convert the primary bromide to an alkyne (which you can't do in one step anyway) you'd still be 2 carbons short. Thus you need to think "How can we introduce 2 more carbons and convert this primary bromide to an alkyne."
Here the primary bromide is a great electrophile for a straight Sn2 reaction. So why not choose sodium acetelyide (the deprotonated alkyne) as your nucleophile. Now you kick out the bromide, have added your two extra needed carbons, and installed an alkyne all in one step!
I suggest that it may be helpful to make notecards with themes of overall reactions. For example, you could have a card with "How to convert an alkyne to a carbonyls"  or "How to convert alcohols to good leaving groups" and so on. There's almost always more than one correct answer to synthesis problems (though some answers are shorter and better than others!).
It sounds like it may be a bit late for this exam, but for the final I'd definitely start on those notecards as a means to organize all the info you've learned.

[orgopete]

This reminds me of where I was with my teaching. I had many students who professed confusion. I have talked about my solutions and written about them. I began with a different starting point. "How do we learn?" or "What does out brain do?" I concluded that fundamentally, our brains are pattern matching machines. In order to remember random facts, one must put order into them. The posters question implies that the reagents are without properties or implied reactivity. The suggestion that NaNH₂ could be reacted with an alkyl bromide (it can), and confusion as to why that was not the reagent of choice implies to me that the poster did not have a specific idea of what NaNH₂ was able to do. (An alkyl amine, sort of, it would work, but not ideal; an anion from an alkyl halide, never.)

My solution (and I concede to having broken some rules) was to make reaction mechanisms both consistent and understandable. From some simple polls I have conducted, I have concluded that many students attempt to memorize reaction mechanisms without regarding what curved arrows might tell them. Students will give the same answer whether curved arrows are present or absent. Many don't know how to use them correctly. And the curved arrow paradigm is ambiguous for many reactions.

I written some mechanisms that you can print out and do, see Minisampler Part A. Do, them. I can virtually guarantee that you can do them. It shouldn't take more than 5-10 minutes. Then do Minisampler Part B. These will be a little more difficult, but you should still be able to do them. Then you could try, Minisampler Part C. These may be easy or difficult for you, it will depend on you. They are the same problems though, so you should still be able to do them. You may need to go back to one of the prior examples in order to practice more. Completed mechanisms are on this page, Part D.

That is a different way of teaching, example based teaching. For organic chemistry, I thought you needed to be able to write the solution to at least one problem in order to write a solution to another problem with the same mechanism. Those examples are taken from the book I used in my organic chemistry classes. I had really good results with my classes in using it.

[nj_bartel]

Whilst this is all right, and I have no problem with it, is the problem not just wanting to use the reagents in the picture?

Hm.  I  somehow managed to skim over that completely.  Going back and looking though, I don't see a way to transform into a with those reagents, do you?

[toadesque]

Hm okay I must have spent 8 hours studying today and it's finally starting to click . Still a little shaky but better than I was this morning.

[MAFII]

This reminds me of where I was with my teaching. I had many students who professed confusion. I have talked about my solutions and written about them. I began with a different starting point. "How do we learn?" or "What does out brain do?" I concluded that fundamentally, our brains are pattern matching machines. In order to remember random facts, one must put order into them. The posters question implies that the reagents are without properties or implied reactivity. The suggestion that NaNH₂ could be reacted with an alkyl bromide (it can), and confusion as to why that was not the reagent of choice implies to me that the poster did not have a specific idea of what NaNH₂ was able to do. (An alkyl amine, sort of, it would work, but not ideal; an anion from an alkyl halide, never.)

My solution (and I concede to having broken some rules) was to make reaction mechanisms both consistent and understandable. From some simple polls I have conducted, I have concluded that many students attempt to memorize reaction mechanisms without regarding what curved arrows might tell them. Students will give the same answer whether curved arrows are present or absent. Many don't know how to use them correctly. And the curved arrow paradigm is ambiguous for many reactions.

I written some mechanisms that you can print out and do, see Minisampler Part A. Do, them. I can virtually guarantee that you can do them. It shouldn't take more than 5-10 minutes. Then do Minisampler Part B. These will be a little more difficult, but you should still be able to do them. Then you could try, Minisampler Part C. These may be easy or difficult for you, it will depend on you. They are the same problems though, so you should still be able to do them. You may need to go back to one of the prior examples in order to practice more. Completed mechanisms are on this page, Part D.

That is a different way of teaching, example based teaching. For organic chemistry, I thought you needed to be able to write the solution to at least one problem in order to write a solution to another problem with the same mechanism. Those examples are taken from the book I used in my organic chemistry classes. I had really good results with my classes in using it.

So Pete,

Based on what you're saying, you're saying that best results in teaching Organic is by matching patterns?  i.e. a higher level of memorization?

Have you ever tried teaching from a perspective where you teach the students electron flow and why two compounds would react and what they are more likely to do based on Structure, polarity, electronegativity, etc?

I don't mean to be intrusive or offensive, I would really just like to know your take on the difference in both methods of teaching.

[orgopete]

Based on what you're saying, you're saying that best results in teaching Organic is by matching patterns?  i.e. a higher level of memorization?

Have you ever tried teaching from a perspective where you teach the students electron flow and why two compounds would react and what they are more likely to do based on Structure, polarity, electronegativity, etc?

I don't mean to be intrusive or offensive, I would really just like to know your take on the difference in both methods of teaching.

What you describe is exactly how I taught. In memorizing the Gettysburg Address, our brain knows the order of the letters and words because of the logical sense contained in them. For this reason, it is much easier to learn it in a language you know. While you could learn in a similar language, it would be more difficult to pick up errors if you were unfamiliar with the structure of the language.

If you printed out one of the pages I have available, you should recognize the logic of the reactions. The nucleophiles and leaving groups are written to be easily understood. The examples in the book illustrate mechanistic principles. I discuss greatly pKa's in class. Because the examples use those principles, it is beyond the scope of that book to drone on about them.

This is what happens to most students. They really don't pay much attention to mechanisms and the arrows. When I give them the worksheets in my classes, they must do so. However, they are "easy". When I say easy, I mean you can look at them and learn the mechanistic steps that go from starting materials to products. Part A contains the logic of a reaction, Part B uses that logic. When students face Part B, they must think for themselves what must happen from step to step. I don't use Part C in class as it consumes too much class time. However, I had made it a custom to choose between five and eight of the mechanisms and use five of them on each exam. In order for students to draw those mechanisms, students made many photocopies in order to write the mechanisms.

If we look at results, you would find that some students really struggle with being able to complete all five mechanisms. Furthermore, I use one or two of those same mechanisms on other problems on the exam (no mechanism required). Of the students that can write the mechanism from the worksheets, only a portion of them can take that same mechanism and apply it to a new problem.

For me, that describes the education process. When I first began teaching, I thought if I wrote the mechanisms in class, students would use them to answer questions. Practically speaking, only a limited number of students actually can. A colleague suggested that students didn't know how to student. The worksheets are exactly how I studied as an undergraduate. However, just knowing a mechanism does not guarantee application to a new problem. I don't know if that is a function of the number of repetitions I am able to give in homework problems or limitation of student abilities. (If you were in my class, you would find I primarily limit the reactions to those covered in my book.)

By using my book, teaching mechanisms, quizzes, exams, I was able to raise my class average on the ACS organic chemistry exam approximately 20 percentile points. 

If there might be any instructors reading this, I am interested in finding someone to apply for an NSF grant.

[Scatter]

Based on what you're saying, you're saying that best results in teaching Organic is by matching patterns?  i.e. a higher level of memorization?

Have you ever tried teaching from a perspective where you teach the students electron flow and why two compounds would react and what they are more likely to do based on Structure, polarity, electronegativity, etc?

I don't mean to be intrusive or offensive, I would really just like to know your take on the difference in both methods of teaching.

What you describe is exactly how I taught. In memorizing the Gettysburg Address, our brain knows the order of the letters and words because of the logical sense contained in them. For this reason, it is much easier to learn it in a language you know. While you could learn in a similar language, it would be more difficult to pick up errors if you were unfamiliar with the structure of the language.

If you printed out one of the pages I have available, you should recognize the logic of the reactions. The nucleophiles and leaving groups are written to be easily understood. The examples in the book illustrate mechanistic principles. I discuss greatly pKa's in class. Because the examples use those principles, it is beyond the scope of that book to drone on about them.

This is what happens to most students. They really don't pay much attention to mechanisms and the arrows. When I give them the worksheets in my classes, they must do so. However, they are "easy". When I say easy, I mean you can look at them and learn the mechanistic steps that go from starting materials to products. Part A contains the logic of a reaction, Part B uses that logic. When students face Part B, they must think for themselves what must happen from step to step. I don't use Part C in class as it consumes too much class time. However, I had made it a custom to choose between five and eight of the mechanisms and use five of them on each exam. In order for students to draw those mechanisms, students made many photocopies in order to write the mechanisms.

If we look at results, you would find that some students really struggle with being able to complete all five mechanisms. Furthermore, I use one or two of those same mechanisms on other problems on the exam (no mechanism required). Of the students that can write the mechanism from the worksheets, only a portion of them can take that same mechanism and apply it to a new problem.

For me, that describes the education process. When I first began teaching, I thought if I wrote the mechanisms in class, students would use them to answer questions. Practically speaking, only a limited number of students actually can. A colleague suggested that students didn't know how to student. The worksheets are exactly how I studied as an undergraduate. However, just knowing a mechanism does not guarantee application to a new problem. I don't know if that is a function of the number of repetitions I am able to give in homework problems or limitation of student abilities. (If you were in my class, you would find I primarily limit the reactions to those covered in my book.)

By using my book, teaching mechanisms, quizzes, exams, I was able to raise my class average on the ACS organic chemistry exam approximately 20 percentile points. 

If there might be any instructors reading this, I am interested in finding someone to apply for an NSF grant.

This is how I've actually been studying.  It's not how we do things in class...everyone seems to get caught up in memorizing properties that account for different reactions.  I take that stuff in, but on my own time I've been studying arrow pushing and mechanisms because I figure it's the language to understand reactions.  Instead of learning reactions, I'm learning how reactions work, where the electrons go, where things bond, and where bonds break so I can do problems like the ones in your worksheet without having directly memorized a named reaction.  Coupled with the fact that you included the types of reactions (like E2 elimination or aromatic nucleophilic substitution reaction), it makes everything very intuitive.  In short, I'm all for teaching based around mechanisms and electron pushing.  Thanks for the sample problems!  I think they'll be good preparation for the exam I have on Monday. 

[nj_bartel]

Orgopete, I'm still a bit confused as to what your teaching method is.  Based on your initial description, I got the impression you were teaching patterns to recognize in reactant -> product transformations to provide a mental algorithm to work with.  Looking at your book's page however, it seems like the method is the traditional mechanism-based teaching method, in which you learn why things react the way they do so the information can be applied more broadly.  Could you clarify for me please?

[orgopete]

Re: patterns
The mini sampler is meant to allow a preview of what the book is like. It isn't comprehensive. If you look at the Table of Contents, you will see that the book is organized by mechanism. I was using Paula Bruice when I wrote the book.

However, the question does raise an issue of how chemistry might be (ought to?) taught. I had changed textbooks from functional group to mechanism and back several times. While I had learned by mechanism and believed in mechanisms, I tried functional group books in an effort to blunt the decreasing class scores as mechanisms became lengthy late on the course. When changing books, I had not noted a five point improvement in the median score when using a mechanism based book. The averages were about the same, so I hadn't checked to see how well the average student was doing.

Now, you might argue that should be expected. That is implicit in the question about whether I was using patterns in my class. If a chapter is about electrophilic reactions of alkenes, the reactions all start with an alkene donating electrons to an electrophile. Therefore, without knowing the product of a reaction, by virtue of mechanistic similarity, it seems logical that a student would have a reasonable chance in predicting the product. If you know the first step, how difficult can it be to predict the second step?

I suppose a similar argument could be made for functional group books in that a chapter on alcohols means that an alcohol will be formed or reacted. The difference is that in the functional group books, no implicit expectations of a mechanism is present. The mechanisms in a chapter may not follow a mechanistic pattern from reaction to reaction. I believe this also asks students to use rote memorization, something I am averse to. I argue that this lack of repetition and similarity is not good pedagogy if our brains are pattern matching machines. (If you advocate memorization and memory devices like flash cards, it won't matter.)

I have taught organic chemistry the last two summers. I had to use the functional group based book that is used during the year. This is what I ended up doing. I first created a concordance to match the problems in the textbook with the mechanisms in my book. However, I found this totally insufficient as the problems and their mechanisms were not as rigorously linked as I had wished. That is, it was not unusual for the book to introduce a reaction without a mechanism and the mechanism may be given (or not) later in the book. Finally, after completion of structural and spectral topics, I organized the class around my book for introducing course content and linked the reading from the textbook as appropriate.

I appreciate the question and my opportunity to reflect upon it. I actually believe I gave much attention to pattern matching. Even random mechanisms contain a level of pattern matching in the chemistry itself. I actually believe I learn more chemistry by thinking about reaction mechanisms than reading about chemistry. The logic and similarity of one mechanism to another mechanism is a chemistry pattern. However, I find there is a practical limit to the extent to which such pattern matching may be employed. While additions to alkenes, ketalization reactions, and Fischer esterification reactions are mechanistically similar, I find it simpler to refer to prior examples than it is to make an effort to lump them all together into a single topic.

If anyone is teaching a class and wishes more information about my book, please contact me.