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As promised my master post of all general organic chemistry reactions. Please credit me if needed and understand this took a very long time to complete. So respect my post and don’t be afraid to ask me any questions!

Disclaimer: Not every reaction contains practice problems or full details of the mechanism. The purpose of this master post is to help students start somewhere with synthesis reactions. Also, to have a list of the possible reactions that will be covered in organic chemistry. Some universities might cover more than what I’ve posted so message me if you need any other help or I should add anything to this master post!

#Mine #Chemistry #Master Post #Synthesis #Reaction #Organic Chemistry #Help #Studyblr #Student #Study #Amine #Halogens #Carbon #Enol #Enolate #Carbonyl #Ester #Ketones

Condensation: It's Not Just For Soda Anymore, Part 1

Condensation reactions incidentially have jack all to do with actual condensation (that happens because the cold temp of your drink causes the gaseous water in the air to cool down when it hits the surface and become liquid. So the next time someone tells you to put a coaster under a room temp drink, laugh at them.). Condensation reactions are called condensation reactions because they managed to squeeze out a water molecule during the reaction. You may think that it's the same thing as dehydration, and I suppose technically it is, but the reactions are much more complicated. These reactions are actually a combination of Nu Add'n and alpha substitution. I'd review those, but you can go back and check the previous entries for them. I'm getting better at tagging, BTW. :) At the moment though there's only like 11 entries, so it shouldn't be too much of a challenge to go look backwards.

Note: The order of carbons goes like this: carbonyl --> Alpha --> Beta. It's really important to keep this in mind for this chapter.

In short, to quote my teacher directly: "There is Nu Add'n of the enolate ion of the donor molecule to the carbonyl C of the acceptor molecule".

Man, that's fancy sounding. My teacher is a brilliant and kind women who cares about us and our learning, but one of her few weak spots is that she doesn't often relate these complex concepts in simple language. She calls a thing what it is, which makes sense, but doesn't always help you really understand.

Maybe if she learned Tumblr speak and used more gifs.

Kidding (ok not really.). ;)

Alright, so in my last massive post we covered enolate ions with their jumpy bonds, right? Yeah. That part of the molecule ("the donor") attaches to the C that's next to the O of the carbonyl group (the "carbonyl carbon" of the "acceptor" molecule.). So let's get to it, shall we?

1. Aldol reaction to produce beta-hydroxy alds and kets - If you'll remember, hydroxy is alcohol (ROH's substituate name is "hydroxyl".) So essentially what this means is that we'll be sticking an alcohol to the carbon that's in a beta position relative to the aldehyde or ketone (completely unrelated: I just googled ketones and found raspberry ketones. What a load of horse shit. Shame on you Dr. Oz, you should KNOW BETTER. Proof he's only after the money. I hate TV doctors.). The mechanism here is completely and utterly different from the grignard, and I do want to stress that because you won't see that in this reaction, but the result of it is very similar. If you, like me, do not have to memorize mechanisms for your test then it is probably safe to at least categorize them together in your head. The reagents are Small, catalytic amounts of NaOH, EtOH. If you over saturate with base, the reaction doesn't work. You need just enough to get the hydrogens off of the carbons. If you have more, it starts reacting with the enolate ions and you don't want that to happen.

Now, I am not gonna lie. I had to stare at this for awhile to understand what it's saying. Then I went to the bathroom and for some reason the change of scenery or something made it click in my head: for some reason I thought we were reacting beta carbons, and we're not, we're *creating* a hydroxy group ON the beta carbon. Honestly, the base way to explain it is with an example:

MS PAINT SKILLZ ACTIVATE LOOOOOOOOOLZ

Here we have two ethaldehyde (otherwise known as acetaldehyde, but I don't like this name because this is NOT ACETONE.) molecules combining like Voltron (<--showing my age.) to form a new molecule, and an alcohol appearing at the site where the old ketone of the second molecules was. Important things to know about these reactions:

It's an equilibrium reaction (as you might have noticed in my drawing), and the equilibrium depends on how substituted the alpha carbon is. Mono favors the product, and di substitution of the alpha and carbonyl C favor reactants. That means this reaction works better with aldehydes.

The single difference between ending up with the aldol product you want instead of an alpha alkylated product is the amount of base. The reaction conditions are critical, and you need to be exact. You use a weak base at room temp, instead of a strong base at lower temps.

Alright, that's it for those reactions. On to the next! Afterall, there are only so many hours in the day and this is only reaction #1.

2. Dehydration of Aldols: synthesis of enones - What does that mean? Well, we'll be removing water from the aldol that we just made to produce an enone. A hint here: use your words. Aldol can be broken down to it's parts to understand what it is: ald - aldehyde. -ol - alcohol. An alcohol on an aldehyde. enone is the same way: en is short for -ene, which if you dredge that up from first semester is a C=C. -one is the name for a KetONE. A ketone with an alkene. Dehydration - DE, removal, hydra - water. Removal of water. So, just by the name you can guess that we're removing a water molecule from the aldol to create an enone. Since the only place to get the OH for the water is the alcohol, that's where the double bond ends up. The reagents are: H or OH/heat.. Meaning simply dump it in an acid or a base. So your teacher may decide to write NaOH over the arrow...it's the same thing. See my big list of reagents for a list of bases, and for acids. The double bond ends up on the left side of where the OH was not because of markovnikov, but because of the mechanism and the way that an enolate works.

Some notes about this reaction:

Usually this reaction happens in conjunction with the previous ones because of the difficulty involved in controlling the reaction conditions.

This is an equilibrium reaction, and the product can actually react with the water that is created from the reaction, so if you remove the water you will get more product

We did this in lab (practical, whatever you call it.), so you might as well. We have a microscale (small) lab, so let me show you the ridiculousness of this method:

Ok, so the green stuff is the product and the blue is water. So we removed the water by having the condensation generated by the heat slide down into the little teeny-tiny arm of that piece of glass piping (not what it's generally used for, FYI.), along with some product, We were supposed to decant what we could off the top back into the flask, but to get the rest of it we were supposed to manage to somehow magically remove that cork and ONLY LET THE WATER OUT. Cause that happens. Even tho we have those little valve things in our kit...there's got to be a better way. Luckily, I'm the boss at decanting so I got most of my product back. Good thing % yield isn't THAT important. x.x Ha...I should post more lab photos for you guys. :) Synthesis in second semester is way better than all the testing you do 1st semester. Prepare to get really friendly with IR testing though.

Ok, so there are still a TON of reactions in this chapter, so I'm going to post this now in an effort to control the length. Part 2 will follow in probably like an hour or two, depending on how long it takes me to write it. I'm at work and people (also the internet. My eyes are literally burning from my lazer-like focus.) keep interrupting me so we'll see.

#aldol #enolate #aldehyde #ketone #beta-hydroxy #spellcheck hates chemistry #raspberry ketones are horse shit #doctor oz the dumbass #volron molecules #enone #aldol synthesis #condensation reactions #ochem #ochem help #chem #chem help #chemistry #chemistry help

Carbonyl Alpha Substitution Reactions

Alright, so, I'm kinda skipping around the order here a little bit because apparently there's just something about this I didn't get for whatever reason. I got a not awesome grade on the homework for these, and not awesome grades on the quiz, and so I really want to make sure I try to get to them before the test. I haven't been tested on them, and the final is 40% this material from the last three chapters....except I lost my notes packet for ch. 24 and that makes me =******( because all the reactions I got right were in the first half that I made into flash cards, and the ones I missed were in the second half that I didn't make into flash cards (on my phone...awesome app called Study Droid. Speaking of apps, one of the girls in my class loved this iphone-only app: https://itunes.apple.com/us/app/reagents/id453336174?mt=8 I don't have an iphone, so I don't personally know if it's good or not.).

ANYWAY, ok, so what *are* these reactions? If you'll recall, we talked about the way that an e- withdrawing group (usually something containing O) will cause the alpha carbon to be vulnerable to certain types of reactions. One of these reactions is an acid/base reaction. The H is lost, but because of the stabilizing effect of the surrounding atom, there's a lot of resonance. So the double bond can jump from place to place. Remember, the more resonance, the more stability. When that H is lost, the resulting ion is called a Enolate ion. Your teacher, like mine, may ask you to draw this on a test, so let me explain it.

An enolate ion is an ion that is able to perform something called keto-enol tautomerism, due to its lost electron. At first, the actual ion itself is missing an H. So: O-C-C-R, with dotted double bonds on those first two bonds indicating that the electrons of the double bond shift between those two spots. Like all electron movement, this is really fast, so we can't just say "it hangs out here". When these ions accept protons, something weird happens. The movement of the double bond causes the O to have a very, very negative charge. A lot of the time it doesn't have the double bond that normally makes it less negative, so it will be all like PROTONS OMNOMNOM, and grab them. What you get is this: HO-CH=CH-R. That isn't stable. That double bond is just way too close to the O, and so basically the double bond and the H trade places and we get: O=CH-CH2-R This movement switches from the ROH - the enol - to the keto form, hence the name keto-enol tautomers. This is very stable, and this happens really quickly. You won't be able to isolate that first form, although these do exist in equilibrium (where the keto form overwhelmingly predominates.). But you can't do it without spare Hs. Which is kind of funny when you consider that to get it to do this in the first place you have to remove the H. It's almost like...why bother? Well, that's a good question. I used to think it was just because teachers liked making us memorize reams of information that had no use whatsoever, and that keto-enol tautomer was a cool word, but it turns out that's not exactly right.

That electron movement allows us to DO STUFF to them. Take, for example, acid promoted bromination. The reagents: Br2/HC2H3O2 (<-- when you see something written with an H in front like that it's a giant neon sign saying that that thing is an acid.). The movement of the H from the alpha carbon allows us to sneak a Br on there when no one's looking and you end up with an acid halide. USEFUL THINGS. For example, you can expose them to Pyridine and heat to turn them into beta unsaturated ketones: O=C-CH=CH2. The tautomerism doesn't happen here because the double bond is attached to the beta C and not the alpha C.

Adding more groups onto a ring, as long as they are e- w/drawing, promotes stability. So a highly substituted enol is more stable, just like more highly substituted alkenes are more stable.

Apparently this is a good way to make a C=C bond. WHO KNEW? ;)

(Side note, my dumbass neighbor's kid will NOT stop screeching its aggravating little lungs out. It's 9:30 at night, what is your baby doing up still? >.< PUT IT TO BED SO I CAN STUDY BETTER.)

Iodoform test - So, when you mix a ketone, a halide, and a base a long mechanism happens and you get: O=C-O- + CHX3. This is actually really useful. You can attach all sorts of things to that hanging negatively charged O. When you use Iodine as the halide, your leftover product is CHI3 and it's a QA test for methyl ketones. Now, my notes have this as being performed on a benzene ring substituate, but *says* methyl ketones (which is anything where the ketone is on the 2 C). I'm thinking it isn't the stabilizing effect of the ring that causes this.

The other important thing to note about this reaction is that the last step of the mechanism is a COOH + CX3, negatively charged. The negative charge steals the H from the COOH, resulting in the more stable of the two being negatively charged. I'm telling you this because I've been asked a lot about this reaction's last two steps. So my teacher gives the reactant, the X/OH reagents, and then asks for the COOH, adds another arrow, and asks for the haloform. Keep this in mind when studying.

Alpha Bromination of RCOOH, the Hell-Volhard-Zelinskii rxn - Is it me, or would it be helpful if ochemists stopped naming reactions after themselves and started naming them after what they do? For instance, you could call this the "make an acid bromide from a COOH" reaction and that'd be more useful than knowing who came up with it. Cause, frankly, I don't care. I might be a little annoyed at you for coming up with yet another thing for college ochem students to memorize. See? I'm giving you bitchface, Hell-Volhard-Zelinskii:

So in a NOT AT ALL pleasing turn of events, somehow adding the bitchface picture deleted a bunch of stuff I wrote afterwards. So I'm going to write it again, but it'll be shorter and not as amusing. NOT NICE BITCHFACE.

Ok, real quick: COOH with Br2, PBr3/H2O yields a Bromine attached to the alpha carbon. This is then used for other stuff, yay!

Ok, moving on. Next we have Alkylation of Enolate Anions. We're back to Enolates. So you put a ketone in a base, then allow it to undergo Sn2, and you end up with a ketone on a longer carbon chain. The way you do this is that you add an RX molecule during the Sn2 portion of the reaction. The reactivity of the X groups is:

Tosylate > -I > -Br > -Cl

The reactivity of the R groups:

H3C- > RCH2 -

Vinylic (C=C) and Aryl (aromatic) halides are unreactive. So you can't tack a benzene ring onto something with this.

Malonic Ester Synthesis - You should definitely learn this. I was tested on this, and I didn't know it, and i lost a slew of points. Looking at it now it makes me mad because i know this reaction really well, but I somehow neglected to add the *name* of it to my memory. Do not be fooled like I was - this is not a way to MAKE esters, this is a way to synthesize something FROM esters.

This reaction is used to stick extra R groups onto a diester. Really quickly since we haven't done anything on Esters yet, this is an ester:

R-O,O=C-R

It's basically a ketone and an ether on the same C. A DIester is two esters on the same molecule. For this synth reaction we're using a malonic ester, which if you think back to that list of molecule names I made a few entries ago, is a 3 carbon molecule. So it's ester-CH2-ester. If you do 1.NaOEt/EtOH 2. RX 3. H2O/heat, what happens is that the R group from the X gets tacked onto the C in between the two ketones, and then one of the esters gets removed and hydrolyzed to a COOH.

REALLY IMPORTANT NOTE!!!! The 3rd step isn't necessary! You can skip it if you'd like to keep the two esters on the molecules instead of getting a COOH. This is, in fact, sometimes preferable. So sometimes it will be left off of questions, and sometimes it won't.

The chemistry behind understand why this happens is really in line with what we've already been talking about. Remember e- withdrawing O? Yeah, me too! Well, that C that's between two esters is extra positive because it's between four O atoms. This means it's really susceptible to losing those H's in an acid-like reaction. The NaOEt (EtOH is ethanol - grain alcohol - and it's just a solvent.) steals the H atom, leaving the carbon with a negative charge. The R group that's on the halide loves that, so it attaches there. This can, in fact, be done twice to remove both H's if you don't do step 3 (hydrolysis). So you can actually tack 2 R groups onto that middle molecule.

I could have, in fact, drawn this all out on a board for you without even looking at my notes and would have done it on the test...had I remembered the term Malonic ester synth. Not gonna forget THAT one any time soon. :/ Watch, now it won't be on the test tomorrow... ;)

Acetoacetic Ester Synthesis - This is another one that isn't actually creating an ester, it's using acetoacetic ester to create something else. Ok, so the difference between this one and the previous one is that this one isn't a diester, it's just an ester. My teacher told use that you can tell the difference by looking at the molecule of the starting material. If you can see acetate in it, it's this one. if not, it's the other one.

The reagents are the same as the previous reaction, 1.NaOEt/EtOH 2. RX 3. H2O/Heat. Because I'm tired I'm going to shorten this and say, it does pretty much the exact same thing as the previous reaction. The difference is that when you do the hydrolysis portion at the end, you end up with a ketone and not a COOH, and the ester is gone. The end of the molecule ends up staying as acetate, and the ester is removed. So if you had 3 Os in the starting material and you elect to do step 3, you'll end up with the acetate ketone staying behind and 1 O on the molecule. If you skip step three, you also can add two R groups to that poor, abused C.

Ok you guys, there's actually one more reaction in this chapter but it's almost 11 and I need to go to sleep or i won't be able to get up for work tomorrow. I'll add it tomorrow, I promise. :)