Let’s look at the following for all examples (review from previous post):

• Type of carbon
• Solvent
• Nucleophile

In this first example, we have:

Type of carbon:

• Alkyl halide attached to a secondary carbon
• Fairly good a stabilizing carbocations

Solvent:

• Polar protic solvent mixture
• Good solvent system for ionization (carbocation formation)

Nucleophile:

• Poor nucleophiles (H₂O and methanol (CH₃OH))
• Therefore, we need assistance to make this reaction proceed (need to form a carbocation)

Looking at our assessment, it all leans towards S_N1:

OK, on to the second example:

Type of carbon:

• Alkyl halide attached to a primary carbon
• Good for backside attack
• Also, bromide is a good leaving group

Solvent:

• Polar aprotic solvent
• Good solvent for solubilizing counter ions (..like the Na⁺ in NaBr. This makes the CN^- more reactive, meaning more nucleophilic)
• Not a good solvent for stabilizing anions (CN^-); cyanide anion can react (attack)

Nucleophile:

• Strong nucleophile
• Speaks for itself

All of our information points to S_N2:

So what about our third example?

Type of carbon:

• Alkyl halide attached to a secondary carbon
• Good for both S_N1 and S_N2…this is that grey area in the last post (on algorithm)
• Bromide is a good leaving group

Solvent:

• Polar aprotic solvent
• Good solvent for S_N2 reactions; bad solvent for S_N1 reactions

Nucleophile:

• Strong nucleophile

Once again, it all points to S_N2:

So, I am pretty sure you all are experts by now. See if you can figure out these last two examples:

cyclic bromide product answer…click here

cyclic bromide mechanism answer…click here

alkyl bromide  product answer …click here

alkyl bromide  mechanism answer…click here

The patient’s medical history included gout, type 2 diabetes (well-controlled by insulin for 16 years), cardiomyopathy, chronic atrial fibrillation, and chronic renal insufficiency of four years’ duration associated with past nonsteroidal anti-inflammatory drug use. He was taking colchicine, allopurinol, warfarin, digoxin, and furosemide. Past surgical history consisted of right knee arthrocentesis and right midfoot fusion.

Muscle biopsy revealed variations in fiber size and configuration, as well as focal sarcoplasmic vacuoles. There were few neurovascular changes and no evidence of infiltration, vasculitis, or fibrosis.

Diagnosis: Colchicine-induced myopathy

Treatment: Cessation of the medication

Colchicine is a drug used to treat gout. In this case, the drug that was being administered to treat the patient’s gout was actually causing the onset of progressive weakness (due to chronic renal insufficiency). Let’s take a look at the structure of Colchicine:

Now, let’s identify a few functional groups on this molecule:

If we specifically focus on the ether functional groups, we could ask…How does nature make the ether bonds?  Well, it accomplishes this by using S-Adenosylmethionine (SAM):

We then could ask…how do chemists make ether bonds in the laboratory? They use the Williamson ether synthesis reaction:

This reaction involves an alkoxide and an alkyl halide. With every reaction, you should break it down to what is the nucleophile and what is the electrophile; the nucleophile is what attacks and the electrophile is what is being attacked. Nucleophiles are either negatively charged or will have a lone pair that can be used to attack. Electrophiles are either positively charged or will contain double bonds, such as carbonyl compounds. Breaking the reaction down will help if the reaction involves complex molecules. Let’s take a look at the reaction of S-Adenosylmethionine (SAM) with an aromatic alcohol:

In this case, the oxygen is our nucleophile (negatively charged) and the sulfur is our electrophile (positively charged). But wait….now that the positive charge is gone on the sulfur, what about the negative change on the carbonyl group? Well, I have written it in this fashion just to give you an example of more complex structures. If we want to be more accurate, we could possibly rewrite the reaction mechanism as follows:

For practice, write down all the functional groups you see in S-Adenosylmethionine (SAM):

(This case was taken from clinicaladvisor.com)

Numerous questions are associated with S_N2 versus E2. How do I tell the difference? How do know when it is S_N2 and when it is E2? Here is a reaction that demonstrates both:

Let’s first start with the mechanism of S_N2:

In order for a reaction to proceed through an S_N2 mechanism, the nucleophile must be able to attack 180° to the leaving group. When this occurs, the reaction goes through a transition state where all five atoms are associated with the carbon being attacked. Finally, the nucleophile adds and the leaving group leaves simultaneously. The S_N2 mechanism DOES NOT involve a carbocation. It proceeds in a single step.

Now, let’s look at what happens if we begin to add groups (other than hydrogen) to the carbon being attacked:

As we begin to increase the number of non-hydrogen groups, the reaction begins to move towards an E2 mechanism. Why is this the case? Think about the non-hydrogen groups as being much bigger than hydrogen:

Remember that in an S_N2 mechanism, the nucleophile must be able to attack 180° to the leaving group. As the groups get larger, the room for a nucleophile to come in an attack gets smaller. Here is another view point we can look at:

See how it is getting harder and harder to see the carbon atom as more and more groups are added.

Ok, so we now feel more comfortable with S_N2 versus E2, but what about stereochemistry with S_N2? Is that something we need to worry about? Well…it depends on the starting material that is used. In order for a compound, in this case, to be chiral, all four groups must be different. If we look at the first example, this is not the case:

We do not need to worry about chirality or stereochemistry. Let’s look at a structure with four different groups and see if we can figure this out:

If we look at the conversion from an alkyl halide to an alcohol shown above, we can see that the groups on the starting alkyl halide are not located in the same place in space as the groups on the alcohol. The groups are obviously the same, but the compound has gone through an inversion. This is like turning your shirt inside out; it is the same shirt, but the inside and outside are now switched.

If we look at the priorities of the groups, the alkyl halide and alcohol are the highest priority. We can just say for argument sake that R₁, R₂, and R₃ are the priority assignment for the R groups:

If we push the –X and –OH groups into the paper, we can draw that in the following manner:

Now, it is easy to see that the relative position of the groups has changed.

Let’s finish up by looking at the E2 mechanism:

In this case, I have placed a methyl group, R₁, and R₂ on the central carbon. We can think of all these as large groups that block the central carbon from attack. The hydroxide ion is not only a good nucleophile but a great base. Since it does not have the space to attack, it will look for a proton to pull off. Where does it look to pull off a proton? It looks for protons that are attached to the carbon adjacent to the carbon with the alkyl halide. Say what??  Let me illustrate:

Here are a few other examples:

Now that we have that squared away, let’s move on to the mechanism:

The hydroxide comes in and pulls off one of the adjacent hygrogens we talked about earlier. Now, the electrons of the bond can now swing down and kick out the halide, forming a double bond. This reaction proceeds in one step; it does not form a carbocation. The above reaction and the below reaction are the same. I just wanted to write it in two different ways; some prefer to see all the atoms and some prefer line drawings.

NOTE: When I talk about the more groups we add the harder it gets to ‘see’ the carbon, we are going from a methyl group to a primary carbon to a secondary carbon to a tertiary carbon.

Yes, so not only does the IUPAC naming system have its own little twists and turns on the rules, we also have common names.  Obviously, these are the names that we used for compounds before IUPAC came along and created a giant rule book.  Nevertheless, the simpler compounds are rather easy to name and follow a comfortable step-by-step process.  Yay! (Right?)

The Carbon Chain–First and foremost, we must identify what the base chain of the compound is.  Usually, this can be relatively easy as it just entails counting up how many carbons we’ve got.  Of course, it will get difficult when the chain branches into several units.  Just remember, the longest chain may NOT be the one that looks like a straight (if zig-zaggedy) line across the page.  Quite often, if the chain is branched, the longest chain will follow a branch.  Also, you can only number two ways: left to right and right to left.  For now, just number it left to right.  Now, how many carbons do you have?  The nomenclature goes as follows: methane, ethane, propane, butane, pentane, hexane, heptane, octane, nonane, decane and so forth.

There are two exceptions to this:  Is there a ring in your compound?  If yes, then you must use the ring as your base compound.  If there is more than one ring, use the largest one.  The naming follows the above pattern, just with a cyclo- prefix.  Does your compound contain a double or triple bond?  Then drop the -ane and add -ene or -yne respectively.  Are there branches of C chains coming off your main chain?  Then count the number of carbons and name it, then remove -ane and add -yl (i.e. methyl, ethyl, butyl…)

Easy, yes?  Great.  It gets better!

Simple Substituents on the Chain–Now of course, we would all love if everything was just a saturated carbon chain.  It never works out as such since substituents are the atoms we rely on to react organic compounds!  Let’s just do alcohols and halides for time’s sake, though I do plan to go into much further detail at some point in time (ketones, aldehydes, carboxylic acids, esters, ethers etc).  However, today is supposed to be a breif overview.  The rest will require their own topic…

Of course, an alcohol is an organic compound that contains an -OH group.  You, dear reader, will probably be quite familiar with ethanol, since that is the culprit in alcoholic beverages.  As you just saw, to name an alcohol, you drop the -ane, (-ene, or -yne) and add an -ol.  Simple, yes?

Halides are a bit different, as their nomenclature involves a prefix instead of a suffix.  We typically call them alkyl-halides and they are quite simple to name.  If there is a chlorine on your chain, you’d name it chloro-name (or boro, floro or iodo).

Putting it together–Alright, now you didn’t think you could just slap some -ol’s and boro-’s on the name of your chain and get away with it scott-clean, did you?  Of course not, chemistry is never that nice.  You counted the number of substituents on your carbon chain for a reason, remember?

Now, in order to give someone who is reading the name of your compound enough information to actually draw/identify the compound, we must number its substituents.  Here it gets a tad tricky.  You want to number your carbon chain in the direction in which you get the smallest numbers. Ex: If I had this compound, the first thing I would do is count the number of carbons; the base chain is pentane.  Then, I would identify the fact that there is a chlorine group on the carbon chain, so I need to number as such that Cl gets the lowest number possible.  As it turns out, it is in the middle of the carbon and should be numbered as 3.  So, to put this together, the compound is named 3-Chloropentane.

If there is an alcohol somewhere on the compound, it gets numbering priority and you should number your base chain in the direction that gives the OH group the smallest number.  So!  If we have this compound, we should first note that the carbon chain branches!  Lucky for you, however, the branches are the equivalent.  The only difference is that one methyl group comes out of the plane of the page, where as one goes into the plane of the page. So, when counting, we get 4 carbons, so our main chain is butane.  We have two functional groups here, an OH and a CH3 group.  The OH group has numbering priority so we must number such that OH gets the lowest number possible.  That gives us 2.  So we have 2-butanol so far.  Now, we must add the methyl group in.  It is on the same carbon as the OH group; therefore, we get 2-methyl-2-butanol!

Lets do one last example, one that takes into account what happens if we have two of one substituent. Obviously, we only have one carbon, so this is a methyl compound.  Now, we have two Chlorines and and two Flourines.  I said that things need to go alphabetically, right?  Well, what happens when we have two functional groups that start with the same letter? (Dichloro and Difluoro)  Well, we remove the di- and we alphabetize that way. So, here we have dichloro-difluoromethane.

So, how was that for a brief overview of nomenclature?  Not very brief, eh?  Well, I hoped you all enjoyed this and you have a better understanding of the basic ways in which we name organic compounds.

Happy Chemistry!

The Alchemist Kitten