IR spectroscopy: answer to quiz

Dear Students,

The recent quiz question requires you to choose the correct compound between two compounds, C and D, to which a given IR spectrum belongs to:

Let us examine and compare them. Both are aldehydes (having CHO groups) and have aromatic rings. The difference between them is compound C has a C=C while D does not. And this one difference makes for a lot of differences between the IR spectra given off by C and D. Let us look at the spectrum.

IR spectrum given in the quiz

Having this double bond means C is a fully unsaturated compound: all the carbons in the molecules are sp² carbons. Looking at the 3000 cm^-1 region, we see sharp, moderately intense bands to the left of 3000 cm^-1 (3062, 3083), C-H stretching vibrations of sp² or unsaturated carbons. No bands are seen to the right of 3000 cm^-1  except for a pair of bands (2826, 2724) which are stretching vibrations of C-H of the CHO group. This clearly shows that this is a spectrum of an unsaturated compound. So this spectrum belongs to C.

Other IR features that set the two compounds apart is the position of the sharp and strong C=O stretch band. This C=O stretching vibration is at 1678 cm^-1, rather low (<1700). This lowered band frequency could be due to conjugation of the carbonyl to a double bond and the aromatic system, and this is indeed seen in compound C. Additionally, there is the presence of the C=C stretch band at 1615 cm^-1.

Now, shown below is an actual spectrum of compound D. You can see many differences if you compare it with that of C.

IR spectrum of compound D

Calculating absorption maximum using Woodward-Fieser rules - answers to quiz

Dear Students,

In this posting, I take the opportunity to show you how to calculate absorption maximum of UV-absorbing compounds using the Woodward-Fieser rules. I will use the recent quiz question: Calculate absorption maximum for this molecule:

First, you should identify the parent UV-absorbing conjugate system: is this a diene, an α,β-unsaturated carbonyl, or a benzene/aromatic system? It is an α,β-unsaturated carbonyl system (see below, coloured blue):

So, you should use the rule for this system. This is a six-membered cyclic (ring) α,β-unsaturated ketone, so the base value is 215 nm.

Next, look for extensions to this conjugated system, meaning here the C=C double bonds that extend from this parent system as show below, in green) There are two double bonds, so add two values (30 x 2 nm):

Now, treat this extended conjugated system as a whole chain with the carbonyl being the head of the chain. Going along this chain from alpha to delta, and beyond, look for ring residue/alkyl/methyl:

Then, look for any other types of auxochromes. None here. Next on the list, look for any exocyclic C=C. There are two (coloured red), exocyclic to the ring labelled A:

Lastly, is there any homodiene element (two C=C bonds inside the same ring)? None.  So, total this up and you get your calculated maximum absorption (λ max), 361 nm. 

Best regards, Dr Lee.

Heterocycles, an introduction

Heterocycles or heterocyclic compounds are compounds composing of rings. At least one member of the ring are atoms other than carbons. These atoms are called heteroatoms. Commonly found in nature and relevant to biology and pharmacy are the heteroatoms nitrogen, oxygen, and sulfur.

Heterocycles come in various shapes and sizes. They can be five-membered rings, six-membered, or two rings joined together. They can also be non-aromatic types and aromatic types. All of these determine their physicochemical properties such as how strong a base they are and their reactivity towards nucleophiles and electrophiles.

As appetizers to our course, here are some interesting examples of heterocycles in life :

The heme molecule within our red blood cells is crucial in carrying oxygen molecules for respiration. It is made of four heterocycles called pyrroles.                                                               

Red blood cells

Quinine is the first drug used in treating the malaria disease. It is isolated from the cinchona bark. It contains within its structure a heterocycle called quinoline.

Quinine from the barks of Cinchona

In this lesson, you will learn:

-       -  How to draw, name, and identify of some common heterocycles, their aromaticity and basicity.

-       - About the reactions that heterocycles participate in

-      - How to prepare these heterocycles in classical synthesis methods

     Notes on the lesson is availble at this site: 
    http://bit.ly/18Lj32R
    

    

    

   

Elimination reactions in pharmacy: part two

Here is another example of elimination in pharmacy.

Curare is a type of drug called a muscle relaxant. It acts by blocking nerve impulses at the neuromuscular junction thus causing the muscle to relax. Such drugs are very useful during surgery when the patient needs to be immobilised. The downside to curare is that it takes a long time for the effect to wear off after surgery and can cause respiratory depression. The effect would only wear off after the drug gets metabolised – that is it gets changed in the body – to a not active form. (Metabolism is a process where a drug is changed to another form when it enters our body).

Curare is a drug used to relax the muscles during a surgery. Its effect is slow to wear off after surgery
and may cause inconvenience such as breathing suppression.

Newer muscle relaxants such as atracurium have been developed that has a built-in functional group that allows the drug to rapidly metabolised or changed into an inactive form. One such change involves an elimination reaction of the quarternary ammonium group of the drug

(Refer to notes on elimination of amines).

Elimination reactions in pharmacy: part one

Besides understanding basic principles of a reaction like the mechanisms and how to apply them to solve problems, perhaps you would appreciate an organic reaction better if I present some real-life situations especially related to pharmacy which involve elimination reactions.

The first example is elimination in the synthesis of a well known drug tamoxifen. Tamoxifen is an anti-estrogen antagonist which is used to treat breast cancer that is estrogen receptor positive. It works by binding to the estrogen receptor on the cancer cells thus stopping the uncontrolled cell growth fuelled by estrogen activity.

Tamoxifen tablet 20 mg (Nolvadex is the brand name)

A 3-D structure of tamoxifen

Here is how tamoxifen is originally made:

First, the main skeleton of tamoxifen is made by addition of a Grignard reagent, phenyl magnesium bromide (PhMgBr) which is a good nucleophile to the ketone group. This produces a tertiary alcohol. This tertiary alcohol is then treated with sulfuric acid. Here a dehydration happens. It is an E1 elimination as a carbocation is formed (favoured by it being tertiary and benzylic at the same time).

The freely rotating bond (coloured green) allows the three substituents at the carbon (blue) adjacent to the positively charged one to change positions like this:

So in an E1 elimination like this, there is no stereocontrol (stereospecificity). As the proton (coloured red) gets removed, a mixture of E- and Z-isomers are produced.

This method to make tamoxifen is apparently not satisfactory because we can’t get purely tamoxifen. There are better, improved ways to produce pure tamoxifen. Check out this website: http://www.ch.ic.ac.uk/local/projects/h_tanner/introsynth.html

Drawing reaction mechanisms with curved arrows

A reaction mechanism is a detailed step-by-step description of how reactants are converted to products. It consists of a sequence of steps showing the making of bonds and the breaking of bonds. It is a way to explain or rationalize how a reaction happens to change a reactant to a product.

When bonds are made or broken, there are movements of electrons from one molecule or a group of atoms to another.

In most reactions you meet in organic chemistry (except radical reactions), the electrons move in a pair (two). We draw the flow of this pair of electrons as a curved arrow like this:

Another important point to note is that these two electrons always move from a place of more electrons (or negatively charged) to a place with less electrons (positively charged):

Here are some common examples, which you meet in reactions you have learned:

Whichever a reaction may be, when drawing a mechanism, remember that a curved arrow means the flow of two electrons, and the electrons always flow from a place of more electrons to a place of less electrons, never the opposite direction.

Elimination reaction in a nutshell

Dear Students,

In this three-hour class, I will introduce you to another important reaction: 
Elimination.

In the previous lectures, you have seen alkyl halides undergoing nucleophilic 
substitutions (SN), for example:

The reason is that halogens are very good leaving groups. A nucleophile attacks
 the carbon to which the halogen is attached causing the halogen to leave.


An elimination reaction works quite similarly, like this: 

The halogen leaves but also a hydrogen is taken away. The hydrogen is taken away by a base. The result is the formation of an alkene, or double bond.


You will see more examples like this in my lecture. In this class, you will learn about:
-  the two mechanisms of elimination, E1, and E2
-  Stereochemistry of elimination particularly E2
-  Elimination of cyclic alkyl halides
-  Alcohols and amines can also be made to undergo eliminations


Notes for this lesson are availble for download here:
http://bit.ly/18s3joz

Tutorial questions for this topic are available here:
http://bit.ly/H1iRFH


See you in class.