Organic Reactions

In organic chemistry there are four general types of reactions that occur:

1) Addition reaction – This is a reaction where two reactants combine and form one single product.  No atoms are left over in an addition reaction. 

An example of an addition reaction:

The mechanism by which the reaction above occurs is the C-C π bond breaking; this results in one C with a formal charge of +1 and a vacant p orbital. The H-Br bond also breaks, which results in Br becoming a nucleophile* and one of the Carbons becoming an electrophile**.  The Br donates its electrons to the positively charged Carbon resulting in a C-Br bond, this makes Carbon happy because it has no formal charge and all of its valence shells are filled. 

This results in two molecules becoming one single molecule with no atoms “left over”.

*Nucleophile - a chemical species with enough electrons to donate, also considered a Lewis-base, a polar bond is formed when it donates a pair of electrons

**Electrophile – a chemical species that accepts an electron pair from a nucleophile, and forms a polar bond

2)  Elimination reaction – An elimination reaction is essentially the opposite of an addition reaction.  In this, a single reactant is split into two products.  Oftentimes the formation of water or HBr will occur.

In the reaction above an acid catalyst is used to break down 1 C2-H bond and 1 C1-O-H bond. Once this is done there are carbons with empty valences. This results in a π bond forming between C1 and C2. The H and the OH released earlier combine to form H2O.



3) Substitution reaction – In a substitution reaction, 2 or more molecules give way to an equal amount of new products. This is accomplished by part of reactant1 and reactant2 breaking off and exchanging places. This is a common type of reaction in biological pathways such as the metabolism if dietary fats.

In Methyl acetate the C-O bond breaks.  This frees the O-CH₃.  In H₂O the H-O σ bond breaks and the H-O and O-Ch₃ exchange, creating the substitution reaction.

4)  Rearrangement reaction – In a rearrangement reaction, one molecule turns into a different molecule through the rearrangement of bonds.  This yields an isomeric product since none of the elements composing the molecule have changed.

(The carbons labeled left to right C₁, C₂, C₃ in Dihydroxyacetone phosphate) The C₂-O π bond breaks, as do the O-H bond off of C₃ and the C₃-H bond.  The hydrogen from the broken O-H bond bonds to the O from the broken π bond. The hydrogen from the broken C₃-H bond bonds to C₂ to complete its valence.

Describing a Reaction

Each of these four types of reactions has an equilibrium constant K_eq.

Keq= [Products]/[Reactants]

The coefficients of the compounds become the exponents in the equilibrium equation shown above. The value of the equilibrium constants tells which side of the reaction arrow is energetically favored.

K_eq < 1 than the reactants are favored

K_eq  > 1 than the products are favored

K_eq ≈ 1 both concentrations are similar (neither favored)

In order for a reaction to be spontaneous the energy of the products must be lower than the energy of the reactants (energy must be released).

Gibbs free-energy change (ΔG)

            Energy of the products = G_products

                        Energy of the reactants = G_reactants

ΔG=G_products - G_reactants

If the reaction is favorable, ΔG<0, in this case energy is lost by the chemical system usually in the form of heat released to the surroundings. This type of reaction is classified as exergonic. If ΔG > 0 it is unfavorable and energy is absorbed from the surroundings. This type of reaction is classified as endergonic.

            ΔG⁰ means that the reaction is carried out under standard conditions.  In standard conditions pure substances are used in their most stable form while the pressure is at 1 atm and temperature is 298K.

            The K_eq and ΔG⁰ both measure whether a reaction is favorable therefore they are mathematically related by the equation below.

For the equation

CH₂ CH₂ +HBr ----> CH₃CH₂Br       K_eq = 7.1 * 10⁷ This can be used to calculate ΔG⁰

Knowing ΔG⁰ introduces the formula      ΔG⁰=ΔH⁰ – TΔS⁰

ΔH= enthalpy, which is also called the heat of reaction. If ΔH<0 the energy of the products is less than the energy of the reactants, and heat is released so the reaction is exothermic. If ΔH>0 the energy of the products is more than the energy of the reactants, heat is absorbed and the reaction is endothermic.

ΔS = entropy change.  Entropy is the measure of change in the amount of molecular randomness. If ΔS>0 the reaction is more favorable, if ΔS<0 the reaction is less favorable.

Stereochemistry

            When you were a child, did you ever put your shoes on backwards?  Do you remember how uncomfortable it was?  You may have, but just not given it any thought or immediately switched them to the correct feet.  Your right shoe is superimposable on your right foot, and the same goes for your left foot and left shoe.  If you put a shoe on the wrong way, it feels awkward and uncomfortable.  This is because your shoes are non-superimposable on your opposite feet.  Now, place your right shoe in front of the mirror.  It looks like your left shoe, doesn’t it?  Shoes, as well as feet, are non-superimposable mirror images of each other. 

            The name of a non-superimposable mirror image is an enantiomer, one of the groups of stereoisomers.  They are not identical to their mirror images.  Enantio is Greek, meaning “opposite.”  Examples of enantiomers are (+)-Lactic Acid (S) and (-)-Lactic Acid (R).  (+)-Lactic Acid occurs in muscle tissue and sour milk, whereas the (-)-Lactic Acid occurs only in sour milk.  They are exact mirror images of each other, but have different structures and functions.  

Below is another example of enantiomers:

L-Alanine is one of the 20 amino acids coded by the genetic code.  D-Alanine occurs in some bacterial cell walls and in some peptide antibiotics.  Just like feet (or in this case, hands), they are non-superimposable mirror images.  

     The substances above have a property that allows them to bend light!  Dextrorotatory and Levorotatory are both terms that have to do with the Optical Activity of organic substances.  To be Optically Active, the organic solutions of the substances must rotate a plane of polarization through an angle.  Dextrorotatory rotates the light to the right (clockwise) and Levorotatory rotates the light to the left (counterclockwise).  A Racemic Mixture is a 50:50 mixture of two chiral enantiomers.  Racemates show no optical rotation because the dextrorotatory and levorotatory molecules are in equal amounts and therefore cancel each other out.

A molecule that is non-identical to its mirror image is said to be Chiral.  The Greek word for Cheir means “hand.”  A hand does not have a plane of symmetry.  Therefore, a molecule that has a plane of symmetry and is identical to its mirror image is said to be Achiral.  An example of an achiral object could be the Batman Logo.  If you cut the bat in half from top to bottom, it is an exact image on either side.   

                                                Achiral                                             Chiral

Rules for Configuration of Structures – Cahn-Ingold-Prelog Rules

·         These rules are named after the chemists who proposed the rules for configurations of chiral compounds. 

1)                  Find the chirality center, an atom that is bonded to four different substituents, of the molecule in question.  Look at the four atoms/substituents attached.  Rank the atoms according to atomic number.  Rank the atom with the highest atomic number the highest number (4).  The atom with the lowest atomic number is therefore ranked the lowest number (1) [The example below is depicted as highest as #1 and lowest as #4.  Therefore, you could do it either way].  For Example: I > Se > F > O > C > H.  Hydrogen is almost always ranked as the lowest priority substituent.

2)                  Re-orient the molecule so that the lowest priority is facing away from you.  Follow from highest to lowest priority (drawing an arrow sometimes helps).  If (the arrow is) clockwise, R is the correct configuration.  If counterclockwise, S is the correct configuration.

The other group of stereoisomers is called Diastereomers, which are not mirror images at all.  Take the shoe analogy explained above for example.  Suppose you have one of your shoes and some other random shoe.  They may be similar in shape and makeup, but they are not identical and are not mirror images.  Diastereomers have the same configuration at one or more chirality centers, but differ at other chirality centers.  The molecules below are Diastereomers.

Lastly, a Meso Compound is a compound that has chirality centers, but is achiral because it has a plain of symmetry.  An example of this is Tartaric Acid, or Tartrate. 

Cycloalkanes

Alkanes that are bonded into rings are known as cycloalkanes. Cycloalkanes, less commonly known as saturated cyclic hydrocarbons, are the basis for countless types of organic molecules, and are constituted by many different conformations.  Defining these cycloalkanes can be determined by Some common ones are shown below:

                              Cyclopropane (3 Carbons)            Cyclobutane (4 Carbons)

                       
                              Cyclopentane (5 Carbons)            Cyclohexane (6 Carbons)

                             Cycloheptane (7 Carbons)               Cyclooctane (8 Carbons)

Some cycloalkanes appear more readily in nature than others, and the common cycloalkanes differ greatly in stability. This is due to strain, which affects a molecule’s stability and ability to maintain a certain shape. There are three types of strain:

1.)   Angle Strain: When bonds in a cycloalkane ring are either compressed or expanded; the ideal tetrahedral angle is 109.5 °, but if the angle is forced to be greater or less, strain results.

2.)   Torsional Strain: eclipsing bonds cause strain, and so if a ring has a great number of bonds on adjacent atoms that are eclipsing one another, the torsional strain is greatly increased.

3.)   Steric Strain: atoms tend to repel each other, so if two atoms get too close to one another, steric strain results.

All forms of strain increase the energy of a cycloalkane ring. However, some cycloalkanes are much higher energy because of the way strain manifests itself.  

Below is an analysis of the source of strain for four of the more common cycloalkanes.

Cyclopropane

                                                     Typical conformation of cyclopropane

Cyclopropane is the highest energy cycloalkane, and also the smallest, since it has the fewest carbons. Cyclopropane exhibits all forms of strain.

Angle Strain: Angle strain in cyclopropane is incredibly high. This is because the normal tetrahedral angles are compressed to 60°.

Torsional Strain: Torsional strain is also high in cyclopropane, as the bonds of all neighboring hydrogens are eclipsing, which boosts the energy level.

                                    Side view of cyclopropane: eclipsing bonds

Steric Strain: There is very little steric strain in cyclopropane.

                                                                    Cyclobutane 

                                          Typical conformation of cyclobutane

Cyclobutane has less strain than cyclopropane, but again because of angle strain, it is a rather unstable cycloalkane.

Angle Strain: Cyclobutane’s angles are at 90°, so angle strain is still an issue due to the compression of the bond angles.

Torsional Strain: Just like cyclopropane, cyclobutane’s bonds with attached hydrogens are all eclipsing, which creates a good deal of strain; there is actually more strain than cyclopropane here.

                                        Side view of Cyclobutane: demonstrates eclipsing bonds

Steric Strain: Again, steric strain is not much of a factor for cyclobutane.

Cyclopentane

                         

                                   Flat conformation of                   “Envelope” conformation of 

Cyclopentane                                  Cyclopentane

Cyclopentane is the first ring in ascending order of size that experiences

torsional strain as a result of conformation; as such, it has another shape in addition to the traditional flat ring. This is called the “envelope”, where one point of the pentagon is pointed up, so that there are less eclipsing interactions. This form is the more common one in nature, since it is more stable.

            Angle Strain: 108° is actually very close to the ideal tetrahedral angle, so angle strain is greatly reduced in cyclopentane. However, it is overtaken by torsional strain in regards to the shape of the most stable molecule.

            Torsional Strain: Because the envelope conformation of cyclopentane allows a few bond interactions to become staggered, it is more stable and therefore more common. The rest of the bond interactions stay eclipsed however.

“Envelope” conformation of cyclopentane demonstrates staggered bonds.

            Steric Strain: Steric strain is still not a problem for a single cyclopentane ring, though like other cycloalkanes its substituents can cause steric strain based on the relative positions to one another.

Cyclohexane

    

                   “Flat” conformation of cyclohexane      “Chair” conformation of cyclohexane

    

“Boat” conformation of cyclohexane                                  “Twist-boat” cyclohexane

           

Cyclohexane is a unique cycloalkane; it is known as the most stable of all cycloalkanes. However, it is not the flat conformation of cyclohexane that allows it most of its stability; it is the much more common “chair” form that makes it so stable. “Chair” conformation cyclohexanes allow for angles close to the tetrahedral angle, and they are configured in such a way so that there are far less eclipsing interactions between attached hydrogens. There are two other forms of cyclohexane, known as “boat” and “twist-boat”. The “boat” form of cyclohexane is less common due to increased strain, and “twist-boat” only exists briefly in specific circumstances.

            Angle Strain: In the “chair” conformation of cyclohexane, bond angles are at 111.5°, which is very close to the ideal angle width.  Thus, “chair” cyclohexane is almost angle strain-free.

            Torsional Strain: “Chair” conformation cyclohexane also is free of torsional strain, as the shape of the molecule allows all of the bond interactions to be staggered, and therefore free of strain.

Side view of “chair” cyclohexane demonstrates

staggered bond formations and relaxed angle strain.

            Steric Strain: cyclohexane runs into steric strain because of the way its carbon-hydrogen bonds are oriented. Half of them are known as axial, which run along a vertical plane that is perpendicular to the ring itself, and the other half are known as equatorial. Axial hydrogens repel each other, as do equatorial hydrogens, even more so when substituents are attached to adjacent axials or equatorials.

It is very much worth noting that medium sized rings (7-13 carbons) suffer from steric and torsional strain, but not from angle strain. 14 carbon cycloalkanes and anything larger do not have strain problems because their shape allows them to configure in a way that has ideal angles and no torsional strain.