You Know That One Russian Guy…

                 Vladimir Vasilyevich Markovnikov was a Russian organic chemist who worked in the mid 1800’s. During his research working with halides and alkenes, he was looking for any similarities between all of the different reactions.  He noticed a common occurrence that some reactions yielded only one product when they were thought to be able to yield more than one possible product. After examining the reaction more closely, it was noticed that the halide in the only product was bonded to the carbon with a higher degree of substitution. Therefore, the halide would be bonded to, for example, a tertiary carbon rather than a primary or secondary carbon. This and later research led to the formation of the Markovnikov rule, which was widely accepted in the world of organic chemistry. This rule states that in the addition of HX, X being a halide such as bromine and chlorine (excluding fluorine and iodine), to an alkene, the more highly substituted carbocation is formed as the intermediate rather than the less highly substituted one.

                Markovnikov wasn’t the only one to notice the absence of a product after predicting more would occur. This has been a common dilemma for many other researchers as well, including George Kimball and Irving Roberts who conducted research in 1937. During Kimball and Robert’s research with bromine gas and chlorine gas additions to alkenes, they observed only one product, which led them to question why this occurred. The answer to this, they proposed, was instead of the intermediate being a carbocation, like one would normally predict, the intermediate was a bromonium ion or a chloronium ion. These ions would form from a nucleophilic attack from bromine or chlorine. The formation of the ion results in anti-stereochemistry, which is observed in reactions of cycloalkenes with halides. Rather than both a cis and trans product, only trans product was formed. This is because once there’s a bromonium ion on one side of the cycloalkane; the other negatively charged bromine will attack from the opposite side since the large bromine is shielding one whole side. 

                There are also reactions that yield a halohydrin. This involves a reaction taking place between an alkene, X2, and H2O, when X is either Br or Cl. Since this reaction takes place in water, the water molecules are able to compete with the Br- ion as a nucleophile and reacts with the bromonium ion intermediate. This results in the formation of a bromohydrin.

                 In the reaction, once the bromonium ion is formed, water acts as a nucleophile, breaking the ion ring and attaching itself to a carbon. The oxygen becomes positively charged, and as a result of being in water, the oxygen loses a proton in a process called deprotonation, and creates a H3O+.

                 Alkene oxymercuration is closely analogous to halohydrin formation. The reaction is initiated by electrophilic addition of Hg2+ ion to the alkene to give an intermediate mercurium ion, whose structure resembles that of a bromonium ion. Nucleophilic addition of water as in halohydrin formation, followed by deprotonation, then yields a stable organomercury product.

                  The final step, demercuration of the organomercury compound by reaction with sodium borohydrate. Note that the regiochemistry of the reaction corresponds to Markovnikov addition of water, that is, the –OH group attaches to the more highly substituted carbon atom, and the –H attaches to the less highly substituted carbon. The hydrogen that replaces mercury in the demercuration step can attach from either side of the molecule depending on the exact circumstances. All of these are regiospecific reactions, meaning that they produce one structural, or constitutional, isomer over all others.

Naming Alkenes

Alkenes are named using a series of rules that are similar to those for alkanes, except with the suffix –ene instead of –ane to identify the functional group.

Step 1: Name the parent hydrocarbon.  Find the longest carbon chain containing a double bond. 

Name the compound based off the number of carbons, using the suffix –ene.

Step 2: Number the carbon atoms in the chain.  Begin at the end closest to the double bond, or if

the double bond is exactly in the center of the chain, begin at the end closer to the first branch point. 

This assures that the double bond receives the lowest number possible.

Step 3: Write the Full Name.  Number the substituents according to their position on the parent

chain, and list alphabetically.  Show the position of the double bond by giving the number of the first

alkene carbon directly before the parent name.  If there is more than one double bond, show the

position of each double bond and use the suffix  –diene, -triene and so forth.

In 1993 IUPAC changed their naming recommendations to place the position of the double bond immediately before the –ene suffix rather than before the parent name.  This change is not widely accepted in the United States, so the old system is used.

Cycloalkenes are named in a similar fashion, but because there is no end to the chain the cycloalkene is named so the double bond is between C1 and C2.  The first substituent has the lowest possible just like in a regular chain.  The position of the double bond is not necessary to mention in the name, because the double bond is always assumed to be located between C1 and C2.  In the new naming system the locant in position right before the suffix in a diene.

Some alkenes names have been used for so long that they are accepted despite the fact that they do not follow the IUPAC naming system.  For example, ethene is the alkene derived from ethane, but the name ethylene has been used for so long that it has been accepted by IUPAC.

Here are a few molecules with more accepted common names:

Naming alkenes are very similar to naming alkanes.  Identifying where the double bond is, is the key to successfully naming the molecule.

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. 

  

IUPAC Naming

From the beginning of documented history, the human race has sought to classify and label chemical compounds, even before these compounds were properly understood. Urea is one example of a complex chemical compound named after where it was originally found (in urine). Naming compounds in this manner was acceptable when the number of known compounds was small. When it became apparent that there existed an infinite number of compounds, a new naming system had to be developed in order to distinguish the compounds from each other. Nomenclature of alkanes, or saturated hydrocarbons, is no exception.

            Straight-chain alkanes are named according to the number of carbon atoms they contain. The prefixes below make the basic part of naming fairly easy. Once the number of carbons in the chain has been determined, the appropriate prefix can be picked and combined with the suffix -ane.

Number of Carbons (n)	Name	Formula (CnH2n+2)
1	Methane	CH4
2	Ethane	C2H6
3	Propane	C3H8
4	Butane	C4H10
5	Pentane	C5H12
6	Hexane	C6H14
7	Heptane	C7H16
8	Octane	C8H18
9	Nonane	C9H20
10	Decane	C10H22
11	Undecane	C11H24
12	Dodecane	C12H26

If you remove a hydrogen from an alkane, the partial structure becomes an alkyl group. Alkyl groups are named by replacing the –ane ending with an –yl ending. For example if you remove a hydrogen atom from methane the partial structure becomes methyl. Alkyl groups are not stable compounds by themselves, they are parts of larger compounds. Hence methyl is only one part of 4-methylhexane.

            The name of an alkane consists of  four parts: locant—prefix—parent--suffix. Locant refers to the location of the substituents (the smaller groups branching off from the main carbon chain), the prefix denotes the substituents in the molecule, parent refers to the number of carbons in the longest chain, and the suffix identifies the primary functional group within the molecule.

            To examine how these components are found, take a look at the following skeletal structure.

            Step 1: find the longest continuous carbon chain in the molecule. It is acceptable to “round corners” to find the longest chain. In this molecule's case, there are several options, all yielding the same carbon chain length.

            There are two different ways to obtain a 7-carbon chain. By convention, the chain with the most branching should be selected. Both options in this case yield the same number of branches off the parent chain. Either numbered chain can be used. For simplicity, the red numbered chain will be selected as the parent chain for discussion. There are seven carbons. Our “parent” is heptane.

            Step 2: number the chain, placing “1” at the end of the chain that is closet to a substituent.  This particular molecule's main carbon chain can be numbered two different ways.

            Notice that if we start from the left, the first substituent is at “2”. If we start from the top, the first substituent reached is at carbon “4”. The blue-numbered chain is the correct way to number this alkane because the first substituent reached has the lowest number. If the first substituent reached has the same number regardless of which end of the chain was used as a starting point, the substituent locants are added together and the chain with the lowest number is the correct chain. For example, an alkane could be named 2,4,5-trimethylhexane, or 2,3,5-trimethylhexane. The second option is preferred, as 2,3,5 has a lower sum than 2,4,5.

            Step 3: identify substituents and provide each with a locant, and a prefix if necessary. The “locant” is merely the number on our properly numbered carbon chain where the substituent is located.

           

            There are two methyl groups on the main chain, at “2” and “3”. Our locant is thus 2,3-, and our multiplier prefix is “di” because there are two methyl groups. All together, this is denoted as: 2,3-dimethyl. Take note that if there were two methyl groups at the same locant (for example, two methyl groups at “2”) the proper way to denote the groups would not be 2-dimethyl. It would be 2,2-dimethyl because we have to account for both methyl groups.

           

            Other prefixes include “tri” and “tetra” for 3 groups and 4 identical groups, respectively.

            Step 4: name complex substituents. In this molecule there is a complex substituent at carbon 4. This substituent is not a simple chain. It is structured as a molecule in itself. Therefore it must be named as if it were another molecule and should be numbered and named as such, but with an -yl ending. This complex substituent is 4-(1,1-dimethylmethane). This is also more commonly known as 4-isopropyl.

            Step 5: put the locants, prefixes, and parent together to create the entire name. From the previous sections the following components were found:

-        the parent is heptane.

-        there are two methyl groups, denoted as “2,3-dimethyl.”

-        there is one complex substituent named “4-isopropyl.”

-        the primary functional group is an alkane, so the suffix will be “ane.”

            To arrange all of these pieces into one name, they must be alphabetized. The multiplier prefixes do not count when alphabetizing, so the “di” in “2,3-dimethyl” does not count, but the “methyl” component does. In a complex substituent, however, the first letter counts even if there is a prefix. Thus “isopropyl” comes before “dimethyl” because “i” comes before “m”. This results in the following name:

           

            4-isopropyl-2,3-dimethylheptane

           

            There are a few exceptions to the naming scheme. There are several simpler-branched alkyl groups that have common names that are not systematic.

            These common names are acceptable to use and can be alphabetized by their names. There is one exception. Those common group names that begin with an italicized “tert” or “sec” do not count towards alphabetization. For example, in tert-Pentyl, the “tert” would not matter when alphabetizing, but “Pentyl” would. The prefixes “tert” and “sec” merely refer to whether the carbon connected to the rest of the molecule is a secondary or tertiary carbon. A secondary carbon has two other carbons attached to it; a tertiary carbon has three other carbons attached to it.

            A final evaluation should be made regarding the substituents of the molecule. The substituents may not all be alkyl groups, but an alcohol or a halogen. Many of these extra “things” in the carbon chain are considered “functional groups.” Functional groups are groups of atoms, in a specific pattern, that have characteristic chemical behavior. Below are the most common functional groups.