Priorities for Plane Drawings of Cyclcohexane

6.3: Absolute Configuration and the (R) and (S) System

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Learning Objective

• proper noun chiral compounds using (R) & (S) nomenclature

USE YOUR MODELING KIT: Models assistance in visualizing the structure. When using a model, make sure the lowest priority is pointing abroad from y'all. Then decide the direction from the highest priority substituent to the lowest: clockwise (R) or counterclockwise (Due south).

IF You lot Exercise NOT Take A MODELING KIT: recall that the dashes mean the bond is going into the screen and the wedges means that bond is coming out of the screen. If the lowest priority bond is non pointing to the dorsum, mentally rotate it and then that it is. However, it is very useful when learning organic chemical science to use models.

If yous have a modeling kit use it every bit you read through this section and work the do problems.

Introduction and the Cahn-Ingold-Prelog rules of Priority

To name the enantiomers of a chemical compound unambiguously, their names must include the "handedness" of the molecule. The letters "R" and "South" are determined past applying the Cahn-Ingold-Prelog (CIP) rules. The optical activeness (+/-) can also exist communicated in the name, but must be empirically derived. There are also biochemical conventions for carbohydrates (sugars) and amino acids (the edifice blocks of proteins).

The method of unambiguously assigning the handedness of molecules was originated by three chemists: R.Due south. Cahn, C. Ingold, and V. Prelog and, as such, is besides frequently called the Cahn-Ingold-Prelog rules. In addition to the CIP system, in that location are two ways of experimentally determining the absolute configuration of an enantiomer:

1. X-ray diffraction analysis. Note that there is no correlation between the sign of rotation and the structure of a particular enantiomer.
2. Chemical correlation with a molecule whose structure has already been adamant via 10-ray diffraction.

Still, for not-laboratory purposes, it is beneficial to focus on the R/S system. The sign of optical rotation, although different for the ii enantiomers of a chiral molecule,at the same temperature, cannot be used to constitute the accented configuration of an enantiomer; this is because the sign of optical rotation for a particular enantiomer may change when the temperature changes.

The Cahn-Ingold-Prelog rules of priority are based on the atomic numbers of the atoms of interest. For chirality, the atoms of involvement are the atoms bonded to the chiral carbon.

1. The atom with higher diminutive number has college priority (I > Br > Cl > South > P > F > O > N > C > H).
2. When comparing isotopes, the atom with the college mass number has higher priority [¹⁸O > ^xviO or ^fifteenDue north > ¹⁴Due north or ¹³C > ¹²C or T (³H) > D (²H) > H].
3. When in that location is a necktie in (2) in a higher place, establish relative priority by proceeding to the next cantlet(south) along the chain until the first difference is observed.

Multiple bonds are treated as if each bond of the multiple bond is bonded to a unique cantlet. For case, the ethenyl group (CH₂=CH) has higher priority than the ethyl group (CH₃CH₂). The ethenyl carbon priority is "two" bonds to carbon atoms and one bond to a hydrogen cantlet compared with the ethyl carbon that has simply one bail to a carbon atom and two bonds to two hydrogen atoms. Similarly, the carbon-carbon triple bond of acetylene would give it higher CIP priority than the ethenyl group as summarized below.

Stereocenters are labeled R or Southward

The "right paw" and "left paw" nomenclature is used to name the enantiomers of a chiral compound. The stereocenters are labeled as R or S.

Consider the diagram above on the left: a curved arrow is drawn counter-clockwise (c-cw) from the highest priority substituent (one) to the lowest priority substituent (four) in the Due south - configuration ("Sinister" → Latin= "left"). The counterclockwise direction can be recognized past the motility left when leaving the 12 o' clock position. At present consider the diagram higher up on the right where a curved pointer is drawn clockwise (cw) from the highest priority substituent (ane) to the everyman priority substituent (4) in the R configuration ("Rectus" → Latin= "correct"). The R or Southward is then added as a prefix, in parenthesis, to the name of the enantiomer of involvement. A locator number is required if in that location is more one chiral centre. Otherwise, the person reading the name is expected to recognize the chiral center.

Example ane

The two chiral compounds below are drawn to emphasize the chiral carbon with the full chemical proper noun below each construction.

Accented Configurations of Perspective Formulas

Chemists need a convenient way to distinguish 1 stereoisomer from another. The Cahn-Ingold-Prelog system is a fix of rules that allows usa to unambiguously ascertain the stereochemical configuration of whatever stereocenter, using the designations ' R ' (from the Latin rectus, meaning right-handed) or ' S ' (from the Latin sinister, meaning left-handed).

The rules for this system of stereochemical nomenclature are, on the surface, fairly simple.

Rules for assigning an R/Southward designation to a chiral center

1: Assign priorities to the four substituents, with #1 being the highest priority and #4 the everyman. Priorities are based on the atomic number.

2: Trace a circle from #i to #2 to #3.

3: Determine the orientation of the #4 priority group. If it is oriented into the plane of the page (away from you), become to step 4a. If it is oriented out of the airplane of the page (toward you) go to stride 4b.

4a: (#four group pointing away from yous): a clockwise circle in office 2 corresponds to the R configuration, while a counterclockwise circle corresponds to the Southward configuration.

4b: (#iv group pointing toward you lot): a clockwise circle in function 2 corresponds to the S configuration, while a counterclockwise circle corresponds to the R configuration.

Nosotros'll utilize the three-carbon saccharide glyceraldehyde as our showtime example. The first matter that we must do is to assign a priority to each of the 4 substituents bound to the chiral center. Nosotros beginning expect at the atoms that are straight bonded to the chiral center: these are H, O (in the hydroxyl), C (in the aldehyde), and C (in the CH₂OH group).

Assigning R/Southward configuration to glyceraldehyde:

Two priorities are easy: hydrogen, with an atomic number of 1, is the everyman (#4) priority, and the hydroxyl oxygen, with atomic number 8, is priority #1. Carbon has an atomic number of half dozen. Which of the two 'C' groups is priority #2, the aldehyde or the CH_twoOH? To determine this, nosotros move one more bond away from the chiral center: for the aldehyde we take a double bond to an oxygen, while on the CH₂OH grouping we have a single bond to an oxygen. If the cantlet is the same, double bonds have a college priority than single bonds. Therefore, the aldehyde group is assigned #2 priority and the CH₂OH group the #3 priority.

With our priorities assigned, we wait next at the #4 priority group (the hydrogen) and come across that it is pointed dorsum away from us, into the aeroplane of the page - thus pace 4a from the procedure above applies. So, we trace a circle defined past the #1, #2, and #three priority groups, in increasing order. The circle is clockwise, which by step 4a tells u.s.a. that this carbon has the 'R' configuration, and that this molecule is (R)-glyceraldehyde. Its enantiomer, past definition, must be (S)-glyceraldehyde.

Next, allow's look at one of the enantiomers of lactic acid and determine the configuration of the chiral center. Clearly, H is the #4 substituent and OH is #1. Owing to its three bonds to oxygen, the carbon on the acrid group takes priority #two, and the methyl group takes #3. The #4 group, hydrogen, happens to be drawn pointing toward us (out of the plane of the folio) in this figure, then nosotros use stride 4b: The circle traced from #ane to #two to #three is clockwise, which ways that the chiral center has the S configuration.

The drug thalidomide is an interesting - but tragic - case written report in the importance of stereochemistry in drug design. Outset manufactured by a German drug visitor and prescribed widely in Europe and Australia in the late 1950's as a sedative and remedy for morning sickness in meaning women, thalidomide was soon implicated every bit the cause of devastating birth defects in babies built-in to women who had taken it. Thalidomide contains a chiral center, and thus exists in two enantiomeric forms. It was marketed as a racemic mixture: in other words, a 50:l mixture of both enantiomers.

Let's effort to make up one's mind the stereochemical configuration of the enantiomer on the left. Of the four bonds to the chiral heart, the #4 priority is hydrogen. The nitrogen group is #i, the carbonyl side of the ring is #2, and the –CH₂ side of the ring is #iii.

The hydrogen is shown pointing away from us, and the prioritized substituents trace a clockwise circumvolve: this is the R enantiomer of thalidomide. The other enantiomer, of course, must have the S configuration.

Although scientists are yet unsure today how thalidomide works, experimental prove suggests that information technology was actually the R enantiomer that had the desired medical effects, while the S enantiomer acquired the birth defects. Even with this knowledge, however, pure (R)-thalidomide is not condom, considering enzymes in the body rapidly convert betwixt the two enantiomers - nosotros will see how that happens in chapter 12.

As a historical note, thalidomide was never approved for apply in the U.s.. This was thanks in large part to the efforts of Dr. Frances Kelsey, a Food and Drug officeholder who, at peril to her career, blocked its approving due to her concerns well-nigh the lack of adequate safety studies, particularly with regard to the drug's ability to enter the bloodstream of a developing fetus. Unfortunately, though, at that time clinical trials for new drugs involved widespread and unregulated distribution to doctors and their patients across the country, and then families in the U.S. were not spared from the impairment caused.

Very recently a close derivative of thalidomide has get legal to prescribe again in the The states, with strict condom measures enforced, for the treatment of a class of blood cancer chosen multiple myeloma. In Brazil, thalidomide is used in the treatment of leprosy - just despite condom measures, children are nonetheless beingness built-in with thalidomide-related defects.

Exercise 1.: Make up one's mind the stereochemical configurations of the chiral centers in the biomolecules shown below.

Practice 2. : Should the (R) enantiomer of malate accept a solid or dashed wedge for the C-O bond in the figure below?

Exercise 3. : Using solid or dashed wedges to evidence stereochemistry, draw the (R) enantiomer of ibuprofen and the (Southward) enantiomer of 2-methylerythritol-iv-phosphate (structures are shown earlier in this chapter without stereochemistry).

Solutions to exercises

Absolute Configurations of Fischer Projections

To determine the absolute configuration of a chiral center in a Fisher projection, use the following two-stride process.

Step 1
Assign priority numbers to the four ligands (groups) bonded to the chiral center using the CIP priority system.

Stride ii - vertical choice
If the everyman priority ligand is on a Fiveertical bond, then it is pointing away from the viewer.

Trace the three highest-priority ligands starting at the highest-priority ligand (① → ② → ③) in the direction that will give a Very correct answer.

In the compound beneath, the movement is clockwise indicating an R-configuration. The complete IUPAC proper name for this chemical compound is (R)-butan-ii-ol.

Step 2 - horizontal option

If the lowest-priority ligand is on a Horizontal bail, then information technology is pointing toward the viewer.

Trace the three highest-priority ligands starting at the highest-priority ligand (① → ② → ③) in the management that will requite a Horribly wrong answer. Note in the table below that the configurations are reversed from the first example.

In the compound beneath, the movement is clockwise (R) which is Horribly wrong, then the actual configuration is South. The consummate IUPAC name for this chemical compound is (S)-butan-2-ol.

Manipulating Fischer Projections with NO Change to Configuration

A Fischer project restricts a iii-dimensional molecule into ii dimensions. Consequently, at that place are limitations as to the operations that can be performed on a Fischer project without changing the absolute configuration at chiral centers. The operations that do non change the absolute configuration at a chiral heart in a Fischer projections tin can be summarized as two rules.

Dominion 1: Rotation of the Fischer project by 180º in either direction without lifting information technology off the plane of the paper does not modify the absolute configuration at the chiral center.

Dominion ii: Rotation of three ligands on the chiral center in either direction, keeping the remaining ligand in place, does not change the accented configuration at the chiral center.

Manipulating Fischer Projections with Alter to Configuration

The operations that do alter the accented configuration at a chiral heart in a Fischer project can be summarized every bit two rules.

Dominion i: Rotation of the Fischer projection past 90º in either direction changes the accented configuration at the chiral center.

Rule 2: Interchanging any two ligands on the chiral center changes the absolute configuration at the chiral heart.

The above rules assume that the Fischer projection nether consideration contains only 1 chiral center. Nevertheless, with care, they tin be practical to Fischer projections containing any number of chiral centers.

Exercise i

Classify the post-obit compounds as R or S?

Solution

1. S: I > Br > F > H. The lowest priority substituent, H, is already going towards the back. It turns left going from I to Br to F, so it's a S.
2. R: Br > Cl > CH_iii > H. You have to switch the H and Br in order to place the H, the lowest priority, in the back. And so, going from Br to Cl, CH₃ is turning to the right, giving you a R.
3. Neither R or Due south: This molecule is achiral. Only chiral molecules tin can be named R or Southward.
4. R: OH > CN > CH₂NH₂ > H. The H, the lowest priority, has to be switched to the back. Then, going from OH to CN to CH₂NH₂, you are turning right, giving yous a R.
5. (5) South: \(\ce{-COOH}\) > \(\ce{-CH_2OH}\) > \(\ce{C#CH}\) > \(\ce{H}\). Then, going from \(\ce{-COOH}\) to \(\ce{-CH_2OH}\) to \(\ce{-C#CH}\) you are turning left, giving yous a S configuration.

Exercises

6. Orient the post-obit so that the least priority (4) atom is paced behind, then assign stereochemistry (R or South).

7. Draw (R)-ii-bromobutan-2-ol.

8. Assign R/S to the following molecule.

Solutions

6.

A = South; B = R

vii.

viii. The stereo middle is R.

Other Resource

Kahn Academy video tutorial on the R-S naming system

References

1. Schore and Vollhardt. Organic Chemistry Structure and Function. New York:W.H. Freeman and Visitor, 2007.
2. McMurry, John and Simanek, Eric. Fundamentals of Organic Chemical science. 6th Ed. Brooks Cole, 2006.

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