Determining Absolute Configuration

How to Assign Absolute Configuration

How to Determine Absolute Configuration Examples (Practice Problems)

Organic Chemistry → Stereochemistry → Isomers → Stereoisomers → Enantiomers → Stereocenters

The McLaurin Method

(aka: The Rock-On Method)

The Fastest, Easiest, Simpliest and most Realistic Method for Assigning Absolute Configuration to Chiral Centers (Stereocenters)

 

Title of Method: The McLaurin Method - Determining Absolute Configuration with Maximum Separation

                     aka: The Rock-On Method  - Determining Absolute Configuration with Maximum Separation

                               Named due to Avril Lavigne's arrangement of her hand and fingers forming the Rock-On hand

                               gesture demonstrated in Figure 2-c. The Rock-On hand gesture is one of Avril Lavigne's favorite

                               hand gestures.

 

 Authors name: Timothy (Tim) McLaurin

 

 Institutional Addresses: Independent Work - Earned 430 semester hours, at nine (9) Universities, over a 26 year 4

                                              month span from age 18 to age 44.  The 430 semester hours I earned is claimed as the United

                                              States and World Record, is it?  In addition, the 430 semester hours I earned at nine (9) different

                                              universities without being a teachers assistant (TA), teacher or professor, is claimed as the current

                                              United States and World Record, is it?  As well, the 26 years and four months spent as a college

                                              student, without being a teachers assistant (TA), teacher or professor, is claimed as the World

                                              Record, is it?  If not, send me a message at: This email address is being protected from spambots. You need JavaScript enabled to view it..

 

 

 

The method addresses the following problem that students frequently encounter when first confronted with assigining/determining Absolute Configuration (RS Configurations).

 

Beginning students have found it confusing and difficult to determine the 'Absolute Configuration' of a stereocenter when the lowest priority group is not directed

away. Students' attempts to mentally rotate the structure, in order to view the three highest priorities and thus determine 'Absolute Configuration', has been

described as traumatizing by students. The ability to mentally visualize and rotate a chemical structure takes practice, usually requiring a model. The authors

of every chemistry textbook, college and high school level, have written in their textbooks, practice with a model. All college chemistry professors and high school

chemistry teachers state to the beginning student, practice with a model. The model represents the tetrahedral shape, that of a carbon element with four different

elements bonded to it. The following method, is the first method to specifically mimic the tetrahedral shape of a stereocenter, as much as humanly possible. By

using a method that depicts (resembles) that of the tetrahedral shape, the student is provided with the best resources (method and model) to not only determine

the 'Absolute Configuration', yet to mentally conceptualize and rotate the structure. All the published methods using three fingers, hand and arms, do not take

into account that the method itself, should look like (mimic) the tetrahedral structure, as does the following method. In addition, students can use this method

while taking a quiz, exam or final exam.

 

McLaurin Method (aka: The Rock-On Method)


(The photo's are of my hand. I understand it is not the most aesthetically pleasing hand, yet I am looking for female volunteers.)

The method requires one hand, either the right or the left hand. The following Figures and examples will demonstrate the method using the right hand. The fingers

used with the method are the thumb, index finger, and the pinky finger. Students need to assign priority to the four groups bonded to the stereocenter (chiral

carbon) and then place the priorities to the corresponding fingers and the arm. The fingers (thumb, index finger, and the pinky finger) are outstretched from the

hand as illustrated in the following photo.


A. The fingers (digits) outstretched from the right hand.

 

 

Photo-111

                                                                                                                Figure-A

 

 

 

B. Examples Showing Relationship of Prioritized Groups to Arm and Fingers.


          The four examples illustrate the assignment of fingers and arm in relation to the prioritized structure. The four examples have one chiral carbon with four

different groups bonded to it. The four groups have been assigned a priority number according to the Cahn, Ingold, Prelog (CIP) sequence rules. The photo to

the right of each structure represents the starting position of the method and has the prioritized groups already assigned to the fingers and arm.

          The orientation of the structures in the following four examples is that so the starting position of the hand can easily be aligned with the 3-dimensional

structure.  The three dimensional structure is that of an upside down tripod with the thumb, index finger, and the pinky finger extended upwards and outward.

If one thought of making a fist with their hand and placing the hand in the place of the chiral carbon and extended the three fingers (the thumb, index finger,

and the pinky finger) upward and outward to represent methyl, bromine, and hydrogen respectively, as illustrated in Figure 1-b, then the viewer would find that

the three groups would be represented by the three fingers of the method. The arm would be the group extending downward, the chlorine. The priority sequence

determined for the four groups would be assigned to the corresponding fingers (thumb, index finger, and the pinky finger) and arm, thereby assigning the priority

sequence to the fingers and arm. Once the fingers and arm have an assigned priority sequence it is a matter of viewing the fingers and arm so that the 1-2-3

priority sequence can be observed by the viewer, of which, may require rotating the hand to view the 1-2-3 priority sequence, as illustrated Figures 1-b, 2-b, 3-b,

and 4-b. The following examples have been prioritized and the photo to the right of the structure has the fingers and arm already assigned a priority. Note: the

highest priority is represented by the number 1 and the lowest priority is represented with the numeral 4.

 

 

index.70

 

 

 

C. Viewing the 1-2-3 priority sequence of the hand model by the appropriate rotation of the hand, and determining the absolute configuration.


The following four examples illustrate the rotation of the hand to appropriately view the 1-2-3 priority sequence, with the lowest priority group, 4, directed away

from the viewer. The viewer then decides the direction of the priority sequence and determines the configuration of the stereocenter.

 

 

7th-Example

 

 

 

D. Using the McLaurin Method with a Fischer Projection.


When determining absolute configuration of Fischer Projections, the method requires the arm to always be designated as the bottom vertical group. The thumb

and index finger represent the groups to the left and right of the horizontal line, respectively. The pinky finger is designated as the vertical line above the

stereocenter and the hand mimics as the stereocenter (chiral carbon).

 

 

index.75

 

 

 

E. Determining the absolute configuration from Natta Projections.


When orientations that do not have a specific vertical and horizontal illustration of groups (for example, Fischer projections and three-dimensional structures) the

arm represents the bottom right group of the structure in question (the bottom right group is only for convenience: the method can determine the correct absolute

configuration when the arm represents any group). The arm is assigned to the bottom right group, therefore the pinky finger is assigned one of two positions

depending upon which group the arm represents. When the arm represents a group that lies on the plane of the paper the pinky finger always represents the

group that lies behind the plane of the paper (Figures 1-e and 2-e). When the arm represents the group that lies behind the plane of the paper and keeping the

fingers in the starting position as depicted in Photo-1, the pinky finger represents a group that lies on the plane of the paper (Figure 3-e). The thumb and the

index finger always represent groups that are left and right of each other, respectively.

 

 

index.72

 

 

Conclusion


The method described in this manuscript for assigning R,S-configuration, is the first method in which either hand can be used as a chiral template and which

makes use of the pinky finger.  By doing so, the method provides a clearer approximation of the actual three-dimensional shape of the tetrahedral geometry.

As demonstrated above, the method works equally well for either of the commonly used representations of the three-dimensional geometry: Fischer

Projections or Natta (wedge-dash) projections. Absolute configuration from the Fischer Projections is easily determined by the method without exchanging

groups as required by the exchange rules. The method facilitates the students' ability to successfully mentally rotate structures over a shorter period of time

by using a method that accounts for the tetrahedral shape. Students will always find conceptualizing spatial arrangement in three dimensions to be challenging.

The method described in this manuscript is a fast, comprehensive, reliable and a rapidly learned method for students to use whenever they need the

assistance of a 3-dimensional model.

 

Acknowledgments


I would like to acknowledge and thank the following for their time and effort: Denise for her help with her editing skills, Dr. and Mrs. Greever (Organic Chemists)

for making Organic Chemistry interesting and learnable when I was an undergraduate Organic Chemistry student in 1982-1983, the girls of Physical Therapy

(Zofia (Chairman of the Physical Therapy Department) Julie, Debbie, Sharon and Gloria) for making me realize my academic success and excellence is the

number one priority, aside from my nearly four (4) consecutive years of work with patients (not customers or clients) in the Physical Therapy Department

(while going to college full-time during the fall, spring and summer semesters, of 1980-1984). In addition, I would like to thank very much, the Chairman (Dean)

of the University of Mississippi Medical School, for providing me the inspiration and wisdom, at the end of every semester, to continue my undergraduate

studies to be a future physician, during the years of 1981-1984, in addition to the time Dr. Corbett (Dean of the Basic Sciences - Ross Medical School -

1994-1996) provided me, with my unannounced 20-30 minute visits to his office in the administration building, about every week or two, during my two years

of basic sciences in medical school. Dr. Corbett, for two years, never said he was too busy to talk with me. Dean Corbett and his wife, even asked me over

to their house, for supper many times! And last but least, a special thanks to Avril Lavigne for being instrumental and thus providing me with the key to the

development of this method and my parents for which none of this would have ever happened if it was not for their unyielding positive support,

that no other could equal.

 

Why was the Method developed?

When I took Organic Chemistry in 1982-83, I missed 80-85% of the questions related to determining the configuration(s) of enantiomers (that is,

RS configurations).  Of which, I still have my Organic Chemistry quizzes and exams from 1982-83. Twenty-one (21) years later, I wrote a review book on

Organic Chemistry and when I got to Stereochemistry, I remembered the trouble I had with determining/assigning RS configurations. As a result, I decided

to try to develop a method that would make it as easy as possible for students to determine/assign the correct configuration.

Most of my goals in the endeavor are as follows:

 

1. I decided that the following list contained most of the appropriate expectations of students.

     a. The method has to be as easy, fast and simple, as any method that has ever been published, if not better than all methods that have been published.

     b. The method should be used in the classroom during quizzes and exams, even on the medical college admission test (MCAT).

     c. The method should be as to scale as a 'Real' molecule (as similar to the model set as possible).

     d. The method should demonstrate the four (4) elements bonded to the chiral carbon.

     e. The method should help students develop their 'stereoperception' (the ability to visualize the 3-dimensional spatial arrangement of the molecule at and around

         the stereocenter and be able to mentally rotate the molecule), thus the use of the 'Pinky' finger, Index finger, Thumb and Arm, with the hand acting as the

         chiral carbon.

     f. The method should work with all molecular representations that show some 3-dimensional direction, for example, a dash or wedge, as well as, work with

        Fischer Projections.

     g. The method should only require the student to use one (1) hand for all the stereocenters of each chiral molecule, even if the molecule has two or more

         stereocenters.

     h. The method has to determine the correct configuration 100% of the time.

     i. The method should be easy to learn, use and remember.

     j. The method should be FREE for all students, faculty and others.

 

2. In addition, the method should not do the following.

     a. The method should not be a 'Trick of the Trade', for example, exchanging elements (groups). For this to happen in real life, bonds are broken and made,

         involving energy. In real life, this exchanging of elements (groups) does not occur. In addition, exchanging of elements does not help the student develop

         their 'Stereoperception', mental visualization of 3-dimensional spatial arrangement of the molecule(s) (chiral molecules).

     b. The method should not require two (2) hands to determine/assign an RS configuration, or multiple configurations on the same molecule (increases

         confusion).

     c. The method should not require the student to be a contortionist, in order to use the method.

     d. The method should not provide the opposite answer (aka: opposite configuration)!

     e. The method should not have been published in the Journal(s) by anyone, ever before.

 

*Historical Origin of Stereochemistry (1)

It was . . . Louis Pasteur's separation of a racemic form of tartaric acid in 1848 that led to the discovery of the phenomenon called enantiomerism. Pasteur,

consequently, is considered to be 'The Founder of the field of Stereochemistry'. Pasteur's discovery of enantiomerism and his demonstration that the optical

activity of the two forms of tartaric acid was a property of the molecules themselves led, in 1874, to the proposal of the tetrahedral structure of carbon by

van't Hoff and Le Bel.  In 1877, Hermann Kolbe (of the University of Leipzig), one of the most eminent organic chemists of the time, wrote the following:

Not long ago, I expressed the view that the lack of general education and of thorough training in chemistry was one of the causes of the deterioration of

chemical research in Germany . . . Will anyone to whom my worries seem exaggerated please read, if he can, a recent memoir by a Herr van't Hoff on

"The Arrangements of Atoms in Space," a document crammed to the hilt with the outpourings of a childish fantasy . . . This Dr. J. H. van't Hoff, employed

by the Veterinary College of Utrecth, has, so it seems, no taste for accurate chemical research. He finds it more convenient to mount his Pegasus

(evidently taken from the stables of the Veterinary College) and to announce how, on his bold flight to Mount Parnassus, he saw the atoms arranged in space. 

Kolbe, nearing the end of his career, was reacting to a publication of a 22-year-old Dutch scientist. This publication had appeared earlier, in September 1874,

and in it, van't Hoff had argued that the spatial arrangement of four groups around a central carbon atom is tetrahedral. A young French scientist, J. A. Le Bel,

independently put forth the same idea in a publication in November 1874.  Within 10 years after Kolbe's comments however, abundant evidence had accumulated

that substantiated the "childish fantasy" of van't Hoff. Later in his career (in 1901), and (also) for other work, van't Hoff was named the first recipient of the Nobel

Prize in Chemistry.  Together, the publications of van't Hoff and Le Bel marked an important turn in a field of study that is concerned with the structures of

molecules in three dimensions: 'Stereochemistry'

Literature

1. Solomons, T. W. G.; Fryhle, C. B. Organic Chemistry, 9th ed.; Wiley: New York, 2008; pp. 188-189, 214.

 

DIASTEREOMERS ENANTIOMERS
are Isomers are Isomers
same Molecular Formula same Molecular Formula
are Stereoisomers are Stereoisomers
same Connectivity same Connectivity
Identical with it's Mirror Image NOT identical with it's Mirror Image
Superposable on it's Mirror Image NON-Superposable on it's Mirror Image
Has a Plane of Symmetry NO Plane of Symmetry
Mirror Symmetric Dissymmetric
Achiral Chiral
NO Handedness Handedness
Different Chemical and Physical Properties Same Chemical and Physical Properties
NO Optical Activity Optically Active (aka: Optical Isomers)
NO Tetrahedral Center Tetrahedral Center
Could be sp3 hybridized, yet Not Tetrahedral sp3 Hybridized (Chiral carbon is sp3)
More than 1 Stereocenter, could be an Enantiomer When a Stereocenter exists, it is an Enantiomer
EZ, Cis-Trans or Syn-Anti nomenclature RS nomenclature (RS or Absolute Configuration)
Cis Isomers have a Dipole Moment (therefore, Polar) D, L or d-l nomenclature (outdated)
Trans Isomers do NOT have a Dipole Moment (therefore, Non-Polar)  

 

 

 Stereochemistry Glossary 

 

1800 Rotation Conformational Isomers Fischer Projection(s) Molecular Formula Regioselective Reaction Stereogenic Carbon
Achiral Connectivity Geometric Isomers Non-Racemic Regiospecific Reaction Stereoisomers
Asymmetric Constitutional Isomers Handedness Nonsuperposable Resolution Stereoselective Reaction
Chemical Properties Diastereomers Horizontal Flip Optical Isomers Retention Stereospecific Reaction
Chiral Dissymmetric Interconvert Optically Active Separation Methods Structural Isomers
Chirality Empirical Formula Inversion Physical Properties a. Chromatography Superposable
Chirotropic Enantioenriched Isomerism Plane of Symmetry b. Crystallization Syn-Anti Nomenclature
Chiral Elements/Groups Enantiomers Isomers Prochiral c. Distillation Tetrahedral
Cis-Trans Isomers Enantiopure Meso Racemates Spatial Arrangement Tetrahedral Stereocenter
Cis-Trans Nomenclature Epimer Mirror Image Racemic Stereocenter Vertical Flip
Configurational Isomers EZ Nomenclature Mirror Symmetric Racemization Stereochemistry Coincide

 

 

Future Chemistry and Organic Chemistry Websites

StereoChemistry.net
StereoIsomer.com
StereoIsomers.net

ChemistryTerminology.com

 

 

NOTE: This method is copyrighted with the Library of Congress located in an Organic Chemistry Review Book, I wrote years ago.

 

Written permission needs to be obtained from
Tim McLaurin for reproduction and duplication.

Tim McLaurin is the Webmaster and Web owner.

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