5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (2024)

5.5 • Sequence Rules for Specifying Configuration

Structural drawings provide a visual representation of stereochemistry, but a written method for indicating the three-dimensional arrangement, or configuration, of substituents at a chirality center is also needed. The method used a set of sequence rules to rank the four groups attached to the chirality center and then looks at the handedness with which those groups are attached. Called the Cahn–Ingold–Prelog rules after the chemists who proposed them, the sequence rules are as follows:

RULE 1
Look at the four atoms directly attached to the chirality center, and rank them according to atomic number. The atom with the highest atomic number has the highest ranking (first), and the atom with the lowest atomic number (usually hydrogen) has the lowest ranking (fourth). When different isotopes of the same element are compared, such as deuterium (2H) and protium (1H), the heavier isotope ranks higher than the lighter isotope. Thus, atoms commonly found in organic compounds have the following order.

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RULE 2
If a decision can’t be reached by ranking the first atoms in the substituent, look at the second, third, or fourth atoms away from the chirality center until the first difference is found. A −CH2CH3 substituent and a −CH3 substituent are equivalent by rule 1 because both have carbon as the first atom. By rule 2, however, ethyl ranks higher than methyl because ethyl has a carbon as its highest second atom, while methyl has only hydrogen as its second atom. Look at the following pairs of examples to see how the rule works:

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RULE 3
Multiple-bonded atoms are equivalent to the same number of single-bonded atoms. For example, an aldehyde substituent (–CH═O–CH═O), which has a carbon atom doubly bonded to one oxygen, is equivalent to a substituent having a carbon atom singly bonded to two oxygens:

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (3)

As further examples, the following pairs are equivalent:

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Having ranked the four groups attached to a chiral carbon, we describe the stereochemical configuration around the carbon by orienting the molecule so that the group with the lowest ranking (4) points directly away from us. We then look at the three remaining substituents, which now appear to radiate toward us like the spokes on a steering wheel (Figure 5.8). If a curved arrow drawn from the highest to second-highest to third-highest ranked substituent (1 → 2 → 3) is clockwise, we say that the chirality center has the R configuration (S for the Latin rectus, meaning “right”). If an arrow from 1 → 2 → 3 is counterclockwise, the chirality center has the S configuration (Latin sinister, meaning “left”). To remember these assignments, think of a car’s steering wheel when making a Right (clockwise) turn.

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Figure 5.8 Assigning R and S configurations to chirality centers. When the molecule is oriented so that the lowest-ranked group (4) is toward the rear, the remaining three groups radiate toward the viewer like the spokes of a steering wheel. If the direction of travel 123 is clockwise (right turn), the center has the R configuration. If the direction of travel 123 is counterclockwise (left turn), the center is S.

Look at (−)-lactic acid in Figure 5.9 for an example of how to assign configuration. Sequence rule 1 says that −OH is ranked 1 and −H is ranked 4, but it doesn’t allow us to distinguish between −CH3 and −CO2H because both groups have carbon as their first atom. Sequence rule 2, however, says that −CO2H ranks higher than −CH3 because O (the highest second atom in −CO2H) outranks H (the highest second atom in −CH3). Now, turn the molecule so that the fourth-ranked group (−H) is oriented toward the rear, away from the observer. Since a curved arrow from 1 (−OH) to 2 (−CO2H) to 3 (−CH3) is clockwise (right turn of the steering wheel), (−)-lactic acid has the R configuration. Applying the same procedure to (+)-lactic acid leads to the opposite assignment.

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Figure 5.9 Assigning configuration to (a) (R)-(−)-lactic acid and (b) (S)-(+)-lactic acid.

Further examples are provided by naturally occurring (−)-glyceraldehyde and (+)-alanine, which both have the S configuration as shown in Figure 5.10. Note that the sign of optical rotation, (+) or (−), is not related to the R,S designation. (S)-Glyceraldehyde happens to be levorotatory (−), and (S)-alanine happens to be dextrorotatory (+). There is no simple correlation between R,S configuration and direction or magnitude of optical rotation.

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Figure 5.10 Assigning configuration to (a) (−)-glyceraldehyde. (b) (+)-alanine. Both happen to have the S configuration, although one is levorotatory and the other is dextrorotatory.

One additional point needs to be mentioned—the matter of absolute configuration. How do we know that the assignments of R and S configuration are correct in an absolute sense, rather than a relative, sense? Since there is no correlation between the R,S configuration and the direction or magnitude of optical rotation, how do we know that the R configuration belongs to the levorotatory enantiomer of lactic acid? This difficult question was finally solved in 1951, when an X-ray diffraction method was found for determining the absolute spatial arrangement of atoms in a molecule. Based on those results, we can say with certainty that the R,S conventions are correct.

Worked Example 5.3

Assigning Configuration to Chirality Centers

Orient each of the following drawings so that the lowest-ranked group is toward the rear, and then assign R or S configuration to each:

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Strategy

It takes practice to be able to visualize and orient a chirality center in three dimensions. You might start by indicating where the observer must be located—180° opposite the lowest-ranked group. Then imagine yourself in the position of the observer, and redraw what you would see.

Solution

In (a), you would be located in front of the page toward the top right of the molecule, and you would see group 2 to your left, group 3 to your right, and group 1 below you. This corresponds to an R configuration.

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (9)

In (b), you would be located behind the page toward the top left of the molecule from your point of view, and you would see group 3 to your left, group 1 to your right, and group 2 below you. This also corresponds to an R configuration.

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (10)

Worked Example 5.4

Drawing the Three-Dimensional Structure of a Specific Enantiomer

Draw a tetrahedral representation of (R)-2-chlorobutane.

Strategy

Begin by ranking the four substituents bonded to the chirality center: (1) −Cl, (2) −CH2CH3, (3) −CH3, (4) −H. To draw a tetrahedral representation of the molecule, orient the lowest-ranked group (−H) away from you and imagine that the other three groups are coming out of the page toward you. Then, place the remaining three substituents such that the direction of travel 1 → 2 → 3 is clockwise (right turn), and tilt the molecule toward you to bring the rear hydrogen into view. Using molecular models is a real help in working problems of this sort.

Solution

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (11)

Problem 5-7

Which member in each of the following sets ranks higher?

(a)

−H or −Br

(b)

−Cl or −Br

(c)

−CH3 or −CH2CH3

(d)

−NH2 or −OH

(e)

−CH2OH or −CH3

(f)

−CH2OH or −CH =O

Problem 5-8

Rank each of the following sets of substituents:

(a)

−H, −OH, −CH2CH3, −CH2CH2OH

(b)

−CO2H, −CO2CH3, −CH2OH, −OH

(c)

−CN, −CH2NH2, −CH2NHCH3, −NH2

(d)

−SH, −CH2SCH3, −CH3, −SSCH3

Problem 5-9

Orient each of the following drawings so that the lowest-ranked group is toward the rear, and then assign R or S configuration:

(a)

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(b)

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(c)

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (14)

Problem 5-10

Assign R or S configuration to the chirality center in each of the following molecules:

(a)

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (15)

(b)

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (16)

(c)

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (17)

Problem 5-11

Draw a tetrahedral representation of (S)-2-pentanol (2-hydroxypentane).

Problem 5-12

Assign R or S configuration to the chirality center in the following molecular model of the amino acid methionine (blue = N, yellow = S):

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (18)

5.5 Sequence Rules for Specifying Configuration - Organic Chemistry | OpenStax (2024)

FAQs

What are sequence rules in organic chemistry? ›

The Sequence Rule for Assignment of Configurations to Chiral Centers. Assign sequence priorities to the four substituents by looking at the atoms attached directly to the chiral center. 1. The higher the atomic number of the immediate substituent atom, the higher the priority. For example, H– < C– < N– < O– < Cl–.

What is the Cip rule in organic chemistry? ›

For double bonded molecules, Cahn–Ingold–Prelog priority rules (CIP rules) are followed to determine the priority of substituents of the double bond.

What are the priority rules for R and S configuration? ›

If the arrow points clockwise, the compound is R. If the arrow points in a counterclockwise direction, the chiral carbon is S. When we draw our arrows, we can see that the compound on the left is S and the one on the right is R.

How to determine R and S configuration? ›

When using a model, make sure the lowest priority is pointing away from you. Then determine the direction from the highest priority substituent to the lowest: clockwise (R) or counterclockwise (S).

What are the four sequencing rules? ›

studies, the following four sequencing rules are included: (1) Shortest processing time rule (2) Slack per operation rule (3) First-in, first-out rule (4) Due date rule.

What are the rules for sequence? ›

Players compete to fill the entire board with complete sequences of five chips (in each player's preferred color). Keep score of one point per sequence created. Different from standard game play, chips from completed sequences may be removed to prevent opponents from scoring.

What is an example of a CIP sequence rule? ›

For example, if an atom A is double-bonded to an atom B, then A is treated as singly-bonded to two atoms. The multiple-bonded atoms are counted twice for double bond and thrice for triple bond. Thus, \[-COOH\] is given priority over \[ - CHO\] .

What are the main requirements of the CIP rule? ›

The CIP Rule requires a bank to implement a program that includes risk-based verification procedures that enable the bank to form a reasonable belief that it knows the true identity of its customers.

What is the CIP system of configuration? ›

The Cahn-Ingold-Prelog priority rules, CIP system or CIP conventions are a set of rules used in organic chemistry to name the stereoisomers of a molecule. A molecule may contain any number of stereocenters and any number of double bonds, and each gives rise to two possible configurations.

What is the trick for R and S configuration? ›

It is important to note that if the lowest priority is on the dash line meaning if it goes backwards (behind the plane) then in clockwise rotation and configuration is R and for anticlockwise the configuration is S and if the lowest priority group is on the wedge line meaning if it comes forward (in front of the plane) ...

What are the rules for R and S in chemistry? ›

Draw an arrow starting from priority one and going to priority two and then to priority 3: If the arrow goes clockwise, like in this case, the absolute configuration is R. As opposed to this, if the arrow goes counterclockwise then the absolute configuration is S.

What is the thumb rule for R and S configuration? ›

There are two general methods for determining the R- or S-configuration: The hand method and the clock method. The hand method points the thumb in the direction of the atom of lowest priority. The curled fingers point in the direction of descending priority of the remaining atoms.

What do s and r mean in organic chemistry? ›

The R means Rectus in Latin (means right) and S means Sinister in Latin (means Left). Molecules that rotate the plane polarised light to right is said as R isomer. Molecule that rotate the plane polarised light to left is said as S isomer.

How do you separate R and S? ›

Chromatography can also be used to separate a racemic mixture. Using chiral column chromatography or gas chromatography, a chiral stationary phase that will only bind to the R or S confirmation is used to isolate one of the confirmations. This can be used with a suitable solvent to resolve the racemic mixture.

Does CL or BR have higher priority? ›

So, following naming, bromine is named first than chlorine and given higher priority. Also, the atomic number of bromine is higher than chlorine, so it is numbered first while writing the E-Z configuration.

How do you explain the rule of a sequence? ›

In an arithmetic sequence, each successive term is obtained by adding the common difference to its preceding term. In a geometric sequence, each successive term is obtained by multiplying the common ratio to its preceding term.

How is a rule defined for a sequence? ›

A pattern rule is a mathematical relationship used to find the value of each term in a sequence. To describe certain sequences, a pattern rule can be established. This is an algebraic equation that enables you to quickly find the value of a term in a sequence using its rank.

What is the rule of number sequencing? ›

Number sequences are sets of numbers that follow a pattern or a rule. If the rule is to add or subtract a number each time, it is called an arithmetic sequence. If the rule is to multiply or divide by a number each time, it is called a geometric sequence. Each number in a sequence is called a term.

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