The Stereochemistry: Theory and Fundamentals

Stereochemistry: Detailed Notes and Questions & Answers

These notes delve into the fundamental principles of stereochemistry, which is the study of the three-dimensional arrangement of atoms in molecules and how this arrangement affects their properties and reactions.

Part 1: Detailed Notes on Stereochemistry

1. Isomers

Isomers are different compounds that have the same molecular formula. There are two main types:

  • Constitutional (Structural) Isomers:
    • Differ in the connectivity (bonding sequence) of their atoms.
    • Have different IUPAC names, different functional groups, or different positions of functional groups.
    • Example: n-butane (linear) and isobutane (branched) both have the formula C$4H{10}$.
  • Stereoisomers:
    • Have the same connectivity of atoms but differ in the spatial arrangement of their atoms.
    • Cannot be interconverted without breaking and reforming bonds (except for conformational isomers which are not “true” isomers as they interconvert readily).
    • Conformational Isomers (Conformers):
      • Stereoisomers that can be interconverted by simple rotation around single bonds.
      • Example: Staggered and eclipsed conformations of ethane.
      • They are typically not isolable as distinct compounds at room temperature due to rapid interconversion.
    • Configurational Isomers:
      • Stereoisomers that can only be interconverted by breaking and reforming chemical bonds.
      • These are the “true” stereoisomers.
      • They include enantiomers and diastereomers.

2. Chirality

Chirality (from Greek cheir, meaning “hand”) is the property of an object (or molecule) that is non-superimposable on its mirror image. Just as a left hand cannot be superimposed perfectly on a right hand, a chiral molecule cannot be superimposed on its mirror image.

  • Chiral Molecule: A molecule that is non-superimposable on its mirror image. Chiral molecules are also referred to as optically active.
  • Achiral Molecule: A molecule that is superimposable on its mirror image. Achiral molecules are optically inactive.
    • Achiral molecules typically possess elements of symmetry, such as a plane of symmetry (an imaginary plane that divides the molecule into two halves that are mirror images of each other) or a center of inversion.
  • Chiral Center (Stereocenter or Asymmetric Carbon):
    • The most common source of chirality in organic molecules.
    • Defined as a carbon atom bonded to four different groups.
    • Example: In 2-butanol (CH$_3CH(OH)CH_2CH_3$), the carbon bonded to -OH, -H, -CH$_3$, and -CH$_2CH_3$ is a chiral center.

3. Types of Configurational Stereoisomers

  • Enantiomers:
    • Stereoisomers that are non-superimposable mirror images of each other.
    • They always occur in pairs.
    • Must have at least one chiral center.
    • Identical Physical Properties: Melting point, boiling point, density, refractive index, solubility in achiral solvents.
    • Differing Properties:
      • They rotate the plane of plane-polarized light to the same magnitude but in opposite directions (see Optical Activity below).
      • They react differently with other chiral molecules (e.g., enzymes, chiral reagents).
  • Diastereomers:
    • Stereoisomers that are not mirror images of each other.
    • Occur in molecules with two or more chiral centers.
    • Different Physical and Chemical Properties: Melting point, boiling point, density, solubility, and reactivity are all generally different. This allows them to be separated by conventional methods (e.g., distillation, chromatography).
    • Example: (2R,3R)-2,3-dibromobutane and (2R,3S)-2,3-dibromobutane are diastereomers. (The mirror image of (2R,3R) is (2S,3S), which is its enantiomer).
  • Meso Compounds:
    • A special type of achiral compound that contains two or more chiral centers.
    • It is achiral because it possesses an internal plane of symmetry (or sometimes a center of inversion), making the molecule superimposable on its own mirror image.
    • Optically inactive (does not rotate plane-polarized light) because the rotation caused by one chiral center is cancelled out by the opposite rotation of another internal chiral center.
    • Example: Meso-tartaric acid.
  • Number of Stereoisomers: For a compound with ‘n’ chiral centers, the maximum number of possible stereoisomers is 2$^n$. This number can be less if meso compounds exist.

4. Optical Activity

Optical Activity is the ability of a chiral substance to rotate the plane of plane-polarized light.

  • Plane-polarized light: Light in which the oscillations of the electromagnetic field are confined to a single plane.
  • Polarimeter: An instrument used to measure the rotation of plane-polarized light by an optically active substance.
  • Dextrorotatory (+ or d-): Rotates the plane of polarized light clockwise.
  • Levorotatory (- or l-): Rotates the plane of polarized light counter-clockwise.
  • Observed Rotation (αobs​): The measured rotation in degrees.
  • Specific Rotation ([$ \alpha $]): A standardized physical constant for a pure chiral substance, independent of concentration and path length. It allows for comparison of optical activities.
    [α]λT​=c×lαobs​​ Where:
    • T is the temperature in degrees Celsius.
    • λ is the wavelength of light used (often the sodium D-line, 589 nm).
    • αobs​ is the observed rotation in degrees.
    • c is the concentration of the sample in g/mL.
    • l is the path length of the sample cell in decimeters (dm).
  • Racemic Mixture (Racemate):
    • A 50:50 mixture of two enantiomers.
    • Optically inactive because the equal and opposite rotations of the two enantiomers cancel each other out.
  • Resolution:
    • The process of separating a racemic mixture into its pure enantiomers. This typically involves converting the enantiomers into diastereomers (by reacting with a chiral auxiliary), separating the diastereomers (which have different physical properties), and then regenerating the pure enantiomers.

5. Configuration (R/S System – Cahn-Ingold-Prelog Rules)

The Cahn-Ingold-Prelog (CIP) Rules (also known as the R/S system) provide an unambiguous way to assign the absolute configuration (spatial arrangement) of groups around a chiral center.

  1. Assign Priorities to Groups:
    • Rank the four groups attached to the chiral center based on the atomic number of the atom directly bonded to the chiral center. Higher atomic number means higher priority (Priority 1 = highest, Priority 4 = lowest).
    • If there’s a tie at the first atom, move outwards to the next atoms in each group until the first point of difference.
    • Isotopes: Higher mass number gets higher priority (e.g., Deuterium (D) > Hydrogen (H)).
    • Multiple Bonds: Treat double bonds as if the atoms are duplicated, and triple bonds as if they are triplicated.
      • Example: C=O is treated as C-O and C-O (the carbon is bonded to two oxygens, and the oxygen is bonded to two carbons).
  2. Orient the Molecule:
    • Mentally orient the molecule so that the lowest priority group (Priority 4) is pointing away from you (typically represented by a dashed wedge or directly down in a Newman projection/Fischer projection when converted).
  3. Trace Path (1 to 2 to 3):
    • Draw an imaginary arc or trace a path from the highest priority group (Priority 1) to the second highest (Priority 2), and then to the third highest (Priority 3).
  4. Assign R or S:
    • If the path is clockwise (to the right), the configuration is R (Rectus).
    • If the path is counter-clockwise (to the left), the configuration is S (Sinister).
    • Special Case (Lowest Priority in Front): If the lowest priority group (Priority 4) is pointing towards you (on a solid wedge), assign R/S as usual, then reverse the result. (e.g., if it appears R, it’s actually S).

6. Fischer Projections

Fischer Projections are a simplified two-dimensional way to represent the three-dimensional structures of chiral molecules, especially those with multiple chiral centers (e.g., carbohydrates, amino acids).

  • The chiral carbon is at the intersection of horizontal and vertical lines.
  • Horizontal lines: Represent bonds coming out of the page (towards the viewer).
  • Vertical lines: Represent bonds going into the page (away from the viewer).
  • The main carbon chain is typically oriented vertically, with the most oxidized carbon atom at the top.
  • Assigning R/S from Fischer: If the lowest priority group is on a vertical line, assign directly (clockwise = R, counter-clockwise = S). If the lowest priority group is on a horizontal line, assign and then reverse the result.

7. Stereoselectivity in Reactions

Many organic reactions exhibit stereoselectivity, meaning they preferentially form one stereoisomer over others.

  • S$_N$2 Reactions:
    • Always proceed with inversion of configuration at the chiral center. This is known as Walden inversion. The nucleophile attacks from the backside, directly opposite to the leaving group’s departure, leading to a “flipping” of the stereochemistry.
    • If a chiral starting material with a specific configuration (e.g., (R)) undergoes S$_N$2, the product will have the inverted configuration (e.g., (S)).
  • S$_N$1 Reactions:
    • Typically lead to racemization (formation of a racemic mixture) if the reaction occurs at a chiral center.
    • The carbocation intermediate formed in the rate-determining step is planar. The nucleophile can attack this planar carbocation from either face with approximately equal probability, leading to a 50:50 mixture of the two enantiomers (racemic mixture), which is optically inactive.
  • Electrophilic Addition to Alkenes (e.g., Halogenation with Br$_2$/Cl$_2$):
    • Often exhibits anti-addition stereospecificity.
    • Mechanism involves the formation of a cyclic intermediate (e.g., a bromonium ion). The second attacking group (e.g., bromide ion) must attack from the face opposite to the already-formed cyclic intermediate, leading to the anti-product.
    • Example: Addition of Br$_2$ to cis-2-butene yields racemic 2,3-dibromobutane (mixture of (2R,3S) and (2S,3R)). Addition of Br$_2$ to trans-2-butene yields meso-2,3-dibromobutane.
  • Dihydroxylation of Alkenes:
    • Syn-dihydroxylation: Both new hydroxyl (-OH) groups add to the same face of the double bond. Reagents include osmium tetroxide (OsO$_4$) followed by sodium bisulfite (NaHSO$_3$) or cold, dilute potassium permanganate (KMnO$_4$).
    • Anti-dihydroxylation: The two new hydroxyl groups add to opposite faces of the double bond. This is typically achieved by first forming an epoxide (using a peroxy acid like m-CPBA) and then acid-catalyzed ring opening with water.

Part 2: Questions and Answers

Section A: Conceptual / Explanatory Questions (10 Questions)

  1. Q: Distinguish between constitutional isomers and stereoisomers. Provide an example for each. A: Constitutional isomers have the same molecular formula but differ in the connectivity of their atoms (how the atoms are bonded together). Example: n-pentane and isopentane (both C$5H{12}).∗∗Stereoisomers∗∗havethesamemolecularformulaandthesameconnectivity,butdifferinthespatialarrangementoftheiratoms.Example:(R)−2−butanoland(S)−2−butanol(enantiomers,C4H{10}$O).
  2. Q: What is a chiral center? How many chiral centers does 2,3-dichlorobutane have, and what is its maximum number of stereoisomers? A: A chiral center is typically a carbon atom bonded to four different groups. 2,3-Dichlorobutane has two chiral centers (C2 and C3). The maximum number of stereoisomers for a compound with ‘n’ chiral centers is 2ⁿ. So, for 2,3-dichlorobutane, the maximum is 2² = 4 stereoisomers.
  3. Q: Explain why a meso compound is optically inactive, despite possessing chiral centers. A: A meso compound is optically inactive because it possesses an internal plane of symmetry (or a center of inversion). This internal symmetry causes the rotation of plane-polarized light by one chiral center to be exactly cancelled out by the opposite rotation of another equivalent chiral center within the same molecule, resulting in a net observed rotation of zero.
  4. Q: Describe the physical and chemical properties that differentiate enantiomers from diastereomers. A:
    • Enantiomers: Have identical physical properties (e.g., melting point, boiling point, density, refractive index, solubility in achiral solvents). Their chemical properties are also identical when reacting with achiral reagents. However, they differ in their interaction with plane-polarized light (rotate equally but in opposite directions) and their reactivity with other chiral molecules (e.g., enzymes, chiral reagents).
    • Diastereomers: Have different physical properties (e.g., different melting points, boiling points, densities, solubilities). They also have different chemical properties and react differently with both chiral and achiral reagents.
  5. Q: What is a racemic mixture, and what is its optical property? How can one be separated into pure enantiomers? A: A racemic mixture (or racemate) is a 50:50 mixture of two enantiomers. It is optically inactive because the equal and opposite optical rotations of the individual enantiomers cancel each other out. A racemic mixture can be separated into pure enantiomers through a process called resolution. This typically involves reacting the racemic mixture with a chiral resolving agent to form a pair of diastereomeric salts, which can then be separated by fractional crystallization due to their different physical properties. Once separated, the pure enantiomers are regenerated from their diastereomeric salts.
  6. Q: Outline the general procedure for assigning R or S configuration using the Cahn-Ingold-Prelog (CIP) rules. A:
    1. Prioritize: Assign priorities (1=highest, 4=lowest) to the four groups attached to the chiral center based on atomic number of the directly bonded atoms.
    2. Orient: Orient the molecule in space so that the lowest priority group (4) points away from you (on a dashed wedge).
    3. Trace: Draw an arc from priority 1 to priority 2 to priority 3.
    4. Assign: If the arc is clockwise, the configuration is R. If the arc is counter-clockwise, the configuration is S. If the lowest priority group was inadvertently pointed towards you, assign and then reverse the result.
  7. Q: Explain the concept of “inversion of configuration” in the S$_N2reactionmechanism.∗∗A:∗∗Inversionofconfiguration(Waldeninversion)inanS_N$2 reaction means that if the reaction occurs at a chiral center, the spatial arrangement of the groups around that carbon is reversed. This happens because the nucleophile attacks the carbon atom from the side opposite to the departing leaving group. This “backside attack” causes the other three groups attached to the carbon to flip to the other side, much like an umbrella turning inside out in a strong wind.
  8. Q: How does the stereochemical outcome of an S$_N1reactiondifferfromanS_N$2 reaction at a chiral center? Justify your answer based on the reaction mechanisms. A: At a chiral center:
    • S$_N$2 reactions lead to complete inversion of configuration due to the concerted backside attack of the nucleophile.
    • S$_N$1 reactions typically lead to racemization (formation of a racemic mixture). This is because the S$_N$1 mechanism involves a planar carbocation intermediate. Once formed, the nucleophile can attack this planar intermediate from either face with approximately equal probability, leading to the formation of both enantiomers in roughly equal amounts.
  9. Q: Differentiate between syn-addition and anti-addition in alkene reactions. Provide a reaction example for each. A:
    • Syn-addition: Both new groups add to the same face of the carbon-carbon double bond. An example is the dihydroxylation of an alkene using osmium tetroxide (OsO$_4$) followed by a reducing agent like NaHSO$_3$/H$_2$O.
    • Anti-addition: The two new groups add to opposite faces of the carbon-carbon double bond. An example is the halogenation of an alkene with Br$_2$ or Cl$_2$, which proceeds through a cyclic halonium ion intermediate, forcing the second halide to attack from the opposite side.
  10. Q: What is a Fischer projection, and what do its horizontal and vertical lines represent in terms of 3D orientation? A: A Fischer projection is a two-dimensional representation used to depict the three-dimensional structure of chiral molecules, especially those with multiple chiral centers (like sugars). In a Fischer projection:
    • Horizontal lines represent bonds coming out of the page (towards the viewer).
    • Vertical lines represent bonds going into the page (away from the viewer). The main carbon chain is usually drawn vertically, with the most oxidized carbon at the top.

Section B: Multiple Choice Questions (25 Questions)

  1. Q: Which term describes stereoisomers that are non-superimposable mirror images? A) Diastereomers B) Constitutional Isomers C) Enantiomers D) Conformers A: C) Enantiomers
  2. Q: A carbon atom bonded to four different groups is called a: A) Alkene carbon B) Carbonyl carbon C) Chiral center D) Methylene carbon A: C) Chiral center
  3. Q: What property do a pair of enantiomers share? A) The same direction of rotation of plane-polarized light. B) Identical boiling points. C) Identical reactivity with a chiral enzyme. D) Different solubilities in an achiral solvent. A: B) Identical boiling points.
  4. Q: A compound with chiral centers that is optically inactive due to an internal plane of symmetry is a: A) Racemic mixture B) Diastereomer C) Meso compound D) Conformational isomer A: C) Meso compound
  5. Q: For a molecule with ‘n’ chiral centers, the maximum number of stereoisomers is typically: A) n B) 2n C) n! D) 2^n A: D) 2^n
  6. Q: The Cahn-Ingold-Prelog (CIP) rules are used to assign: A) Zaitsev products B) Markovnikov orientation C) R/S configuration D) Relative stability of carbocations A: C) R/S configuration
  7. Q: A 50:50 mixture of two enantiomers is called a: A) Meso mixture B) Diastereomeric mixture C) Racemic mixture D) Optically pure solution A: C) Racemic mixture
  8. Q: Stereoisomers that are not mirror images of each other are classified as: A) Enantiomers B) Constitutional isomers C) Diastereomers D) Conformers A: C) Diastereomers
  9. Q: Which instrument is used to measure the rotation of plane-polarized light? A) Spectrophotometer B) Mass spectrometer C) Polarimeter D) Chromatograph A: C) Polarimeter
  10. Q: If a chiral compound rotates plane-polarized light counter-clockwise, it is denoted as: A) (R) B) (S) C) Dextrorotatory (+) D) Levorotatory (-) A: D) Levorotatory (-)
  11. Q: Which of the following is an example of a constitutional isomer of n-hexane? A) Cyclohexane B) 2-methylpentane C) (R)-3-methylpentane D) Hex-1-ene A: B) 2-methylpentane
  12. Q: The process of separating a racemic mixture into its individual enantiomers is known as: A) Racemization B) Inversion C) Resolution D) Epimerization A: C) Resolution
  13. Q: Consider (2R,3R)-2,3-dibromopentane. Its enantiomer would be: A) (2R,3S)-2,3-dibromopentane B) (2S,3R)-2,3-dibromopentane C) (2S,3S)-2,3-dibromopentane D) Meso-2,3-dibromopentane A: C) (2S,3S)-2,3-dibromopentane
  14. Q: Which of the following is a necessary condition for a molecule to be chiral? A) It must contain a double bond. B) It must have at least one plane of symmetry. C) It must be superimposable on its mirror image. D) It must not be superimposable on its mirror image. A: D) It must not be superimposable on its mirror image.
  15. Q: How many chiral centers does 2-chlorobutane have? A) 0 B) 1 C) 2 D) 3 A: B) 1
  16. Q: Cis-1,3-dimethylcyclobutane and trans-1,3-dimethylcyclobutane are examples of: A) Enantiomers B) Diastereomers C) Constitutional isomers D) Identical compounds A: B) Diastereomers
  17. Q: In a Fischer projection, what do the vertical lines represent? A) Bonds pointing out of the page. B) Bonds pointing into the page. C) Bonds in the plane of the page. D) Bonds rotating freely. A: B) Bonds pointing into the page.
  18. Q: If the specific rotation of a pure enantiomer is +25°, what is the specific rotation of its mirror image? A) +25° B) -25° C) 0° D) Cannot be determined A: B) -25°
  19. Q: Which statement is true about meso compounds? A) They are optically active. B) They always have an odd number of chiral centers. C) They are superimposable on their mirror image. D) They are separated from their enantiomers by resolution. A: C) They are superimposable on their mirror image.
  20. Q: The reaction of a chiral molecule with an achiral reagent typically produces: A) A single enantiomer B) A single diastereomer C) A racemic mixture of products D) A mixture of diastereomers if new chiral centers are formed A: D) A mixture of diastereomers if new chiral centers are formed
  21. Q: Which type of reaction typically results in inversion of configuration at a chiral center? A) S$_N1B)E1C)S_N2D)E2∗∗A:∗∗C)S_N$2
  22. Q: The addition of Br$_2$ to cis-2-butene primarily yields what stereochemical outcome? A) A meso compound B) A racemic mixture C) A single enantiomer D) A single diastereomer A: B) A racemic mixture (due to anti-addition to a cis alkene)
  23. Q: Which of the following conditions might lead to racemization of a chiral alkyl halide? A) Reaction with a strong nucleophile in a polar aprotic solvent. B) Reaction via an S$_N1mechanism.C)ReactionviaanE2mechanism.D)Reactionwithastrongbaseinanon−polarsolvent.∗∗A:∗∗B)ReactionviaanS_N$1 mechanism.
  24. Q: Dihydroxylation of an alkene using OsO$_4$ followed by NaHSO$_3$/H$_2$O is an example of: A) Anti-addition B) Syn-addition C) Markovnikov addition D) Elimination A: B) Syn-addition
  25. Q: If the lowest priority group in a chiral center is pointing towards you (on a solid wedge) in a 3D representation, and tracing from P1-P2-P3 goes clockwise, what is the actual configuration? A) R B) S C) Cannot be determined D) It’s a meso compound A: B) S (Assign R, then reverse because the lowest priority group is in front)

Section C: Comprehensive Answer Key and Explanations

Section A: Conceptual / Explanatory Questions – Explanations

  1. Q: Distinguish between constitutional isomers and stereoisomers. Provide an example for each. A: Constitutional isomers have the same molecular formula but differ in the connectivity of their atoms (the order in which they are bonded). For example, ethanol (CH$_3CH_2OH)anddimethylether(CH_3OCH_3$) are constitutional isomers; both are C$_2H_6Obuthavedifferentbondingarrangements.∗∗Stereoisomers∗∗havethesamemolecularformulaandthesameconnectivityofatoms,buttheydifferinthespatialarrangementoftheiratoms.Forinstance,cis−2−buteneandtrans−2−butene(bothC_4H_8$) are stereoisomers because the methyl groups are positioned differently in space relative to the double bond.
  2. Q: What is a chiral center? How many chiral centers does 2,3-dichlorobutane have, and what is its maximum number of stereoisomers? A: A chiral center is a carbon atom bonded to four different groups. For 2,3-dichlorobutane, both C2 and C3 are chiral centers:
    • C2 is bonded to H, Cl, CH$_3$, and -CH(Cl)CH$_3$.
    • C3 is bonded to H, Cl, CH$_3$, and -CH(Cl)CH$_3$. So, it has two chiral centers. The maximum number of stereoisomers for a compound with ‘n’ chiral centers is 2ⁿ. Therefore, for 2,3-dichlorobutane, the maximum is 2² = 4 stereoisomers. (Note: One of these is a meso compound, reducing the actual number of distinct stereoisomers to 3).
  3. Q: Explain why a meso compound is optically inactive, despite possessing chiral centers. A: A meso compound is optically inactive (does not rotate plane-polarized light) because it contains an internal plane of symmetry. This plane divides the molecule into two halves that are mirror images of each other. The rotation of plane-polarized light caused by one chiral center in the molecule is exactly cancelled out by the equal and opposite rotation caused by the other chiral center(s) within the same molecule. This internal compensation leads to a net observed rotation of zero.
  4. Q: Describe the physical and chemical properties that differentiate enantiomers from diastereomers. A:
    • Enantiomers: Have identical physical properties (e.g., melting point, boiling point, density, refractive index, solubility in achiral solvents). Their chemical properties are also identical when reacting with achiral reagents. However, they differ in their interaction with plane-polarized light (rotate equally but in opposite directions) and their reactivity with other chiral molecules (e.g., enzymes, chiral drugs, or chiral reagents).
    • Diastereomers: Have different physical properties (e.g., different melting points, boiling points, densities, solubilities). This means they can be separated by standard physical methods (like distillation, recrystallization, or chromatography). They also have different chemical properties and react differently with both chiral and achiral reagents.
  5. Q: What is a racemic mixture, and what is its optical property? How can one be separated into pure enantiomers? A: A racemic mixture (or racemate) is a 50:50 mixture of two enantiomers. It is optically inactive because the dextrorotatory (+) and levorotatory (-) effects of the individual enantiomers cancel each other out precisely. A racemic mixture can be separated into pure enantiomers through a process called resolution. A common method involves reacting the racemic mixture with a pure chiral resolving agent (e.g., a chiral acid or base). This reaction forms a pair of diastereomeric salts, which have different physical properties (e.g., solubilities). These diastereomers can then be separated by fractional crystallization. Once separated, the pure enantiomers can be regenerated from their respective diastereomeric salts by a simple acid-base reaction.
  6. Q: Outline the general procedure for assigning R or S configuration using the Cahn-Ingold-Prelog (CIP) rules. A: The CIP rules for assigning R/S configuration involve:
    1. Assign Priorities: Rank the four groups directly attached to the chiral center from highest (1) to lowest (4) priority based on atomic number. Higher atomic number gives higher priority. If the first atoms are the same, move to the next atoms until a difference is found. Double and triple bonds are treated as if the atoms are duplicated or triplicated, respectively.
    2. Orient: Mentally orient the molecule so that the lowest priority group (Priority 4) is pointing away from the viewer (typically on a dashed wedge).
    3. Trace: Draw an imaginary arc from Priority 1 to Priority 2 to Priority 3.
    4. Assign: If the arc goes clockwise, the configuration is R (Rectus). If the arc goes counter-clockwise, the configuration is S (Sinister). (A special rule applies if the lowest priority group is pointing towards you: assign R/S as if it were pointing away, then reverse the result).
  7. Q: Explain the concept of “inversion of configuration” in the S$_N2reactionmechanism.∗∗A:∗∗Inversionofconfiguration,alsoknownasWaldeninversion,isahallmarkoftheS_N$2 reaction mechanism when it occurs at a chiral center. It means that the spatial arrangement of the groups around the reacting carbon atom is completely reversed in the product compared to the starting material. This occurs because the nucleophile attacks the electrophilic carbon from the side opposite to the departing leaving group. As the new bond forms and the old bond breaks simultaneously, the other three groups attached to the carbon are forced to move to the other side, much like an umbrella turning inside out in a strong wind, resulting in an inverted stereochemistry.
  8. Q: How does the stereochemical outcome of an S$_N1reactiondifferfromanS_N$2 reaction at a chiral center? Justify your answer based on the reaction mechanisms. A:
    • S$_N$2 Reaction: Results in complete inversion of configuration at the chiral center. This is due to the concerted, one-step mechanism where the nucleophile attacks from the backside of the leaving group, causing a stereochemical flip.
    • S$_N$1 Reaction: Results in racemization (formation of a racemic mixture, a 50:50 mix of both enantiomers). The S$_N$1 mechanism proceeds through a planar carbocation intermediate in the rate-determining step. Once this planar carbocation is formed, the nucleophile can attack from either the top face or the bottom face with equal probability, leading to the formation of both possible enantiomers in roughly equal amounts. Consequently, the product mixture will be optically inactive.
  9. Q: Differentiate between syn-addition and anti-addition in alkene reactions. Provide a reaction example for each. A: These terms describe the relative stereochemistry of adding two new groups across a carbon-carbon double bond:
    • Syn-addition: Both new groups add to the same face of the double bond.
      • Example: Dihydroxylation of an alkene using osmium tetroxide (OsO$_4$) followed by sodium bisulfite (NaHSO$_3$) or hydrogen peroxide (H$_2O_2$). The two -OH groups are added to the same side.
    • Anti-addition: The two new groups add to opposite faces of the double bond.
      • Example: Halogenation of an alkene with bromine (Br$_2$). The reaction proceeds through a cyclic bromonium ion intermediate. The second bromide ion attacks from the opposite face of the ring, resulting in the two bromine atoms being on opposite sides of the former double bond.
  10. Q: What is a Fischer projection, and what do its horizontal and vertical lines represent in terms of 3D orientation? A: A Fischer projection is a two-dimensional representation of a three-dimensional molecule, commonly used for compounds with multiple chiral centers, such as carbohydrates and amino acids.
    • Horizontal lines: Represent bonds that project out of the page (towards the viewer).
    • Vertical lines: Represent bonds that project into the page (away from the viewer). The carbon chain is typically drawn vertically, with the most oxidized carbon (e.g., aldehyde or carboxylic acid) at the top. This convention allows for quick comparison of stereochemistry among related molecules.

Section B: Multiple Choice Questions – Explanations

  1. C) Enantiomers
    • Explanation: By definition, enantiomers are stereoisomers that are non-superimposable mirror images of each other.
  2. C) Chiral center
    • Explanation: A carbon atom bonded to four different atoms or groups is known as a chiral center (or stereocenter/asymmetric carbon).
  3. B) Identical boiling points.
    • Explanation: Enantiomers have identical physical properties (like boiling point, melting point, density, refractive index) in an achiral environment. They differ only in their interaction with plane-polarized light and their reactivity with other chiral substances.
  4. C) Meso compound
    • Explanation: A meso compound contains chiral centers but is achiral overall due to an internal plane of symmetry, making it optically inactive.
  5. D) 2^n
    • Explanation: This formula gives the maximum possible number of stereoisomers for a compound with ‘n’ chiral centers. The actual number can be less if meso compounds exist.
  6. C) R/S configuration
    • Explanation: The Cahn-Ingold-Prelog rules are a set of rules used to assign the absolute configuration (R or S) to each chiral center in a molecule.
  7. C) Racemic mixture
    • Explanation: A racemic mixture is an equimolar (50:50) mixture of two enantiomers.
  8. C) Diastereomers
    • Explanation: Diastereomers are stereoisomers that are not mirror images of each other. They must have at least two chiral centers.
  9. C) Polarimeter
    • Explanation: A polarimeter is the instrument used to measure the angle and direction of rotation of plane-polarized light by an optically active substance.
  10. D) Levorotatory (-)
    • Explanation: The direction of rotation of plane-polarized light is indicated by (+) for clockwise (dextrorotatory) and (-) for counter-clockwise (levorotatory). The R/S designation refers to the absolute configuration, not the direction of rotation.
  11. B) 2-methylpentane
    • Explanation: Constitutional isomers have the same molecular formula but different connectivity. n-Hexane is C$6H{14}.2−methylpentaneisalsoC6H{14}$ but with a different branching pattern. Cyclohexane and hex-1-ene have different molecular formulas. (R)-3-methylpentane is a stereoisomer, not a constitutional isomer, of n-hexane.
  12. C) Resolution
    • Explanation: Resolution is the chemical and/or physical process of separating a racemic mixture into its pure enantiomers.
  13. C) (2S,3S)-2,3-dibromopentane
    • Explanation: An enantiomer is the non-superimposable mirror image, meaning the configuration at all chiral centers must be inverted. If the original is (2R,3R), its enantiomer must be (2S,3S).
  14. D) It must not be superimposable on its mirror image.
    • Explanation: This is the fundamental definition of a chiral object or molecule.
  15. B) 1
    • Explanation: In 2-chlorobutane (CH$_3CH(Cl)CH_2CH_3$), only the C2 carbon (bonded to -Cl, -H, -CH$_3$, and -CH$_2CH_3$) is a chiral center.
  16. B) Diastereomers
    • Explanation: Cis/trans isomers (also known as geometric isomers) are a type of diastereomer. They have the same connectivity but different spatial arrangements and are not mirror images.
  17. B) Bonds pointing into the page.
    • Explanation: In Fischer projections, vertical lines represent bonds going away from the viewer, while horizontal lines represent bonds coming towards the viewer.
  18. B) -25°
    • Explanation: Enantiomers rotate plane-polarized light to the same magnitude but in opposite directions.
  19. C) They are superimposable on their mirror image.
    • Explanation: This is what makes them achiral and optically inactive despite having chiral centers.
  20. D) A mixture of diastereomers if new chiral centers are formed.
    • Explanation: When a chiral molecule reacts with an achiral reagent, if the reaction creates new chiral centers, it can lead to a mixture of diastereomers (or potentially a single diastereomer if the reaction is stereoselective). If no new chiral centers are formed, and the original chiral center is not affected, the product will retain its original chirality. If the original chiral center is involved in the reaction that loses its chirality, then achiral products might form. However, forming a single enantiomer or a racemic mixture of products from a single chiral reactant with an achiral reactant would be incorrect unless specific conditions apply (like racemization in S$_N$1). The most general answer when new chiral centers can form is a mixture of diastereomers.
  21. C) S$_N$2
    • Explanation: S$_N$2 reactions proceed with complete inversion of configuration at the chiral center (Walden inversion) due to backside attack.
  22. B) A racemic mixture
    • Explanation: Anti-addition of Br$_2$ to a cis alkene (like cis-2-butene) leads to the formation of a racemic mixture of enantiomers (e.g., (2R,3S) and (2S,3R)-2,3-dibromobutane). If it were trans-2-butene, it would yield a meso compound.
  23. B) Reaction via an S$_N$1 mechanism.
    • Explanation: S$_N$1 reactions involve a planar carbocation intermediate, which can be attacked from either side by the nucleophile, leading to a racemic mixture (racemization) if the reacting carbon is chiral.
  24. B) Syn-addition
    • Explanation: OsO$_4$ and dilute KMnO$_4$ are known for causing syn-dihydroxylation, where both -OH groups add to the same face of the alkene.
  25. B) S (Assign R, then reverse because the lowest priority group is in front)
    • Explanation: According to CIP rules, if the lowest priority group is pointed towards you (on a wedge), you determine the configuration as if it were pointing away (which would be R in this case, given the clockwise trace), and then you reverse the assignment. So, R becomes S.

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