Organic Chemistry 1 ReKaps

Passage #1 Map: P1: Info on Styrene P2: Styrene Synth P3: Compound A/E reactions Note: The figure in the passage can effectively act as our map! The passage simply explains it. Questions: 1: D Stop: Answers are functional groups Think: STP Q1:

STP Q2: Amide:

O R C NH2
NH2

R' R

Imine:
C N R"

Amine: R

Predict: Phenyl, amide, imine Match: D 2: A Stop: Answers are IUPAC names Think: Where is Compound A? Figure 1 STP Q.1 IUPAC Rules Identify the longest carbon chain containing the primary functional group (f.g.). Identify the substituents. Number the carbon chain so the principal f.g. receives the lowest number. Arrange substituent prefixes in alphabetical order and attach them to the name of the longest carbon chain.

STP Q.2- Alcohol Predict: Root is eth, suffix is ol, and phenyl on #1 C Match: A 3: B Stop: Answer choices are hybridized orbitals. Think STP Q.1: Removal of H2O (H2SO4 involved in two reactions with Compound A, but dehydration only occurs when A is converted to styrene) STP Q2: sp3

STP Q3: sp2

Predict: sp3 to sp2 Match: B 4: C Stop: Answer choices are compound names Think: STP Q.1: Rxn of A to E: forms a ketone STP Q2:

Predict: 3-phenyl-2-butanone Match: C

ISOMERISM - Structural/Constitutional isomers: Same molecular formula but different connectivity. - Stereoisomers: large group of isomers with same connectivity, but different spatial arrangement of atoms (even if only temporarily). Conformational Isomers: Same compound, just in different conformation. No difference between them. Configurational isomers: Isomers that differ in spatial arrangement of atoms on chiral carbons. Enantiomers: Non-superimposable mirror images of each other. Diastereomers: Non-superimposable non-mirror images of each other. Geometric Isomers: Differ in their arrangement around a -double bondCONFORMATIONAL ISOMERS - Torsional strain results from electron repulsion between groups located on -adjacent- carbons. - Staggered conformation: when the groups on adjacent groups are as far as possible from each other (Newman projections!) - Eclipsed conformation: When the groups on adjacent carbons are as close as possible (Newman projections!) Cyclohexane Conformations: Chair conformation is much better than boat, because boat conformation results in eclipsed position, while chair produces anti-staggered! Angle Strain: Whenever angles on the carbon deviate from its ideal angle of tetrahedral arrangement, 109.5 degrees. When we form structures resulting in smaller angles, we will have angle strain. Non-Bonded Strain: The strain occurring from electron repulsion between groups that are -not- on adjacent carbons (Ex. boat form of cyclohexane). Additional Cyclohexane facts: - Cyclohexane has 2 positions on each atom, axial and equatorial. Equatorial is preferable for larger atoms/substituents. - Axial positions will always alternate in direction on adjacent carbons. Same is true for equatorial positions. - When cyclohexane switches from one chair to the other, all axial and equatorial positions will switch to opposites. GEOMETRIC ISOMERS

- Cis (same side across double bond) and Trans (opposite side across double bond) are used for simple geometric isomers where one of the groups on each side is a Hydrogen atom. - E (opposite) and Z (same) are used when one or both sides of the double bond contain no hydrogen atom. The priority will then be assigned according to Atomic Number. CHIRAL CENTERS - Chiral carbons are carbons that are connected to 4 different groups. - By convention, clockwise rotation around that chiral center are denoted R, and counter-clockwise are denoted S. - The following system of priorities is used to denote R and S configuration: 1. Atomic number (not molecular weight) is the first tiebreaker. One atom of higher atomic number beats any number of atoms of lower atomic number. 2. First, consider only the atoms directly attached to the carbon in question. For example, an NH attached to the carbon takes precedence over a COOH. 3. If theres a tie, then consider the atoms attached to the tied atoms.

4. Double- and triple-bonded atoms count as two atoms or three atoms, respectively. (Thus, an aldehyde has priority over an alcohol; an aldehyde counts as C-H-O-O, while an alcohol is C-H-H-OH.) 5. Assign R or S priority based -only- on 1, 2 and 3 priority groups. Then check if the lowest priority group is in or out of the page. If it is into the page, leave configuration as is. If it is out of the page, then flip configuration. - Fisher Projections: are often used to look at chirality. Carbon atom is at intersection of the 2 lines. The groups on the horizontal line are always out of the page. The groups on the vertical line are always into the page. CRITICAL THINKING QUESTION 5

Stop: Answer choices are molecules. Think: Which 3 answer choices show the exact same molecule? Evaluate the easiest ones first (A, C and D). A and D are both S, and C is R. Predict/ Match: C

ENANTIOMERS VS DIASTEREOMERS - Diastereomers differ in configuration around 1 or more (but not all) chiral carbons. - 2 enantiomers have very similar physical and chemical properties and cannot be separated based on them. - 2 enantiomers will, however, rotate plane-polarized light in opposite directions. Also, they will react differently with other chiral compounds! - 2 diastereomers have similar chemical properties, but different physical properties. So they can be separated based on boiling point, melting point, etc.

Isomerism
Diastereomers and Enantiomers
Diastereomers
Diastereomers are non-superimposable, non- mirror images. They differ in chirality at one or more stereocenters, but not at every stereocenter.

Enantiomer

Diastereomer

Diastereomer

Diastereomer

Enantiomer

- Meso compounds: Compounds that contain internal plane of symmetry, indicating that chiral centers inside the molecule will cancel each other out, making molecule as a whole achiral (like individual bond dipoles vs. molecular dipole).

Isomerism
Isomerism and Physical Properties
Isomer Structural (constitutional) Conformational Geometric (cis/trans) Enantiomers Diastereomers Same physical properties? Same chemical properties?

no yes no yes no
*react

no yes no yes* yes

differently with chiral reagents

CIS vs TRANS - Cis molecules have higher boiling point due to net dipole present. - Trans molecules will have higher melting point due to being able to "stack" better.

CRITICAL THINKING QUESTION 6 Stop: Answer choices are lists of alkanes. Think: When does a compound exist in the liquid state? Above melting point but below boiling point At -50 C, which alkanes will be in the liquid state? Alkanes between n=3 and n=6 Predict: Propane, butane, pentane, hexane Match: C

REACTION MECHANISMS

Sn2 REACTIONS - Occur in concerted/1-step mechanism - Kinetics -> Rate=k[Nu][R-L] - Sterics: Since Nu has to come in, we need space. So we want unsubstituted carbon. The trend is CH3L > RCH2L > R2CHL > R3CL. - Nucleophile is essentially a Lewis acid, something that is willing to donate a pair of electrons to form a bond with the substrate. Sn2 reactions want strong nucleophile! - We must have good leaving group, something that is stable once it dissociates into the solution (ex. Triflates, Tosylate, Mesylate, I, Br, Cl) - Solvent: Sn2 reactions proceed faster in polar aprotic solvent (ex. acetone, DMSO) to avoid attraction of nucleophile to free protons in solution - Stereochemistry: Sn2 reactions result in molecular geometry inversion. It may or may not cause the (R) or (S) designation to change. The (R)/(S) designation changes -only- if Nu is the same priority as the leaving group. Sn1 REACTIONS - Proceeds through 2-step mechanism. The formation of carbocation is the rate-determining step. - Kinetics is unimolecular. Rate=k[R-L] - Since we want more stable carbocation, Sn1 reactions will prefer more substituted carbons (opposite trend of Sn2). - Strength of Nu is irrelevant - We want a good leaving group, same as in Sn2. - Sn1 reactions want polar protic solvent to help stabilize carbocation. - Stereochemistry: Since carbocation is trigonal planar configuration, Nu has 2 equally possible positions of attack. This results in racemic mixture.

Reaction Mechanisms
Nucleophilic Substitutions: SN2 vs SN1

Properties
1-step (concerted)

SN2
Two steps

SN1

Mechanism

Kinetics

Rate = k[RL][Nu:] methyl > 1 > 2 > 3

Rate = k[RL] 3 > 2 > 1 > methyl

Sterics in substrate

SN1 vs SN2 chart 1

Reaction Mechanisms
Nucleophilic Substitutions: SN2 vs SN1

Properties

SN2

SN1

Nucleophile

strong nucleophile
Examples:

any nucleophile

Leaving group

best are weak bases

Examples:

best are weak bases

Examples:

Solvent effects

faster in polar aprotic

Examples:

best in polar protic

Examples:

CH3CH2OH
Stereochemistry
SN1 vs SN2 chart 2

H2O

inversion of configuration

partial racemization

CRITICAL THINKING QUESTION 7: Stop: Answer choices are products (nomenclature and stereochemistry). Think: STP 1: Solvent is polar aprotic SN2.

 Its normal to get unknown compounds, but its still easy to see from the Lewis structure that the solvent cannot hydrogen bond.. Electrophile = 1 alkyl halide. Contains iodine, a good l.g. SN2. Note that F is a poor l.g. b/c it is not stable in solution by itself; it is the conjugate base of a -weakacid, and therefore will be attracted back to the parent molecule if it is removed as a leaving group. Nucleophile = N3- (azide) = strong nucleophile SN2 STP 2: N has lower priority than the leaving group, I. Therefore, no inversion of configuration. Predict: N3 substitutes for I, and no inversion of configuration Match: A

E1 REACTIONS - Sn1 and E1 always compete with each other due to similar mechanism and reaction conditions. - Occurs in 2-step mechanism. Carbocation formation is rate-determining step. In 2nd step, the base will abstract a beta-hydrogen and double bond between the carbons will form. - Kinetics is unimolecular. Rate=k[R-L] - Same sterics and substrate requirements as Sn1. - Strong base is not required. - Polar protic solvents are favored for E1 reactions. E2 REACTIONS - Occurs in concerted/1-step mechanism. - Kinetics is bimolecular. Rate=k[Base][R-L] - Stereochemistry: The base abstracting a beta-hydrogen and the leaving group going away occur in antiperiplanar configuration. Essentially the 2 processes occur as far apart from each other as possible. - Zaitsev elimination results in most substituted double bond, and will be major product. - Hoffman elimination results in least substituted double bond. - All primary, secondary and tertiary substrates can undergo E2 reaction. - Strong base is required. Bulky bases will favor E2 over Sn2 reaction. - Polar protic solvents are favored for E1 reactions. Often, conjugate acids of strong bases are used as solvents because they regenerate the base used in the reaction.

Reaction Mechanisms
Elimination Reactions: E1 vs E2
Properties
1-step (concerted)

E2
Two steps

E1

Mechanism

Kinetics

Rate = k[sub][base]

Rate = k[sub]

Sterics in substrate

no steric factor

3 >2 >1

E1 vs E2 chart 1

Reaction Mechanisms
Elimination Reactions: E1 vs E2
Properties
Base

E2

E1
Doesnt matter; solvent usually acts as base

best are strong, bulky

Examples:

Solvent effects

Conjugate acid of the strong base

Polar protic
Examples: CH3CH2OH H2O

Stereochemistry

Anti-periplanar (H-C-C-LG lie in the same plane)

Doesnt matter

E2 vs E1 chart 2

Reaction Mechanisms
Comparing structure and reactivity for substitution and elimination reactions
Predicting Reactivity in Substitutions and Eliminations
Substrate Bad base, good nucleophile i.e. IGood base, good nucleophile i.e. OHGood base, poor nucleophile i.e. tBuOProtic/acidic conditions

Methyl

SN2 SN2 SN2

SN2 SN2 > E2 E2 > SN2

no rxn E2 E2

no rxn no rxn SN1 or E1

Primary

Secondary

Tertiary

no rxn

E2

E2

SN1 or E1

Directed Practice Organic Chemistry Review Notes: Chapter 4 (Alkanes, Alkyl Halides, and Substitution Reactions), 5 (Alkenes, Alkynes, and Elimination Reactions)
Reaction Type Chart

PASSAGE #2 Map: P1: Exp. background -> cis to trans conversion P2: Student 1 exp. P3: NMR data P4: Student 2 exp. (mistake) Questions: 8: B Stop: Answer choices are intermediates Think: STP Q.1: Since the double bond must be broken at some point for rotation to occur, the reaction must be an addition reaction followed by an elimination reaction. STP Q.2: Passage states in para. 1 that rate of rxn depends only on maleic acid, thus unimolecular mechanism. Predict: Rxn proceeds through a carbocation intermediate. Match: B 9: D This is a Roman numeral question. Often you dont have to make a judgment on every statement. Start off with the most common one. But you don't have to check RN I as seen in strategy, but must be true because arrows in Reaction 1 show conversion of maleic acid to fumaric acid favored over the other direction of isomerization. II. Fumaric acid (the product) is a trans- or E-alkane, so II can be eliminated. A & D left, both include I, so read III. III obviously true, since cis/trans and E /Z isomers are diastereomers and will have different physical properties, thus automatically choose (D).

10: C Stop: Answers are isomers. Think: STP Q.1: No Predict: Differ in arrangement of substituents around double bond, thus stereoisomer = geometric isomers. Match: C

11: B Stop: Answers are sentences, so logic. Think: STP Q.1: It must explain the difference between maleic acid and fumaric acid. Where does the water come from? From the two OH groups How are the trans and cis isomers different in relation to their hydroxyl groups? In maleic acid, they are close together whereas in fumaric acid they are far apart. Predict: Hydroxyl groups are too far apart in fumaric acid.

12: B Stop: Answer choices have stereochemistry Think: STP Q.1: Addition to the same side. What type of geometry does maleic acid have about the C=C double bond? Planar since sp2 hybridized Predict: Given planar nature, syn addition will yield meso compound. Match: B NOTE: If started with fumaric acid racemic mixture