Exam 2

2 mechanisms for beta elimination reactions

- a concerted mechanism: both events occur simultaneously - stepwise mechanism: even occur separately (LG leaves, then proton transfer)

anti-conformation

- a conformation with a 180 degree dihedral angle between the largest groups - usually the lowest energy conformation

reversibility of carbocation rearrangement

- equilibrium is established in which all of the possible carbocations are present, with the most stable carbocation dominating equilibrium - diff in energy between possible carbocation is often significant, so carbocation arrangements will generally be drawn as irreversible processes - there are exceptions to these rules: when step involves liberation of a gas, which is free to exit reaction vessel reaction is expected to react to completion

aryl and vinyl halides

- halogen connected to sp² hybridized carbon atom

high energy transition state

- high activation energy - slow reaction

steps to locating chirality centers

- ignore sp and sp^2 hybridizeed carbons - ignore CH2 and CH3 groups - identify carbon atoms bearing four different groups

cyclobutane

- less angle strain than cyclopropane but more torsional strain - almost same total level of strain as cyclopropane - slightly bent to relieve torsional strain, but that increases angle strain

low energy transition state

- low activation energy - fast reaction

more ringed member

- lower energy

chair conformation of cyclohexane

- lowest energy for cyclohexane in which all bonds are fairly close to 109.5 degrees and H atoms are staggered

drawing enantiomers

- mirror behind molecule(skeleton drawn exact same way, but dashes become wedges and wedges become dashes) - mirror on side of molecule - mirror beneath the molecule

drawing curved arrows

- never place tail of curved arrow on a + charge - head of curved arrow must be placed so that it shows either the formation of a bond or the formation of a lone pair - never give C,N,O more than 4 orbitals - make sure that all curved arrows you draw accomplish one of the 4 characteristic arrow pushing patters

Mechanisms and Arrow Pushing Patters

- nucleophilic attack - loss of a leaving group - proton transfers - rearrangements

polarization

- orientation of the electric field - when many waves of light are traveling the same direction, they each have a different polarization, randomly oriented

factors contributing to nucleophilicity

- presence of a charge --> more nucleophilic - polarizability --> related to size of an atom -> more polarizable = more nucleophilic (F can behave as either strong or weak nuc, while many halides (I, Br, Cl) are strong nucs strictly)

effect of substrate structure on rate of SN2 process

- presence of substrate structure at alpha or beta positions can significantly decrease the rate

summary of symmetry and chirality

- presence or absence of rotational symmetry is irrelevant to chirality - cmpd that has plane of symmetry will be achiral - cmpd without plane of symmetry will probably be achiral (there are exceptions though!!!)

ionic reactions/polar reactions

- reaction that involves the participation of ions as reactants intermediates or products - occur when one reactant has a site of high electron density and other reactant has site of low electron density - major part of reactions we will cover - other 2 major categories (radical reactions and pericyclic reactions)

mirror behind the molecule

- skeleton is drawn the exact same except wedges become dashes and vice versa

1,3-diaxial interaction

- steric interactions that occur in the chair conformation of a di- or polysubstituted cyclohexane when groups located at C1 and C3 both occupy axial positions

Tertiary alkyl halides undergo E2 reactions quite rapidly: why do they undergo E2 reactions, but not substitution

- subsitution reactions occur when reagant functions as a nuc and attacks the alpha position - elimination reaction occurs when reagant functions as a base and abstracts a proton from beta position - with tertiary substrate, steric hindrance prevents reagant from functioning as a nucleophile at an appreciable rate, but reagant can still function as a base without encountering much steric hindrance

regiochemistry

- term describing a consideration that must be taken into account for a reaction in which 2 or more constitutional isomers can be formed - both are formed, but the more substituted alkene is generally observed to be the major product

rearrangements in unimolecualr processes

- there is additional evidence that solvolysis processes involve carbocation intermediates

conformational analysis of butane

- three staggered and three eclipsed - the repulsion between the electron clouds of the two methyl groups isn't much

rearrangements

- we focus on carbocation arrangement - carbocations are stabilized by neighboring alkyl groups - presence of a neighboring alkyl group will stabilize carbocation becuase a bonding MO slightly overlaps with empty p orbital placing some of its electron density in empty p orbital

ring flip

-atoms/groups that were equatorial become axial and vice versa

gauche

the interaction between two atoms or groups who dihedral angle is more that 0 degrees but less than 120 degrees

bulkier the group...

the more energy required to put it in axial position

strong base

unstable base

reversible reactions with proton transfers

all proton transfer steps are technically reversible

secondary alkyl halide

an alkyl halide in which the halogen is bonded to a secondary carbon

tertiary alkyl halide

an alkyl halide in which the halogen is bonded to a tertiary carbon

strong bases are __________ leaving groups

bad

superimposable

identical in all respects. the three-dimensional positions of all atoms coincide when the molecules are placed on top of each other.

good electrophiles

linked to electronegative or electron-withdrawing leaving groups

irreversible reactions with nucleophilic attacks

proceed only in one direction - used if the nucleophile is a poor leaving group

nucleophile reactivity

protic solvents surround nucleophile anions very well

Rate of SN1 reaction

rate = k [electrophile] of rate = k [substrate]

nucleophilicity

rate at which a nucleophile will attack a suitable electrophile

substrate

refers to alkyl halide

SN2

refers to biomolecular nucleophilic substition reactions - reactions of this type involve unhindered electrophiles (primary or secondary) reaction with nucleophiles in a single step via an approximately triganol bipyramidal transition state

angle strain

results when bond angles deviate from their ideal values by being stretched or compressed

Stereoisomers

same molecular formula and constitution but different spatial arrangement of atoms

racemic reaction

solution containing = amounts of both enantiomers - optically active

weak base

stabilized base

Diastereomers

stereoisomers that are not mirror images

bad leaving groups

strong bases

good nucleophiles

strong bases - contain high electron density

anti-periplanar

substituents are attached to parallel bonds on opposite sides of a molecule

chair conformation lower in energy when

substituents occupy equitorial positions -> more stable

Stereospecificity

substrate is sterisomeric and the stereochemical outcome is dependent on which stereoisomeric substrate is used

achiral

superimposable on their mirror image

increasing stability alkyl halides

tertiary>secondary>primary

dihedral angle (torsional angle)

the angle by which 2 groups are separated in a newman projection - changes as the C-C bond rotates

summary of when irreversible reaction arrows are used

1) for a nucleophile attack involving strong nucleophile attack that is also poor leaving group 2) for a proton transfer step with vast difference in pKa values between acids on either side of equilibrium 3) for a carbocation rearrangement

in an alkyl halide, the halogen serves 2 critical functions that render the alkyl halide reactive towards substitution and elimination process

1) halogen withdraws ED via induction, rendering the adjacent carbon atom electrophilic and subject to attack by nucleophile 2) halogen can serve as leaving group and substitution/elimination processes can only occur when leaving group is present - good leaving groups are conjugate bases

how to draw a Newman projection

1) identify the three groups connected to the front atom - if atom coming out of the board is below observance site, front group will have top portion pointing up - if atom coming out of the board is above observance site, front group will point down - wedge coming out of the board will be either on the right or the left 2) identify the three groups connected to the back carbon - must be in the same plane as the corresponding molecules in the front group 3) put both of these together in a newman projection

Why does is proceed through back side attack?

1. lone pairs of leaving group create regions of high electron density that block front side of substrate, so nucleophilic can only approach from backside 2. MO theory, electron density flows from HOMO of nucleophile into LUMO of electrophile

3 key players in nucleophilic substitution

1. nucleophile 2. carbon atom, electrophile 3. leaving group (losses bond to C, bond breaks, formal energy decreases)

when we compare relative rates, the following trends emerge

1. rate of an SN2 reaction is most sensitive to number of substituents at the alpha position - SN2 reactions are most effective for methyl halides and primary alkyl halides - SN2 reaction cannot be performed with tertiary alkyl halides 2. rate of SN2 reaction is also sensitive to presence of substituents at beta position - with 3 substituents at beta position, reate of SN2 process is too slow to be of any practical use - an SN2 process will generally not occur if there are 3 substituents at alpha position or 3 substituents at beta position

cyclopropane

2 main factors contributing to high energy - angle strain: from small bond angles - torsional strain: eclipsing Hs

regioselective

2 products formed, but one will be the major product

max number of stereoisomers

2^n where n = number of chiral centers

polar aprotic solvents

polar solvents that can't form hydrogen bonds - DMSO, DMF

meso compound

A compound with chirality centers and an internal plane of symmetry causing it to be an achiral molecule

trans stereoisomer

A compound with similar groups on the opposite sides of the double bond - there is not C-C rotation with double bond because it would destroy the pi bond

periplanar

A conformation in which a hydrogen atom and a leaving group are approximately coplanar.

racemic mixture

A mixture that contains equal amounts of the (+) and (-) enantiomers. Racemic mixtures are not optically active.

La Chatelier's Principle

A reaction in equilibrium will adjust concentrations to counter stresses

the Sn1 mechanism

A substitution reaction mechanism featuring nucleophilic substitution at an sp3 carbon, in which carbon-nucleophile bond formation and carbon-leaving group bond scission are not simultaneous (i.e., the reaction is never concerted). The mechanism always includes a carbocation intermediate. SN1 is an abbreviation for 'substitution nucleophilic unimolecular -- core steps 1) loss of LG to give carbocation intermediate 2) nucleophilic attack 3) if nucleophile uncharged

primary alkyl halide

An alkyl halide in which the carbon atom bonded to the halogen is also bonded to 1 other carbon atom.

E2 mechanism

An elimination reaction mechanism in which three bond changes occur simultaneously: carbon-leaving group bond scission, pi bond formation, and deprotonation by base. In the most common E2 mechanism, the proton removed is beta to the leaving group; this type of elimination is called beta elimination. Removal of an alpha hydrogen (alpha elimination) usually leads to a carbene.

polarizability

The ability of an atom to distribute its electron density unevenly in response to external influences. - directly related to size of atom (more specifically, number of electrons that are distant from the nucleus)

ring strain

Energy created in a cyclic molecule by angle strain, torsional strain, and nonbonded strain; determines whether a ring is stable enough to stay intact.

concerted mechanism

Everything happening at the same time

flagpole interactions

For cyclohexane, the steric interactions that occur between the flagpole hydrogen atoms in a boat conformation.

back side attack

In SN2 reactions, the side opposite the leaving group, which is where the nucleophile attacks.

Drawing the Transition State of an SN2 Process

Step 1: Identify the nucleophile and the leaving group. Step 2: Draw the carbon atom with Nuc and LG on either side Step 3: Draw the three groups attached to the carbon atom. Place the brackets and the symbol indicating a transition state

beta elimination

The elimination of two atoms or groups from adjacent carbon atoms. This is the most common type of elimination.

observed rotation

The extent to which plane-polarized light is rotated by a solution of a chiral compound - dependent on the number of molecules that the light encounters as it travels through the solution - if concentration/pathlength doubles, alpha doubles

solvolysis

The solvent acts as the nucleophile

proton transfers

The third pattern for arrow pushing of an ionic mechanism is a proton transfer. They can be drawn with only one curved arrow, but if only one is drawn, the base involved is not indicated. It is preferable to show the base involved in a proton transfer and to use two curved arrows, but sometimes more than two arrows can be used. When a compound is pronated, the first arrow is drawn from the ketone to the proton, and the second shows what happens to electrons that were previously holding the proton. When a compound is depronated, a base must be involved so that the compound can lose a proton.

conformation

a 3D shape that can be adopted by a compound as a result of rotation about single bonds

dextrorotatory

a compound exhibiting a positive rotation

staggered conformation

a conformation about a carbon-carbon single bond in which the atoms or groups on one carbon are as far apart as possible from atoms or groups on an adjacent carbon

Boat conformation of cyclohexane

a conformation of cyclohexane in which all bonds angles are fairly close to 109.5 degrees and many H atoms are eclipsing each other - less stable because of flagpole interactions and torsional strain along the bottom of the boat

plane of symmetry

a plane that bisects a compound into two halves that are mirror images of each other

optically pure

a solution containing just one enantiomer, but not it's mirror image

chirality center

a tetrahedral carbon atom that is bonded to four different groups

anionic base

bears a negative charge

reversible reactions with nucleophilic attacks

can go in either direction under different circumstances - for step in which nucleophile attacks an electrophile, a reversible reaction arrow is generally used if nuc is capable of functioning as good leaving group after attack has occured

dialectric constant

captures the ability of a solvent to support and separate ions of opposite charge - high-dielectic solvents support ion-forming steps

nucleophilic attack

characterized by a nucleophile attacking an electrophile

levoratory

compound exhibiting negative rotation

optically active

compound that rotates the plane of polarized light, have chiral center, nonsuperimposable mirror image

optically inactive compounds

compounds that don't rotate plane-polarized light, does not have chiral center or has internal plane of symmetry (meso compound)

Alkyl Halide

compounds with halogen (Cl, Br, I) connected to an sp³ hybridized atom

EM radiation

comprised of oscillating electric and magnetic fields propogating through space - each oscillating field is located in a plane and these planes are perpendicular to each other

inversion of configuration

configuration of chiral center is changed during a reaction

stereospecific

configuration of product dependent of configuration of starting material

twist boat conformation

conformation of cyclohexane that is lower in energy than a boat conformation but higher in energy than a chair conformation

gauche conformation

conformation that exhibits a gauche interaction

protic solvents

contain at least one hydrogen atom connected directly to an electronegative atom - can hydrogen bond

planar carbocation

created by departure of leaving group

polarimeter

device used to measure rotation of plane-polarized light caused by optically active compound

polar solvents

dissolve polar solutes

transition state for typical SN2 reaction

dotted lines indicate bonds that are in the process of being broken/formed

Newman projection

drawing style designed to show the conformation of a molecule

hyperconjunction

effect that explains why alkyl groups stabilize a neighboring positively charged C atom

electrophile

electron deficient center lewis acids

Nucleophile

electron rich center - an atom with localized lone pair can be a nuc

cis stereoisomer

exhibits groups on the same side of the ring

strong nucleophile

fast SN2 reaction

mirror beneath molecule

flips molecule upside down

enantiomeric excess

for a mixture containing two enantiomers, the difference between the percent concentration of the major of the enantiomer and the percent conc of its mirror image

irreversible reactions in proton transfers

generally irreversible reaction arrows are used for reactions in which the acids differ in strength by 10pKa units

Weak bases are ________ leaving groups

good

alkyl sulfonates

good leaving group

syn-coplanar

having a dihedral angle of 0 degrees

anti-coplanar

having a dihedral angle of 180 degrees

non polar solvents

hexane, benzene

eclipsed conformation

highest energy no separation. or 120 separation.

Sn1 reaction

involve formation of an intermediate carbocation, which can then be attacked from either side, leading to both inversion of configuration and retention of configuration

Nucleophilic substitution

involve the exchange of one nucleophile for another - important atoms in these reactions are the electron-pair donor (nucleophile) and atom that accepts the pair (electrophile) and the group that leaves the electrophile with a pair of electrons (LG or nucleofuge)

elimination reactions

involve use of bases rather than nucleophiles

biomolecular

involving 2 chemical entities

polar aprotic solvents

lack H atom - speed up rate of an SN2 reaction by many orders of magnitude

mirror on side of molecule

left and right sides switch

Hoffmann product

less substituted alkene

plane-polarized light

light for which all photons have the same polarization, generally formed by passing light through a polarizing filter

methyl shift

migration of CH3 - secondary carbocation transformed to tertiary carbocation - in order for methyl shift to occur, methyl group must be attached to the carbon atom that is adjacent to carbocation

hydride shift

migration of negatively charged H atom - secondary carbocation transformed into more stable tertiary carbon

zaitsez product

more substituted alkene - sometimes it can be the minor product - when both the substrate and the base are sterically hindered, less substituted alkene is often the major product

reactivity towards SN2 reactions

most reactive --------------------- unreactive H3C-X > 1 degree > 2nd degree > 3rd degree methyl

cyclohexane

most stable = "chair conformation" = no ring strain - all bond angles are 109.5 degrees and all C-H bonds are prefectly staggered

cyclopentane

much less angle strain than cyclobutane or cyclopropane - can also reduce much of its torsional strain by adopting the following conformation

enantiomers

non-superimposable mirror images - a chiral compound will have exactly one enantiomer

chiral

object that is not superimposable upon mirror image - carbond bearing 4 different groups is the most common source of molecular chirality

specific rotation

observed rotation under standard conditions of concentration - 1g/mL and pathlength 1dm

stepwise mechanism

occurs in steps

nucleophile will attack more often...

on the side opposite of the LG, leading slight preference to inversion over retention

polar protic solvents

polar solvents that can hydrogen bond - tend to increase rate of Sn1 reaction

rate determining step

the slowest step in a reaction mechanism - for Sn1: its the first step, first transition state

good leaving groups

weak bases (conjugate bases of strong acids) Br, Cl, I, Water

loss of a leaving group

when a bond breaks and one atom from the bond takes both electrons

elimination

when treated with a base, pi bond is formed

substitution

when treated with nucleophile, nucleophile replaces halogen