Organic Chem 1 Review

Organic Chem 1 Review

Ch.1

Ch.11

4.11

Ch.4

Achiral molecules with double chirality centers

4.1

Ch.10

-three, not four possibilities for an achiral disubstituted molecule

-(R,R) enantiomer to (S,S) but (R,S) suerimposable with (S,R)

-

-Meso Compounds possible

10.1

10.7

Structure, Bonding, and Stability

Free Radicals and Retrosynthesis

4.10

Two Chirality Centers

-see book and slides for examples

4.2

-methyl to tertiary radicals, tertiary being most stable

-sp2 hybridized

-result from homolytic bond dissociation (whereas ions result from heterolytic)

-be able to find Enthalpy of a reaction (products - reactants)... negative is exothermic

4.12

-both (all) chirality centers change is enantiomer...mirror image

-one (not all) is diastereomer...not mirror image

-fischer projections of double chirality centers is showed as eclipsed conformation

-for vertical carbon chain, fischer projection with same-side substituents is erythro, opposite sides are threo

-diastereomer physical properties may differ significantly

-chiral disubstituted rings have 2 cis, 2 trans enantiomers, and cis/trans are diastereomers

Multiple Chirality Centers

-2^n is maximum number of stereoisomers if n=chirality centers

-meso compounds create fewer stereoisomers

10.6

10.2

4.9

Chirality axis

4.3

Methyl-Ammonia reduction of Alkynes

Free Radical Halogenation

10.8

Free Radical Polymerization

- Metal ammonia reduction gives trans alkene (hydrogenation gives cis)

-Protons come from NH3

-mechanism 10.3

-Cl2 and Br2 useful when broken by uv light, F2 explosive and I2 unreactive

-Cl2 in methane favors monosubstituted, but excess can make CCl4 (polyhalogenation)

-Each halogen added one at a time

-alkene + peroxides ---> Polymer

-dibenzoyl peroxide

-chirality in polymers may result in all the same backbone (isotactic), alternating (syndiotactic), or random (atactic)

-mechanism 10.4

-table 10.2

4.13

-w/o chirality center, a molecule can still have chirality axis

-

-mainly occurs with biaryls

-if carbons next to rotatory bond have large unequivalent substituents, steric strain hinderes rotation enough to be separated by conformation

-called atropisomers

4.14

Resolution of stereoisomers

Chirality Centers other than Carbon

-Resolution: separation of enantiomeric components. Methods:

-add a chiral compound to create diastereomers which can be separated, then break into original components (figure 4.12)

-kinetic resolution using different reaction rates w/chiral molecule (most commonly enzymatic resolution)

4.8

-Silicon can be a chirality center, but organosilicon compounds not found in nature

-trigonal pyrimids can be chiral if it has 3 different groups, but pyrimidal interconversion is so rapid for N, enantiomers usually cannot be separated. P interconversion is slower making it possible to separate enantiomers

Properties of enantiomers

4.4

10.5

10.3

Mechanism of Methane Chlorination

-Enantiomers w/different smells(Carvone) chiral recognition

-left/right hands fit in left/right gloves but not opposites... chiral olfactory receptors

-(+)/(-) or (R) and (S) enantiomerism

Free Radical addition of HBr to Alkenes and Alkynes

-Initiation: homolytic dissociation Cl2

-Propagation: HCl formed and Methyl Radical

-Termination: Methyl radical steals Cl and forms another Cl radical

-Other forms of termination intervene (Cl Cl, Methyl Methyl)

4.7

Fischer Projections

4.5

-peroxide effect: HBr added Markovnikov without peroxides, and anti-Markovnikov in their presence

-Mechanistically, Peroxide O-O bond breaks with heat or light, then starts propagation chain

-It snags the proton from Br, which then attacks terminal alkene and forms secondary radical, which is more stable than primary radical.

-Radical snags a Hydrogen

-mechanism 10.2

10.4

Halogenation of higher Alkanes

4.6

-Vertical lines point away, horizontal point towards

-https://www.khanacademy.org/science/organic-chemistry/stereochemistry-topic/optical-activity/v/fischer-projection-introduction

-

-deal with each chirality center separately

-https://www.khanacademy.org/science/organic-chemistry/stereochemistry-topic/optical-activity/v/fischer-projection-practice

-enantiomers are exact flips and each chirality center switches

-photochemical reactions triggered by light

-Halogenation of higher alkanes can create constitutional isomers, more stable one favored slighty for Cl, and a lot for Br

-stability tertiary > secondary > primary

Ch.5

5.1

8.1-8.3

Ch.8

Ch.7

Hydrogenation of Alkenes

(Functional Groups)

7.1, 7.2, 7.3

7.19, 7.20

Ch.9

6.1

Substitution vs. Elimination

Ch.6

Nomenclature, Structure/Bonding, Isomerism

9.13

9.3-9.5

Functional Group Transformation by Nucleophilic Substitution

Ozonolysis of Alkynes

5.11

Physical Properties, Structure, Bonding, Acidity

-alkene +H2 in presence of Pt, Pd, Ni, or Rh---> alkane

-syn addition of 2 H's

-exothermic process... heat of hydrogenation

-heats of hydrogenation used to estimate stability... more stable less energy

-more stable with increased substitution

-https://www.khanacademy.org/science/organic-chemistry/substitution-elimination-reactions/sn1-sn2-e1-e2-sal/v/comparing-e2-e1-sn2-sn1-reactions

-structure alkyl halide/basicity of anion

-default elimination, sometimes substitution

-alkyl sulfonates react similarly, just different leaving group

5.2

Stereochemistry and SN1 Mechanism

-ene ending, number with lowest numbers

-alcohol group takes priority, ends with enol

-vinyl group directly attached to double bonding carbon

-allyl group attached to C adjacent to doubly bonding C

-isopropenyl attached to secondary double bonded carbon

-C doubly Bonded to a ring prefix Methylene

-sp2 hybridized

-https://www.khanacademy.org/science/organic-chemistry/gen-chem-review/hybrid-orbitals-jay/v/pi-bonds-and-sp2-hybridized-orbitals

-cis/trans isomerism by substitution

-Step 1 Ozone (still)

-Step 2 just water, because alkynes are one step more oxidized already

-each side of triple bond forms a Carboxylic Acid

6.9

IUPAC Nomenclature of Alkyl Halides

-Alkyl halides undergo substitution by stronger nucleophiles

-metal alkoxides, metal carboxylates, metal hydrogen sulfates, metal cyanides, metal azides (p.207/table 6.1)

-NaI in acetone displaces Alkyl Chlorides and Bromides

8.4 -8.5

8.14

Effect of solvent on rate of Nucleophilic Substitution

-favors inverion of configuration because leaving group still blocks one side when detached

-consider cis/trans stability with SN1

-same carbocation can be formed from cis/trans molecules

6.10

Electrophilic addition of HX to alkenes

Retrosynthetic Analysis and Alkene Intermediates

-similar physical properties to alkenes/alkynes

-sp hybridization, 180 degree bond angle

-from single to double to triple bonds...

C-C and C-H bonds get shorter and stronger, C-H becomes more acidic

-table 9.1

-smallest stable cycloalkyne is nonyne

- hydroxide ion too weak a base to convert acetylene to anion in large amounts, but Amide ion can snag the hydrogen (p.328)

-HC=CNa prepared by adding NaNH2 to acetylene with liquid ammonia solvent

7.16, 7.17

7.4

-Substitutive nomenclature:

"halo- alkane" chain

-halides and alkyl groups given equal priority, number from side that gives lower substituents

Nucleophilic Substitution of alkyl Sulfonates

E/Z Naming

- see page 308 / powerpoint for examples

-work backwards

_

5.10

5.12

Anti Elimination and Isotope Effects in E2

Effect of Alcohol Structure on Rate

Carbocation Rearrangements

6.2

-solvent effects rate, not outcome

-protic (hydrogen-bonding)/aprotic (not)...polar/nonpolar (like dissolves like)

-table 6.3

-SN2 polar aprotic (solavtion/clustering around nucleophile inhibits

-SN1 polar protic b/c hydrogen bonding stabilizes transition state

9.6

9.12

Reactivity of Halide Leaving Groups

-use kahn ingold prelog sequencing rules to give priority

-entgegen (E)= opposite... highest priority groups are opposite each other

-Zusammen (Z)= same... highest priority groups on same side of double bond

6.8

-Alkyl Sulfonates (Methanesulfonic Acid)(para-Toluene Sulfonate) formed from alcohols with retained stereochemistry in presence of Pyridine

-undergo similar substitutions to alkyl halides

-see table 6.6 for rates

-strong bases pKa 2 or greater not good leaving groups

-same substitutions as alkyl halides w/ inversions as appropriate with SN1 and SN2 reactions

-rate for SN1 is unimolecular

rate=k[concentration rate determining reactant]

-more stable carbocations formed faster than less stable ones

-alkene + HX ---> Alkyl Halide

-HI reacts fastest, HF slowest

-rate increases with alkene substitution

-Markovnikov Addition: H adds to side with most H's, X adds to more substituted side (mechanism 8.2)

-forms racemic mix of products, cannot form chiral product from achiral reactants without a chiral catalyst

-carbocation rearrangement possible, shift after protonation step

-reaction rate for anti-coplanar elimination much faster

-https://www.khanacademy.org/science/organic-chemistry/substitution-elimination-reactions/e1-e2-tutorial/v/e2-elimination-stereospecificity

-stereoselectivity vs stereospecificity

-RI>RBr>RCl>RF reactivity rate

-RF far less, basically unreactive

Prep of Alkynes by alkylation of Acetylene and terminal Alkynes

-mechanism 5.2

-carbocation formed, can undergo hydride shift or methyl rearrangement to stabilize

-takes place by partial bonded transition state

Carbocation Rearrangement SN1

Addition of Halogens to Alkynes

5.3

-Acetylene converted to conj. base by NaNH2

-Alkyl Halide added, SN2 mechanism carried out in liquid ammonia, diethyl ether, or THF

-dialkylation by repeating reaction (2eq. of reactants)

-only works well for methyl and primary alkyl halides

IUPAC Nomenclature of Alcohols

-mechanism 6.3...hydride shift

-carbocation rearrangement... never seen in SN2

-Alkyne reacts with 2eq X2 (Cl or Br) to form tertahaloalkanes

-Dihaloalkane is an isolable intermediate with equimolecular amounts

-Anti addition

6.12

9.1, 9.2

9.14

5.15

Intro to Retrosynthesis

Sources and Nomenclature

8.6, 8.7

8.13

Alkynes in Synthesis and Retrosynthesis

Sulfonates as Alkyl Halide Surrogates

-double line arrow

-work backwards to synthesize a molecule from starting compounds in multiple steps

Acid-Catalyzed Hydration & Thermodynamics

-Functional class naming: start numbering at alcohol group (see 1-methylpentyl alcohol)

-

-Substitutive names number longest C chain but give lowest substituent number to alcohol

-outrank alkyl and halogen groups

Enantioselective Addition to Alkenes

-see examples in slides and textbook

7.5, 7.6

5.9

7.14, 7.15, 7.18

5.13

Dehydrohalogenation

Nucleophilic Substitutution Summary

Structure, bonding, stability of carbocations

-methanesulfonyl chloride (and triethylamine) or

p-Toluenesulfonyl chloride (and pyridine) to react with alcohol

-retained stereochemistry b/c reacts with O of alcohol not the carbon it is attached to

Physical Properties and Relative Stabilities

Methyl/Primary Alcohols:SN2 Reaction

-CaO + 3C ---> CaC2 +CO at very high temperatures (1800-2100 Celcius)

-other alkynes from natural and synthetic sources

-ane suffix replaces by yne suffix

-double and triple bond present... give lowest overall numbering, or precedence to double bond as tiebreaker

-en comes before yne when naming a coupound with a double and a triple bond

-monooxygenase w/Beta Carotene

-Fumaric acid and Fumarase---> Malic Acid

6.3

-Alkene + water and acid catalyst ---> alcohol

-mechanism 8.3

-exact reverse of dehydration (microscopic reversibility)

-rate increases with substitution

-Le Chatelier's Principle shifts one way or other for reversible reactions

-Spontaneity

9.7

9.11

-nucleophile pushes off leaving group

-alkyloxonium ion is first elementary step (same as SN1)

-transition state is doubly bonded

-mechanism 5.3

-tertiary>secondary>primary stability of carbocations

-inductive effect-stabilizes by bond polarization

-hyperconjugation- electron delocalization (resonance-like) only Beta carbons can stabilize

Hydration of Alkenes

SN2 mechanism of Nucleophilic Substitution

6.7

Prep of Alkynes by Elimination Reactions

-alkyl halide + strong base (sodium ethoxide)---> alkene

-primary base gives Zaitsev Elim, tertiary base used to make primary alkene by Hoffman elim.

-favors more stable E stereoisomer

-rings ten and under form exclusively cis isomes

-E1 elimination unimolecular, E2 elimination bimolecular (most rxns E2)

-rate of dehydrohalogenation F<Cl<Br<I

-bimolecular transition state has partial bonds like SN2

-E1 (mechanism 7.5) halogen leaves, hydrogen is pulled off by base, carbocation stability to consider, tertiary fastest rate

5.4

6.13

-C4H8 and smaller gases at room temperature

-halide groups withdraw electron density, methyl groups contribute, magnify dipole moment alone or when paired

-alkyl groups like methyl stabilize double bonds by hyperconjugation and inductive effect, delocalizing the electrons

-more substituted (directly attached)is more stable (electronic effect)

-cis stereoisomers destabilized by Van Der Waals strain (Steric Effect)

-branched chains more stable

Stereochemistry of SN1

Classes of Alcohols and Alkyl Halides

Substitution vs. Elimination

5.14

-Methyl Bromide + OH- yields Methyl Alcohol and Bromide Ion

-inversion of configuration

-HOMO OH- must overlap LUMO of CH3Br

-Primary, secordary or Tertiary

-high degree of inversion

-leaving group lingers, blocking nucleophile from attacking

-partial loss of optial activity possible

-When water is added to alkynes it forms a keto-enol equilibrium

-a.k.a keto-enol tautomers

-see mechanism 9.1 for interconversions

-keto form more stable, isolated as follows:

-alkyne + H2O, H2SO4, and HgSO4---> ketone

-Markovnikov formation

-double dehydrohalogenation of Dihaloalkanes (may be geminal...on the same carbon, or vicinal...on neighboring carbons)

-use 2 eq. NaNH2 (NaX formed and NH3)

-for prep of terminal alkynes, use 1 eq. base NH3 to 3 eq. NaNH2, then add water or acid to dissolve salt to alkyne

-same for vicinal dihalides

-alternative: heat geminal or vicinal dihalide in KOC(CH3)3 in DMSO

-see two-step synthesis p.331

Other methods conversion alcohols to alkyl halides

-similar conditions can lead to elimination, but the reactions discussed so far will favor substitution

8.8, 8.9

8.12

5.8

Ozonolysis

SN1 Mechanism

Hydroboration-Oxidation

7.7

7.9-7.13

-Thionyl Chloride

ROH+ SOCl2--->RCl + SO2 + HCl

in presence of pyridine or triethylamine [(CH3CH2)3N]...inversion of configuration

-PCl3 or PBr3 react with alcohols to give substituted product by SN1 or SN2 relative to class of alcohol

-https://www.khanacademy.org/science/organic-chemistry/alkenes-alkynes/alkene-reactions-tutorial/v/ozonolysis-1

Cycloalkenes

Dehydration of Alcohols

6.4

9.8

9.10

Reactions of Alkynes

6.6

5.5

-ozonide intermediate

-reductive ozonolysis: 1.O3 2. Zn, H2O or (CH3)2S *forms Ketones

-Oxidative Ozonolysis: 1. O3 2. H2O2 or H2O *forms Carboxylic Acids

-Oxidative Cleavage

Addition of Hydrogen Halides to Alkynes

Steric Effects and SN2 Rates

-https://www.khanacademy.org/science/organic-chemistry/alkenes-alkynes/alkene-reactions-tutorial/v/hydroboration-oxidation-regio-stereo

-Alkene + (Boron Tetrahydrofuran) or (B2H6 and Diglyme) then H2O2 and OH-(NaOH)--->alcohol

-anti-Markovnikov (OH adds to less substituted)

-syn addition

-Pi complex formed... complicated mechanism.

-Mechanism 8.4 & 8.5

-similar reactions to alkenes

SN1 Mechanism

Bonding in Alcohols and Alkyl Halides

-Standard enthalpy change of reaction = Standard enthalpy of formation (products- reactants)

-Mechanism 5.1

-Transition state in protonation step H is partially bonded to alcohol gropup and Cl

-Transition state highest energy, Ea is energy to get there

-Intermediate is tert-butyl oxonium ion **not a transition state**

-Hammond's Postulate: Transition State resembles preceding or following structure more (Early or late transition state)

-Step 2 carbocation formation

-for small rings, cis more stable than trans

-chair conformation becomes half chair with sp2 hybridized bond, bonds are pseudoaliual and pseudoequatorial

-lowest stable trans- ring cyclooctene

-rings 12 or higher act like noncyclic alkenes

8.11

8.10

5.7

-SN2 reactivity increases from tertiary to secondary to primary to methyl

-steric hindrance to nucleophilic attack

-alkyl groups on neighboring carbon also hinder, decreasing rate

-sp3 hybridization for alcohols and alkyl halides

-polarity of alcohols and alkyl halides

6.5

Epoxidation

Addition of Halogens

-alcohol + acid catalyst ---> alkene + water

-reactivity primary<secondary<tertiary

-Regioselectivity: Zaitsev Elimination (favors more substituted alkene)

-Stereoselectivity favors more stable trans

-E1 mechanism (mechanism 7.1)

-E2 mechanism is adjusted where water pushes off leaving group from opposite side of bond (p.254)

-rearrangement possible in E1 with carbocation (mechanism 7.2 & 7.3)

9.9

Prep of alkyl Haldes from Hydrogen Halides

7.8

-Add HX to alkyne

-Markovnikov

-Anti-addition

-Mechanism adds H and X from separate molecules rate=k[alkyne][HX]^2

-adding 2eq HX results in disubstituted alkane

5.6

-carbocation formation b/c too much steric hindrance for SN2 in tertiary alkyl halides

-tert-butyl Bromide + water--->tert-butyl alcohol + hydronium ion + Bromide ion

-reactivity:

methyl<primary<secondary<tertiary

***Secondary react with strong nucleophiles by SN2, weak by SN1

Hydrogenation of Alkynes

Prep of alkenes: Elimination reactions

Nucleophiles and Nucleophilicity

Intermolecular Forces

-alkene +peroxy acid ---> epoxide and carboxylic acid

-https://www.khanacademy.org/science/organic-chemistry/alkenes-alkynes/alkene-reactions-tutorial/v/epoxide-formation-and-anti-dihydroxylation

-R-OH+ H-X---> R-X + H-OH

-Substitution Nucleophilic Unimolecular (SN1)

-Reactivity I>Br>Cl>F

-tertiary alcohols most reactive

-primary and secondary alcohol reaction too slow with HCl

-alternative: alcohol with NaBr, H2SO4, heat yields alkyl bromide

-Beta eliminations (adjacent carbons)

-example dehydrogenation... but not carried out in a lab setting

Reactions:

-add 2eq of H2 with an appropriate metal catalyst to form an alkane

-heat of hydrogenation greater than 2X alkene

-To stop hydrogenation alkene, use Lindlar Palladium (Pd/CaCO3, Lead Acetate, Quinoline)...gives cis alkenes

-faster rate with increased substitution

-look at steric hindrance to see which stereoisomer is formed (bicyclic rings)

-

-Lewis base acting as nucleophile is often an anion (neutral bases include R3N, R2S and R3P)

-Solvolysis reactions

(Hydrolysis):

RX + 2H2O ---> ROH + H3O+ + X-

(Methanolysis):

CH3OH + RX ---> X- +CH3OR + CH3OH2+

-nucleophilicity is measure of nucleophile strength, how fast it replaces leaving group

-correlates with basicity (table 6.2)

-basicity applies in periodic table rows but not columns

-polarizability and solvation (size, blockage by solvent molecule)

-X2 + Alkene ---> vicinal dihalide

-Vicinal= attached to adjacent carbons

-Br and Cl react fast with CH3Cl, acetic acid,Chloroform, or Dichloromethane

-anti addition (trans)

-mechanism has cyclic halonium ion

-rate of addition increases with substitution

-mechanism 8.6

-stereospecific reaction, E yields erythro diastereomer (meso compound) and Z yields threo enantiomer pair

-If water is present, vicinal halohydrin is formed (OH bonds to more substituted carbon)

-Boiling Point: 3 types of forces (Induced dipole-Induced dipole)

(Dipole-Induced Dipole)(Dipole-Dipole)

-hydrogen bonding is a very strong dipole-dipole interaction (it's FON)

-polarizability: ease of distortion of an electron cloud for instantaneous dipoles. (easier with larger atoms w/electrons farther from nucleus)

-induced dipoles stronger with addition of halogens (except Fluorine)

-alkyl halides not soluble in water, alcohols 3C and under completely soluble, longer chains hydrophobic

-alkyl F/Cl less dense than water, alkyl Br/I more dense

-HX with alcohol substitution

-PX3 with alcohol

-SOCl2 with alcohol

-p-Toluene Sulfonyl Chloride with alcohol

-Methanesulfonyl Chloride with alcohol

-Table 5.3 page 199