U of S CHEM250 - Organic Chemistry Final Notes

Midterm Notes

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I. Chapter 1 A. Electronegativity Electronegativity B. Hybridization Hybridization C. Function al groups D. Priority E. Resonance Resonance

II. Acids & Bases A. Arrhenius Arrhenius B. Bronsted-Lowry Bronsted-Lowry 1. pKa a) struc structu ture re (1) (1) reson resonanc ancee (2) inductiv inductivee effect b) rank rankin ing g C. Lewis

III. Cycloalkanes A. Neuman projections B. Cyclohexane 1. chair/boa chair/boatt conformat conformations ions 2. axial/equat axial/equatorial orial positions positions a) equatorial monosubstituted most stable stable

IV. Alkenes & Alkynes A. Cis/trans isomerism B. E/Z isomerism isomerism

V. Reactions of Alkenes A. Hydration Hydration 1. ALKE + H2O —[H+]—> ALKY–OH ALKY–OH 2. Markoni Markonikoff koff's 's rule B. Halogenation 1. ALKE + Br2 or Cl2 —> Br–ALKY–Br Br–ALKY–Br 2. trans-diax trans-diaxial ial addition addition a) no cis cis isome isomerr b) 2 entanti entantionome onomers rs C. Hydrohalogenation Hydrohalogenation 1. ALKE + HX (X=halo (X=halogen) gen) —> ALKY—X ALKY—X D. Hydr ogenation (Reduction) 1. ALKE ALKE + H2 —Ni, —Ni, Pd, Pt—> Pt—> ALKY E. Energy Diagrams Diagrams 1. ΔH —> energy difference between products and reactants

VI. Stereochemistry A. Constitutional Isomers B. Stereoisomers Stereoisomers 1. diaster diasteriome iomers rs a) trans/ trans/cis cis b) non-mir non-mirror ror images images 2. entant entantiom iomers ers a) non-superimposabl non-superimposablee mirror images 3. meso compound compoundss a) not isomers isomers b) has plane plane of symet symetry ry c) can be rotated rotated to form form original compound

VII. Haloalkanes A. SN1 vs SN2 1 . SN1 a) 2 step step proces processs b) formatio formation n of carbocati carbocation on c) at stereoc stereocentr entres es (1) racemic mixture of products products (2) random random attac attack k 2 . SN2 a) 1 step step b) formation of intermediate intermediate c) at steroc sterocentr entres es (1) backside backside attack attack (2) inversion of configuration B. E1 vs E2 — ß- Elimination 1. Zaitsev' Zaitsev'ss Rule Rule a) major product will will be most substituted substituted at double double bond 2. E1 a) 2 step step b) formatio formation n of carbocati carbocation on (1) protic protic solvent solventss 3. E2 a) Concerted Concerted proces processs (1) 2° & 3° haloalka haloalkanes nes

VIII. Alcohols, Ethers Ethers & Thiols 1

Midterm Notes

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A. Alcohol reactions 1. ROH + Ca/Na/K 2. ROH + HX —> R–X + HOH 3. ROH —H2SO4 or H3PO4—> 4. ROH —PCC—> R=O H carbonyl group B. Ethers 1. Epoxide formation a) in cyclic compounds (1) cis product 2. Epoxide reactions a) trans product 

IX. Benzene and Derivatives A. Resonance energy 1. difference in energy between resonant structure and its most stable contributing structure without resonance B. [D1]Aromaticity (Huckel's rule) 1. Must be cyclic

a)

2. Must be planar 3. each atom of the ring must have a p orbital perpendicular to the plane of ring

a)

4. must contain 4n+2 pi electrons

a)

C. [D2]Heter ocyclic Aromatics 1. Heterocyclic compound a) compound that contains one or more atoms other than carbon in its ring

b)

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2. Heterocyclic aromatic compound a) heterocyclic compound whose ring is aromatic

b)

D. Nomenclature 1. Phenyl group (Ph-) 2. Disubstituted benzenes a) ortho (1,2) b) meta (1,3) c) para (1,4) 3. Polysubstituted benzenes a) number atoms of ring b) if a group imparts special name, use as parent (1) eg. phenol, toluene c) otherwise number to give smallest numbers and list alphabetically E. [D2,D3,D4]Reactions of benzene 1. characteristic reaction of aromatic compounds is  Electrophilic Aromatic Substitution a) General Mechanism:

(1)

2. Nitration a) substitution with nitro group NO2

b)

3. Friedel-Crafts Alkylation a) forms C-C bond with an alkyl group b) Arene + alkyl halide —AlCl3—> Arene-alkyl + H-halide

(1)

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c) practical only with stable carbocations as electrophiles (2° & 3°) d) fails if benze ring bears electron-withdrawing group (1) double or triple bond (2) alkyl halides (3) nitro (4) 4° amines 4. Friedel-Crafts Acylation a) Arene + Acyl halide —AlCl3—> Arene-acyl (ketone) + H-halide

(1)

5. Sulfonation: a) Arene + Sulfuric acid —> Arene-SO3H + H2O 6. Other Benzene Alkylations

a)

F. Di and polysubstitution 1. pre-existing groups influence further substitution in rate and orientation 2. orientation a) ortho-para directors (1) lone pairs b) meta directors (1) no lone pairs 3 . R ate a) activating (1) electron donating groups b) deactivating (1) electron withdrawing groups 4. Ortho-Para directors — all activating except for halogens — all have lone pair of electrons a) strongly activating (1) amines (2) hydroxyl (3) alkoxy 4

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b) moderately activating (1) NHCOR (2) OCOR c) weakly activating (1) aryl (2) alkyl d) weakly deactivating (1) halogens 5. Meta-directors — all carry full or partial positive charge where bonded to ring a) moderately deactivating (1) aldehyde (2) ketone (3) carboxylic acid (4) ester (5) amide (6) SO3H b) strongly deactivating (1) NO2 (2) NH3+ ( 3) C F3 ( 4) C Cl 3 6. Rate-determining step usually formation of cation intermediate G. Phenols 1. Phenols greatly more acidic than alcohols a) greater stability of phenoxide ion b) ring substituents, particularly X and NO2, increase acidity

X. Amines A. Structure & Classification 1. 1°,2°,3° a) N atom is bonded to 1, 2 or 3 groups 2. 4° a) N atom is bonded to 4 groups and bears a positive charge (no lone pair) 3. Aliphatic a) N bonded only to alkyl groups 4. Aromatic a) N bonded directly to one or more aryl group 5. Heterocyclic a) amine in which nitrogen is one of the atoms of a ring B. [D4,D5]Nomenclature 1. Aliphatic 1°

a)

2. 2° & 3°

a)

3. Aromatic a) aniline is parent

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b)

4. Amine has very low priority

a)

(1) should be 2-aminobenzoic acid C. Basicity 1. all amines are weak bases 2. aromatic amines weaker bases than aliphatic a) no resonance stabilization once protonated (1) benzene aromatic ring interrupted 3. electron-withdrawing groups decrease basicity by decreasing availability of lone pair on nitrogen D. Reaction with Acids 1. amines form water-soluble salts in strong acids

XI. Aldehydes and Ketones A. [D5]Structure 1. Aldehyde group

a)

2. Ketone Group

a)

B. [D5]Nomenclature 1. Aldehydes a) parent is longest chain including the carbonyl group (1) suffix is -al

(2)

b) cyclic molecules (1) suffix is -carbaldehyde

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(2)

2. Ketones a) linear or cyclic (1) suffix is -one

(2)

3. If priority is lower than other functional groups, then use prefix oxo-

a)

C. Physical Properties 1. polar compounds with dipole-dipole interactions 2. higher boiling point and more soluble than non-polar compounds D. [D6,D7,D8,D9]Reactions 1. Grignard reacents a) carbon nucleophiles with formula R-Mg-X b) carbanion adds to the carbonyl group of aldehydes and ketones c) Grignard reactants are very strong bases (1) react with protic acids to form alkanes i) CH3-CH2-MgBr + H(+) —> CH3-CH2-H + Mg(2+) + Br(-) (2) any compound with OH, NH, or SH bond reacts with a grignard reagent by proton transfer

i)

ii) Water iii) Alcohols iv) Phenols v) Carboxylic Acids vi) Amines vii) thiols d) Reaction with methanal (formaldehyde) gives 1° alcohol

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e) reaction with other aldehydes gives 2° alcohol

(1)

f) reaction with ketones gives 3° alcohol

(1)

2. Hemiacetal a) molecule with -OH and -OR bonded to same carbon

(1)

b) minor components of equilibrium unless cyclic

(1)

3. Acetal a) molecule with 2 -OR groups bonded to same carbon

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(1)

b) Examples

(1)

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(2)

4. Imines a) molecule with a C=N bond, also schiff base b) formed by reaction of an aldehyde or ketone with ammonia or 1° amine

(1)

5. Keto-Enol Tautomerism a ) e no l (1) molecule containing an -OH group on a carbon-carbon double bond of an alkene (2) proportion of enol form generally insignificant

(3)

b) interconversion between tautomers catalyzed by both acids and bases (1) enantiomerically pure aldehydes and ketones slowly become racemic in acids or bases as the tautomers interconvert, since enols are achiral

(2)

6. α-Halogenation a) aldehydes and ketones with alpha hydrogen, react with Br2 and Cl2 to give an alpha haloaldehyde or ketone b) intermediate is an enol

(1)

7. Metal Hydride Reduction a) aldehydes can be reduced to 1° alcohols b) ketones reduced to 2° alcohols c) common reagents NaBH4 and LiAlH4

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d)

XII. Carboxylic Acids A. Structure 1. functional group is a carboxyl group a) -COOH

b)

B. Nomenclature 1. suffix -oic acid

a)

2. -dioic acid for dicarboxylic acids

a)

3. group has higher priority than most others 4. cyclic carboxylic acids name cyclic chain and add suffix -carboxylic acid

a)

5. aromatic carboxylic acids

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Midterm Notes

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a)

C. Physical Properties 1. hydrogen bonding a) significantly higher boiling points b) more soluble in water 2. weak acids a) acidity greater than alcohols due to resonance stabilization b) pKa 4–5 c) electron withdrawing substituents near carboxyl group increase acidity due to inductive effects D. Reactions 1. Reaction with bases a) carboxylic acids react with strong bases (NaOH, KOH), ammonia and amines to form water soluble salts b) carboxylic acids react with NaHCO3 and NaCO3 to form water-soluble salts and carbonic acid (H2CO3) which breaks down to CO2 and H2O 2. Reduction a) carboxyl group very resistant to reduction (1) not reduced by H2/metal catylist (2) not reduced by NaBH4 b) LiAlH4 reduces carboxyl group to a 1° alcohol

(1)

3. Fischer Esterification a) Esters prepared by treating carboxylic acid with an alcohol with acid catylist

(1)

4. Acid Chlorides a) carbonyl group bonded to Cl b) prepared by treating a carboxylic acid with thionyl chloride

(1)

5. Decarboxylation a) loss of CO2 from carboxyl group b) most carboxylic acids if heated to very high temperature undergo thermal decarboxylation c) if carbonyl group beta to carboxyl group, mild heating only required

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Midterm Notes

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XIII. Functional Derivatives of Carboxylic Acids A. Types 1. Acid Chlorides a) acyl group bonded to a halogen b) name with suffix -yl chloride

(1)

2. Acid Anhydrides a) two acyl groups bonded to an oxygen atom b) name by replacing acid of parent by anhydride

(1)

3. Esters a) acyl group bonded to -OR or -OAr b) name by replacing -ic acid with -ate

(1)

4. Amides a) acyl group bonded to a trivalent nitrogen b) name by replacing -ic acid with -amide c) if amide nitrogen bonded to alkyl or aryl group, name group using N as locator

(1)

B. Reactions 13

Midterm Notes

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1. Characteristic reaction: Nucleophilic acyl substitution a) an substitution of one nucleophile for another b) forms tetrahedral intermediate like SN1 reactions

(1)

c) COR group stays d) Nucleophile (1) weaker the lewis base, the better the leaving group i) (best) X > COOR > OR > NR2 ii) (highest nucleophlic substitution reactivity) Acyl chloride > Acid anhydride > Ester > Amide 2. Hydrolysis a) Acid Chlorides (1) low molecular weight acid chlorides react rapidly with water; higher weight less reactive

(2)

b) Acid Anhydrides (1) low weight very reactive; higher weight, less reactive

(2)

c) Esters (1) hydrolysed very slowly unless with aqueous acid or base (2) Acid-catylized (catylitic ammounts)

i)

ii) reversible (3) Base-promoted (1 mole per mole ester)

i)

ii) irreversible d) Amides (1) Both acid and base reactions require equimolar quantities (2) acid-promoted i) products are carboxylic acid and ammonium or amine salt

ii)

(3) base-promoted i) products are carboxylate salt and an amine

ii)

3. Reaction with Alcohols 14

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a) Acid chlorides react with alcohols to give an ester and HCl

(1)

b) Acid Anhydrides react with alcohols to give an ester and a carboxylic acid

(1)

c) Esters undergo tranesterification (1) acid catalysed exchange of the OR group

(2)

d) Amides do not react with alcohols under any conditions 4. Reaction with Ammonia and Amines a) Acid halides (1) react with ammonia, 1° amines and 2° amines to form amides (2) not 3° amines: require free hydrogen (3) require 2 moles of amine: 1 to form amide, 1 to neutralize HCl

(4)

b) Acid anhydrides (1) react with ammonia, 1° amines and 2° amines to form amides (2) 2 moles required

(3)

c) Esters (1) react with ammonia, 1° amines and 2° amines to form amides i) less reactive than either acid halides or anhydrides ii) only 1 mole required

(2)

d) Amides do not react with Ammonia or Amines 5. Esters with Grignard Reagents a) an ester reacted with 2 moles of Grignard reagents gives a 3° alcohol (2° with methanoate)

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6. Reduction of Esters a) unlike aldehydes and ketones, esters are only reduced by LiAlH4 to two alcohols

b)

7. Reduction of amides a) LiAlH4 reduction of an amide gives 1°, 2°, or 3° amines

b)

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