Ch 42-45 reactions and functional groups

epimer

*subtype of diatereomers *differ in configuration at exactly one chiral carbon

imine formation

- Ammonia (NH3) is added to the carbonyl, resulting in the elimination of water - can undergo tautomerization and form enamine - Example of condensation reaction since a small molecule is lost during the formation of a bond between two molecules.

Ether Synthesis

- condensation of two molecules of an alcohol -metal oxides with primary alkyl halides or tosylates - phenol and NaOH, H2O - oxirane

equatorial

- in the place of the molecule - largest substituent will generally take this position to reduce strain

SN1

-2 steps -Rate limiting step, so reaction rate is dependent on concentration of R-X tertiary substrate is best do not require strong base good leaving group required prefer protic solvent (acid) varied steriochem because nucleophile can attack from top or bottoms can produce racemic mixture

E1

-2 steps -Rate limiting step, so reaction rate is dependent on concentration of R-X tertiary substrate is best do not require strong base good leaving group required prefer protic solvent (acid) major product is the more substituted heat makes this more favorable over SN1

synthesis of anyhydrides

-acyl chloride reaction -cyclic anhydride self-condensation -condension of 2 cooh

ring flip

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

anhydrides

-carboxylic acid derivative -had water molecule removed during formation -formed from 2 carboxylic acid molecules -named by replacing acid with anhydride in the name of the carboxylic acid if anhydride is formed from only 1 type of carboxylic acid -if anhydride is not symmetrical, both carboxylic acids are named before the anhydride is added to the name (ex: ethanoic propanoic anhydride) -no hydrogen bond less poor and lower bp and melting points not soluble in water

Hofmann Rearrangement

-converts amides to primary amines with the loss of the carbonyl carbon as a molecule of CO2 formation of nitrene which rearranges to form isocyanate which is hydrolyzed into amine

carboxylic acid

-oic acid Always terminal most highly oxidized organic compound H of OH is highly acidic (3-6 pKA) can form hydrogen bonds high boiling point, which increases wth molecular weight adding EDG- decreases acidity adding EWG- increases acidity

ketone

-one location must be specified oxo- dipole moment -> elevation in bp but still lower than OH because no H bonding

Synthesis of Aldehydes and Ketones

-oxidation of alcohols -oxidative cleavage of alkenes - acetylation

acyl halide

-yl halide the most reactive of the derivatives carbonl always reforms No H bonding so slightly lower bp and mp

SN2

1 step concerted backside attack rate depended on both nucleophile and substrate reaction less substituted carbon is most reactive strong nucleophile strong leaving group prefer aprotic (acetone, DMSO) if chiral -> flip when Lg and nuc have same priority

E2

1 step concerted loss of H+ and LG rate dependent on both nucleophile and substrate strong base required good leaving group required often performed in conjugate acid of strong base used heat gives an advantage over SN2 trans>cis

alkene to ketone

1) KMnO4, OH-, heat 2) H+

alkene to aldehyde

1) O3 2) Zn, H20 (or CH3SCH3)

tosylate

A compound containing the functional group -SO3C6H4CH3, derived from toluenesulfonic acid used to convert alcohol into something else

racemic mixture

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

aldol condensation

A reaction in which an aldehyde or ketone acts as both the electrophile and nucleophile, resulting in the formation of a carbon-carbon bond in a new molecule called an aldol water becomes a good leaving group and the extra electrons left over becomes a double bond leto-target enol- nucleophone

electrophilic aromatic substitution

A reaction in which an electrophile is substituted for a hydrogen on an aromatic ring.

nucleophilic substitution

A type of substitution reaction in which a nucleophile is attracted to an electron-deficient centre or atom, where it donates a pair of electrons to form a new covalent bond. nucleophile attacks carbonyl and then OH becomes a good leaving group and the carbonyl reforms

electrophile

An electron pair acceptor loves electrons gets attacked by nucleus

nucleophile

An electron pair donor loves the nucleus attacks the electrophile

meta directors

CHO COOR COOH COCl CN SO3H NR3+ NO2

phosphate esters

Can form between a phosphate and a free hydroxyl group. Phosphate groups are often attached to proteins in this way.

Synthesis of Carboxylic Acids

Carboxylic acids can be prepared via oxidation of aldehydes and primary alcohols. The oxidant used for this is usually dichromate salt (Na2Cr2O7 & K2Cr2O7), chromium trioxide (CrO3) or potassium permanganate (KMnO4) can also use oxidative cleavage of alkenes, organometallic reagents, hydrolysis of nitrils

geometric isomers

Compounds that have the same molecular formula but differ in the spatial arrangements of their atoms. cis/trans e/z

wittig reaction

Converts a ketone (C=O) to and alkene (C=C). 1) A phosphorus ylide (a neutral molecule with a negatively charged carbanion) acts as the nucleophile toward the carbonyl C forming a betaine (beta-ine) with a P+ and an O-. 2) Betaine is unstable so cyclization quickly gives the alkene (C=C) and a triphenylphosphine oxide (P=O). When possible, a mixture of cis and trans isomers is formed.

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.

acyl halide to aldehyde

H2 Pd/BaSO4

alkynes to alkenes

H2, Lindler's catalyst (cis) or Na, NH3 (trans

hydration of alkenes

H2C=CH2 + H2O -> CH3CH2OH alkenes + h2o with acid to form an alcohol

sulfonation of benzene

H2SO4 fuming

aldehyde and ketone reaction with HCN

HCN attacks the carbonyl etc

nitration of benzene

HNO3, H2SO4

Anti-Markovnikov Addition

In the presence of peroxides (ROOR), Bromine from HBr, not the hydrogen, will add to the least-substituted Carbon (does not apply with other halogens - those will still add Markovnikov).

torsional strain

Increased energy that results when molecules assume eclipsed or gauche staggered conformations more -> more energy ->. less stable

acyl group

It is a functional group of organic compounds which is usually obtained by replacing the hydroxyl group (--OH) from any carboxylic acid.

Aldehyde oxidation

KMnO4, CrO3, Ag2O or H2O2 makes carboxylic acid

ester reduction

LAH produces primary alcohol

aldehyde/ketone reduction

LAH or NaBH4

amide reduction

LiAlH4 is used to reduce this to a amine

LiAlH4

Lithium aluminum hydride is a very strong reducing agent. It will reduce aldehydes, ketones, esters, and carboxylic acids to alcohols, and amides and nitriles to amines. It will also open epoxides.

ortho/para directors

NH2 OH OR R Benzene H X (Br, Cl, I)

L sugar

OH on left

D sugar

OH on right

enantiomer

One of two compounds that are mirror images of each other and that differ in shape due to the presence of an asymmetric carbon. nonsuperimposible mirror images that cannot be rearranged to be the same

Cleavage of ethers

Only under vigorous conditions using HBr or HI; proceeds by either Sn1 or Sn2 mechanism produces two alkyl halides most substituted carbon- attacked by acid least substituted carbon- attacked by base

oxidation of alcohols

Primary alcohols can be oxidized using PCC and further oxidized to carboxylic acids using KMnO₄, Na₂Cr₂O₇, or CrO₃. Secondary alcohols can be oxidized to ketones using any of these oxidants.

PCC

Primary alcohols to aldehydes and secondary alcohols to ketones

alcohols

R-OH hydroxyl group suffix: -ol, high priority for naming attached to a aromatic ring: phenol form hydrogen bonds high boiling points -> increasing with increasing hydroxyl groups

Friedel-Crafts Acylation

RCOCl, AlCl3 product more reactive than reactnat

amide

RCONR2 peptide bonds that link amino acids into proteins ar these bonds -amide have the ability to form hydrogen bonds very high melting and boiling points good water solubility least reactive

ether

ROR two alkyl or aryl groups bonded to a single oxygen atom no hydrogen bonding boil at low temps only slightly polar only slightly soluble in water frequently used as solvents can form highly reactive peroxides

Friedel-Crafts Alkylation of Benzene

RX, AlCl3

reaction with weak base and aprotic solvent

SN2 (methyl, primary, secondary)

reaction in aprotic solvent

SN2 or E2

acyl halide formation

SOCl2

NaBH4

Sodium borohydride is a reagent for the reduction of ketones and aldehydes, it will also reduce acid halides. It is also used in the oxymercuration reaction to replace mercury with H. DOES NOT REDUCE COOH or ESters

decarboxylation

The complete loss of a carboxyl group as carbon dioxide

Zaitsev's Rule

The most substituted alkene is formed preferentially

steric hindrance

The prevention of a reaction at a particular location in a molecule by substituent groups around the reactive site.

z isomer

The same groups are on the same side of the double bond Cis isomer

SOCl2

Thionyl chloride is used for the formation of alkyl chlorides from alcohols and acid chlorides (acyl chlorides) from carboxylic acids.

Markovnikov's Rule

When adding to an alkene, put the H on the C with the most H's already. ("The rich get richer")

Halogenation of benzene

X2, FeX3

aldehyde/ketone to alkane

Zn(Hg), Hg (clemmensen ) or H2NNH2, Base and heat (wolff-kishner)

Clemmenson Reduction

Zn(Hg)/aqHCl ketone to alkane

carboxylic acid synthesis

[carboxylic acids] oxidation of primary alcohols with KMnO4, hydrolysis of nitriles, carbonation with girgnard

KMnO4

a very strong oxidizing agent. primary alcohols and aldehydes -> carboxylic acids, secondary alcohols -> ketones alkenes -> diols oxidatively cleave carbon-carbon multiple bonds.

hydrolysis of amide

acidic conditions allow carbonyl O to become protonated => Nu attack by water => carb acid and ammonia basic conditions - attack and form carboxylate

carboxylic acid derivatives

acyl halides, anhydride, ester, amide all have highly polarized c=o

Ester and Grignard reagent

add to the carbonyl or the ester -> ketone ketone reacts quickly to produce tertiary alcohol

addition reaction to create alcohol

addition of water to double bonds addition of organometallic compounds to carbonyl groups

synthesis of alcohol

addition, substitution, reduction, phenol

electron donating group (activators)

adds e- density NH2 OH OR R Benzene H

transesterification

alcohol acts as a nucleophile and displaces the alkoxy group

acyl halide to ester

alcohol attacks and cl leaves and bonds with hydrogen when the carbonyl is reformed

anhydride to ester and carboxylic acid

alcohol reaction -> 1 of each

PCC

alcohol to aldehyde

conc. H2SO4

alcohol to alkene

dichromate salt

alcohol to ketone

addition of H2O

alkene to alcohol

mCPBA

alkene to epoxide

acyl halide to amide

amine (ammonia) attacks and displaces the halide as it reforms the carbonyl primary and secondary amines can be used as the nucrlophile

aryl group

an aromatic carbon ring system from which one hydrogen atom has been removed

michael addition

an enolate attacks an alpha,beta-unsaturated carbonyl, creaing a bond

aprotic solvent

any solvent that cannot donate H+

protic solvent

any solvent that contains H+ that is easily displaced

phenol synthesis

arylsulonic acid with heat hydrolysis of diazonium salts

least substituted carbon

attacked by a base

most substituted carbon

attacked by an acid

phenyl

benzene as a substituent

radical propagation

can occur multiple times starts with 1 radical, ends with 2 different radical chain reaction

aldehyde

carbonyl and alkyl group and hydrogen -al must be terminal highest priority group in a molecule

acyl halide to anhydride

carboxylate salt attacks and the cl is leaves as leaving group when carbonyl reforms

highest priority to lowest priority functional groups

carboxylic acid, esters, amides, nitriles, aldehydes, ketones, alcohols, amines, ethers the more oxidized the higher priority

Condensation of two carboxylic acids

condense to form anhydride anhydrous conditions only

hydrolysis of acyl halide

conversion back into carboxylic acid form irritating odor

substitution reactions with alcohol

convert OH to water-> good leaving group

anhydride hydrolysis

converts an anhydride back into a carboxylic acid

anti addition of halogens

cyclic intermediate that prevents nucleophilic attack on same side

pKa decreases

decrease in acidity potentially due to an EDG

elimination reactions with alcohol

dehydrated in a strongly acidic solution -> alkenes more stable produce: the more substituted

esters

dehydration products of carboxylic acids and alcohols -oate no H bonding less polar low mp and bp solubility depends on leith of hydrocarbon chain smaller- more soluble longer- less soluble

conformational isomers

differ by rotation around a single sigma bond

Reactions of Alcohols

elimination substitution oxidation

claisen condensation

enolate ion of one ester acts as nucleophile attacking another ester

triaglycerol

esters of long chain carboxylic acids

peroxide formation

ethers react w/ oxygen => highly explosive peroxides

radical initiation

extreme conditions (uv light or heat) generates radicals starts with 0 and ends with 2

polar head

face outwards

hydration of alkynes

form a carbonyl

aldehyde hydration

form geminal diols water attacks carbonyl and gets deprotonated and the o- gets protonated

Carbonation of Organometallic Reagents

grignard used with co2 to for cooh adds one carbon to the chain

catalytic hydrogenation of alkenes and alkynes

h2/pt end in a single bond

meso compound

have an internal plane of symmetry so do not have enantiomers do not exhibit optical activity

chiral centers

have four different groups attached to the central carbon

Cyclic anhydride self-condensation

heating carboxylic acids creates a ring releases water

SN2 can be inhibited

high substituted substrates or bulky bases

pKa increase

increase in acidity potentially due to an EWG

Wolff-Kishner Reduction

ketone to hydrazine (NNH2) using H2NNH2 then use a base to remove the hydrazone

micelle

lipid molecules that arrange themselves in a spherical form in aqueous solutions

soap formation

long chain hydrocarbon cooh react with NaOH or KOH -> salts which are soluble in aqueous solutions

reaction with strong base and aprotic solvent

methyl- SN2 primary- SN2 >E2 secondary - E2 > SN2 tertiary - E2

condensation of carboxylic acids and alcohols

mixture wil condense into esters under anhydrous conditions

leaving group

molecular fragment that departs with a pair of electrons ex) weak base, conj base of a weak acid, halogen

PBr3

molecule that replaces OH with Br in an Sn2 style reaction

isomerism

molecules built from the same part

structural (constitutional) isomers

molecules with same molecular formula but different bonds between atoms can have many different physical and chemical properties

phenols

more acidic than aliphatic alcohols (resonance) readily form salts with inorganic bases (NaOH) intermolecular hydrogen bonds high mp and bp only slightly soluble in water EWG -> increases acidity EDG -> decreases acidity

hydrolysis of nitriles

nitrile + hcl + 2h20 ---> carboxylic acid + nh4cl

ester to amide

nitrogen base attacks the carbonyl

ketone oxidation

not possible unless extraordinarily Harsh condition

nucleophilic addition to a carbonyl

nucleophile attacks carbonyl and the o- is protonated

anhydride acylation

occurs readily with AlCl3 aryl ketone and a cooh

trans

opposite side

ether reactions

peroxide formation cleavage

bulky nucleophile

primary, secondary tertiary E2

anhydride to amide

produces an amide and a carboxylic acid cleaved by ammonia then reacts with ammonia to form ammonium carboxylate

ester formation (starting with COOH)

reaction with alcohol under acidic conditions acidic- pronate the O first forms water also

acyl halide reduction

reduced to acolho with LAH selectively reduced to aldehyde using H2 and Pd/BaSO4

reduction reaction to form alcohol

reduction of aldehydes, ketones, carboxylic acids, esters LiAlH4 - stronger, less specific (reduces cOOH and esters ) NaBH4- milder more selective (not COOH or esters, but aldehydes and ketones)

dibromination to synthesize alkynes from alkenes

repetitive E2

optical activity

rotation of the plane of polarized light

cis

same side of the carbon chain

reaction with protic solvent and weak base

secondary or tertiary SN1 and E1

keto-enol tautomerization

shift from a carbonyl to an alkene with an alcohol. It is a reaction at equilibrium; these structures are not resonance structures

substitution to create alcohol

sn1 and sn2

radical termination

starts with 2 and ends with 0

Diastereomers

stereoisomers that are not mirror images opposite at some but not all sterocenters

electron withdrawing groups

strongly electronegative and pull electron density away from rest of the molecule, and stabilize negative charge. X CHO COOR COOH COCl CN SO3H NR3+ NO2

E isomer

the isomer with the high-priority groups on opposite sides of the double bond

radical reaction

three steps: initiation, propagation, termination cl2 (less selective) and br2 (more selective) will generate useful radicals that will react with alkanes f2 too reactive and I2 too unreactive

acetal and ketal formation

two. eq. of alcohol => acetal or a ketal in aldehyde => H is characteristic one eq. of OH => hemiacetal or hemiketal contains one OH in base, rxn would stop here

reaction of carboxylic acid

use LAH to return to primary alcohol

AlCl3

used in the presence of an acyl halide to add that thing to the benzene

R

used to resemble a generalized alkyl group

sugar

usually end in -ose aldoses - aldehyde ketoses- ketone

I-

very good leaving group because of its size

H of alcohol

weakly acidic

acyl halide acylation

with AlCl3 can react an attack a benzene and be added to the ring

Acyl chloride to ester

with alcohol under anhydrous condition

Hydrolysis of esters

yields carboxylic acid and alcohols acid- proton first, then attack carbonyl basic- attack first