Chem 6bl Final UCSB Gainer

Fisher esterification

formation of ester from carboxylic acid and an alcohol initiated by an acid catalyst (sulfuric acid)

acid catalyst protonates the alcohol --> forms oxonium ion --> protonates carboxylic acid --> carboxylic acid open to nucleophilic attack by the alcohol --> water eliminated yields protonated ester

What is the solvent in the fischer esterification?

the carboxylic acid

What is a protonated alcohol called?

oxonium ion

What causes the fischer esterification to go to completion?

it is an equilibrium based reaction so carboxylic, a starting reagent is also the solvent. Starting material in excess pushes rxn to completion

Pure acetic acid hazard

acts both as an irritant and is corrosive

sulfuric acid hazard

corrosive and irritant

propionic acid hazard

corrosive and irritant

Purpose of a boiling stone

keeps the refluxing liquid from "bumping"

Role of 5% NaHCO3 in Fischer esterification

neutralizes any excess acid and provides an aqueous layer for neutralized acids to be extracted from

purpose of drying tube in Fischer esterification

the alcohol has a lower boiling point than the carboxylic acid, so it vaporizes at high temperatures. a drying tube allows condensation of the vapor back into the reaction, also driving the reaction to completion

What does sodium sulfate do?

"Dries" solution by absorbing any excess water

Basic overall mech of multistep synthesis of Nylon-6,6

cyclohexene is oxidized with sodium tugstate --> adipic acid with catalytic amount of dimethylformamide solvent --> adipoyl chloride --> polymerized Nylon-6,6

(DMF solvent) DMF + oxalyl chloride --> Vlismeier chlorinating agent

type of polymerization in multistep synthesis of Nylon-6,6 & what it is

unstirred interfacial polymerization

-using two immiscible solvent, each containing a different monomer, and at the solution interface the polymer forms (we don't mix it)

what monomers make up the nylon 6, 6

diamine and diacid chloride with 6 carbons on each monomer unit chain

monomers are linked via amide bonds

what steps are taken in the unstirred interfacial polymerization to make sure it works

monomers in each phase are in low concentration

steps taken in nylon synthesis to reduce temperature and reaction rate

use of an acid chloride instead of carboxylic acid

sodium tungstate in nylon synthesis

oxidized cyclohexene to adipic acid, it is a oxidant and is charged and not very soluble in organic solvent

aliquat 336 in Nylon-6,6 synthesis

used as a phase transfer catalyst. Transfers tungstate from aq. to organic phase b/c tungstate isn't very soluble in organic solvent. It is re-oxidized to be a catalyst via hydrogen peroxide. Speeds up rxn by brining 2 necessary compounds into the same phase

Why was Nylon-6,6 prepared in a biphasic solution?

The aqueous layer contained the hexamethylenediamine and the organic layer contained the adipoyl chloride. At the interface, the two reactants react and form Nylon-6,6.

How is the Vilsmeir reagent formed?

DMF + oxalyl chloride

What is a lachrymator?

eye irritant

hydrogen peroxide in Nylon-6,6 synthesis

used to oxidize tungstate

added in excess to ensure rxn runs to completion

What product forms if oxalyl chloride and adipic acid sit for too long?

The anhydride corresponding to the starting material.

the adipic acid will react to each other to form a long chain of adipic acids

Polymerization: How come it's not possible to isolate the adipoyl chloride in this course?

The adipoyl chloride is extremely reactive

Why do we not purify the adeptly chloride prior to using it in step 3 of the nylon synthesis?

we want to keep it insoluble in the hexanes

Why must the solution of a polymerization reaction be basic?

The solution must be basic because the hexamethyldiamine must be in its basic form in order to react with adipoyl chloride

-neutralizes the HCl produced when the diamine reacts with the diacid chloride

-acidic HCl could protonate any unreacted diamine, leaving it unable to act as a nucleophile to attack the adipoyl chloride --> leads to a smaller yield.

DMF in Nylon-6,6 synthesis

reacts with oxalyl chloride to produce Vilsmeier reagent -> this active species allows the conversion of the carboxylic acid to the corresponding acid chloride. the more reactive acid chloride species allows the polymerization to happen at a faster ate and at room temperature

step 2 of nylon synthesis

conversion of adipic acid into adipoyl chloride

-dimethylformamide reacts with oxalyl chloride to create the Vilsmeier chlorinating reagent

-adipic acid adds to the Vilsmeier reagent to form the adipoyl chloride & regenerated DMF

why was the glassware flame-dried in step 2 of nylon synthesis?

oxalyl chloride is very water reactive

step 3 of nylon synthesis

diacid chloride & diamine react to form polymer chain

-newly formed polyamide is continuously pulled from the solution interface to create space for the monomers to diffuse through the membrane & react with each other

-no need to ensure correct stoichiometry b/c removal & diffusion are at equilibrium

-happens until the limiting reagent monomer is used up

why do we need a catalytic amount of tungstate & aliquat 336, but excess H2O2 in nylon synthesis?

when the tungstate oxidizes cyclohexene, it returns to the aqueous phase in its reduced form where it will react with hydrogen peroxide to become oxidized again, allowing it to oxidize another molecule of cyclohexene

how to maintain anhydrous conditions?

- cap all vials

-use drying tube, containing cotton and CaCl2

Reflux

a running boil, use boiling stone to prevent bumping

How to prepare a TLC plate/Chamber

take beaker and place a filter paper in it

put solvent in and a watch glass on top to keep solvent from evaporating

Then place the TLC once the filter paper is saturated!

What does a TLC tell you?

To check the progress of the reaction

how pure a product is

comparing the relative polarities of several compounds

How to find Rf

see how far the product has moved relative to the solvent and this ratio is the Rf

TLC theoretical

mobile phase solvent

solid phase polar plate

for polar products --> the more polar the solvent the more it outcompetes the solid phase and the product moves on

main 3 steps of nylon-6,6 oxidation

1. oxidation of cyclohexene using sodium tungstate

2. conversion of adipic acid to adipoyl chloride

-involves a catalyic amount of DMF which reacts with oxalyl chloride to make Vilsmeier reagent

3. polymerization of hexamethylenediamine with adipoyl chloride

sodium tungstate warning

irritant and lachrymator

cannot be mixed with oxidizers

role of potassium bisulfate in Nylon-6,6 synthesis

In addition to Aliquat, also acts as a phase transfer catalyst

What will happen if thionyl chloride and adipic acid sit at room temp too long together?

They will form long chains of adipic acid

Why can't adipoyl chloride be isolated in this course?

Highly reactive

basic structure of azo dyes

Ar-N=N-Ar

how are all azo dyes synthesized?

azo coupling between a diazonium ion and an activated aromatic substrate

electrophilic aromatic substitution in which the positively charged diazonium ion is the electrophile

explain the effects of electron-donating/withdrawing groups on the reactivity of aromatic substrates

-electron-donating (amines, ethers, alkyl groups) activate the aromatic substrate & are ortho-para directors

-electron-withdrawing (nitro, carboxylic acid, esters) deactivate the aromatic substrate & are meta-directors

What is a chromophore?

a group of atoms and electrons forming part of an organic molecule that causes it to be colored

methyl orange pH indicator

base - yellow (pH >4.4)

methyl orange exists mostly as a yellow negative sulfonate ion

red - acid (pH >3.2)

the dipolar red ion (helianthin) predominates

nitrous acid in methyl orange synthesis (how is it formed and what does it do)

formed by rxn of sodium nitrite and HCl; it precipitates out the reacive sulfanilic acid b/c its not soluble in acids

why is nitrous acid/sulfanilic acid rxn tough

sulfanilic not soluble in acids... so an alkaline solution is made w/ sodium bicarbonate then HCl is added, forms nitrous acid which precipitates out reactive sulfanilic acid

methyl orange starting materials

diazonium salt: sulfanilic acid --> diazonium ion

azo coupling: N,N-dimethylaniline + diazonium salt

"salting out"

the solubility of the organic compound in aqueous medium is reduced, facilitating the separation of organic and aqueous parts

Interactions of methyl orange die with different fabrics

The dye bound most strongly to wool worsted, silk, and polyamide nylon 6.6, all of which are amides. After dyeing, these fabrics showed a strong color which persisted after washing with soap and water. The dye did not bind as strongly to fabrics with less polar groups.

What would be the result if cuprous chloride were added to the diazonium salt prepared in the methyl orange reaction

degradation of the N2 portion of azo dye, replaced with chlorine

Grignard rxn

A carbon-carbon bond forming rxn

takes a grignard regent, reacts with benzophenone to produce triphenylmethanol

ether solvent is vital and run must be carried out under strict anhydrous conditions

why must grignard not react with water?

very strong nucleophile and strong base

bromobenzene will form benzene

What is the purpose of the ether solvent in the Grignard rxn?

necessary for stabilization of the grignard reagent b/c the magnesium is electron deficient; ether solvent uses its lone pair electrons to coordinate to the magnesium and donate electron density to it

Mechanism of grignard

begins w/ insertion of magnesium into the carbon-bromine bond to generate the Grignard reagent --> this acts as the nucleophiles and attacks the carbonyl carbon of benzophenone. acidic workup forms the alcohol as the final product

What molecules can't be used in a grignard?

molecules that have acidic hydrogens such as alcohols and carboxylic acids

which experiment used syringes?

Grignard

What is the purpose of the drying tube made out of a syringe in the grignard?

to equalize the pressure in the conical vial when liquids are drawn out by an additional syringe

What conditions to ensure anhydrous conditions for grignard?

capping all vials, drying tube, heat gun to dry glassware

What would happen if water were to interfere in the Grignard reaction?

a hydroperoxide would be produced which is not usually isolated from the solvent, resulting in impurities in the product

role of petroleum ether in grignard reagent rxn

extremely nonpolar, dissolves biphenyl rather than the intended product triphenylmethanol

radical transfomrations occur that make it possible for biphenyl to have been produced by two radical benzene intermediates combining -> titration removes these non polar byproducts

what is a titration?

the process of grinding an impure solid in a solvent in which the desired compound is insoluble and the impurities are soluble

1,4-dihydropyridine privileged structure type of synthesis

Hantzsch synthesis

What happens in a Hantzch synthesis?

a one-pot cyclocondensation reaction between an aldehyde, ammonia, and two equivalents of a B-ketoester --> synthesizes a 1,4-dihydropyridine which can be oxidized to form the corresponding pyridine derivative

usually performed in refluxing acetic acid or alcohol as the solvent

bioactivites of 1,4-dihydropyridines

cardiovascular diseases such as hypertension, calcium channel blockers; influence movement of calcium ions into the heart and surrounding blood vessel cells which causes a vasodilation and improves blood flow to the heart, antioxidants, agriculture, diabetes, alzheimer's diabetes, alzheimer's

why is our product in the dihydropyridine synthesis not an effective calcium channel blocker?

while it was thought that most dihydropyridines were effective calcium channel blockers, case studies have shown to prove that only compounds with celiac substituents in the 4-position produced solid hypotensive activity. without this cyclic substituent, as a relatively simple dihydropyridine, our compounds has limited biological activity and is not as significant as compounds with this group, specifically in the ortho position

pharmacophore

an abstract description of molecular features that are necessary for molecular recognition of a ligand by a biological macromolecule.

privileged structure

molecular frameworks which are able of providing useful ligands for more than one type of receptor or enzyme target by judicious structural modifications

multistep day 2 synthesis w/ what starting materials

synthesis of diphenylacetylene from stilbene via bis bromination and bis elimination

electrophilic addition reaction

stilbene + pyridinium perbromide = dibromide

dibromide + potassium hydroxide = diphenyl acetylene

role of pyridium perbromide and why is it better than br2 in multistep day 2

exists in equilibrium with bromide and pyridinium hydrobromide so it provides a slow release of bromine into the reaction rather than volatile and corrosive elemental bromine

why is water added to the second workup in the multistep synthesis day 2?

washes away the impurities: Hbr, AcOH, and ethylene glycol

why is triethylene glycol used in diphenyl acetylene synthesis?

nonpolar enough to dissolve dibromide but also polar enough to dissolve potassium hydroxide

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activation barrier for run is high so high temp is required to supply the required activation energy. solvent used to a low the reactants to mix homogeneously in the same phase but also not evaporate away b/c of its high boiling point

what catalyzes oxidation of benzoin to benzil?

copper II acetate

copper has what function in the redox reaction in the multistep day 3?

oxidizing agent. meaning it is reduced.

paired with nh4no3 which reacts as a co-oxidant

cu accepts electron from oxygen while the acetate ion removes a hydrogen

What is ammonium nitrates purpose in the redox in the multistep?

regenerate the copper species

why does benzoin turn purple in naoh

radical anion concentration is high

intense coloring due to the visible light by the extended delocalized pi system of electrons from the radical anion

multistep day four reaction

formation of hexaphenylbenzene from benzil

(bis-aldol rsn followed by Diels Alder [4+2] cycloaddition

1. benzil + triton B + dibenzyl ketone = tetraphenylcyclopentadienone

2. tetraphenyl + diphenylacetylene = hexaphenylbenzene

what is a dies-alder [4+2] cycloaddition

The [4+2]-cycloaddition of a conjugated diene and a dienophile (an alkene or alkyne), an electrocyclic reaction that involves the 4 π-electrons of the diene and 2 π-electrons of the dienophile. The driving force of the reaction is the formation of new σ-bonds, which are energetically more stable than the π-bonds.

why do we use silicon oil in step 4

very nonpolar and has high boiling point

purpose of triton B in step 4

can be used as a base in organic solvent

aldol condensation; general mechanism and what it is

conversion of an aldehyde to an alcohol (only intermediate step); or ketone instead of aldehyde

ketone as nucleophile, aldehyde as the electrophile (cross aldol condensation w/ two diff. carbonyl compounds)

forms an enolate intermediate

also forms a B-hydroxy ketone

aldol condensation mechanism

carbonyl carbon is highly polar w/ significant partial positive charge, making it a good electrophile, and alpha carbon is a good nucleophile when a base is added;

ketone deprotonated w/ hydroxide to form enolate, which can attack carbonyl carbon of an aldehyde forming a new carbon carbon bond and a beta hydroxy ketone; newly formed alcohol can under go elimination reaction to form a alpha beta unsaturated ketone and water

double aldol condensation product

when the aldol condensation product has an alpha hydrogen, the product can form an elongate and react with another equivalent of something, to give a double aldol condensation product

Why is the alcohol of a beta hydroxy ketone easier to eliminate than a normal alcohol?

b/c the double bond is conjugated, increasing stability

What are the advantages of using aldehydes without alpha hydrogens in the crossed aldol condensation?

prevents the aldehyde from being converted into the nucleophiles from the base that can easily remove that alpha hydrogen and turn it into a elongate ion, just like the ketone (the aldehyde can then remain as the electrophile with the carbonyl caron remaining intact)

reductive amination basic starting materials and formation

The reaction of an aldehyde/ketone and amine with excess ammonia in the presence of a reducing agent

imine formation and reduction in tandem

imination

reaction of aldehyde/ketone with a primary or secondary amine to form an immune

secondary amines produce an ammonium ion which can tautomerize into an enamine

reduced imine

is an amine

sodium borohydride in reductive amination

reducing agent;

donates electrons to the imine and then becomes oxidized

REDUCES THE IMINE AFTER IMINE FORMATION DURING IMINE REDUCTION STEP

starting materials in reductive amination

ortho-vanillin, aldehyde, and para-toluidine, primary amine

purpose of acetic anhydride in reductive amination

helps us convert the new secondary amine to a more stable amide

purpose of acetic acid in reductive amination

quench the excess borohydrive and to neutralize the phenoxide ion

What happens during the first step of the reductive amination?

the solids react, turn to a liquid, and then transform back to a dry powder; impurities are being introduced into the solid, lowering the melting point and causing it to melt, before the two solid reacts and become a new product

What do you observe during the reduction of the imine?

solution bubbles, all of the solid ends up dissolving

Why is water added during the last step of the reductive amination?

neutralizes any unreacted acids, like acetic acid, tahat would've been formed as a byproduct of acetylation of the amine

Why is it necessary to wait until the amine is fully formed before adding NaBH4?

b/c the sodium borohydride can reduce an unreacted aldehyde to form an alcohol

what are the three steps, simple versions, of the reductive amination?

imine formation, reduction of the imine, acetylation of the amine

What happens in the gold catalysis?

rearrangment of propargyl alcohols to cis and trans isomers to a ketone using a gold catalyst