orgo lab exam 1

salicylic acid structure

carboxylic acid and alcohol substituents

salicyclic acid properties

keratolytic agent: common ingredient in acne creams, antidandruff sahmpoo, antibacterial properties: toothpaste, mouthwash, precursor to aspirin

aspirin structure

synthesis of salicyclic acid (equation)

methyl salicylate + 2 naoh > salt + meoh + h2o
salt + 2hcl > salicyclic acid + 2nacl

what transformation of fxnal group to form salicylic acid

from methyl salicylate, phenol functional group remains, but ester (R-O-OCH3) is transformed to carboxylic acid (R-O-OH)

what transformation of fxnal group to form aspirin from salicylic acid

phenol functional group goes to ester functional group (R-OH > R-(C=O)-OH)

general hydrolysis of esters? R-(C=O)-OR’

acidic condition: form carboxylic acid, but basic condition: carboxylate anion (R-(C=O)-O-)

base-promoted hydrolysis of methyl salicylate to salicylic acid

Hydrolysis is base promoted, not base catalyzed -- because the base (OH–)

is the nucleophile that adds to the ester. It participates in the reaction and is

not regenerated later.

hydrolysis of triacylglycerols

A triacylglycerol is a triester containing three long hydrocarbon side chains

(Typically, the R groups have 12-20 C’s) .

 Metabolism of a triacylglycerol: Hydrolysis of three ester linkages forms Glycerol and

three long-chain fatty acids.

 Hydrolysis of a Lipid is the same as the Hydrolysis of an Ester Hydrolysis.

 This lipid hydrolysis is catalyzed by the enzyme lipases

BASE-promoted hydrolysis of triacylglycerols

saponification

experimental details of lab A

reaction flask: clamped erlenmeyer
stir bar
grad cylinder
pasteur pipette
hot plate/stirrer

limiting reactant

The reactant that is present in the smallest

amount and would limit the amount of product possible. The

moles of product (i.e. theoretical yield) is determined by the

moles of “limiting reactant” on a molar equivalent basis.

theoretical yield

The yield of a reaction assuming 100%

conversion of the limiting reactant to the product

percent yield

is calculated based on the amount of product

actually obtained in the experiment and the Theoretical Yield.

% Yield = Actual Yield / Theoretical Yield x 100

multistep synthesis percent yield

the overall percent yield is determined by multiplying the yield of

each step expressed as a decimal.

- multiply the answer by 100 to convert final value back to

% yield

recrystallization

Convenient way to purify a solid organic compound by using a suitable

solvent.

steps of recrystallization

Step 1. Impure solid is dissolved in an appropriate hot solvent – the

impure crystal lattice breaks down

Step 2. Slow cooling of the solution - (first on bench top, undisturbed, and

later, later cool in an ice-water bath)– allows for the formation of purer,

larger crystals. This is because impurity molecules have sufficient time to

return to the solution

why no rapid cooling for recrystallization

results in precipitation – impurities are trapped due

to rapid formation of the lattice

choose good solvent for recrystallziation

The solid you are trying to purify should be soluble in

the hot solvent and insoluble in a cold or room

temperature solvent

vacuum filt

that is used

to quickly & completely

separate a solid from the

liquid with which it is mixed; buchner, adapter for right seal, clamp, vacuum filt, ring stand

vacuum filt tubing

Employs Heavy-walled rubber tubing – to prevent the tubing from collapsing from atmospheric pressure on the

outside when the vacuum is applied.

when washing filtered crystals with solvent

Always use small portions of solvent – to avoid washing away small amounts of your product

ensure efficient drying of product

after first round of filt, Empty the mother liquor from the vacuum filter flask; Connect the filter flask back to

vacuum line. Pull air only over the crystals inside the filter funnel

sources of vacuum

1. Water Aspirator or

2. Compressor-driven

Vacuum System (we are using)

Drying product for lab a

our Product is wet! - even after Vacuum filtration.

• Weigh an empty watch glass.

• Transfer the product to the watch glass.

• Weigh the product – record this weight as wet mass

in your lab notebook.

• Break down big clumps of the product, and leave it to

air dry in your drawer until the next lab period.

• Following week - weigh the dry product – Compare

the wet mass and dry mass of the product.

how to characterize sample

Melting Point Range/ Boiling Point Range

• Thin Layer Chromatography (TLC)

• Column Chromatography

• Nuclear Magnetic Resonance (NMR)

Spectroscopy

• Infra-Red (IR) Spectroscopy

determine MP range

Always record the OBSERVED Melting Point as a Range

- First reading of the range – temperature at which the

solid block first begins to liquefy.

- Second reading of the range – temperature at which

the solid is completely melted.

impurities will ___ observed mp range

lower

melting

Solid Phase changes to Liquid Phase

• Loss of order in crystalline lattice

digi melt

Rate at which the temperature of

the heating block increases can be programmed.

You can input the Start temp., End Temp.,

and Ramp Rate.

heating rate digimelt

to be maintained at 2 oC per minute – Sample has to be melted

SLOWLY > A. Thermometer Lag – occurs when the sample melts before the thermometer

has a chance to reach that temperature.

B. Broad range – is observed when melting too quickly.

digimelt melting range considerations

Samples should never be re-melted.

• Used Melting point (MP) capillary tubes should be disposed off into the Red

Sharps container

prep sample digimelt

Melting point capillary tubes (labeled MP) – should be closed on

one end

 Efficient packing of sample in capillary tube - Tap the capillary tube

on the bench inside the hood or let it fall through a long glass tube.

 Digi-melt also has a “tube tapper” option to pack the MP capillary

tubes more uniformly.

 Sample height in capillary tube – approx. 2-3 mm

safety precuations

Dress appropriately for lab (per Lab Safety Guidelines handout).

• Wear your apron, safety goggles and gloves at all times inside the lab.

• Keep all chemicals covered and INSIDE your chemical fume hood. There should

be no chemicals or glassware on your writing tables. Those are only meant for

your lab notebooks.

• Do not stick your head inside the chemical fume hood.

• Do not kneel, when doing experiments in the lab.

• Keep the fume hood window shut when not in use.

• Do not handle the door knobs with your gloves on.

• Keep your cell phones INSIDE your backpacks and leave your backpacks by

the wall.

• NO FOOD OR DRINKS, and no chewing gum are allowed inside the lab.

• Listen to your TAs.

• At the end of lab, take care of waste disposal first, followed by glassware

rinsing (prep, per instructions provided), and finish writing lab notebook

waste acidic filtrates

label, ph paper, bicarb, ph , dump in sink, rinse beaker with water

claisen adapter, vacuum adapter

3 way distillation, thermometer

vigreux column

keck clip

procedure for salicylic acid (formation)

formation of salicylic acid:

Dispensing pipette: 10mL methyl salicylate in grad cyl, transfer to 50mL Erlenmeyer flask

Add 30mL 4M NaOH > formation of heavy white precipitate (disodium salt of salicylic acid)

Clamp Erlenmeyer (avoid spilling), place magnetic stir bar and put on hot plate

Bring solution to boil (half stir, full heat) > solution goes completely clear/homogenous because salt has dissolved. only then will solution boil at 100C > go for 15 minutes

considerations are if solid gets stuck on wall, floating, stir bar stuck to bottom > use glass rod to unstick

after 15 min, move flask into ice water bath for 5 min. insert thermometer inside flask until 16C, then take off.

Obtain 6M HCl to acidify solution. Stir and add HCl in 10mL increments (2x). White precipitate formed > SALICYLIC ACID crashing out only when enough HCl added. Add add’l mL of HCL to ensure solution is acidic. If adding HCl when flask is still on hot plate, acidic content will spill over + burn me.

vacuum filtration (round 1 lab A)

250mL filter flask connected to vacuum + clamp; buchner funnel w filter paper

Pour Erlenmeyer flask into buchner, along with stir bar > impure salicylic looks powdery; rinse rxn flask with a bit of water (avoid losing product, which has some solubility in water)

Let SA sit under vacuum. Pour out contents of filtrate flask in waste acidic filtrate beaker (neutralize later!).

recrystallization of salicylic acid

transfer impure solid to 125mL erlenmeyer flask. add 60mL water. place flask flush to hotplate stirrer (full heat, mid stir). remember, solution must be homogenous before boil.

Observe rolling boil > move clamped erlenmeyer to ring stand and leave undisturbed until u see crystals forming. Put in 400mL ice water bath.

Filter with buchner, empty flask, filter. Preweigh watchglass and transfer! Break down big clumps to help dry faster.

hazards for lab a

methyl salicylate (harmful if swallowed), naoh + hcl (corrosive)

if you wash crystals with too much water

dissolve and enter the filter flask decreasing the percent yield

why to empty the filtrate from the vacuum filter flask

to create a tighter seal so that the bulk of the vacuum pressure is on the solid crystals

large crystals are more likely to be formed…

when the solution is cooled slowly to allow the crystal lattice time to develop and for impure molecules to return to solution

limiting reagent for lab a

methyl salicylate

general overview of lab a

base-promoted ester hydrolysis (methyl salicylate + xs naoh > disodium salt of salicylic acid + meoh + h2o)
acidification (disodium salt + xs hcl > salicylic acid + nacl)

aspirin

develop by bayer in 1897, marketed as aspirin in 1899; oldest and most widely used drug worldwide; analgesis, antipyretic, anti-inflammatory

reaction scheme for aspirin

salicylic acid + acetic anhydride (h3po4 catalyst) > aspirin (acetylsalicylic acid) and acetic acid

equilibrium reaction; use 3x of acetic anhydride (to push reaction towards formation of aspirin) and an acid catalyst

fxnal group transformation for synthesis of aspirin

acetylation of phenol -OH fxnal group in salicylic acid to form an ester in aspirin

equivalent

experimental ratio in which reactants are added to the reaction; in aspirin rxn, 3:1 acetic anhydride to salicylic acid

calculations done for labs a+b

theoretical and actual yield; use 90% SA for aspirin synthesis, keeping 10% for MP

aspirin recystallization

small scale solvent test: sample of impure aspirin (transfer a small amount using a spatula) to two test tubes + 1/3 of the test tubes with solvent (h2o or ethanol) respectively

purity check of aspirin with aq fecl3 solution

test salicylic acid (containing phenol group) to react w fecl3 aq; to produce a deep purple solution

set up two test tubes: 1ml ethanol + 3 drops 0.02M aq FeCl3

tube 1: salicylic acid (control)

tube 2: aspirin

KEY: identify phenolic -OH groups, which react w aq. fecl3 to form a deep purple complex; SA has phenolic OH group

purple=colored solution indicates

presence of a phenolic OH group > residual salicylic acid is present in aspirin product

acetic anhydride

corrosive; irritating to nose

h3po4

corrosive if concentrated; avoid contact with skin + clothing and flush contaminated area with copious amount of water ; catalyst for aspirin formation

waste disposal for aspirin

non-halogenated (CHO, ethanol), halogenated (CHOX, not used); waste acid filtrate from buchner neut w nahco3, then poured down sink; aq fecl3 waste special container

classification based on chemical hazards

flammable, corrosives, lachrymator, carcinogen, teratogen, reactive

flammable

(Low flash point)

Flash point is the lowest temperature at which a liquid can form an ignitable mixture in air near the surface of the

liquid.

• The lower the flash point, the easier it is to ignite the material

flammable

corrosives

are materials that can attack and chemically destroy

exposed body tissues, causing severe chemical burns.

Some examples of ____: H2SO4, NaOH, HNO3, Ca(OH)2, Br2

corrosives

lachrymator

A lachrymator is an irritant that causes tearing (watering of the

eyes).

(Some examples of lachrymators: Thionyl chloride, Acrolein,

Methacryloyl chloride)

carcinogen

A carcinogen is a substance that is capable of causing cancer.

(example: Benzene, Arsenic, Methylene chloride

(or Dichloromethane))

teratogen

A teratogen is a drug or other substance capable of interfering with

the development of an embryo fetus that may lead to birth defects

or developmental malformations.

(Some examples: Phenol, Benzene, Dinitrotoluene, Dioxane)

reactive

Things that go BOOM

(Some examples: Na metal, sodium hydride, calcium carbide)

national fire protection association (nfpa) ratings

blue nfpa

4 Deadly

3 Extreme Danger

2 Hazardous

1 Slightly Hazardous

0 No Health Threat

HEALTH HAZARD

red

FIRE HAZARD

Flashpoints

4 Below 73 F

3 Below 100F

2 Below 200F

1 Above 200F

0 Will not burn

White

Specific hazard

W Water reactive

OX Oxidizing agent

ACID Acid

CORR Corrosive

Yellow

Reactivity Hazard

4 May detonate

3 Shock or Heat may detonate

2 Violent chemical reaction; water reactive

1 Unstable if heated

0 Stable

Extreme health danger

phosphoric acid

flammable

acetone

extremely corrosive

bromine

sources of chemical info

MSDS Sheets – Good resource for chemical information

 How to look up the following chemical information:

A) Physical Properties (MP, Density)

B) Chemical Properties (Solubility, etc.)

C) Toxicity

 Use the Merck Index link on Canvas

 Sigma-Aldrich Catalog

merck index phosphoric acid

Molecular Formula: H3O4P

• Molecular Weight: 98.00

Properties: orrosive.

Misc with water, alc; sol in 8 vols of a 3:1 ether: alc mixture. Properties of phosphoric

acid solns. d25 1.8741 (100% soln); 1.6850 (85% soln); 1.3334 (50% soln); 1.0523 (10%

soln). d= density, nD = refractive index

acetic anhydride boiling point range

138-140 C

thermometer lag result

sample melts before thermometer can reach that temp; affect melting point range through causing a higher, broader recorded range compared to the actual range

why do synthesis of aspirin in erlenmeyer

carrying out this synthesis in an erlenmeyer flask allows for more efficient mixing, and its sloped sides decrease the risk of solvent evap or products spill

procedure for synthesis of aspirin

• heat up beaker for warm water bath

• clamped 50mL erlenmeyer flask and put 90% shiny white salicylic acid in w powder funnel

• 3eq acetic anhydride (liq) added to reaction flask w 1 eq SA; add 5 drops of phosphoric acid using pipette bulb (TA)

• cover flask and let sit for 10 min

• clamp flask and put in warm water bath uncovered for 10 min > solution CLEAR!

• clamp flask and put in ice water bath uncovered for 10 min; scratch sides with glass rod to induce WHITE SOLID PASTE formation

• add 10mL of ice and 10mL water to rxn flask. stir w glass rod

• vacuum filt; rinse w 2mL ice cold water x2 (rxn flask), 2 min vacuum then empty filtrate and vacuum 2min more > SOFT WHITE POWDER

vacuum filt

quickly and complete separate a solid from the liquid with which it is mixed. make sure ring stand FACING you. filter flask clamped. rubber adapter used to ensure tight seal. use heavy walled tubing to prevent tube from collapsing when high pressure applied. sidearm on flask connects to source of vacuum. wet paper with solvent that rxn corresponds w (otherwise product seeps thru and under filter paper)

Solvent test for recrystallization of aspirin

• 2 test tubes: asp + h2o, asp+ etoh

• polarity of solvent used for recrys and cpd being recrys should be similar (like dissolve like)

• if dissolved at rt > etoh bad for recrys!

Recrystallization of aspirin

• transfer crude aspirin from buchner to new 50ml erlenmeyer flask

• clamp flask and add 10ml solvent (water)

• crank hot plate to hottest setting, flush rxn flask to bring to a boil > CLEAR HOMOGENOUS SOLUTION, then rolling boil

• move clamped flask away to cool at RT until crystals form > CLOUDY FIRST, then crystals

• Cool in ice water bath for 2 min, then vacuum filt

lab b overview

Aspirin synthesis from salicylic acid
Recrystallization (solvent test)
Purity test FeCl3

lab c 3 solids

benzoic acid, 2-naphthol, 1,4-dimethoxybenzene

separation of ternary mixture procedure

tertiary butyl methyl ether 25ml; clearless organic solvent covered by inverted beaker; transfer with pyrex funnel (long stem) with the stopcock in horizontal position.

switch to powder funnel (short stem) and transfer 1g in each of benzoic acid (strong acid), 2-naphthol (weak acid), 1,4-dimethoxybenzene (neutral) twisted weighboats

shake sep funnel until homogenous solution > complete dissolution in tBME

place sep funnel back on ring clamp; tBME was colorless, solids were white except for 2-naphthol > now, homogenous solution is light brown

pyrex funnel > add aq 10% sodium bicarbonate in 2 increments (15mL x2, 30mL total). flask underneath is BICARBONATE EXTRACT.

immediate phase separation inside sep funnel between aqueous and organic (based on densities of solvent; aq is 1g/mL, but organic is 0.74g/mL)

stopper and shake with finger on top of stopper. this time, VENT funnel frequently (burp)

back in clamp; remove glass stopper and wait until fizzing stops. drain bottom aqueous layer into BICARB EXTRACT thru moving stopcock to vertical position. x2. after this, only organic solvent in sep funnel w 2-naphthol and 1,4-dmb

NaOH extract flask put underneath stem of sep funnel; obtain 15mL 10% naoh. immediately see formation of 2 separate phases. shake, no need to vent. give layers a chance to separate > switch between color of layers: bottom aq is colored, organic is not bc of shift of 2-naphthoxide to aq layer.

treat extracts with conc. HCl using pasteur pipette (4). after precipitates form, stir w separate glass rods and check pH < 4.

cool each extract in ice-water bath (set aside)

label 3rd erlenmeyer flask and drain remaining liquid (yellowish).

vacuum filt extracts w buchner funnel. use EXTRACTS to wet the filter paper. liquid that enters filter flask is water. rinse erlenmeyer flask w water to recover solids coating sides of flask. RECOVER BENZOIC ACID + 2-NAPHTHOL

3rd ernlenmeyer flask; add anhydrous calcium chloride as drying agent, then swirl flask. gravity filtration w 100mL RBF + shaping GF paper into a cone in powder funnel. can use spatula to remove stuff in erlenmeyer.

use spatula to transfer wet solids onto watchglasses, weighing empty before.

place RBF with tBME and 1,4dmb in rotary evaporator

sep funnel setup

125mL sep funnel with horizontal stopcock (closed), ring clamp for support, 125mL erlenmeyer flask positioned by stem of sep funnel, glass stopper on top of funnel

why erlenmeyer flask under sep funnel good practice?

catch any leaks

organic solvent lab c

tertiary butyl methyl ether 25ml organic solvent

1,4 dmb lab c

big chunky solid; may need to be crushed before added and then pushed down w glass rod. a neutral compound

2-naphthol lab c

pinkish brown solid; -OH fxnal group (phenol); weakly acidic relative to benzoic acid. pka = 9.5

right sized glass stopper lab c

19/22 standard taper joint (19mm width, 22mm length) to match sep funnel dimensions

when to vent sep funnel while shaking lab c

after adding 15mL sodium bicarb to homogenous mixture of 3 solids + dmb > phase separation prior to shaking. lots of fizzing due to generation of co2

purpose of adding sodium bicarb in lab c

by adding a weak base, we have deprotonated benzoic acid into its sodium salt (sodium benzoate + co2); sodium benzoate is ionic and can be extracted into aqueous layer. we do it twice in order to ensure we have extracted ALL of benzioc acid from organic layer to aqueous layer.

color shift in lab c

originally, color in organic layer. after addition of naoh, color in aqueous layer. this is caused by the addition of naoh to 2-naphthol; strong base addition causes it to form its sodium salt, 2-naphthoxide. 2-naphthoxide is an ionic species that will enter the aqueous layer, which can then be drained

inside bicarb extract

sodium benzoate (benzoic acid + sodium bicarb); clear. when conc hcl added, thick, fluffy precipitate formed

inside hydroxide extract

2-naphthoxide and naoh; yellowish brown; when conc hcl added, brownish pink solid precipitates at

if u drain organic along w aqueous lab c

organic layer will form film over aqueous layer, making it very difficult for product to crash out of solution when treated w concentrated acid later