Exam 1 ORG Exp 1-10

experimental mp will almost never ...

be higher than the literature value

Acetone is completely miscible in ....

water at all proportions and temps

How much solvent do you add for recrystallization? When do you remove glassware from heat? After?

-enough to form clear solution when hot, based on solubility data -solid dissolves -sit to room temp > ice bath, scratch glass while on ic > vacuum filter

Despite the instability of benzyne, why does the diazonium salt decompose so rapidly to form benzyne?

the diazonium salt is more unstable than benzyne; it has a more negative deltaG

retention factor

the distance traveled by the solute divided by the distance traveled by the solvent

Was your rxn under kinetic or thermodynamic control, or is it possible that both adducts were produced? Discuss the role of time in the latter case

the kinetic products are endo and the thermodynamic products are exo to favor endo, mix & heat the rxn and let it sit; the transition state is more stable without cooling for exo, give the rxn time to react & settle (exo takes longer)

diels-alder preference

transition state to endo stabilized by electron overlap causing it to form faster = under kinetic control (less stable) thermodynamic control = exo adduct

SN1 reaction

-for tertiary and some sec alkyl halides -use lewis acid in polar solvent asists in dissociation of halide anion, stabilize intermediate *unimolecular nucleophilic substitution reactions, stability of cation determined by solvent polarity and leaving group ability of halogen: 2 steps 1. Leaving group leaves forming a positively charged carbocation (rate limiting step) *The rate of rxn depends only on the concentration of the substrate *Anything that accelerates the formation of the carbocation increase the rate of rxn 2. Nucleophile attacks the carbocation (unstable) *results in substitution product

Iodoform Test

-gives positive result for methyl carbonyl -if under reaction iodoform is insoluble, yellow precipitate forms (evidence of methyl ketone)

SN2 reaction

-prim and sec alkyl halides -use nucleophile in less polar solven discourages intermediate -rate depends on steric hindrance around reacting center, nucleophili character of attacking group -bimolecular nucleophilic substitution reactions - only 1 step (concerted reaction) -nucleophile attacks the compound at the same time as the leaving group leaves -Nucleophile actively displaces the leaving group in a backside attack for this to occur, nucleophile must be strong & substrate can't be sterically hindered -concentrations of substrate & nucleophile have role in determining the rate -Position of the substituents around the substrate carbon is inverted

Jones Test

-test for alcohols -strong oxidation converts primary alcohols to carboxylic acid -ketones and tertiary alcohols will not react -positive for secondary/primary = opaque suspension, green/blue color -positive for tertiary = no visible reaction, remains orange in color

Lucas Test

-test for primary, secondary, and tertiary alcohols -converts alcohols to alkyl chlorides (primary alcohols will not react)

Ferric Chloride Test

-tests for phenols (Ar-Oh groups) -Fe(III) forms colored complex -positive result = red/blue/violet color change

Bromine Test

-tests for unsaturation (presence of C=C bonds) -takes advantage of propensity of C=C groups to add Br across double bond -color change = positive result (vs. remains red/brown = saturated, no C=C bonds)

What are two properties of a good recrystallization solvent?

1. Dissolve molecule in hot solvent but not cold 2. Dissolves impurity in hot and cold

Give two reasons for knowing the literature solubility data when doing a recrystallization.

1. So you know if they will mix 2. The solvents need to be able to dissolve the solute in high temps but not low temps in order for crystals to form.

Make a list of at least four experimental factors that should be considered when attempting to isolate polymorphic forms of a solid pure substances.

1. pressure 2. type of solvent 3. temperature 4. absolute humidity extra. concentration of solute, rate of evaporation, agitation of solution, solubility, polarity

dielectric constant

A physical property that reflects the number of dipoles in a solvent insulating (attracted to charges in solute) ability to balance part of solute's charge

Woodward-Hoffman rules

A set of symmetry rules that predict whether a particular pericyclic reaction occurs via thermal pathway or photochemical pathway

How well do the solvent's dipole moments correlate with their dielectric constants or the polarity index? (page 60, lab manual)

As the dipole moment decreases, so does the dielectric constants

To promote SN1 mechanism we use AgNO3 in a polar, protic solvent. Why

Because AgNO3 can pull off a leaving group well enough to make a carbocation

Why does ethyl acetate have a higher boiling point than hexanes, even though both are approximately the same molecular weight?

Because ethyl acetate is polar and has dipole-dipole forces which are strong than the forces hexanes have.

Why is bromobenzene unreactive under both SN1 and SN2 conditions

Because the bromide is directly attached to the very stable benzene ring

Why does benzyl bromide react under both SN1 and SN2 conditions?

Benzyl bromide is 2° so it will react under both, depending on the stability of the molecule

If bromocyclohexane reacts faster than chlorocyclohexane in an SN2 reaction what could the reason be

Bromide is a bigger molecule than chlorine so it is further away from the ring, making it easier for it to be pulled off

Four of the common solvents in Table 1-1 are denser than water. Which are they? Explain why this might be the case.

CCl4, CH2Cl2, CHCl3, Acetic Acid mol geo/packing = SA

In the reaction of salicylic acid and caffeine, which is the Lewis acid and Lewis base? Why does caffeine protonate at N-9? What is the hybridization of the non-bonded pair at N-9?

Caffeine acid, salicylic acid base N-9 less involved in resonance of caffeine and can be protonated, sp2 hybridized

Given a mixture of caffeine and benzoic acid, what would happen if they were added to a separatory funnel with CH2Cl2 and 1M HCl? Which compound goes into which layer and why?

Caffeine would be protonated by the HCl and become water-soluble. Benzoic acid would be more soluble in the organic solvent and would dissolve into the CH2Cl2. Caffeine would create the organic solvent.

The reaction of ClCH₂OCH₂CH₃ with ethanol (without catalyst) yields a di-ether in nearly quantitative yield. Provide the structure of the product. Mechanistically, provide two routes that account for the observed product.

ClCH₂OCH₂CH₃ + C₂H₅OH → C₂H₅OCH₂OCH₂CH₃ + HCl Mechanistically, this can go either with SN1 or SN2. SN1: the O in ethanol attacks the carbon with chlorine on it SN2: the Cl leaves, making a carbocation, and then the O in ethanol attacks the carbon with the positive charge

Noble gases and non-polar hydrocarbons have an intrinsic physical property in common that helps us understand why these elements and compounds are typically gases at room temperature but can be condensed to form liquids at lower temperatures. What is that physical property?

Enthalpy of vaporization

Many important drugs contain the amine functional group which makes them basic. Many drugs also contain an amide group, which is effectively neutral. Suggest a way to separate ephedrine, a stimulant and decongestant drug, from phenacetin.

Ephedrine has a basic amine group and phenacetin has a neutral amide group. Only the amine group in ephedrine will attack HCl and accept the hydrogen, which will protonate the ephedrine. While protonated, ephedrine is water-soluble. It will not dissolve with the organic solvent. Phenacetin remains immiscible with water because it stays neutral. It is soluble in the organic layer. This makes it possible to separate the compounds.

Why does methanol have a lower boiling point than ethanol even though ethanol is more polar? Why does ethanol have a higher boiling point than ethyl ether even though ethyl ether has a greater molecular mass?

Ethanol has a higher boiling point than methanol because it has a longer carbon chain and is heavier. Ethanol has a higher boiling point than ethyl ether because it has hydrogen bonding.

Consider acetanilide and cinnamic acid samples. Which one appeared to benefit the most from recrystallization? How can you tell?

For acetanilide the 20mL system benefited most. For TCA the sample that contained ethanol and H2O benefited most. You can tell by comparing m.p. values to lit values.

Geranial Citral

HBA's: 2 HBD's: 0 (Trans Isomer) -chemical shift of aldehyde hydrogen =4.2 -splitting = doublet

Neral Citral

HBA's: 2 HBD's: 0 -rel. energy different from geranial because of steric interaction between vinyl hydrogens and aldehyde group (Cis Isomer)

Caffeine

HBA's: 5 HBD's: 0 Function as a Base: will deprotonate salicylic acid to form salt (proton added to most basic nitrogen) -not basic enough to take a proton from acetaminophen Hybridization of orbital that contains the non-bonded pair on nitrogen? (p when nitrogen has no pi bonds , sp2 when directly attached to double bond)

aspirin

HBD: 1 HBA: 8

acetaminophen

HBD: 2 HBA: 4 with caffeine, will act as base

salicylic acid

HBD: 2 HBA: 6

Succinylsulfathiazole

HBD: 3 HBA: 11

Why must you allow recrystallized samples to dry completely before determining the m.p.?

If they are not completely dry then the water will act as an impurity and lower the melting point.

We used the Bromine in DCM method to test for unsaturation. We also took an IR spectrum of the compound. However, neither method could really give a direct answer for the number of C=C bonds present. What methods could we use to discern this information?

If you know the molecular formula of the compound , you can calculate the double bon d equivalent to calculate the number of C=C. The formula is a s follows: DBE = (C+1) -H/2 +N/2-X/2

Tertiary-butyl iodide reacts faster than t-butyl bromide via SN1 mechanism because iodide is a better leaving group than bromide. Why?

Iodine is a very large molecule making it easier to pull off and make a carbocation while bromide is a lot smaller

In TLC, what will happen if the initial spot is very large when preparing a plate?

It could reduce the resolution and make results blurry and two or more spots of a sample may overlap on the TLC plate

liquids w weak IMFs

NP

Petroleum ether is another organic solvent that is a mixture of simple hydrocarbons obtained by the distillation of petroleum. Would it be classified as polar or non-polar? Would you expect it to be miscible or immiscible with water?

Non-polar so it would not be miscible with water because water is extremely polar.

Organic liquids A, B, and C have densities of 0.691, 0.955, and 1.126 g/mL. A and C are low polarity solvents, while B is a high polarity solvent. When each is added to water, how would you expect them to behave?

Organic liquids A and C are not miscible with water and will form separate layers. Liquid A will form a layer above water because it is less dense and liquid C will form a layer below water because it is more dense. Organic liquid B will be miscible with water.

Propofol, the anesthesia-induction medication does not give a positive test when tested with ferric chloride in water. Briefly suggest a practical reason for this. How would you modify the standard procedure to address the difficulty in performing this test?

Propofol isn't soluble in water due to bulky isopropyl groups, using ethanol/methanol would work better.

Why do we not perform a simple distillation on lemon grass oil at atmospheric pressure to separate the components? What's the advantage of steam distillation? Can you imagine another distillation method that might serve the same purpose?

Simple distillation is only effective when attempting to separate two non-volatile substances. Citral is a moderately volatile compound, and immiscible in water (good for steam distillation). -Advantage of steam distillation: b/c the lower pressure reduces the boiling point, you need less heat to achieve distillation. -Vacuum distillation would also be effective, also reduces pressure. OR rotovap

Which solvent system appears to give the best spread of Rf values? Can you explain why this might be so?

The 10:1 ethyl acetate:hexane gives the best spread because it is primarily ethyl acetate which has intermediate polarity.

We used to perform this exp using diethylether as the rxn solvent. We now use DCM, which has similar solvent properties. Give a practical reason for this change to DCM

The change to DCM could be because DCM is more polar than diethylether. For crystallization, dissolving the reaction in a more polar solvent makes the sample less soluble in hexanes, the rinsing solvent. This would help facilitate crystallization.

Some of the polymorphs of SST may have higher melting points compared to the published literature values. How could this be possible?

The interactions between the crystals in the different order may influence the strength of IMFs.

In TLC, what will happen if the initial spot is below the level of the solvent in the developing chamber?

The spot will dissolve into the solvent instead of being carried up the plate.

2-methylbenzamide and 3-nitrobenzoic acid both have a melting point of 140.1 - 140.4 C. However, if you mixed them together and took the melting point, it would not be 140.1 - 140.4 C. Why not?

They would contaminate each other and act as impurities which would disrupt IMFs and lower the melting point.

Draw the chemical reaction that occurs when the benzoic acid reacts with the NaOH/H2O. Then write the chemical reaction that occurs when HCl is added to the now basic aqueous soln. Why is this sequence of reactions necessary?

This sequence of reactions is necessary in order to separate an acid from an organic layer. NaOH deprotonates benzoic acid and makes it water-soluble. Next, the addition of HCl is done to separate the organic and aqueous layers. This reacidifies the benzoic acid. The acid can be extracted and isolated by the addition of an organic solvent.

In the chemically active extraction you performed, to separate benzoic acid from caffeine, you added 1M NaOH to the benzoic acid + caffeine in DCM solution within a separatory funnel. You separated the organic and aqueous layers into different Erlenmeyer flasks, returned the organic layer. You again separated the two layers, combining the new aqueous fraction with the old one. Why would you want to extract with the aqueous NaOH twice?

To ensure that all of the desired substance has been extracted

items to visualize TLC plates

UV light, Iodine vapor

In an effort to rectify the problem, the chemist rinses the crystals with solvent, only to find that pouring the solvent over the crystals causes many of them to dissolve and be pulled through the filter paper into the filtrate. What could the chemist have done to the solvent to alleviate this, and why does this help mitigate the dissolution of the crystals?

Use cold solvent, the crystals are only soluble in the solvent at higher temperatures.

For some of the polymorphs, the melting point is much lower than the published value. Is it likely that there are contaminants present? If so, what are the likely contaminants? If not, what could cause this?

Yes, impurities lower m.p. Some contaminants could be sulfanilamide, succinct acid, or sulfathiazole.

Did the literature values for the solubility of acetanilide in H2O hold true? Which solvent system (20 mL or 40 mL) worked better for yield? Which for purity?

Yes, it didn't dissolve in room temp but did at high temp. -20 mL system produced greater yield (the reduced volume allowed for a greater collision of molecules) -40 mL system produced greater purity (reduced volume allowed for a greater chance of incorporation of impurities into crystal structure)

recrystallization

a common way to purify a solid tested for purity by comparing mp with literature mp

pure pharmaceutical compounds

amorphous solids (no ordered arrangement of molecules/distinguishable lattice), solvates (solvent in lattice), hydrate (water in lattice)

ionic compounds dissolve in polar solvents bc

attractive interaction btw NB pairs and polarized H of water, +/- of ions

Why is benzyne such a reactive molecule? In other words, why is it so unstable?

because of the bond angle strain triple bonds want to be 180 degrees but that is impossible in a six membered benzene ring

bp inversely proportional to VP, in steam distillation...

bp of mixture of immiscible liquids lower than that of lowest boiling component mixture boils when total VP is equal to atmospheric pressure > presence of immiscible material contributes to VP > high bp to drop below 100C of water allows high bp compounds to be co-distilled below 100C

aspirin, acetaminophen, caffeine polarity

caffeine > acetaminophen > aspirin

polymorphs

compounds capable of existing in different crystalline phases, arrangements and/or conformations in crystal lattice can change

TLC technique

compounds separated even if part of a mixture -inexpensive, little sample needed, many samples at a time, can be recovered, determines when rxn is done by appearance of product and disappearance of reagent

diels-alder reaction

concerted mechanism whereby 2 reactants, one a diene and other adienophile, undergo alignment of their mol orbitals to form a product not ionic, cat by Lewis acids reversible, concerted mech best when diene has e- donating sub (nucleophile) and dienophile e- withdrawing (electrophile)

2,4 DNP Test & Semicarbozone Test

convert liquid aldehydes/ketones into solids

solvent and solute polarity depend on 2 intrinsic, elemental prop ... third prop important in aromatic mol

electroneg diff dipole moment (mol geo affects) electron polarizability

carbon atom takes on _____ character, halogen _____

electrophilic nucleophilic

log P

how soluble a compound is in NP solvent or water solubility measurement ratio of amount of sub that partitions into the NP phase vs the amount that remains in aqueous phase -partitions 1/1 logP = 0 -more soluble in NP = positive -more soluble in water, polar = negative

Dalton's Law of Partial Pressures

immiscible mixture of water and oils, in steam distillation, each component contributes to total VP = total VP of mixture is sum of the VPs

hydroxyl groups/ functional groups only have HBA .....

increase the solubility by both HBD/A

salts of pharmaceutical agents more ordered ....

increased attractive lattice energy due to ionic interactions

molecules with weak IMFs have ....

low densities

if atmospheric pressure is lower ....

measured bp will be lower

organic solvent and water separate layer with a visible boundary ______ btw them

meniscus

problems with creating, isolating, characterizing polymorphs

more than one polymorph, variables, starting material can be contaminated (mixture of polymorphs itself), lower energy p cause higher energy to revert back, sensitive to humidity, microscopic evaluation needed, long time for evaporation/drying/isolation, difficult IR XRPD best definitive tech

impurities spread ...

mp

Give the IUPAC names for both acetanilide and trans-cinnamic acid.

n-phenylethanamide (E)-3-phenyl-2-propenoic acid

water always appropriate fro extinguishing chem fire?

no, can cause rxn and spread oils

water-miscible solvents

organic solvent and water mix in all proportions

polarity of benzene dervatives

ortho (partial charges add) > meta > para (cancel out)

presence of a non-polar SA decreases ...

overall polarity somewhat relative to the polarity of the polar SA

lower mass but higher mp?

pack densely, H bond with self

liquids w strong IMFs

polar

silica gel

polar polar compounds stick, lower Rf NP prefer solvent, higher Rf

solubility of organic compound in water will be increases by the addition of a ...

polar functional group (primary amines, hydroxyl, carboxyl)

Rf values are dependent on ...

polarity of solid suppoer and developing solvent polar developing solvents = attract polar from gel = higher Rf for polar compounds less polar developing solvents = lower Rf for polar compounds -use mixtures as developing solvents so polarity can be controlled

TLC factors to consider

polarity of the solid support (silica/alumina = immobile phase), of the solvents used to develop plate (mobile), and of the compound/solute itself

increasing polarity of solvent makes it better at solvating the ....

polarized transition state > lowering activation barrier increases rate of hydrolysis moving to better H bond donating solvent allow stabilization of transition state and enhance rate

steam distillation

process of co-distilling compound with water route for separating lower boiling 'insoluble' compounds from either higher boiling organic components or physical/plant matter

polymorphic ambiguity changes...

rate and degree of distribution of drug

why is mp of salicylic acid less than caffeine?

salicylic h-bonds with self, doesn't bond as strongly w/ other molecules

boiling point of solvent is determined by

size and shape/symm, IMFs

reason for impure sample of SST?

solvent trapped in crystals > solvates formed

solvent's degree of solubility is a function of .....

solvent's volume = multi IMFs from multi functional groups

variables that influence rate of sn1

solvent, alkyl halide structure, leaving group ability

Use drawings, and explain why dichloromethane has a higher dielectric constant than acetic acid

structure = DCM higher dipole moment

in IR, if a mol is ______ structurally, probable there will be weak/missing vibrational freq for the bond/bonds that confer this prop

symmetric