CHM 314L Exam

formation of phenyl magnesium bromide

kinda the picture

Know the acid dilution calculation (Electrophilic Aromatic Substitution)

m1v1=m2v2

Identify the techniques used in the work-up and characterization of triphenylmethanol. The quick, numeric analysis used to characterize the product and assess the purity

melting point

true or false The sodium thiosulfate (Na2S2O3) removes any residual iodine from the reaction solution prior to acidification. (Electrophilic Aromatic Substitution)

true

Know how to calculate the theoretical yield and percent yield (Grignard Reaction)

(mass of bromobenzene divided by its molar mass) x ( the molar ratio) x (the molar mass of the product) % yield= grams of product/grams of theoretical x 100% (Theoretical yield- find limiting reagent, determine mass of final product when limiting reagent is used. Percent yield= actual yield/ theoretical yield)

Order the following statements into a correct procedure outline: (Electrophilic Aromatic Substitution)

- Dissolve salicylamide with absolute ethanol in an Erlenmeyer - Add sodium iodide to salicylamide solution and chill in an ice bath - Add sodium hypochlorite solution, swirl to mix, and let the flask sit undisturbed - Add sodium thiosulfate to the reaction mixture - Acidify the mixture with 1 M HCl and test the pH - Collect the product and recrystallize with ethanol - Analyze the product with IR spectroscopy

Know the purpose of a sodium bicarbonate wash (Grignard Reaction) - what impurity is neutralized - be able to write the chemical reaction - what gas is evolved - what happens if you forget to vent frequently

- The purpose of washing the organic layer with 5% sodium bicarbonate is to neutralize residual sulfuric acid. -To neutralize an organic layer that may contain trace acidic components - H2 - the pressure builds up

What is the purpose of the EAS: Iodination of salicylamide experiment?

- To determine how the substituents on an aromatic ring affect the electrophilic aromatic substitution reaction. - To synthesize iodosalicylamide. - To use IR spectroscopy analysis to help confirmation of the substitution position of Iodo in the iodosalicylamide.

Know the TLC technique to determine the identity and purity of the product (Synthesis of Aspirin)

- compare the line of the product to the two other lines and see which one it is closest to - A pure solid will show only one spot on a developed TLC plate. - The Rf of the compound will be the same as the known standard. (the same rf does not mean sea chemical) (put 10 mL ethyl acetate in beaker with a few drops of acetic acid. Mark on the TLC plate for store aspirin, your sample product, and salicylic acid. Sample is pure if there is only one spot in that lane; sample identify is aspirin if it has same rf value of aspirin.)

Understand the technique of recrystallization in electrophilic aromatic substitution (Electrophilic Aromatic Substitution)

- hot gravity filtration (use boiling 95% ethanol to dissolve and then recrystallize)

The bleach reacts with what to create the electrophile? What is the electrophile? (Electrophilic Aromatic Substitution)

- reaction of sodium hypochlorite (NaOCl, bleach) with iodide ion - electrophile = iodine cation

Sodium thiosulfate is a mild redundant. You need to know what is reduced and what is created. (Electrophilic Aromatic Substitution)

- removes any residual iodine from the solution - thiosulfate reduces the hypochlorite (the active ingredient in bleach) and in so doing becomes oxidized to sulfate.

Understand the technique of recrystallization (Grignard Reaction)

- separate the layers - wash organic layer with sodium bicarbonate then with water - using drying salt ( anhydrous magnesium sulfate) - remove drying agent with gravity filtration - evaporate ether layers with hot tap and air stream - transfer content with cold ligroin to buchner funnel - dry with vacuum for 5 minutes (dissolve crystals from buchner funnel in 95% boiling ethanol, then allow it to cool and recrystallize and put through vacuum filtration again)

Suppose you are going to perform a TLC experiment, which materials will you use to prepare the TLC development chamber?

- watch glass - filter paper - beaker

Recognize the major product formed in the reaction as it was performed in the lab (Electrophilic Aromatic Substitution)

1,2,4 trisubstituted major product formed is 1,2,4- iodo-salicylamide

Make 10 mL of 1M Hydrochloric acid from 12M concentrated acid: (EAS)

.83 mL

safety diamond 0-4

0 = no hazard 4 = very hazardous

Bromobenzene used in the experiment is 3.2 g. What is the mass of magnesium turnings (Mg) that is 1.25 molar equivalent to the amount of bromobenzene used? Use the molar mass data available in the manual.

0.61 g

Know steps taken to prevent deactivation of the Grignard reagent

1) Dry all the equipment 2) Use Drierite as a drying agent in the drying tube with cotton - water will cause the reaction to fail (phenyl magnesium bromide decompose in water) (make sure there is no water present, partial negative charge on carbon causes reagent to be more reactive, sulfuric acid added for protonation and excess Mg)

when you added the HCl to the reaction mixture a white solid formed, what was this solid (Electrophilic Aromatic Substitution)

1,2,4 trisubstituted 2-hydroxy-5-iodobenzamide ???

Order the following statements into a correct procedure outline: Grignard Reagent

1. Assemble the apparatus for the Grignard reaction 2. Add bromobenzene solution to Mg turnings and a small amount of iodine and mix well to react 3. Reflux the bromobenzene and Mg reaction on a hot plate 4. Add carbonyl compound solution into the synthesized phenylmagnesium bromide solution and reflux the reaction mixture 5. Mix the reaction mixture with a dilute sulfuric acid solution 6. Extract and wash the organic layer 7. Evaporate the diethyl ether and isolate the product with cold ligroin 8. Recrystallize the product, obtain the final mass and H-NMR of the purified product

Calculate the mass of Salicylamide (7.5mmol and 137.136 g/mol) and the mass of Iodide needed (8mmol and 126.9) (EAS)

1.02 g 1.015 g

How many grams are in 7.5 mmol of salicylamide? Use the molar mass data available in the manual. (137.136)

1.0g

ratio of magnesium to bromobenzene

1.25:1

How many grams are in 8.0 mmol of NaI (MW = 149.89 g/mol)?

1.2g

Know the m.p of the aspirin and how to determine the purity of the product using the m.p data (Synthesis of Aspirin)

134-138 aspirin sample is pure because the experimental melting point range falls within the literature melting point for aspirin. In addition to this, the experimental melting point range is within 2 degrees Celcius which means that the sample is pure.

What should the aromatic region of triphenylmethanol in the 1H NMR spectra integrate to? (Grignard Reaction)

15

ratio of bromobenzene to benzophenone

1:1

How many "types of hydrogens" do you expect to see in the 1H NMR spectra of triphenylmethanol (assume hydrogens in the phenyl group are equivalent)? (Grignard Reaction)

2

Aspirin can be prepared from salicylic acid (C7H6O3C7H6O3), which has a molar mass of 138.12 g/mol, and acetic anhydride (C4H6O3C4H6O3), which has a molar mass of 102.04 g/mol. The density of acetic anhydride is 1.082 g/mL. C7H6O3 + C4H6O3 ⟶ C9H8O4 + C2H4O2 What is the yield, in grams, of aspirin (C9H8O4C9H8O4), which has a molar mass of 180.15 g/mol, possible when reacting 2.05 g of salicylic acid with 1.05 mL of acetic anhydride?

2.00

Be able to convert from "molar equivalents" to mass (Grignard Reaction)

3.2/157.02 = .02038 .02038*1.25 = .02547 .02547*24.1 = .6139 look at chegg for more help (1 molar equivalent of everything, 1.25 molar equivalent of solid magnesium turnings)

Based on the stoichiometry of the reaction, how many grams of benzophenone is an equimolar amount to the bromobenzene used in the experiment?

3.7

Aspirin can be prepared from salicylic acid (C7H6O3C7H6O3), which has a molar mass of 138.12 g/mol, and acetic anhydride (C4H6O3C4H6O3), which has a molar mass of 102.04 g/mol. The density of acetic anhydride is 1.082 g/mL. C7H6O3+C4H6O3⟶C9H8O4+C2H4O2 What is the theoretical yield, in grams, of aspirin (C9H8O4C9H8O4), which has a molar mass of 180.15 g/mol, possible when reacting 3.18 g of salicylic acid with 3.60 mL of acetic anhydride?

4.15

Be able to determine the volume needed to dilute a concentrated acid (Grignard Reaction)

5 ml

What is used to oxidize I− to I+ in this experiment?(Electrophilic Aromatic Substitution)

sodium hypochlorite

Identify the effect of each error during a thin layer chromatography experiment. The TLC plate remains in the chamber even after the solvent has reached the top of the plate.

Accurate Rf values cannot be determined.

Identify the effect of each error during a thin layer chromatography experiment. The solvent line is not marked after the TLC plate is removed from the chamber.

Accurate Rf values cannot be determined.

Why is it often necessary to break up the magnesium turnings in order to start the Grignard reaction?

Air causes magnesium to oxidize which will deactivate the Grignard reagent. Breaking up the magnesium turnings exposes pure magnesium to the surface in order for the reaction to occur.

Know the meaning of the term "absolute" in absolute ethanol (Electrophilic Aromatic Substitution)

An alcohol, like ethanol, is considered "absolute" when it has no more than 1% water; it is 99% pure (you can search the Internet for this one).

Which substance would not work as a Grignard reagent? Select one: A. Ethylmagnesium bromide B. Methylcalcium bromide C. Isopropylmagnesium chloride D. Phenylmagnesium chloride

B

Know how to read the H-NMR of the final products (Grignard Reaction)

C-H: 15.00 to contain the 15 bonds around 7.5 which is the area for aromatic rings O-H: 1.00 to contain the one bond around 3 which is the area for OH groups (has 2 Hydrogen signals , one from OH group the other from the phenyl groups)

Equation for the reaction of a Grignard reagent with water to show why it is essential to keep it dry

CH3CH2MgBr + H2O --->CH3CH3 + Mg(OH)Br The product of Mg(OH)Br is not a complete product. It is similar to a halfway stage of magnesium bromide and magnesium hydroxide

Which key feature is formed in a Grignard reaction?

Carbon-carbon bond

Know the mechanism of the EAS reaction done in the lab (Electrophilic Aromatic Substitution)

Electrophilic aromatic substitution (EAS) is a common reaction of benzene and its derivatives. All EAS reactions follow the same general mechanism. The reaction occurs in two steps (Figure IS.1). First, the aromatic ring acts as a nucleophile and attacks an electrophile. The aromatic ring is then regenerated through the loss of a proton. (OH group is the EDG (which activates ring and directs ortho para), H attacks electrophile (NaI) sigma complex is formed and then a base attacks extra H)

Recognize the electrophile of the mechanism (Electrophilic Aromatic Substitution)

I+ The electrophile (I+) then attacks on salicylamide to give the desired product. (electrophile is provided byNaI (iodide is electrophile)

Know the technique to purify aspirin in the experiment (Synthesis of Aspirin)

Iron(III) chloride can be used to assess the purity of aspirin synthesized from salicylic acid. recrystallization and vacuum filtration (recrystallize with ethanol and wash crystals with cold water)

What is the main safety concern of the Ether (diethyl ether) in the experiment?

It is very flammable so keep it away from the heat source.

Know why the Mg "disappears" during the reaction (Grignard Reaction) - be able to explain this using a chemical reaction. Be able to write down this reaction from memory.

Magnesium is easily oxidized and goes after the water in the reaction. It becomes a sub-product connected with (an) oxygen, but is not part of the main final product the addition of bromophenone This forms the alkoxide which is protonated with acid to give the alcohol. The overall reaction is shown in Figure 2 sulfuric acid reacts with excess magnesium

Know how to interpret the IR spectra of the product (Electrophilic Aromatic Substitution)

NH around 3490 OH around 3333 CH around 3295 C=O around 1645 CI around 816 new signal at 800-850 ppm, OH group present

Identify the techniques used in the work-up and characterization of triphenylmethanol. The analytical method used to confirm the structure and functional groups of the product

NMR spectroscopy

Know how to read the IR spectrum of the final products (Grignard Reaction)

OH bond around 3,456 (broad band) C-H bond around 3081

Understand the NMR analysis of the product (Electrophilic Aromatic Substitution)

OH: one peak @ 13ppm H btw I and O: one peak @8.14 NH2: @ 7.7 H near I @7.3 H near OH @ 6.78 (5 different hydrogen signals from 5-15 ppm)

what layer is on top (Grignard Reaction)

Organics are less dense than water except for chlorinated solvents like methylene chloride and chloroform.

safety diamond white

Special hazards or notices

What are the techniques used in the Grignard reaction experiment procedure?

Recrystallization melting point determination extraction

Be able to calculate the Rf value of the spots on the TLC plate (Synthesis of Aspirin)

Rf = distance it traveled/ distance of solvent front

The purpose of the phosphoric acid in the reaction (Synthesis of Aspirin)

Specifically, the phenol group is converted to an acetyl ester with an anhydride or acid chloride in the presence of an acid catalyst, usually phosphoric acid. (catalyst to protonate acetic anhydride (causes carbonyl groups to become more electrophilic)

Know the overall reaction equation and be able to name the reactants and products (Electrophilic Aromatic Substitution)

Salicylamide + NaI/NaOCl/ethanol ----> iodosalicylamide (salicylamide reacts with sodium iodide iodo- salicylamide (add 6% hypochlorite and 1 M HCl))

Know the signs of a chemical reaction (Grignard Reaction)

Signs that a chemical reaction is occurring include the evolution of heat, an increase in the turbidity (cloudiness) of the solution, and small bubbles forming on the surface of the magnesium. It may take a few minutes for the reaction to start—the heat from your hand can actually help get things going. If your reaction hasn't started after about five minutes of swirling, ask your instructor for assistance. - evolution of heat - increase in turbility (cloudiness) - small bubbles forming on the surface

Know which compound was used that made this experiment "green" (Electrophilic Aromatic Substitution)

The iodination of salicylamide experiment is considered a greener method because the household bleach is used as the oxidizing agent and sodium iodide is the source of iodine. sodium iodide and bleach:both are better and "greener" than iodine and nitric acid Fortunately, greener methods exist for carrying out iodination reactions. You will use sodium iodide as a source of iodine and household bleach (a solution of sodium hypochlorite, NaOCl) as an oxidizer. instead of nitric acid

Where was the product found during the extraction?(Grignard Reaction)

The organic layer at the top

Identify the effect of each error during a thin layer chromatography experiment. The mobile phase used does not move any of the spots at all.

There can be no separation of components.

Identify the effect of each error during a thin layer chromatography experiment. Pen rather than pencil is used to draw the lines on the plate.

There will be smears on the TLC plate.

What is the difference between recrystallization with a hot gravity filtration and without a hot gravity filtration? (Electrophilic Aromatic Substitution)

This means that a saturated solution will contain more dissolved solute if prepared at a higher temperature than at a cold temperature. When the hot solution then cools, it will be supersaturated - it will hold more dissolved solute than its cold equivalent would. Letting the solution cool during a hot filtration will cause crystals to form prematurely in the filter funnel.

Why should anhydrous ether be used as the solvent for the Grignard reaction?

To prevent the magnesium from contacting moisture because the presence of water deactivates the reagent because magnesium will combine with the water instead of the organic materials

Know the reason the reaction solution was poured over ice instead of water (Grignard Reaction)

You pour the reaction mixture in to the Erlenmeyer with 30 mL of 3M H2SO4 and 25 g of ice because it prevents the evaporation of ether and also slows reaction with water Grignard carbon is highly nucleophilic, so it would have formed a hydrocarbon, destroying the Grignard reagent. (pour over ice bc it is hot)

Identify the medical applications of aspirin.

anti-inflammatory agent pain killer fever reducer

electron donating group

activate the ring and direct the new substituent into the ortho and para positions

A Grignard reagent is prepared when ______________ reacts with ___________in the solvent ___________

an organohalide magnesium ether

ions dissolved in the aqueous or organic layer (Grignard Reaction)

aqueous ( highly polar and ionic compounds will dissolve in the aqueous phase)

Identify characteristics that describe a Grignard reagent.

basic nucleophile

Calculate the mass of carbonyl compound needed, given the mass of bromobenzene (3.2) (Grignard Reaction)

benzophenone 3.71

Be able to write the chemical reaction from memory. (Grignard Reaction)

bromobenzene + Mg = grignard reagent (phenyl magnesium bromide) grignard reagent + anydrous ether/benzophenone and dilute sulfuric acid -- triphenylmethanol

Aspirin is usually packaged with ________ to reduce its _________ and the related ________

buffering agents acidity stomach irritation

Aspirin was formed to reduce the irritation of salicylic acid. However, aspirin can still disturb the stomach. Which functional group in aspirin is responsible for stomach irritation?

carboxylic acid

electron withdrawing group

deactivate the ring and direct the new substituent into the meta position

when is a hot gravity filtration required what type of impurity is present (Electrophilic Aromatic Substitution)

insoluble impurity

Iron(III) chloride can be used to assess the purity of aspirin synthesized from salicylic acid. Iron(III) chloride ________ react with aspirin because the reaction requires ___________ which is present in __________

does not a phenolic functional group salicylic acid but not aspirin

Understand the NMR analysis of the Aspirin (Synthesis of Aspirin)

ester group: 3.000 @ 2-ish carboxylic acid: 1.00 @ 12 CH: 4.00 @ 7.5 (hydrogen ratio will be 3:4:1, 4 hydrogens at benzene ring at 8 ppm, 1 H from carboxylic acid group will appear at 10-15 ppm, 3 hydrogens from carbonyl group appear at 2-3 ppm)

Understand the technique of extraction (Grignard Reaction)

extraction using a separatory funnel - shake the funnel and vent the pressure (bottom layer (aqueous layer) is on bottom and being disposed of, the ether layer on top has product in it)

True or False The magnesium was cleaned by the addition of 3M sulfuric acid in this experiment. (Grignard Reaction)

false

True or False The magnesium was cleaned by the addition of anhydrous diethyl ether in this experiment. (Grignard Reaction)

false

safety diamond red

flammability

Be able to calculate the percent yield (Electrophilic Aromatic Substitution)

grams of product/ theoretical x 100%

safety diamond blue

health risk

Know the reason we use each component in the set up. Understand what would happen if the component was omitted. For example: What would happen to the percent yield if the drying tube was omitted? What impurity would be generated? (Grignard Reaction)

heating mantel: to heat and stir the mixture round bottom flask: heat help reflex the reaction addition funnel: to allow a controlled dispension of the liquids into the round bottom flask condensing tube: used to cool the vapors back to liquids drying tube: limit the amount of water from the atmosphere entering the reaction -Why bother with all these precautions? Well, because water is the natural enemy of the Grignard reagent, and of organometallic reagents in general . Not only will water react irreversibly with your Grignard, the molecular mass of water is so low that a little goes a long way, and ineptly dried solvent or glassware will seriously reduce your yield. - water causes the reaction to fail (phenyl magnesium bromide decompose in water)

Know the purpose of the bleach and sodium thiosulfate (Electrophilic Aromatic Substitution)

household bleach is used as the oxidizing agent sodium thiosulfate (Na2S2O3) removes any residual iodine from the reaction solution prior to acidification. (bleach=oxidizing agent, sodium thiosulfate= used to consume excess I3)

Understand the technique of melting point (Grignard Reaction)

if the product has a melting point close to the literature melting point and is within 2 degrees then it is pure

Know the purpose of the addition of hydrochloric acid after the reaction (Electrophilic Aromatic Substitution)

once the reaction is complete, the solution will be acidified by adding HCl in the end to promote the formation of precipitation . Here the solvent is polar like water or ethanol hence, the charge dramatically increase solubility. However when acid is added , the charge is removed by adding HCl and the organic compound is no longer soluble, resulting precipitate formation. (HCl activates the product in order to get the final product)

organics dissolve in the aqueous or organic layer (Grignard Reaction)

organic (dissolve in non-polar)

______ is used to change a neutral organic molecule into an ion. For example an organic acid (neutral molecule) becomes an anion when base is added. Thus it changes from organic soluble to water soluble. (Grignard Reaction)

pH

Consider the charge distribution of a Grignard reagent. There is a partial _______ charge on Mg−XMg−X, where XX is a halogen, and a partial ______ charge on the adjacent carbon.

positive negative

safety diamond yellow

reactivity

Be able to recognize the reagents and products of the reaction (Grignard Reaction)

reagent: grignard reagent (phenyl magnesium bromide), carbonyl compound (benzophenone) product: triphenylmethanol (Step 1-benzophenone and solid Mg makes phenyl magnesium bromide. Step 2- phenyl magnesium bromide reacts with benzophenone to make triphenyl methanol)

Identify the techniques used in the work-up and characterization of triphenylmethanol. The technique used to separate the pure product from any excess reagent, impurities, and byproducts

recrystallization

What is the technique used in this experiment to purify the synthesized product? (Electrophilic Aromatic Substitution)

recrystallization

Know the apparatus setup used for the reaction (Grignard Reaction)

reflux apparatus with an additional funnel -separatory funnel directly above the rbf and then a condensing tube to the right (reflux- condenser with an addition funnel and a thermometer in the condenser, later separation funnel used)

Know the overall reaction equation and be able to name the reactants, catalyst, and products (Synthesis of Aspirin)

salicylic acid + acetic anhydride --> acetylsalicylic acid (aspirin) + acetic acid reactant: salicylic acid product: aspirin catalyst: phosphoric acid (H3PO4)

Understand the IR analysis of the aspirin and be able to identify the peaks on the spectrum (Synthesis of Aspirin)

salicylic acid: carboxylic acid @ 3229.5, OH at 2851.3 aspirin: carboxylic acid @ 2833, ester group @ 1751 (OH signal will disappear, additional C=O signal appears around 1600)

True or False The magnesium was cleaned by grinding it using a mortar and pestle in this experiment. (Grignard Reaction)

true

True or False The magnesium was cleaned by the addition of a small crystal of iodine in this experiment. (Grignard Reaction)

true

true or false Sodium hypochlorite and hydrochloric acid are irritants and corrosive compounds so handle the reagents with care. (Electrophilic Aromatic Substitution)

true

true or false To prepare 10 mL of 1.0 M HCl from a concentrated HCl (concentration = 12.1 M), mix 0.83 mL of the concentrated HCl with water into a 10 mL acid solution. (Electrophilic Aromatic Substitution)

true

true or false To prepare 30 mL of 3.0 M H2SO4 from a concentrated H2SO4 (concentration = 18.0 M), mix 5.0 mL of the concentrated H2SO4 with water into a 30 mL acid solution.

true