Basic nucleophilic acyl substitution reactions work better with acid catalysts.
acetic anhydride and salicylic acid are used to make aspirin.
The reaction goes slowly when the reagents are mixed.
The reaction can be completed in a minute or two with the addition of a drop of sulfuric acid.
The acid-catalyzed reaction of salicylic acid with acetic anhydride can be proposed.
Explain how a single drop of sulfuric acid increases reaction rate.
Acid derivatives hydrolyze to produce carboxylic acids.
Most of the time, hydrolysis occurs under acidic or basic conditions.
Under neutral conditions acid halides and anhydride hydrolyze.
Exposure to moist air can cause hydrolysis of an acid halide or anhydride.
Storage acids and anhydrides under dry nitrogen and using dry solvent and reagents can help avoid hydrolysis.
The reverse of the esterification equilibrium is acid-catalyzed hydrolysis.
The equilibrium is driven by the addition of excess water.
The carbonyl group is attacked by Hydroxide ion.
The acid and the carboxylate ion are created by thepulsion of alkoxide ion.
The exothermic transfer drives the completion of the process.
A full mole of base is eaten.
This is a standard addition-elimination mechanism that ends with a protons transfer.
When a fat is hydrolyzed, the resulting long-chain sodium carboxylate salts are what we know as soap.
Chapter 25 talks about detergents and soaps in more detail.
Under basic conditions, draw a mechanism for the hydrolysis of this compound.
Which products will have the 18O label?
How would you prove that the 18O label is in the products?
Base is used by soap manufacturers to hydrolyze fats.
There are two reasons that basic hydrolysis is preferred.
Amides hydrolyze to carboxylic acids in both acidic and basic conditions.
Amides are the most stable of the acid derivatives, and stronger conditions are required for their hydrolysis.
In most hydrolysis conditions, heating is done in 6 M HCl or 40% NaOH.
The basic hydrolysis mechanism is the same as the one for the ester.
The carbonyl is attacked by Hydroxide to give a tetrahedral intermediate.
A carboxylic acid is quickly deprotonated to give the salt of the acid and ammonia.
This is a standard addition-elimination mechanism that ends with a protons transfer.
As the very poor leaving group leaves, the final proton transfer is very fast.
The acid catalyzed hydrolysis of an ester is similar to the mechanism of amide hydrolysis under acidic conditions.
The carbonyl group is activated by the formation of the carbonyl group.
The amine can leave as a group of protons.
The acid and the amine can be transferred quickly.
The mechanism takes place in two stages.
The leaving group was acid-catalyzed elimination in the second half.
The products are favored under both acidic and basic conditions.
To show which steps are exothermic to drive the reactions to completion.
Aqueous acid or base is used to heating nitriles to Amides and carboxylic acids.
Mild conditions can hydrolyze a nitrile.
It can hydrolyze all the way to the carboxylic acid.
The elec trophilic carbon of the cyano group is attacked by hydroxide.
The tautomer of an amide is unstable.
The amide is given when a protons is removed from oxygen and nitrogen.
The same basepromoted mechanism is used in the further hydrolysis of the amide to the carboxylate salt.
The enol of an amide can be found in the form of protons.
The amide is caused by the removal and replacement of a protons.
There is a mechanism for the basic hydrolysis of benzonitrile to the benzoate ion and ammonia.
The mechanism for acidic hydrolysis of a nitrile is the same as the basic hydrolysis, except that the nitrile is first protonsated and then weakened by water.
Under acidic conditions, the tautomerism involves deprotonation on oxygen and nitrogen.
There is a mechanism for the acid-catalyzed hydrolysis of benzonitrile to benzamide.
Alcohols, aldehydes, and amine can be reduced to alcohols, aldehydes, and amine.
Acid derivatives are relatively difficult to reduce and need a strong agent such as LiAlH4 to do so.
The other acid derivatives are less reactive than acid chlorides.
Acid chlorides can be converted to primary alcohols by either lithium aluminum hydride or sodium borohydride.
Both acid chlorides and esters react through an addition-elimination mechanism to give aldehydes.
Diluted acid is added to the alkoxide after the reduction is complete.
An aldehyde is reduced further to an alcohol by nucleophilic acyl substitution.
Add acid to the workup.
There is a mechanism for the reduction of octanoyl chloride.
Diisobutylaluminum hydride reduces nitriles to aldehydes at low temperatures.
Sections 18-9 and 18-10 covered these reductions.
Some of the best synthetic routes to amine are provided by the reduction of amides and nitriles to amines.
Primary amine is reduced to primary amides and nitriles.
Both secondary and tertiary amines are reduced.
The mechanism of this reduction is similar to a typical nucleophilic acyl substitu tion, with hydride ion adding to the carbonyl group.
The nitrogen atom is a poor leaving group and the former carbonyl oxygen atom is a fair leaving group.
An imine or iminium salt is created when the oxygen atom leaves.
Second hydride is added.
Primary amines are reduced to nitriles.
The products of the reduction of aluminum hydride will be given.
Grignard and organolithium reagents add more acid to give alkoxides.
The alkoxides give alcohols.
The mechanism involves substitution at the acyl carbon atom.
Attack by the carbanion-like organometallic reagent, followed by elimination of alkoxide, gives a ketone.
A second equivalent of the organometallic reagent is added to the ketone.
Unless the original ester is a formate, hydrolysis gives tertiary alcohols.
Two of the groups on the product are derived from the same reagent.
Add acid to the alkoxide.
Acid chlorides only react once with dialkylcuprates to give ketones.
A Grignard or organolithium reagent is used to form the salt of an imine.
The imine is further hydrolyzed to a ketone by acidic hydrolysis of the salt.
Grignards add to esters and acid acetophenone with magnesium salt.
There is a mechanism for the reaction of propanoyl chloride with 2 moles of phenylmagnesium a hydrogen from the ester and two bromide.
After discussing the reactions and mechanisms of all the common acid derivatives, we now look at the reactions of each type of compound.
Any reactions that are peculiar to a specific class of acid derivatives are covered in these sections.
Acid chlorides are made using a variety of reagents.
The most convenient reagents are Thionyl chloride and oxalyl chloride.
Acid chlorides are not found in nature.
Acid chlorides are easy to convert to other acid derivatives because they are the most reactive.
The acyl chloride may be used as an intermediate in the best synthetic route to an anhydride.
Acid chlorides are added twice to give 3deg alcohols.
Just once, lithium dialkylcuprates add to give ketones.
hydride is reduced to 1deg alcohols after being added to acid chlorides.
The hydride gives aldehydes.
In the presence of aluminum chloride, acyls acylate benzene, halobenzenes, and activated benzene derivatives.
Section 17-11 talks about Friedel-Crafts acylation.
There is a mechanism for the acylation of anisole.
Friedel- Crafts acylation involves an acylium ion.
Anhydride are activated acid derivatives and are often used for the same types of acylations.
Acid chlorides are more reactive than anhydrides, and they are occasionally found in nature.
The toxic ingredient "Spanish fly" is used as a vesicant to destroy warts on the skin.
The most important carboxylic acid anhydride is acetic anhydride.
It is produced at a rate of 4 billion pounds per year.
Dehydrating acetic acid to give ketene is the most common industrial synthesis.
A large increase in entropy is caused by breaking one molecule into two.
The equilibrium favors the products at a high temperature.
The rate of the reaction can be improved by adding triethylphosphate.
acetic acid is fed directly into ketene, where it reacts quickly and quantitatively to give acetic anhydride.
acetic anhydride is an inexpensive acylating reagent.
The beetle between the fingers is less specialized than the one in the center of the body.
Horses can eat methods.
The most common method for making anhydride is the reaction of acid hay containing blisters with a carboxylic acid or a carboxylate salt.
The failure was caused by cantharidin poisoning.
The heating of the corresponding diacid can be used to make some cyclic anhydride.
A dehydrating agent, such as acetic anhydride, can sometimes be added to accelerate this reaction.
The equilibrium favors the products of the five- and six-membered anhydride.
Acid chlorides and anhydride reactions are the same.
Anhydride can be converted to less reactive acid derivatives.
The Friedel-Crafts acylation is similar to acid chlorides.
The catalyst may be an acidic compound.
Cyclic anhydride can be used on the aromatic product's side chain.
One of the two acid molecules is lost in most anhydride reactions.
Half of the acid groups wouldn't react if a precious acid was converted to anhydride.
It would be more efficient to convert the acid to an acid chloride.
There are three instances when anhydrides are preferred.
It's easy to use acetic anhydride and it gives better yields than acetyl chloride for acetylation of alcohols.
Formyl chloride can't be used for formylation because it quickly degrades to CO and HCl.
The formyl group is whereacetic formic anhydride reacts.
The formyl group is less hindered than the acetyl group because it lacks a bulky, electron-donating alkyl group.
acetic formic anhydride forms alcohols and amines with formate and formamides.
The use of anhydride to make difunctional compounds.
It is often necessary to convert just one acid group of a diacid.
There is a substituted coumarin used as an is expelled as a carboxylate ion and a monofunctionalized derivative results.
The most common acid derivatives are es.
They are found in plant oils where they give fruity aromas.
The odor of ripe bananas comes mostly from isoamyl acetate.
The oil of wintergreen has been used as a medicine.
Coumarin is found in lavender oil and sweet clover.
The heads of sperm whales have large chambers of spermaceti, a waxy ester that helps to regulate their buoyancy in the water and that may help the head to serve as a resonating chamber for communicating underwater.
The industry uses es as a solvent.
It is a good solvent for a wide variety of compounds, and its toxicity is low compared with other solvents.
Household products that contain ethasone include cleaners, polishes, glues, and spray finishes.
Butyrate and butyl butyrate were once used as a solvent for paints and finishes, including the "butyrate dope" that was sprayed on the fabric covering of aircraft wings to make them tight and stiff.
The most common materials used in fabrics, films, and solid plastic bottles arePolyesters, covered later in this section and in Chapter 26.
The synthesis of erythropoietin is usually done by the esterification of an acid with an alcohol or by the reaction of an acid chloride with an alcohol.
The acid can be treated with diazomethane.
The alcohol group can be changed by transesterification with either acid or base.
Acid chlorides and anhydrides are unstable.
Most esters don't react with water under neutral conditions.
They hydrolyze under acidic conditions and can form an amide with an amine.
Grignard and organolithium reagents add twice to give alcohols after the hydride reduces the esters to primary alcohols.
Under acidic conditions, such lactones form spontaneously.
O apples, eat them from within.
Lactones that are not favored by the body may be synthesised to attract and trap the librium.
The equilibrium to the right is shifted because sticky insect traps baited remove water and the reaction is driven to completion.
The human diet needs L-ascorbic acid to avoid the disease scurvy.
The equilibrium mixture of the two forms is called ascorbic acid.
It stops the growth and development ofbacteria.
As shown in the preceding figure, propose a mechanism for the formation of 9-Hydroxynonanoic acid lactone.
Explain your choice of reagent for each synthesis.
At the moment, you are using at least five things that are made from polyesters.
Your clothes are almost certainly sewn with Dacron(r) thread because they have some Dacron(r) fiber in them.
The optical film in your DVD is made of Mylar.
Some of the electronics in your cell phone are made out of Glyptal(r) polyester.
The soft drink in your hand was made with metallized Mylar film.
It was launched in 1964 to reflect radio a plastic bottle that was blow-molded from poly(ethylene terephthalate) resin, better waves for intercontinental telephone.
The phthalic acid is esterified with ethylene glycol.
When it reentered base-catalyzed transesterification of dimethyl terephthalate with ethylene glycol at the atmosphere in 1969 it burned up.
Methanol escapes as a gas at this temperature.
In Chapter 26 we will look at more of the polymers.
Amides are the least reactive acid derivatives and can be made from any of the others.
Amides are usually synthesised in the laboratory by the reaction of an acid and amine.
Industrial synthesis involves heating an acid with an amine to drive off water and promote condensation.
This simple industrial technique is rarely used in the laboratory, but it may work with the use of a reagent.
The partial hydrolysis of nitriles and amine give amides.
Amides are not basic.
There is a nonbonding pair of electrons in the NH2 group.
The lone pair is involved in strong resonance with the carbonyl group, which prevents it from being basic or nucleophilic.
Only a strong acid can cause an amide to be protonsated.
Pro tonation usually occurs on the carbonyl group because of resonance stabilization.
Amides are the most stable acid derivatives, so they are not easy to convert to other derivatives.
Reduction to amines is one of the best ways to synthesise amines.
Amides can be made by a strong acid or strong base.
Amides can be dehydrated of nitriles.
Dehydrating agents can remove water from a primary amide and give it a nitrile.
Dehydration of Amides is a common method for synthesis of nitriles.
The traditional reagent for this dehydration is P2O5.
Five-membered lactams and six-membered lac tams are formed when heating or adding a dehydrating agent to the appro priate.
Smaller or larger rings are hard to form under these conditions.
The unusual reactivity of b@lactams appears to be the result of the strain in the four-membered ring.
The ring strain is relieved when a b@lactam acylates a nucleophile.
The b@lactam ring is found in three important classes of antibiotics.
B@lactam antibiotics interfere with the synthesis of cell walls.
The acylatedidase is inactive for synthesis.
The acylation step converts an amide to an ester by hydrolyzing the amide linkage of the lactam ring.
The Show would be able to accomplish the following synthetic transformations with this combination.
amoxicillin can be used to avoid being deactivated.
You can use any necessary reagents.
nylon's discovery in 1938 made possible a wide range of high-strength fibers, fabrics, and plastics that we take for granted today.
nylon 6,6 is the most common form of nylon because it consists of a six-carbon diacid and a six-carbon diamine in repeating blocks.
The nylon fibers have strong amide hydrogen bonding between the chains, which gives them great strength.
Chapter 26 contains more detail on nylon chemistry.
nitriles are considered acid derivatives because they hydrolyze to carboxylic acids.
The same number of carbons and carboxylic acids are used to make nitriles.
They are also made from primary alkyl halides and tosylates.
Aryl cyanides can be made by the Sandmeyer reaction of aryldiazonium salt.
It is possible that nitriles are further hydrolyzed to carboxylic acids.
Reduction of a nitrile by aluminum hydride gives a primary amine, and the reaction with a Grignard reagent gives an imine that hydrolyzes to a ketone.
The building blocks of proteins can be found in nitriles.
The majority of carboxylic esters are alcohols and carboxylic acids.
Thioesters are less reactive than acid chlorides and anhydride.
The resonance stabilization of a thioester is less than that of an ester.
The different sizes of the orbitals are located at different distances from the nucleus.
The alkyl sulfide anion is a better leaving group than the alkoxide because it is less basic and the larger sulfur atom carries a negative charge.
Sulfur is more polarizable than oxygen, which allows more bonding as the alkyl sulfide anion leaves.
The resonance overlap in an ester is more effective than that in a thioester.
CoA is a thiol with thioesters that serve as biochemical acyl transfer reagents.
Acetyl CoA transfers an acetyl group to a nucleophile, with coenzyme A serving as the leaving group.
Acid halides and anhydrides are not good for acylating.
They hydrolyze under the conditions found in living organisms.
Thioesters are good atselective acylating reagents.
In living systems, thioesters are common acylating agents.
Transfer of acyl groups from thioesters of CoA is one of the many biochemical acylations.
In living systems, acetyl CoA serves as a water-stable equivalent of acetic anhydride.
Carbonic acid is found in all carbonated beverages.
Carbonic acid is always in equilibrium with carbon dioxide and water, but it has several important stable derivatives.
TMU is often used as a polar solvent with a high boiling point.
It can be washed out of a solution.
The urethane is stable even though it is unstable.
This is how it is made.
There is a mechanism for the reaction of isocyanate with 1-naphthol.
The development of sevin and Polycarbonates are bonds between the carbonate ester linkage and the carbamate ester linkage.
The alkaloid physostigmine is used in bulletproof windows and crash helmets.
The studies led to the synthesis.
A diol reacts with a diisocyanate, a compound with two isocyanate groups.
Functional groups can be converted to carboxylic acids by acidic or basic hydrolysis.
The hydroxy group of the acid is replaced by a halogen in an activated acid derivative.
Reduce to primary alcohols.
The hydroxy group of the acid is replaced by a nitrogen atom and its attached hydrogens or alkyl groups.
A amide is a mixture of two acids.
An amine is cleaved to give an alcohol and amide.
A molecule of water is lost in the formation of an activated acid derivative.
Chapter 21 has reactions shown in red.
Reactions are shown in blue.
Carbonic acid is in equilibrium with water and carbon dioxide.
The amides and esters are stable.
The hydroxy group of the acid is replaced by an alkoxy group.
An alcohol and a carboxylic acid are components of an ester.