Oxirane and Four-Membered Rings Quiz

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Questions and Answers

What type of reaction does furan undergo with maleic anhydride?

Hydrolysis reaction

Dehydrogenation

Electrophilic substitution

Diels-Alder cycloaddition (correct)

How does pyrrole react with maleic anhydride?

Hydrolysis

No reaction occurs

Electrophilic substitution at C-2 (correct)

Cycloaddition

What effect does the addition of nitrogen units have on the hydrolysis rate of N-acetylazoles?

Decreases the hydrolysis rate

Reverses the hydrolysis reaction

Has no effect on hydrolysis

Increases the hydrolysis rate (correct)

What is thiamine's role in biochemical reactions?

It is a coenzyme for decarboxylation reactions Signup and view all the answers

What is the pKa of the C-2 hydrogen of thiazolium salts?

Approximately 13 Signup and view all the answers

In what way do thiazolium salts catalyze reactions compared to cyanide ions?

They catalyze the formation of acyloins Signup and view all the answers

Which of the following is true about the benzoin condensation?

It is limited to aromatic aldehydes Signup and view all the answers

What kind of intermediate is formed in the mechanisms of both thiazolium-catalyzed reactions and benzoin condensation?

Acyl anion equivalent Signup and view all the answers

What effect does charge delocalization have on the stability of the intermediate formed by electrophile attack at C-2 compared to C-3?

It stabilizes the C-2 intermediate to a greater degree. Signup and view all the answers

How does the activation energy for substitution at the C-2 position compare to that at the C-3 position?

It is less for C-2. Signup and view all the answers

Which type of substituent generally increases the rate of substitution reactions in heterocycles?

Electron donating groups. Signup and view all the answers

What distinguishes the basicity of the nitrogen in diazoles compared to sp^3-hybridized nitrogen?

Diazoles are more basic by over a million times. Signup and view all the answers

What functional role can furan be considered to exhibit?

An enol ether. Signup and view all the answers

What type of reactions can furan and pyrrole undergo due to their structure?

Hydrolysis and Diels-Alder cycloaddition reactions. Signup and view all the answers

In terms of directing influence, how do substituents affect heterocyclic ring substitution?

They influence in the same way as for cyclohexane. Signup and view all the answers

What is a key differentiation point in behavior between pyrroles and thiophenes?

Pyrroles and thiophenes behave differently in terms of hydrolysis and substitution reactions. Signup and view all the answers

What type of reaction can be illustrated by the formation of N-alkylpyridone from an N-alkyl pyridinium cation?

Hydroxide addition followed by mild oxidation Signup and view all the answers

Which of the following compounds can be derived from the Birch reduction of pyridines?

Dihydropyridines Signup and view all the answers

What is the preferred formation of pyridyne intermediates during amination reactions involving 3-halopyridines?

3-pyridyne Signup and view all the answers

Which statement about the pyridine ring is accurate regarding its ability to support a negative charge?

It can support a negative charge, particularly when substituted. Signup and view all the answers

Which of the following alkaloids is a quinoline that inhibits topoisomerase I?

Camptothecin Signup and view all the answers

What is the expected product of alkylation reactions in substituted pyridines?

N-alkylpyridone Signup and view all the answers

Which of the following does NOT participate in addition-elimination substitution reactions similar to 2- and 4-isomers?

3-halopyridines Signup and view all the answers

Which neurotoxins are characterized by guanidinium moieties and have marine origins?

Saxitoxin and Tetrodotoxin Signup and view all the answers

What type of hybridization does the nitrogen in pyridine have?

sp^2 Signup and view all the answers

Which of the following is TRUE regarding substituents on pyridine?

Substituents at the 2 and 4-positions significantly increase basicity. Signup and view all the answers

What is the common name for methyl pyridine?

Picoline Signup and view all the answers

Which derivative is a useful catalyst for acylation reactions in pyridine?

4-Dimethylaminopyridine Signup and view all the answers

Which of the following diazines is considered a weaker base than pyridine?

Pyrimidine Signup and view all the answers

Why is pyridazine's basicity considered anomalous?

It has electron pair repulsion effects involving neighboring nitrogens. Signup and view all the answers

What is the pKa value of pyridine?

5.2 Signup and view all the answers

What is the effect of the basic unshared electron pair in pyridine?

It is not involved in the aromatic system. Signup and view all the answers

What directs nucleophilic attack in the acid-catalyzed opening of an oxirane with an unsaturated substituent?

The π-electron system of the substituent Signup and view all the answers

Which method is generally effective for preparing four-membered heterocyclic compounds?

Treating a 3-halo alcohol with base Signup and view all the answers

What dominates in the formation of thietane when a 3-halo alcohol is treated with a weak base?

Nucleophilicity of sulfur Signup and view all the answers

Which reaction is particularly suited to oxetane formation?

Paterno-Buchi photocyclizations Signup and view all the answers

What effect does gem-dimethyl substitution have on azetidine formation?

It favors coiled chain conformations Signup and view all the answers

Which four-membered ring formation is favored due to a relatively rigid substrate configuration?

Oxetane Signup and view all the answers

In the electrophilic chlorination of thietane, what does the sulfur form as an intermediate?

Chlorosulfonium Signup and view all the answers

What common feature is observed in many ring-opening reactions of four-membered heterocycles?

Acid-catalysis Signup and view all the answers

Study Notes

Oxirane Ring Opening

If oxirane has an unsaturated substituent (vinyl or phenyl), acid-catalyzed opening occurs at the allylic (or benzylic) carbon in a 6-endo fashion.
The π-electron system of the substituent assists development of positive charge at the adjacent oxirane carbon, directing nucleophilic attack to that site.

Four-Membered Rings

Several methods are used to prepare four-membered heterocyclic compounds.
Treating a 3-halo alcohol, thiol or amine with base is generally effective, but has mediocre yields.
Dimerization and elimination are common side reactions.
In the case of thietane formation, the greater nucleophilicity of sulfur dominates, especially if a weak base is used.
Azetidine formation is possible, but aziridine formation is typically favored.
The Thorpe-Ingold effect favors coiled chain conformations, which can be beneficial in obtaining high yields for azetidine formation.
The relatively rigid conformation of some substrates favors oxetane formation and prevents oxirane cyclization.
The Paterno-Buchi photocyclizations are particularly well-suited for oxetane formation.

Reactions of Four-Membered Heterocycles

Reactions of four-membered heterocycles are influenced by ring strain.
Acid-catalysis features commonly in ring-opening reactions.
In thietane reactions, sulfur undergoes electrophilic chlorination to form a chlorosulfonium intermediate followed by a ring-opening chloride ion substitution.
Strong nucleophiles can also open the strained ether.
The intermediate formed by electrophile attack at C-2 is stabilized by charge delocalization to a greater degree than the intermediate from C-3 attack.
The Hammond postulate suggests that the activation energy for substitution at C-2 is less than that at C-3.

Functional Substituent Influence on Heterocyclic Reactions

Functional substituents influence the substitution reactions of heterocycles similarly to how they do for benzene.
Electron donating substituents direct to ortho/para positions, while electron withdrawing substituents direct to meta positions.
Basicity of the sp^2^-hybridized nitrogen in diazoles is over a million times greater than that of the apparent sp^3^-hybridized nitrogen, the electron pair of which is part of the aromatic electron sextet.

Hydrolysis of Heterocycles

Furan can be considered an enol ether and pyrrole an enamine.
Acid-catalyzed hydrolysis of these functions results in carbonyl compounds and alcohols or amines.
Furan hydrolyzes to 1,4-dicarbonyl compounds, but pyrroles and thiophenes behave differently.
Furan and pyrrole can undergo Diels-Alder cycloaddition reactions with strong dienophiles like maleic anhydride.
Additional nitrogen units in a series of N-acetylazoles greatly increase the rate of hydrolysis.

Thiamine Chemistry

Thiamine, as its pyrophosphate derivative, is a coenzyme for several biochemical reactions, notably decarboxylations of pyruvic acid to acetaldehyde and acetoin.
The C-2 hydrogen of thiazolium salts is unexpectedly acidic, forming a relatively stable ylide conjugate base.
This ylide acts as an acyl anion equivalent, facilitating decarboxylation and deuterium exchange at C-2.
Thiazolium salts catalyze the conversion of aldehydes to acyloins, similar to how cyanide ion catalyzes the formation of benzoin from benzaldehyde in the benzoin condensation.

Pyridine Chemistry

Pyridine and its derivatives are weak bases due to the sp^2^ hybridization of the nitrogen.
Electron donating substituents increase pyridine basicity.
2 and 4-position substituents influence basicity more than equivalent 3-substituents.
Methyl substituted derivatives have common names picoline, lutidine, and collidine.
4-Dimethylaminopyridine is a useful catalyst for acylation reactions carried out in pyridine as a solvent.
Though the sp^3^ hybridized nitrogen might appear to be the stronger base, the sp^2^ ring nitrogen is the site at which protonation occurs.

Diazine Chemistry

Diazines pyrazine, pyrimidine, and pyridazine are all weaker bases than pyridine due to the inductive effect of the second nitrogen.
The order of base strength is unexpected, with pyridazine being the weakest base.
Electron pair repulsion involving the vicinal nitrogens destabilizes the neutral pyridazine base relative to its conjugate acid.

Electrophilic Substitution of Pyridine

Pyridine is a modest base with a pKa of 5.2.
The basic unshared electron pair is not part of the aromatic sextet, so N-substitution retains the aromaticity of pyridine.
N-alkylation and N-acylation products are stable crystalline solids in the absence of water or other reactive nucleophiles.
N-acyl salts can serve as acyl transfer agents for the preparation of esters and amides.
The stability of the pyridinium cation has led to its use as a moderating component in complexes with reactive inorganic compounds.
Alkyl substituents in the 2- and 4-locations of pyridine (and to a greater degree the N-oxide ring) are activated in the same fashion as by a carbonyl group.
Birch reduction converts pyridines to dihydropyridines, which are bis-enamines and may be hydrolyzed to 1,5-dicarbonyl compounds.
Pyridinium salts undergo a one electron transfer to generate remarkably stable free radicals.
3-halopyridines do not undergo addition-elimination substitution reactions as do their 2- and 4-isomers, but strong base sodium amide effects amination by way of a pyridyne intermediate.
3-pyridyne is formed in preference to 2-pyridyne, unless C- 4 is occupied by an alkyl substituent.
The pyridyne intermediate is similar to benzyne.

Polyclyclic Heterocycles

Heterocyclic structures are found in many natural products.
Many nitrogen-containing compounds, known as alkaloids (due to their basic properties), have been discovered.
Examples include Camptothecin (quinoline alkaloid), Reserpine (indole alkaloid), Ajmaline (indole alkaloid), Strychnine (indole alkaloid), Saxitoxin (neurotoxin with marine origins), and Tetrodotoxin (neurotoxin with marine origins).

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Description

Test your knowledge on the mechanisms involved in the opening of oxirane rings and the synthesis of four-membered heterocyclic compounds. This quiz covers concepts like the Thorpe-Ingold effect, nucleophilicity, and various methods of preparation. Challenge yourself with questions that explore both theoretical and practical aspects of these chemical processes.