Five-Membered Heterocycles and Their Applications

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Questions and Answers

What do pyrrole substitution reactions typically exhibit in terms of selectivity?

Variable regioselectivity (correct)

Universal α-selectivity

Universal β-selectivity

No selectivity

Why is the intermediate formed by electrophile attack at C-2 of pyrrole more stable than that from C-3?

It undergoes faster reaction

It is less sterically hindered

It has fewer substituents

It is stabilized by charge delocalization (correct)

Functional substituents influence pyrrole substitution reactions similarly to which other compound?

Cyclohexane

Hexane

Benzene (correct)

Naphthalene

What characterizes the directing influence of functional substituents on heterocyclic ring substitution?

It follows ortho-para and meta-directing patterns Signup and view all the answers

In the reactions described, how are the substituents in the thiophenes positioned?

Mixed types at 2 and 5 positions Signup and view all the answers

Which of the following compounds is considered a saturated derivative of pyrrole?

Pyrrolidine Signup and view all the answers

What is the primary bioactive function of ranitidine?

H2-receptor antagonist Signup and view all the answers

Which rule do pyrrole, furan, and thiophene follow that classifies them as aromatic compounds?

Hückel’s rule Signup and view all the answers

Which compound is known to treat parasitic worms in livestock?

Pyrantel Signup and view all the answers

Thiophene can be industrially synthesized through a reaction between which two substances?

n-butane and sulfur Signup and view all the answers

What is the boiling point of thiophene?

84°C Signup and view all the answers

Which of the following compounds is not a bicyclic compound?

Furan Signup and view all the answers

Which of the following statements is true regarding the formation of resonating structures in these compounds?

Pyrrole, furan, and thiophene can support their aromatic nature with resonating structures. Signup and view all the answers

What is the basic unit of the porphyrin system?

Pyrrole Signup and view all the answers

Which reaction occurs readily with furan?

Electrophilic substitution Signup and view all the answers

Which of the following represents the correct reactivity order of the five-membered heterocycles for electrophilic substitution?

Pyrrole > Furan > Thiophene > Benzene Signup and view all the answers

Which reaction can cause N-protonation in pyrrole?

Halogenation Signup and view all the answers

What is a common method to prepare furan?

Decarbonylation of furfural Signup and view all the answers

Which position on the rings of furan and thiophene is preferred for substitution?

2-position (α) Signup and view all the answers

Which of the following statements is true about pyrrole?

Pyrrole reacts readily with iodine. Signup and view all the answers

Which of the following compounds is prepared from pyrrole by substitution?

2-acetylpyrrole Signup and view all the answers

Study Notes

Structure and Types of Five-Membered Heterocycles

Pyrrole, furan, and thiophene are the simplest five-membered heterocyclic compounds, each featuring one heteroatom.
Saturated derivatives: pyrrolidine (pyrrole), tetrahydrofuran (THF) (furan), and thiophane (thiophene).
Bicyclic compounds: indole (pyrrole fused with benzene), benzofuran (furan fused with benzene), benzothiophene (thiophene fused with benzene).
These compounds exhibit aromatic properties, adhering to Huckel's rule (4n+2 π electrons).

Bioactive Compounds Containing Heterocycles

Ranitidine: an H2-receptor antagonist used for lower stomach acid levels, effective in treating ulcers.
Ketorolac: a potent analgesic and anti-inflammatory medication.
Pyrantel: an anthelmintic agent administered to eliminate parasitic worms in livestock.

Sources and Synthesis

Pyrrole and thiophene are found in coal tar, with thiophene present in about 0.5% of ordinary benzene from fractional distillation.
Industrial synthesis of thiophene can occur by the high-temperature reaction of n-butane with sulfur.
Pyrrole can be synthesized through various methods, including being a fundamental component of porphyrins, present in biomolecules like hemoglobin and chlorophyll.
Furan is primarily produced through decarbonylation of furfural, derived from pentosans.

Electrophilic Substitution Reactions

Pyrrole, furan, and thiophene are reactive with electrophiles, undergoing nitration, halogenation, sulfonation, and Friedel-Crafts acylation.
Reactivity order for electrophilic substitution: pyrrole >> furan > thiophene > benzene.
Pyrrole displays exceptional reactivity, allowing it to react with iodine and form 2-acetylpyrrole in the absence of a catalyst.

Substitution Preferences and Mechanisms

Substitution most frequently occurs at the 2-position (α) for furan and thiophene compounds.
Pyrrole's reactions require care, as N-protonation can disrupt its aromatic properties.
N-protonation is often performed before other reactions; N-acetylpyrrole can be formed via interactions with acetic anhydride or acetyl chloride.
The mechanism explains regioselectivity in electrophilic attack: C-2 intermediate exhibits more stabilization through charge delocalization than C-3.

Influence of Functional Substituents

Functional groups impact substitution reactions in a manner similar to benzene, affecting regioselectivity.
Different substituents (e.g., electron-donating or electron-withdrawing groups) alter the orientation and outcome of the reactions involving heterocycles.
Observations reveal the directing influence of substituents in curvature and position for both thio- and pyrroles.

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Description

Explore the structure and types of five-membered heterocycles, focusing on compounds like pyrrole, furan, and thiophene. The quiz also covers their bioactive derivatives such as ranitidine and ketorolac, as well as the sources and synthesis methods of these important chemical compounds.