Medicinal and Pharmaceutical Chemistry – Alkyl Halides III

Flashcards created for reviewing the key concepts in Medicinal and Pharmaceutical Chemistry, specifically focusing on Alkyl Halides and their reactions in biological systems.

What does SN1 stand for in reaction mechanisms?

SN1 stands for nucleophilic substitution unimolecular.

What is the rate determining step in an SN1 reaction?

The formation of the carbocation.

What type of alkyl halides do not undergo SN2 reactions?

Tertiary (3o) alkyl halides.

What is the role of S-adenosylmethionine (SAM) in biological methylation?

SAM acts as an electrophilic donor to transfer a methyl group.

Which enantiomer results from the reaction of chiral tertiary alkyl halides in SN1 mechanisms?

A racemic mixture of products.

How can one tell if a racemic mixture was obtained?

No optical rotation is observed when measured by polarimeter.

What type of reaction is involved in nearly all biological methylations?

SN2 reactions.

What is the leaving group in the SN2 reaction of SAM?

S-adenosylhomocysteine (SAH).

What happens when a nucleophile attacks a planar carbocation in terms of stereochemistry?

It yields 50% retention and 50% inversion of configuration.

What characteristic of SN1 reactions contributes to the formation of racemic mixtures?

The formation of a planar, achiral carbocation intermediate.

Which nucleophile reacts faster in an SN2 reaction, (CH3)2N- or (CH3)2NH?

(CH3)2N- is more reactive due to its negative charge.

What type of product is expected from the reaction of (S)-3-chloro-2,3-dimethylpentane with ammonia?

The product is racemic.

What effect do organo-halogen drugs have on DNA?

They can form cross-links, preventing DNA unraveling during replication.

What is the mechanism of methylation in living systems?

Methylation typically involves an SN2 reaction mechanism.

When does the SN1 mechanism favor a tertiary carbocation formation?

When higher steric hindrance hinders an SN2 mechanism.

What is the best representation of the transition state in a bimolecular nucleophilic substitution?

A state where the nucleophile and the substrate are both partially bonded.

What determines the reaction rate in an SN1 reaction?

The concentration of the alkyl halide.

What is an example of a toxic methyl halide that can react through SN2?

Methyl chloride (CH3Cl).

How does the reactivity of bromobutane compare to chlorobutane in nucleophilic substitution?

Bromobutane reacts faster due to bromine being a better leaving group.

What product is expected from the SN2 reaction of 1-bromobutane with NaI?

1-iodobutane.

Why does the configuration inversion occur in SN2 reactions?

Because the nucleophile attacks the substrate from the opposite side of the leaving group.

What configuration do the products of SN1 reactions have?

Racemic, mixed configurations.

Which substance is a stronger base, acetate or (CH3)3N?

(CH3)3N is a stronger base and, therefore, a better nucleophile.

What is the significance of the empty 2p orbital in SN1 reactions?

It allows for the formation of a carbocation intermediate.

What happens to optical activity when a racemic mixture is formed?

The specific rotation is zero.

What is the effect of methylating agents like SAM on nucleophilic substrates?

They facilitate the transfer of a methyl group.

What is required for a reaction to be classified as SN2?

It must involve a nucleophile and a leaving group with a simultaneous reaction.

How does steric hindrance affect the nucleophilic substitution mechanism?

It impedes the approach of the nucleophile, favoring SN1 over SN2.

What determines if a nucleophile is strong or weak?

The presence of a negative charge typically indicates a stronger nucleophile.

What would happen if a chiral 3o alkyl halide reacts through SN2?

An inversion of configuration occurs.

Which enantiomer is associated with (R)-3-chloro-2,3-dimethylpentane?

The reaction produces a racemic mixture.

What is the formula for S-adenosylmethionine?

SAM is C₁₄H₁₈N₆O₄S.

How are toxic methyl halides typically referenced in the context of nucleophile reactivity?

They are considered to react in an uncontrolled fashion.

Explain the significance of pKa values in organic chemistry.

pKa values indicate the strength of an acid; lower pKa = stronger acid.

What happens in an SN2 reaction with a strong nucleophile like cyanide?

It results in a stable product with inversion at the chiral center.

How can the structures of SAM and SAH be represented chemically?

They can be noted without memorization but understanding the mechanism is crucial.

What type of organic compounds typically undergo SN2 reactions fastest?

Primary and methyl halides.

What is one limitation of SN1 reactions?

They may lead to racemic mixtures due to planar carbocation.

In biological contexts, how are SN2 reactions utilized?

In the methylation processes that occur in living systems.

What distinguishes SN2 from SN1 in terms of steps involved?

SN2 is a one-step mechanism; SN1 is a multi-step process.

When are hybridization types important in nucleophilic reactions?

They determine the selectivity and reactivity of substrates.