Alkyl Halides and Nucleophilic Substitution

Telfairine, a naturally occurring insecticide, and halomon, an antitumor agent, are two polyhalogenated compounds isolated from red algae. (a) Classify each halide bonded to an sp3 hybridized carbon as 1°, 2°, or 3°. (b) Label each halide as vinyl, allylic, or neither.

Question: Telfairine, a naturally occurring insecticide, and halomon, an antitumor agent, are two polyhalogenated compounds isolated from red algae. (a) Classify each halide bonded to an hybridized carbon as  or  (b) Label each halide as vinyl, allylic, or neither

Give the IUPAC name for each compound

a)

b)

c)

d)

Question: Give the structure corresponding to each name. 

 a. 3-chloro-2-methylhexane                    

b. 4-ethyl-5-iodo-2,2-dimethyloctane    

c. cis-1,3-dichlorocyclopentane            

d. 1,1,3-tribromocyclohexane

e. sec-butyl bromide

f. 6-ethyl-3-iodo-3,5-dimethylnonane

Question: An sp³  hybridized C-Cl bond is more polar than a sp²  hybridized C-Cl bond. (a) Explain why this phenomenon arises. (b) Rank the following compounds in order of increasing boiling point.

Question: Chondrocole A is a marine natural product isolated from red seaweed that grows in regions of heavy surf in the Pacific Ocean. (a) Predict the solubility of chondrocole A in water and . (b) Locate the stereogenic centers and label each as R or S. (c) Draw a stereoisomer and a constitutional isomer of chondrocole A.

Question: Identify the nucleophile and leaving group and draw the products of each substitution reaction.

a.

b.

c.

d.

Question: CPC (cetylpyridinium chloride), an antiseptic found in throat lozenges and mouthwash, is synthesized by the following reaction. Draw the structure of CPC.

Question: Draw the product of nucleophilic substitution with each neutral nucleophile. When the initial substitution product can lose a proton to form a neutral product, draw the product after proton transfer.

a.

b.

Question: What neutral nucleophile is needed to convert dihalide A to ticlopidine, an antiplatelet drug used to reduce the risk of strokes?

Question: Which is the better leaving group in each pair?   

a.${\mathrm{Cl}}^{-},{\mathrm{I}}^{-}$ 

b.  ${\mathrm{NH}}_3,{\mathrm{NH}}_2$

c.  ${\mathrm{H}}_2\mathrm{O},{\mathrm{H}}_2\mathrm{S}$

Question: Which molecules contain good leaving groups?

a.

b.

c.

d.

                 CH_3$-$CH₃

Question: Does the equilibrium favor the reactants or products in each substitution reaction?

a.

b.

Question: Identify the stronger nucleophile in each pair

a.NH₃ NH₂ ${\mathrm{NH}}_3,{\mathrm{NH}}_2$

b.CH₃ NH₂ ,CH₃ OH ${\mathrm{CH}}_3 {\mathrm{NH}}_2,{\mathrm{CH}}_3\mathrm{OH}$

c.CH₃CO₂^- ,CH₃CH₂O^- ${\mathrm{CH}}_3{{\mathrm{CO}}_2}^{-},{\mathrm{CH}}_3{\mathrm{CH}}_2{\mathrm{O}}^{-}$

Question: Classify each solvent as protic or aprotic

a.

b.

c.

Question: Identify the stronger nucleophile in each pair of anions.

a. Br^- or Cl^-   in a polar protic solvent. 

b. OH^-or Cl^-  in a polar aprotic solvent.

c. HS^- or F^- in a polar protic solvent.

Question: Rank the nucleophiles in each group in order of increasing nucleophilicity.

a. OH^-,NH₂^- , H₂O 

b. OH^- ,Br^- , F^- (polar aprotic solvent)   

c. H₂O, OH^-,CH₃CO₂^-

Question: What nucleophile is needed to convert to each product?

a.

b.

c.

d.

Question: What happens to the rate of an S_N2  reaction under each of the following conditions?

a. [RX] is tripled, and $\left[:{\mathrm{Nu}}^{-}\right]$  stays the same.

b. Both [RX] and   $\left[:{\mathrm{Nu}}^{-}\right]$ are tripled.  

c. [RX] is halved, and $\left[:{\mathrm{Nu}}^{-}\right]$ stays the same.

d. [RX] is halved, and   $\left[:{\mathrm{Nu}}^{-}\right]$is doubled.

Question: Draw an energy diagram for the following S_N2 reaction. Label the axes, the starting materials, and the product. Draw the structure of the transition state.

Question: Draw the product of each S_N2  reaction and indicate stereochemistry.

a.

b.

Question: Which compound in each pair undergoes a faster S_N2 reaction?

a.

and

b.

and

Question: What neutral nucleophile is needed to convert C to D? Imatinib, an effective treatment for certain cancers, is prepared in one step from D.

Question: What happens to the rate of an S_N1  reaction under each of the following conditions?

a. [RX] is tripled, and $\left[:{\mathrm{Nu}}^{-}\right]$stays the same.

b. Both [RX] and $\left[:{\mathrm{Nu}}^{-}\right]$are tripled.  

c. [RX] is halved, and $\left[:{\mathrm{Nu}}^{-}\right]$ stays the same.

d. [RX] is halved, and$\left[:{\mathrm{Nu}}^{-}\right]$ is doubled.

Question: Draw the products of each S_N1  reaction and indicate the stereochemistry of any stereogenic centers.

a.

b.

Question: Classify each carbocation as $1°$ ,$2°$ ,$3°$ .

a.

b.

c.

d.

Question: Draw the structure of a $1°,2°,3°$, , carbocation, each having molecular formula . Rank the three carbocations in order of increasing stability.

Question: Rank the following carbocations in order of increasing stability.

Question: Which alkyl halide in each pair reacts faster in an S_N1 reaction?

a.

or

b.

 or

Question: What is the likely mechanism of nucleophilic substitution for each alkyl halide?

a.

b.

c.

d.

Question: For each alkyl halide and nucleophile:

 [1] Draw the product of nucleophilic substitution.

[2] determine the likely mechanism (or) for each reaction.

a.

b.

c.

d.

Question: Draw the products (including stereochemistry) for each reaction.

a.

b.

Question: Which compound in each pair reacts faster in nucleophilic substitution?

a.

b.

c.

d.

Question: Which solvents favor S_N1 reactions and which favor S_N2 reactions?

_a.

b.  CH₃CN

c.

d.

Question: For each reaction, use the identity of the alkyl halide and nucleophile to determine which substitution mechanism occurs. Then determine which solvent affords the faster reaction

a.

b.

c.

Question: Determine the mechanism and draw the products of each reaction. Include the stereochemistry at all stereogenic centers.

a.

b.

c.

d.

Question: Rank the following carbocations in order of increasing stability.

a. 

b.

c.

Question: Nicotine, a toxic and addictive component of tobacco, is synthesized from A using SAM. Write out the reaction that converts A into nicotine.

Question: What alkyl halide and nucleophile are needed to prepare each compound?

a.

b.

c.

d.

Question: The ether CH₃OCH₂CH₃ can be prepared by two different nucleophilic substitution reactions, one using CH₃O^- as a nucleophile and the other using CH₃CH₂O^- as a nucleophile. Draw both routes

Question: Give the IUPAC name for each compound, including any R,S designation.

a.

b.

Question: Give the IUPAC name for each compound.

a.

b.

c,

d.

e.

f.

Question: Give the structure corresponding to each name.

1. 3-bromo-4-ethylheptane
2. 1,1-dichloro-2-methylcyclohexane
3. 1-bromo-4-ethyl-3-fluorooctane
4. (S)-3-iodo-2-methylnonane
5. (1R,2R)-trans-1-bromo-2-chlorocyclohexane
6. (R)-4,4,5-trichloro-3,3-dimethyldecane

Question: Draw the eight constitutional isomers having the molecular formula C₅H₁₁Cl .

1. Give the IUPAC name for each compound (ignoring R and S designations).
2. Classify each alkyl halide as $1°,2° or 3°$.
3. Label any stereogenic centers.
4. For each constitutional isomer that contains a stereogenic center, draw all possible stereoisomers, and label each stereogenic center as R or S.

Question: Which compound in each pair has the higher boiling point?

a.

b.

Question: Draw the products formed when each alkyl halide is treated with NaCN.

a.

b.

Question: Draw the products of each nucleophilic substitution reaction.

b.

c.

d.

e.

f.

Question: Which of the following molecules contain a good leaving group?

a.

b.

c.

d.

Question: Rank the species in each group in order of increasing leaving group ability.

a. Br^-,Cl^-,I^-

b. NH₃,H₂S,H₂O

Question: Which of the following nucleophilic substitution reactions will take place?

a.

b.