Ch. 9 - Week 2 (Quiz 2) Flashcards
Why do 1,2 shifts occur?
to make a more stable carbocation
What is a 1,2-methyl shift?
when a 2º carbon becomes a 3º carbon by movement of a methyl group from adjacent carbon to carbocation
When might a 1,2 shift occur from 2º to 2º or 3º to 3º?
if the carbocation will be resonance stabilized
What should you do if a carbocation can undergo both 1,2-hydride and 1,2-methyl shift?
do both and show all possible products
What are SM and products of halodehydration-alkyl halid synth?
SM = alcohol Prod = alkyl halide
What are reagents of halodehydration alkyl halide synthesis?
HX (X = Cl, Br, I)
If HCl is used for Sn2 and primary alcohol (chlorodehydration), what also must be used?
ZnCl2
What type of mechanism is halodehydration alkyl halid synthesis?
Sn1 for 2º, 3º and 1º allylic/benzylic
Sn2 for 1º alcohol
What are the two major steps of of halodehydration alkyl halide synthesis?
protonation of OH to make good leaving group, substitution of X
Can RAR occur for halodehydration alkyl halide synth?
Yes, for 2º, 3º and allylic/benzylic 1º
What is the solvent for halodehydration alkyl halide synthesis?
HX is considered to be solvent
What are SM and P of POCl3 mediated alcohol dehydration (alkene synthesis)?
SM = alcohol P = alkene
What are reagents of POCl3 mediated alcohol dehydration (alkene synthesis)?
POCl3 and pyridine
What type of mechanism is POCl3 mediated alcohol dehydration (alkene synthesis)?
always E2 no matter alcohol substitution
What are major steps of POCl3 mediated alcohol dehydration (alkene synthesis)?
alcohol binds to POCl3 which makes it lose a Cl
pyridine takes proton off to make good leaving group
pyridine take beta H via E2 to make alkene
Can RAR occur for POCl3 mediated alcohol dehydration (alkene synthesis)?
No, E2 so no carbocation
What is an important stereochemical consideration for POCl3 mediated alcohol dehydration (alkene synthesis)?
alpha C and beta H must be antiperiplanar!
What is solvent for POCl3 mediated alcohol dehydration (alkene synthesis)?
pyridine
What are SM and P of of chlorodehydration with SOCl2 (alkyl chloride synthesis)?
SM = 1º or 2º alcohol P = alkyl chloride
What are reagents for chlorodehydration with SOCl2 (alkyl chloride synthesis)?
SOCl2 (thionyl chloride)
pyridine or other 3º amine
What type of mechanism is chlorodehydration with SOCl2 (alkyl chloride synthesis)?
Sn2 only so NR for 3º
What are major steps of chlorodehydration with SOCl2 (alkyl chloride synthesis)?
alcohol reacts with POCl2
pyridine proton sponge takes proton off O
Cl- attacks alpha carbon in Sn2 rxn
Can RAR occur fpr chlorodehydration with SOCl2 (alkyl chloride synthesis)?
No, Sn2 so no carbocation
What stereochemical considerations are there for chlorodehydration with SOCl2 (alkyl chloride synthesis)
Sn2 so inversion at alpha carbon if being attacked
What is solvent for chlorodehydration with SOCl2 (alkyl chloride synthesis)?
amine base (polar / aprotic)
What are SM and P of bromodehydration with PBr3 (alkyl bromide synthesis)?
SM = 1º or 2º alcohol only P = alkyl bromide
What are reagents of for bromodehydration with PBr3 (alkyl bromide synthesis)?
PBr3 and pyridine (or Br-)
What type of mechanism is bromodehydration with PBr3 (alkyl bromide synthesis)?
Sn2 only! so NR for 3º alcohols
What are major steps of bromodehydration with PBr3 (alkyl bromide synthesis)?
O grabs P which makes carbon electrophilic and converts OH to good LG
Pyridine proton sponge removes H, now activated alcohol
Sn2 only! to make alkyl bromide
Can RAR occur for bromodehydration with PBr3 (alkyl bromide synthesis)?
No, Sn2 so no carbocations form
What stereochemical considerations are there for bromodehydration with PBr3 (alkyl bromide synthesis)?
Sn2 rules so inversion at alpha carbon if st. center
What is solvent for bromodehydration with PBr3 (alkyl bromide synthesis)?
amine base
What is tosylate?
derivative of alcohol that is THE BEST LG!!
How are alcohols converted to tosylates?
Tosylation with TsCl
Why is tosylate a good LG?
because its conjugate acid is tosic acid which is strong (pKa = -7)
Why are alkyl tosylates called the “middle man”?
they are rarely the final product of synthesis, usually they are a synthetic intermediate
Is alpha carbon electrophilic when bonded to OH?
No, only when OH becomes good LG
What are SM and P for tosylation with TsCl?
SM = alcohol (any sub, Csp3 not required) P = alkyl tosylate
What are reagents of tosylation with TsCl?
TsCl and pyridine
What type of mechanism is tosylation with TsCl?
oxygen binds to Ts and kicks off Cl… not Sn2 (but can go under Sn2 after it becomes alkyl tosylate)
What are major steps of tosylation with TsCl?
oxygen of hydroxyl group graphs S of Ts and kicks off Cl
pyridine proton sponge grabs proton which gives e- to oxygen to become alkyl tosylate
Can RAR occur or tosylation with TsCl?
No, not a chance for carbocations
What are the stereochemical considerations for tosylation with TsCl?
NO inversion at alpha carbon because reaction takes place at hydroxyl carbon
inversion only occurs if alkyl tosylate undergoes Sn2 afterwards
What is solvent for tosylation with TsCl?
polar aprotic
Do epoxides have a good LG? Why are they reactive?
No good LG but they are highly strained with 2 polar bonds so they are pretty reactive (ring-opening is favored)
What are five nucs that can open an epoxide ring?
-OH, -OR, -CN, -SR, NH3
What is SM and P of nucleophilic epoxide opening?
SM = epoxide P = alcohol
What are reagents of nucleophilic epoxide opening?
strong anionic nucleophile and H2O
Why is nucleophilic epoxide opening considered to be a regioselective reaction?
nuc only attacks at less sterically hindered carbon
What type of mechanism is nucleophilic epoxide opening?
Sn2
What are major steps of nucleophilic epoxide opening?
strong anionic nuc attacks less sub’d carbon on epoxie via Sn2 (makes alkoxide)
water protonates oxygen in water quenching to neutralize negative charge and create an alcohol
Can RAR occur for nucleophilic epoxide opening?
No, Sn2
What are stereochemical considerations for nucleophilic epoxide opening?
Sn2 so inversion at attacked carbon (but doesn’t mean dashes and wedges just switch)
if it is a symmetrical epoxide, it will still be Sn2 but both carbons are attacked equally so a racemic mixture will form
What is solvent for nucleophilic epoxide opening?
polar aprotic
What are SM and P of acid-catalyzed epoxide opening?
SM = epoxide P = alcohol
What are reagents of acid-catalyzed epoxide opening?
HX and Nu-H
or
strong acid (TsOH and H2So4) and neutral nuc
What is mechanism of acid-catalyzed epoxide opening?
Sn2-like
What are major steps of acid-catalyzed epoxide opening?
epoxide oxygen binds to hydrogen of acid
nuc attacks more sub’d carbon which opens ring
(if strong acid, it will be deprotonated by the neutral nuc as well)
Can RAR occur for acid-catalyzed epoxide opening? ?
No
What are stereochemical considerations for acid-catalyzed epoxide opening?
inversion at alpha carbon
What is solvent for acid-catalyzed epoxide opening? ?
acid or nuc
What type of nuc should NOT be used with strong acid for acid-catalyzed epoxide opening?
anionic nuc (will undergo acid-base chemistry)
