Sn1 or Sn2 Reactions: A Guide to Deciding Which Reaction is Occurring

The following is a discussion of the approach you should use in order to determine if a chemical reaction occurs via a Sn1 or Sn2 mechanism. This approach involves systematically analyzing all aspects of the reaction, then coming up with a decision based upon what you know. You should analyze the following aspects of each reaction, in the order introduced below. STEP 1: THE STRUCTURE OF THE SU STRATE Re!e!"er the structure of the substrate is a very important consideration in determining if a reaction occurs by an Sn1 or Sn2 mechanism. !hat is the structure of the substrate" Deter!ine this# #emember the trend of substrate reactivity for Sn1 $ Sn2 o Sn1: %& ' 2& ' 1& ' methyl o Sn2: methyl ' 1& ' 2& ' %& (f your substrate is tertiary )%& * Sn1 high$% &a'ored# (t won+t go by Sn2. (f your substrate is secondary )2& * ,ot the best substrate for Sn1, but it still is ok. ,ot the best for Sn2 also, but it could still go by this mechanism. (n other )ords* it cou$d go either )a%* so %ou !ust $oo+ at other &actors "e&ore !a+ing %our decision# (f your substrate is primary )1& * Sn2 &a'ored# (t won+t go by Sn1. (f your substrate is methyl Sn2 high$% &a'ored# (t won+t go by Sn1.

STEP 2: THE ,ATURE OF THE ,UC-EOPH(-E (s the nucleophile strong or weak" )alternate good or bad*. Sn2 reactions &a'or strong nuc$eo.hi$es# Sn1 reactions &a'or )ea+ nuc$eo.hi$es# What !a+es a nuc$eo.hi$e strong/ o ,egative charge - negatively charged species is a better nucleophile than a similar, uncharged species. (n particular, a base is a stronger nucleophile than its con.ugate acid. o /lectronegativity ,ucleophilicity decreases from right to left on the periodic table, following the increase in electronegativity. o Size and 0olarizability ,ucleophilicity increases down a group on the periodic table, following the increase in size and polarizability. What !a+es a nuc$eo.hi$e )ea+/ o ,eutral charge Re!e!"er sterics0 1ulky nucleophiles slow down reaction rates

STEP 1: ,ATURE OF THE -EA2(,G GROUP Sn1 and Sn2 reactions favor good leaving groups. Therefore, this aspect really not a ma.or factor in deciding if a reaction follows a Sn1 or Sn2 mechanism. HOWE2ER: the nature o& the $ea'ing grou. .$a%s an i!.ortant ro$e in deter!ining i& a reaction )i$$ undergo a su"stitution reaction at a$$0 What is a good $ea'ing grou./ o /lectron withdrawing, to polarize the carbon atom on the substrate o stable )not a strong base* once it has left o polarizable )able to stabilize the transition state* !eak bases that are common, good leaving groups o 2l 3 , 1r 3, ( 4 o Sulfonate, sulfate, phosphate )see your notes* o neutral molecules 526 -lcohols )#365* -mines )#%,* 0hosphines )#%0* THE FO--OW(,G ARE ,E2ER -EA2(,G GROUPS: o 5ydro7ide )653* o -lko7ide )#63*, like 25%25263 o -mide ),523*

STEP 3: THE ,ATURE OF THE SO-2E,T Solvent does play a role in determining whether a reaction goes by a Sn1 or Sn2 mechanism. Ho)e'er* it is t%.ica$$% not a !a4or ro$e5"ut it can 6ti. the sca$es7 in the &a'or o& one !echanis! de.ending on the nature o& the nuc$eo.hi$e and the su"strate# Po$ar .rotic so$'ents: o o o o 5ave acidic hydrogens 8ery strong solvating power 2er% good &or Sn1 reactions# E8a!.$es: )ater* a$coho$s

Po$ar a.rotic so$'ents: o o o o Do not ha'e acidic h%drogens 9ood solvating power, but not as strong as polar protic solvents. 2er% good &or Sn2 reactions# E8a!.$es: acetone* acetonitri$e* di!eth%$&or!a!ide* cro)n ethers

A.rotic so$'ents: o ,on3polar solvents. o ,ot good for either Sn1 or Sn2. o 0roblem nucleophiles not typically soluble in these solvents. Therefore, they are not really useful for substitution reactions.

STEP 9: PUTT(,G (T A-- TOGETHER 2onsider all your analyses. #emember, nature of nucleophile and structure of substrate are most important. ,ature of leaving group less important, since good leaving groups are important for both mechanisms. Solvent not a ma.or factor, but its identity )polar protic, polar aprotic, etc* can be a deciding factor in your decision.

WOR:ED E;A<P-ES:

a*

CH1 CH1CH2C H C$ = CH1OH CH1OH

Ana$%sis: 1* Substrate secondary. 2an go either Sn1 or Sn2 2* ,ucleophile !eak nucleophile )it+s neutral*. %* Solvent polar protic. 9ood for Sn1. :* ;eaving group 2l, which is a good leaving group. Decision: #emember that substrate structure and the nucleophile play ma.or roles in this decision. The substrate is secondary, which can go either Sn1 or Sn2. Therefore, you must consider other factors. The nucleophile is weak, which is good for Sn1. The solvent is polar protic, which is also good for Sn1. The leaving group is good, which doesn+t really matter here, but it does indicate that a substitution reaction )whichever mechanism* will occur.

Ans)er: Sn1 !echanis!#

b*

CH1CH2CH2CH

,H2

,aOH

acetone

< Ana$%sis: 1* Substrate primary. 9ood for Sn2. 2* ,ucleophile 653 , Strong nucleophile, good for Sn2. %* Solvent polar aprotic. 9ood for Sn2. :* ;eaving group ,523 , )hich is an e8tre!e$% "ad $ea'ing grou.# Decision: /verything points to a Sn2 mechanism until the leaving group is considered. (n this case, the leaving group is very poor. Therefore, it is doubtful if this reaction will even work at all. Ans)er: ,o reaction#

c*

CH1CH2CH2CH2CH2 (

,aOCH1

CH1C,

Ana$%sis: 1* Substrate primary. 9ood for Sn2. 2* ,ucleophile 625%3 , Strong nucleophile, good for Sn2. %* Solvent polar aprotic. 9ood for Sn2. :* ;eaving group (3, a very good leaving group. Decision: 2lassic e7ample of an Sn2 reaction. /verything points to it. Ans)er: Sn2 reaction#

d* = r ,a( CH1OH

Ana$%sis: 1* Substrate primary. 9ood for Sn2 2* ,ucleophile (3, Strong nucleophile, good for Sn2. %* Solvent polar protic. 9ood for Sn1, not the best for Sn2. :* ;eaving group 1r 3, a very good leaving group. Decision: The data suggests Sn2, e7cept for the solvent. =ethanol is a polar protic solvent, which is good for a Sn1 reaction. 5owever, given the nature of the substrate and nucleophile )both good for Sn2*, the solvent won+t be that important. Ans)er: Sn2 reaction#