Chapter 9 Flashcards
nucleophilic substitution refers to any reaction in which an electron rich … replaces a …
nucleophile; leaving group
the leaving group can be a …. or another … group that can form a … or another stable species
halide; electronegative group; stable anion
if the nucleophile is negatively charged (e.g. OH-), in a substitution rxn, the atom donating the pair of electrons (i.e. Nu) becomes … in the product
neutral
if the nucleophile is uncharged (e.g. NH3) in the sub rxn, the atom donating the pair of e- becomes … in the initial product
positively charged
a fundamental difference between SN2 and SN1 rxns is the timing of … between and the leaving group and of … between C and the nucleophile
bond breaking; bond forming
for SN2, bond breaking and bond forming occur … Thus departure of the leaving group is … by the incoming nucleophile
simultaneously; assisted
S in SN2 stands for …, n for … and 2 for a …
substitution; nucleophilic; biomolecular rxn
SN2 is bimolecular because the haloalkane and nucelophile are involved int he
rate-determining step
mech for SN2 rxn: make a new bond between a nu and an electrophile and simultaneously break a bond to give stable molecules/ions: the nucleophile attacks the reactive center from the side … the leaving group; that is, an SN2 rxn involves … attack of the nu.
opposite; backside
backside attack by the nu is facilitated through the … of the C-Lv bond, by which the C has a … charge and therefore attracks the electron rich nu. Secondly, the electron density of the nucleophile entering from the backside assists in …, thereby helping the Lv to leave
polarization; partially positive; breaking the C-Lv bond
the electron density of the nu attacking from the backside can be thought of as populating the … of the C-Lv bond, weakening that bond as the new C-Nu sigma bond becomes … Therefore, upon collision with a nu, the most effective way to fill this orbital is by collision from the … of the C, which … the C-Lv bond on the other side of the C
antibonding molecular orbital; stronger; backside; breaks
for an Sn1 rxn, bond breaking between the C and Lv is entirely … before bond forming with the nucleophile begins
completed
in the designation Sn1, 1 stands for a … rxn. This is because only the … is invovled in the rate-determining rate
unimolecular; haloalkane
For SN1, the nucleophile is also the …, hence the name …
solvent; solvolysis
mech for SN1:
- break a bond to give stable molecules/ions: ionization of the C-Lv bond forms a … intermediate. because no nu is assisting the departure of the halide anion, this is the relatively …, … step of the rxn
- make a new bond between a nucleophile and an electrophile: rxn of the carbocation with the nucleophile occurs, and can yield a positively charged species. attack of the nu occurs with approximately equal probability from either … of the planar carbocat. intermediate
- take a … away to make the species neutral
carbocation; slow; rate-determining; face; proton
in an sn1 rxn, the rate-determining step is the cleavage of the … to form a carbocation intermediate
C-Lv bond
when one of these collisions between the solvent molecules and the haloalkane is of high enough E to distort the haloalkane into a geometry in which the bond to the leaving group is almost …, the transition state for departure of the leaving group can be achieved and the Sn1 mech is enabled
completely broken
an Sn2 rxn involves a … step and therefore has no …
single; intermediates
an Sn1 rxn has … steps (or … steps when a … as the last step), each with a … Importantly, an intermediate carbocat is formed
two; three; proton is removed; transition state
those rxns whose rate is dependent only on the concentration of haloalkane are classified as …; those rxns whose rate is dependent on the concentration of both haloalkane and nucleophile are classified as …
Sn1; Sn2
because the transition state for formation of the carbocation intermediate in an SN1 mechanisms invovles only the haloalkane and not the nucleophile and this step isr ate-determining, it is a … process. the result is a … rxn. In this instance, the rate of rxn is expressed as the rate of … of the starting material. the rate has no dependence on the concentration of the
unimolecular; first-order; disappearance; nucleophile
we can conclude that any substitution rxn whose rate depends only upon [R-Lv] proceeds via an
Sn1 mechanism
For Sn2, both species must collide and are present in the transition state; that is, the rxn is … and is …
biomolecular; second order
when the rate of a substitution rxn depends on both [R-Lv] and [Nu-], we conclude that an … mechanism is occurring
Sn2
although examples of complete racemization for Sn1 have been observed, it is common to find only …, with the predominant product being the one with … of configuration at the chriral center. Although bond breaking between C and the Lv is complete, the Lv remains associated for a short time with the carbocation in an ion pair
partial racemization; inversion
to the extent hat the laving group remains associated with the carbocation as an ion pair, it … approach of the nucleophile from that side of the carbocation. The result is that somewhat moe than 50% of the product is formed by attack of the nucleophile from the side of the carbocation … that of the leaving group. whenever we observe partial to complete racemization of stereochemistry, we conclude that an … mechanism is operative
hinders; opposite; Sn1
every sn2 rxn proceeds with … attack by the nucleophile and therefore .. of configuration
backside; inversion
whenever complete inversion of configuration is found in a substitution rxn, we conclude that an … mechanism is occurring
Sn2
the rates of sn1 rxns are governed mainly by … factors, namely the relative .. of … intermediates. the rates of sn2 rxns, on the other hand, are governed mainly by … factors, and their transition states are particularly sensitive to … at the site of rxn. The ability of groups, because of their size, to hinder access to a rxn site within a molecule is called …
electronic; stabilities; carbocation; steric; bulky groups; steric hindrance
allylic carbocations are considerably more stable than comparably substituted … because … is associated with the .. interaction between the positively charged carbon and the adjacent pi bond
alkyl carbocations; delocalization; resonance interaction
benzylic carbocations show approximately the same stability as … carbocations. both are stabilized by … of the positive charge due to adjacent pi bonds. benzylic carbocations can be written as …
allylic; resonance delocalization; C6H5-CH2+
Sn1 rxns rarely occur with … C and never on … carbons. The carbocations derived from these C bonds are too … to form
sp2; sp; unstable
tertiary haloalkanes react by an … mechanism because tertiary carbocations are relatively … and tertiary haloalkanes are protected against … In fact, tertiary haloalkanes are never observed to react by an … mechanism
Sn1; stable; backside attack; Sn2
Halomethanes and primary haloalkanes are never observed to react by an … mechanism. they have little crowding around the reaction site and react by an … mechanism because methyl and primary carbocations are …
SN1; SN2; unstable
secondary haloalkanes may react by either … or … mechanisms, depending on the … and …
Sn1; Sn2; nucleophile; solvent
the carbon bearing the halogen in a haloalkane is called the ..-C and the next C is called the …-C
alpha; beta
For all practical purposes, primary halides with … do not undergo Sn2 reactions. these screen the corresponding carbon, hindering nucleophilic approach
beta branches
SN2 rxns never occur on … or … hybridized C. Hence, you should never consider performing a substation on a … halide, an … halide, or an … halide
sp2; sp; vinyl; aryl (benzylic); alkynyl
in the transition state for nucleophilic substitution on a haloalkane, the leaving group develops a … in both sn1 and sn2 rxns; therefore, the ability of a group to function as a leaving group is related to how … it is as an … The most stable anions, and therefore the .. leaving groups are the … of …
partial negative charge; stable; anion; best; weak conjugate bases; strong acids
the best leaving groups in the series in the txtbk are .., .., and …
…, … ion (…), and … ion (…) are such poor leaving groups that they rarely, if ever, are displaced in nucleophilic aliphatic substitution
I-; Br-; Cl-; OH-; methoxide (CH3O-); amide (NH2-)
the common protic solvents for nucleophilic substitution rxns are …., low molecular weight …, and low molecular weight …
water; alcohols; carboxylic acids
protic solvents solvate ionic substances by …
hydrogen bonding
common protic solvents: .. ... acid (...) ... (...) ... (...) ... acid (...)
water; formic; HCOOH; methanol; CH3OH; ethanol; CH3Ch2OH; acetic; CH3COOH
polar aprotic solvents:
… (… abbrev. not structure), … (…), … (…abbrev.) , …
dimethyl sulfoxide; DMSO; acetonitrile; CH3C=_N (triple bond); N,N-dimethylformamide; DMF; acetone
aprotic solvent: a solvent that cannot serve as a
hydrogen bond donor
the rate of Sn1 rxns depends on both the ability of the solvent to keep opposite charges … and its ability to … both … and … sites by solvation.
separated; stabilize; positive; negative
the solvents that best solvate charges are … such as .water; … such as methanol and ethanol; and, to a lesser degree, … such as formic acid and acetic acid
polar protic solvents; low-molecular-weight alcohols; low-molecular-weight carboxylic acids
the stronger the solvation of the nucleophile, the … the energy required to remove the nucleophile from its solation shell to reach the trasnition state and hence the .. the rate of the Sn2 rxn
greater; lower
polar aprotic solvents can solvate … very well, but they solvate … relatively poorly, bc they cannot donate a H bond to an .., as can a protic solvent. For this reason, nucleophiles are … and more … in polar aprotic solvents than in protic solvents; so the rates of SN2 rxns are dramatically …
cations; anions; anion; freer; reactive; accelerated
you should realize that the SN2 mechanism is viable in all solvents that … the … and … Only … solvents are viable for SN1
dissolve; nucleophile; electrophile; polar protic
nucleophilicity is a … property measured by relative ..
kinetic; rates of rxn
the more rapidly a nucleophile reacts with a substrate in an SN2 rxn, the more … it is
nucleophilic
good nucleophiles include: ..., ... ..., ... ..., ..., ..., ..., ..., ..., ... (ones at top are best)
Br-; I-
CH3S-; RS-;
HO-; CH3O-; RO-; R-C=_C- (triple bond)
CN-; N3-; H2N-
moderate nucleophiles include (ones at top are best): ..., ... ..., ... ..., ..., .. .., ..., ..., ...
Cl-; F-;
CH3COO-, RCOO- (have carbonyl groups)
CH3SH; RSH; R2S
NH3; RNH2; R2NH; R3N
poor nucleophiles include (ones at top are best):
..
…, …
…, ….
H2O;
CH3OH; ROH
CH3COOH, RCOOH (carboxylic acids)
basicity and nucleophilicity are often related because they both involve a … making a bond to another atom
lone pair of electrons
in general, … bases are good nucleophiles
sterically unhindered strong bases
… anions (…) are classified as moderate nucleophiles
carboxylate; RCO2-
neutral oxygen species are … nucleophils
weak
nucelophiles that have conjugate acids with pKas above 11 are …, around 11 are .., and below 11 are …
strong; moderate; weak
all other factors being equal, the stronger the interaction of the nucleophile with the solvent, the … its nucleophilicity
solvent
because anions are only … solvated in polar aprotic solvents, they are freer and participate … in nucleophilic substitution rxns. In these solvents, their relative nucleophilicities … their relative basicitiies. The relative nucleophilicities in polar aprotic solvents for halides is …
poorly; readily; parallel; F->Cl->Br->I-
in polar protic solvents, iodide ion, the least basic of the halide ions, has the … nucleophlicity
greatest
in polar aprotic solvents, anions are only … solvated and therefore relatively free to participate in nucleophliic sub rxns and … dictates nucleophilicity
weakly; basicity
in polar protic solvents, anions are … solvated by … with solvent molecules and are therefore less free to participate in nucleophilic sub rxns and … dictates nucleophilicity
highly; H-bonding; polarizability
because there is little or no carbocation character at the substitution center, SN2 rxns are free of … In contrast, SN1 rxns often proceed with …
rearrangement; rearrangement
for methyl halides:
… is favored, … does not occur bc the cation is so … that it is never observed in solution
Sn2; Sn1; unstable
for primary halides:
… is favored, … rarely occurs bc the cation is so unstable that it’s not formed in solution (… and … are the exceptions)
SN2; SN1; allylic; benzylic
secondary halides:
… is favored in aprotic solvents with good nucleophiles
… is favored in protic solvents with poor nucleophiles
SN2; SN1
tertiary halides:
… does not occur becasue of … around the rxn center
… is favored bc of the ease of formation of tertiary carbocats
SN2; steric hindrance; Sn1
substitution at a chiral center for SN2 results in … of config, whereas for SN1 .. is favored bc the carbocat intermediate is … and attack of the nu occurs with more or less equal probability from either side
inversion; racemization; planar
… is the competing process to substituion
beta elimination
beta elimination is the combination of take a … away and … to give stable molecules/ions
proton; break a bond
… promote B-elim rxns
strong bases
examples of strong bases: …, …, …, and … anions
OH-; OR-; NH2-; acetylide
the solvent used for B-elim rxns is commonly the … of the base used
conjugate acid
when the more substitued alkene is the dominant product for elim, the reaction is said to follow …, or to undergo …
Zaitsev’s rule; Zaitsev elim
E1: breaking of the C-Lv bond to give a carbocation is … before any rx occurs with the base to lose a H and form the double bond
complete
for E1, e tands for … and 1 stands for …
elim; unimolecular
E1 mechanism:
- break a bond to give stable molecules/ions: rate-determining … of the C-Lv bond gives a …
- take a proton away: proton transfer from the … to … gives the alkene
ionization; carbocat intermediate; carbocat; solvent
in an E1 mech., one transition state exists for the … and a second for the …
formation of the C+; loss of H
E1 competes with …, but they mostly occur together
SN1
For Sn2: proton transfer to the base, formation of the C=C, and ejection of the X ion occur ..; all bond-breaking and bond-formings teps are …
simultaneously ;concerted
the transition state for SN2 has considerable
double bond character
E2 mech: take a proton away and simultaneously break a bond to give stable molecules/ions–bond breaking and bond forming are …;
E stands for …
2 stands for …: both the … and the … are involved in the transition state for rate-determining step
concerted; elimination; bimolecular; haloalkane; base
one simplifying aspect of the competition between sub and elim is to consider an E2 pathway only when …, …, …, and … anions are used
hydroxide; alkoxides (RO-); acetylides; amide ions
the rate determining step in an E1 is … to form a …
thus the rxn is unimolecular and follows … kinetics
ionization of the leaving group; carbocation; first–order
only one step occurs in an E2 mechanism, and the transition state is bimolecular. the rxn is …: … in haloalkane and … in base
second order; first order; first order
the major product in E1 rxns is the …
… is possible
more stable alkene; rearrangement
For E2 rxns the major regioisomeric product tends to be formed following …
… double bonds predominate over … double bonds when either is possible
with larger, sterically hindered bases, the major product is often the … bc rxn occurs primarily at the most accessible H
Zaitsev’s rule; trans; cis; less substituted alkene
the lowest-energy transition state of an E2 rxn is commonly the one in which the … and … are oriented .. and … to each other. It allows for proper orbital overlap between the base, the proton being removed, and the leaving group
H; Lv; anti; coplanar
the required anti and coplanar transition state geo can also be used to predict the regiochem of E2 elim in halocyclohexanes. In these molecules, anti and coplanar correspond to … and …
trans; diaxial
primary halides for elim:
… not observed. carbocat unstable
… is favored, but usually requires … base
E1; E2; sterically hindered strong base
secondary halides for elim:
… is the main rxn with weak bases
… is the main rxn with strong bases
E1; E2
tertiary halides for elim:
… main rxn with weak bases
… rxn with strong bases
E1; E2
For E2 a … and … arrangement is still possible
syn; coplanar
it is difficult to predict the ratio of substition to elimination for first order rxns. the majority of the time, tho, … predominates when weak bases are used
SN1
For Sn2 vs E2, the guiding principles are:
- branching at the alpha or beta carbons increases … and retards … rxns, but increases the rate of … bc of the increased stability of the … product
- the greater the … of the attacking reagent, the greater the SN2/E2 ratio. the greater the … of the reagent,t he greater the E2/SN2 ratio
steric hindrance; SN2; E2; alkene; nucleophilicity; basicity
if a nucleo/base has a conjugate acid with a pka …. and is a … nu, then an SN2 will dominate. If the pka is …, the .. character will usually outcompete the other and an … will dominate
below 11; good; above 11; basic
in general, higher temps result in increasing extents of … at the expense of …
elimination; substitution
whent he alkyl group is methyl the only possible outcome is an …, SN1 doesnt happen cuz C+ is too unstable, and there’s only one C so elim can’t happen either
SN2 rxn
for methyl halides only … occurs
for primary, SN2 occurs with …./…, E2 occurs with …, … , SN1/E1 … occurs
SN2; good nu; weak bases; strong, bulky; rarely
for secondary, SN2 occurs with bases/nu where pka of conj acid is … or less, E2 occurs when pka of conjugate acid is … or greater, SN1/E1 is common in rxns with … in … solvents
11; 11; weak nu; polar protic
for tertiary:
e2 occurs with ..
sn1/e1 occurs with …/… if the solvent is ..
SN2 … occurs
strong bases; poor nu; weak bases; never
if the nuc/base is a strong base and sterically hindered, it will … nucleophile and … is the major pathway
not be a good; E1
withany of the basic or weakly basic good/moderate nu, products predominantly form from … pathways
Sn2
primary: if the nuc/base is neither good/moderate nu, we are likely to get SN2/E2 in ratio that is difficult to predict/no rx. examples are…, …, and … acids
water; alcohols; carboxylic
secondary: if nuc/base is strong, … will dominate, despite whether it is hindered or not
with a weak base that is good/moderate nu, … will dominate
when nuc isn’t good, if the solvent is …, we can induce Sn1/E1
if the solvent is neither polar nor protic and the nuc/base is neither strong/good, … are possible
E2; SN2; polar protic; all four pathways
tertiary: if nuc/base is strong, … will dominate
if the solvent is polar and protic, we can induce … and … often by applying heat
if nuc/base isn’t good, and solvent isn’t plar and protic … are possible
E2; SN1, E1; E1, SN1, and E2
when there is an internal nu, it participates in the .. to give an intermediate, which then reacts with an … to complete the rxn. thus, although this rxn has kinetic charcteristics of an .., it actually involves two succesisve … displacement rxns;
departure of the Lv; external nu; Sn1; SN2
