Chapter 13 Organic Reactions
We will look at organic reactions in the context of:
· hydrolysis
· Acid / Base
- definition of acids and bases
- nucleophilic and electrophilic compounds
- nucleophilic substitution reactions
4. Elimination Reactions
5. acid and base catalyzed hydrolysis rates and life times in the environment
- Hammett and Taft rate constant observations
halomethanes
DDT and DDE
carboxylic acid esters
carboxylic acid amides
carbamates
Bronstead-Lowry acid - bases
acid is defined as a species that can give up a proton, [H+]
a base is a species that will accept a proton.
HNO3---> H+ + NO3-
CH3COOH ---> H+ CH3OO- conjugate bases
C6H5OH ---> H+ +C6H5O-
Lewis Acids and Bases (1923)
Acids have less than a full octet of electrons and are “electron deficient or electron poor” (electrophiles)
What the Lewis system does for us is allow species besides the hydrogen ion to display acidic behavior
page 116, Holt
Nucleophilic compounds:
From a reaction perspective nucleophilic species carry a negative charge and are usually polar in character.
They may have an electron rich bond or unbonded electron pair which is often the site of attack.
In the environment the majority of the nucleophiles that react with organics are inorganic. A measure of nucleophilicity is:
CH3-Br + H2O ---> CH3-OH + H+ + Br-
log (kx/kH2O) = n
Because of its great abundance, water plays a pivotal role among the nucleophiles in the environment
A reaction in which water (or hydroxide) substitutes for another atom or group is called hydrolysis.
The resulting organic products of hydrolysis are typically more polar than their parent compounds and generally of less environmental concern
CH3-Br + H2O ---> CH3-OH + H+ + Br-
Chlorinated organics often find their way into the environment and hence their reaction with nucleophiles is of interest
Relative Nucleophilicty of inorganic Nucleophiles
Swain and Scot (Table 13.3) observed that for different nucleophiles, x, attacking different methyl halides that
X- + CH3-Br à -X--CH3--Br -à CH3-X + Br -
log (kx/kH2O) = s x n
Where n is an indicator of the attacking ability of x, the nucleophile, and s is the sensitivity of the organic to nucleophilic attack; n is really important because it represents the ability of the nucleophile to donate electrons
As a standard for methyl bromide, s is set equal to 1; we can now ask what does the concentration of a given nucleophile have to be to compete with water; ie when is its rate similar?
log (kx/kH2O) = 1 x n; so kH2O/kx = 10-n
To be similar, the nucleophilic rate must equal the water, d(CH3BrH2O /dt) or d CH3Brx/dt = d(CH3BrH2O)/dt
for the nucleophile CN- as an example,
CH3-Br + CN- à CH3-CN +Br ; how does this compare to:
CH3-Br + H2O à CH3-OH +Br + H+
d(CH3BrCN-)/dt = kCN [CN- ] and d CH3BrH2O /dt = kH2O [H2O ]
so kCN [CN- ]50% = kH2O [H2O ] and using the ratio of the rate constants above
[CN- ]50% = [H2O ] X 10-n
using values for n (page 359) for different
nucleophiles and [H2O ]= 55 mol/L
see Table 12.6 page 364 of Schwarznebach for [x-]50%
NO3- = 6 molar Br- = 7x10-3
SO42- = 2x10-1 OH-= 4X10-3
Cl- = 6x10-2 I- = 6X10-4
In fresh water Cl-= 10-3; SO42-= 2x10-4; OH-=10-6 mol/L;
so what do we conclude??
SN2 substitution (Substitution, nucleophilic bimolecular)
A nucleophile attacks a carbon from the opposite side of the leaving group. An intermediate is theorized in which the nucleophile is partially bonded to the molecule, while the leaving group is partially dissociated.
The nucleophile donates two electrons and the leaving group takes two electrons
blow up page 109 of Richard Larson’s book on Environmental Organic Mechanisms
The free energy of activation DG‡ and the rate of reaction will depend on the:
nucelophlicity of Y:
steric factors
Hydrolysis t1/2 of chloromethanes (years)
CH3Cl CH2Cl2 CHCl3 CCl4
0.93 704 3,500 7,000
Sterioisomers,dieldrin and endrin, are two examples of insecticides that contain epoxide moieties. Both hydrolyze by SN2 reaction with H2O and OH-, resulting in diols
Carbon skeleton sterically impedes nucleophilic attack by H2O and OH-. As a result persistence in aquatic eco-systems are long and they have been banned in the US, but still used in other countries.
Epichlorlhydrin is used for the manufacture of glycerol and expoy resins. Its calculated half-life in distilled water at 20oC is 8 days
The SN1 Mechanism
This mechanism (nucleophilic substitution, monomolecular) differs from the SN2 in that a dissociation of the organic molecule 1st takes place to form a carbonium ion (carbocation). The carbonium ions is then attacked by a nucleophile
· exhibits 1st order behavior
· factors that stabilize the carbonium ion
will increase reactivity, such as resonance or inductive effects
Figure 13.2 page 496
SN1 vs. SN2
For mono and di halomethanes, an increase in the # of halogen substituents on carbon increases the hydrolysis half-life. Why?
R-Cl+H2O --> R-OH + HCl
Cl Cl
H-C-Cl Cl-C-Cl
H Cl
SN2
By contrast, as the steric bulk in the form of methyl addition to the central carbon bearing the halogen occurs, a significant INCREASE in reactivity can be observed. Why?
Cl Cl
CH3-C-CH3 CH3-C- CH3
H CH3
38 days 23 seconds
As halogen electronegativity decreases (F>Cl>Br) hydrolysis rates increase
Page 505, Table 13.6
Explaining mechanisms
Under neutral or basic conditions nucleophilic attack on the primary carbon occurs by SN2; the epoxide opens up and the deuterated oxygen appears at the primary carbon site
Under acidic conditions, the high conc. of [H]+ attacks the epoxide oxygen and water attacks the secondary carbon.
Write analogous SN1 and SN2 mechanisms for the neutral hydrolysis of a substituted epoxide.
Elimination Reactions
· sterically hindered nucleophilic substitution
· when acidic protons are present next to the carbon of the leaving group
· presence of strong bases
b-elimination
-C-C------> C=C
H X -HX
example of such a reaction is the conversion of 1,1,2,2-tetrachlorethane to trichloroethylene. This can be viewed as an SN2 reaction followed by elimination
DDT conversion to the more environmentally stable DDE via elimination as a function of increasing pH or increasing strength of nucleophilic OH-
rearranges in the environment to
Pesticides
About 50% of the pesticide use in North America is associated with agriculture(lawns and gardens account for a significant part of the rest); in the world ~85%
Is for agricultural use.
Insecticides
herbicides
fungicides
this equals about 1 billion kilograms per year in North America
What is under your sink?? And think about exposures of small children
Half the foods eaten in the US contain measurable levels of one pesticide.
Young children eat more food compared to adults (mass/mass) and tend to eat more fruit and vegetables (grapes, apples, etc)
Traditional Insecticides
~1000 BC the burning of sulfur to fumigate homes in Greece was used
S + O2 à SO2
Sulfur was used in candles into the 1800s and is still used in dusts and sprays as an insecticide and a fungicide on plants.
Sodium fluoride is used control ants. It and boric acid are used to control cockroaches
The Romans used arsenic to control insects, as did the Chinese dating back to the 1500s.
In 1867 Paris-green was introduced in the US as an insecticide….arsenic compounds act as a stomach poisoning.
During WWII organic pesticides replaced many of the inorganic pesticides and specifically
organochlorines
Stability in the environment
Low solubility in water unless N or O are present
High solubility in fatty material
Relatively high toxicity to insects and low toxicity to humans; low toxicity does not mean there are not other kinds of long term health effects.
An example is hexachlorobenzene (HCB).
After WWII it was used as at fungicide for cereal crops
It causes liver cancer in laboratory rodents and possibly in humans (it can be measured in most humans body fat)
UN Environmental program has developed a list of Persistent Organic Pollutants (POPs) and specifically a list of dirty dozen compounds or compound classes
DDT, Aldrin, Dieldrn, Endrin, Chlordane, Heptachlor, HCB, Mirex, Toxaphene, PCBs, Dioxins and Furans
DDT (para-dichlorodiphenyltrichloroethane)
Used in malaria control and the WHO estimates it has saved the lives of about 5 million people
Rachel Carson’s book “Silent Spring” brought to light the relationship between decreasing bird populations and DDT concentrations in the environment; premature human birth rates were much higher in the 1960s than now.
Of the “Dirty Dozen” DDT is the only one that will not be completely banned
Undeveloped countries argue that is necessary and saves almost 1 million children in Africa/ year. They will continue to use DDT till less expensive pesticides become available.
Most western countries cut production of DDT in the 1970s.
In the US bald eagles have come back to Lake Erie. The Arctic peregrine flacons have come back from virtual extinction.
DDT reacts in the environment and in our bodies to DDE, which is very persistent environmentally
DDT and DDE in Swedish women’s breast milk has declined dramatically over the past 20 years
Bioconcentration vs. Bio-magnification
Bioconcentration we have already discussed
BFC = ratio of compound in an organism/concentration in water
The average concentration increases as one proceeds up the food chain
Over a lifetime an organism (oyster, fish, etc.) consumes many times its weight in food. Toxics tend to accumulate in the fatty tissues, so while metabolized waste is excreted, the toxics may remain to a much greater extent in the fatty tissue.
This process is called bio-magnification.
DDT in Long Island sound.
At one time (1960s) the water concentration was
Salt water Long Island sound 3x10-7 ppm
Plankton 0.04 ppm
Fat of minnows 0.5 ppm
Needle fish 2 ppm
Cormorant (bird) 25 ppm
How does DDT act as a pesticide?
Given its three space geometry, it lodges in the nerve channel of insects that leads out from the nerve cell.
The nerve endings transmit signals via Na+ initiated nerve impulses. When DDT is lodged in the nerve endings a continues signal is transmitted via Na+ . The muscles controlled by the nerve, twitch continually until the insect dies of exhaustion.
DDT, however, environmentally degrades via hydrolysis (reaction with water) to DDE with a fixed “not so three dimensional shape. This does not block the insect nerve endings.
Other DDT like molecules (methoxychlor) have been “designed” that have the shape or geometry of DDT so that its toxicity to insects is similar, but they degrade more rapidly in the environment and tend to be less toxic to other organism because they are excreted rather than absorbed by organisms.
Carboxylic Acid Esters: Esters are important because they are derived from many organic acids and show up in lipids, plasticizers, pesticides, etc
X
R1- C the ester bond; if x is oxygen,
O-R2 its a typical called an acid ester;
If it is sulfur it is thioester
O
R1-C R1COOH + R2OH-->R1COOR2
O-R2
Carbamates
This class is an ester derivative of carbamic acid
O
HO-C-NH2 carbamic acid
O
R-O-C-NR2R3 carbamic acid ester
They exhibit both ester and amide charter
These compounds are widely used as herbicides and insecticides, and were introduced in the 1950s because they rapidly react with water to form “non toxic products”
But they can be acutely toxic to humans and animals that ingest them before they decompose.
They interrupt the metabolic acetychlone cycle. Acetycholine expedites communication between cells and is then destroyed. Carbamates and organophosphates interfere with the actions of enzymes that destroy acetycholine by bonding to the enzymes (acetylcholinesterase).
This has the effect of suppressing the continued transmission of impulses between nerve cells.
Can we estimate the 2nd order rate constant for an aromatic carbamate if we know the rate constants of similar carbamates that have different substituted groups on the aromatic portion of the molecule?
Using the Hammett argument
DG‡o= DG‡oH + S DG‡oi
we said we could show that
log(krate) = log krateH + r sm,p
or log(krate/krateH) = r sm,p
What this means is the for aromatics with different substituted groups, if we know the r value we can calculate the rate constant from the sigma (sm,p) and the hydrogen substituted rate constant.
If we know the rate constant for a number of similar aromatics with different substituted groups, we can create a
y=mx+b plot and solve for the slope r value. see example 13.6 in new book page 4
Use the Hammett equation to relate the kb values to corresponding sigma values via
logkb= = r Ssm,p,o + const
log kb
Ssm,p,o
Hydrolysis Rates (page 514 Figure 13.8 new book)
R1COOR2 + H2O -->R1COOH + R2OH Influence of pH
Basic hydrolysis seems to occur for all species; acid hydrolysis is important for only the slow reacting compounds
Let’s look at a mechanism for acid catalyzed reactions of esters
Acid catalyzed reactions (page 521 new book)
Are steric and inductive forces important in acid catalyzed reactions of carboxylic acid esters?
ester protonated-species
The equilibrium for the protonated species is
K’a = [ ester] [H+]/ [p-species]
The concentration of [p-species]
[p-species] = [ ester] [H+]/ K’a
d[ester]/dt = k’a [p-species] [H2O]
substituting
d[ester]/dt = k’a / K’a [ester] [H2O] [H+]
so the overall rate constant k’a
ka = k’a / K’a [H2O] [H+]
so let’s look at what influences k’a / K’a
looking at page 521 Figure 13.10 (new book)
2nd step is the rate determining step with a rate constant of k’A
what will electron with drawing groups do to the
protonated species [p-species]??
???
It will make the [p-species] more +
What will this do in terms of water attack on the positive carbonyl carbon and the rate constant k’A??
Going back to the 1st reaction in the acid catalyzed reaction, what will increase with electron drawing R1 groups do to the equilibrium??
We said the rate constant was
ka = k’a / K’a [H2O] [H+] and both k’a and K’a
Increase with increasing with drawing groups; these are approximately the same order of magnitude and hence qualitatively, ka does not change with induction