Objective Reaction Type Structural Feature How to figure out how reactants react?

Objective Reaction Type Structural Feature How to figure out how reactants react?

Objective: Determine products of a reaction
How to figure out how reactants react?
Reaction Type
Structural Feature
H+ transfer
Addition
electrophilic addition pi bond
nucleophilic addition carbonyl C
Acidic H+
Objective: Determine products of a reaction
How to figure out how reactants react?
Reaction Type
Elimination
Structural Feature
H bonded to β-C; LG
Substitution
nucleophilic substitution
LG bonded to α-C
electrophilic aromatic substitution
aromatic pi bond
nucleophilic acyl substitution
carbonyl C; LG
Acids are Prepared from Different Functional Groups
Identify the reaction conditions for each reaction.
HBr
HCN
NaBH4
KMnO4
O3
CO2
Carboxylic Acids are Weak Acids
The acid strength depends on the group bonded to the
carbonyl carbon.
Rank the acids from strongest to weakest:
(i)
(ii)
(iii)
A>B>C>D
B>C>A>D
D>A>C>B
Objective: Determine the charge of acid based on pH
Every Acid (HA) has a Conjugate Base (A-): HA <==> H+ + A-
Biology: pH determines the form (acid or conjugate base) and
charge. See pKa and a titration curve.
[A-]
_______
Henderson-Hasselback equation: pH = pKa + log
[HA]
Weak Acids Can be used in Buffers
Objective: Determine the charge of acid based on pH
What is the charge on acetic acid at pH 3?
What is the charge at pH = 9?
pH
4.7
Volume of base
Glycine is the simplest amino acid.
How many protons can glycine donate?
Which H+ is donated first?
What is the charge on glycine at pH 2? pH 7? pH 10?
What is the isoelectric point of glycine?
At what pH can glycine be used as a buffer?
Glycine titration curve
pH
9.78
2.35
Volume of base
Carbonyl Carbon is Electrophilic ==> reacts w/ Nucleophiles.
Lone pair on O is Nu:- ==> reacts with Electrophiles (H+).
At which atom will the Nu:- react first?
(i) Carbonyl carbon
(ii) H bonded to O
Which carbonyl carbon is more reactive (electrophilic)?
(iii) On acid
(iv) On aldehyde/ketone
Objective: Predict product of reactions of acids
Acids React To Form A Variety of Functional Groups
Acid-Base and Nucleophilic Acyl Substitution
1. What do 4 of the 5 reactants have in common? (Nu:-, E+)
What atom in the acid reacts?
What is the reaction type? (acid-base, addition, elimination, substitution)
What is the intermediate formed in each reaction?
2. What are acyl chlorides used for? (see Ch. 19)
Objective: Describe Nu: acyl substitution mechanism
Nucleophilic Acyl Substitution (Nu:- subs for OH) involves
a Tetrahedral Intermediate
NEED a LG!
E.g., Nu:- = ROH (esterification)
RCOOH + ROH -- H+ catalyst --> RCOOR + H2O
Describe the mechanism of ester formation.
Objective: Predict product of Nu:- acyl substitution reaction
E.g., Nu:- = RNH2 (amide formation)
RCOOH + RNH2 -- H+ catalyst --> RCONHR + H2O
E.g., Nu:- = H:- (hydride from LiAlH4 or NaBH4)
RCOOH + H- -- H+ catalyst --> RCHO or RCHOH + H2O
E.g., Nu:- = Cl- (from SOCl2)
RCOOH + Cl- -- H+ catalyst --> RCOCl + H2O
1. Synthesize the following compound from the indicated starting
material and any necessary organic or inorganic reagents:
2. Predict the product of the reaction of pentanoic acid with each of
the following reagents:
a. NaOH
b. Benzyl alcohol, H2SO4 (catalytic amount)
c. LiAlH4, then hydrolysis
3. Predict the product:
Possibilities:
H2SO4 reacts with -OH
Now what?
H2SO4 reacts with O=C
Now what?
A compound that contains -COOH and -OH can form a 5 or 6
sided Lactone ring (Intramolecular Cyclic Ester Formation).
1. What is Compound A? How is
Compound B converted to lactone?
2. Describe how to prepare Vitamin C.
Mevalonolactone is an intermediate in the biosynthesis of terpenes
and steroids.
a. For (1), would you use HCN or NaCN? Give reasons.
b. Suggest a synthesis of (2). Use ethylene or propylene as your source of
carbon atoms and any necessary inorganic reagents.
c. On standing in dilute aqueous acid, Compound A is smoothly converted
to Mevalonolactone. Suggest a reasonable mechanism for this reaction. For
each step, use curved arrow to show bonds breaking and forming. What
other organic product is formed?
Compound A
Mevalonolactone
Some Foods interfere with drug activity
Found in grapefruit juice,
which inactivates a
cytochrome P450 enzyme
http://cen.acs.org/articles/88/i39/
Foods-Drugs-Collide.html
Reaction Roadmap:
What group undergoes Nu:- acyl substitution? And what group is
produced? What are β-keto acids used for?
alkyne
alkane
alkene
alkyl halide
alcohol
R-M
epoxide
acid
amide
w/ ROH
aldehyde
ketone
ester
Ether
acetal
Diols, cyanohydrins, imines
1. Synthesize the following compound from the indicated starting
material and any necessary organic or inorganic reagents:
2. Predict the product:
a.
b.
c.
ID structure or reaction conditions.
Which reactions involve a carbonyl carbon?
Which reactions make a C-C bond?
CEN, 3/21/11, p. 46. Olive oil compound (oleocanthal) blocks
cyclooxygenase (COX) enzymes like Ibuprofen does.
COX enzymes are involved in inflammation and pain. (Inflammation is
our body’s response to injury and infection.)
Is olive oil good for you?
“Curbing Inflammation with Aspirin and Omega-3s” (CEN,
2/25/13, p. 29)
Inflammation causes or exacerbates heart, lung, and kidney
disease
Resolvins serve as a signal our bodies use to start shutting
down inflammation.
Aspirin helps trigger “aspirin-triggered resolvin D3.”
Omega-3 fatty acids are required as building blocks to create
the signal.
CEN, 3/14/11, p. 40. “Inflammation Stokes Cancer”
Inflammation -- signal --> neutrophils and macrophages -- release
--> reactive O, N, and X species -- damage --> biomolecules
Oxidation of guanosine
in DNA leads to 8-oxo7,8-dihydroguanosine,
which can be further
oxidized to form
spiroiminodihydantoin
and guanidinohydantoin.
R = ribose.
http://www.news-medical.net/news/2005/05/02/9722.aspx
When highly unsaturated vegetable oils are heated
at frying temperature (365oF) for extended periods--or even
for half an hour--a highly toxic compound, HNE (4-hydroxytrans-2-nonenal) forms in the oil.
May 2, 2005,
What is the reaction type?
Match the atoms in linoleic acid with HNE.
Unsaturated fats, especially polyunsaturated fats, go rancid
Three pathways: http://en.wikipedia.org/wiki/Rancidification
1. Microbial
2. Oxidative - the double bonds of an unsaturated fatty acid
can undergo cleavage, releasing volatile aldehydes and
ketones.
3. Hydrolytic - ester hydrolysis
triglyceride (ester) --> ROH + 3 RCOOH
Which chain is unsaturated? Polyunsaturated?
Is the same acid formed when this triglyceride hydrolyzes?
1. Predict the products:
2. How are these two reactions similar?
Acids and Acid Derivatives Can Be Converted From
One to Another (Nu:- Acyl Substitution at carbonyl C (E+))
Reference: Virtual Textbook of Organic Chemistry
http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/crbacid2.htm#react
Nucleophilic Acyl Substitution Involves A Tetrahedral Intermediate
How is nucleophilic acyl substitution reaction similar to a nucleophilic
addition reaction of aldehydes and ketones?
Where is the LG?
Reference: Virtual Textbook of Organic Chemistry
http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/crbacid2.htm#react
Objective: Convert one acid derivative to another
Identify the Reaction Conditions to Convert One Functional Group
to Another (Hint: What Nu:- to use?)
Many Types of Nylon for Many Uses (CEN, 2/18/13, p. 28)
Carpets, fabric, food
packaging, balloons
Flexible tubing in
autos
As # of C’s
increase, chemical
resistance and
flexibility increase,
specific gravity
decreases
Brake and gas
lines in cars
Nylon is a common plastic. (See Chang, 6th ed., Fig. 22.4, p. 765)
1. Identify the functional group(s) in nylon.
2. How is nylon made? Or How is this functional group made?
a. Condensation (or reverse)
b. alkene addition
c. alcohol oxidation
Another way to make Nylon: use adipoyl chloride instead of
adipic acid. Which reaction is faster?
Predict the product:
Hint: A is soap
(Klein, “Organic
Chemistry”, p. 1002)
CEN, 2/14/11, p. 11 “Race To The Pump: Biofuel technologies
vie to provide a sustainable supply of transportation fuels.”
CEN, 2/14/11, p. 11 “Biofuel Technologies”
2nd
generation
1st
generation
3rd
generation
See also CEN, 8/15/11, p. 10 “Biofuels Policy”
Biodiesel Cetane Number measures Combustion Quality of
fuel during compression ignition (CEN, 6/13/11, p. 30)
Fuel
Cetane Number
US biodiesel from soybean oil
47
Europe biodiesel from
rapeseed and canola oil
54
* More efficient
Difference in cetane number is due to number of C=C bonds
Biodiesel synthesis from vegetable oil
OH- catalyst
alcohol
+
acid
ester
+ CH3OH --->
acid
alcohol
Ester = Biodiesel
FAMEs = fatty acid methyl esters
Analyze by: IR - check for ?
GC - FAMEs. Which fatty acid type has
the higher b.p.?
Prodrugs: inactive form of a drug that makes the active form in
the body
E.g., epinephrine is used in the treatment of glaucoma.
What is the structure of epinephrine?
Biology: Cyclic Amides (Lactams) Are Found in Antibiotics
β-Lactams = 4 sided ring
Reference: Carey, 8th ed., p. 847
β-Lactam antibiotics work by deactivating a transpeptidase
enzyme, which is required for biosynthesis of bacterial cell
walls.
Draw the structure of the product.
Amides: used in Sedatives (Klein, “Organic Chemistry”, p. 981)
Draw the structure of a
metabolic product of
each compound.
Sprayed by a Skunk!
Should I use tomato juice or hydrogen peroxide?
1. The compound shown was subjected to the following
series of reactions to give a product having the molecular
formula, C9H9ClO3. What is this product?
2. Write a structural formula for the principle product or
products of the following reaction:
propanoyl chloride and sodium propanate
Carey, 8th ed. Problem 19.40
Ambrettolide (C16H28O2) has a musk-like odor and is obtained from
hibiscus. Its synthesis consists of 7 steps:
Step
Reactant
Reagents
Product
1
A
H2O, H+, heat
C16H32O5 (B)
2
B
HBr
C16H29Br3O2 (C)
3
C
Ethanol, H2SO4
C18H33Br3O2 (D)
4
D
Zinc, ethanol (converts vicinal
C18H33BrO2 (E)
dibromides to alkenes)
5
E
NaCH3COO, CH3COOH
C20H36O4 (F)
6
F
KOH, C2H5OH, then H+
C16H30O3 (G)
7
G
Heat
Ambrettolide
Determine the structures of
Compounds B through G.
Objective: predict reactions of nitriles
Carey, 8th ed., Problem 19.29t, u, and v
Klein, Ch. 21.50e and h, 65e
Reaction Roadmap:
Acid derivatives: acyl chlorides, anhydrides, esters, amides
What group makes nitriles? What group is made from nitriles?
alkyne
alkane
alkene
alkyl halide
alcohol
R-M
epoxide
acid
w/ ROH
aldehyde
ketone
ester
amide
Ether
acetal
Diols, cyanohydrins, imines
Knowing Reactive Sites of a Functional Group Helps ID Product
How are the compounds in the top row similar?
What reaction type do these compounds undergo?
How are the compounds in the bottome row similar?
What reaction type do these compounds undergo?
Knowing How to Make a Functional Group Helps You Design
a Synthesis
Synthesize (convert) a compound from the top row to a
compound in the bottom row.
Synthesize (convert) a compound from the bottom row to a
compound in the top row.
1. Predict the product in each reaction:
2. Using toluene, sodium cyanide, and carbon dioxide as the
sources of carbon atoms, along with any necessary inorganic
reagents, show how you would prepare the following:
Benzoyl chloride
Acid or Acid Derivative + Nu:- --> reaction occurs at carbonyl C
Nu:- = H- (from LiAlH4 or NaBH4), N (from amine), O (from ROH), etc.
Acid or Acid Derivative + HCl (or other
acid) --> reaction occurs at carbonyl O
Tetrahedral
intermediate
product
1. Compound A is a derivative of the carbohydrate perosamine,
which is found in the antibiotic perimycin. When A is treated with
excess acetic anhydride in methanol, a mono-acyl derivative B
(C9H17NO5) in 73% yield. Draw the structure of B. (Hint: consider
that methanol reacts with acetic anhydride.
2. Using toluene, sodium cyanide, and carbon dioxide as the
sources of carbon atoms, along with any necessary inorganic
reagents, show how you would prepare the following:
phenylacetic acid
Anatomy of a tear gas (http://pubs.acs.org/cgi-bin/bottomframe.cgi?7751gov1box)
Police in Seattle released copious quantities of tear gas in their efforts to disperse demonstrators at the
World Trade Organization meeting.
The tear gas they used contained o-chlorobenzylidene malononitrile, according to a Seattle police
spokeswoman. The substance is called CS after the two men who developed it in 1928, Ben B. Corson and
Roger W. Stoughton. CS, a white crystalline solid at room temperature, is classified as an "antiriot agent"
by the U.S. military. Law enforcement agencies in the U.S. began using CS tear gas in the 1960s, and now
police around the world use it.
U.S. sales of CS powder and munitions containing it, such as grenades and projectiles, are limited to law
enforcement agencies. However, small aerosol cans containing a formulation of CS are available to the U.S.
public.
According to the Army, exposure to CS causes pain and burning in the eyes and skin within seconds. The
chemical is an alkylating agent that reacts readily at nucleophilic sites, and
sulfhydryl-containing enzymes such as those found in the eye are a prime
target, the Army says.
Effects of CS exposure include an extreme burning sensation in the eyes with a copious flow of tears,
coughing, sneezing, a perception of chest tightness, and dizziness. Most of these effects subside within 30
minutes of exposure. High concentrations may trigger nausea and vomiting.
A study by the National Toxicology Program found no evidence of carcinogenic activity in mice and rats
exposed to CS for up to two years.