Homework # 6 Amines and Amides - Elmhurst University



Week # 8: Amines and Amides

Lectures: 20,21, 22

Concepts:

Classification of amines - primary, secondary, tertiary

Properties of amines and amides - solubility, hydrogen bonding

Basic property - self ionization

Amine salts

Heterocyclic amines

Reaction Summary: Write the word equations

Self ionization of amines in water:

Neutralization (Salt formation) of amines with acid:

Amide Synthesis:

Amide Hydrolysis (acidic conditions)

Ques. 1. Identify the following amines as primary, secondary, tertiary, or ammonium ion. Also name each one.

Ques. 2. For the following amines in Health and Medicine list all functional groups present, and identify the amines as primary, secondary, or tertiary, and finally list the use or occurrence of each compound.

Histamine

Diphenylhydramine

Epinephrine

Dopamine

Benzedrine

Neo-Synephrine or phenylephrine

methedrine

Ques. 3. A. Draw three molecules of ethylamine engaged in hydrogen bonding.

b. Explain why trimethylamine can not form hydrogen bonds.

Ques. 4. Explain the difference and rank them in order of lowest to highest boiling points of ethyl methylamine, 1-propanol, trimethyl amine, and propylamine,. Include points about relative polarity and hydrogen bonding.

Ques. 5. Write the ionization reactions for

dimethylamine

trimethylamine

ethylamine.

Neutralization Reaction or Salt Formation

|Reaction Name |Word Equation |Example |

|21. Amine Salt reaction |Amine + HX X = Cl, Br, I |methylamine + HCl |

| |( amine halogen ion salt | |

|22. Acid / amine salt reaction |Acid + amine |Methylamine + ethanoic acid |

| |( acid amine salt | |

Ques. 6. Write the following neutralization reactions:

a. ethylamine + HCl --->

b. ethyl propylamine + HBr --->

c.

Ques. 7. Why are many drugs listed in the ingredients as the hydrochloride - example Sudafed is listed as ephedrine hydrochloride; Novocain, local anesthetic is the hydrochloride salt of procaine. Think about polarity of amines , salts, and solubility in water.

Ques. 8: Name the amides in the above structures:

Ques. 9. For each of the heterocyclic amines or alkaloids list the following:

Number and type of amine present, whether a heterocyclic amine is present, source and or use.

Nicotine

Caffeine

Quinine

Atropine

Heroin

Morphine

Codeine

Cocaine

Meperidine (Demerol)

Ques. 10. Look carefully at the structures of: Morphine, Codeine, Cocaine and draw them. Point out the differences.

If morphine is naturally produced from the poppy, what chemical reactions are used to change it to codeine and heroin. Be specific and show the reactions - you have studied them previously.

|13. Amide Synthesis |Amine + acid |Ethanoic acid + methylamine |

| |( amide + water | |

Ques 11. Write the products of reactions for the amidation or synthesis of amides. Give the names of both the reactants and the products.

d.

e.

d.

Ques. 12. Discuss the relative basic properties of amines vs. amides. Which is more polar and can have more possibilities for hydrogen bonding? Ethylamine or ethanamide. Explain

Ques. 13. For each of the amides in Health and Medicine, identify those that have amide groups only and those that have both amides and amines, those that are heterocyclic amines. Give the uses.

Aspartame

Saccharin

Phenobarbitol

Valium

|18. Amide Hydrolysis |Amide + HOH |N-methylpropanamide + HOH |

| |( amine + acid | |

Ques. 14. Complete the acid hydrolysis of the following amides. Give the names of the reactants and the products. Note: First make the amine and the acid, then if an acid is used as a catalyst, then the amine must form a salt with the excess acid.

c.

d.

Focus on Molecular vs. Ionic Structures of acids & bases:

Whether an acid or base exists predominately in the molecular, undissociated form, or the ionic form, is determined by the pKa or pKb and the pH. pKa is the negative logarithim of the Ka and likewise for pKb. Ka and Kb are the equilbirum constants which give information about the strength of the acid or base. Forour discussions here the acids and bases are weak. The mathematical equations show that when pKb or pKb = pH, there are equal concentrations of the molecular and ionic forms of the acid or base

ACIDS

Acid Equilibrium: HA (( A- + H+

If the pH is less than the pKa, the acid is predominately in the molecular form. This occurs because excess H+ ions are attracted to the negative acid ion

A- + excess H+ ( HA

ionic form molecular form

If the pH is greater than the pKa, the acid is predominately in the ionic form because an excess of OH- ions has neutralized the H+ ions leaving the ionic form of the acid.

HA + excess OH- ( A- + HOH

molecular form ionic form

Summary:

( ( ( ( pH increasing

pH less than < pKa < pH greater than

[ HA ] [ A-]

molecular form ionic form

predominates predominates

Example:

If Acetic acid (pKa = 4.7) is in a solution of pH 2, what is the form, molecular or ionic, using the summary diagram above?

Solution: pH 2 < pKa 4.7 therefore the form is molecular (CH3COOH)

Example:

If acetic acid (pKa = 4.7) is in a solution of pH of 10, what is the form, molecular or ionic?

Solution: pKa = 4.7 < pH 10, therefore the form is ionic (CH3COO-).

BASES - Amines:

If the pH is less than pKb, the base is predominately in the ionic

form because excess H+ ions are attracted to the amine nitrogen. If the

pH is greater than the pHb, the base is predominately in the molecular

form because an excess of OH- ions has neutralized the H+ ions attached

to the amine

Amine Equilibrium: B + HOH (( BH+ + OH

Summary:

( ( ( ( pH increasing

pH less than < pKb < pH greater than

[BH+ ] [ B ]

ionic form molecular form

predominates predominates

QUES. 15: Complete the equations below which are derived from the statements above. Which form ionic or moleulcar is the end result?

a) If pH is less than pKb = B + H+ (

b) If pH is greater than b: BH+ + OH- (

QUES. 16 : If methylamine (pKb = 3.6) is at pH 2 and 10, what is the

form: molecular or ionic in each case?

Summary Diagram:

( ( ( increasing pH

pH < pKa < pH

HA A-

BH+ pKb B

Example:

Ammonia (NH3) may be formed by kidney cells when blood pH is low. It can pass through a lipid membrane by filtration into the developing urine. Under these conditions, the aqueous urine has a pH of 4.0. If the pKb for NH3 is 4.7, what is the form (ionic or molecular) for ammonia in urine? Can this form repenetrate the kidney cells? Explain on the basis of solubility principles.

Solution

pH < pKb < pH

4.0 4.7

BH+ B

NH4+ NH3

The above analysis shows that NH4+ ions are present at a pH of 4. The ionic form is soluble in water and insoluble in the lipid membranes. Therefore, NH4+ ions will not repenetrate kidney cells but will be excreted.

Ques. 17: Many drugs are weak acids (pKa = 3-10) and are absorbed in the acidic environment of the stomach. These drugs include barbiturates, penicillin,

and sulfonamides. Which form (ionic or molecular) are the weak acid drugs

absorbed through the lipid bilayers in the stomach with a pH of 1.

Solution:

HA (( H+ + A-

pH < pKa < pH

1 3-10

HA A- + H+

The analysis shows that the ___?___ form is present. The ___?___ form will be more non-polar and thus more lipid soluble than the ionic form.

Ques. 18: Weak bases such as amphetamines, antihistamines, erythromycin, and opiates, tend to be absorbed in the small intestine rather than the stomach. If the weak bases have pKb of 3-9, the stomach pH = 1, and the small intestine pH = 10. What is the form (ionic or molecular) for the weak base drugs in the stomach and small intestine? Explain the solubility behavior of the drug in each area. Solution (next page)

Solution:

B + HOH (( BH+ + OH-

stomach small intestine

pH < pKb < pH

1 3-9 10

BH+ B

ionic molecular

The above analysis shows that the __?___ form of the drug is present in the stomach. The __?__ form is insoluble in the lipid bilayer of the stomach. On the other hand, the __?___ form is present in the small intestine. The __?__ form is non-polar and is soluble in the lipid bilayer.

QUES. 19: Acute phenobarbital (weak acid) (pKa - 7.2) poisoning can be treated by an intravenous solution of sodium bicarbonate. The bicarbonate raises the pH of the blood and urine (normal pH is 7.4) to a pH of 8. If the pH remains normal the barbiturate, phenobarbital, is removed only very slowly from the body lipid tissues. Suggest the form (ionic or molecular) of the phenobarbital in both cases - normal pH and after bicarbonate treatment and explain how it is excreted using solubility principles.

QUES. 20: The bases acetanilid (phenacetin) and caffeine with pKb of 0.3 and 0.5, respectively, are absorbed in the stomach at rates of about 30% per hour. On the other hand, quinine (pKb = 8.4) is not appreciably absorbed in the stomach. Suggest the form (ionic or molecular) of all three drugs and explain their solubility behavior.

QUES. 21: Studies on the distribution of certain chemicals and dyes in the body led to the belief in the existence of a blood-brain barrier. Studies with sulfonamides (weak acids) show that those with pKa values of 3-7 do not enter the brain. On the other hand, sulfonamides with a pKa of 10 do enter the brain. General plasma pH is about 7.4. Can you suggest a reason for this behavior and suggest whether this blood-brain barrier is made from a polar or nonpolar material.

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