Chemistry

Chemistry

• Freidel crafts reagent (AlCl3):

CH3Cl + AlCl3 + + HCl + AlCl3

ROCl + AlCl3 + + HCl + AlCl3

• Canizaro’s reaction:

2 aldehyde + NaOH one is reduced & the other is oxidized.

2 + NaOH +

• Markonikov’s reaction: Addition of HX to alkenes

CH3 – CH = CH2 + HCl CH3 – CHCl – CH3

• Markonikov’s rule: Hydrogen is added to the more hydrogenated carbon (with HCl or HI).

• Anti-markonikov’s reaction: due to free radicle reaction to alkenes.

CH3 – CH = CH2 + HBr ROOR CH3 – CH2 – CH2Br

HCl & HI cannot give anti-markonikov’s reaction. Only HBr can because of free radicles.

• Grignard’s reagent: Mg + RX R – MgX.

Mg + ArX Ar – MgX

R – MgX + R’CHO R R’ – CH – OH 2ry alcohol

R – MgX + HCHO R – CH2 – OH 1ry alcohol

R’ – MgX + R2CHO R’R2 C – OH 3ry alcohol

• Cyclohexane does not react with Grignard’s reagent as it neither contains double bonds nor functional gps.

• Inductive Mechanism:

– Electron donating gps: NH2, OH, OR, CH3CONH, CH3

– Electron withdrawing gps: NO2, CN, SO3H, CHO, RC=O, X

– Reactivity of halogen (X) atoms: F > Cl > Br > I

– 3ry amines are more basic > 2ry > 1ry > CH3CONH2

• Nucleophilic substitution reactions:

– Nu + R – X R – NU + X

– OH + R – X R – OH + X

– NH3 + R – X R – NH4 + X

Cl

COR

CHO COONa CH2OH

• Kinetics of Nucleophilic Substitution:

– SN 2 Reaction: Increasing conc. increases the rate of the reaction

e.g. CH3Cl + OH CH3OH + Cl –

The rate of the reaction depends on both reactants thus Bimolecular

In SN 2 reactions RX > R – CH2 – X > R2 – CH – X . 3ry halides do not react by SN 2

– SN 1 Reaction:

e.g. (CH3)3C – Cl + OH (CH3)3C – OH + Cl –

The rate of the reaction depends on the conc. of only one reactant.

• Permanganate is an oxidizing agent:

2 MnO4- + 6 H+ + 5 NO2

- 2 Mn2+ + 3 H2O + 5 NO3-

This is an example of oxidation-reduction reaction in which nitrite is oxidized to nitrate in acidic medium.

• Hg acetate (mercuric acetate): in a non-aqueous titration of NH2 (halo amine), will offer protonated

species, i.e. it will speed of the reaction (ppt Hg).

• Na barbital is H2O soluble but if an acid is added precipitate barbeturic acid (insoluble).

• Oxalic acid is the principle oxidation product of ethylene glycol.

HO–CH2–CH2–OH HOOC–COOH

• Chloroform / Trichloromethane (CHCl3): when oxidized phosgene (a very toxic gas).

• Amides are used in medicine: as local anesthetics & anti-arrhythmics.

• Sodium bisulfite: is a mixture of NaHSO3 and sodium meta-bisulfite Na2SO3. When dissolved in

water it converts to sodium bisulfite. Bisulfites are reducing agents used to protect oxygen sensitive drugs from oxidation.

• Fixed oil upon hydrolysis High m wt fatty acid + glycerol.

• Waxes Fatty acid + high mol wt alcohol

• Cholesterol is a polyalcohol w/o emulsion.

• An ampholyte: is a substance capable of functioning both as an acid & base, e.g. NaH2PO4, water,

tetracycline.

• Co-precipitation: is due to rapid cooling.

• Types of isomers:

– Position (structural) isomers Isosters

– Configurational isomers (single bond) Conformers (Rotomers)

– Mirror image Stereo isomers

– Mirror image & optical isomers Enantiomers

– Not mirror image but optical isomers Diesters (diastereomers)

Predicting Water Solubility

I - The Empiric Method: The chemical properties of a functional gp. are not usually affected by the presence of another chemical gp. within the molecule.

• The presence of a single functional gp. (Liberal Method) there is no liability of intra-molecular bonding; however there is a probability of inter-molecular bonding; e.g. hexanol binds to another molecule of hexanol (each having only 1 functional gp., -OH) through dipole-dipole bonding. In order to dissolve hexanol in water, one must 1st overcome (break) this dipole-dipole bond so that water molecules can bind to the functional gps.

• The presence of a Poly-functional gps. (Conservative Method) there is probability of intra-molecular bonding as well as of inter-molecular bonding. See the example of Tyrosine:

– The phenol gp will solubilize 6 – 7 carbons

– The amino gp will solubilize 6 – 7 carbons

– The carboxyl gp will solubilize 5 – 6 carbons

– The total solubilization potential 17 – 20 carbons.

– The molecule contains only 9 carbons.

– It is expected to be soluble in water.

– However, in reality it is insoluble (0.5 gm / L)

– This is mainly due to intra-molecular bonding. Amino-acids undergo intra-molecular ion-ion bonding (Zwitterion effect).

– As a result this intra-molecular bonding destroys the ability of these 2 functional gps. (amino & carboxyl) to bond with water. Meanwhile, the phenol gp. is unable by itself to dissolve the molecule.

– If the intra-molecular bonding is destroyed by the addition of either HCl or NaOH, the resulting compound becomes water soluble.

– CH2 – CH – NH2

COOH

HOPhenol gp. Amino gp. (1ry amine)

Carboxyl gp.

– CH2 – CH – NH3+

COO -

HO

Zwitterion Effect

– CH2 – CH – NH2

COONa+

- HO

Very Soluble

– CH2 – CH – NH3+ Cl -

COOH

HO

Very Soluble

NaOH + H 2O HCl + H

2 O

Example 2:

• Consider the shown compound which contains two 3ry amine functional gps.

• Using the liberal method: (mono-functional gp.)

– Each 3ry amino gp will solubilize 7 carbons

– The 2 amino gps will solubilize 14 carbons



• Using the conservative method: (poly-functional gp.)

– Each 3ry amino gp will solubilize only 3 carbons

– The 2 amino gps will solubilize 6 carbons

– The molecule contains 13 carbons.

– It is expected to be insoluble in water.

• In fact: the compound is soluble because it contains similar functional gps (no liability for intra- nor inter-molecular bonding).

Example 3:

• Using the liberal method: (mono-functional gp.)

– The aldehyde gp will solubilize 5 carbons

– The 3ry amino gp will solubilize7 carbons



• Using the conservative method: (poly-functional gp.)

– The aldehyde gp will solubilize 1 carbon

– The 3ry amino gp will solubilize3 carbons

– The molecule contains 13 carbons.

– It is expected to be insoluble in water, which is the case.

– The conservative method is more appropriate for this example.

N – C6 H5

N

CH3 CH3

CHO

N

CH3 CH3

II - The Analytical Method: This method is based on the partitioning of a drug between octanol (a standard lipophilic medium) & water (a standard hydrophilic medium).

Log P = Conc. of drug in octanol / Conc. of drug in water

– Where P is the partition coefficient of the drug.

– The P value measures the solubility characteristics of the molecule as whole.

• How to measure Log P: This is calculated as the summation of the hydrophilic-lipohilic values ( value) of different fragments of the molecule

Log P =

– In order to use this method you must fragment the molecule into basic units.

– Hence for each fragment, assign appropriate values depending on the atoms & groups of atoms present (in this specific fragment).

– Positive values: means that the fragment, relative to hydrogen, is lipophilic, or favors solubility in octanol.

– Negative values: means that the fragment, relative to hydrogen, is hydrophilic, or favors solubility in water.

• Normal log P value = + 0.5

• Log P value > + 0.5 compound is water insoluble ( solubility in water < 3.3%).

• Log P value < + 0.5 compound is water soluble.

Example 1: Calculating water solubility of salicylic acid + intra-molecular H-bonding (IMHB).

Log P – IMHB Log P + IMHB

Phenyl gp + 2 + 2

Hydroxyl - 1 - 1

Carboxylic - 0.7 - 0.7

IMHB ----- + 0.6

Sum + 0.3 + 0.9

Result Soluble Insoluble

• In fact: the compound is insoluble (IMHB is present & is expected to water solubility).

Example 2: Predicting the water solubility of procaine.

6 C atoms X 0.5 each + 3.0

1 Phenyl X 2.0 + 2.0

2 Nitrogen X - 1.0 each - 2.0

1 C=O X - 0.7 - 0.7 Sum = 2.3 Water insoluble.

• N.B: There is no need to investigate the possibility of IMHB, since the result is insoluble, adding the value for IMHB will only make the result more water insoluble.

C – OH

OH

O

NH2 CO–CH2–CH2 – N (C2H5)2

1. The addition of a catalyst, the reaction will:

a. Give more products

b. Give less products

c. Get products rapidly (proceed rapidly)

2. What is the type of reaction of HCl + H2O:

a. It is an ionization reaction (as HCl is a proton donor).

3. Perchloroacetic acid can protonate acetic acid because:

a. Acetic acid is stronger than perchloroacetic acid

b. Perchloroacetic acid is stronger than acetic acid

c. Acetic acid accepts protons easily

d. Acetic acid is a strong oxidizing agent

e. Perchlorate is more basic than acetate

f. Acetic acid is more basic than perchloroacetic acid.

4. In 1,4 dimethyl cyclohexane, the best confirmation of the 2 methyl gps. Is when they are:

a. Equatorial - equatorial

b. Axial - axial

c. Equatorial – axial

5. A drug in its state of 1S2 2S1 P2 is in:

a. Its ground state.

b. Its excited state.

c. Hybrid.

6. Phenols are acidic because they have:

a. Mesomeric interaction. c. Strong induction anion.

1. Strong induction cation.

a. The titrable result of Codeine phosphate + acetic acid is:

a. [Codeine] PO43-.

b. Codeine H2PO4. (codeine hydrogen phosphate)

1. Codeine HPO4

b. To increase the rate of chemical reaction:

1. Remove the resultant as it is formed d. Increase temp

2. Increase stirring force e. Addition of catalyst

3. Decrease pH

An acid capable of protonating another acid is the stronger acid

Equatorial

Axial

9. In gravimetric analysis the pH is adjusted to:

a. To complete pptn (facilitate pptn).

b. To avoid unwanted pptn (avoid co-pptn).

c. To obtain fine filterable particles.

d. Favorable pH for pptn.

10. Why is mercuric acetate used in non-aqueous titration:

a. To produce protonation species.

11. For the given structures, which is soluble in NaOH:

a. The one with the COOH gp.

12. For the given structures, which is soluble in HCl:

a. The one with the NH2 gp.

13. Which of the following is a differentiating solution in non-aqueous titration:

a. Acetic anhydride. c. Glacial acetic acid.

b. Quinine / Quinidine d. Acitonitrile.

14. In sulphonamide titration, what is the role of dimethyl formaldehyde:

a. It acts as a basic solvent.

15. From the given structures which is an azodye:

a. Ph – N = N – naphthyl with ortho hydroxyl.

b. Ph – NH – naphthyl.

9. Ph – NH – NH – naphthyl

a. What is the base for titration of perchloric acid:

a. Acetic acid b. Cl- c. SO4--

CH3COOH + HClO4 CH3CH(OH)2 + ClO4

b. The structure shown is:

9. A zwitterion. c. A resonant form.

a. An ion pair

9. In the titration of codeine phosphate with glacial acetic acid, color change is due to the formation of:

a. R3 – NH+

10. In the structure shown, which carbon is least acidic:

a. C 1 b. C 2 c. C 3

a. In the structure shown, which carbon is least basic:

9. C 5 b. C 2 c. C 3

b. NO2 + O2 (KMnO4) in acidic medium:

15. NO3

22. Which of the following is more basic in water:

23. Soap is:

a. Na+ salt of fatty acid.

24. Which can give cis & trans isomers:

a. 2 butene b. 1 butene c. 3 butene

25. Arrange the following gps in decreasing order of reactivity:

a. COO– > COOH > OCH3 > CH3

26. Isoxazole & oxazole contain:

a. Elecron withdrawing gps.

27. RCH2NH2 + A RCH2COCH3 , A stands for:

a. CH3COCl

28. A hydroxyl containing compound undergoes a reaction to give COOH, The OH gp is:

a. Terminal hydroxyl c. 3ry hydroxyl

b. Secondary hydroxyl

29. Which is formed by alcohol metabolism:

a. Aldehyde b. Alkene c. Alkane

a. Which is free oxygen radicle:22. O. b. H2O

. c. HO.

b. How can we differentiate by a simple reaction between 1ry, 2ry, & 3ry alcohol:

22. By using CrO4 / SO4 which can oxidize 1ry alcohol to aldehyde, 2ry alcohol to ketone

while 3ry alcohol does not react.

c. NH4+ + OH– NH3 + H2O; this is a :

22. Neutralization reaction b. Esterification reaction

d. In the assay of ephedrine HCl we use:

22. NaOH b. Acetic acid

e. Which compounds are affected by hydrolysis:

22. Esters b. Amides

f. Which compounds react with schiffs base but not with fehling:

28. Ketones b. Aldehydes

36. Ortho dinitro phenol is a stronger acid than phenol because of:

a. The electron withdrawing effect of the nitro gps.

37. Compared to formic acid, acetic acid is a weaker acid because:

a. The methyl gp in acetic acid is electron donating.

38. Hinsberg reaction is used for differentiation of amines since:

a. 1ry amines react with the reagent & dissolve in NaOH

b. 2ry amines react with the reagent but do not dissolve in NaOH

c. 3ry amines do not react with the reagent

39. How many chiral carbon atoms are in the shown compound:

a. Zero c. One

b. Two

40. Enantiomers:

a. Have a chiral carbon c. Are optical isomers

b. Rotate plain polarized light

41. How many isomers are there for 2 butene:

a. Four c. Two

36. None

a. E – Z isomers are :

a. Geometric isomers b. Enantiomers

36. Diasteriomers

b. Which gp forms salt with:

36. NaHCO3 4

37. NaOH 2 & 4

a. HCl 1

c. Hg acetate is used in the assay of histamine to:

36. Provide a protonated species

d. Acidity of carboxylic acid (COOH) but not phenol (OH) is due to:

a. Anaionic resonance.

36. Amphoteric agents can form salts with:

a. Acids b. Bases

a. SN 2 reactivity is more with:

36. CH3X

48. SN 1 reactivity is more with:

a. (CH3)3 – X

49. How can we obtain a di-carbonyl gp:

a. By Claisen’s condensation.

50. Grignard’s reagent is:

a. R – Mg – X

51. Which compound does not react with Grignard’s reagent:

a. Cyclohexane (as it contains no functional gps nor double bonds)

52. ROH + A CH3COOR, A is :

a. CH3COOH / pyridine c. KMnO4 / H2O

b. Br2 / UV

53. Nicotinic acid nucleus is:

a. Pyridine

54. Folic acid nucleus is :

a. Ptyredine

55. Zn differs from Ca in their reactions because:

48. Zn is a Lewis base

a. + KMnO4

+ Br2 / CCl4

b. In acid base titration, which affects the reaction:

48. The change in pH of the solution

c. Boron 1 S , 2 S 2 , 2 P 2; this is in th:

48. Excited state b. Hybrid c. Ground state

d. Which compound reacts with schiffs base but does not reduce fehling’s solution:

48. Buterophanones

e. Which gp forms salt with NaHCO3:

a. Strong acid

48. Which compound reacts by SN mechanism:

a. Butene (C = C)

49. Amphetamine (weak base) is extracted by:

a. ether

50. Which of the following does not discolour Br2 / CCl4:

48. ????

64. Phenol is weakly acidic because:

a. It weakly dissociates

65. In the assay of ephedrine HCl, we dissolve in water, add a reagent X, filter then extract with methylene chloride, what is the reagent X:

a. 0.1 N NaOH (or Na2CO3)

66. Perchloric acid is stronger than acetic acid because:

a. Acetic acid is more basic ???

67. Codeine phosphate is dissolved in acetic acid & titrated with perchloric acid,:

a. RN2 ???

68. Several organic compounds are given, which compound has water solubility characteristics:

a. The structure showing a phosphate salt

69. Given the chemical structures of quinine & quinidine, these are:

a. Optical isomers

70. In the shown structure:

a. Which carbon is the most acidic C 6

b. Which carbon is the most basic C 2

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