Nitration (2)

it contains all the subtopic of the topic nitration that is to be studied in M.pharm pharmaceutical chemistry

1. Pharmaceutical Process Chemistry Topic: Nitration Presented By: Neha Priya

2. Contents What is nitration Importance of nitration Nitrating agents Mixed acid for nitration Aromatic nitration Kinetics and mechanism of aromatic nitration Process equipment for technical nitration Multiple choice questions

3. Nitration Introduction of one or more nitro groups (-NO2 ) into a reacting molecule. The reaction between a nitration agent and an organic compound that results in one or more nitro ( --NO2) groups becoming chemically bonded to an atom in this compound. A process in which a nitro group (--NO 2 ) becomes chemically attached to a carbon, oxygen, or nitrogen atom in an organic compound. A hydrogen or halogen atom is often replaced by the nitro group.

4. Three general reactions summarize  nitration chemistry 1. Nitro aromatic or Nitro paraffinic compound: C nitration, in which the nitro group attaches itself to a carbon atom 2 . Nitrate ester: O nitration (an esterification reaction), in which an ON bond is formed to produce a nitrate 3 . Nitramine: N nitration, in which a NN bond is formed

5. Importance of Nitration products : As • Solvents • Dyestuffs • Pharmaceuticals • Explosives They also serve as useful intermediates for the preparation of other compounds, particularly amines which are prepared by the reduction of the corresponding nitro compound.

6. Nitrating agents: • Fuming, concentrated, and aqueous nitric acid • Mixtures of nitric acid with sulfuric acid, acetic acid, acetic anhydride, phosphoric acid, and chloroform. • Nitrogen pentoxide , N2O5 • Nitrogen tetroxide, N2O4 NOTE :In order to make an intelligent choice of nitrating system for particular nitration, it is desirable to know what species are present in the various systems and to understand the mechanism of the reaction under consideration.

7. Mixed acid for nitration The Nitryl ion NO2 + * Mixed acid: • The system nitric acid-sulfuric acid is the most important nitrating medium from a practical standpoint. • Nitric acid exists in strong sulfuric acid as the Nitryl ion, NO2 + • The Van’t Hoff I factor ( the number of particles generated by one molecule of solute) of nitric acid in sulfuric acid is found to be 4.

8. Formation of N itryl ion:

9. Mixed Acid Composition: From technical standpoint of using mixed nitric and sulfuric acid, there are two primary conditions that must be met. these are 1. The amount of 100% nitric acid present in nitration must be enough to satisfy the stoichiometric requirements of nitration reaction. it is usually present in excess in order to maintain reasonably fast overall reaction 2. The amount of100% sulfuric acid with its associate so3 must be sufficient to promote reaction • D.V.S (dehydrating value of sulfuric acid): D.V.S is the ratio of H2SO4 to H2O present at the end of reaction. • Nitric ratio :nitric ratio is the ratio of the weights of 100% nitric acid to weight of material being nitrated.

10. D.V.S and stability of nitrator charge • Increase in D.V.S favors high stability of nitrator charge, while decrease in D.V.S results in lowering stability. • Increasing D.V.S tends to derive the nitration or esterification farther towards completion, whereas too low D.V.S would permit accumulation of incompletely nitrated materials, with increase dilution and it would be favorable to oxidation • D.V.S. ratio is always on the high, safer side, kind of automatic safety factor.

11. Aromatic nitration: • Nitryl ion is an electrophilic reactant. • Carbon atom of aromatic ring contains strong electron density. • Nitro group can attach to ortho, meta or para positions depending upon the electron density. • The amount of these isomeric product will depend upon the substituent. • Certain substituent cause the electron density to be greater at ortho and para position than meta position, hence they yield nitration products in which ortho, and para isomers predominate. • Other substituent cause the electron density to be greater at meta position rather than ortho and para, hence they are called meta directing.

12. Kinetic of Aromatic Nitration The kinetics of aromatic nitration are functions of temperature, which affects the kinetic rate constant, and of the compositions of both the acid and hydrocarbon phases. In addition, a larger interfacial area between the two phases increases the rates of nitration since the main reactions occur at or near the interface. Larger interfacial areas are obtained by increased agitation. The viscosities and densities of the two phases and the interfacial tension between the phases are important physical properties affecting the interfacial area. Such properties are, of course, dependent on both temperature and the respective compositions of the phases.

13. Temperature also changes the solubilities of various compounds in either the acid or hydrocarbon phase Such dissolved compounds often result in by-product formation. Rates of nitration determined over a range of temperatures in two-phase dispersions have been used to calculate energies of activation from 59-75 kJ/mol (14-18 kcal/mol). Such energies of activation must be considered as only apparent, since the true kinetic rate constants, NO + 2 concentrations, and interfacial area all change as temperature is increased. Increased agitation of a given acid-hydrocarbon dispersion results in an increase in interfacial areas owing to a decrease in the average diameter of the dispersed droplets. As the droplets decrease in size, the ease of separation of the two phases, following completion of nitration, also decreases.

14. Mechanism Of Aromatic Nitration The reaction take place in Three steps: Formation of nitronium ion Formation of arenium ion as a result of electrophilic addition Loss of proton

15. Process Equipment's For Technical Nitration  Batch Nitration  Continuous Nitration

16. Batch Nitration: Nitration is usually done in closed cast iron or steel vessels. Modern practice is to use mild carbon steel. Nitrator consists of a cylindrical vessel containing some kind of cooling surface, a means of agitation, feed inlets and product outlet lines. They are also equipped with a large diameter quick dumping line for emergency use if the reaction gets out of control. The contents of the nitrator are dumped rapidly into a large volume of water contained in a drowning tub.

17. A common accessory for the nitrator is a suction line in the vapor space above the liquid charge to remove the acid fumes and oxides of nitrogen which may be liberated. Two factors which are of prime importance in the design of nitrators are: Degree of agitations Control of temperature

18. Continuous Nitration The actual nitration reactions in a continuous process are carried out in the same type of vessel as used for batch nitration, with the exception that an overflow pipe or weir arrangement is provided for the continuous withdrawal of product and that continuous feed of reactants is provided. Atomization is there is continuous processes. Agitating mechanism can be Single impeller , Double impeller , Propeller or turbine with cooling sleeve .

19. Advantages And Disadvantages of Batch And Continuous Reaction Processes . Advantage of a Batch Process Advantage of a Continuous Process More cost effective if large quantities of the chemical are being made. Disadvantage of a Batch Process Disadvantage of a Continuous Process High capital cost of setting up the plant No expensive ‘down time’ when plant is not being used. A variety of different products can be made using the plant. Slow reactions can be carried out. Automated process requires less labour. Risk of contamination if more than one than one product made in reaction vessel Can use reactants in any state including solids. Expensive down time while reactor is being filled and emptied. Larger workforce required. Costs rise if plant not operated continuously. Can be difficult to control highly exothermic reactions.

20. Multiple choice questions: 1. A process in which benzene is converted into nitrobenzene is known as : Nitration b. Sulphonation c. Both of the above d. None of the above 2. Nitration is an example of: Electrophilic aromatic elimination Nucleophilic aromatic substitution Electrophilic aromatic substitution Nucleophilic aromatic elimination

21. 3. The nitrating agent is a ______ reactant. a) Electrophilic b) Nucleophilic c) All of the mentioned d) None of the mentioned 4 . The electron density is least at which position? a) Ortho b) Para c) Meta d) Equal at all places 5. Nitration products at ortho and para position predominates? a) True b) False 6. The Nitration reaction serves to introduce one or more ______ groups into a reacting molecule. a) Nitro group b) Nitrite group c) Ammonia group d) None of the mentioned

22. 7. What is ” N 2 O 4 ” called? a) Nitrogen pentoxide b) Nitrogen Trioxide c) Nitrogen Dioxide d) Nitrogen Tetroxide 8 . What is the mixture of Nitric acid and Sulphuric acid called? a) Nitrite ion b) Combined acid c) Addition acid d) Mixed Acid 9. Which is more Flexible batch process or continuous process equipment? a) Batch process equipment b) Continuous process equipment c) Flexibility does not affect the process d) Both provide same flexibility

23. 10 . What is/ are the major type of equipment for nitration processing? a) Batch process equipment b) Continuous process equipment c) Both of the mentioned d) None of the mentioned 11. What factors are of prime importance for the designing of a nitrator ? (a) Degree of agitation (b) Control of temperature (c) Both of the mentioned (d) None of the mentioned 12. Why is there a need to have one of the reactant in excess? (a) To achieve equilibrium faster (b) Satisfying the stoichiometric requirement (c) Stable reaction (d) All of the mentioned

24. 13. What does D.V.S stand for? a) Denitration of Sulphuric acid b) Dehydrating value of sulphuric acid c) Decomposition of Sulphuric acid d) None of the mentioned 14. What is NO 2 + called? a) Nitryl ion b) Nitronium ion c) Both of the mentioned d) None of the mentioned 15. What is the correct name for a nitro group that is ready to react with an aromatic ring? ( a) Carbanion (b) Nitronium ion (c) carbocation (d) nucleophile

25. 16. In the nitration of benzene using a mixture of conc. H2SO4 and conc. HNO3,the species which initiates the reaction is __________. (a) NO2 (b) NO+ (c) NO2+ (d) NO2 17. The vant’t Hoff I factor of nitric acid in sulphuric acid is found to be (a)5 (b) 6 (c) 4 (d) 3 18 . Formation of arenium ion in the mechanism of nitration is a result of (a) Electrophilic addition (b) Substitution (c) Both (d) none

26. 19. Which of the following substances acts as the base to pull off a hydrogen atom from the aromatic ring to re-generate the aromatic system in the nitration reaction? (a) Nitric acid (b) Sulfuric acid (c) Benzene (d) Water 20.   Nitrobenzene can be prepared from benzene by using a mixture of conc. HNO 3  and conc. H 2 SO 4 . In the nitrating mixture HNO3 acts as a: ( a) Base (b) Acid (c) Reducing agent (d) Catalyst