Organic Chemistry- Iii; Che-352

Programme: B.Sc. B.ed. (Integrated) Course: ORGANIC CHEMISTRY- III Semester: VI Code: CHE-352

Topic: Antipyrine y Date- 14/04/2020 Only

PPe Dr. Angad Kumar Singh ForF Department of Chemistry, Central University of South Bihar, Gaya (Bihar)

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Preparation of Succinic acids Succinic acid is prepared by reaction of one moles of the sodium salt of EAA with ethylchloroacetale followed by hydrolysis. This is shown in the following reaction. y

C2H5O C2H5O C2H5O Only O O O e C H ONa/EtOH ClCHCH2COOEt/EtOHCOOE EtOOC 2 5 Na+ UseU O O O

al H3C H3C H3C Ethyl acetoacetate (i) KOH, Heat (ii) HCl/H2O, Heat PersonalPe

ForF HO CH COOH 3 OH

Succinic Acid O

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Preparation of Adpic acids Adipic acid or other higher dicarboxylic acid are prepared by reaction of two moles of the sodium salt of EAAEEAy with suitable diiodoalkanes (having iodo group at the terminalrminal carbons) followed Only byacid hdhydro lys is. This isshown in the fllfolleowo i ng reaction. Use nalal

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Reaction Mechanism

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. ,-unsaturated acid

Preparation of Crotonic acid -Knoengel condensation Knoengel condensation is the reaction of ann aldehydes or ketone with an active methylene group containing compoundmpoundy in presence of weak base. The product is conjugated due to loss off waterwwatOnlymolecule after addition e of the active methylene compound to thehe carbcarbonylUse group. Weaker bases are used to avoid side reaction of the aldehydesldehydehyal and ketones, such as the aldol condensation. EAA on tttreatmen twPersonaPeith acetldhdtaldehyde in thepresenceof pyridine or diethylamine as catalystalyst ggives alkylidine derivative of EAA by Knoengel condensation. This derivativeerF on hydrolysis gives crotonic acid which is ,-unsaturated acid.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Reaction Mechanism

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Cinnamic Acid EAA on treatment with benzaldehyde in the presence of pyridine or diethylamine as catalyst gives alkylidine derivative of EAA by Knoengel condensation. y

O H O C2H5O Only O e H Pyridineine C OC2H5 Knovangelvangel CondensationUseU O l al O CH3 H3C Benzaldehyde Ethyl acetoacetateetoaceta (i) KOH, Heat (ii) HCl/H2O,Heat

PersonalPe H O

ForF C OH H C2H5OH CH3COOH Cinnamic Acid

Reaction Mechanism O U O

OC2H5 l OC H ala H 2 5 NH n 2 N N CH3 on N CH 3 H H so H O HO Phenyl Hydrazine EthylacetoacetateacetoacetaPersonalPe -H2O

CH + - CH3 3 CH3SO4 ForF N N CH3 N N N CH3 N Ether N N CH3 H CH3 (CH3)2SO4 (Cyclization) O - CH3SO4H NaOH - C2H5OH O H O H - OC2H5 Antipyrine OH O

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Preparation of 4-methyl uracil EAA reactswith urea in thepresenceof (i) NOHNaOH, EtOH and (ii) Conc. HCl, EtOH to form 4-methyl uracil, which is heterocyclic compound.

O y

O O O O Only H2N NH2 NHH e OC2H5

H3C OC2H5 H2N UseU Ethyl acetoacetate alH3C NaOH EtOH

HN O O PersonalPe Conc. HCl, EtOH O oroNH NH ONa ForF H2N H C CH3 3 4-methyl Uracil

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Preparation of Acetyl acetone When EAA in benzene is treated with Acetyl chloride in presence of Mg and the resulted product is subjectedubjectedy to hydrolysis to give 1,3-diketone derivative i.e. acetyl acetone Only see

ForF

Topic: NITRO COMPOUNDSPOO Date- 16/04/2020 Only

PPe Dr. Angad Kumar Singh ForF Department of Chemistry, Central University of South Bihar, Gaya (Bihar)

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. NITRO COMPOUNDS

In this compounds are primary source of organic compounds

with functional group -NO2 to start the synthesisnthese of many other important compounds to Nitro Compound. The NO group attach e d with organiOnlycchihain iscalle d as nitro 2 e functional group. Use •All the compounds contaontaaliiini ng thenitro filfunctional group are called as organic nitro compounds.pound They are classifiedsifiedPersonalPe as • Aliphaticatic nitronitr compounds ForF • Aromatic nitro compounds Nitro Compound

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Aliphatic Nitro Compounds If the nitro functional group is attached with aliphatic carbon chain it is called as aliphatic nitro compound. Theyey are weakly acidic due to their azinitro form and they are solubleoluble in alkalies and can undergo condensation reaction with aldehydesydydeesOnly. CH -NO - Nitro methane 3 2 Use Aromatic Nitro Compounds al If the nitro functionalal grougroup is attached with benzene ring it is called as aromatic nitro compoundcompocomp . All aromatic nitro compounds are yellow colored liquidsds whichwhPersonalPe may change to dark brown color due to oxidation. ForF O N

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. The NO2 group is called as nitro group.Itiselectron withdrawing group due to its (-) Inductive effect as well as (-) Resonance effect y O O– Only O e R N+ R N+ Use RN all O– O O

Organic nitro compoundsompoumpoun are obtained by replacing one or more PersonalP hydrogen in the hydrocarbonrocarbo with nitro group. Here, the nitrogen is directly attachdhed to the carbonForF atoma intheorganicchihain.

R/Ar-NO2 Nitro compounds are named by prefixing the nitro with the root alkane name with the position. y CH NO is amino methane 3 2 Only CH3-CH(NO2)-CH3 is 2-nitropropaneropanee General method of preparation Use 1. Nitration of alkanes al 2. From alkyl halides 3. From salts of -halogenoogenoPersonalPe carboxylic acid 4. From primary amines ForF 5. From a-nitroalkenes 6. From oximes

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. By direct nitration of alkanes Alkanes are treated with nitrating mixture (fuming nitric acid) with concentrated sulfuric acid to give nitro compounds. This method will not give good yildield in case of alip hat icnitro compounds, buty will give best yildield for aromatic nitro compounds like nitro benzene. Ethane on nitration gives nitro Only ethane. e CH3-CH3 +HNO3/H2SO4 CH CHUse3-CH 2-NO2 From alky l ha lides al By treating iodoalkanesnes wiwith silver nitrite. Iodoalkanes on reacting wihith sililver niiitrite give nitroro comcompounPersonalPe ds. Thismethdhod will not give good yildield for nitro benzene. Butut all thet aliphatic nitro compounds can be prepared by thismethod . For exampmF le idiodoe thane on ttitreating with silver nitr itegives nitroethane.

CH3-CH2-I + ANOAgNO2 CH3-CH2-NO2 + AIAgI

alkanes are obtained by boiling aqueous NaNO2 with sodium salt of - halocarboxylic acids. y O O

OnlyHCl/H2O Cl Na NaNO2 O2N Na H3CNO2 NaHCO3 O seO e Use From -nitroa lkene By hdhydro lalysy i ng -nilkitroalkene inacidicmedium. CH H3C NO2 3 +/ H H2O O C CCH PersonalPeP H3CNO2 CH H3C F 3

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. From OiOxime-Primary and secondary nitro alkane are obtained in good yield by oxidizing aldooximes and ketoximes with help of trifluoroperoxyacetic acid y Only R O H R OH e R sN N UseU CH NO2 H O Trifluoroperoxyaceticacid H al H [O] n onaR O H R OH R N N CH NO2 PersonalPe R O R R ForF

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. By treating amines with alkaline KMnO4 Primary amines on treating with alkaline KMnO4 gives tertiary nitro compounds. This method works only withw primary amines. y CH3 CH3 KMnO Only H C C NH 4 e 3 2 se H3C C NO2 Use CH3 al CH3 Physical Properties of Nitroro CoCompoundssonal Aliphatic nitroocom compoundsPersPe are mostly gaseous in nature and higher members are liquids.liqu Aromatic nitro compounds are yellow color ForF liquids which intensified to brown color by time. They are polar due to the presence of nitro group.

Topic: Isomerism in Nitroo CompoundsCCo Date- 18/04/2020 Only

PPe Dr. Angad Kumar Singh ForF Department of Chemistry, Central University of South Bihar, Gaya (Bihar)

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Isomerism in Nitro Compounds The isomerism exhibited by organic nitro compounds can be classified into the following types. 1. Chain isomerism Compounds havingg samey molecularm formula and difference in the nature of carbonbonOnlychainc is called as chain isomers. For example 1-nitro butane;utane; CCH -CH -CH -CH -NO Use 3 2 2 2 2 and 2- methyl 1-nitro propanenee. CHC -CH(CH )-CH -NO al 3 3 2 2 2. Position isomerism Compoundsompouonal having same molecular formula and difference in thehe positionpospo of attachment of fu nctional group is PersPe called as positionition isisomers. For example ForF 1-nitro propane;ne CH3-CH2-CH2-NO2

and 2- nitro propane CH3-CH(NO2)-CH3

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. 3- Functional group isomers Nitro compounds are functional group isomers for nitrite compounds in which the oxygen is bonded with the carbon chain. The following diagram explains theydifference between nitro methane and methyl nitrite. Isomerism inn Nitro Compounds Only e O– H3C N + O Use H3C N O al O methyl nitrite nitro methane 4- Tautamerism In solutionolutionolutioersonalthe nitro form is in equilibrium with azinitro form. The azinitrozini Pe form is acidic in nature and hence nitro methane is soluble innForFalkalis. Hence, all the nitro compounds are weakly acidic in nature.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. O OH H3C H3C N+ + H2C HC N O– O– Nitro form Azinitrozinitroy form Only Chemical Properties of Nitro Compoundsds e Nitro compounds are dissolveve inUse bases to give salts and can be regenerated by adding a strongerrongeal acid like HCl. Similarly they can bereduc reduced to amino compounds in acidic or basic medium. PersonalPe Reaction of nitroalkaneroalkForF 1. Reduction 3. Halogenation 5. Condensation with 2. Hydrolysis 4. Reaction with nitrous acid aldehydes and ketones

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. 1. Re duc tion of ali ph ati c nit ro compound s Aliphatic nitro compounds can be reduced to amines by treating with Sn/HCl. This is the effect way to convert nitroro compoundscoy to amines. CH NO CHNH 3 2 3 2 Only Aliphatic nitro compound canbe reducedrede to hydroxyl amines by treating with diborane. Use al CH3NO2 CHH3NHOHNH Aliphatic nitro compoundsompoun are reduced to oximes using stannous chloride. PersonalPe CH NO CH-N = OH 3ForF 2 3 Reduction of aromatic nitro compounds Nitro benzene can be reduced to aniline by Sn/HCl.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. NO2 NH2

Sn/HCl y nlyl Nitro benzene is reduced to phenylyl hydroxylaminehydOnly , when nitro e benzene on treating with Raney Nickle.e Use OH NO2 al HN

erser Ni PersonalPe or +/ 2. Hydrolysis of nitro compoundsco ForF H H2O RCOOH H2NOH R NO2 R O +/ H H2O C N2O H2O R NO2 R R

H Br

R C NO2 2Br2 2NaOH R C NON 2 2NaBr 2H2O y H Brn R OnlyR e R C NO H O 2 Br2 NaOH UseUs R C NO2 NaBr 2 H al Br 4. Reaction of nitro compoundsds witwith nitrous acid Tertiary Nitro compound do not react with Nitrous AcidPersonalPe bbecause they have no -Hydrogen H H OH ONa

+ NaOH + R C NO2 HO N O R C NO2 R C N R C N -H2O -H2O ForF O– – H NO NO NO O Blue Solution Red Solution

R R

R C NO2 HO N O R C NO2 -H2O H NO Blue Solution

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. 5. Condensation with aldehydes and ketones The condensattion of a nitroalkane and an aldehyde or ketone in the presence of a base to form -nitro alhllcohols. Thisstyp typey of reaction isalso referred to as a nitroaldol reaction (nitroalkane,kane, aaldehyde, and alcohol) Only or Henry Reaction. e

ForF

Topic: Nucleophilic Aromatic Substitutionstitut Reaction Date- 19/04/2020 Only

PPe Dr. Angad Kumar Singh ForF Department of Chemistry, Central University of South Bihar, Gaya (Bihar)

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia.

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Nucleophilic Aromatic Substitution Reaction In nucleophilic aromatic substitution reaction, a strong nucleophile replaces a leaving group e.g. a halide. A nucleophile can be introduced into the ring provided it is sufficientlyy -yelectron deficient due to the presence of an electron withdrawing grouproup e.g.e.g nitro (-NO2). Only The more effective leaving groupsgrouroe are the halogens. The nucleophile attacks the carbon atomomUse to which the leaving group (a halogen atom) is attached. In thehealproductp the nucleophile is on the position of the original substituent.ituent The aryl halidede themselvesthemthe undergo nucleophilic substitution PersonalPe with great difficultyulty unlessun strong electron withdrawing groups are present in ortho or parapapForF position to the halogen atom. It is only then that the mesomeric withdrawal of electrons is possible to make the stable intermediate (cyclohexadienyl anion).

substitution (represented as SNAr mechanism) In the mechanism first slow step, addition by nucleophilen gives an y anion with highly delocalized charge. Only Insecond ftfast step, the lileaving groupeiselimi nat ed to regenerate the aromatic ring. Use al Cl Cl OH OH Cl OH Cl OH Cl OH OH-

Fast Slow erers PersonalPeP

+ + N NO NO N+ N – 2 2 NO2 O O ForF –O O –O O-

Resonance Stablization

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. The reactivity of haloarenes in the nucleophilic substitutions increases with the number of electron withdrawing groups on the ring, particularly if they are in ortho or para positions.s. y The reaction become facile when twooorOnly or more nitro groups are present in ortho or para positions asindicate indicatede by rate data ( reaction with –OCH /CH OH, 50ºC) Use 3 3 al Cl Cl Cl Cl

NO2 O2N NO2 PersonalPeP orr NO ForFoF 2 NO2 NO2

Increasing rate of Aromatic Nucleophilic Substitution

In strong acidic medium,edium, nitrobenzene is reduced to aniline in presence of Sn/HCl. PersoPe In neutralmedium medium, nitrobenzene is reduced to nitrosobenzene in presence of Zn dust anForFd ammonium chloride. In acidic medium, nitrobenzene is reduced to a mixture of nitrosobenzene and phenylhydroxyl amine

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. NH2

lyy Cl /H Sn Only O N NO2 e Use Zn/NH4Clnal

H + O OH PersonalPeP N HN ForF

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. PICRIC ACID The aromatic ring of phenol is highly activated towards eelectrophiliclectrophilic substsubstitutionitutionrreactions,eactions, aandnd atteattemptedmptedd ninitrationtration ooff pphenol,henol, even with dilute nitric acid, results in the formationy of high molecular Only weight tars. e In order to minimize theseside Use rereactions, anhydrous phenol is su lfonated with fmingfuming slfricsulffurical acid, and the resu lting p- hydroxyphenylsulfonic aciddist is then nitrated with concentrated nitric acid. During this reaction,PersonalPe nitro groups are iddintroduced,and thesulfoni c acid group is displaced.placed. The reaction is highly exothermic, and careful temperature controlForFi is required.

OH OH OH

O2N NO2 PersonaPe SO3H Conc. H2SO4 Conc. H2SO4 ForFoF

NO2 SO3H

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia. Uses of nitro compounds • They are useful intermediates in the preparation of amino compounds and diazonium salts which arey synthetic important materials to prepare almost all organicicOnly compounds.com • Nitro benzene is used in shoe and floorflooe polishes. • It is also used in paint andsolv solventsUse and to mask unpleasant odor al in chemicals. • They are used to ppprepare the azo-dyes and in soil sterility. • It is used innt thehePersonalPe manufacture of Paracetamol (a popular analgesic) ForF

Note: These materials are only for classroom teaching purpose at Central University of South Bihar. All the data taken from several books, research articles including Wikipedia.