Heterocyclic Chemistry Flashcards
Heterocyclic compounds
Cyclic compounds in which a ne or more ring atoms are other than carbon. These are also known as heterocycles. Most of the common heterocyles contains nitrogen, oxygen, sulphur, etc replaced for a carbon atom. The numbering of the compound starts at the herero-atoms
Pyridine
An aromatic heterocyclic compound in which one -CH is replaced by a nitrogen.
Pyridine physical properties
Colourless liquid
Very soluble in water
Found in bone oil
Sour
Fish like odour
Pyridine chemical properties
Planar
Hexagonal
All atoms are sp2 hybridized and has one unhybridized p orbital
6 pi electrons
Follows huckles rule
Basicity of pyridine
Pyridine is weaker base than aliphatic
amines because the sp electron paint is held more tigthly, due is the greater sā character and it is thus available for sharing than an sp3 electron pair in aliphatic amine
-pyridine is more stronger base than pyrrole becz the lone pair of the nitrogen is present in the third sp2 orbital (not part of aromatic sextet ) and thus available for sharing with a proton (Lewis base). However, in Pyrole the lone pair is past of series, not available for sharing
Preparations of pyridine
1- by passing a mixture of acetylene and hydrogen cyanide through RHT
2- by hearing pentomethylene dianine initially the product pipeudine is formed which after dehydrogenation either catalytically or by hearing with concentrated H2SO4 is converted to pyridine
3- hantzsch synthesis
General method for the preparation of pyridine variations, which involves the condensation of Alderney and B ketoester and ammonia with another B Ketoester.
Reactions of pyridine
1- reaction as base: due to the free lone pair of pyridine, it acts as a weak base and form pyridinium salts with strong acids
2- reactions as nucleophile: reacts with alkyl halides tonforn alkyl pyramidine salts with acyl chloride to form acyl pyridinium salts
ES of pyridine
ES occurs in most of the aromatic compounds the structure of pyridine shows that the electron withdrawing effect of the electron atom makes the aromatic ring of pyridine electron deficient towards the EAS. Thus the aromatic ring in deactivated to the EAS rxns. But these r two positions (ie 3,5) at which the carbon atoms are still electron rich so if EAS rxn takes place it will occur at (c3, 5). For pyridine only nitration, sulphonation, and halogenation takes place. Fried crafts rxns do not occur for pyridine at all
NS rxn for pyridine
The pyridine ring decactivales for the EAS due to electron withdrawing group. However, for NS reactions the pridine ring is activated. Thus, the pyridine is more reactive towards NS rxn. By canonical forms, the position 2, 4 and 6 are election deficient so the nucleophile wil attack at C 2,4, or 6
Hydrogenation
Alkylation and acylation
Hydrogenation- the pyridine is hydroxylated to 2-hydropyridine by heating with KoH at 320c. It does not give phenolic properties
Alkylation/ acylation- pyridine can alkylated or acylated on heating with an appropriate organolithiun compound
Reduction and oxidation of pyridine
Reduction- either catalytically of with sodium and ethanol yeikda piperidine
Oxidation- pyridine is resistant to oxidation it is used as solvent in chromium trioxide oxidation. However, pyridine can be oxidize to pyridine N- oxide on treatment with per acids such as peracetic acid or perbenzoic acid
Pyrrole
5 membered ribg
Aromatic
Colourless liquid
b.P 131C
Turn dark on exposure to light
Physical properties of pyrrole
Planar
Hexagonal
Aromatic
Sp2 hybridized
Basicity of pyrrole
Extremely weaker base because usually the lone pair of nitrogen in pyrrole is part of aromatic sexlet and is this not available for the proton to bind with
Preparations of pyrrole
1-by the pyrolysis of Diammonium mucate
2- heating acetylene with NH3 in red hot tube
3- steam distillation of succinamide in Zn dust
4- on commercial scale it is prepared by passing a mixture of furan, ammonia Steam over hearted alumina at 400c
5- paal-knor synthesis: pyridine derivative is prepared by heating 1,4 dicarbonyl compounds
6- knorr pyrrole synthesis: condensation of alpha amino ketone and beta Keto ester
Reactions of pyrrole
1- salt formation: lacks basicity is acidic enough to form potassium salt when fused with KOH. The imino hydrogen is replaced by potassium
2- reduction- catalytic hydrogenation of pyrrole converts it into pyrrolidine
3-polymerization- in the presence of concentrated acids pyrrole undergoes polymerization
EAS rxn if pyrrole
Pyrrole is more reactive towards EAS rxns becz the lone pair is part of aromatic sexlet and the charge density increases in the aromatic ring. All positions of the ring are equal charge density for the attack if electrophile. However less the charge separation grater the stability, less charge separation at C2 and C5. So the electrophile will preorder to attack at C2 and 5. Mildest conditions are required for carrying out EAS rxns
Furan
furan gets its name from the latin word āfurfurā which means bran. it is penagon, planar, aromatic, and sp2 hybridized. the lone pair of oxygen resides in sp2 hybrid orbital and second lone pair of oxygen resides in completely filled unhybridizeed p-orbital
propertis of furan
five memebered
pentagonal heterocyclic compound
sp2 hybridized and thus planar
the CH is replaced with O having two lone pairs in which lone pair resides in the sp2 orbital and the other lies n the unhybridized p obital (not part of aromatic sexlet).
colourless mobile liqud
BP is 32C
odour of chlorofom
insoluble in water
soluble in alcohol and ether
basicity of furan
furan>pyrrole>thiophene
-it is a hughly weak base as oxygen can donate lone pair easily
more reactive than pyrrole
preparations of furan
1- by oxidiing furfural by K2Cr2O7 to furoic acid which is then headted ti remove CO2 to form furan
2- by dehydration of succinicdialaldehyde by dehydrating agent
reaction of furan
EAS rxn- is more reactive towards EAS rxns than benzene and pyridine. The electron density inside the aromatic sexlet is greater so mildest conditons are required to carry out EAS rxns
-sulphonation
-nitration
-bromination
-FC alkylation
Reduction- catalytic hydrogenation of furan reduces it to tetra-hydrofuran
Thiphene
analogus of pyrrole but the heteroatom is replaced by āsā
properties of thiophene
pentagonal
heterocylci aromatic compound
with heteroatom S
colourless liquid
BP 84C
close to benzene like benzene found in coal tarr.
Insoluble in water
soluble in organic solvents
sp@ hybridized
plnar
Sp2 hybrid orbitals are surrouned by lone pairs
Preparatiosn of thiophene
1- by passing acetylene with hydroen sulphide over heated alumina
2- by reacting n-butane with sulphur
reactions of thiophene
highyl reactive towards EAS rxns as pyrrole an furan occurs profreutically at C2
-nitration
-sulphonation
-chlorination
-bromination
-acylaion
-reimer teiman
-nitronation
-diazocoupling
diazines
are the group of organic compound which contains the benzene ring in which two -CH units are replaced by two nitrogen atoms. Thus, the structural formula is C4H4N2. the two most common diazines are pyrimidine and pyrazine
Pyrimidine
pyrimidine is an aromatic heterocyclic compound similar pyridine with addition of a second nitrogen. The two nitrogens are present at C-1 and C-3. Thus, pyrimidine is also called 1, 3-diazine. Pyrimidine is found in nucleic acids i.e the nitrogenous bases uracil, cytosine, and thyamines are derivitives of pyramidine
physical properties of pyrimidine
colourless crytalline solid with melting point 22C
dissovles in water to give neutral solution
reacts with mineral acids to form salts
bp 123-124 C
chemical properties of pyrimidine
pi electron dedfficient due to addition of anotheer N-atom (electronegative) make it more electron defficien and thus more weaker base than pyridine. Due to de-activation of aromatic ring, pyrimidine does not undergo EAS reactions. Howeevr ubstitution reactions and acid-base reacion occur in pyrimidien
preparation of pyrimidine
1- by cyclization of B-carbonyl compounds with N-CN compounds
reactions of pyrimidine
1- with acids
pyrimidine acts as weaker base so it reacts with string acids to form pyrimidinium saks
2- nucleophillic substitution reacionpoition number 2,4, and are elctron defficient so nuclephile will prefer to attack at the position 2 preferably
-chichibabin rxn
-hydroxylation
-alylation and acylation
pyrazine
pyrazine is also heterocyclic aromatic ompound with two atoms at position 1 and 4. Thus, pyrazine is also called para-diazine. pyrazines and variety of alkylpyrazines are flavor and aroma compounds found in baked and roasted goods
physical properties of pyrazine
deliquescent crystal or wa-like solid with a pungent, sweet, corn like nuttry odour
chemical prperties of pyrazine
weaker base due to electron withdrawing effect of the electronegative atom whih makes the ring elecron defficiant (deacivate it) thus, pyrazine also does not undergoes EAS rxns. however favours nucleophilic substitution
preparation of pyrazine
pyrazine can be prepared by reacting dicarbonyl compound with amictine
reactions of pyrazine
1-with acids: same as pyrimidine
2- nuclephillic substitution
-chichibabin
-hydroxylation
-alkylation and acylation
3-reduction: pyrazine also undergoes reduction catalytically and form piprazine by hydrogenation
Indole
it is also called benzopyrrole, made up of benzene ring fused with pyrrole ring. it occurs in coal tar, in jasmine flower and in orange blossom. it is the prent substance of indigo
physical properties of indole
indole forms plate like crystals
mp=52C.
when not quite pure it has a strong feacal odour, in contrast pure indole in high dillution has a flowery odour. it is a planar heterocyclic aromatic compound
sp2 hybridized and follows huckles rule becz 10 pi electrons in whcih two are shared by N-atoms
`
chemical propertes of indole
resembles qith pyrrole in i chemical reactiit the elctron ensity inside the ring is increased due to the lone pair of pyrrole and favours EAS rxns with milder condition. Also undergoes reduction. Nucleophillic substitution reactions are not favoured as the ring is already electron rich
preparations of indol
1- by fischer method which involves the reaction of phenyl hydrazine with ketone in the presence of ZnCl2
2- by treating alpha-amino styryl chloride with sodium alcohalate
reactions of incole
1- EAS rxns: as reacitivity resembles to pyrrole so EAS rxns also occurs at position 3 as in pyrrole
-nitration
-culphonation
-bromination
FC acyation
-mannich reaction
2- reduction: indole undergoes two types of reduction with different condition to form two different products
Quinoline
also called 2,3 benzopyridine. It is a bicyclic compound formed by the fusion of benzene and pyridine ring. It is also known as 1 azanaphthalene or made up of a benzene ring fused with a pyridine ring in a,b-positions. Thus, it has the same relation to napathalene as pyridine has to benzene
-it is present in small amount in coal tar and bone oil
pysical properties in quinoline
it is a colourless oily liquid
bp- 238C having a sharp disogreable odour, resembling somewhat to quiline. it is volatile in steam
chemical properties in quinoline
combines tehe behaviour of both the benzene and pyridine. Thus, will carry out EAS rxns for benzene ring ans nuleophillic substitution for pyridine. It also undergoes acid-base reactions reduction, oxidation and also act as nucephile like pyridine
preparation of quinoline
1- Skroups method: reaction which incolves the heatng of aniline, glycerol, conc H2SO4 and a mild oxiding agent such as nitrobenzene togehter. FeSO4 is also added after to make reaction less violent
reactions of quinoline
1- acid-base rxn: as a weak base, reacts with strong acid to form salts
2- with alkyl halide: act as a nucleophile
3- EAS rxns- occurs on the benzene ring. as only position 5 ad 8 are elctron rich so elctrophile will preferably attack at these posiion.
-nitration
-sulphonation
-bromination
4- nuclephillic substitution rxn: nucleophilic substitution occurs at position 2 in the pyridine ring as it is electron deffiennt position so nucleophile will prefer to attack
-chichibabin
-hydroxylaion
-alkylation and acylaion
5- oxidation
6-reduction
isoquinoline
it is made up of benzene ring fused with a pyridine ring in a different posiion than in quiniline. Isoquiniline is present in coal tar, along with quinoline, it may be separated from he latter by ractional crystallization of theur sulphates fromalcohol in which isoquinoline sulphate is only sparingly soluble
physical properties of isoquiniline
colourless crystalline solid
mp 24
bp 20
odour resembling somewhat of benzalaldehyde
-stronger base than quinoline
chemical properties of isoquinoline
chemical properties of isoquoniline, both have same chemical rxns but pyridine ring in isoqinoline is not very stable as in quinline so give different products on oidation. the position and numbering will be same even if the position of nitrogn changes because it is the isomer of quinoline.
reactions of isoquinoline
1- oxidation: benzene and pyrimidine ring are both oxidised
