ORGANIC CHEMISTRY REACTION SCHEME AN OVERVIEW ALKANES

Preparation of Alkanes 1. Hydrogenation of Alkenes

H2 + Ni, Pd or Pt CnH2n CnH2n+2

2. Reduction of Alkyl Halides a. Hydrolysis of Grignard Reagent dry et!yl et!er "ater RX + g R gX RH +

g#$H%X

&Note' R gX is t!e Grignard reagent, alkyl(agnesiu( !alide. )!e alkyl group is co*alently +onded to (agnesiu(, and (agnesiu(-!alogen +ond is ionic ie. .R' g/+.X/0. 1n t!e second step of t!e reaction, it is a displace(ent reaction in "!ic! "ater #t!e stronger acid% displacing t!e "eaker acid #R0H% fro( its salt #R gX%.

+. Reduction +y

etal and Acid

2+ 0 2n + H RX RH + 2n + X
+

Reactions of Alkanes 1. Halogenation [Free Radical Substituti !" !eat, or 34 CnH2n+1H + X2 CnH2n+1X + HX 2. Co(+ustion !eat CnH2n+2 + e5cess $2 nC$2 + #n+1%H2$ 6. Pyrolysis Cracking 788-988 C H2 + s(aller alkanes + alkenes alkane "it! or ":o catalyst

ALKENES
Preparation of Alkenes 1. ;e!ydro!alogenation of Alkyl Halides H H

H H C

H C + < X + H 2$ H

C H

C X

alco!olic <$H H + $H reflu5

2. ;e!ydration of Alco!ols H H

H
e5cess conc H2 =$7 , 1>8 C H H or Al2 $6 , 788 C or H6P$7 , 288-2?8 C

H C H+ H 2$

C H

C $H

6. ;e!alogenation of 4icinal ;i!alides H H

H
2n H H

H C H+ 2 n X
2

C X

C X

Reactions of Alkenes 1. Addition of Hydrogen. Catalytic Hydrogenation H2 + Ni, Pd or Pt CnH2n+2 CnH2n Heat

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2. Addition of Halogens [Electr #$ilic Additi ! usi!% br &i!e'et$e!e" H H H H

X2 :CCl7 H dark, roo( te(perature

C X

C X

6. Addition of A@ueous Halogen. Aor(ation of Halo!ydrin H H H

H C $H H H C H H H C $H H H C $H H+ H 2= $
7

X2 :H2 $ H H

C X

H+ H X

;ark, roo( te(p

7. Addition of Hydrogen Halides H

H C
HX H H

C X

?. Addition of Bater. Hydration a% 1ndustrial et!od H H

H2 $#g% conc H6 P$7 688C, 98at(

C H

+% Ca+oratory H H

et!od

H H C H

H C H
H2 $, !eat H #!ydrolysis%

conc H2 =$7 cold

C H

$= $ 6 H

9. $5idation a% Cold, alkaline < n$7 =olution H H

H
alkaline < n$ 7 H cold

H C H

$H $H
+% Hot, acidic < n$7 =olution H H

H $ + $ C H

n$7 :H2 =$7 H !ot

&Note' )er(inal car+ons "ill +e o5idiDed into car+on dio5ide. &Note' 3nder suc! o5idiDing conditions, t!e alde!ydes "ill +e o5idiDed to car+o5ylic acid *ery @uickly. )o e5tract t!e alde!yde only, "e (ust use i((ediate distillation.

>. Co(+ustion

ARENES
Reactions of EenDenes 1. Nitration [Electr #$ilic Substituti ! i! & ! !itrati ! ( be!)e!e" N$2
conc. HN$6 conc. H2 =$7

??oC

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2. =ulp!onation
H2 =$7 # l % reflu5

$=$ 2H + H 2$

6. Halogenation

X + X
2
cold, dark AeX6 , or AlX6

+ HX

$r Ae 7. Ariedel-Crafts Alkylation

R + RX
AeX6 , or AlX6 Ce"is Acid

+ HX

?. Ariedel-Crafts Acylation

C$R
Note' acyl group

+ R C $ C l : .#R C $ % 2$ /

AeX6 , or AlX6

+ HX
R C

9. Hydrogenation

+ 6H

Ni 1?8C

Preparation of Alkyl+enDenes 1. Attac!(ent of Alkyl Group. Ariedal-Crafts Alkylation

R + HX

+ RX

AeX6 , or AlX6 Ce"is Acid

2. Con*ersion of side c!ain R

H C $
2n#Hg%, HCl, !eat or N2H7 , +ase, !eat

H R
NX 2 + H2 $ + H

C
$r H2:Pd, et!anol

&Note' )!is is kno"n as t!e Cle&&e!se! r W l((*Kis$!er Reducti !

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Reactions of Alkyl+enDenes 1. Hydrogenation

R + 6H
2
Ni, Pt, Pd 1?8C

2. $5idation a. ild $5idation

R
n$2 o5idation

CH$

+. =trong $5idation

R
n$7 :H2 =$7 or acidified < 2 Cr2 $>

C$$H " ! ite c r y s ta ls

6. Aree Radical Alip!atic Halogenation RCH6

X2 34, lig!t or !eat

RCH2X

&Note' Reaction a+o*e is only a generic reaction. Actual position of t!e !alogen is dependent on t!e sta+ility of t!e car+ocation inter(ediate.

7. Flectrop!illic Aro(atic Halogenation +y Flectrop!illic Addition R R

X
X2 AeX6 , AeX?

X
?. Flectrop!illic Aro(atic Nitration +y Flectrop!illic Addition R R

R N$2

conc HN$6 conc H2 =$7

68 C

N$2
9. Flectrop!illic Aro(atic Ariedal-Crafts Alkylation +y Flectrop!illic Addition

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R R1
R1X AlX6

R1

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>. Flectrop!illic Aro(atic =ulp!onation +y Flectrop!illic Addition R R

$=$ 2H
H2 =$7 # l %

$=$ 2H
G. Flectrop!illic Aro(atic Ariedal-Crafts Acylation +y Flectrop!illic Addition R R

C$R1 + R 1C $ C l : .#R 1C $ %2$ /

AeX6 , or AlX6

C$R1
Alkyl+enDenes clearly offers t"o (ain areas to attack +y !alogens' t!e ring and t!e side c!ain. Be can control t!e position of t!e attack si(ply +y c!oosing t!e proper reaction conditions. Refer to Appendi5 for (ore details.

HALOGEN +ERIVATIVES
Preparation of Halogenoalkanes 1. =u+stitution in Alco!ols a. 3sing HX #suita+le for 6 alco!ols% dry HX, 2nX2 #catalyst% R0X + H2$ R0$H Reflu5 +. 3sing PX6:PX? #suita+le for 1, 2 alco!ols% PX6 :PX ? R0X + P$X6 + HX R0$H Reflu5 c. 3sing =$Cl2 #sulp!onyl c!loride% =$Cl2 , Pyridine#C? H? N% R0Cl + =$2 + HCl R0$H Reflu5
&Note' )!is is t!e +est (et!od +ecause it is *ery clean. =$2 can +e +u++led off and HCl, +eing an acid, "ill react "it! pyridine.

2. Flectrop!illic Addition to Alkenes a% Addition of Hydrogen Halides H H

H
HX H H

H C H H H C X H H

C X

+% Addition of Halogens H H

X2 :CCl7 H dark, roo( te(perature

C X

6. Aree Radical =u+stitution of Alkanes !eat, or 34 CnH2n+1H + X2 CnH2n+1X + HX

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Reactions of Halogenoalkanes 1. Alkaline Hydrolysis of Alco!ols [Nucle #$ilic Substituti !" a@ueous <$H R0$H + X0 R0X + $H0 reflu5
&Note' ec!anis( is =N2 for 1 !alogenoalkane and =N1 for 6 !alogenoalkane

2. Nitrile =ynt!esis
a@ueous et!anol R0CHN + NaEr R0X + NaCN reflu5

&Note' Nitriles are useful +ecause t!ey can +e used to synt!esiDe 1o a(ines and car+o5ylic acids. Reduction to A(ine' CiAlH7 , dry et!er RCH2NH2 R0CHN or 2H2 , Ni, !eat Acidic Hydrolysis' RC$$H + NH7+ R0CHN reflu5
HCl # aq %

Easic Hydrolysis' RC$$0Na+ + NH6 R0CHN reflu5

Na$H # aq %

6. Aor(ation of A(ines
et!anol, reflu5 NH6 .H6N---R---X/ RNH2 + NH7+X0 R0X + e5cess conc NH6 sealed tu+e
+

&Note' NH6 acts as t!e nucleop!ile and t!e +ase. &Note' 1n t!e presence of e5cess RX, t!ere "ill +e polyalkylation of t!e !alogenoalkane and 1, 2, 6 and e*en 7 a((oniu( salt "ill +e for(ed.
RX RX RX RX NH6 RNH2 R2NH R6N R7N+X0

Conc H =$ , 178 C 7. Billia(son =ynt!esis #Aor(ation of Ft!er% 0 R0$0RI + NaX R0X + RI$ Na+
2 7 o

&Note' )!e sodiu( or potassiu( alko5ide #anion of alco!ol% is prepared +y dissol*ing sodiu( and potassiu( in appropriate alco!ol. R$H + Na R$0Na+ + JH2

?. ;e!ydro!alogenation #Fli(ination% H H

H C

H C H + < X + H 2$

C H

C X

alco!olic <$H H H + $H #aq % reflu5

Preparation of Halogenoarenes #Aryl Halides% 1. Flectrop!ilic Aro(atic Halogenation +y =u+stitution

X + HX

+ X

cold, dark AeX6 , or AlX6

Reactions of Halogenoarenes 1. 1ndustrial Hydrolysis #Replace(ent of Halogen Ato(, difficult due to strong C0X +ond% + X $ Na
2Na$H 6?8C, 1?8at(

+ N aX

+ H 2$

+ $ Na
H # aq %
+

$H + Na
+

2. Billia(son =ynt!esis #Aor(ation of Ft!er% R0$0Ar + NaX R0X + Ar$0Na+

Conc H2=$7, 178oC

>

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HY+RO,Y COM-O.N+S
Preparation of Alco!ols 1. Alkene Hydration. Addition of Bater. H H

H C H

H C H
H2 $, !eat H #!ydrolysis%

H C H

H C $H H+ H 2= $
7

conc H2 =$7 cold

$= $ 6 H

2. Alkaline Hydrolysis of Halogenoalkanes a@ueous <$H R0$H + X0 R0X + $H0 reflu5 6. Reduction of Car+o5ylic Acids, Alde!ydes and <etones a. Car+o5ylic Acids and Alde!ydes are reduced to t!eir pri(ary alco!ols. H R

C H$ R

7 .H /

1. CiAlH7 #et!o5yet!ane%, reflu5 2.H :H2 8 or H2 , Ni

C H

$H

+ H 2$

H C $

7 .H /

1. CiAlH7 #et!o5yet!ane%, reflu5 2.H :H2 8 or H2 , Ni

C H R

$H

H
+. <etones are reduced to t!eir secondary alco!ols. R

7 .H /

1. CiAlH7 #et!o5yet!ane%, reflu5 2.H :H2 8 or H2 , Ni

R1

$H

R1 H &Note' Cit!iu( alu(iniu( !ydride #or Cit!iu( tetra!ydridoalu(inate#111%%, CiAlH 7, is one of t!e fe" reagents t!at can reduce an acid to an alco!ol, t!e initial product is an alko5ide "!ic! t!e alco!ol is li+erated +y !ydrolysis.
)!e 0H ion acts as a nucleop!ile, and can attack t!e car+on ato( of t!e car+onyl group. )!e inter(ediate t!en reacts "it! "ater to gi*e t!e alco!ol. $H R $ H6C H6C H 2$ C C $ C H H 0 H H H H H2$ Car+o5ylic Acid' 7RC$$H + 6CiAlH7 7H2 + 2CiAl$2 + #RCH2$%7AlCi 7RCH2$H
H2$ <etones' 7R2CK$ + CiAlH7 #R2CH$%7AlCi 7R2CH$H + Ci$H + Al#$H%6

Reactions of Alco!ols 1. =u+stitution in Alco!ols a. 3sing HX #suita+le for 6 alco!ols% dry HX, 2nX2 #catalyst% R0X + H2$ R0$H Reflu5 +. 3sing PX6:PX? #suita+le for 1, 2 alco!ols% PX6 :PX ? R0X + P$X6 + HX R0$H Reflu5 c. 3sing =$Cl2 #sulp!onyl c!loride% =$Cl2 , Pyridine#C? H? N% R0Cl + =$2 + HCl R0$H Reflu5
&Note' )!is is t!e +est (et!od +ecause it is *ery clean. =$2 can +e +u++led off and HCl, +eing an acid, "ill react "it! pyridine.

2. Reaction "it! =odiu(:Potassiu( H

H
=odiu(:Potassiu( H

C H

C H

$ Na

1 H 2

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&Note' Alco!ols are too "eak to react "it! !ydro5ides and car+onates.

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6. $5idation to Car+onyl Co(pounds and Car+o5ylic Acids a. Pri(ary Alco!ols are o5idiDed to alde!ydes first, t!en car+o5ylic acids. R R R $H < 2 Cr2 $> :H2 =$7 < 2 Cr2$> :H2=$ 7 C $ C C i((ediate or < n$7 :H2 =$7 distillation H H H$ H
&Note' n$2 is also a (ilder o5idiDing agent.

+. =econdary Alco!ols are o5idiDed to ketones. R R $H < 2 Cr2 $> :H2 =$7 C C or < n$7 :H2 =$7 R1 R1 H c. )ertiary alco!ols are not readily o5idiDed.

7. ;e!ydration to Alkenes a. F5cess conc H2=$7 H H

H
e5cess conc H2 =$7 , 1>8 C H H or Al2 $6 , 788 C or H6P$ 7 , 288-2?8 C

H C H+ H 2$

C H

C $H

+. F5cess alco!ol 178C R0CH2$H + conc H2=$7 R0CH20$0 CH20R e5cess alco!ol ?. Fsterification

$ $ R1
conc H2 =$ 7 !eat

R C $H

$ H

C R $

R1

#can use acid or alkaline as catalyst%

H 2$

9. Acylation a. Acid C!loride

Note' acyl group

C $

Cl

R1

$H

roo( te(perature

C $

R1

+ HCl
R C

+. Acid An!ydride

C $

C $

+ R1 $H

roo( te(perature

C $

R1

C $

$H

>. )ri-1odo(et!ane #1odofor(% Aor(ation

&Note' Reaction is only positi*e for alco!ol containing a (et!yl group and a !ydrogen ato( attac!ed to t!e car+on at "!ic! t!e !ydro5yl group is also attac!ed.
H R C CH6 $H
12 , Na$H # aq % "ar(

H H C CH6 $H

CH16

a. =tep 1' $5idation of Alco!ol to t!e corresponding car+onyl co(pound +y iodine.

CH CH6

$H

1 2 + 2 H$

C CH6

+ 2 H2 $

+ 2 1

18

n!8?

+. =tep 2' Aurt!er o5idation to car+o5ylate salt and for(ation of iodofor(

C CH6
c.

+ 6 12 + 7 H$

C $
-

+ CH16 + 6 1

+ 6 H 2$

H C

$*erall F@uation'

$H + 7 1 2 + 9 H$

C $
-

+ CH16 + ? 1

+ ? H 2$

CH6
Preparations of P!enols 1. Replace(ent of $H0 group in diaDoniu( salts N

$
-

NH2

+ N $

= $

$H

$H

NaN$2 , H2 =$7

"ater, H , !eat

Reactions of P!enols 1. Reaction "it! Reacti*e

etals #e.g. Na or

g%

$H

$ Na

Na

1 H 2 2

2. Reaction "it! Na$H

$H

$ Na

+ Na$H
&Note' P!enols !a*e no reactions "it! car+onates

1 H $ 2 2

6. Fsterifications

$H
Na$H

$ Na

+
RC$Cl

$ C R

&Note' P!enols do not react "it! car+o5ylic acids +ut t!eir acid c!lorides to for( p!enyl esters. &Note' Fsterification is particularly effecti*e in Na$H#a@% as t!e alkali first reacts "it! p!enol to for( p!eno5ide ion "!ic! is a stronger nucleop!ile t!an p!enol.

11

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7. Halogenation a. Bit! +ro(ine#a@%

$H Er
6Er2 # aq %

$H

Er

+ 6HEr

Er
&Note' 2,7,9-tri+ro(op!enol is a "!ite ppt.

+. Bit! +ro(ine#CCl7% $H
Er2 #CCl7 %

$H

$H

+
Er Er

?. Nitration a. Bit! conc nitric acid

$H $ 2N
conc HN$6

$H N$2

N$ 2
+. Bit! dilute nitric acid $H
dil HN$6

$H

$H

+
N$2 $ 2N

9. Reaction "it! AeCl6#a@%

&Note' )!is is a test for p!enol. 4iolet co(ple5 upon adding iron#111% c!loride "ill confir( presence of p!enol. Colour (ay *ary depending on t!e su+stitution on t!e ring.
6 --

$H
Ae
6+

$ Ae
9

12

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CAR/ONYL COM-O.N+S
Preparation of Alde!ydes 1. $5idation of Pri(ary Alco!ols R $H < 2 Cr2$> :H2=$ 7 C i((ediate distillation H H

R C H $

H 2$

Preparations of <etones 1. $5idation of =econdary Alco!ols R R $H < 2 Cr2 $> :H2 =$7 C C or < n$7 :H2 =$7 R1 R1 H 2. $5idati*e Clea*age of Alkenes R2 R6

+ H 2$

R2
n$7 :H2=$7 !ot

R6 + $ $ C R7

C R1

C R7

C R1

Reactions of Car+onyl Co(pounds 1. Addition of Cyanide. Cyano!ydrin for(ation. [Nucle #$ilic Additi ! ( H0dr %e! C0a!ide t Alde$0de a!d Ket !e" H H H C HCN, s(all a(ount of +ase + CN C CN H

$
&Note' Cyano!ydrins can +e !ydrolysed to for( 2-!ydro5y acids. Acidic Hydrolysis
R C $H R C $H H CN
"ater, HCl #a@% !eat

$H

C$$H

+ NH7Cl

Easic Hydrolysis
H

R C $H CN
"ater, Na$H # aq % H !eat

R C $H C$$ Na
+

NH6

&Note' Cyano!ydrins can undergo reduction.

R C $H R CN
CiAlH7 in dry et!er or H2 , Ni, !eat

C $H

CH2NH2

R2

2. Reaction "it! 2,7-;initrop!enyl!ydraDine #EradyMs Reagent%. Condensation Reaction. R2

C $ + H2N NH N$2 R1 $ 2N $ 2N &Note' 2,7-dinitrop!enyl!ydraDones for(ed are orange or yello" crystalline solids "it! c!aracteristic (elting points. )!ey are useful for identifying indi*idual alde!ydes and ketones. C N NH N$2 + H2$

R1

16

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6. $5idation Reactions
&Note' Alde!ydes are easily o5idiDed to car+o5ylic acids. <etone are not.

a. $5idation of Alde!ydes using !ot, acidified potassiu( dic!ro(ate#41%

&Note' <2Cr2$> turned fro( orange to green if test is positi*e.

R
< 2 Cr2 $> :H2 =$ 7 !eat

$H C $

C $ $ C R C $ H R1

$
< 2Cr2 $> :H2 =$7 !eat

C $H

< 2 Cr2 $> :H2 =$7 N o R e a c tio n !eat

+. $5idation of Alde!ydes using !ot, acidified potassiu( (anganate#411%

&Note' < n$7 turned fro( purple to colourless if test is positi*e.

R
< 2 n$7 :H2 =$7 !eat

$H C $

C $ $ C H
c.

$
< 2 n$7 :H2 =$7 !eat

C $H
-

$5idation of Alip!atic Alde!ydes using Ae!lingMs =olution #Ae!lingMs )est%

R C $

H
Ae!lingIs =olution "ar(

R C $ $ C H

Cu2$ #s%

Ae!lingIs =olution N o R e a c tio n "ar(

R C $

R1
Ae!lingIs =olution N o R e a c tio n "ar(

&Note' Alip!atic alde!ydes reduce t!e copper#11% in Ae!lingMs solution to t!e reddis!-+ro"n copper#1% o5ide. R0CH$ + 2Cu2+ + ?$H0 R0C$$0 + Cu2$ #s% + 6H2$ &Note' et!anal #strongest alde!yde reducing agent% produces (etallic copper as "ell as copper#1% o5ide. HCH$ + Cu2$ + $H0 HC$$0 + 2Cu #s% + H2$

d. $5idation of Alde!ydes using )ollenMs Reagent #=il*er

irror )est%

R C $

H

)ollenIs Reagent "ar(

R C $

Ag #s% $

$ C H
)ollenIs Reagent "ar(

C $
-

+ Ag #s%

17

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d. $5idation of Alde!ydes using )ollenMs Reagent #=il*er irror )est% #ContMd% R R1 )ollenIs Reagent C N o R e a c tio n
"ar(

$
&Note' Alde!ydes redyce t!e Ag#1% in )ollenMs reagent to Ag, for(ing a sil*er (irror. !eat RCH$ + 2.NH6AgNH6/+ + 6$H0 RC$$0 + 2Ag #s% + 7NH6 + 2H2$

7. Reduction Reactions a. Reduction of Alde!ydes to Pri(ary Alco!ols CiAlH7 in dry et!er R0CH$ + 2.H/ R0CH2$H or NaEH7 # aq % R0CH2$H R0CH$ + H2 !eat +. Reduction of <etones to =econdary Alco!ols
Ni catalyst

R C $ R C $

R1

H C $H H R1

+
R1

H2

CiAlH7 in dry et!er or NaEH7 # aq %

H2

Ni catalyst !eat

C $H

R1

?. Reaction "it! Alkaline A@ueous 1odine #)ri-1odo(et!ane #1odofor(% Aor(ation%

&Note' Reaction is only positi*e for alco!ol containing a (et!yl group attac!ed to t!e car+on at "!ic! t!e car+onyl group is also attac!ed i.e. (et!yl car+onyl co(pounds. Aor alde!ydes, only et!anal "ill for( iodofor(. All (et!yl ketones "ill for( iodofor(. Na$H, "ar( R C $ + CH16 + 61 + 6H2$ R C $ + 6 1 2 + 7 H$

C CH6

CH6
9. C!lorination using P!osp!orus Pentac!loride #PCl?%

&Note' Alde!ydes and ketones react "it! p!osp!orus pentac!loride to gi*e ge(inal-dic!loro #cf. *icinal% co(pounds. )!e o5ygen ato( in t!e car+onyl group is replaced +y t"o c!lorine ato(s.

CH6CH$ + PCl? CH6CHCl2 + P$Cl6 CH6C$CH6 + PCl? CH6CCl2CH6 + P$Cl6

CAR/O,YLIC ACI+S 1 +ERIVATIVES

Preparation of Car+o5ylic Acids 1. $5idation a. $5idation of Pri(ary Alco!ols and Alde!ydes R R R $H < 2 Cr2 $> :H2 =$7 < 2 Cr2$> :H2=$ 7 C $ C C i((ediate or < n$7 :H2 =$7 distillation H H H$ H +. $5idati*e Clea*age of Alkenes H H

H C $H

H C $H

C H

C H

< n$7 :H2 =$7 , !eat

1?

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c.

$5idation of an Alkyl+enDene #Aor(ation of EenDoic Acid%

$ C

CH6 + 6 .$ /
< n$7:H2 =$7 , !eat

$H

+ H 2$

2. Hydrolysis a. Hydrolysis of Nitriles #R0CHN%

Acidic Hydrolysis

RC$$H + NH7+ R0CHN reflu5

HCl # aq %

Easic Hydrolysis

RC$$0Na+ + NH6 R0CHN reflu5 +. Hydrolysis of Fsters #RC$$RM%

Na$H # aq %

Acidic Hydrolysis
HCl # aq %, reflu5 RC$$H + RM$H RC$$RM + H2$ conc H2 =$7

Easic Hydrolysis
Na$H # aq % RC$$0Na+ + RM$H RC$$RM + H2$ reflu5 H RC$$H RC$$0Na+ reflu5
+

Reactions of Car+o5ylic Acids 1. =alt Aor(ation a. Reaction "it!

etal RC$$H + Na RC$$0Na+ + JH2 +. Reaction "it! Eases RC$$H + Na$H RC$$0Na+ + H2$ c. Reaction "it! Car+onates 2RC$$H + Na2C$6 2RC$$0Na+ + H2$ + C$2

2. Fsterification

$ R1
conc H2 =$ 7 !eat

R C $H

$ H

C R $

R1

#can use acid or alkaline as catalyst%

H 2$

6. Con*ersion into Acyl C!lorides #RC$Cl% RC$$H + PCl? RC$Cl + P$Cl6 + HCl 6RC$$H + PCl6 6RC$Cl + H6P$6 RC$$H + =$Cl2 RC$Cl + HCl + =$2 7. Reduction to Alco!ols
1. CiAlH7 in dry et!er RCH2$H + H2$ RC$$H + 7.H/ 2. H2 =$7 # aq %

Preparation of Acyl C!lorides 1. Aro( Car+o5ylic Acid RC$$H + PCl? RC$Cl + P$Cl6 + HCl 6RC$$H + PCl6 6RC$Cl + H6P$6 RC$$H + =$Cl2 RC$Cl + HCl + =$2

19

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Reactions of Acyl C!lorides 1. Con*ersion into Acid. Hydrolysis RC$Cl + H2$ RC$$H + HCl ArC$Cl + H2$ ArC$$H + HCl
&Note' EenDoyl c!loride reacts (uc! slo"er t!an acyl c!lorides +ecause of t!e reduce in t!e positi*e nature of t!e car+onyl car+on caused +y resonance.

2. Fster Aor(ation. Alco!olysis. roo( te(perature RC$Cl + RM$H RC$$RM + HCl

&Note' Reaction is slo" "!en p!enol is directly reacted "it! acyl c!loride. slo" RC$Cl + Ar$H RC$$Ar + HCl &Note' Eecause p!enol is a "eaker nucleop!ile #lone pair of electron delocaliDes into t!e ring%, it is con*erted to p!eno5ide to increase nucleop!ilic strengt!. Ar$H + Na$H Ar$0Na+ + H2$ RC$Cl + Ar$0 RC$$Ar + Cl0

6. A(ide Aor(ation. A((onolysis. RC$Cl + NH6 RC$NH2 + HCl RC$Cl + RMNH2 RC$NHRM + HCl RC$Cl + RMRMMNH RC$NRMRMM + HCl 7. Reduction to Alde!yde, t!en Alco!ol CiAlH7 in dry et!er CiAlH7 in dry et!er RC$Cl RCH$ RCH2$H H2 =$7 # aq % Preparations of Fsters 1. Condensation Reaction of Acid and Alco!ol a. Ft!yl Ft!anoate

$ C R $ R1

R C $H

R1

$ H

conc H2 =$ 7 !eat #can use acid or alkaline as catalyst%

H 2$

+. P!enyl EenDoate Ar$H + Na$H Ar$0Na+ + H2$ ArC$Cl + Ar$0Na+ ArC$$Ar + NaCl Reaction of Fsters 1. Hydrolysis a. Acidic Hydrolysis
HCl # aq %, reflu5 RC$$H + RM$H RC$$RM + H2$ conc H2 =$7

+. Easic Hydrolysis
Na$H # aq % RC$$0Na+ + RM$H RC$$RM + H2$ reflu5

2. Reduction to Pri(ary Alco!ols

CiAlH7 in dry et!er RC$$RM RCH2$H H2 =$7 # aq %

Preparation of Polyesters 1. Condensation Reaction acid # $CRC$$RM$ % nH$$CRC$$H + nH$RM$H reflu5

+ 2nH2$

1>

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NITROGEN COM-O.N+S
Preparation of A(ines 1. Reaction of Halides "it! A((onia or A(ines. A((onolysis + et!anol, reflu5 NH6 .H6N---R---X/ RNH2 + NH7+X0 R0X + e5cess conc NH6 sealed tu+e
RX RX RX RX NH6 RNH2 R2NH R6N R7N+X0

2. Reduction a. Reduction of A(ide +. Reduction of Nitrile

CiAlH7 in dry et!er RCH 2NH2 RC$NH2 RNH 2 H2 : Ni or Pt

RCH2NH2 R0CHN or 2H , Ni, !eat

CiAlH7 , dry et!er
2

c.

Reducti*e A(ination

H C H
Reactions of A(ines 1. =alt Aor(ation

H $

H C NH i(ine
H2 , Ni H or NaEH6 CN

+ NH6
H

C H

NH2

RNH2 + HCl RNH6+ Cl0 RNH2 + RMC$$H RNH6+ 0$$CRM

NH2

NH6 Cl

HCl

&Note' P!enyla(ine is not solu+le in "ater +ut dissol*es in acid.

2. Aor(ation of A(ides. Acylation. RNH2 RRINH

RIC$Cl RIC$NHR + HCl Ar=$2 Cl Ar=$2NHR + HCl RIIC$Cl RIIC$NRRI + HCl Ar=$2 Cl Ar=$2NRRI + HCl RIIIC$Cl no reaction Ar=$2 Cl no reaction

RRIRIIN

&Note' =ince HCl is for(ed, so(e of t!e a((onia:a(ine "ill +e protonated and cannot act as a nucleop!ile. Hence, at least dou+le t!e a(ount of a((onia : a(ine (ust +e used. &Note' Acylation of 1 and 2 a(ines leads to t!e for(ation of su+stituted a(ides. 6 do not undergo acylation +ecause t!ey do not !a*e any replacea+le H ato(s. CH6CH2NH2 + CH2C$Cl CH6CH2NHC$CH6 + HCl ArNH2 + ArMC$Cl ArNHC$ArM + HCl ArNH2 +RC$Cl ArNHC$R + HCl

6. Ring =u+stitution Reactions of Aro(atic A(ines a. Halogenation NH2

NH2 Er Er #s%

6Er2 #a@%

+ 6HEr

B!ite ppt

Er
1G
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&Note' )o get (onosu+stituted co(pounds, react p!enyla(ine "it! et!anoyl c!loride to reduce t!e Nstrongly acti*atingM nature of t!e a(ino group to for( p!enylaceta(ide.
NH2 NHC$CH6

CH6C$Cl

&Note' NHC$CH6 is also 2,7-directing +ut (oderately acti*ating. Halogenation of ArNHC$CH6 "ill gi*e N-#2+ro(op!enyl%aceta(ide or N-#7-+ro(op!enyl%aceta(ide. Reacting t!is "it! a@ueous Na$H and !eating "ill gi*e 2-+ro(op!enyla(ine or 7-+ro(op!enyla(ine.

+. Nitration

NH2 $ 2N conc HN$6 + conc H =$ 2 7

NH2 N$2

N$ 2 &Note' )!e sa(e steps as a+o*e can +e taken if "e "ant (onosu+stituted nitrop!enyla(ine.
Preparations of A(ides 1. A((onolysis of Acid ;eri*ati*es RC$Cl + NH6 RC$NH2 + HCl RC$Cl + RMNH2 RC$NHRM + HCl RC$Cl + RMRMMNH RC$NRMRMM + HCl 2. Reaction +et"een A(ine and Acid C!loride RIC$Cl RIC$NHR + HCl RNH2 Ar=$2 Cl Ar=$2NHR + HCl RRINH Reactions of A(ides 1. Acidic Hydrolysis
HCl, H2 $ R0C$$H + NH7+ RC$NH2 !eat RIIC$Cl RIIC$NRRI + HCl Ar=$2 Cl Ar=$2NRRI + HCl

2. Easic Hydrolysis
Na$H, H2 $ R0C$$0 + NH6 RC$NH2 !eat

Preparations of A(ino Acids 1. Hell-4ol!ard-2elinsky Reaction H

H C Er
e5cess conc NH6 C$$H H2N R

H C R C$$H

C H R C$$H

Er2 , PEr6 !eat

Reactions of A(ino Acids 1. =alt Aor(ation a. Reaction "it! H+. Cationic + H6N0CH20C$$0#a@% + H+#a@% +H6N0CH20C$$H #a@% +. Reaction "it! $H0. Anionic + H6N0CH20C$$0#a@% + $H0 #a@% H2N0CH20C$$0 #a@% + H2$#l%
&Note' )!e a+o*e t"o e@uations e5plains t!e +uffering capa+ility of a(ino acids.

2. Acylation #Aor(ation of A(ides% CH6C$Cl + H2N0CH20C$$H CH60C$0NH0CH2C$$H + HCl 1L

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6. Fsterification
HCl H2N0CH20C$$H + R$H +

H6N0CH20C$$R + H2$

7. Peptide Aor(ation
&Note' A peptide is any poly(er of a(ino acids linked +y a(ide +onds +et"een t!e a(ino grup of eac! a(ino acid and t!e car+o5yl group of t!e neig!+ouring a(ino acid. )!e 0C$0NH0 #a(ide% linkage +et"een t!e a(ino acids is kno"n as a peptide +ond.

H2N

CH R

C $

$H

+ H2N

CH R1

C $

$H

H2N

CH R

C $

N H

CH R1

C $

$H

+ H2 $

?. Hydrolysis of Peptides a. Acidic Hydrolysis H $ H

H
H2=$ 7 # aq % ----------- !eat

$ C $H

------

C R

N H

C R1

C R

H6N

C R1

------

H -----C R

+. Easic Hydrolysis $ H

H
Na$H # aq % ----------- !eat

$ C $
-

N H

C R1

C R

H2N

C R1

------

&Note' A peptide +ond can +e clea*ed +y !ydrolysis in t!e presence of a suita+le enDy(e #trypsin, pepsin etc% or +y !eating in acidic or alkaline (ediu(.

28

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A--EN+I,
Halogenation of Alkyl+enDenes' Ring *s =ide c!ain Alkyl+enDenes clearly offer t"o (ain areas to attack +y !alogens' t!e ring and t!e side c!ain. Be can control t!e position of attack si(ply +y c!oosing t!e proper reaction conditions. Halogenation of alkanes re@uires conditions under "!ic! !alogen ato(s are for(ed, t!at is, !ig! te(perature or lig!t. Halogenation of +enDene, on t!e ot!er !and, in*ol*es transfer of positi*e !alogen, "!ic! is pro(oted +y acid catalysts like ferric c!loride #AeCl6%. !eat or lig!t CH7 + Cl2 CH6Cl + HCl + Cl2
AeCl6 , cold
Cl

+ HCl

Be (ig!t e5pect, t!en, t!at t!e position of attack in, for e5a(ple, (et!yl+enDene "ould +e go*erned +y "!ic! t!e attack particle is in*ol*ed, and t!erefore +y t!e conditions e(ployed. )!is is so' if c!lorine is +u++led into +oiling (et!yl+enDene t!at is e5posed to ultra*iolet lig!t, su+stitution occurs al(ost e5clusi*ely in t!e side c!ain, in t!e a+sence of lig!t and in t!e presence of ferric c!loride, su+stitution occurs (ostly in t!e ring.

CH6

ClO

At &2 Attacks side chain

Cl+

I !2 Attacks ring

arko*niko*Ms Rule 1n t!e ionic addition of an acid to t!e car+on-car+on dou+le +ond of an alkene, t!e !ydrogen of t!e acid attac!es itself to t!e car+on ato( t!at already !olds t!e greater nu(+er of !ydrogens. =aytDeffMs Rule Aor eli(ination reactions, t!e preferred product is t!e alkene "it! t!e (ost alkyl groups attac!ed to t!e dou+ly +onded car+on ato(s i.e. t!e (ost su+stituted product.

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