1
PART L
EXPERIMENTAL
PART L
E X P E R I M E N T A L
SECTION I PREPARATION OF SUBSTITUTED ANILINES
2:4-DICHLORO ~~ILINE
• •
2:4-dichloro acetanilide was prepared by chlorination
of acetanilide in presence of fused sodium acetate in
glacial acetic acid, according to the method of Reed and
Orton ( J. c. s., 1907, 1553 ). The chloro acetanilide
on hydrolysis by heating it with four times the quantity
of concentrated hydrochlori~ acid for four hours, gave
2:4-dichloro aniline; crystallised from alcohol, white 0 needles, M.P. 63 c. Pierson and Heumann record the
same melting point ( Ber., 1883, 1049 ).
2:5-DICHLORO ANILINE
2:5-dichloro nitrobenzene, obtained by nitration of
p-dichloro benzene with fuming nitric acid, gave on
reduction by tin and concentrated hydrochloric acid,
2:5-dichloro aniline, which on crystallisation from alcohol
gave white needles, M.P. 51° c. Lesimple and Witt record
- 76 -
the same melting point ( Ann. z., 1868, 226 ).
3:5-DICHLORO-~-METHOXY ANILINE
(i) Preparation of 3:5-dichloro-~-hydroxy nitrobenzene
Para nitrophenol ( 6.4 g. ) was dissolved in hot
concentrated hydrochloric acid ( 250 c.c. ). The solution
was then cooled under tap and to the cold solution was
added drop by drop a solution of potassium chlorate
( 3.6 g. in 75 c.c. water ) with occasional shaking. A
yellow solid began to separate in a few minutes after the
addition was over. A good amount of heat was evolved
during the addition; and the reaction mixture was allowed
to attain room temperature by leaving it aside for some
time. It was then filtered, washed with water to remove
the traces of the acid and dried. It crystallised as 0
small white needles from benzene, M.P. 125 C ( decamp.);
yield : 5 g.
Analysis :
0.198 g. of substance gave 0 .• 2733 g. AgCl
Found : Cl, 34.15 per cent.
Cl, 34.13 per cent.
l
77
(ii) Derivatives of 3:5-dichloro-~-hydroxy nitrobenzene
(a) The sodium salt. -- Sodium ( 2 g. ) was carefully
dissolved in absolute alcohol (. 30 c. c. ) and 3:5-dichloro
-4-hydroxy nitrobenzene ( 5 g. ) was added to it. It
went into solution. on· evaporation to dryness, yellowish
red solid was obtained. It was crystallised from minimum
quantity or water; small yellow needles, yield was almost
quantitative.
Analysis :
0.516 g. or the dry salt gave 0.1562 g. Na2so4 Found : Na, · 9. 82 per cent.
c6
H2cl
203
NNa requires : Na, 10.00 per cent.
•
(b) Silver salt. -- The ahove mentioned sodium salt
( 5 g. ) was dissolved in minimum quantity or warm water,
and a concentrated solution of silver nitrate added; a
heavy yellow solid separated. It was filtered, washed
with distilled water and dried. This was sufficiently
pure for the next reaction ; yield was almost quantitative.
Analysis :
0.336 g. of the dry silver salt gave 0.1142 g. Ag.
•
- 78 -
Found : Ag, 34.04 per cent.
Ag, 34.28 per cent.
(c) Met boxy derivative. - The preparation of the
methoxy derivative was attempted by dimethyl sulphate as
well as methyl iodide-potassium carbonate method but the
methylation did not succeed. The following method has
been found to be suitable for the purpose of the yield.
The best conditions are given below :--
The silver salt of 3:5-dichloro-4-hydroxy-nitro
benzene ( 5 g. ) suspended in absolute alcohol ( 30 c.c.)
was mixed with methyl iodide ( 10 g. ) and the mixture
was kept overnight at room temperature. It was then
refluxed for five hours on water bath and was filtaed
hot. On cooling the filtrate, white needles separated, 0 M.P. 102 C ; yield : 1 g.
Anaihysis :
0.168 g. of the substance gave 0.2178 g. AgCl
Found Cl, 32.08 per cent.
- 79 -
REDUCTION OF THE METHOXY COMPOUND : PREPARATION OF -- -
3:5-DICHLOR0-4-METHOXY ANILINE
A mixture of 3:5-dichloro-4-methoxy-nitrobenzene
( 8 g. ), concentrated hydrochloric acid ( 40 c.c. ) and
tin ( in small pieces, 16 g. ) was slowly heated on wire
gauze with a very low flame, and the heating was continued
till tin was completely dissolved. Care was taken to avoid
vigorous reaction during the reduction. The reaction
mixture was then cooled and made alkaline by adding
concentrated solution of sodium hydroxide ( 60 g. in 100
c.c. water ) and was steam-distilled when 3:5-dichloro-4-
methoxy aniline was obtained in the distillate as a white
solid. It was filtered orr and crystallised from alcohol,
white long needles, M.P. 87° C ; yield : 2 g.
Analysis :
0.213 g. or the substance gave 0.3221 g. AgCl
Found : Cl, 37.4 per cent.
c7
H?cl2 0N requires : Cl, 36.97 per cent.
ACETYL DERIVATIVE OF 3:5-DICHLORO-~-METHOXY-ANILINE
3:5-dichloro-4-methoxy aniline on treatment with
acetic anhydride gave the acetyl derivative. It
- 80 -
crystallised from alcohol, fine white needles, M.P. 195°.
Analysis :
0.280 g. of the substance gave 3.462 g. AgCl
Found : Cl, 30.59 per cent.
C9HgC12o2N requires : Cl, 30.35 per cent.
SECTION II PREPARATION OF SUBSTITUTED
DIPHENYL ~~INE-2-CARBOXYLIC ACIDS . •
(J.oot\B R __ --X <:.
. ----y l'iH
(I)
2 1 :4'-DICHLORO-~-METHOXY DIPHENYL AMINE-g-CARBOXYLIC ACID
2:4-dichloro aniline ( 7 g. ), anhydrous potassium
carbonate ( 6 g. ) and isoamyl alcohol ( 30 c.c. ) were
mixed together : and to the mixture 6-bromo-3-methoxy
benzoic acid ( 9 g. ) and copper powder ( 0.4 g. ) were
added. It was then refluxed on oil bath at 140° C for
five hours, with CaC12 guard tube to prevent access of
moisture. The resulting brown mass was treated with
- 81 -
water ( 25 c.c. ) and subjected to steam distillation to
remove amyl alcohol. The non-volatile residue in the
flask was treated with animal charcoal, and filtered hot.
The filtrate, on cooling, gave the potassium salt of the
acid as needles. It was filtered and decomposed by
concentrated hydrochloric acid. The acid, thus obtained,
was collected. The filtrate after the removal of the
potassium salt was also acidified when a further quantity
of the acid was o.btained. It was filtered, washed with
water and dried. Both the samples of the acid were mixed
and crystallised from dilute acetic acid, pale green 0 small needles, M.P. 230 c. Yield : 5 g.
Analysis :
(a) 0.1989 g. substance required 5.5 c.c. of 0.1159 N
alkali.
Found eq. wt. : 312.
c14
H11
o3
Ncl2 requires eq. wt. : 312.
(b) 0.198 g. of substance gave 0.1836 g. AgCl
Found : Cl, 22.94 per cent.
Cl, 22.76 per cent.
The acid is sparingly soluble in hot alcohol and
insoluble in hot water, benzene, chloroform and petroleum
- 82 -
ether.
The above reaction was carried out in presence of
nitrobenzene instead of amyl alcohol, the quantity of
the reactants being kept unchanged. The temperature was.
maintained at 160° C for five to six hours. On working
up the reaction mixture as before, the same acid was
obtained in slightly better yield.
Derivatives :
(i) Acid chloride. -- The acid ( 1 g. ), dry benzene
( 30 c.c. ) and thionyl chloride ( 1 c.c. ) were heated
for about fifteen minutes on water bath. On evaporation
of benzene, the acid chloride separated as yellow
crystalline substance, recrystallised from behzene, yellow
needles, M.P. 142° c. Yield : almost quantitative.
Analysis
0.176 g. of the substance gave 0.2347. g. of AgCl.
Found : Cl, 32.99 per cent.
c14
H10
o2Ncl3
requires : Cl, 32.23 per cent.
(ii) Ethyl ester. -- The above acid chloride (0.5 g.)
and absolute alcohol (5 c.c.) were refluxed for fifteen
minutes on water bath; the reaction mixture was then left
~ --------------------
- 83 -
at room temperature. The ester separated on standing as 0 small colourless plates,. M.P. 96 c.
Analysis :
0.236 g. ~f the substance gave 0.200 g. of AgCl
Found : Cl, 20.97 per cent.
c16H15o3Ncl2 requires : Cl, 20.88 per cent.
(iii) Methyl ester. -- It was similarly prepared using
methyl alcohol. It crystallised from alcohol as colourless 0 tiny needles, M.P. 114 c.
Analysis :
0.216 g. of the substance gave 0.1904 g. of AgCl.
Found Cl, 21.81 per cent.
c15H13o3Ncl2 requires Cl, 21.78 per cent.
2 1 :4 1-DICHLORO-DIPHENYL AMINE-2-CARBOXYLIC ACID
(I) R(4) = H and X(2) and Y(4) = Cl
2:4-dichloro aniline ( 16 g. ), dry potassium
carbonate ( 14 g. ), amyl alcohol ( 30 c.c. ), o-chloro
benzoic acid ( 14 g. ) and copper powder ( 0.4 g. ) were
mixed together. The mixture was then refluxed on oil bath
- 84 -
0 at 150 C for five hours, with CaC12 guard tube. The
reaction mixture was worked up as before after the steam
distillation of amyl alcohol to get the acid. A yellow
solid was obtained. It was collected and crystallised
from acetic acid, small white needles, M.P. 245° c.
Yield : 7 g. Ullmann records M.P. 249° C ( Ann., 1909,
355, 340 ).
Analysis
(a) 0.201 g. of the acid required 6.3 c.c. of
0.1133 N alkali.
Found : eq. wt. 281.6
(b) 0.215 g. of the substance gave 0.2235 g. AgCl
Found Cl, 25.72 per cent.
Calculated for c13
H9
02Ncl2 Cl, 25.19 per cent.
The acid is sparingly soluble in hot alcohol, but
insoluble in hot water, benzene, chloroform and petroleum
ether.
Derivatives :
(i) Acid chloride. -- The acid ( 1 g. ), dry benzene
- 85-
( 30 c.c. ) and thionyl chloride ( 1 c.c. ) were refluxed
for.about fifteen minutes on water bath. The mixture was
then left at room temperature : the yellow crystals of
the acid chloride began to separate on evaporation of 0 benzene as small yellow plates, M.P. 158 c. Yield :
almost quantitative.
Analysis :
0.168 g. or the substance gave 0.2421 g. AgC1
Found Cl, 35.66 per cent.
c13HgONC13 requires : Cl, 35.44 per cent.
{ii) Ethyl ester. The acid chloride ( 0.5 g. )
and absolute alcohol { 5 c.c. ) were refluxed for about
ten minutes on water bath as before. The ester separated 0 on standing in clusters of prismatic needles, M.P. 96 c.
Anal~sis :
0.177 g. of the substance gave 0.1663 g. AgCl
Found : Cl, 23.24 per cent.
c15H13o2Ncl2 requires : Cl, 22.91 per cent.
(iii) Methyl ester. This ester was prepared as
before using methyl alcohol and crystallised from alcohol, 0
tiny colourless needles, M.P. 104 c.
- 86 -
Analysis :
0.207 g. of the substance gave 0.2049 g. of AgCl
Found : Cl, 24.49 per cent.
c14Hl1o2Ncl2 requires : Cl, 23.99 per cent.
2 1 :5 1-DICHLOR0-4-METHOXY DIPHENYL M~INE-2-CARBOXYLIC ACID - - - --( I : R(4) = OCH3 ; X(2) and Y(5) = Cl )
2:5-dichloro aniline ( 5 g. ), 6-bromo-3-methoxy
benz9ic acid ( 7 g. ), anhydrous potassium carbonate
( 4 g. ), isoamyl alcohol ( 30 c.c. ) and copper powder
( 0.3 g. ) were refluxed on oil bath at 140° C for nearly
four hours. The acid was isolated by working up the
reaction mixture as described previously. The acid
obtained crystallised from acetic acid, small gre~n
needles, M.P. 216° c. Yield : 2 g.
!nalYsis :
(a) 0.2605 g. of the acid required 7.2 c.c. of
0.1159N alkali
Found eq. wt. 312.2
(b) 0.214 g. of the substance gave 0.1974 g. of AgCl
- 87 -
Found : cl, 22.83 per cent.
c14H11o3Ncl2 requires : Cl, 22.76 per cent.
Derivatives :
(i) Aci£ chloride. -- The acid chloride was prepared
as before. It crystallised from benzene as green plates, 0 M.P. 104.105 c. Yield : nearly quantitative.
AnalYsis :
0.2468 g. or the substance gave 0.3243 g. of AgCl
Found : Cl, 32.51 per cent.
c14H10o2Ncl3 requires : Cl, 32.23 per cent.
(ii) Ethyl ester. The above acid chloride was
refluxed with absolute alcohol as before. The ethyl ester 0 separated on standing as needles, M.P. 96-97 c.
Analysis :
0.1683 g. of the substance gave 0.1422 g. AgCl
Found : Cl, 20.91 per cent.
C16H15o3NCl2 requires : Cl, 20.88 per cent.
(iii) Methyl ester. -- It was prepared as before.
It crystallised from alcohol as greenish needles, 0 M.P. 115 C.
- 88 -
Analysis :
0.1937 g. of the substance gave 0.1722 g. of AgCl
Found : Cl, 21.99 per cent.
c15H13o3Ncl2 requires : Cl, 21.78 per cent.
2':5 1-DICHLORO DIPHENYL AMINE-2-CARBOXYLIC ACID - - -( I : R(4) = H ; X(2) and Y(5) = Cl ) • •
A mixture of 2:5-dichloro aniline ( 5 g. ), o-chloro
benzoic acid ( 14 g. ), dry potassium carbonate ( 4 g. ),
amyl alcohol ( 30 c.c. ) and copper powder ( 0.3 g. ) was
refluxed on oil bath at 140° C for five hours. Following
the usual procedure as described previously, the acid was
isolated. It crystallised from acetic acid, small white 0 needles, M.P. 235 c. Yield : 3 g. Gomberg and D. L.
Tavern record the same melting point 235° C ( J.A.C.s.,
1926, ~' 1356 ).
Analys~.s
0.2029 g. of acid required 6.2 c.c. of 0.1159N alkali.
Found eq. wt. : 282.3
c13Hg02Ncl2 requires eq. wt. : 282.
The acid is sparingly soluble in hot water, benzene
l
- 89 -
and petroleum ether.
Derivatives :
A (i) Acid chloride. -- 2 1 :5 1-dichloro diphenyl
amine-2-carboxylic acid prepared as described before
crystallised from benzene, thin plates, M.P. 150° c.
Analysis :
0.1953 g. or the substance gave 0.2871 g. AgC1
Found : Cl, 35.81 per cent.
c13HgONC13 requires : Cl, 35.45 per cent.
(ii) Ethyl ester. -- The ethyl ester prepared from
the acid chloride as before crystallised from alcohol,
long needles, M.P. 90° c.
Analysis :
0.250 g. of the substance gave 0.2334 g. of AgCl
Found Cl, 23.10 per cent.
C15H1302Nc12 requires C1, 22.91 per cent.
(iii) Methyl ester. The methyl ester prepared as 0
before crystallised from alcohol, small needles, M.P. 120 •
Analysis :
0.1648 g. or the substance gave 0.1620 g. Agel.
l
- 90 -
Found : Cl, 24.33 per cent.
c14H11o2Ncl2 requires Cl, 23.99 per cent.
3 1 :5 1-DICBLOR0-4 1 -METHOXY-DIPHENYL AMINE-2-CARBOXYLIC ACID - - - -{ II : R{4) = H; X{3) and Y{5) ~ Cl; R1(4 1 ) = OCH3 )
Z{5)
R
z /
NH
(II)
y
A mixture of 3:5-dichloro-4-methoxy aniline { 4 g. ),
o-chloro benzoic acid ( 3 g. ), anhydrous potassium
carbonate ( 3 g. ), amyl alcohol ( 30 c.c. ) and copper
powder { 0.2 g. ) was refluxed at 155° C for five hours.
The crude acid was isolated as before. On crystallisation
from suitable solvent, the substance obtained did not give
a sharp melting point. It gave a range of temperature,
indiacting that it was a mixture. To separate it,
various attempts were made and it was found that boiling
water removed one of the constituents, leaving an
insoluble residue (R). The filtrate on working up gave
a small quantity of unchanged o-chloro benzoic acid,
•
- 91 -
identified by mixed melting point. The residue (R) was
crystallised from acetic acid, small white needles, 0
M.P. 213 C. Yield : 1.5 g.
Analysis :
(a) 0.1241 g. of acid required 4.6 c.c. of
0.0864N alkali
Found eq. wt. : 312•3
c14H11N~3c12 requires eq. wt. : 312.
(b) 0.198 g. of the substance gave 0.160 g. of Ag61
Found Cl, 22.85 per cent.
c14H11o3Ncl2 requires : Cl, 22.76 per cent.
In this reaction it has been found that whatever may
be the experimental conditions, some unchanged o-chloro
benzoic acid is recovered. The experimental details
given above gave the minimum quantity of the unchanged
chloro benzoic acid with the best yield of the diph~nyl
amine-2-carboxylic acid.
Derivatives :
(i) Acid chloride. -- The above acid was converted
into its acid chloride as before. The acid chloride
separated on long standing as yellowish green plates,
- 92 -
M.P. 195° C.
Analysis :
0.176 g. of the substance gave 0.2347 g. of AgCl
• Found Cl, 32.99 per cent.
c14H10o2Nc13 requires : Cl, 32.23 per cent.
(i{) Ethyl ester. -- The acid·chloride obtained
above was converted into its ethyl ester, small needles, 0 M.P. 188 C.
Analysis :
0.135 g. of the substance gave 0.1143 g. of AgCl
Found : Cl, 20.96 per cent.
c16H15o3Nc12 requires Cl, 20.88 per cent.
{iii) Methyl ester. This ester similarly prepared
crystallised very slowly from alcohol, fine needles, 0
M.P. 184 C.
!nalysis
0.216 g. of the substance gave 0.1904 g. AgC1
Found : C1, 21.81 per cent.
c15H13o3Ncl2 requires : c1, 21.78 per cent.
l
- 93 -
~ 1 :.§ 1 :.§- TRICHLOR0-1: 1-METHOXY DIPHENYL .AMINE-g-CARBOXYLIC ACID
( II : R(4) = H; X(3 1 ), Y(5 1 ), Z(5) = Cl ) . .
3:5-dichloro-4-methoxy aniline ( 4 g. ) , 2:4-dichloro
benzoic acid ( 4 g. ), dry potassium carbonate (4 g.),
amyl alcohol ( 30 c.c. ) and copper powder ( 0.2 g. )
were refluxed at 150° C for six hours. The acid was
isolated as before. It crystallised from dilute acetic
acid, small pale yellow needles, M.P. 217° c. Yield : 1 g.
In this reaction also, some 2:4-dichloro benzoic
acid was always recovered unchanged. During
crystallisation it remained in the mother liquor, as it
is highly soluble in acetic acid.
!nalysis :
(a) 0.1375 g. of acid required 4.6 c,c. of
0.0864U alkali
Found eq. wt.
c14
H10c13No3 requires eq. wt.
346.2
346.5
(b) 0.201 g. of the substance gave 0.245 g. AgCl
Found : Cl, 30.90 per cent.
c14H1ocl3No3 requires Cl, 30.73 per cent.
- 94-
Derivatives :
(i) .Acid chloride. -- The acid was converted into
its acid chloride by the method described before. It
crystallised from benzene, green needles, M.P. 125° C
( decomp. ) •
Analysis :
0.123 g. of the substance gave O.l9p g. AgCl.
Found : Cl, 39.21 per cent.
c14Hg02Ncl4 requires : Cl, 38.90 per cent.
(ii) Ethyl ester. -- The acid chloride was heated
under reflux with absolute alcohol for ten minutes. The
ester separated on keeping as small clusters of needles, 0 M.P. 108 C.
Analysis : .-
0.211 g. of the substance gave 0.2458 g. of AgCl
Found : Cl, 28.81 per cent.
c16H14o3Ncl3 requires : Cl, 28.64 per cent.
Top Related