deriv. of barbituric acid. primidone-2
TRANSCRIPT
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LECTURELECTURE №№ 1144
Theme:Theme: Derivatives of barbituric acid:Derivatives of barbituric acid:
properties, analysis, storage, action andproperties, analysis, storage, action anduse. Primidone as structural analog ofuse. Primidone as structural analog of
barbituratesbarbiturates
Associate prof Associate prof .. Mosula L.M.Mosula L.M.
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The planThe plan
1.1. Medical preparations from group ofMedical preparations from group of derivativesderivatives
of arituric acidof arituric acid!! aritalarital"" arital sodiumarital sodium""
phenoaritalphenoarital"" phenoarital sodiumphenoarital sodium""
en#onalen#onal"" he$enalhe$enal"" thiopental sodiumthiopental sodium..
%.%. &rimidone&rimidone as structural analog of barbituratesas structural analog of barbiturates ..
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Derivatives of pyrimidineDerivatives of pyrimidine
In structure of many natural and synthetic drugs isIn structure of many natural and synthetic drugs is
pyrimidinepyrimidine – – hexatomic heterocycle with two atoms ofhexatomic heterocycle with two atoms of
Nitrogene,Nitrogene, which are in the position 1,3:which are in the position 1,3:
HN
HN
1
2
3 4
5
6
N
N
N
N
1
2
3
1
2
3
Completely hydrogenated cycle of p'rimidine names
he$ah'drop'rimidine:
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In medical practice the synthetic preparations, which containsIn medical practice the synthetic preparations, which containshexahydropyrimidinehexahydropyrimidine cyclecycle with three hydroxy-groupswith three hydroxy-groups --СС!! in the position 2,",# $in the position 2,",# $ derivatives of barbituric acidderivatives of barbituric acid areare
widely appliedwidely applied::
Barbituric acidBarbituric acid – – isis hexahydropyrimidinehexahydropyrimidine(%"4")((%"4")(trionetrione..
Barbituric acidBarbituric acid is cyclic ureideis cyclic ureide – – product of product of condensationcondensationof carbamideof carbamide (urea)(urea) and dibasic malonic acidand dibasic malonic acid (propane(propanediacid)diacid)::
HN
HN
%
%
%1
3
2
"
&
#
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% 'NH2
NH2
''
'
H%
H%
%
%
(1
(2 HN
HN
%
%
%
(1
(2
)-2H2%
1
3
2
"
&
#
*eri+ati+es of arituric acidarituric acid
areare
products of products of
condensation ofcondensation of
carbamidecarbamide (urea)(urea) and deriaties of malonic acidand deriaties of malonic acid:
% '
NH2
NH2'
'
'
H%
H%
%
%
H
H HN
HN
%
%
%
H
H) -2H2%
1
3
2
"
&
#
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*ariturates*ariturates are c'clic imides used as h'pnotics andare c'clic imides used as h'pnotics and +in the+in thecase of phenoarital,case of phenoarital, as anticonvulsants.as anticonvulsants. The' are derivativesThe' are derivativesof arituric acid +-hich is not pharmacologicall' active, andof arituric acid +-hich is not pharmacologicall' active, anddiffer onl' in their sustituents on the (position of the ring.differ onl' in their sustituents on the (position of the ring.
The h'pnagogue action of ariturates -as revealed in theThe h'pnagogue action of ariturates -as revealed in theearl'earl' ////(th(th centur' 'centur' ' 0isher0isher and Meringand Mering.. n then the 12341234 0isher0isher-as s'nthesi#ed arital-as s'nthesi#ed arital"" after that -ere s'nthesi#ed man'after that -ere s'nthesi#ed man'ariturates and -as fi$ed relationship et-een structure andariturates and -as fi$ed relationship et-een structure andactionaction..
1.1. The h'pnagogue action is characteristic for derivatives ofThe h'pnagogue action is characteristic for derivatives ofarituric acidarituric acid"" -hich have in the position-hich have in the position "" al'lal'l"" ar'l orar'l orother radicalsother radicals..
%.%. The impact surface and valid time of ariturates areThe impact surface and valid time of ariturates areincreased at increase of lenght of h'drocaronic chain in theincreased at increase of lenght of h'drocaronic chain in the
al'l sustitute in the positional'l sustitute in the position "" until () atoms of Caron.until () atoms of Caron. Then lenght of h'drocaronic chain in the ariturates isThen lenght of h'drocaronic chain in the ariturates ismore5 6uch drugs have stimulant actionmore5 6uch drugs have stimulant action..
7.7. The pharmacological effect at h'drocaronic chain ranchingThe pharmacological effect at h'drocaronic chain ranching""presence of unsaturated ondspresence of unsaturated onds"" aloholic h'dro$'laloholic h'dro$'l 89:" 89:" atomatom
of halogenof halogen ++especiall'especiall' *r,*r, is intensifiedis intensified..
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4.4. Then action of ariturates is more intensified theThen action of ariturates is more intensified the
h'pnagogue effect is shoth'pnagogue effect is shot..
.. ;ith one phen'l radical;ith one phen'l radical +C+C)). ThenThen atoms of h'drogen of imide groups +1( and 7(positionsatoms of h'drogen of imide groups +1( and 7(positions
of the ring, are sustituted such drug can maeof the ring, are sustituted such drug can maeconvulsionsconvulsions..
2.2. ?erivatives of thioarituric acid +atom of sulphur on the %(?erivatives of thioarituric acid +atom of sulphur on the %(
position of the ringposition of the ring ,, have more intensive and short(timehave more intensive and short(time
action unlie o$'gen analogue of arituratesaction unlie o$'gen analogue of ariturates..
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Chemical properties of arituric acid and ariturates*ariturates contain nitrogen atoms" ut the lone pair on the*ariturates contain nitrogen atoms" ut the lone pair on the
nitrogen is not availale for reaction -ith protons" sonitrogen is not availale for reaction -ith protons" so arituratesariturates
are not asic.are not asic.
*arituric acid and derivatives hae the acid nature! "hus
arituric acid in 5–6 times is stronger then acetic acid! (
Monosustituted of arituric acid (for e#ample$ 5%ethylbarbituric
acid) – enough strong acids$ and "(disustituted of arituric acid
(for e#ample$ 5$5%diethylbarbituric acid) – ery &ea' acid!cid properties of these compounds are caused keto-enol
tautomerism of arituric acid – at the e#pense of Hydrogene atoms of
methylene groups –*2–!
+,
+,
-
-
-
+
+ +,
+,
-+
-
-
+
./0% /789
+,
+,
-
-
-
+
H
+,
+,
-
-+
-
H
./0%/789
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esides$ at the e#pense of Hydrogene atoms of imide groups%,+
% it is possible imido-imidolnic tautomerism!
HN
HN
%
%
%
(1
(2 HN
N
%
OH
%
(1
(2 N
HN
%
%
OH
(1
(2 HN
N
HO
%
%
(1
(2
;or barbiturates$ &hich
+ydrogene atoms of
methylene groups are
substituted on radicals$ is
possible only imido-imidolnic tautomerism
(lactam-lactim
tautomerism)!
H N
H N
%
%
%
H N
N
%
O H
%
N
H N
%
%
O H
H N
N
H O
%
%
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"hus it is necessary to notice$ that unli'e barbituric acids deriaties of
barbituric acid in &ater solutions almost not dissociates< at presence of
ions =*–– they are dissociated as acids also are capable to gie salts
&ith metals:
HN
N
O
%
%
(1
(2 N
N
%
%Na
%Na
(1
(2
H
Na%H
-H2%
HN
N
O
%
%
(1
(2
!a Na%H "
pH 1.
"
pH13
arbituric acid and its salts do not hae medical properties and
conse>uently are not drugs!
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#eneral formula of barbiturates#eneral formula of barbiturates $imide form%:$imide form%:
N
N
%
%
%
&'
&(
H
&
1
2
3
"
&
#
N
N
!aO
%
%
&'
&(
&
$!a)%1
2
3
"
&
#
@eneral formula of a(salts +imidol(form,!
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)ynthesis of barbiturates)ynthesis of barbiturates Derivatives of barbituric acid are synthe*ed byDerivatives of barbituric acid are synthe*ed by condensation of urea andcondensation of urea and
corresponding esters of malonic acid.corresponding esters of malonic acid. Therefore synthesis consists ofTherefore synthesis consists of
t+o stagest+o stages..
'. )ynthesis corresponding esters of malonic acid:'. )ynthesis corresponding esters of malonic acid:
(1
'
'
(2 '
%
%
%'2H&
%'2H&
%. Condensation of ester and urea in the presence of ,a%alcoholate in
the solution of absolute alcohol!
N
HN
!a%
%
%
'2H&
'2H&
H
'
'
H '
%
%
%'2H&
%'2H&
2'2H
&/r
'2H&%Na
(H-
'
'
(H- '
%
%
O(H-
O(H-
' %H2N
H2N'2H&%Na
-'2H&%H
HN
HN
%
%
%
'2H&
'2H&
H'l
-2H/r
;or e#ample$ synthesis of barbital:
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Chemical structure and properties of
derivatives of arituric acid
N
HN
%
%
%
,(H-
,(H-
H
1
2
"
&
#
3
*arital
@eneral otices (Ph Eur monograph 0170) arbitalumC?+12,2-3
1?4!2
57-44-3
?E0TB arbital contains not less than @@!A per cent and not more than the e>uialent of
1A1!A per cent of 5$5%diethylpyrimidine%2$4$6(1 H $3 H $5 H )%trione$ calculated
&ith reference to the dried substance!C
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HN
HN
%
%
%
,(H-
,.H-1
2
"
&
#
3&henoarital@eneral otices (Ph Eur monograph 0201)
henobarbitalum
C12+12,2-3
?E0TB &henoarital contains not less than 22.3 per cent and not morethan the euivalent of 131.3 per cent of (eth'l((
phen'lp'rimidine(%"4")+1 H "7 H " H ,(trione" calculated -ithreference to the dried sustance.
C
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N
HN
%
%
%
,(H-
,H-
,O
,H-
*en#onal
enDonalum
1%benDoyl%5%ethyl%5%phenyl%barbituric acid
C
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N
N
!aO
%
%
,H/
H/,
1
2
"
&
#
3
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H2'
H2' 'H
'H3
'H3N
HN
!aO
%
%
,(H-
,-H''1
2
"
&
#
3
*aram'l
arbamylum
sodium 5%ethyl%5%isoamyl%1*$3*$5*%pyrimidine%2$4$6%trion
C
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H'
H2'
H2' 'H3
'H3
2 3 " &
1
N
HN
!a)
%
%
,(H-
,-
H''
Thiopental sodium(Thiopental Sodium and Sodium ar!onate"
Ph Eur monograph 0212)
"hiopentalum%,atriFum(mi# &ith anhydrous ,a
2C-
3)
?E0TB
Thiopental sodium and sodium caronate is a mi$ture of the sodium derivative
of (eth'l((D+1 #S ,(1(meth'lut'l(%(thio$o(%"7(dih'drop'rimidine(
4")+1 H " H ,(dione +C11
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0dentification0dentification '. 1ormation of the painted comple2es'. 1ormation of the painted comple2es $various colours for$various colours for
different barbiturates%different barbiturates% +ith salts of heavy metals $o $!O/%+ith salts of heavy metals $o $!O/%
( in the presence of al(, u)O3 in the presence of( in the presence of al(, u)O3 in the presence of45674567/ and/ and 44((6767/, u)O3/, u)O3 in neutral medium $that not arein neutral medium $that not are
formed precipitatesformed precipitates MeMe++B
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(. 1usion +ith al8alis(. 1usion +ith al8alis
Golecules of barbiturates are brea' up to ammoniaGolecules of barbiturates are brea' up to ammonia ,+ ,+33 andand
sodium carbonatesodium carbonate ,a ,a22C-C-33!!
"hen product of reaction dilute in &ater and add dilute hydrochloric"hen product of reaction dilute in &ater and add dilute hydrochloric
acidacid +Cl+Cl$$ gasgas C-C-22 is allocated and is present characteristic smell ofis allocated and is present characteristic smell of
conformingconforming disubstituted aciddisubstituted acid ((for e#amplefor e#ample$$ diethylacetic acid –diethylacetic acid –
smell of rancid butter smell of rancid butter $ 2%$ 2% phenylpentanoic acid phenylpentanoic acid – – smell of acaciasmell of acacia))
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/. &eactions of condensation +ith/. &eactions of condensation +ith
aldehydes and the concentrated sulphaticaldehydes and the concentrated sulphatic
acidacid 0t heating with 0t heating with formaldehydeformaldehyde С!С! andand
concentrated sulphatic acid concentrated sulphatic acid H2%"H2%" $the 9ar8$the 9ar8
reactant%reactant% the products painted in +ariousthe products painted in +ariouscolour are formed:colour are formed: phenobarbitalphenobarbital andand
ben*onalben*onal $ $ pink colouring pink colouring for phenylaceticfor phenylacetic
acid45acid45 he2enalhe2enal $ $ dark red dark red colouring withcolouring with greengreenfluorescencefluorescence66
7rom steam-dimethylaminoen8aldehyde7rom steam-dimethylaminoen8aldehyde
and concentrated H2%":and concentrated H2%":
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4. nteraction -ith solution of chloride acid (for sodium
salts of barbiturates – arital(sodium$ he$enal$ aram'l)!t interaction of test solution &ith +Cl there is a reaction of
neutralisation &ith formation of precipitate (barbiturates)! "he precipitate of barbiturate filter$ &ash out &ater$ dry and identify on
fusion temperature, and in a filtrate find out Sodium ions!
!
HN
HN
Na%
%
%
(1
(2 HN
HN
%
%
%
(1
(2
) H'l ) Na'l
H' '
%'H3
%
%
H' '
%'H3
%
%Na
9 ) Na
)
R ti f d fi iti f f ti l
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Reactions for definition of functional group
+on position 1 and ",
1. Reaction nitration +for phen'l radical C)
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(. &eaction for ben*oateion after al8aline(. &eaction for ben*oateion after al8aline
hydrolysis of preparationhydrolysis of preparation $ben*onal%$ben*onal%
)P;. To ' ml of test solution add
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3. &eactions for revealing of )ulphur 3. &eactions for revealing of )ulphur $thiopental sodium%$thiopental sodium%
a% >t heating of test substance in the presence ofa% >t heating of test substance in the presence ofsodium hydroxidesodium hydroxide !aOH and!aOH and lead acetatelead acetate $H/OO% (Pb a$H/OO% (Pb a
blac8 precipitateblac8 precipitate is formed $is formed $lead sulphidelead sulphide Pb)%.Pb)%.
blac8 precipitateblac8 precipitate
b% >tb% >t minerali8ation of preparationminerali8ation of preparation with mix for sinteringwith mix for sintering mixmixNa2'%3 and NaN%34 ulphur passes in anions %"2 - whichNa2'%3 and NaN%34 ulphur passes in anions %"2 - whichre+eals y means of solution /a'l2:re+eals y means of solution /a'l2:
6B6B44%8 %8 GG *a*a%G%G HH *a6B*a6B44II
-hite precipitate-hite precipitate
HN
N
Na
%
%
'2H&
'H
'H3
H2
'
H2
' 'H3
#Na%HH'
'2H&
'%%Na
H'
'H3
H2'
H2' 'H3 ) Na2 ) NH3 ) 2Na2'%3
Na2 ) =,'H3'%%42=, ) 2'H3'%%Na
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-. &eaction +ith silver nitrate >g!O/ in the-. &eaction +ith silver nitrate >g!O/ in the
medium of soda !a(O/medium of soda !a(O/
>t interaction +ith ions >g are formed one>t interaction +ith ions >g are formed one
substituted $soluble in +ater% and t+o substitutedsubstituted $soluble in +ater% and t+o substituted$insoluble in +ater% silver salts. 0n the presence of !a(O/$insoluble in +ater% silver salts. 0n the presence of !a(O/
at first !asalt, and then >gsalt in positions 3 and at first !asalt, and then >gsalt in positions 3 and areare
formedformed
N
N
%
OH
OH
(1
(2 N
N
%
O!a
OH
(1
(2
Na2'%3 0gN%3
-NaN%3
N
N
%
O>g
OH
(1
(2
N
N
%
O>g
OH
(1
(2
Na2'%3
N
N
%
O>g
O!a
(1
(2
0gN%3
N
N
%
O>g
O>g
(1
(2
TT t
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TestsTests
)pecific impurities – products of)pecific impurities – products ofsemisynthesissemisynthesis
'. Barbital – ethylbarbituric acid'. Barbital – ethylbarbituric acid
(. Phenobarbital – phenylbarbituric acid(. Phenobarbital – phenylbarbituric acid
/. Barbamyl, thyopental sodium, he2enal/. Barbamyl, thyopental sodium, he2enal
– methanol – methanol
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>ssay of barbiturates>ssay of barbiturates 7or >uantitati+e definition of ariturates7or >uantitati+e definition of ariturates
various methods are used:various methods are used: '. Titrimetric:'. Titrimetric: a% acid base titration in +ater,a% acid base titration in +ater,
a?ueousalcoholic and nona?ueousa?ueousalcoholic and nona?ueous
mediums=mediums= b% argentometry=b% argentometry= c% bromatometry=c% bromatometry=
d% iodochlorometry $for barbituratesd% iodochlorometry $for barbiturates+ith nonsaturated bonds, for e2ample,+ith nonsaturated bonds, for e2ample,he2enal%.he2enal%.
(. #ravimetry.(. #ravimetry.
/. Photocolorimetry./. Photocolorimetry.
1 Alalimetr' non aueous titration
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1. Alalimetr'" non(aueous titrationThis method is applied to uantitative definition of arital" phenoarital"
en#onal.
Gedium – mi#ture of HG; and benDene (1!7)$ preliminarily neutraliDed bythymol blue in the HG; (protophilic solent$ &hich can intensify acid properties of
barbiturates)!
Itandard solution – solution of sodium methylate C+3-,a or sodiumhydro#ide ,a-+ in the mi#ture of methanol C+3-+ and benDene C6+6 to blue colour!
"his method is based on ability of barbiturates to tautomeric
transformations and formation imidolic or the acid-form$ &hich hae
acid character:
N
HN
O
%
%
(1
(2
(
H '
%
N'H3
'H3
N
N
O
%
%
(1
(2
(
H '
%
N'H3
'H3H
) )
9
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J, "itrant 8 solution of sodium meth'late C+3-,a: E m K . m.
H '
%
N'H3
'H3H
N
N
O
%
%
(1
(2
(
'H3%HH '
%
N'H3
'H3
N
N
!aO
%
%
(1
(2
(
9
) 'H3%Na ) 'H3% 9
) 'H3% 9
)
, Titrant 8 solution of sodium h'dro$ide ,a-+: E m K . m.
H '
%
N'H3
'H3H
) Na%H
N
N
O
%
%
(1
(2
(
H '
%
N'H3
'H3
N
N
!aO
%
%
(1
(2
(
9
) Na)
) H2% ) Na)
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%. Alalimetr'" non(aueous sustitute titration
+phenoarital" etc.,3"133 g sustance dissolve in ml p%ridine #" add 3" ml of
th%molphthaleine solution #" 13 ml &7 g'l siler nitrate AgB7 in
p%ridine # and titrate -ith 0"1 $ sodium h%droide aB< in the
ethanol efore not disappearing !lue colour.
E E m K .m K . mm..
N
HN
%
%
%
(1
(2
(
N
N
H%
%
%
(1
(2
(
'2H&%H
N
N
!aO
%
%
(1
(2
(
) NaOH ) H2%
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/. >l8alimetry in the a?ueousalcoholic medium/. >l8alimetry in the a?ueousalcoholic medium This methodThis method can be usedcan be used for for ?uantitative definition of?uantitative definition of
all barbitrate, +hich haveall barbitrate, +hich have acid acid character.character.
Titrant Titrant solution sodium hydroxidesolution sodium hydroxide !aOH.!aOH.
0ndicator –0ndicator – thymolphthaleinethymolphthaleine..
)hot of preparation dissolve in)hot of preparation dissolve in neutralised on thymolphthaleineneutralised on thymolphthaleinealcohol alcohol 66((55--7575 $$for solubility improvement of barbiturates andfor solubility improvement of barbiturates and
preventions of hydrolysis formed sodium salt preventions of hydrolysis formed sodium salt %.%.
E E m @ A.m @ A. mm..
N
HN
%
%
%
(1
(2
(
N
N
H%
%
%
(1
(2
(
'2H&%H
N
N
!aO
%
%
(1
(2
(
) NaOH ) H2%
4 Acidimetr' in the -ater medium4 Acidimetr' in the -ater medium
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4. Acidimetr' in the -ater medium4. Acidimetr' in the -ater medium"his method can be used for >uantitatie definition"his method can be used for >uantitatie definition of sodium salts ofof sodium salts of
arituratesariturates$ &hich hae$ &hich hae basicbasic character character ((arital(sodiumarital(sodium$$ aram'laram'l$$ he$enalhe$enal)!)!
"itrant %"itrant % hydrochloric acidhydrochloric acid +Cl!+Cl!
Bndicator – Bndicator – methyl orange or methyl red.methyl orange or methyl red. ,a%salts of barbiturates ,a%salts of barbiturates are hydrolyzed are hydrolyzed in &ater solutionsin &ater solutions
&ith formation&ith formation alaline mediumalaline medium ((:: ====) and therefore their can titrate) and therefore their can titrate
&ith acids$ for e#ample$ &ith&ith acids$ for e#ample$ &ith hydrochloric acidhydrochloric acid +Cl in the presence of+Cl in the presence of
methyl orangemethyl orange oror methyl red methyl red as indicator (toas indicator (to pin pin colour)!colour)! E m K . N.
N
N
Na%
%
%
(1
(2
(
N
HN
%
%
%
(1
(2
(
) H'l ) Na'l
"he free al'aly (,a-+)$ &hich is formed at hydrolysis of sodium salts of barbiturates$
titrate &ith acid too:
N
N
Na%
%
%
(1
(2
(
N
N
H%
%
%
(1
(2
(
) H%H ) Na%H
"herefore the maintenance of ,a%salt of barbitutates (J K)
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"herefore the maintenance of ,a%salt of barbitutates (J$ K)
calculate by means of formula:
$
Lhere:
K ,a-+ – the maintenance of free al'ali in substance$ in K<
M – coefficient (factor)$ &hich calculate as a parity bet&een molar
&eights of salt and sodium hydro#ide ,a-+!t >uantitatie definition of thiopental sodium by means of acidimetrydefine the total maintenance of Sodium (titrate &ith sulphatic acid +2I-4 in the
presence of methyl red as indicator)!
! "a#H moisturem
$ !p% &
shot
H'l ⋅−
−⋅
⋅⋅⋅⋅
= K)K!1AA(
1AA1AA
. Argentometr'1. Method of 0ialov and emplo'ees +en#onal,
Ihot of test substance (the acid or salt form) dissole in O
anhydrous solution of sodium carbonate ,a2C-3 and titrate &ith
nitrate g,-3 (ithout the indicator to occurrences of not
disappearing dregs (the t&o%substituted g%salt)!
di i i ibl l
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roceeding processes it is possible e#planes so!t first barbiturate it is dissoled in sodium carbonate ,a2C-3 &ith formation
one% substituted ,a%salt$ &hich reacts &ith siler nitrate g,-3 &ith formation
soluble one% substituted g%salt! "hen soluble ,a%g%salt is formed!
Bn e>uialence point e#cess of titrant g,-3 destroys ,a%g%salt and the
insoluble t&o% substituted g%salt is formed$ that specifies in the titration end!
Na2'%3 0gN%3
N
N
%
O>g
OH
(1
(2N
N
%
O!a
OH
(1
(2N
N
%
OH
OH
(1
(2
-NaN%3
Na2'%3 0gN%3
N
N
%
O>g
OH
(1
(2 N
N
%
O>g
O!a
(1
(2N
N
%
O>g
O>g
(1
(2
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). *romatometr'" ac titration" -ith iodometric
finishingThe method is used for uantitative definition of ariturates
-ith nonsaturated !ound " for e$ample" he$enal.This method is ased on !romination sustance in a place of
dou!le !ound .
Mr-3 N 5Mr N 6+Cl O 7*r% N 6MCl N 3+2-
N
N
Na%
%
%
'H3
H3'
N
N
Na%
%
%
'H3
Br
Br
H3'
) /r 2
r 2 N 2MB O % N 2Mr
B2 N 2,a2I2-3 O 2,aB N ,a2I4-6
Carry out the control test!
* m+he$enal, K . m.P%
i i
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=. odo(chlorometr'" ac titration"his method is used for >uantitatie definition of barbiturate &ith
nonsaturated bound (for e#ample$ he#enal)!)*odochloride BCl reacts &ith he#enal in a place of double bound in cyclohe#enyl
group):
N
N
Na%
%
%
'H3
H3'
N
N
Na%
%
%
'H3
,l
0
H3'
) I'l
Cl G Q K % G QCl% G a%6%B7 K %a G a%64B)
Carry out the control test!
* m+he$enal, K . m.P%
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>. @ravimetr'Praimetric method usually is used for >uantitatie definitions of
a(salts of ariturates (for e#ample$ thiopental sodium)$ and also at
the analysis of medicinal mi#tures!"o &ater solution of preparation add diluted chloride acid +Cl!
"he receied acid form (thiopental%acid) e+tract by means of
chloroform ( times in the small portions)! ll chloroformic e#traction
connect$ chloroform distillates$ and the rest dry at =3°
C to constant mass
HN
HN
Na%
%
%
(1
(2 HN
HN
%
%
%
(1
(2
) H'l ) Na'l
6torage
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6torage @roup of strong preparations.
n the dense cored container.
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Action and use
6edative and h'pnagogue! a, Long action 8 arital" phenoarital" arital sodiumF
, Average duration 8 aram'lF
c, 6hot(term action 8 he$enal" thiopental sodium.
&rotiepileptic +anticonvulsant, means! phenoarital and
en#onal +h'pnagogue action has not,.
0or intravenous narcosis! he$enal and thiopental sodium.
At long application and high doses of ariturates can e a poisoning " therefore their application should e supervised ' the
doctor.
n case of ariturates poisoning applied stimulators of the
central nervous s'stem 8 str'chnine" corasole" etc.6useuentl' it has een estalished" that the antagonist of
ariturates is emegride.
&rimidone
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&rimidone
3 t t 13% 3 t +d i d t ,
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Content. 2>.3 per cent to 13%.3 per cent +dried sustance,.
6'nthes'srimidone is syntheDed from phenylethylmalonic ester:
C
'2H&
'2H&
C- -C2+5
C- -C2+5
M-+
C
'2H&
'2H&
C--+
C--+
Cl5C
'2H&
'2H&
'%'l
C-Cl
2,+4-+
%
%
+,
+,
C2+5
C6+6
%+Cl%C2+5-M
C
'2H&
'2H&
C-,+2
C-,+2
+C
%
,+2
1
2
3
5
4
6
%2+Cl
C
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A. +*r&h,. Measure of ratio of the asorance.
*. +*r&h,. nfrared asorption spectrophotometr'.
?. +*r&h" 6& S,. Melting -ith anh'drous sodium caronate +*r&h, or
alalis +6& S,. Mi$ 3.% g and 3.% g of anh%drous sodium car!onate #.
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C. +*r&h" 6& /,. Reaction -ith sodium salt of chromotropic
acid and concentrated sulphuric acid at heating +for
formaldeh'de,
Hissole A!1 g in 5 ml of a 5 gRl solution of chromotropic acid,
sodium salt in a mi#ture of 4 olumes of (ater and @ olumes of
sulphuric acid ! pin'ish%blue colour deelops on heating! %H
%H
%3Na
%3Na
'H%
H
H2%
"'H
2
%H
%H
%3H
%3H
%H
%H
H%3
H%3
'H
%H
%H
%3H
%3H
%H
%
H%3
H%3
2 ) ?%@
H2%
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TE6T6
M&URTE6
Specified impurities
" ." " /" E" .
A. R1 K ?. R1 K *. phenoarital"
0. (eth'l((phen'l(%(D+1 #S ,(1(phen'lprop'ldih'drop'rimidine(4")+1 H " H ,(
dione. Ph Eur
A66A
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A66A +*p&h,. ?issolve )3.3 mg -ith heating in =3 ml of ethanol ( per cent) #"
cool and dilute to 133.3 ml -ith the same solvent. &repare a reference solution in
the same manner using )3.3 mg of primidone #S . Measure the asorance
(232324) of the % solutions at the asorption ma$imum at %= nm.
Calculate the content of C1%
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6torage List of strong preparations.
n the dense cored container.
Action and use nticonulsant!
&reparations
rimidone -ral Iuspension
rimidone "ablets
h ur
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"han's for attentionS