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Analytical applications of hydroxycoumarins
Talanta, 1968, Vol. IS, P&I. 1043 to 1054.
Penwmon Press. Printed in Northern Irelattd
ANALYTICAL APPLICATIONS HYDROXYCOUMARINS
OF
MOHAN KATYAL St. Stephen’s College, Delhi-7, India H. B. SINGH* Charles University, Albertov 2030, Prague 2, Czechoslovakia (Received 7 December 1967. Accepted 3 March 1968)
Summary-A review is presented of the analytical potentialities and physico-chemical properties of hydroxycoumarins. COUMARINS, derivatives of benzo-a-pyrone (I.), occur in plants belonging to the natural orders of Orchidaceae, Leguminaceae, Rutaceae, Umbelll$erae and Labiatae.l
Some coumarin derivatives exhibit distinct physiological, photodynamic and bacteriostatic activity. 2-4 Besides application of their physiological activity, a number of uses have been found for them.5 The chelating characteristics of the coumarins have long been known; Cmethylumbelliferone is a well known fluoresence indicator and the bacteriostatic properties of some of the coumarins have been attributed to chelation, In the last decade various coumarins have been extensively studied as analytical reagents. Physico-chemical studies of the ligands and the complexes have also been reported.6 The relative positions of the hydroxy and carbonyl groups have been found to alter the spectral characteristics of the compounds and the reactivity of the hydroxy groups, and the effect of substitution on the absorption spectrum of the parent compound has been studied. The dissociation constants of the various ligands have been determined potentiometrically. The effect of substitution on the basicity of the ligands has been investigated and an attempt made to correlate the basicity of the ligands with the frequency of the hydroxy group absorption bands in the infrared region. A linear relationship between the Hammett u function for the substituted ligands and the infrared absorption frequency of the hydroxy group has been established. Methylation studies of o-dihydroxycoumarins derived from esculetin and daphnetin show that the hydroxy group at the 7-position can be preferentially methylated, though ordinarily a dimethyl derivative is obtained. It is concluded that the 7-hydroxy group is slightly more reactive than the other but not significantly so. Infrared studies indicate the presence of only weak intramolecular hydrogen bonding. Coumarins show maximum absorption at about 300 rnp, with log E = 4. The spectrum usually shows additional strong bands between 250 and 340 rnp. The introduction of a hydroxy group into the coumarin molecule modifies its absorption characteristics,’ generally causing a bathochromic shift of the principal absorption band. This shift due to the auxochromic hydroxy group results from the transition
* Present address: Hindu College, Delhi-7, India. 4
1043
1044
M.
KATYAL
and H. B.
SINGH
from the ground state to the excited state by an interaction of the type:
which would result in a decrease in transition energy and hence displacement to longer wavelengths. Compounds such as 5,7dihydroxy-, 6,7-dihydroxy- and 7,8dihydroxycoumarins all exhibit bathochromic shifts. The substitution of a hydroxy group at the S-position results in a significant hypsochromic shift. This is possible because a hydroxy group in this position binds the electron pair of the pyrone oxygen atom, leading to the suppression of the n-rr interactions of coumarins as shown in II. The substitution of a hydrogen atom by a methyl group* either in the benzene ring or in the heterocyclic ring does not produce any significant change in the absorption characteristics of the coumarins. Any hypsochromic effect is attributed mainly to steric hindrance with the hydrogen atom at the ortho or peri position. A methyl group substituted in the 4-position does not have any marked effect on the spectrum of esculetin but causes a significant hypsochromic shift of the principal absorption band of daphnetin. This shift has been attributed to weakening of the conjugation between the 7-hydroxy group and the lactone carbonyl group. O--H
fl
..
HO /
/
’
1’
3
I-1.: 0
o /’
W)
4-Phenylesculetin shows a considerable bathochromic shift as a result of an increase in the number of resonating forms. The phenyl group substituted in the 4-position of daphnetin exhibits a weak electron donor effect, this effect being particularly marked because the electron contribution to the carbonyl group from the heterocyclic oxygen atom is reduced by hydrogen bonding by the 8-hydroxy group (III). As this structure does not involve any increase in conjugation of the carbonyl group, there is no great shift in the principal absorption band. The inductive and resonance effects due to the substituents on the reacting centre of the ligand can be measured by the magnitude of the Hammett u function, which covers both effects. The Hammett c function has been calculated for some coumarins and their derivatives (Table I) and plotted against the infrared frequency for the hydroxy groups. Substitution of a methyl group in esculetin and daphnetin has an electron donating effect; substitution of a phenyl group has the reverse effect. The c values calculated from the first dissociation constant give a linear relationship with the frequency shifts, but those calculated by use of the second dissociation constant or the overall dissociation constant do not. This shows that only one hydroxy group is affected by substitution in the 4-position. The slopes of the graphs for the esculetin and daphnetin series are of opposite sign.
Analytical applications
of hydroxycoumarhrs
1045
TABLEI Compound
PKI
PKI
Esculetin 4-Methylesculetin CPhenylesculetin Daphnetin CMethyldaphnetin 4-Phenyldaphnetm
7.31 744 7.27 7.32 7.63 740
8.03 8.12 8.01 8.15 8.42 8.20
Hammett
u function
-0.13 +0*04 -;31 -0.08
Apparent stability constants of metal complexes with various o-dihydroxycoumarins have been calculated (Table II) and increase with increase in the basic strength, p&e, of the l&and. The greater stability of phenyl -substituted complexes appears to be due to resonance effects, but the values for molybdenum complexes with daphnetins have not yet been explained. TABLE II
log K for complex L&and Esculetin 4-Methylesculetin 4-Phenylesculetin Daphnetin CMethyldaphnetin CPhenyldaphnetin
p&z
15.34 15.56 15.28 15.47 16.05 1560
MO
Nb
Ti
U
3.65 7.55 8.20 8.01 7.21 7.45
10.43 12.07 12.94 13.24 -
8.8 10.7 14.9 -
3.56 4.03 4.30 3.21 4.15 4.23
The wavelength of maximum absorption for transition metal chelates with dihydroxycoumarins depends on the concentration of l&and, the pH, and the type of solvent. In view of the reducing character of the dihydroxycoumarins, it has been suggested that the metal complexes have charge-transfer spectra. SYNTHESIS
OF
COUMARINS
Coumarins, in general, can be synthesized by the Pechmann reaction> i.e., by condensing the appropriate phenolic compound, or its derivative, with malic acid or t%ketonic ester in the presence of concentrated sulphuric acid. The methods used for analytically important hydroxycoumarins are outlined below. Though many methods11-14 are available for synthesis of Chydroxycoumarin and its subsequent acetylation in the 3-position, the one due to Stahmarm et a1.l” appears to be the best. In this method salicylate is acetylated with acetic anhydride and concentrated sulphuric acid at 40” to yield methyl acetylsalicylate, which is then separated and condensed with sodium in liquid pa&in. The reaction mixture is kept at 250” for about 2 hr and then filtered hot. Acidification and crystallization yield 4-hydroxycoumarin, m.p. 200-206”. The coumarin is then acetylated with acetyl chloride in dry pyridine containing a few drops of piperidine. The mixture is kept at 37” for 48 hr, then poured into ice and dilute hydrochloric acid to yield 3-acetyl-4-hydroxycoumarin. The product, crystallized from aqueous ethanol and then sublimed, melts at 138”. Oximidobenzotetronic acid15 The preparation involves the treatment of Chydroxycoumarin with aqueous sodium nitrite solution and subsequent acidification in ice-cold medium. On crystallization from hot chloroform, shining pale yellow crystals of oximidobenzotetronic acid are obtained, m.p. 149” (decomp.). 6,7-Dihydroxycoumarin (esculetin)ls An intimate mixture of hydroxyhydroquhrone triacetate, malic acid and concentrated sulphuric acid is heated on a boiling water-bath till effervescence ceases. The reaction mixture, after cooling,
1046
M. KATYAL
and H. B. SINGH
is poured into crushed ice, stirred and left overnight. esculetin as pale yellow prisms, decomposing 4Methyl-6,7-dihydroxycoumarin
Crystallization
from dilute alcohol gives
above 270”.
(4methylesculetin)1s
To an ice-cold solution of hydroxyhydroquinone triacetate in acetoacetic ester, concentrated sulphuric acid is added gradually with stirring, the temperature being kept at 0” for about 1 hr. The deep red viscous product is kept in the refrigerator for 24 hr and then poured, with constant stirring, into water. The resulting solid is filtered off, washed with water, dried, and crystallized from ethanol as yellow needles (m.p. 276-8”). 4Phenyl-6,7-dihydroxycoumarin
(4-phenylesculetin)ls
A paste of benzoylacetic ester and hydroxyhydroquinone triacetate is added to 75% sulphuric acid and dissolves in it with evolution of heat to form a deep red solution. This solution is heated to 80” on a water-bath for about an hour and is occasionally shaken. After cooling to room temperature it is poured, with stirring, into cold water and the resultant mixture allowed to cool to room temperature. After filtration, the precipitate is washed with cold water till free from acid, and is then dissolved in hot borax solution, whereupon Cphenylesculetin borate separates. This borate is decomposed with dilute sulphuric acid and the product is crystallized from alcohol as rectangular tablets and tiny prisms, m.p. 267-8”. 7,8-Dihydroxycoumarin (daphneti@ An intimate mixture of requisite amounts of pyrogallol, malic acid and concentrated sulphuric acid is heated for about 2 hr on an oil-bath maintained at 120”. till effervescence ceases. The uroduct. after cooling, is poured with stirring into crushed ice and left overnight in the refrigeratbr. The solid that separates out, after filtration, is crystallized from dilute alcohol; the daphnetin is obtained as pale yellow needles melting at 256-7”. 4Methyl-7,8-dihydroxycoumarin
(4methyldaphnetin)18
To an ice-cold solution of pyrogallol in acetoacetic ester, concentrated sulphuric acid is added gradually with constant stirring, the temperature being kept at 0” for about an hour. The deep red viscous liquid is kept in the refrigerator for about 24 hr and then poured with stirring, into water. The solid which separates is filtered off, washed with water and dried. It is crystallized from benzene as colourless needles melting at 234-5”. 4Phenyl-7,8-dihydroxycoumarin
(4phenyldaphnetin)‘s
To a cold solution of pyrogallol in benzoylacetic ester, the requisite amount of concentrated sulphuric acid is gradually added with stirring, the temperature being kept at 0”. The deep red viscous product is kept in the refrigerator for about 24 hr and then poured with stirring into water. The solid which separates is tiltered off, washed with water and dried. It is crystallized from benzene as colourless needles, m.p. 190-92”. 3-Phenyl-7,8-dihydroxycoumarin (3-phenyldaphnetin)“” The compound can be synthesized by the method of BargellnFl as modified by Krishnaswamy.oa Pyrogallol, sodium acetate and acetic anhydride are refluxed for 10 hr, cooled, and poured into water. The acetate which separates out is deacetylated with cold concentrated sulphuric acid. The compound, on crystallization from aqueous alcohol, melts at 213-5”. 3-Ben.zyl-4,5-dihydroxycoumarin2a An equimolar mixture of resorcinol, ethyl benzyl malonate and diphenyl ether is condensed and the resulting product is treated with petroleum ether. It is then filtered off, washed several times with ether, and crystallized from ethanol, m.p. 259-60”. ANALYTICAL
APPLICATIONS
The applications are summarized in Table III. Cerium
Cerium(IV)-3-acetykl-hydroxycoumarin complex is quantitatively precipitated at pH 468.5, and as little as 4 mg of cerium has been estimated with this reagent.23 The complex is usually ignited to CeO, and weighed. As the reagent does not form
Analytical applications TABLE III.-ANALYTIUL
coumarin
of hydroxycoumarins
1047
USES OF HYDROXYCOUMARINS Metal ion determined
: ’ “,‘“,,,, (:i,r
cm9 (g,
23 30 44 46 53
Fe(II1) (s)
OH (Iv) 3-Acetyl-4-hydroxycoumarin
corn (9 COOI)
0 Oximidobenzotetronic
WI)
2% il
wm 6) (s), ww (s)
&yH$l>
01
OS0 acid
Reference
% 41 42 43
FeWI) 6) MoWI) 6) NW? 6) WW (4
34 35 39 50
MoWI) (4 NW9 (4 ‘NW (4
35 39 50
Esculetin
wm 4-Methylesculetin
MoWI) 6)
TiN
Cgl. WW
(g>
35 49
CPhenylesculetin
MOO 6) Ti(Iv) 6) @r) Daphnetin
,6 51
.
M. KATYALand H. B.
1048
SINGIS
Table (III) continued Coumarin
Metal ion determined
Reference
OH
4-Methyldaphnetin OH Mom) (9 NhO (g), TaO TiO (~9 zr(rv) (g)
(a
6 37 48 57
GH, 0 CPhenyldaphnetin OH MoWI) (s)
uwu (9
36 55
3-Phenyldaphnetin
3-Benzyl-4,5-dihydroxycoumarin (g) gravimetric determination;
(s) spectrophotometric determination.
complexes with the tervalent rare earth metals, it can be used for the separation of cerium(IV) from large quantities of lanthanum, yttrium and gadolinium, etc. An attempt24 to use the ammonium salt of the reagent (which is soluble in water and thus avoids use of organic solvents) failed because this salt is unstable, tending to lose ammonia and give a mono-imide.
insoluble
Analytical applications of hydroxycoumarins
1049
Cobalt In his monograph, 25Young has summarized the known methods of determination of cobalt and mentions oximidobenzotetronic acid (V). This coumarin derivative has certain advantages for the spectrophotometric estimation of cobalt.2s From infrared studies,= it appears that the oxime and the 4-carbonyl group take part in chelation, forming a 6-membered ring with the metal ion. Cobalt forms a deep red complex soluble in water and not extractable into chloroform, ether, n-pentanol, benzene, etc. The complex is quite stable and the colour remains constant for at least a week. The absorbance of the complex is maximal and independent of alkalinity at pH > 10. The complex has maximum absorption at 485 rnp and obeys the Beer-Lambert law over the range O-4.7 ppm of cobalt. As little as 0.01 ppm of cobalt can be determined, and Ni(II), Cu(II), Mn(II), Be(H), Zn(II), Al(III), Cr(IlI), V(V), Mo(VI), W(VI), F-, Cl-, Br-, I-, CHsCOO-, SOda-, C20da-, Boss-, tartrate and citrate do not interfere. For the gravimetric determination27*28 cobalt is precipitated quantitatively with an ethanolic solution of the reagent in the pH range 3G6.0 in the presence of ammonium chloride or nitrate. The complex can be weighed as such, Co(C,H,NO& after drying at 120-170” or as CoSO, after treatment with sulphuric acid. In amounts ten times that of the cobalt, Cd(H), Zn(II), Mn(II), Al(II1) and Cr(III) do not interfere. Nickel can be tolerated in amounts equal to that of cobalt but CH,COO-, &Od2-, CpHpOs2and POd3- interfere. In a mixture of palladium and cobalt, the latter can be estimatedBO in the filtrate after separation of palladium with this reagent. Iron
3-Acetyl4hydroxycoumarin has been used for the spectrophotometric determination of iron(IQSOwith which it forms an orange 3 : 1 ligand: metal complex soluble in aqueous ethanol. The complex has maximum absorption at 400 m,u, obeys Beer’s law over the range 1-5-5-3 ppm of iron and is unaffected by acidity over the pH range 2-8-4.3. The tolerances for various ions in determination of 2 ppm of iron are: Cl-, Br-, I-, SCN-, Na and K 200 ppm each; Mg(II) 125 ppm; Pb(II) 115 ppm; Mn(II) 15 ppm; C20,” 10 ppm; Ni(II) 5.8 ppm; Be(H) 4.5 ppm. Even extremely small quantities of Cu(II), MoOda-, WOd2- and citrate interfere. Oximidobenzotetronic acid forms a deep blue, water-soluble complex with iron(II),31 absorption maximum 625 m,u. A similar reaction occurs with iron(III) but with iron(H) the reaction is more sensitive and rapid. The iron complex is stable over the pH range 2.5-10.0, and obeys Beer’s law over the range 0.54-5.4 ppm of iron; its absorbance is unaffected by temperature between 10 and 50”. The reagent is fairly selective for iron, only cobalt, nickel, cerium, zirconium and some of the platinum metals giving serious interference. Oximidobenzotetronic acid has also been useds2 for gravimetric determination of iron(H), in the presence of tenfold amounts or more of Mn(II), Al(III), Cr(III), Ti(IV), Zr(IV), Th(IV), Ni(II), Zn(II), Mo(VI), Ca(II), Mg(II), CH,COO-, F-, SCN-, POd3-, citrate, tartrate, W(VI), Cu(II), Bi(III) and SnQ. The interference due to the last four ions was eliminated by using tartaric acid as masking agent. Cerium(III) and (IV), vanadium(V) and EDTA interfere. The final alcohol concentration was kept below 5 %, the pH was varied from 0.8 to 9-O and large amounts of ammonium chloride or nitrate were added.
1050
M.
KATYAL
and H. B.
SINGH
The qualitative application of the colour reaction between iron and esculetin was reported by Casparis and Manella, 33 followed by more detailed investigations by others.= It has been shown that iron(m) forms two water-soluble complexes, an unstable green one at pH 0.5-4.5, and a comparatively stable red one at pH > 7-O. The latter is a 3 : 1 1igand:iron complex, shown by electrophoretic studies to be negatively charged. Iron can be estimated with this reagent in the presence of F-, Cl-, Br-, I- CHaCOO-, SCN-, C2042-, CqH4062-, BOa3-, Pope- and citrate though most cations interfere owing to their precipitation at high pH. Molybdenum
In esculetin and its derivatives the 7-hydroxy group is very reactive owing to electromeric effects indicated in structure XIV. When a nucleophilic group such as methyl or phenyl is substituted in the 4-position, the dissociation of the 7-hydroxy group decreases and the ligand becomes less acidic. When complex formation between molybdenum and esculetin or its derivatives was studied35 it was found that stability of the complex increases with basicity of the ligand. Molybdenum(VI) complexes formed with esculetin, 4-methylesculetin and 4phenylesculetin are orange-red and show maximum absorption between 384 and 415 rnp. Between pH 5.5 and 6.0 the complex obeys
(XIV)
Beer’s law up to 4.8 ppm of molybdenum. Fe, Ti, Th, Ce, V, W, citrate and acetate ions interfere seriously. The complexes are 2: 1 ligand: molybdenum. Similarly, complex formation between molybdenum(VI) and daphnetin or its Cmethyl and 4-phenyl derivatives has been studied. 6 In each case the complex formed is orange-red, water-soluble and has Lax N 400 rnp. The major species formed is 1: 2 molybdenum : ligand but the presence of a lower complex (1: 1) is also indicated. Ce, Fe, Ti, Th, V, Nb, W, U, Be, Mn, Zn, Cd, citrate, fluoride and oxalate interfere. The 1: 1 yellow complex s6 formed when 3-phenyldaphnetin reacts with molybdenrun has A,,_ 400410 m,u in the pH range l-7 and obeys Beer’s law between l-7 and 5.7 ppm of molybdenum. The interfering ions are the same as for daphnetin and its Csubstituted derivatives. Niobium and tantalum
Niobium has been quantitatively precipitated and separated from tantalum and molybdenum with 4-phenyldaphnetin3’ at pH 5-0-8-5; the complex is ignited to Nb,O, which is then weighed. From infrared studies it appears that the hydrogen atoms of the hydroxy groups are replaced by the metal ion. Tantalum is also precipitated quantitatively at pH 50-8.5 but the precipitate is insoluble in alcohol, in contrast to the alcohol-soluble niobium complex. This difference in solubility has been utilized for the separation of niobium and tantalum. Molybdenum(VI) forms an orange-red water-soluble complex with an alcoholic solution of bphenyldaphnetin. 7,8-Dihydroxy-4-methylcoumarin has also been used for quantitatively precipitating niobium and tantalum.3s
Analytical applications
of hydroxycoumarins
1051
Esculetin and its Cmethyl derivative form orange-red water-soluble complexes with niobium and these have been investigated for its spectrophotometric determination3s at pH 6.5 and 400-405 rnp. The colour of the complexes remains unchanged for 72 hr and they obey Beer’s law. The complexes have been assigned a 1: 3 metal : ligand structure. For the esculetin complex log /I is 10.43 and for the 4-methyl derivative it is 12.07. Be(II), FeOT), Fe(IIQ Cu(II), COO, Pb(IIL V(V), MoOrI), Zr(Iv), CeO, Ce(IV), Ti(IV), Ta(V), W(VI), SCN-, CHaCOO-, POp3- and citrate interfere. Platinum metals Oximidobenzotetronic acid has been recommended for the gravimetric determination of palladium. 40 An ethanolic solution of the reagent quantitatively precipitates Pd(II) as Pd(C,H,NO&, at pH O-5-1. In 0.5N acid solution, Fe(III), Ni(II), Ru(III), RhOI% Os(IQ Irov>, PtO, CrO, Mo(VI), Se(VI), Te(VT), AsO, Sb(lTI), BiO, Ti(Iv), Zr(Iv), PbO, AlO, zn(IU, Cd(IJJ Hg(Q, WTI), AgO, Au@), CH,COO-, F-, C20:-, C,H,O, 2- , PO,% and citrate do not interfere. Cobalt can be determined in the filtrate. Spectrophotometric studies of the coloured complexesfl formed by oximidobenxotetronic acid (OBTA) with ruthenium and rhodium have been carried out and the two metals simultaneously determined. Ru(III) forms a purple-violet complex (2 max 520 rnll> which is stable in the pH range 1.1-l 1.4 and contains ruthenium and ligand in 1: 3 molar ratio. Ion-exchange studies show the complex is uncharged. The complex obeys Beer’s law from 045 to 20.25 ppm of ruthenium and its molar absorptivity is 7.08 x 103. Rh(III) forms a yellow-brown complex (Lax 385 rnp) at pH 2-8 but at higher pH(> 11.5) the complex is reddish-brown with Lar 475 m,u. From ion-exchange studies both complexes appear to be [RhCI,(~H,NOJ,]. The red complex obeys Beer’s law from O-7 to 15.7 ppm of rhodium and its molar absorptivity is 7.06 x 103. Large amounts of NO,, NO,-, Cl-, CH,COO-, F-, SO,“, C!,O,2-, CpH40B2-, BOs3-, POa3-and citrate do not interfere but iron@), cobalt@) and other platinum metals do. OBTA has been used for spectrophotometric determination of iridium.42 Boiling chloroiridate(IV) with ethanolic OBTA solution at pH 10-12 yields an anionic wine-red complex with absorption maximum at 476 rnp. The molar absorptivity is 9.05 x 103 and log /3 is 12.5 -f O-2 (at 30” in 30% ethanol). Ru(III), Fe(U), Co(II), Pd(II), Rh(III) and Pt(IV) interfere but Os(IV), Ni(II), PbQ, NO,, Cl-, ClO,- do not. Complexes of OBTA with Os(IV) and Pt(IV) have been studied spectrophotometrically.43 Ethanolic OBTA solution forms an anionic brown-red 3 : 1 complex (&,, 520-540 mp) with chloro-osmate(IV), stable over the pH range l-1-5.0. With chloroplatinate(IV) two complexes have been characterized, one being yellow (&_ 425 mp) and stable at pH 16-4.0, and the other red (&, 480 m,u) and stable only at pH > 10.2; both complexes are 2 : 1 and anionic. A method for the separation of Ru(III) from other platinum metals by use of Amberlite IRA-410 resin has been suggested, since the Ru-OBTA complex is neutral. The formation constants (log @) for the Os(IV) and Pt(IV) complexes are 15.6 and 11.6 respectively. Thorium Thorium has been estimated gravimetrically at pH 2-4 with 3-acetyl-4-hydroxycoumarin.44 Cerium(III) and lanthanum do not interfere. The thorium complex is
1052
M. KATYALand H. B. SINOH
very soluble in alcohol whereas the uranium(W) complex is insoluble and this can be used to estimate thorium in presence of uranium. 7,8-Dihydroxy-4methylcoumarin has also been recommended for determining thorium.& Titanium Many hydroxycoumarins have been used for gravimetric and spectrophotometric determination of titanium. The complexation of titanium with 3-acetyWhydroxycoumarin in ethanolic solution takes place at pH 7G9.0.~ The yellow precipitate is ignited to TiO,. Patrovskp’ recommended 4-methyl-7,8-dihydroxycoumarin for the quantitative precipitation of titanium. A method& for the separation and estimation of titanium from iron(H) solutions with 4-phenyl-7,8-dihydroxycoumarin at pH 2G6.5 has been described. Even traces of tartrate, citrate, zirconium and EDTA interfere but large amounts of sulphate, acetate and oxalate can be tolerated. Titanium forms an insoluble complex with Cphenylesculetin at pH 1.8-3-7 whereas iron(H) does not.” Tartrate, citrate, zirconium and EDTA interfere. The composition of the complex has been found by applying the method of continuous variations to the precipitated species, and is 1: 1. No band is observed at 3500 cm-l in the infrared spectrum of the complex indicating the absence of hydroxy groups, whereas there is such a band in the infrared spectrum of the free ligand. Evidently the hydrogen atoms of both hydroxy groups in the ligand are liberated in complex formation. o-Dihydroxycoumarins and their derivatives have been used for spectrophotometric determination of titanium. All the chelates formed are 1: 3 (metal :ligand). Esculetin and its 4-methyl derivatives0 form orange-red, water-soluble titanium complexes at pH 5.5. Daphnetin 51has been used for estimating up to 3-Oppm of titanium at pH 4+4*5, the tolerance limits (in ppm) for common anions being BOe3- (200), citrate (lo), F- (50), S042- (200), PO,% (200) and &042- (120) in determination of 0.5 ppm of titanium. 3-Benzyl-4,5-dihydroxycoumarins2 has been used to determine titanium at pH 1.8-2.5. The system obeys Beer’s law at 380 m,u up to 6-2 ppm of metal ion. The orange complex contains titanium and ligand in the ratio 1: 3. Uranium Uranium has been separated from thorium and determined even in the presence of ten times its amount of Ce(IlT) and La@) by use of 3-acetyWhydroxycoumarin as precipitating agent. 44 The uranium complex is insoluble in aqueous ethanol but the thorium complex is soluble. The uranyl complex is soluble, however, in 95 % ethanol and has been found to be 1: 1 and to obey Beer’s law at 380 rnp over the range O-57 ppm of uraniumF3 In view of Sommer’s conclusion 54 that compounds containing ortho and peri dihydroxy groups are chromogenic for uranium, 3-phenyldaphneti@ and 3-benzyl4,5-dihydroxy coumari@ were studied. 3-Phenyldaphnetin in ethanolic solution forms a water-soluble 1: 1 orange-yellow complex with uranyl ions between pH 5.4 and 6.0. The complex obeys Beer’s law up to 9 ppm of uranium; log p is 4-O i O-2 at 30-32” in 30 ‘A alcoholic solution. Tolerance limits (ppm) for common anions are: Boss-(30), citrate (lo), F- (20), C,O42- (20), POZ- (20), SOa2- (200). Th(lV), Fe(III), Co(H), Ni(II), Ti(lV), Ce(IV), Mo(V1) etc. interfere because of their tendency to complexation with o-dihydroxy ligands. Similarly, 3-benzyl-4,5-dihydroxycoumarin reacts with uranium at pH 4.0, forming an orange 1: 1 complex solublein % alcohol.
Analytical applications
1053
of hydroxywumarins
The complex obeys Beer’s law up to 30 ppm of uranium; ferences are similar to those for 3-phenyl daphnetin.
log p is 50 f 0.2. Inter-
Zirconium
The complex formed between zirconium and 3-acetyl4hydroxycoumarirF has been used for gravimetric determination of zirconium. The complex obtained at pH 3.5-7.0 is Anally ignited to ZrO, and weighed. Zirconium forms an insoluble 1: 1 complex with 4-phenylesculetin4Q in the pH range 2.0-3.0 whereas iron does not. This fact has been utilized to separate these two ions. That complexation takes place through the hydroxy groups is proved from infrared studies. Tartrate, citrate and EDTA interfere but acetate, oxalate and sulphate do not. PPhenyldaphnetin 57 has also been used for gravimetric determination of zirconium at pH l-8-7.5. The light yellow, alcohol-soluble complex is contaminated with excess of reagent, which cannot be readily washed out, so it is ignited to the oxide and weighed. Interferences are similar to those for the esculetin method. CONCLUSION
It is evident that hydroxycoumarins are potentially useful analytical reagents. They give quite sensitive reactions and can be made selective by appropriate variation in pH or alcohol concentration and the use of suitable masking agents. They can be used with advantages in the detection and determination of many metals by spectrophotometric and gravimetric techniques. Certain analytically important separations and subsequent estimations have been performed with their aid. Acknowledgement-The authors are grateful to Prof. B. D. Jain for constant encouragement and to the University Grants Commission (India) for the scheme “Analytical Study of Chelates” under which the present review has been written. Zusammenfassung-Es wird eine Ubersicht iiber die analytischen Mbglichkeitcn und die physikalish-chemischen Eigenschaften von Hydroxycumarinen gegeben. R&&-Gn propriettb
pr&sente une revue sur les possibilites physico-chimiques d’hydroxycoumarines.
analytiques
et les
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.
E. Spgth, Ber., 1937, TOA,83. T. R. Seshadri and S. Varadarajan, Proc. Indian Acad. Sci., 1952, 35A, 75. G. Annoni, Riv. Gerontol. Geriat, 1957, 6,243. G. Di Maggio, Biochim. Appl. 1958,5,45. K. T. Gleirn, U.S. Patent 2740761, Apr. 3, 1956; Chem. Abstr., 1956,50, 13338~. H. B. Singh, Ph.D. Thesis, Delhi University, 1966. K. Sen and P. Bagchi, J. Org. Chem., 1959,24,316. B. K. Ganguli and P. Bag&i, ibid., 1956,21,1415. H. von Pechmann, Ber., 1884,17,929. H. R. Eisenhaur and K. P. Link, J. Am. Chem. Sot., 1953,75,2044. R. Anschiitz, Ber., 1903,36,465. A. Somr, ibid., 1917, 50, 1292. H. Pauly and K. Lockmann, ibid., 1915,48,28. M. A. Stahmann, I. Wolff and K. P. Link, J. Am. Chem. Sot., 1943,65,2285. R. Anschtitz, Annalen, 1909,367, 169. G. Amiard and A. Allais, Bull. Sot. Chim. France, 1947, 512. V. K. Ahluwaiia and T. R. Seshadri, J. Chem. Sot., 1957,970. H. von Pechmann and J. B. Cohen, Ber., 1884,17,2187. St. von Kostanecki and C. Waber, ibid., 1893, 26,2906. N. R. Krishnaswamy, Ph.D. Thesis, Delhi University, 1962.
1054 21. 22. 23. 24. 25. 26. 27.
M. KATYAL~~
H.B.
SINGH
G. Bargellini, Gazz. Chim. Ital., 1927,57,457. K. N. Trivedi, J. Sci. Ind. Res. (India), 1962,21,402. A. N. Bhat and B. D. Jam, J. Less-Common Metals, 1961,3, 259. A. N. Bhat, Ph.D. Thesis, Delhi University, 1961. R. S. Young, The Analytical Chemistry of Cobalt, Pergamon, Oxford, 1966. A. N. Bhat and B. D. Jam, J. Indian Chem. Sot., 1961,38,779. G. S. Manku, A. N. Bhat and B. D. Jam, Paper presented at Joint Convention of Chem. Res. Comm. CSIR and Sot. Biol. Chem. (India), Dec. 1966. 28. Idem, Anal. Chim. Acta, 1967,39, 128. 29. Idem, ibid., 1967,39, 369. 30. A. N. Bhat and B. D Jam, Talanta, 1960,5,271. 31. Idem, Anal. Chim. Acta, 1961, 25, 343. 32. G. S. Manku, A. N. Bhat and B. D. Jain, Proc. Indian Acad. Sci., 1968, 63 (in press). 33. I. P. Caparis and E. Manella, Hundert Jahre Schweiz Apoth.-Ver., 1843-1943,347; Chem. Abstr., 1944,38,18418. 34. B. D. Jain and H. B. Singh, J. Indian Chem. Sot., 1963,40,263. 35. Idem, Indian J. Chem., 1963, 1, 369. 36. B. D. Jain and R. Kumar, Current Sci., (Zndia), 1966, 35, 557. 37. B. D. Jain and H. B. Singh, J. Less-Common Metals, 1964, 7,464. 38. V. Patrovskp, Collection Czech. Chem. Commun., 1962,27, 1824. 39. B. D. Jain and H. B. Singh, Anal. Chim. Acta, 1967,37, 135. 40. G. S. Manku, A. N. Bhat and B. D. Jain, ibid., 1967,39,369. 41. Idem, Talanta, 1967,14, 1229. 42. Idem, unpublished work. 43. Idem, unpublished work. 44. A. N. Bhat and B. D. Jain, Talanta, 1960,4,13. 45. V. Patrovskjr, Chemie, 1958,10,93. 46. A. N. Bhat and B. D. Jam, Proc. Indian Acad. Sci., 1961,53,147. 47. V. Patrovski, Collection Czech. Chem. Commun., 1962, 27, 1824. 48. B. D. Jain and H. B. Singh, Indian J. Chem., 1963,1,317. 49. Idem, ibid., 1964,2,246. 50. Idem, J. Indian Chem. Sot., 1964, 41,29. 51. Idem, Indian J. Chem., 1964,2,245. 52. B. D. Jain and R. Kumar, Proc. Indian Acad. Sci., 1964,6OA, 265. 53. A. N. Bhat and B. D. Jain, J. Inorg. Nucl. Chem., 1961,23, 136. 54. L. Sommer, Z. Anal. Chem., 1962,187,7. 55. B. D. Jain and R. Kumar, Proc. Indian Acad. Sci., 1964,59,185. 56. Idem, Current Sci. (India), 1966,35, 173. 57. 33. D. Jain and H. B. Singh, Proc. Indian Acad. Sci., 1964, 59, 362.
Penwmon Press. Printed in Northern Irelattd
ANALYTICAL APPLICATIONS HYDROXYCOUMARINS
OF
MOHAN KATYAL St. Stephen’s College, Delhi-7, India H. B. SINGH* Charles University, Albertov 2030, Prague 2, Czechoslovakia (Received 7 December 1967. Accepted 3 March 1968)
Summary-A review is presented of the analytical potentialities and physico-chemical properties of hydroxycoumarins. COUMARINS, derivatives of benzo-a-pyrone (I.), occur in plants belonging to the natural orders of Orchidaceae, Leguminaceae, Rutaceae, Umbelll$erae and Labiatae.l
Some coumarin derivatives exhibit distinct physiological, photodynamic and bacteriostatic activity. 2-4 Besides application of their physiological activity, a number of uses have been found for them.5 The chelating characteristics of the coumarins have long been known; Cmethylumbelliferone is a well known fluoresence indicator and the bacteriostatic properties of some of the coumarins have been attributed to chelation, In the last decade various coumarins have been extensively studied as analytical reagents. Physico-chemical studies of the ligands and the complexes have also been reported.6 The relative positions of the hydroxy and carbonyl groups have been found to alter the spectral characteristics of the compounds and the reactivity of the hydroxy groups, and the effect of substitution on the absorption spectrum of the parent compound has been studied. The dissociation constants of the various ligands have been determined potentiometrically. The effect of substitution on the basicity of the ligands has been investigated and an attempt made to correlate the basicity of the ligands with the frequency of the hydroxy group absorption bands in the infrared region. A linear relationship between the Hammett u function for the substituted ligands and the infrared absorption frequency of the hydroxy group has been established. Methylation studies of o-dihydroxycoumarins derived from esculetin and daphnetin show that the hydroxy group at the 7-position can be preferentially methylated, though ordinarily a dimethyl derivative is obtained. It is concluded that the 7-hydroxy group is slightly more reactive than the other but not significantly so. Infrared studies indicate the presence of only weak intramolecular hydrogen bonding. Coumarins show maximum absorption at about 300 rnp, with log E = 4. The spectrum usually shows additional strong bands between 250 and 340 rnp. The introduction of a hydroxy group into the coumarin molecule modifies its absorption characteristics,’ generally causing a bathochromic shift of the principal absorption band. This shift due to the auxochromic hydroxy group results from the transition
* Present address: Hindu College, Delhi-7, India. 4
1043
1044
M.
KATYAL
and H. B.
SINGH
from the ground state to the excited state by an interaction of the type:
which would result in a decrease in transition energy and hence displacement to longer wavelengths. Compounds such as 5,7dihydroxy-, 6,7-dihydroxy- and 7,8dihydroxycoumarins all exhibit bathochromic shifts. The substitution of a hydroxy group at the S-position results in a significant hypsochromic shift. This is possible because a hydroxy group in this position binds the electron pair of the pyrone oxygen atom, leading to the suppression of the n-rr interactions of coumarins as shown in II. The substitution of a hydrogen atom by a methyl group* either in the benzene ring or in the heterocyclic ring does not produce any significant change in the absorption characteristics of the coumarins. Any hypsochromic effect is attributed mainly to steric hindrance with the hydrogen atom at the ortho or peri position. A methyl group substituted in the 4-position does not have any marked effect on the spectrum of esculetin but causes a significant hypsochromic shift of the principal absorption band of daphnetin. This shift has been attributed to weakening of the conjugation between the 7-hydroxy group and the lactone carbonyl group. O--H
fl
..
HO /
/
’
1’
3
I-1.: 0
o /’
W)
4-Phenylesculetin shows a considerable bathochromic shift as a result of an increase in the number of resonating forms. The phenyl group substituted in the 4-position of daphnetin exhibits a weak electron donor effect, this effect being particularly marked because the electron contribution to the carbonyl group from the heterocyclic oxygen atom is reduced by hydrogen bonding by the 8-hydroxy group (III). As this structure does not involve any increase in conjugation of the carbonyl group, there is no great shift in the principal absorption band. The inductive and resonance effects due to the substituents on the reacting centre of the ligand can be measured by the magnitude of the Hammett u function, which covers both effects. The Hammett c function has been calculated for some coumarins and their derivatives (Table I) and plotted against the infrared frequency for the hydroxy groups. Substitution of a methyl group in esculetin and daphnetin has an electron donating effect; substitution of a phenyl group has the reverse effect. The c values calculated from the first dissociation constant give a linear relationship with the frequency shifts, but those calculated by use of the second dissociation constant or the overall dissociation constant do not. This shows that only one hydroxy group is affected by substitution in the 4-position. The slopes of the graphs for the esculetin and daphnetin series are of opposite sign.
Analytical applications
of hydroxycoumarhrs
1045
TABLEI Compound
PKI
PKI
Esculetin 4-Methylesculetin CPhenylesculetin Daphnetin CMethyldaphnetin 4-Phenyldaphnetm
7.31 744 7.27 7.32 7.63 740
8.03 8.12 8.01 8.15 8.42 8.20
Hammett
u function
-0.13 +0*04 -;31 -0.08
Apparent stability constants of metal complexes with various o-dihydroxycoumarins have been calculated (Table II) and increase with increase in the basic strength, p&e, of the l&and. The greater stability of phenyl -substituted complexes appears to be due to resonance effects, but the values for molybdenum complexes with daphnetins have not yet been explained. TABLE II
log K for complex L&and Esculetin 4-Methylesculetin 4-Phenylesculetin Daphnetin CMethyldaphnetin CPhenyldaphnetin
p&z
15.34 15.56 15.28 15.47 16.05 1560
MO
Nb
Ti
U
3.65 7.55 8.20 8.01 7.21 7.45
10.43 12.07 12.94 13.24 -
8.8 10.7 14.9 -
3.56 4.03 4.30 3.21 4.15 4.23
The wavelength of maximum absorption for transition metal chelates with dihydroxycoumarins depends on the concentration of l&and, the pH, and the type of solvent. In view of the reducing character of the dihydroxycoumarins, it has been suggested that the metal complexes have charge-transfer spectra. SYNTHESIS
OF
COUMARINS
Coumarins, in general, can be synthesized by the Pechmann reaction> i.e., by condensing the appropriate phenolic compound, or its derivative, with malic acid or t%ketonic ester in the presence of concentrated sulphuric acid. The methods used for analytically important hydroxycoumarins are outlined below. Though many methods11-14 are available for synthesis of Chydroxycoumarin and its subsequent acetylation in the 3-position, the one due to Stahmarm et a1.l” appears to be the best. In this method salicylate is acetylated with acetic anhydride and concentrated sulphuric acid at 40” to yield methyl acetylsalicylate, which is then separated and condensed with sodium in liquid pa&in. The reaction mixture is kept at 250” for about 2 hr and then filtered hot. Acidification and crystallization yield 4-hydroxycoumarin, m.p. 200-206”. The coumarin is then acetylated with acetyl chloride in dry pyridine containing a few drops of piperidine. The mixture is kept at 37” for 48 hr, then poured into ice and dilute hydrochloric acid to yield 3-acetyl-4-hydroxycoumarin. The product, crystallized from aqueous ethanol and then sublimed, melts at 138”. Oximidobenzotetronic acid15 The preparation involves the treatment of Chydroxycoumarin with aqueous sodium nitrite solution and subsequent acidification in ice-cold medium. On crystallization from hot chloroform, shining pale yellow crystals of oximidobenzotetronic acid are obtained, m.p. 149” (decomp.). 6,7-Dihydroxycoumarin (esculetin)ls An intimate mixture of hydroxyhydroquhrone triacetate, malic acid and concentrated sulphuric acid is heated on a boiling water-bath till effervescence ceases. The reaction mixture, after cooling,
1046
M. KATYAL
and H. B. SINGH
is poured into crushed ice, stirred and left overnight. esculetin as pale yellow prisms, decomposing 4Methyl-6,7-dihydroxycoumarin
Crystallization
from dilute alcohol gives
above 270”.
(4methylesculetin)1s
To an ice-cold solution of hydroxyhydroquinone triacetate in acetoacetic ester, concentrated sulphuric acid is added gradually with stirring, the temperature being kept at 0” for about 1 hr. The deep red viscous product is kept in the refrigerator for 24 hr and then poured, with constant stirring, into water. The resulting solid is filtered off, washed with water, dried, and crystallized from ethanol as yellow needles (m.p. 276-8”). 4Phenyl-6,7-dihydroxycoumarin
(4-phenylesculetin)ls
A paste of benzoylacetic ester and hydroxyhydroquinone triacetate is added to 75% sulphuric acid and dissolves in it with evolution of heat to form a deep red solution. This solution is heated to 80” on a water-bath for about an hour and is occasionally shaken. After cooling to room temperature it is poured, with stirring, into cold water and the resultant mixture allowed to cool to room temperature. After filtration, the precipitate is washed with cold water till free from acid, and is then dissolved in hot borax solution, whereupon Cphenylesculetin borate separates. This borate is decomposed with dilute sulphuric acid and the product is crystallized from alcohol as rectangular tablets and tiny prisms, m.p. 267-8”. 7,8-Dihydroxycoumarin (daphneti@ An intimate mixture of requisite amounts of pyrogallol, malic acid and concentrated sulphuric acid is heated for about 2 hr on an oil-bath maintained at 120”. till effervescence ceases. The uroduct. after cooling, is poured with stirring into crushed ice and left overnight in the refrigeratbr. The solid that separates out, after filtration, is crystallized from dilute alcohol; the daphnetin is obtained as pale yellow needles melting at 256-7”. 4Methyl-7,8-dihydroxycoumarin
(4methyldaphnetin)18
To an ice-cold solution of pyrogallol in acetoacetic ester, concentrated sulphuric acid is added gradually with constant stirring, the temperature being kept at 0” for about an hour. The deep red viscous liquid is kept in the refrigerator for about 24 hr and then poured with stirring, into water. The solid which separates is filtered off, washed with water and dried. It is crystallized from benzene as colourless needles melting at 234-5”. 4Phenyl-7,8-dihydroxycoumarin
(4phenyldaphnetin)‘s
To a cold solution of pyrogallol in benzoylacetic ester, the requisite amount of concentrated sulphuric acid is gradually added with stirring, the temperature being kept at 0”. The deep red viscous product is kept in the refrigerator for about 24 hr and then poured with stirring into water. The solid which separates is tiltered off, washed with water and dried. It is crystallized from benzene as colourless needles, m.p. 190-92”. 3-Phenyl-7,8-dihydroxycoumarin (3-phenyldaphnetin)“” The compound can be synthesized by the method of BargellnFl as modified by Krishnaswamy.oa Pyrogallol, sodium acetate and acetic anhydride are refluxed for 10 hr, cooled, and poured into water. The acetate which separates out is deacetylated with cold concentrated sulphuric acid. The compound, on crystallization from aqueous alcohol, melts at 213-5”. 3-Ben.zyl-4,5-dihydroxycoumarin2a An equimolar mixture of resorcinol, ethyl benzyl malonate and diphenyl ether is condensed and the resulting product is treated with petroleum ether. It is then filtered off, washed several times with ether, and crystallized from ethanol, m.p. 259-60”. ANALYTICAL
APPLICATIONS
The applications are summarized in Table III. Cerium
Cerium(IV)-3-acetykl-hydroxycoumarin complex is quantitatively precipitated at pH 468.5, and as little as 4 mg of cerium has been estimated with this reagent.23 The complex is usually ignited to CeO, and weighed. As the reagent does not form
Analytical applications TABLE III.-ANALYTIUL
coumarin
of hydroxycoumarins
1047
USES OF HYDROXYCOUMARINS Metal ion determined
: ’ “,‘“,,,, (:i,r
cm9 (g,
23 30 44 46 53
Fe(II1) (s)
OH (Iv) 3-Acetyl-4-hydroxycoumarin
corn (9 COOI)
0 Oximidobenzotetronic
WI)
2% il
wm 6) (s), ww (s)
&yH$l>
01
OS0 acid
Reference
% 41 42 43
FeWI) 6) MoWI) 6) NW? 6) WW (4
34 35 39 50
MoWI) (4 NW9 (4 ‘NW (4
35 39 50
Esculetin
wm 4-Methylesculetin
MoWI) 6)
TiN
Cgl. WW
(g>
35 49
CPhenylesculetin
MOO 6) Ti(Iv) 6) @r) Daphnetin
,6 51
.
M. KATYALand H. B.
1048
SINGIS
Table (III) continued Coumarin
Metal ion determined
Reference
OH
4-Methyldaphnetin OH Mom) (9 NhO (g), TaO TiO (~9 zr(rv) (g)
(a
6 37 48 57
GH, 0 CPhenyldaphnetin OH MoWI) (s)
uwu (9
36 55
3-Phenyldaphnetin
3-Benzyl-4,5-dihydroxycoumarin (g) gravimetric determination;
(s) spectrophotometric determination.
complexes with the tervalent rare earth metals, it can be used for the separation of cerium(IV) from large quantities of lanthanum, yttrium and gadolinium, etc. An attempt24 to use the ammonium salt of the reagent (which is soluble in water and thus avoids use of organic solvents) failed because this salt is unstable, tending to lose ammonia and give a mono-imide.
insoluble
Analytical applications of hydroxycoumarins
1049
Cobalt In his monograph, 25Young has summarized the known methods of determination of cobalt and mentions oximidobenzotetronic acid (V). This coumarin derivative has certain advantages for the spectrophotometric estimation of cobalt.2s From infrared studies,= it appears that the oxime and the 4-carbonyl group take part in chelation, forming a 6-membered ring with the metal ion. Cobalt forms a deep red complex soluble in water and not extractable into chloroform, ether, n-pentanol, benzene, etc. The complex is quite stable and the colour remains constant for at least a week. The absorbance of the complex is maximal and independent of alkalinity at pH > 10. The complex has maximum absorption at 485 rnp and obeys the Beer-Lambert law over the range O-4.7 ppm of cobalt. As little as 0.01 ppm of cobalt can be determined, and Ni(II), Cu(II), Mn(II), Be(H), Zn(II), Al(III), Cr(IlI), V(V), Mo(VI), W(VI), F-, Cl-, Br-, I-, CHsCOO-, SOda-, C20da-, Boss-, tartrate and citrate do not interfere. For the gravimetric determination27*28 cobalt is precipitated quantitatively with an ethanolic solution of the reagent in the pH range 3G6.0 in the presence of ammonium chloride or nitrate. The complex can be weighed as such, Co(C,H,NO& after drying at 120-170” or as CoSO, after treatment with sulphuric acid. In amounts ten times that of the cobalt, Cd(H), Zn(II), Mn(II), Al(II1) and Cr(III) do not interfere. Nickel can be tolerated in amounts equal to that of cobalt but CH,COO-, &Od2-, CpHpOs2and POd3- interfere. In a mixture of palladium and cobalt, the latter can be estimatedBO in the filtrate after separation of palladium with this reagent. Iron
3-Acetyl4hydroxycoumarin has been used for the spectrophotometric determination of iron(IQSOwith which it forms an orange 3 : 1 ligand: metal complex soluble in aqueous ethanol. The complex has maximum absorption at 400 m,u, obeys Beer’s law over the range 1-5-5-3 ppm of iron and is unaffected by acidity over the pH range 2-8-4.3. The tolerances for various ions in determination of 2 ppm of iron are: Cl-, Br-, I-, SCN-, Na and K 200 ppm each; Mg(II) 125 ppm; Pb(II) 115 ppm; Mn(II) 15 ppm; C20,” 10 ppm; Ni(II) 5.8 ppm; Be(H) 4.5 ppm. Even extremely small quantities of Cu(II), MoOda-, WOd2- and citrate interfere. Oximidobenzotetronic acid forms a deep blue, water-soluble complex with iron(II),31 absorption maximum 625 m,u. A similar reaction occurs with iron(III) but with iron(H) the reaction is more sensitive and rapid. The iron complex is stable over the pH range 2.5-10.0, and obeys Beer’s law over the range 0.54-5.4 ppm of iron; its absorbance is unaffected by temperature between 10 and 50”. The reagent is fairly selective for iron, only cobalt, nickel, cerium, zirconium and some of the platinum metals giving serious interference. Oximidobenzotetronic acid has also been useds2 for gravimetric determination of iron(H), in the presence of tenfold amounts or more of Mn(II), Al(III), Cr(III), Ti(IV), Zr(IV), Th(IV), Ni(II), Zn(II), Mo(VI), Ca(II), Mg(II), CH,COO-, F-, SCN-, POd3-, citrate, tartrate, W(VI), Cu(II), Bi(III) and SnQ. The interference due to the last four ions was eliminated by using tartaric acid as masking agent. Cerium(III) and (IV), vanadium(V) and EDTA interfere. The final alcohol concentration was kept below 5 %, the pH was varied from 0.8 to 9-O and large amounts of ammonium chloride or nitrate were added.
1050
M.
KATYAL
and H. B.
SINGH
The qualitative application of the colour reaction between iron and esculetin was reported by Casparis and Manella, 33 followed by more detailed investigations by others.= It has been shown that iron(m) forms two water-soluble complexes, an unstable green one at pH 0.5-4.5, and a comparatively stable red one at pH > 7-O. The latter is a 3 : 1 1igand:iron complex, shown by electrophoretic studies to be negatively charged. Iron can be estimated with this reagent in the presence of F-, Cl-, Br-, I- CHaCOO-, SCN-, C2042-, CqH4062-, BOa3-, Pope- and citrate though most cations interfere owing to their precipitation at high pH. Molybdenum
In esculetin and its derivatives the 7-hydroxy group is very reactive owing to electromeric effects indicated in structure XIV. When a nucleophilic group such as methyl or phenyl is substituted in the 4-position, the dissociation of the 7-hydroxy group decreases and the ligand becomes less acidic. When complex formation between molybdenum and esculetin or its derivatives was studied35 it was found that stability of the complex increases with basicity of the ligand. Molybdenum(VI) complexes formed with esculetin, 4-methylesculetin and 4phenylesculetin are orange-red and show maximum absorption between 384 and 415 rnp. Between pH 5.5 and 6.0 the complex obeys
(XIV)
Beer’s law up to 4.8 ppm of molybdenum. Fe, Ti, Th, Ce, V, W, citrate and acetate ions interfere seriously. The complexes are 2: 1 ligand: molybdenum. Similarly, complex formation between molybdenum(VI) and daphnetin or its Cmethyl and 4-phenyl derivatives has been studied. 6 In each case the complex formed is orange-red, water-soluble and has Lax N 400 rnp. The major species formed is 1: 2 molybdenum : ligand but the presence of a lower complex (1: 1) is also indicated. Ce, Fe, Ti, Th, V, Nb, W, U, Be, Mn, Zn, Cd, citrate, fluoride and oxalate interfere. The 1: 1 yellow complex s6 formed when 3-phenyldaphnetin reacts with molybdenrun has A,,_ 400410 m,u in the pH range l-7 and obeys Beer’s law between l-7 and 5.7 ppm of molybdenum. The interfering ions are the same as for daphnetin and its Csubstituted derivatives. Niobium and tantalum
Niobium has been quantitatively precipitated and separated from tantalum and molybdenum with 4-phenyldaphnetin3’ at pH 5-0-8-5; the complex is ignited to Nb,O, which is then weighed. From infrared studies it appears that the hydrogen atoms of the hydroxy groups are replaced by the metal ion. Tantalum is also precipitated quantitatively at pH 50-8.5 but the precipitate is insoluble in alcohol, in contrast to the alcohol-soluble niobium complex. This difference in solubility has been utilized for the separation of niobium and tantalum. Molybdenum(VI) forms an orange-red water-soluble complex with an alcoholic solution of bphenyldaphnetin. 7,8-Dihydroxy-4-methylcoumarin has also been used for quantitatively precipitating niobium and tantalum.3s
Analytical applications
of hydroxycoumarins
1051
Esculetin and its Cmethyl derivative form orange-red water-soluble complexes with niobium and these have been investigated for its spectrophotometric determination3s at pH 6.5 and 400-405 rnp. The colour of the complexes remains unchanged for 72 hr and they obey Beer’s law. The complexes have been assigned a 1: 3 metal : ligand structure. For the esculetin complex log /I is 10.43 and for the 4-methyl derivative it is 12.07. Be(II), FeOT), Fe(IIQ Cu(II), COO, Pb(IIL V(V), MoOrI), Zr(Iv), CeO, Ce(IV), Ti(IV), Ta(V), W(VI), SCN-, CHaCOO-, POp3- and citrate interfere. Platinum metals Oximidobenzotetronic acid has been recommended for the gravimetric determination of palladium. 40 An ethanolic solution of the reagent quantitatively precipitates Pd(II) as Pd(C,H,NO&, at pH O-5-1. In 0.5N acid solution, Fe(III), Ni(II), Ru(III), RhOI% Os(IQ Irov>, PtO, CrO, Mo(VI), Se(VI), Te(VT), AsO, Sb(lTI), BiO, Ti(Iv), Zr(Iv), PbO, AlO, zn(IU, Cd(IJJ Hg(Q, WTI), AgO, Au@), CH,COO-, F-, C20:-, C,H,O, 2- , PO,% and citrate do not interfere. Cobalt can be determined in the filtrate. Spectrophotometric studies of the coloured complexesfl formed by oximidobenxotetronic acid (OBTA) with ruthenium and rhodium have been carried out and the two metals simultaneously determined. Ru(III) forms a purple-violet complex (2 max 520 rnll> which is stable in the pH range 1.1-l 1.4 and contains ruthenium and ligand in 1: 3 molar ratio. Ion-exchange studies show the complex is uncharged. The complex obeys Beer’s law from 045 to 20.25 ppm of ruthenium and its molar absorptivity is 7.08 x 103. Rh(III) forms a yellow-brown complex (Lax 385 rnp) at pH 2-8 but at higher pH(> 11.5) the complex is reddish-brown with Lar 475 m,u. From ion-exchange studies both complexes appear to be [RhCI,(~H,NOJ,]. The red complex obeys Beer’s law from O-7 to 15.7 ppm of rhodium and its molar absorptivity is 7.06 x 103. Large amounts of NO,, NO,-, Cl-, CH,COO-, F-, SO,“, C!,O,2-, CpH40B2-, BOs3-, POa3-and citrate do not interfere but iron@), cobalt@) and other platinum metals do. OBTA has been used for spectrophotometric determination of iridium.42 Boiling chloroiridate(IV) with ethanolic OBTA solution at pH 10-12 yields an anionic wine-red complex with absorption maximum at 476 rnp. The molar absorptivity is 9.05 x 103 and log /3 is 12.5 -f O-2 (at 30” in 30% ethanol). Ru(III), Fe(U), Co(II), Pd(II), Rh(III) and Pt(IV) interfere but Os(IV), Ni(II), PbQ, NO,, Cl-, ClO,- do not. Complexes of OBTA with Os(IV) and Pt(IV) have been studied spectrophotometrically.43 Ethanolic OBTA solution forms an anionic brown-red 3 : 1 complex (&,, 520-540 mp) with chloro-osmate(IV), stable over the pH range l-1-5.0. With chloroplatinate(IV) two complexes have been characterized, one being yellow (&_ 425 mp) and stable at pH 16-4.0, and the other red (&, 480 m,u) and stable only at pH > 10.2; both complexes are 2 : 1 and anionic. A method for the separation of Ru(III) from other platinum metals by use of Amberlite IRA-410 resin has been suggested, since the Ru-OBTA complex is neutral. The formation constants (log @) for the Os(IV) and Pt(IV) complexes are 15.6 and 11.6 respectively. Thorium Thorium has been estimated gravimetrically at pH 2-4 with 3-acetyl-4-hydroxycoumarin.44 Cerium(III) and lanthanum do not interfere. The thorium complex is
1052
M. KATYALand H. B. SINOH
very soluble in alcohol whereas the uranium(W) complex is insoluble and this can be used to estimate thorium in presence of uranium. 7,8-Dihydroxy-4methylcoumarin has also been recommended for determining thorium.& Titanium Many hydroxycoumarins have been used for gravimetric and spectrophotometric determination of titanium. The complexation of titanium with 3-acetyWhydroxycoumarin in ethanolic solution takes place at pH 7G9.0.~ The yellow precipitate is ignited to TiO,. Patrovskp’ recommended 4-methyl-7,8-dihydroxycoumarin for the quantitative precipitation of titanium. A method& for the separation and estimation of titanium from iron(H) solutions with 4-phenyl-7,8-dihydroxycoumarin at pH 2G6.5 has been described. Even traces of tartrate, citrate, zirconium and EDTA interfere but large amounts of sulphate, acetate and oxalate can be tolerated. Titanium forms an insoluble complex with Cphenylesculetin at pH 1.8-3-7 whereas iron(H) does not.” Tartrate, citrate, zirconium and EDTA interfere. The composition of the complex has been found by applying the method of continuous variations to the precipitated species, and is 1: 1. No band is observed at 3500 cm-l in the infrared spectrum of the complex indicating the absence of hydroxy groups, whereas there is such a band in the infrared spectrum of the free ligand. Evidently the hydrogen atoms of both hydroxy groups in the ligand are liberated in complex formation. o-Dihydroxycoumarins and their derivatives have been used for spectrophotometric determination of titanium. All the chelates formed are 1: 3 (metal :ligand). Esculetin and its 4-methyl derivatives0 form orange-red, water-soluble titanium complexes at pH 5.5. Daphnetin 51has been used for estimating up to 3-Oppm of titanium at pH 4+4*5, the tolerance limits (in ppm) for common anions being BOe3- (200), citrate (lo), F- (50), S042- (200), PO,% (200) and &042- (120) in determination of 0.5 ppm of titanium. 3-Benzyl-4,5-dihydroxycoumarins2 has been used to determine titanium at pH 1.8-2.5. The system obeys Beer’s law at 380 m,u up to 6-2 ppm of metal ion. The orange complex contains titanium and ligand in the ratio 1: 3. Uranium Uranium has been separated from thorium and determined even in the presence of ten times its amount of Ce(IlT) and La@) by use of 3-acetyWhydroxycoumarin as precipitating agent. 44 The uranium complex is insoluble in aqueous ethanol but the thorium complex is soluble. The uranyl complex is soluble, however, in 95 % ethanol and has been found to be 1: 1 and to obey Beer’s law at 380 rnp over the range O-57 ppm of uraniumF3 In view of Sommer’s conclusion 54 that compounds containing ortho and peri dihydroxy groups are chromogenic for uranium, 3-phenyldaphneti@ and 3-benzyl4,5-dihydroxy coumari@ were studied. 3-Phenyldaphnetin in ethanolic solution forms a water-soluble 1: 1 orange-yellow complex with uranyl ions between pH 5.4 and 6.0. The complex obeys Beer’s law up to 9 ppm of uranium; log p is 4-O i O-2 at 30-32” in 30 ‘A alcoholic solution. Tolerance limits (ppm) for common anions are: Boss-(30), citrate (lo), F- (20), C,O42- (20), POZ- (20), SOa2- (200). Th(lV), Fe(III), Co(H), Ni(II), Ti(lV), Ce(IV), Mo(V1) etc. interfere because of their tendency to complexation with o-dihydroxy ligands. Similarly, 3-benzyl-4,5-dihydroxycoumarin reacts with uranium at pH 4.0, forming an orange 1: 1 complex solublein % alcohol.
Analytical applications
1053
of hydroxywumarins
The complex obeys Beer’s law up to 30 ppm of uranium; ferences are similar to those for 3-phenyl daphnetin.
log p is 50 f 0.2. Inter-
Zirconium
The complex formed between zirconium and 3-acetyl4hydroxycoumarirF has been used for gravimetric determination of zirconium. The complex obtained at pH 3.5-7.0 is Anally ignited to ZrO, and weighed. Zirconium forms an insoluble 1: 1 complex with 4-phenylesculetin4Q in the pH range 2.0-3.0 whereas iron does not. This fact has been utilized to separate these two ions. That complexation takes place through the hydroxy groups is proved from infrared studies. Tartrate, citrate and EDTA interfere but acetate, oxalate and sulphate do not. PPhenyldaphnetin 57 has also been used for gravimetric determination of zirconium at pH l-8-7.5. The light yellow, alcohol-soluble complex is contaminated with excess of reagent, which cannot be readily washed out, so it is ignited to the oxide and weighed. Interferences are similar to those for the esculetin method. CONCLUSION
It is evident that hydroxycoumarins are potentially useful analytical reagents. They give quite sensitive reactions and can be made selective by appropriate variation in pH or alcohol concentration and the use of suitable masking agents. They can be used with advantages in the detection and determination of many metals by spectrophotometric and gravimetric techniques. Certain analytically important separations and subsequent estimations have been performed with their aid. Acknowledgement-The authors are grateful to Prof. B. D. Jain for constant encouragement and to the University Grants Commission (India) for the scheme “Analytical Study of Chelates” under which the present review has been written. Zusammenfassung-Es wird eine Ubersicht iiber die analytischen Mbglichkeitcn und die physikalish-chemischen Eigenschaften von Hydroxycumarinen gegeben. R&&-Gn propriettb
pr&sente une revue sur les possibilites physico-chimiques d’hydroxycoumarines.
analytiques
et les
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.
E. Spgth, Ber., 1937, TOA,83. T. R. Seshadri and S. Varadarajan, Proc. Indian Acad. Sci., 1952, 35A, 75. G. Annoni, Riv. Gerontol. Geriat, 1957, 6,243. G. Di Maggio, Biochim. Appl. 1958,5,45. K. T. Gleirn, U.S. Patent 2740761, Apr. 3, 1956; Chem. Abstr., 1956,50, 13338~. H. B. Singh, Ph.D. Thesis, Delhi University, 1966. K. Sen and P. Bagchi, J. Org. Chem., 1959,24,316. B. K. Ganguli and P. Bag&i, ibid., 1956,21,1415. H. von Pechmann, Ber., 1884,17,929. H. R. Eisenhaur and K. P. Link, J. Am. Chem. Sot., 1953,75,2044. R. Anschiitz, Ber., 1903,36,465. A. Somr, ibid., 1917, 50, 1292. H. Pauly and K. Lockmann, ibid., 1915,48,28. M. A. Stahmann, I. Wolff and K. P. Link, J. Am. Chem. Sot., 1943,65,2285. R. Anschtitz, Annalen, 1909,367, 169. G. Amiard and A. Allais, Bull. Sot. Chim. France, 1947, 512. V. K. Ahluwaiia and T. R. Seshadri, J. Chem. Sot., 1957,970. H. von Pechmann and J. B. Cohen, Ber., 1884,17,2187. St. von Kostanecki and C. Waber, ibid., 1893, 26,2906. N. R. Krishnaswamy, Ph.D. Thesis, Delhi University, 1962.
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G. Bargellini, Gazz. Chim. Ital., 1927,57,457. K. N. Trivedi, J. Sci. Ind. Res. (India), 1962,21,402. A. N. Bhat and B. D. Jam, J. Less-Common Metals, 1961,3, 259. A. N. Bhat, Ph.D. Thesis, Delhi University, 1961. R. S. Young, The Analytical Chemistry of Cobalt, Pergamon, Oxford, 1966. A. N. Bhat and B. D. Jam, J. Indian Chem. Sot., 1961,38,779. G. S. Manku, A. N. Bhat and B. D. Jam, Paper presented at Joint Convention of Chem. Res. Comm. CSIR and Sot. Biol. Chem. (India), Dec. 1966. 28. Idem, Anal. Chim. Acta, 1967,39, 128. 29. Idem, ibid., 1967,39, 369. 30. A. N. Bhat and B. D Jam, Talanta, 1960,5,271. 31. Idem, Anal. Chim. Acta, 1961, 25, 343. 32. G. S. Manku, A. N. Bhat and B. D. Jain, Proc. Indian Acad. Sci., 1968, 63 (in press). 33. I. P. Caparis and E. Manella, Hundert Jahre Schweiz Apoth.-Ver., 1843-1943,347; Chem. Abstr., 1944,38,18418. 34. B. D. Jain and H. B. Singh, J. Indian Chem. Sot., 1963,40,263. 35. Idem, Indian J. Chem., 1963, 1, 369. 36. B. D. Jain and R. Kumar, Current Sci., (Zndia), 1966, 35, 557. 37. B. D. Jain and H. B. Singh, J. Less-Common Metals, 1964, 7,464. 38. V. Patrovskp, Collection Czech. Chem. Commun., 1962,27, 1824. 39. B. D. Jain and H. B. Singh, Anal. Chim. Acta, 1967,37, 135. 40. G. S. Manku, A. N. Bhat and B. D. Jain, ibid., 1967,39,369. 41. Idem, Talanta, 1967,14, 1229. 42. Idem, unpublished work. 43. Idem, unpublished work. 44. A. N. Bhat and B. D. Jain, Talanta, 1960,4,13. 45. V. Patrovskjr, Chemie, 1958,10,93. 46. A. N. Bhat and B. D. Jam, Proc. Indian Acad. Sci., 1961,53,147. 47. V. Patrovski, Collection Czech. Chem. Commun., 1962, 27, 1824. 48. B. D. Jain and H. B. Singh, Indian J. Chem., 1963,1,317. 49. Idem, ibid., 1964,2,246. 50. Idem, J. Indian Chem. Sot., 1964, 41,29. 51. Idem, Indian J. Chem., 1964,2,245. 52. B. D. Jain and R. Kumar, Proc. Indian Acad. Sci., 1964,6OA, 265. 53. A. N. Bhat and B. D. Jain, J. Inorg. Nucl. Chem., 1961,23, 136. 54. L. Sommer, Z. Anal. Chem., 1962,187,7. 55. B. D. Jain and R. Kumar, Proc. Indian Acad. Sci., 1964,59,185. 56. Idem, Current Sci. (India), 1966,35, 173. 57. 33. D. Jain and H. B. Singh, Proc. Indian Acad. Sci., 1964, 59, 362.