- Email: [email protected]
Studies on oxine and its derivatives
VOL.
19 (x958)
EMPLOI DU ,.GADION”.
11.
447
Rl%U,Mti II est propose un nouveau microdosage spectrophotomdtriquc
de l’ion mercurique, utilisant un colorant triazbnc, lc , ,Cadion”. La mcthode cut Ir?zs sensible et precise si l’on respectc des conditions cxpdrimentalcs bien determin6cs. L’influence des ions &rangers a et& indiqude. SUMMARY A new method is described for spectrophotomotric microdctermination of the mercury ion by means of a triazine dye, the “Cadion”. If the well-defined cxpcrimental conditions are mamtaincd, the method is very sensitive and accriratc. The influence of foreign ions is dcscribcd. BIBI,lOGRAPHIE 1 P. CHAVANNE
ET CL. GERONIMI,
Chint. Acla,
And.
rg (tgg8) 377. Rccu la 24 janvicr
STUDIES THE
ON
SENSITIVITY
OXINE
AND
AND
ITS
SELECTIVITY
8-HYDROXYQUINOLINE-5-SULPHONIC
DERIVATIVES
OF SOME ACIDS
8-HYDROXYQUINOLINE-+CARBOSYLIC
x958
7-SUBSTITUTED
AND SOME z-SUI3STITUTED
ACIDS
TOWARDS
CERTAIN
METALS* bY R. G. W. The Bralish Drug Hotcscs Ltd.,
BDH
HOLl,1NGSHEAl~
Laborafory Chemrculs
Diviston,
Poole, Dorsef (Great
Bcifain)
1NTIZODUCTIOS
Since the pioneer rcsearchcs of BERG AND HAHN into the analytical applications of oxine and certain of its halogenated derivatives, search has continued for derivatives showing greater selectivity than the parent compound with regard to chelation with trace metals in solution. The fact that oxinc itself chelated with a considerable number of mctalsl caused considerable difficulties in analytical practice, and indeed, it was only by removal of interfering metals or by ‘masking’ with other reagents, that oxine could be employed for the determination of a specific metal in the presence of others. Conseyuently a great number of techniques was published, employing oxine as the precipitating agent, in which interfering metals were complexed with other reagents or removed by physical methods, to give reliable methods for the determination of one metal in the presence of others. Some years after BERG’S initial researches, certain derivatives of oxinc were employed in which substitution of halogen groups or solubilising groups (e.g. sulphonic acid groupings) conferred a certain degree of selectivity, but it is only comparatively recently that a grcatcr understanding of the underlying theory involved has given a more complete picture of the phenomenon of selectivity. * Paper read at XVth International Congress of Puro and Applied Chemistry, (Analytical) Lisbon
rg56. Section VI, Organic Comploxos.
References p. 457
II.
448
G. W.
HOLLINGSHEAD
VOL.
19 (1958)
Through the years research has been directed along three main lines (a) the formation of heavier chelates by the introduction of halogen groupings in positions 5 or 7 of the quinoline ring (e.g. 5,7-dichloro-, 5,7 dibromo-, and 5,7-di-iodo-oxines), where a ‘weighing effect’ with the formation of complexes more stable in solutions of lower PH has conferred a certain degree of selectivity on the derivative; (6) the introduction of groupings in positions 2 and/or 7, giving derivatives in which the possibility of stcric . hindrance to chclatc formation exists (e.g. 2-mcthyloxine, 7-methyloxine), and (c) the introduction of ‘solubilising groups’ such as sulphonic or carboxylic acid groupings, giving, in certain casts, water soluble chelates. Although stcric hinclrance to chelation has been shown to play an important part in conferring selectivity, other factors have to be taken into account so that anomalous bchaviour on the part of certain derivatives may be explained (see below). In the work now described some derivatives of oxine-5-sulphonic acid containing comparatively large groupings in position 7 have hcpn prepared and examined. With these derivatives the possibility of stcric hinclrancc to chclate formation, coupled with increased water solubility of the chelate exists. 130th the above possibilities also exist in the other class of oxinc derivatives prepared and examined, namely the z-substituted oxine-4-carboxylic acids. Although some derivatives of oxinc-5-sulphonic acid containing small groupings e.g. halogens, nitroso, nitro, in position 7 have been reportcd213 and their reactions towards some metals cxamincd, no derivatives containing comparatively large groupings in the stcrically hindering position 7 have been investigated, and it seemed of interest to examine the bchaviour of such derivatives towards some metallic ions. With the other class of compounds, although some carboxylic acid derivatives containing carboxylic acid groupings in positions 4 or 5 have been rcported4pb no derivatives containing a carboxylic acid grouping in position 4 and a substituent in position 2 have been critically examined with respect to their bchaviour with a range of metal ions under standard conditions. As substitution in position z is known to cause stcric hindrance to chclate formation”-8, ancl the cffcct of a carbosylic acid grouping will bc to form water soluble chclatcs, the analytical potentialities of this class of oxinc derivative seemed well worth investigating. A great dcgrce of sclcctivity is confcrrccl by the introduction of sterically hindering groupings in positions 2 and 7 of the oxinc ring and the selectivity is further enhanced by the increased water solubility of the chelates conferred by the presence of the sulphonic acid or carboxylic acid groupings. The incrcascd selectivity is outweighed however by the concomitant decrease in sensitivity. Of particular intcrcst is the formation of aprecipitatc with aluminium and S-hydroxy2-n-hcxylquinoline-4-carbosylic acid, this oxine derivative being unusual in prccipitating aluminium from solution under the conditions of the test, although containing a substitucnt in position 2. Stcric hindrance factors have prevented the formation of a aluminium
tris-comp1e.x
with many
other z-substituted
oxine
derivativese-8.
o/ devivntives
Pve$vzration
8-Jr)~Jroxyqttinoli~te-5-s-s~~Z~J~o~llc acids. These \vcrc prepared hy the reaction of the required base and forxnaldehyclc with 8-hydroxyquinollnc-5-sulphonic acid, working.in ethanol solution. 7-Subsfilatled
References
p. 457
VOL.
19 (x958)
OXINE
AND ITS DERIVATIVES
449
8-Hydroxy-7-nrorpholino,neti~ytq~~~noZ~~te-~-sulphonic acid. S-Hydroxyqumoline-5-sulphonic acid (4 g recrystallized from z y. hydrochloric acid) was stirred with 75 ml of anhydrous ethanol. To the slurry was added 4 ml of formaldehyde (35%) and 4 ml of morphohne . On the additron of the morphohne the 8-hydroxyqumoline-5-sulphonic acid remaining undissolved went into solution. The deep orange solutron was boiled for 5 min when the required dcrivativc began to precipitate. The mixture was allowccl to stand for 3 h with water cooling, then filtered, rmscd with 25 ml of anhydrous ethanol and dried at 40~. Yield 6.1 g of off-white crystalline material. Melting point (recrystallised from anhydrous ethanol) 23$’ (uncorr.) Found C = 51.4%; H = 5.050/O; N = 8.6%. C,,H,,O,N,S requires C = 51.8%; H = 5.0%: N = 8.7%. 8-Hydrory-7-ptpcridi7lo,nclhylq~trnoli~ie-g-slrlphonrc acid. This was similarly prcparcd from 8 g of S-hydroxyquinolme-5-sulphonic acid, 8 ml of formaldehyde and 8 ml of piperidinc. Yield 8.5 g. Melting point (after two recrystallisations from anhydrous ethanol) 23W (uncorr.). Found C = 55.7%; H - 5.6%; N = 8 7%. C,,H,,O,N,S requires C = 55.go/o; H = 5.6%; N = 8.7%. z-Substatuted 8-hydroryquinoliue-q-carboxyllc acrds. These dcrivativcs were prepared by rcfluxing o-aminophenol with pyruvic acid and the required aldchydc. The preparation of 8-hydroxy-n-(3,4dimethoxyphenyl)-quinolme-4-carboxylic acid has prcvtously been rcportcdg. HOLDSWORTH AND LIONS’O during an investigation into the preparation of analogues of cinchophcn, described the preparation of 2-veratryl-7-hydroxyqumolinc-4-carboxylic acid and 2-vcratryl-6-hydroxyquinoline-4-carboxylic acid from m- and p-aminophenol rcspcctivcly. bUt no preparations employing o-aminophenol were camcd out. It is know that other alternative methods of ring closure may opcratc in closely similar cases, but proof of the formation of 2-substitutccl 8-hydroxyquinolinc-.+-carboxylic acid derivatives by this reaction may be cited hcrc. DOEBNBR ANIJ I~ETTBACKI1 have prepared z-phcnyl-oxinc-4-carboxylic acid by rcfluxing o-aminophenol with bcnzaldchydc and pyruvic acid m ethanol solution. On dccarboxylation a-phcnyl-oxine was obtained, identical with samples obtained by unambiguous synthesis (seo IRVING CCal.‘*). It was found that the rcqulred reaction procccdcd most satisfactorily when freshly prcparcd o-amrnophcnol was employed. This was prcparcd ‘as rcquircd by reduction of o-nitrophenol with sodium dithionite in alkaline solution following the method of PETROW AND STURCBON~~. The o-aminophenol so prepared was kept moist with anhydrous ethanol until required. 8-Hydroxy-a-(~,q-dintethoxyplrenyl)-qrti,lolr,rc-J-carboxylic atxd. o-Aminophcnol (14 g freshly prepared) was dissolved in 300 ml of ethanol and to the warm (509 solution was added a mixture of 8.4 g of pyruvic acid and 14 g of veratraldchydc dissolved m 150 ml of anhydrous ethanol. The reactants wem stirred and refluxcd for 4 h. After standing ovcrnrght the required derivative had precipitated. This precipitate was removed, rinsed with anhydrous ethanol and dried at 40’ to give I 5 g of yellow powder. Melting point (rccrystallised from anhVtlrolls ethanol) 237O (UnCorr.). Pound C = 66.6%; 1.K= 4.4%; N = 4.3:&. Cr,H,sO~N r_cquircs d ,- 66.4%; I-l = 4.6O/; N =;I 4.3%. 8-Hydroxy-1-n-hcxylqtcinolinc-q-carboxylrc sod. This was similarly prcparcd using I o g of o-aminophenol, 6 g of pyruvic acid and 12.5 g of n-heptyl aldehyde. After rcfluxmg, the Initial volume of solution (r 30 ml) was reduced to 50 ml. On standing ovornight the required prccipttate was removed, rinsed with ethanol and dried 231uacuo at 40~. Yield 7g. It was naccssary to rccrystallisc three times from anhydrous ethanol to obtain a pure material. Melting point I 37-139~ (uncorr). Found C = requires C = 70~4%; H = 7.0%; N = 5.1%. 69.9%; H = 7.1%; N = 5.1%. C,,H1,02N 8-Hydvoxy-a-(r-ethyZpropyl)-quinoline-q-cayboxylic acid. Similarly prcparcd from 20 g of oaminophenol in 200 ml of anhydrous ethanol and 12 g of pyruvic acid and 22 g of z-ethylbutyraldehyde in 50 ml of the same solvent. Tho volume was reduced to xooml after 4 h reflux. Yield gg. Melting point (after recrystallisation from anhydrous ethanol) 205” (uncorr.). Found C = 69.3%; H = 6.6%; N = 5.6%. C,,H,,O,N requires C = 6g.5%; H = 6.6%; N = 5.4%.
Testing procedure
/or reagents with
metals
SensifrviCy lesls. The theoretical basis for sensitivity tests has been discussed in detail by IRVING ABID ROSSOTTI~~. As these authors point out, a prediction of tho behaviour of any new derivative from a consideration of the relevant physical properties and stability constants of its complexes with metals is not possiblo in practice as insufficient data are available and the required equations are complicated by competitive complex formation. A more empirical approach is necessary, such an approach being the performance of sensitivity testsi*l16,16. The method based on that suggested by IJJTZ~~ modified by IRVING et al.‘=, previously employed by HOLLINGSHEAD~~ References
$. 457
R. G.
450
W. HOLLINCSHEAD
VOL. 19 (1958)
is used here. This consists essentially in recording the sensitivity of the rcagcnt in torms of the smallest amount of metal which will give a pcrccptrblc prcclpitate or colour change in a test solution under standard conditions. Three buffar solutions A, I3 and C having PH’S of 5.3, 8.35 and x3.1 respcctivcly are employed, ancl for each test the total volume of solution is kept constant at 7 ml. One outstanding disadvantage of the tcchniquc IS that the composition and pH of the buffer solutions A, B and C arc purely arbitrary.Prccipitationreactionsof some metal-rctlgcnt combinations may occur in a narrower pH range and may thcrcforc he ovcrlookcd. ‘l’hrs could bc overcome by increasing the number of buffer solutions cmploycd, but it is unlikely that information of great use would result from the consltlcrable extra labour rcquircd. It must also bc born in mind that the appcaranca of a precipitate in one of the sensitivity tests . undor conditions of great dilution, while forming the hasis of a spot-test reaction, must not be rcgardccl as sultablc for cfuantitatlvc purposcn, as precipitation may not bc quantitative or the complex stoicliiometric in its composition. ‘rhc prcscncc or abscncc of precipitates in a series of scnsltivity tests with a new rcagcnt may well give rise thcrcforc to crroncoux conclusions regarding its possibllitics as a selective quantitative reagent. This is clenrly illustrated m the investigation of 8-liydroxy-5-nitrosoqiiinolinc previously rcportedl’. PrepavaCion of Duffer, vcagexl and nrefal solutions and method of Cesli*tg veagenls. The preparations of buffer and metal solutions have previously been described rs,16nrs, Reagent solutions wcrc M/50 in ethanol whercvar possiblo. Some solutions were hT/so in I : I ethanol-water. The m&hod of testing rcagcnts has previously beon clcscribodrs.
IiESULTS 8-Nydroxyqzci?aoline-5-slllpltonic
acid
Reactions of 8-hydroxyquinolinc-5-sulphonic acid with various metals have previously been reported in the literature The reason for including tests with this oxinc derivative in this instance was to obtain a comparison under the same conditions with the unsubstituted sulphonic acid derivative and derivatives containing substitucnts in position 7 of the quinolinc ring. Owing to the sparing solubility of oxine-g-sulphonic acid in anhydrous ethanol a hot (65”) saturated solution was employed. Oxine-g-sulphonic acid precipitates copper, zinc, cobalt and cadmium from solutions of pry 5.3 wzdev the conditiom of the test. ALBEI~T AND M~~~~~~~~~havecarriedout sensitivity tests (using a similar method to the one employed here previously reported by ALBERT AND GLEDHILL~“). At pH 7.0 no precipitation was observed by these workers with calcium, magnesium, manganese, zinc, ferrous and ferric iron, cadmium, cobalt, lead and copper, using a o.oogiIf reagent solution and a 0.0005~1l metal solution. ALBERT AND MAGRATH’S findings regarding non-precipitation with the above metals from an approximately neutral solution are confirmed, no precipitation being observed in the present tests using a buffer of pi-r 8.35. 13~1~~4also reported that, apart from a slight tendency for copper and ferric ions to form precipitates from acid solutions, no method which might appear suitable for analytical purposes could be found for any metal. This statement appeared to refer to gravimctric or volumetric procedures only ; calorimetric methods were not considered. BEHG also noted that precipitation was prevcntcd in neutral solutions containing tartrate ions. This has been confirmed. Zinc is prccipitatcd from acid solutions containing acetic acid and sodium acetate at pH 5.3. Previous reports of precipitation of the zinc complex appear conflicting. An early paper by VAISMAN~~ reported precipitation of the zinc complex using 8-hydroxyquinoline-7-sulphonic acid. MOLLAND~ repeated this work and stated that the comRsforences
p. 457
VOL. 19
(1958)
OXINE
AND
ITS DERIVATIVES
451
pound referred to as S-hydroxyquinoline-7-sulphonic acid was undoubtedly S-hydroxyquinoline-5-sulphonic acid. VAISXIAX’S method consisted in treating a solution of the zinc salt buffered with sodium hydroxide and sodium tartrate with an aqueous solution of the ‘potassium salt of S-hydroxycluinoline-7-sulphonic acid’. As the pn of this mixture would be alkaline, this method has not been confirmed in the present investigation where no precipitation was obtained with Buffer C containing sodium hydroxide and sodium potassium tartrate. 1.1~ AND BAILAR~~ have dcscribcd the preparation of the zinc complex by precipitation from a solution containing zinc sulphatc, sodium tartrate and sodium hydroxide, when on the addition of a solution of S-hydroxyquinoline-5-sulphonic acid dissolved in potassium hydroxide solution followecl by acetic acid until the pn is just acid, the zinc complex was obtained. Some doubt must be cast on VAISMAX’S reported precipitation from alkaline solution. The introduction of the hydrophilic acid grouping confers on the complexes a great degree of intrinsic solubility in water. The definite colour changes seen with Ni, Ga, In, Tl, and Y in acid and neutral solutions point to the formation of water soluble chelates (see Table II). Those metallic complcscs which clo precipitate only do so in acid solution ; in neutral and alkaline solutions they remain in solution. Thcscnsitivityof aprccipitation reaction depends both on the stability of the metal complex and on its intrinsic solubility. From the stability constants of some divalcnt metals including Cd, Co, %n, and Cu, given by NXSX~'EN ASD UUSITAIX) 22, however, it appears that the cffcct of the sulphonic acid grouping on the chclatc stability is relatively slight, so that the decrease in sensitivity obscrvcd with S-hydroxyquinolinc-5-sulphonic acid would appear to stem from the incrcascd water solubility of the chelates. In I3uffcr C, with the highest concentration (4 ml of Jf/xoo) of certain metals, the solution rcmaincd clear after digestion, although precipitation of reagent, and in some cases, metal, occurred at this PH. This occurred with copper, nickel and cobalt, and denoted the formation of water soluble chelates under these conditions.
8-Hydro~y-~-ntor~lroli~~ometltylqIrittoliltc-~-s~rlp/o~~ic
acid
A Jf /so solution of the reagent was prepared in I : I ethanol-redistilled water, owing to the very sparing solubility of this derivative in absolute ethanol. After digestion at so”, solution was complctc and precipitation of the derivative did not occur on cooling. With this derivative the possibility of stcric hindrance to chelate formation exists, with the presence of the large morpholinomcthyl grouping in position 7, in close proximity to the chelating function. This would possibly lead to aslight increase in sclcctivity, although the degree of steric hindrance obtained by substitution in position 7 does not appear to be as great as that conferred by a substituent in position 2. Outweighing any increase in selectivity due to the sterically hindering substituent in position 7, is the water solubility of the chelates conferred by the sulphonic acid grouping, leading to decreased sensitivity. The results obtained with the metals examined show that, with the exception of copper, none of the metals give a precipitate, although colour changes, pointing to chelate formation occur with Ni, Al, Ga, In, Tl, Y, Zn, Mg, Cd, Co, and Fe+a. The colour changes are generally of low sensitivity as would be expected (set Table II). Referewes p. 457
R. G. W.
452
HOLLINGSHEAD
8-Wyd~oxy-~-~i~s~idinomelhqtlqzrino~i~~e-~-~~~~~~onic
VOL.
19 (rg$.3)
acid
This reagent precipitates in Buffer C, but not in ISuffers A and I3, where clear yeiIow sofutions are obtained. The same conditions regarding steric hindrance to &elate formation being outweighed by increased water sofubiiity af the chelates occurs with this derivative, and, with the exception of copper, none of the other metals tested gave insoluble chelates under the conditions of the test. Colour changes occurred with Ni, Al, Ca, In, TX, Y, %n, Mg, Cd, Ca, and Fe +a, but these were generally of low sensitivity (see Table II). The formation of a water sofubfc chef&e with cub& in Buffer C is denoted by the nun-precipitation of the reagent with the greatest ~on~e~tr~ti~~of the metal employed, although the reagent itself precipitates at this PH.
As this compound is sparingly soluhIc in coId ethanol, a hot (so”) soft&ion was used. With this derivative, the possibility of stcric hindrance to chelatc formation exists, cuupled with enhanced water solubility of any chelate formed, due to the presence of the hydrophilic carboxylic acid grouping in position 4. This should lead to greatly increased sclcctivity coupled with decreased sensitivity. Precipitation did not occur with any of the metals examined+ Colour changes were noted with Ni, Zn, Mg, Ga, In, Tl, Co, and Fe+3 (see Table II), denoting the formation of soluble chelates. No differences in colour were obtained in the AI, Y, andCd tests, and it would appear that a small degree of sefcctivity is conferred by the presence of the comparatively large grouping in position 2. The non-formation of a chclate with aluminium under these conditions confirms the previously reported behaviaur of z-substituted derivatives towards this metal, no precipitation occurring with many z-substituted derivativesa-*. C hclation dues not appear to take place with yttrium and cadmium. With this derivative the eolour changes are of low sensitivity (see Table II) _Although both the metal and the reagent precipitate in~vidua~ly in Buffer C, no precipitation occurs with 4 mi of nl/roo cobaft, pointing to the formation of a solubtc &elate or a mixed complex.
O*I-0.04 0.4-0.3 o.t-0.04
3.8~4<2
H-#-C w-f-c
a*3-o,n 0.1-0.04 0.4-o-3
H-+-C
0,4-0.3
EL d
cu
o.uos o.ar o.oox
B
Cc f-f
a
c
c A
Ni
O.QOI 0.01
n C
Al-+3
0.00s
A
Rsfevences ps 457
H-I-C Ifs-C -
NPf 0.4-0.3
dark dark
brawn brawn
yellow
brown
4*4-4.5 3.8-4.2 .~.a-4.4
brown orange yellow
yellow
482-494
brown
yellow
4.2 -4.4
yellow
*
VOL.
19 (1958)
OXINE
AND
TABLE
ITS
I
453
DERIVATIVES
(continued) -_---_
.%rttol Al Al Ga+s Ga Ga Ga In+s In In Tl+s Tl Tl
nr
Rulfrr B C A
0.01 0.01
co+* co co Fc+s FO FO
NP NP
COburC
3.5-3.8
yellow
6 C
C H+C H-j-C
0.4-0.3
4.2 -4.4 3.5-3.8
yellow yellow brown
H+C H+C H+C
0.2-0.1 0.2-0.1
3.5-3.8 3.5-3-g
yellow yellow
0.01
A B C
0.00x
A :
H+C H+c H+C
0.4-0.3 0.4-0.3 NP
4 2-4.4 4.2-4.4
yellow yellow
A B C
H+C H+C H-j-C
2.2-2.4
yellow
4*oE:‘o NL:
A B C
H+C H+C H+C
0.2-0.x
3.5-3.8 3.5-3.8
yellov yellow
H+C H+C Hi-C
NP 4.0-3.0 NP
2.2-2.4
0.01
; C
brown ( yollow)
0.01
A
H+C H-I-C H+C
4-o-3.0
2.2-2.4 2.2-2.4
yellow yellow
H+C H-i-C HCC
0.4-0.3 0.3-O NP
4.2-4.4 5.4-5.5
brown orange brown
3.5-3.8
brown or grcon h (brown or green) i
0.001 0.01 0.01
0.01
0.01
0.001 0.01
0.01
Cd+’ Cd Cd
pf.b
0.2-0.1
0.0x
Mg+’ Mg Mg
H+C H+C
VI b C’,a
--
H
0.01
0.0x
Zn+l Zn Zn
Tube cxomlncJ
0.01 0.01 0.01
0.0x 0.0x
0.01
c”
0.0x
0.00
I
A
0.0001 0.01
:
0.01
A
0.01 0.01
:
HfC HCC H-+-C
0.2-0.x
NP
NP
0.2-0.x
NP
4*oSo
0.2-0.1
NP NP
2
(rose pink) 6 (rose pink) B
V, and It, are the volumes of standard metal solutron which (I) give a precipitate or colour change and (2) fail to give a precipitate or colour change respectively. pLisdefinedas-log(hmitingconccntration), ing.equiv./lforthevolumcsV,and Vsrespectivclylr. This value is to bc preferred as an expression of sensitivity as the use of pg/ml may convey a false impfession of the difference in sensitlvitics of the reagent with metals of differing atomic weight or valency. Colours 16 parentheses refer to solutions and colours not in parentheses rofcr to colours of procipitates. Hot. Cold. NP = No precipitate. Before digesting at 70“ a rose pink colouration occurs on the addition of reagent solution. This is destroyed on heating with the formation of a yellow precipitate Brown precipitate in tube containrng the higher concentration of Fc+e; green precipitate in tubes containing the lower concentrations. Brown colouration in tube containing the higher concentration of Fe+2; green colouration in tubes containing the lower concentrations. Rsfrrences p. 457
R. G. W.
454
8-ir/ydroxy-2-It-ltexylqzlinoline-g-cavboxylic
HOLLINCSHEAD
VOL.
19 (1958)
mid
8-Hydroxy-z-n-hexylquinolinc-4-carboxylic acid is readily soluble in absolute ethanol giving a yellow solution. From the results given in Table I it is seen that precipitationof all the mctalscxamincdoccurs, although the sensitivity with magnesium, yttrium The presence of the long aliphatic chain in position 2 of the and cadmium is very low. quinoline ring does not confer a great dcgrcc of selectivity due to steric hindrance reasons, and in behaviour, this derivatives may be compared to oxinc itself. Although the prcscncc of the carboxylic acid grouping in position 4 would lead to the formation of water soluble complexes, so conferring cnhanccd selectivity, this appears to have been outweighed to a great extent by the aliphatic chain in position 2, which has caused large differences in the intrinsic solubilitics of the chclatcs, with the formation of chelates which are less soluble in water than those of other 4-carboxylic acid derivatives examined. The overall sensitivity of this derivative approaches closely that of oxine itself, the pr, values of the chelates being of the same order as those of the corresponding ovine chelates. The most interesting behaviour of this dcrivativc is its formation of a precipitate with aluminium at prr 5.3. Previous reports of non-chelation with this metal and other z-substituted oxinc derivatives have suggested stcric hindrance factors to be rcsponSibk”-“. IRVING, CUTLER AND RINC.‘~ confirmed iM~lcl
p. 457
VOL. 19 (x958)
OXIKE
A*‘D ITS DERIVATIVES TABLE
LI~llTING
CONCENTRATLONS
OF
MRTALS
455
11
GIVISG
COLOUR
CHANGES
WITH
OXISE
DEHlVATlVOS
--
b-Hydroryqlti~aoline-5-slrIpilo,rzc
acid
Cl]+* Nl+’ Al+3
0.0x 0.00 I
B B .\, B, C
0.)-O 04 o.j-0 3 NC -1
3 Z-4.2 4.2-4.4
cmctalcl green applc~rccn
Ga+a In+3 TI+=
0.0x 0.0 I 0.01
A. B
0.4-o
04 04 0 l-0.04
3.2-4.2
green
A. l-3
0.1-o
3.2-4.2 3.8-4.2
pale yellow ycliow
y+= Zn+* Mg+’
0.01 0.01
A i3 A. 13, C
0.4-0.3 0.1 -0 04 KC
3.2-3.4 3 s-4 2
pale yciiow yellow
ccl+*
0.01
C
OI
3.8-4.2
co+*
0.01
13
0.
yellow yellow brown cnicralti green
Fe+8
0.00 I
A. B
-0
04
-0.04 0.3-0.2
h, B
8-Hydroxy-~-~~rorpholi~~o~~~e~l~ylgurrrol~~te-~-srrIplro~:~c
actd
c
0.4 -0.3 0.4-0.3 0 L-004 0.4-0.3
3.2-3.4 3 2-3.4 3.8-4.2 3.2-34
pale yrccn pale ycilow ycilow green green yellow
x B n, I3
0.4-0.3 0. t-o.04 o-4-0.3
3.2-3.4 3 8-4.2 4.2-4.4
1’“iC yellow tlccp orange cnrcrald green
i3
O.OL
13
0.01
A, I.3
Tl+= y+= %n+’
0 01 0.01 0.01
A, IJ :\ A, I3
xig+*
0.01
Cd+2 co+* &-c+3
0.01 0.01 0.001
acid
8-Hydroxy-7-papertdinonrerlrylgtcrrrolrtot~ac 0.1-0.04 0.1 -O.Od 0.1-O 0; 0.3-0.2
3.8-4.2 3.8-4.2
0.01
I3 A. I3 A; I3 B
0.01
2
0.01
A,
B
0.4 -0.3 0.4-0.3 0.4-0.3
3.2-3.4 3.2-3 4 3.2 -3.4
B
0.4-O 0.4-0.3 0.4-0.3 0.3-0.2
0.01
0.01 0.01
A,
Mg+2
O.OL
Ccl+’ co+*
0.01
B A
0.01
r\
I%+=
0.001
A,
cu+*
4-4.5
3 S-3.8 3.2-3S4 3.2-34
0.01
Y+3 T1+a Zn+l
4
0.2-0.1 0.4-0.3 0.4-0.3
Ni+a Ga+= Itl+J
Ni+* Al+J Ca+3 In+a
3.8-4.2
f
0.001
NI+~ Al+=
0.0:
Ga+3 In+= T1+3
0.0x 0.01 0.001
B B A.
B,
A B A, B
c
3
3.8-4.2
3 4-3
5
yellow pdc green pnic green grfXt1
green pale green
pale
3.2-3.4 3.2-3.4 3.2-3.4 4.4 -4.5
paic green green yellow yellow emcraid green
brown yciiow
0.3-0.2 -0.04 NC
4.4-4.5
0.1
3.8-4.2
0.2-0.1
3.5-3.8 3.8-4.2 4.2-4.4
0. I-O.04 0.4-0.3
green
orange
orange yellow orange
TABCE
y+=
Zn+2 Mg+2
0.01 0.0x
Cd-co+2 I.‘c+3
0.01
0.00 I
A,
NC
B, C
A, u, A, I3 A, I3
c
0.01 0.01
cu42
NI+’ Al+3 Ga+:’ In+a -l-l+”
0.001 0.001
YC3 0.01
Zn42
Mg+2
A, I3
0.2-0.1
0.4-0.3
0.0x 0.0x 0.001
yullow olive green
3.5-3.8 4s4-4.5
orange yellow
3.5-3.8 3.4-3.5
olive green ; green brown yellow
4.2-4~4 4-2-4~4
yellow yellow
NC 0.2-O.
I
0.3-0.2
brown;
orange
A, B, C
0.3-0.2 NC
A, 13, C u A
NC 0.4-0.3 0.4-0.3
A, 13, C
NC 0.3-0.2 NC
3.4-3.5
yellow
0.3-0.2 0.3-0.2
34-3.5 3.4-3.5 4.5-4.8
yellow yellow emerald green
:: B
--
yellow
acid 0.2-0.1
A, B, C
ccl+2 co+2 l%+s
3.5-3.8 3.2-3 4
I3
B
19 (1958)
II (contrnucd)
d-ffydrory-a-(z-ellryfpvopyl)-q~~anoli~re-q-carboxylrc
a NC =
VOL.
R. C. W. HOLLINGSHEAD
456
0.2-0.x
---_-
No dkornablc
colour change.
This derivative is freely soluble in absolute ethanol, giving a yellow solution. With all the metals investigated, precipitation of a complex does not occur. Colour changes denoting chelate formation are found with Cu, Ni, Zn, In, Tl, Cd, Co and Fe+8 (see Table II). The carboxylic acid grouping, conferring water solubility on the chelates, appears to outweigh any influence the branched chain aliphatic grouping may have on the intrinsic solubility, so that water soluble chelates are formed under the conditions of the test. All these colour reactions are of low sensitivity (see Table II). DISCUSSION
None of the derivatives investigated shows any striking analytical advantage over the parent compound. A large increase in water solubility of all the chelates was to be expected, due to the presence of sulphonic acid or carboxylic acid groupings, but the hope that sensitive colour changes, due to the formation of water-soluble chelates would form the basis of new spot test techniques has not been fulfilled. Such colour reactions as were observed have been, largely, of low sensitivity, precluding their analytical use. The one exception is the formation of a rose-pink colouration with trivalent thallium and 8-hydroxy-z-+hexylquinoline-4-carboxylic acid. This may well form the basis of a spot test for the detection of this metal in the presence of others of the same sub-group. References
p. 457
VOL.
19 (1958)
OXINE
AND
457
ITS DERIVATIVES
The hope that the weighing effect of the comparatively large groupings in position 7 of oxine-5-sulphonic acid would further enhance any degree of selectivity conferred by the presence of the solubilising sulphonic acid groupings has not been realised.
My thanks are due to the Directors of The British Drug Houses Ltd., this work.
for permlssion
to publish
SUMMARY A numl>ar of new derivatives
of B-hydroxyquinoline
containing
both solubihslng
groups
and
groups which might stcrlcally hinder chelntlon have been prepared, WE. B-hydroxy-7-morphohnomethylquinoline-5-sulphonic acid, 8-hydroxy-7-p~pcr~di~i~~,~t~~~lquinoline-~-sulphon~c acid, B-hyB-hyclroxy-z-n-hexylquinolinc-4clroxy-2-(3,~-cl~mcthoxyphengl)-qu~nol~ne-~-carb~xyl~c acid. The hmlting sensecarboxylic acid and B-hydroxy-2- (t-ethylpropyl)-qulnolinc-&arboxyhc tivities of the reactIons of these rcagcnts towards copper, nlckol, alumimum, zinc, magnesium, galhum, indlum, thallium, pttnum, cadmium, cobalt ancl iron have been lnvcstlgated
REFERENCES
1 H.G.\V.HOLLINCSHEAD.OXI~~OUI~~IISDC~I~~~~~~CS,\~~~~.
I-IV,Rutterworths,London,rg~~-1956.
4 J. MOLLAND, a J. RIOLLAND,
Awh. Mulh. NaftcwiJorskul. 13 (1940) 67. 19 (rg3g) x60: J. Am. ‘I’adsskr. Kjemr og 13ergvrsen. Kjemh og Uergvesen. 19 (1939) I 19; at (194 I) 49.
Chrm. Sot., 62 (1940) 541; Tidsskr. 4 R. BERG, Z. unorg. Chem., 204 (1932) 208. I (1880) 860; E. LIPPMANN AND 1;. FLEISSNER, Ser. deul. them. Ges., 6 A. U~sz~~~,j\lo~~uIsh.Chem.. 19 (1886) 2467; A. ALDaRT ASD 1). hlAGRATt1, Bwchrm. j., 41 (1947) 53.) 6 I-. I,. MKHHITT AND J. 1;. \VALK~ZR. Ind. Eng. Chern., Anul. Ed., 16 (1944) 387. 7 J. P. L’HILLIPS AND L. L. MLSHRITT, J. Am. Chem. Sot., 71 (1949) 3984. 0 J. P. PHILLIPS, W. H. HUOW. J. M’. CHUNG AND L. L. MERRITT.J. .4rt~.ClJenz.Soc., 73 (rggl) 630. Y 1%. G. W. MOLLINGSH~SAD. Heseurch (London), 8 (1955) SIC. 10 31. G. HOLDSWORTH AND 17. J. LIONS, J. &OC. ROY. SOC. 1v.s. iV&S, 66 (1932) 277. ‘1 0. DOWN~SH ASD H. FETT~~ACK, Ants. Chon , Laebrgs. 281 (1894) 7, g 18 H. IRVING, E. J. BUTLER AND >l. F RING, J. Chem. Sot., (1949) x489. Ia \‘. PeTROW AND u. STUHGBON. J. Chcm SOC., (1954) 570. 14 H. IRVIN<; AND I-1. S. ROSSOTTI, Anuiysl, 80 (x955) 245. 16 0. LUTZ. Z. at&. Chem., 5g (1920) 149. 1’ R. G. W. HOLLINCSIIEAD, .4ul. Chwa. Ado, 12 (1955) 201. 17 H. IRVING. R. G. W. HOLLINOSHEAD AND G. HARRIS, .4nuCysf, 80 (1955) 26o. 10 A. AL~~RC AND D. MAGRATH, Btochem J.. 41 (1947) 534. le A. ALBERT AND W. S. GLEDHILL, Blochrm J.. 4 1 (1947) 529. 90 G. A. VAISMAN, Ukrarn. Gosudars;. Inst. Ehspil Form (Khurkou) ; Konsul’fulsionnye Maferaoly, (1940) ‘43. 11 J. C. 1. Lru AND J. c. BAILAK, J. Am. Chem. Sot , 73 (1951) 5432. ** R. NASXNBN AND E. UUSITALO, Acfa Chem. Stand.. 8 (1954) I 12. 12 J. P. PHILLXPS AND E. >I. BARRALL, J. Org. Chem., 21 (1956) 692. Received
March
1st.
x958
19 (x958)
EMPLOI DU ,.GADION”.
11.
447
Rl%U,Mti II est propose un nouveau microdosage spectrophotomdtriquc
de l’ion mercurique, utilisant un colorant triazbnc, lc , ,Cadion”. La mcthode cut Ir?zs sensible et precise si l’on respectc des conditions cxpdrimentalcs bien determin6cs. L’influence des ions &rangers a et& indiqude. SUMMARY A new method is described for spectrophotomotric microdctermination of the mercury ion by means of a triazine dye, the “Cadion”. If the well-defined cxpcrimental conditions are mamtaincd, the method is very sensitive and accriratc. The influence of foreign ions is dcscribcd. BIBI,lOGRAPHIE 1 P. CHAVANNE
ET CL. GERONIMI,
Chint. Acla,
And.
rg (tgg8) 377. Rccu la 24 janvicr
STUDIES THE
ON
SENSITIVITY
OXINE
AND
AND
ITS
SELECTIVITY
8-HYDROXYQUINOLINE-5-SULPHONIC
DERIVATIVES
OF SOME ACIDS
8-HYDROXYQUINOLINE-+CARBOSYLIC
x958
7-SUBSTITUTED
AND SOME z-SUI3STITUTED
ACIDS
TOWARDS
CERTAIN
METALS* bY R. G. W. The Bralish Drug Hotcscs Ltd.,
BDH
HOLl,1NGSHEAl~
Laborafory Chemrculs
Diviston,
Poole, Dorsef (Great
Bcifain)
1NTIZODUCTIOS
Since the pioneer rcsearchcs of BERG AND HAHN into the analytical applications of oxine and certain of its halogenated derivatives, search has continued for derivatives showing greater selectivity than the parent compound with regard to chelation with trace metals in solution. The fact that oxinc itself chelated with a considerable number of mctalsl caused considerable difficulties in analytical practice, and indeed, it was only by removal of interfering metals or by ‘masking’ with other reagents, that oxine could be employed for the determination of a specific metal in the presence of others. Conseyuently a great number of techniques was published, employing oxine as the precipitating agent, in which interfering metals were complexed with other reagents or removed by physical methods, to give reliable methods for the determination of one metal in the presence of others. Some years after BERG’S initial researches, certain derivatives of oxinc were employed in which substitution of halogen groups or solubilising groups (e.g. sulphonic acid groupings) conferred a certain degree of selectivity, but it is only comparatively recently that a grcatcr understanding of the underlying theory involved has given a more complete picture of the phenomenon of selectivity. * Paper read at XVth International Congress of Puro and Applied Chemistry, (Analytical) Lisbon
rg56. Section VI, Organic Comploxos.
References p. 457
II.
448
G. W.
HOLLINGSHEAD
VOL.
19 (1958)
Through the years research has been directed along three main lines (a) the formation of heavier chelates by the introduction of halogen groupings in positions 5 or 7 of the quinoline ring (e.g. 5,7-dichloro-, 5,7 dibromo-, and 5,7-di-iodo-oxines), where a ‘weighing effect’ with the formation of complexes more stable in solutions of lower PH has conferred a certain degree of selectivity on the derivative; (6) the introduction of groupings in positions 2 and/or 7, giving derivatives in which the possibility of stcric . hindrance to chclatc formation exists (e.g. 2-mcthyloxine, 7-methyloxine), and (c) the introduction of ‘solubilising groups’ such as sulphonic or carboxylic acid groupings, giving, in certain casts, water soluble chelates. Although stcric hinclrance to chelation has been shown to play an important part in conferring selectivity, other factors have to be taken into account so that anomalous bchaviour on the part of certain derivatives may be explained (see below). In the work now described some derivatives of oxine-5-sulphonic acid containing comparatively large groupings in position 7 have hcpn prepared and examined. With these derivatives the possibility of stcric hinclrancc to chclate formation, coupled with increased water solubility of the chelate exists. 130th the above possibilities also exist in the other class of oxinc derivatives prepared and examined, namely the z-substituted oxine-4-carboxylic acids. Although some derivatives of oxinc-5-sulphonic acid containing small groupings e.g. halogens, nitroso, nitro, in position 7 have been reportcd213 and their reactions towards some metals cxamincd, no derivatives containing comparatively large groupings in the stcrically hindering position 7 have been investigated, and it seemed of interest to examine the bchaviour of such derivatives towards some metallic ions. With the other class of compounds, although some carboxylic acid derivatives containing carboxylic acid groupings in positions 4 or 5 have been rcported4pb no derivatives containing a carboxylic acid grouping in position 4 and a substituent in position 2 have been critically examined with respect to their bchaviour with a range of metal ions under standard conditions. As substitution in position z is known to cause stcric hindrance to chclate formation”-8, ancl the cffcct of a carbosylic acid grouping will bc to form water soluble chclatcs, the analytical potentialities of this class of oxinc derivative seemed well worth investigating. A great dcgrce of sclcctivity is confcrrccl by the introduction of sterically hindering groupings in positions 2 and 7 of the oxinc ring and the selectivity is further enhanced by the increased water solubility of the chelates conferred by the presence of the sulphonic acid or carboxylic acid groupings. The incrcascd selectivity is outweighed however by the concomitant decrease in sensitivity. Of particular intcrcst is the formation of aprecipitatc with aluminium and S-hydroxy2-n-hcxylquinoline-4-carbosylic acid, this oxine derivative being unusual in prccipitating aluminium from solution under the conditions of the test, although containing a substitucnt in position 2. Stcric hindrance factors have prevented the formation of a aluminium
tris-comp1e.x
with many
other z-substituted
oxine
derivativese-8.
o/ devivntives
Pve$vzration
8-Jr)~Jroxyqttinoli~te-5-s-s~~Z~J~o~llc acids. These \vcrc prepared hy the reaction of the required base and forxnaldehyclc with 8-hydroxyquinollnc-5-sulphonic acid, working.in ethanol solution. 7-Subsfilatled
References
p. 457
VOL.
19 (x958)
OXINE
AND ITS DERIVATIVES
449
8-Hydroxy-7-nrorpholino,neti~ytq~~~noZ~~te-~-sulphonic acid. S-Hydroxyqumoline-5-sulphonic acid (4 g recrystallized from z y. hydrochloric acid) was stirred with 75 ml of anhydrous ethanol. To the slurry was added 4 ml of formaldehyde (35%) and 4 ml of morphohne . On the additron of the morphohne the 8-hydroxyqumoline-5-sulphonic acid remaining undissolved went into solution. The deep orange solutron was boiled for 5 min when the required dcrivativc began to precipitate. The mixture was allowccl to stand for 3 h with water cooling, then filtered, rmscd with 25 ml of anhydrous ethanol and dried at 40~. Yield 6.1 g of off-white crystalline material. Melting point (recrystallised from anhydrous ethanol) 23$’ (uncorr.) Found C = 51.4%; H = 5.050/O; N = 8.6%. C,,H,,O,N,S requires C = 51.8%; H = 5.0%: N = 8.7%. 8-Hydrory-7-ptpcridi7lo,nclhylq~trnoli~ie-g-slrlphonrc acid. This was similarly prcparcd from 8 g of S-hydroxyquinolme-5-sulphonic acid, 8 ml of formaldehyde and 8 ml of piperidinc. Yield 8.5 g. Melting point (after two recrystallisations from anhydrous ethanol) 23W (uncorr.). Found C = 55.7%; H - 5.6%; N = 8 7%. C,,H,,O,N,S requires C = 55.go/o; H = 5.6%; N = 8.7%. z-Substatuted 8-hydroryquinoliue-q-carboxyllc acrds. These dcrivativcs were prepared by rcfluxing o-aminophenol with pyruvic acid and the required aldchydc. The preparation of 8-hydroxy-n-(3,4dimethoxyphenyl)-quinolme-4-carboxylic acid has prcvtously been rcportcdg. HOLDSWORTH AND LIONS’O during an investigation into the preparation of analogues of cinchophcn, described the preparation of 2-veratryl-7-hydroxyqumolinc-4-carboxylic acid and 2-vcratryl-6-hydroxyquinoline-4-carboxylic acid from m- and p-aminophenol rcspcctivcly. bUt no preparations employing o-aminophenol were camcd out. It is know that other alternative methods of ring closure may opcratc in closely similar cases, but proof of the formation of 2-substitutccl 8-hydroxyquinolinc-.+-carboxylic acid derivatives by this reaction may be cited hcrc. DOEBNBR ANIJ I~ETTBACKI1 have prepared z-phcnyl-oxinc-4-carboxylic acid by rcfluxing o-aminophenol with bcnzaldchydc and pyruvic acid m ethanol solution. On dccarboxylation a-phcnyl-oxine was obtained, identical with samples obtained by unambiguous synthesis (seo IRVING CCal.‘*). It was found that the rcqulred reaction procccdcd most satisfactorily when freshly prcparcd o-amrnophcnol was employed. This was prcparcd ‘as rcquircd by reduction of o-nitrophenol with sodium dithionite in alkaline solution following the method of PETROW AND STURCBON~~. The o-aminophenol so prepared was kept moist with anhydrous ethanol until required. 8-Hydroxy-a-(~,q-dintethoxyplrenyl)-qrti,lolr,rc-J-carboxylic atxd. o-Aminophcnol (14 g freshly prepared) was dissolved in 300 ml of ethanol and to the warm (509 solution was added a mixture of 8.4 g of pyruvic acid and 14 g of veratraldchydc dissolved m 150 ml of anhydrous ethanol. The reactants wem stirred and refluxcd for 4 h. After standing ovcrnrght the required derivative had precipitated. This precipitate was removed, rinsed with anhydrous ethanol and dried at 40’ to give I 5 g of yellow powder. Melting point (rccrystallised from anhVtlrolls ethanol) 237O (UnCorr.). Pound C = 66.6%; 1.K= 4.4%; N = 4.3:&. Cr,H,sO~N r_cquircs d ,- 66.4%; I-l = 4.6O/; N =;I 4.3%. 8-Hydroxy-1-n-hcxylqtcinolinc-q-carboxylrc sod. This was similarly prcparcd using I o g of o-aminophenol, 6 g of pyruvic acid and 12.5 g of n-heptyl aldehyde. After rcfluxmg, the Initial volume of solution (r 30 ml) was reduced to 50 ml. On standing ovornight the required prccipttate was removed, rinsed with ethanol and dried 231uacuo at 40~. Yield 7g. It was naccssary to rccrystallisc three times from anhydrous ethanol to obtain a pure material. Melting point I 37-139~ (uncorr). Found C = requires C = 70~4%; H = 7.0%; N = 5.1%. 69.9%; H = 7.1%; N = 5.1%. C,,H1,02N 8-Hydvoxy-a-(r-ethyZpropyl)-quinoline-q-cayboxylic acid. Similarly prcparcd from 20 g of oaminophenol in 200 ml of anhydrous ethanol and 12 g of pyruvic acid and 22 g of z-ethylbutyraldehyde in 50 ml of the same solvent. Tho volume was reduced to xooml after 4 h reflux. Yield gg. Melting point (after recrystallisation from anhydrous ethanol) 205” (uncorr.). Found C = 69.3%; H = 6.6%; N = 5.6%. C,,H,,O,N requires C = 6g.5%; H = 6.6%; N = 5.4%.
Testing procedure
/or reagents with
metals
SensifrviCy lesls. The theoretical basis for sensitivity tests has been discussed in detail by IRVING ABID ROSSOTTI~~. As these authors point out, a prediction of tho behaviour of any new derivative from a consideration of the relevant physical properties and stability constants of its complexes with metals is not possiblo in practice as insufficient data are available and the required equations are complicated by competitive complex formation. A more empirical approach is necessary, such an approach being the performance of sensitivity testsi*l16,16. The method based on that suggested by IJJTZ~~ modified by IRVING et al.‘=, previously employed by HOLLINGSHEAD~~ References
$. 457
R. G.
450
W. HOLLINCSHEAD
VOL. 19 (1958)
is used here. This consists essentially in recording the sensitivity of the rcagcnt in torms of the smallest amount of metal which will give a pcrccptrblc prcclpitate or colour change in a test solution under standard conditions. Three buffar solutions A, I3 and C having PH’S of 5.3, 8.35 and x3.1 respcctivcly are employed, ancl for each test the total volume of solution is kept constant at 7 ml. One outstanding disadvantage of the tcchniquc IS that the composition and pH of the buffer solutions A, B and C arc purely arbitrary.Prccipitationreactionsof some metal-rctlgcnt combinations may occur in a narrower pH range and may thcrcforc he ovcrlookcd. ‘l’hrs could bc overcome by increasing the number of buffer solutions cmploycd, but it is unlikely that information of great use would result from the consltlcrable extra labour rcquircd. It must also bc born in mind that the appcaranca of a precipitate in one of the sensitivity tests . undor conditions of great dilution, while forming the hasis of a spot-test reaction, must not be rcgardccl as sultablc for cfuantitatlvc purposcn, as precipitation may not bc quantitative or the complex stoicliiometric in its composition. ‘rhc prcscncc or abscncc of precipitates in a series of scnsltivity tests with a new rcagcnt may well give rise thcrcforc to crroncoux conclusions regarding its possibllitics as a selective quantitative reagent. This is clenrly illustrated m the investigation of 8-liydroxy-5-nitrosoqiiinolinc previously rcportedl’. PrepavaCion of Duffer, vcagexl and nrefal solutions and method of Cesli*tg veagenls. The preparations of buffer and metal solutions have previously been described rs,16nrs, Reagent solutions wcrc M/50 in ethanol whercvar possiblo. Some solutions were hT/so in I : I ethanol-water. The m&hod of testing rcagcnts has previously beon clcscribodrs.
IiESULTS 8-Nydroxyqzci?aoline-5-slllpltonic
acid
Reactions of 8-hydroxyquinolinc-5-sulphonic acid with various metals have previously been reported in the literature The reason for including tests with this oxinc derivative in this instance was to obtain a comparison under the same conditions with the unsubstituted sulphonic acid derivative and derivatives containing substitucnts in position 7 of the quinolinc ring. Owing to the sparing solubility of oxine-g-sulphonic acid in anhydrous ethanol a hot (65”) saturated solution was employed. Oxine-g-sulphonic acid precipitates copper, zinc, cobalt and cadmium from solutions of pry 5.3 wzdev the conditiom of the test. ALBEI~T AND M~~~~~~~~~havecarriedout sensitivity tests (using a similar method to the one employed here previously reported by ALBERT AND GLEDHILL~“). At pH 7.0 no precipitation was observed by these workers with calcium, magnesium, manganese, zinc, ferrous and ferric iron, cadmium, cobalt, lead and copper, using a o.oogiIf reagent solution and a 0.0005~1l metal solution. ALBERT AND MAGRATH’S findings regarding non-precipitation with the above metals from an approximately neutral solution are confirmed, no precipitation being observed in the present tests using a buffer of pi-r 8.35. 13~1~~4also reported that, apart from a slight tendency for copper and ferric ions to form precipitates from acid solutions, no method which might appear suitable for analytical purposes could be found for any metal. This statement appeared to refer to gravimctric or volumetric procedures only ; calorimetric methods were not considered. BEHG also noted that precipitation was prevcntcd in neutral solutions containing tartrate ions. This has been confirmed. Zinc is prccipitatcd from acid solutions containing acetic acid and sodium acetate at pH 5.3. Previous reports of precipitation of the zinc complex appear conflicting. An early paper by VAISMAN~~ reported precipitation of the zinc complex using 8-hydroxyquinoline-7-sulphonic acid. MOLLAND~ repeated this work and stated that the comRsforences
p. 457
VOL. 19
(1958)
OXINE
AND
ITS DERIVATIVES
451
pound referred to as S-hydroxyquinoline-7-sulphonic acid was undoubtedly S-hydroxyquinoline-5-sulphonic acid. VAISXIAX’S method consisted in treating a solution of the zinc salt buffered with sodium hydroxide and sodium tartrate with an aqueous solution of the ‘potassium salt of S-hydroxycluinoline-7-sulphonic acid’. As the pn of this mixture would be alkaline, this method has not been confirmed in the present investigation where no precipitation was obtained with Buffer C containing sodium hydroxide and sodium potassium tartrate. 1.1~ AND BAILAR~~ have dcscribcd the preparation of the zinc complex by precipitation from a solution containing zinc sulphatc, sodium tartrate and sodium hydroxide, when on the addition of a solution of S-hydroxyquinoline-5-sulphonic acid dissolved in potassium hydroxide solution followecl by acetic acid until the pn is just acid, the zinc complex was obtained. Some doubt must be cast on VAISMAX’S reported precipitation from alkaline solution. The introduction of the hydrophilic acid grouping confers on the complexes a great degree of intrinsic solubility in water. The definite colour changes seen with Ni, Ga, In, Tl, and Y in acid and neutral solutions point to the formation of water soluble chelates (see Table II). Those metallic complcscs which clo precipitate only do so in acid solution ; in neutral and alkaline solutions they remain in solution. Thcscnsitivityof aprccipitation reaction depends both on the stability of the metal complex and on its intrinsic solubility. From the stability constants of some divalcnt metals including Cd, Co, %n, and Cu, given by NXSX~'EN ASD UUSITAIX) 22, however, it appears that the cffcct of the sulphonic acid grouping on the chclatc stability is relatively slight, so that the decrease in sensitivity obscrvcd with S-hydroxyquinolinc-5-sulphonic acid would appear to stem from the incrcascd water solubility of the chelates. In I3uffcr C, with the highest concentration (4 ml of Jf/xoo) of certain metals, the solution rcmaincd clear after digestion, although precipitation of reagent, and in some cases, metal, occurred at this PH. This occurred with copper, nickel and cobalt, and denoted the formation of water soluble chelates under these conditions.
8-Hydro~y-~-ntor~lroli~~ometltylqIrittoliltc-~-s~rlp/o~~ic
acid
A Jf /so solution of the reagent was prepared in I : I ethanol-redistilled water, owing to the very sparing solubility of this derivative in absolute ethanol. After digestion at so”, solution was complctc and precipitation of the derivative did not occur on cooling. With this derivative the possibility of stcric hindrance to chelate formation exists, with the presence of the large morpholinomcthyl grouping in position 7, in close proximity to the chelating function. This would possibly lead to aslight increase in sclcctivity, although the degree of steric hindrance obtained by substitution in position 7 does not appear to be as great as that conferred by a substituent in position 2. Outweighing any increase in selectivity due to the sterically hindering substituent in position 7, is the water solubility of the chelates conferred by the sulphonic acid grouping, leading to decreased sensitivity. The results obtained with the metals examined show that, with the exception of copper, none of the metals give a precipitate, although colour changes, pointing to chelate formation occur with Ni, Al, Ga, In, Tl, Y, Zn, Mg, Cd, Co, and Fe+a. The colour changes are generally of low sensitivity as would be expected (set Table II). Referewes p. 457
R. G. W.
452
HOLLINGSHEAD
8-Wyd~oxy-~-~i~s~idinomelhqtlqzrino~i~~e-~-~~~~~~onic
VOL.
19 (rg$.3)
acid
This reagent precipitates in Buffer C, but not in ISuffers A and I3, where clear yeiIow sofutions are obtained. The same conditions regarding steric hindrance to &elate formation being outweighed by increased water sofubiiity af the chelates occurs with this derivative, and, with the exception of copper, none of the other metals tested gave insoluble chelates under the conditions of the test. Colour changes occurred with Ni, Al, Ca, In, TX, Y, %n, Mg, Cd, Ca, and Fe +a, but these were generally of low sensitivity (see Table II). The formation of a water sofubfc chef&e with cub& in Buffer C is denoted by the nun-precipitation of the reagent with the greatest ~on~e~tr~ti~~of the metal employed, although the reagent itself precipitates at this PH.
As this compound is sparingly soluhIc in coId ethanol, a hot (so”) soft&ion was used. With this derivative, the possibility of stcric hindrance to chelatc formation exists, cuupled with enhanced water solubility of any chelate formed, due to the presence of the hydrophilic carboxylic acid grouping in position 4. This should lead to greatly increased sclcctivity coupled with decreased sensitivity. Precipitation did not occur with any of the metals examined+ Colour changes were noted with Ni, Zn, Mg, Ga, In, Tl, Co, and Fe+3 (see Table II), denoting the formation of soluble chelates. No differences in colour were obtained in the AI, Y, andCd tests, and it would appear that a small degree of sefcctivity is conferred by the presence of the comparatively large grouping in position 2. The non-formation of a chclate with aluminium under these conditions confirms the previously reported behaviaur of z-substituted derivatives towards this metal, no precipitation occurring with many z-substituted derivativesa-*. C hclation dues not appear to take place with yttrium and cadmium. With this derivative the eolour changes are of low sensitivity (see Table II) _Although both the metal and the reagent precipitate in~vidua~ly in Buffer C, no precipitation occurs with 4 mi of nl/roo cobaft, pointing to the formation of a solubtc &elate or a mixed complex.
O*I-0.04 0.4-0.3 o.t-0.04
3.8~4<2
H-#-C w-f-c
a*3-o,n 0.1-0.04 0.4-o-3
H-+-C
0,4-0.3
EL d
cu
o.uos o.ar o.oox
B
Cc f-f
a
c
c A
Ni
O.QOI 0.01
n C
Al-+3
0.00s
A
Rsfevences ps 457
H-I-C Ifs-C -
NPf 0.4-0.3
dark dark
brawn brawn
yellow
brown
4*4-4.5 3.8-4.2 .~.a-4.4
brown orange yellow
yellow
482-494
brown
yellow
4.2 -4.4
yellow
*
VOL.
19 (1958)
OXINE
AND
TABLE
ITS
I
453
DERIVATIVES
(continued) -_---_
.%rttol Al Al Ga+s Ga Ga Ga In+s In In Tl+s Tl Tl
nr
Rulfrr B C A
0.01 0.01
co+* co co Fc+s FO FO
NP NP
COburC
3.5-3.8
yellow
6 C
C H+C H-j-C
0.4-0.3
4.2 -4.4 3.5-3.8
yellow yellow brown
H+C H+C H+C
0.2-0.1 0.2-0.1
3.5-3.8 3.5-3-g
yellow yellow
0.01
A B C
0.00x
A :
H+C H+c H+C
0.4-0.3 0.4-0.3 NP
4 2-4.4 4.2-4.4
yellow yellow
A B C
H+C H+C H-j-C
2.2-2.4
yellow
4*oE:‘o NL:
A B C
H+C H+C H+C
0.2-0.x
3.5-3.8 3.5-3.8
yellov yellow
H+C H+C Hi-C
NP 4.0-3.0 NP
2.2-2.4
0.01
; C
brown ( yollow)
0.01
A
H+C H-I-C H+C
4-o-3.0
2.2-2.4 2.2-2.4
yellow yellow
H+C H-i-C HCC
0.4-0.3 0.3-O NP
4.2-4.4 5.4-5.5
brown orange brown
3.5-3.8
brown or grcon h (brown or green) i
0.001 0.01 0.01
0.01
0.01
0.001 0.01
0.01
Cd+’ Cd Cd
pf.b
0.2-0.1
0.0x
Mg+’ Mg Mg
H+C H+C
VI b C’,a
--
H
0.01
0.0x
Zn+l Zn Zn
Tube cxomlncJ
0.01 0.01 0.01
0.0x 0.0x
0.01
c”
0.0x
0.00
I
A
0.0001 0.01
:
0.01
A
0.01 0.01
:
HfC HCC H-+-C
0.2-0.x
NP
NP
0.2-0.x
NP
4*oSo
0.2-0.1
NP NP
2
(rose pink) 6 (rose pink) B
V, and It, are the volumes of standard metal solutron which (I) give a precipitate or colour change and (2) fail to give a precipitate or colour change respectively. pLisdefinedas-log(hmitingconccntration), ing.equiv./lforthevolumcsV,and Vsrespectivclylr. This value is to bc preferred as an expression of sensitivity as the use of pg/ml may convey a false impfession of the difference in sensitlvitics of the reagent with metals of differing atomic weight or valency. Colours 16 parentheses refer to solutions and colours not in parentheses rofcr to colours of procipitates. Hot. Cold. NP = No precipitate. Before digesting at 70“ a rose pink colouration occurs on the addition of reagent solution. This is destroyed on heating with the formation of a yellow precipitate Brown precipitate in tube containrng the higher concentration of Fc+e; green precipitate in tubes containing the lower concentrations. Brown colouration in tube containing the higher concentration of Fe+2; green colouration in tubes containing the lower concentrations. Rsfrrences p. 457
R. G. W.
454
8-ir/ydroxy-2-It-ltexylqzlinoline-g-cavboxylic
HOLLINCSHEAD
VOL.
19 (1958)
mid
8-Hydroxy-z-n-hexylquinolinc-4-carboxylic acid is readily soluble in absolute ethanol giving a yellow solution. From the results given in Table I it is seen that precipitationof all the mctalscxamincdoccurs, although the sensitivity with magnesium, yttrium The presence of the long aliphatic chain in position 2 of the and cadmium is very low. quinoline ring does not confer a great dcgrcc of selectivity due to steric hindrance reasons, and in behaviour, this derivatives may be compared to oxinc itself. Although the prcscncc of the carboxylic acid grouping in position 4 would lead to the formation of water soluble complexes, so conferring cnhanccd selectivity, this appears to have been outweighed to a great extent by the aliphatic chain in position 2, which has caused large differences in the intrinsic solubilitics of the chclatcs, with the formation of chelates which are less soluble in water than those of other 4-carboxylic acid derivatives examined. The overall sensitivity of this derivative approaches closely that of oxine itself, the pr, values of the chelates being of the same order as those of the corresponding ovine chelates. The most interesting behaviour of this dcrivativc is its formation of a precipitate with aluminium at prr 5.3. Previous reports of non-chelation with this metal and other z-substituted oxinc derivatives have suggested stcric hindrance factors to be rcsponSibk”-“. IRVING, CUTLER AND RINC.‘~ confirmed iM~lcl
p. 457
VOL. 19 (x958)
OXIKE
A*‘D ITS DERIVATIVES TABLE
LI~llTING
CONCENTRATLONS
OF
MRTALS
455
11
GIVISG
COLOUR
CHANGES
WITH
OXISE
DEHlVATlVOS
--
b-Hydroryqlti~aoline-5-slrIpilo,rzc
acid
Cl]+* Nl+’ Al+3
0.0x 0.00 I
B B .\, B, C
0.)-O 04 o.j-0 3 NC -1
3 Z-4.2 4.2-4.4
cmctalcl green applc~rccn
Ga+a In+3 TI+=
0.0x 0.0 I 0.01
A. B
0.4-o
04 04 0 l-0.04
3.2-4.2
green
A. l-3
0.1-o
3.2-4.2 3.8-4.2
pale yellow ycliow
y+= Zn+* Mg+’
0.01 0.01
A i3 A. 13, C
0.4-0.3 0.1 -0 04 KC
3.2-3.4 3 s-4 2
pale yciiow yellow
ccl+*
0.01
C
OI
3.8-4.2
co+*
0.01
13
0.
yellow yellow brown cnicralti green
Fe+8
0.00 I
A. B
-0
04
-0.04 0.3-0.2
h, B
8-Hydroxy-~-~~rorpholi~~o~~~e~l~ylgurrrol~~te-~-srrIplro~:~c
actd
c
0.4 -0.3 0.4-0.3 0 L-004 0.4-0.3
3.2-3.4 3 2-3.4 3.8-4.2 3.2-34
pale yrccn pale ycilow ycilow green green yellow
x B n, I3
0.4-0.3 0. t-o.04 o-4-0.3
3.2-3.4 3 8-4.2 4.2-4.4
1’“iC yellow tlccp orange cnrcrald green
i3
O.OL
13
0.01
A, I.3
Tl+= y+= %n+’
0 01 0.01 0.01
A, IJ :\ A, I3
xig+*
0.01
Cd+2 co+* &-c+3
0.01 0.01 0.001
acid
8-Hydroxy-7-papertdinonrerlrylgtcrrrolrtot~ac 0.1-0.04 0.1 -O.Od 0.1-O 0; 0.3-0.2
3.8-4.2 3.8-4.2
0.01
I3 A. I3 A; I3 B
0.01
2
0.01
A,
B
0.4 -0.3 0.4-0.3 0.4-0.3
3.2-3.4 3.2-3 4 3.2 -3.4
B
0.4-O 0.4-0.3 0.4-0.3 0.3-0.2
0.01
0.01 0.01
A,
Mg+2
O.OL
Ccl+’ co+*
0.01
B A
0.01
r\
I%+=
0.001
A,
cu+*
4-4.5
3 S-3.8 3.2-3S4 3.2-34
0.01
Y+3 T1+a Zn+l
4
0.2-0.1 0.4-0.3 0.4-0.3
Ni+a Ga+= Itl+J
Ni+* Al+J Ca+3 In+a
3.8-4.2
f
0.001
NI+~ Al+=
0.0:
Ga+3 In+= T1+3
0.0x 0.01 0.001
B B A.
B,
A B A, B
c
3
3.8-4.2
3 4-3
5
yellow pdc green pnic green grfXt1
green pale green
pale
3.2-3.4 3.2-3.4 3.2-3.4 4.4 -4.5
paic green green yellow yellow emcraid green
brown yciiow
0.3-0.2 -0.04 NC
4.4-4.5
0.1
3.8-4.2
0.2-0.1
3.5-3.8 3.8-4.2 4.2-4.4
0. I-O.04 0.4-0.3
green
orange
orange yellow orange
TABCE
y+=
Zn+2 Mg+2
0.01 0.0x
Cd-co+2 I.‘c+3
0.01
0.00 I
A,
NC
B, C
A, u, A, I3 A, I3
c
0.01 0.01
cu42
NI+’ Al+3 Ga+:’ In+a -l-l+”
0.001 0.001
YC3 0.01
Zn42
Mg+2
A, I3
0.2-0.1
0.4-0.3
0.0x 0.0x 0.001
yullow olive green
3.5-3.8 4s4-4.5
orange yellow
3.5-3.8 3.4-3.5
olive green ; green brown yellow
4.2-4~4 4-2-4~4
yellow yellow
NC 0.2-O.
I
0.3-0.2
brown;
orange
A, B, C
0.3-0.2 NC
A, 13, C u A
NC 0.4-0.3 0.4-0.3
A, 13, C
NC 0.3-0.2 NC
3.4-3.5
yellow
0.3-0.2 0.3-0.2
34-3.5 3.4-3.5 4.5-4.8
yellow yellow emerald green
:: B
--
yellow
acid 0.2-0.1
A, B, C
ccl+2 co+2 l%+s
3.5-3.8 3.2-3 4
I3
B
19 (1958)
II (contrnucd)
d-ffydrory-a-(z-ellryfpvopyl)-q~~anoli~re-q-carboxylrc
a NC =
VOL.
R. C. W. HOLLINGSHEAD
456
0.2-0.x
---_-
No dkornablc
colour change.
This derivative is freely soluble in absolute ethanol, giving a yellow solution. With all the metals investigated, precipitation of a complex does not occur. Colour changes denoting chelate formation are found with Cu, Ni, Zn, In, Tl, Cd, Co and Fe+8 (see Table II). The carboxylic acid grouping, conferring water solubility on the chelates, appears to outweigh any influence the branched chain aliphatic grouping may have on the intrinsic solubility, so that water soluble chelates are formed under the conditions of the test. All these colour reactions are of low sensitivity (see Table II). DISCUSSION
None of the derivatives investigated shows any striking analytical advantage over the parent compound. A large increase in water solubility of all the chelates was to be expected, due to the presence of sulphonic acid or carboxylic acid groupings, but the hope that sensitive colour changes, due to the formation of water-soluble chelates would form the basis of new spot test techniques has not been fulfilled. Such colour reactions as were observed have been, largely, of low sensitivity, precluding their analytical use. The one exception is the formation of a rose-pink colouration with trivalent thallium and 8-hydroxy-z-+hexylquinoline-4-carboxylic acid. This may well form the basis of a spot test for the detection of this metal in the presence of others of the same sub-group. References
p. 457
VOL.
19 (1958)
OXINE
AND
457
ITS DERIVATIVES
The hope that the weighing effect of the comparatively large groupings in position 7 of oxine-5-sulphonic acid would further enhance any degree of selectivity conferred by the presence of the solubilising sulphonic acid groupings has not been realised.
My thanks are due to the Directors of The British Drug Houses Ltd., this work.
for permlssion
to publish
SUMMARY A numl>ar of new derivatives
of B-hydroxyquinoline
containing
both solubihslng
groups
and
groups which might stcrlcally hinder chelntlon have been prepared, WE. B-hydroxy-7-morphohnomethylquinoline-5-sulphonic acid, 8-hydroxy-7-p~pcr~di~i~~,~t~~~lquinoline-~-sulphon~c acid, B-hyB-hyclroxy-z-n-hexylquinolinc-4clroxy-2-(3,~-cl~mcthoxyphengl)-qu~nol~ne-~-carb~xyl~c acid. The hmlting sensecarboxylic acid and B-hydroxy-2- (t-ethylpropyl)-qulnolinc-&arboxyhc tivities of the reactIons of these rcagcnts towards copper, nlckol, alumimum, zinc, magnesium, galhum, indlum, thallium, pttnum, cadmium, cobalt ancl iron have been lnvcstlgated
REFERENCES
1 H.G.\V.HOLLINCSHEAD.OXI~~OUI~~IISDC~I~~~~~~CS,\~~~~.
I-IV,Rutterworths,London,rg~~-1956.
4 J. MOLLAND, a J. RIOLLAND,
Awh. Mulh. NaftcwiJorskul. 13 (1940) 67. 19 (rg3g) x60: J. Am. ‘I’adsskr. Kjemr og 13ergvrsen. Kjemh og Uergvesen. 19 (1939) I 19; at (194 I) 49.
Chrm. Sot., 62 (1940) 541; Tidsskr. 4 R. BERG, Z. unorg. Chem., 204 (1932) 208. I (1880) 860; E. LIPPMANN AND 1;. FLEISSNER, Ser. deul. them. Ges., 6 A. U~sz~~~,j\lo~~uIsh.Chem.. 19 (1886) 2467; A. ALDaRT ASD 1). hlAGRATt1, Bwchrm. j., 41 (1947) 53.) 6 I-. I,. MKHHITT AND J. 1;. \VALK~ZR. Ind. Eng. Chern., Anul. Ed., 16 (1944) 387. 7 J. P. L’HILLIPS AND L. L. MLSHRITT, J. Am. Chem. Sot., 71 (1949) 3984. 0 J. P. PHILLIPS, W. H. HUOW. J. M’. CHUNG AND L. L. MERRITT.J. .4rt~.ClJenz.Soc., 73 (rggl) 630. Y 1%. G. W. MOLLINGSH~SAD. Heseurch (London), 8 (1955) SIC. 10 31. G. HOLDSWORTH AND 17. J. LIONS, J. &OC. ROY. SOC. 1v.s. iV&S, 66 (1932) 277. ‘1 0. DOWN~SH ASD H. FETT~~ACK, Ants. Chon , Laebrgs. 281 (1894) 7, g 18 H. IRVING, E. J. BUTLER AND >l. F RING, J. Chem. Sot., (1949) x489. Ia \‘. PeTROW AND u. STUHGBON. J. Chcm SOC., (1954) 570. 14 H. IRVIN<; AND I-1. S. ROSSOTTI, Anuiysl, 80 (x955) 245. 16 0. LUTZ. Z. at&. Chem., 5g (1920) 149. 1’ R. G. W. HOLLINCSIIEAD, .4ul. Chwa. Ado, 12 (1955) 201. 17 H. IRVING. R. G. W. HOLLINOSHEAD AND G. HARRIS, .4nuCysf, 80 (1955) 26o. 10 A. AL~~RC AND D. MAGRATH, Btochem J.. 41 (1947) 534. le A. ALBERT AND W. S. GLEDHILL, Blochrm J.. 4 1 (1947) 529. 90 G. A. VAISMAN, Ukrarn. Gosudars;. Inst. Ehspil Form (Khurkou) ; Konsul’fulsionnye Maferaoly, (1940) ‘43. 11 J. C. 1. Lru AND J. c. BAILAK, J. Am. Chem. Sot , 73 (1951) 5432. ** R. NASXNBN AND E. UUSITALO, Acfa Chem. Stand.. 8 (1954) I 12. 12 J. P. PHILLXPS AND E. >I. BARRALL, J. Org. Chem., 21 (1956) 692. Received
March
1st.
x958