412

PRAKASH CttANDRAGUPTA

Bd. 196

ursprfingliche J o d g e h a l t d u r c h zweimalige Mitf/~llung in der schlie$lich c r h a l t e n c n T e l l u r p r o b e a u f 0,1~ h e r a b g e s e t z t wurde, b e d e u t e t dies, d a $ m a n d u r c h die Messung d e r S t r a h l u n g s - A b s o r p t i o n s k u r v e diescr P r o b e 0,01~ feststellen k a n n , was bei einer 50~ chemisehen A u s b e u t e d e r M e t h o d e einem W e r t y o n 0,02~ d e r Gcsamtaktiviti~t des J o d p r ~ p a r a t e s l a l j in d e r u r s p r i i n g l i c h e n A n a l y s e n p r o b e entspricht.

Zusammenfassung E i n e B e s t i m m u n g s m e t h o d e y o n r a d i o a k t i v e m Tellur in Jod-131P r ~ p a r a t e n w i r d vorgeschlagen. Z u r T r e n n u n g d e r sich teilweise fibers c h n e i d e n d e n A k t i v i t ~ t e n w e r d e n J o d im alkalischen u n d Tellur im sauren M e d i u m a n Quecksilber(I)-ehlorid mitgef~llt. Die M e t h o d e liefert befriedigende Ergebnisse.

Summary A m e t h o d for t h e d e t e r m i n a t i o n o f r a d i o a c t i v e t e l l u r i u m in iodine-131 p r e p a r a t i o n s is proposed. I n o r d e r t o s e p a r a t e t h e p a r t l y o v e r l a p p i n g a c t i v i t i e s iodine is c o - p r e c i p i t a t e d on m e r c u r o u s chloride in alkaline a n d t e l l u r i u m in acid m e d i u m . S a t i s f a c t o r y results are o b t a i n e d .

Literatur 1 AR~OL, W. J.: AERE I/R-777 (1951). -- 2 CO~r R.: J. Inorg. Nucl. Chem. 7, 133 (1958). -- 3 EvAns, C. C., u. J. STEVENSOn: U. K. Pat. 763.865. -4 !VIAc~r,M. : Second United Nations Int. Conf. on the Peaceful Uses of Atomic Energy, A/Conf. 15 (P) 2109 (1958). -- 4a P]~n~so~, D. H.: Nature (London) 173, 990 (1954). -- 5 PIErsoN, G. G.: Ind. Engng. Chem., anal. Edit. 6, 437 (1934); vgl. diese Z. 103, 292 (1935). -- 6 RJABTSC]~KOFr, D. I. : Primjenenije metschenych atomov v analytitscheskoj chimii, Moskva, Izd. Akad. Nauk, 1954, 179. -- 7 TAVGnOL, K., u. K. SAMSAHL:JENER Report 34. -- s US Pharmacopaea XVI., 1961. -9 Z]~LE~Au T., u. R. PLEJ~,WSKI:Kerncnergie 12, 1198 (1960). L. KRO~XD und J. C f F ~ , Inst. Kernforschung d. tschechoslov. Akademie d. Wisscnschaften ]~e~ bei Prag (Tsehechoslowakci)

Analytical Chemistry of Thiocarbamides I. Quantitative Determination of Thiourea By

I~RAKASH CHANDRA. GUPTA.

(Received January 15, 1963) T h i o c a r b a m i d e possesses n u m e r o u s i n d u s t r i a l , a n a l y t i c a l a n d medicinal a p p l i c a t i o n s ; c o n s e q u e n t l y its e s t i m a t i o n u n d e r v a r i e d conditions is of considerable i m p o r t a n c e . Several m e t h o d s h a v e been p r o p o s e d from

1963

Thioearb~mides. I. Thiourea

413

t i m e to t i m e for its q u a n t i t a t i v e d e t e r m i n a t i o n . These m e t h o d s can be r o u g h l y classified as follows: I. Oxidimetric methods. 1. Oxidation with potassium permanganate. 2. Oxidation with potassium dichromate. 3. Oxidation with eerie sulphate. 4. Oxidation with potassium bromate. 5. Oxidation with iodine (iodimetrie methods). 6. Oxidation with potassium iodate and periodate. 7. Oxidation with hypobromite. 8. Oxidation with iodine monoehloride. 9. Oxidation with selenious acid. 10. Oxidation with potassium ferrieyanide. 11. Oxidation with chloramine-T. 12. Oxidation with hydrogen peroxide. II. Complex formation with inorganic salts: 1. Complex formation with mercury salts. 2. Complex formation with copper sulphate. III. Desulphurisation with heavy metals. 1. Argentometrie methods. 2. Desulphurisation with zinc. 3. Desulphurisation with cadmium. 4. Desulphurisation with lead. IV. Aeidimetrie methods. V. Colorimetric methods. VI. Other miscellaneous methods.

I. 0xidimetrie methods T h i o c a r b a m i d e has been s u b j e c t e d to t h e a c t i o n of various oxidising a g e n t s u n d e r v a r i e d conditions. N e u t r a l r e a g e n t s such as p e r m a n g a n a t e in t h e absence of acids s~ give u r e a a n d s u l p h a t e as t h e m a i n o x i d a t i o n p r o d u c t s . I n acidic m e d i u m m i l d oxidising a g e n t s such as iodine, give f o r m a m i d i n e d i s u l p h i d e as t h e i n i t i a l p r o d u c t . 2H2N- C 9NH 2 ~-

II

S

~ (H2N~C--S--S--C--NH2) + 2H + + 2e.

II

NH

II

NH

(1)

PmESlml~ a n d B~I~GER 91 f o u n d o x i d a t i o n - r e d u c t i o n p o t e n t i a l of t h i o u r e a - f o r m a m i d i n e d i s u l p h i d e s y s t e m to be 0.420 volts in 0.05 t o 1 N h y d r o c h l o r i c acid. A c c o r d i n g t o t h e m t h e s y s t e m is analogous to t h e thioldisulphide system : (2 RSH--> lZ--S--S--tL + 2 H + + 2e) I o d i n e does n o t oxidise i t b e y o n d this stage. B u t in m o s t o t h e r oxid a t i o n s t h e f o r m a m i d i n e d i s u l p h i d e f o r m e d c a n be f u r t h e r oxidised to give u r e a a n d sulphate.

414

PRAKASHC~A~D~A GVPTA

Bd. 196

I n alkaline medium, probably the initial product is again formamidinc disulphide. But the compound being unstable under these conditions decomposes or disproportionatcs as follows: (H~N--C--S--S--C--NH2) 2ttX -> H2N. CN -~ S ~ H~N--C--NI-I2 -{- 2HX. (2)

Jl

NH

11

NH

II

S

Sulphur, cyanamide and a molecule of thiocarbamide are the principal products. The thiocarbamide molecule so produced gets further oxidised and the cycle of the changes (1) and (2) again repeated. The sulphur formed is in a colloidal condition and is responsible for the observed turbidity in oxidation reactions of thiocarbamide. I t gets finally oxidised to S Q ~-. The cyanamide formed m a y polymcrise to dicyandiamidc and other cyclic products or undergo hydrolysis to urea. I f medium is acidic hydrolysis to urea predominates but under alkaline conditions polymerisation becomes important*. With an excess of oxidant all the thiocarbamide gradually decomposes into sulphur, which on oxidation gives sulphate. The interaction of chlorine, bromine and iodine with thiocarbamide has been widely investigated by several workers. I n most cases what the earlier workers considered as dithiocarbamidc dichloride ~~ dithiocarbamide dibromide 20,s0 or dithiocarbamidc di-iodidc56, 7s have been shown to be identical with the formamidine disulphide dihydrohalide compounds obtained b y later workersa4,1~ 1~2. Nitric acid oxidises thiocarbamide to formamidine disulphideTS, n2. Nitrous acid oxidises it to formamidinc disulphide n2 in a strongly acidic medium, but in a weak acid medium, thioeyanic acid and nitrogen are obtained as the main products2~,3~176176 1~. acid H2N" C" NH~ ~- H2N" C=NH--H~--> H2N" C---S--S--C 9NH~; 2HX+ 2NO -t-2H~O II II t] [I NIt S SH NH (in strong acid medium) H2N. CS 9NH~ -t- HN0~ -> HCNS ~ N~ ~- 2H20 (in a weak acid medium). According to OEC~SNEE DE Co~r~cK sga thiocarbamide is less readily attacked t h a n carbamide by an alkaline solution of sodium hypochloritc, and the decomposition is represented b y the equation s7 H ~ N " CS "N I t 2 + 7 0 - -

-> CO~ + SO8 -t- N2 -t- 2H20.

When oxidiscd b y chloric or bromic acids thiocarbamidc is vigorously decomposed into urea and sulphateSs, ha. 5H~N" CS" NH2 + 4HBrO~ -[- 3H~O * 7,9,14,31 ,~3,47,55 ~86,116,120

> 3H~N" CO" Ntt~ ~- 4ItBr -~ 3H~SO~.

1963

Thiocarbamides. i. Thiourea

415

Thiocarbamide when treated with normal potassium chromate and sulphuric acid yields ammonium thiocyanate and consequently thiocyanic acid and the products of its decomposition together with ammonium sulphate and ammonium hydrogen sulphate. In some cases small quantities of free nitrogen were also observedSgb,9~ Peracetic acid in acetic acid medium oxidises thiourea to the trioxide or formamidine su]phonic acid 1~. H2N 9C - S03H.

H

NH

The electrolytic oxidation of thiocarbamide in nitric acid solution at a platinum anode has also been studied by FICttTEtr and W ~ K sa. They found the formation of dithioformamidine dinitrate as the main oxidation product; a small amount of thiocarbamide also decomposed to form ammonia and sulphuric acid. H ~ N " CS 9 NI-I2 -~ 4 0 -}- 2 H 2 0 -

-> C02 -b (NHd)~S0~ -b H 2 0 .

MATSW and AsmI)A s3 also obtained dithioformamidine dinitrate by the electrolytic oxidation of thiocarbamide. FgEVZ~DLICtt and F~s~Eg 37 in 1924 studied the kinetics of the oxidation by oxygen of thiourea adsorbed on blood charcoal and SC~E~K and WIDTHT M studied the photo oxidation of thiocarbamide and reported 45--60~ yield of 'amino-imino methane sulphinic acid', HN:C(NI-I2)SO,H, in pyridine with protoporphyrin as sensitiser. Continued oxidation yielded cyanamide and sulphuric acid. Powerful oxidising agents bring about irreversible oxidation of thiocarbamide to carbamide and sulphate. The quantitative oxidation of thiocarbamide by potassium permanganate, potassium dichromate, eerie sulphate, potassium bromate, iodine, potassium iodate, hypobromite, iodine monochloride, selenious acid, potassium ferricyanide, ehloramine-T and hydrogen peroxide etc., under certain specific conditions is employed for the quantitative determinat;on of thioearbamide and is therefore discussed below in detail. 1. Oxidation with potassium permanganate G u ~ E s c ~ I a4 found that thiocarbamide when oxidised with permanganate yields all its sulphur in the state of sulphuric acid. It was shown by ~ALu as that thiocarbamide is oxidised in neutral solution by KS~nO4 with the formation of urea, nearly all the sulphur being oxidised to sulphuric acid. But it was noticed that the amount of oxygen used up fell short of that required by the equation: CS(NII2)~ + 4 0

---+ C0(NH2) + 808,

which was put forward to represent the change.

416

P~)~KAS~ C~ANDBAG ~ e ~

Bd. 196

SC~MIDT 1~ referring to M~LY's work stated t h a t thiocarbamide is quantitatively oxidised b y p e r m a n g a n a t e to urea. W]~NE~ 121, however, found t h a t although 98.7 ~ of the sulphur is oxidised to sulphurie acid, only 44.40/o of the theoretical yield of urea is obtained. Ammonia, C 0 2 and a substance CatITN5 are formed in addition to urea. Experiments carried out b y CtrTEr~L a n d A~KlXS 36 showed t h a t the oxidation of thiocarbamide with p e r m a n g a n a t e does n o t afford a satisfactory means of determining thioearbamide quantitatively.

2. Oxidation with potassium dichromate A mixture of potassium dichromate and sulphuric acid is added to thiocarbamide solution and boiled for thirty rain under reflux. After cooling, the solution is titrated against standard ferrous ammonium sulphate solution, with diphenylamine indicator (5 ml of phosphoric acid of d ~ 1.67 and one drop of a solution of 1 g of diphenylamine in 100 ml of cone. sulphuric acid). Under these conditions three molecules of thiocarbamide react with four molecules of potassium dichromate, suggesting the following reactions 26: 4K2Cr207 ~- 16tI2S0 a = 4K2S04 q- 4Cr~(SOd)a -t- 1 6 H 2 0 @ 1 2 0 3CS(Ntt2) 2 + 1 2 0 -+ 3CO(NH2) 2 q- 3S03.

3. Oxidation with ceric sulphate26, 6s CUT.ILL and A~KINS ~6 f o u n d t h a t under certain conditions, one molecule of thioearbamide reacts with eight molecules of cerie sulphate. T h e y suggested the following reactions to be taking place: 2Ce(SOa) 2 q- t I 2 0 -+ C%(S0~)3 ~- tI2SOa q- 0 CS(NK2)2 + 4 0 + R~O --> CO(NK2) 2 -~- I{~SO~. The ceric sulphate solution was prepared b y the action of eonc, sulphuric acid on ceric oxide 124. A 0.1~ aqueous solution of xylenc cyanol FF was used as indicator in the titration. A mixture of thiocarbamide solution, ceric sulphate and sulphuric acid is boiled under a reflux condenser for 10 rain. After cooling, the excess ceric sulphate is titrated with ferrous ammonium sulphate solution. The method has the disadvantage that when the concentration of thiocarbamide falls below a certain limit (ca. 1 g/l) oxidation is incomplete, even on prolonged boiling. The indicator also is not very satisfactory.

4. Oxidation with potassium bromate Potassium b r o m a t e in neutral m e d i u m reacts with thioearbamide as follows : 3CS(NI-I2) 2 na 4 t l B r O a q- 3 H 2 0 -~ 3C0(Nll2)2 q- 3H2S04 q- 4I-IBr. SZEB~ImEDg and MAP,S ~la titrated a solution of thiocarbamide in presence of potassium bromide at 4 0 - - 6 0 ~ with 0.1 N potassium bromate solution using gold chloride (aurie) as catalyst, The end point in the above

1963

Thiocarbumides. I. Thiourea

417

titration is indicated b y the appearance of a faint yellow colour. I n presence of potassium iodide and sulphnrie acid or hydrochloric acid, MAIdRsl observed t h a t direct titration with bromide-bromate mixture can be performed at 35~ in accordance with the following equation: NH~ 2C--SH + 0

l[

NH

:NH2 ->

NH2

- - S - - S - - ,2HX @ H~O.

II

NH

II

NH

A specific concentration of potassium iodide for the reaction to proceed to the formation of formamidine disulphide, is, however, essential, because an insufficient quantity of the iodide favours the production of urea and sulphate, whereas too large an excess of K I promotes the liberation of iodine b y the disulphide before the end of the titration is reached. Despite strict adherence to the experimental conditions, this titrimetric method gives irregular and irreprodncible results. A r e a RAo and NEELA~:A~TAM9a in the course of investigations on the volumetric determination of thiocarbamide found t h a t MAHg's results could not be readily reproduced nor the accuracy claimed substantiated. Recent investigations b y BANERZE~a show t h a t the amount of acid present and the speed of titration effect the accuracy of the results. Z o r ~ L ~ and VORGAla6 studied the effect of the quantity of bromide in the bromametric determination of thiocarbamide audits derivatives and suggested t h a t the oxidation of S is incomplete in presence of larger amounts of bromide. 5. Iodimetric methods McGowA~ 79 first obtained the compound C~S2NdH6 92 H I (formamidine disulphide dihydriodide) by the interaction of iodine and thiocarbamide in presence of alcohol. HUGH-MARSHALL56 obtained the same compound from the interaction of the two substances in presence of water and examined it in some more detail. But both of t h e m were misled as regards the true nature of the compound formed, which they considered to be an additive compound 'dithiocarbamide diiodide' (CSN2Ha)~I2, the formation of H I and the saline character of the substance having escaped their attention. When iodine and thiocarbamide are allowed to interact in the presence of a solvent capable of bringing about even a feeble degree of ionisation, a reaction ensues in accordanCe with the equation: 2CSN2H4 -k I2 ~ C2S2NdH6 9 2 I t I .

The formation of this base was observed b y STo~cH n2 while investigating the influence of a number of oxidising agents (including iodine) on thioearbamide. FICHTE~ and W ~ K aa, who obtained it by the electrolytic Z. analyt. Chem., Bd. 196 27

418

P~A]~AS~C~AND~ GUPTA

Bd. 196

oxidation of thiocarbamidc in acid solution, called it "formamidine disulphide". The formation of this compound b y the action of iodine on thioearbamide has been investigated in detail by W~RN~l~ ~2~.Lt~TTI~I~GHAVS77 postulated t h a t the oxidation of the thioearbamide does not go through the so-called "iso"-form, but through a zwitterion form, -SC(NHx) : NH2+" 5a. Oxidation with iodine in acid medium. The determination of thiocarbamide b y oxidation with iodine in an acidic medium was originally developed b y R~Y~OLDS and W]~N]~a 96 for the estimation of this compound in presence of thiocyanates. I f iodine solution is added to a strong solution of thiocarbamide, the colour of the halogen disappears until a state of equilibrium is reached. This condition is disturbed by further dilution, and the solution decolourises more iodine. These workers were able fo estimate thiocarbamide quantitatively, requiring 1 molecular equivalent of iodine for every 2 moles of thioearbamide. Because of the unfavourable equilibrium involving formamidine disulphide in concentrated solutions, the method requires very dilute thiocarbamide and iodine solutions to be successfully used. They also found t h a t the dilution required is such t h a t the solution to be titrated should not contain more t h a n 0.05 g of thioearbamide in 250 m112~. The method, however, is not very satisfactory: The end point is difficult to locate and requires very dilute solutions of thiocarbamide. W ~ N ] ~ 12~ tried this reaction in presence of theoretical amounts of sodium acetate required to react with the hydriodic acid, but was unable to obtain any quantitative results. Attempts to modify the above procedures b y using alcoholic instead of aqueous solutions of iodine did not yield any improved results 92. Moreover, iodine m a y react with alcoholic solutions of thiocarbamide 78.

5b. Oxidation with iodine in alkaline medium (oxidation by hypoiodite). CUTH~L and AT~NS as worked out a method for the determination of thiocarbamide with alkaline iodine. I t s details are as follows: 10 ml of approximately 0.025 IV[ thiocarbamide solution is mixed with 10 ml of 2N sodium hydroxide solution; then 50 ml of 0.1N iodine solution is added and the mixture is set aside for 15 rain, after which it is acidified with 20 ml of 4N sulphuric acid and titrated with 0.1N sodium thiosulphate solution. Under these conditions, four molecules of iodine react with one molecule of thiocarbamide, suggesting the following reactions: 2 N a O H + 12 -+ N a I O + N a I + H~O. 4 N a l O + CS(NH2) ~ H~O_+ CO(NI_I2)2 + 4 N a I + H2SO ~. The order of mixing the solutions is important, for if they are mixed in a n y other order, a turbidity, apparently due to sulphur, appears and the reaction does not proceed to completion. I f the alkali concentration recommended in the procedure is excessively increased, high results are obtained.

1963

Thiocarbumides. I. Thiourea

419

SK]gAMOVSKY111 r e c o m m e n d e d a s l i g h t l y different p r o c e d u r e : To a solution containing about 0.02 g of thiourea are added 25 ml of 0.1N iodine solution and 5--10 ml of 10~ potassium hydroxide solution. The reaction nfixture is allowed to stand for 5 - - l 0 rain, after which the solution is acidified with 5--10 ml of approximately 100/0 hydrochloric acid. The oxidation reaction is essentially complete in about 4 rain, and ~ longer reaction time up to 30 rain is reported to have no effect m. l~ormation of turbidity in the reaction mixture may be due to the formation of finely divided sulphur, in which case the order of addition of the iodine and caustic solution should be inverted as recommended by CVTK~Lt, and ATt(I~S 2a. If the Mkali concentration recommended in the procedure is increased, l~gh results are obtained. Jos~I61, 62 r e p o r t e d successful e s t i m a t i o n of t h i o c a r b a m i d e a n d t e t r a m e t h y l t h i o c a r b a m i d e b y t h e m e t h o d of CuTmzL a n d ATOMS 26 a n d D~S~MVX~ a n d BAPAT ~9 followed t h e h y p o i o d i t e o x i d a t i o n of thioc a r b a m i d e b y t i t r a t i o n of t h e excess iodine w i t h p o t a s s i u m i o d a t e using iodine m o n o c h l o r i d e end p o i n t ; a l t e r n a t i v e l y , t h e a m p e r o m e t r i c d e a d stop end p o i n t was also a d o p t e d . 5 e. Oxidation with iodine in n e u t r a l or buffered media. I f a thioc a r b a m i d e solution is a d d e d dropwise to a n iodine solution contaitfing s o d i u m b i c a r b o n a t e , t h e o x i d a t i o n of t h i o c a r b a m i d e is q u a n t i t a t i v e . The e n d - p o i n t c a n be o b s e r v e d v i s u a l l y as u s u a l or p o t e n t i o m e t r i c a l l y 45. T h e m e t h o d gives g o o d results, is convenient, a n d has t h e a d d e d a d v a n t a g e t h a t ff a n excess of iodine is e m p l o y e d , t h e excess o x i d a n t can be t i t r a t e d b a c k a g a i n s t arsenious oxide in t h e same m e d i u m (viz., in presence of s o d i u m b i c a r b o n a t e ) . T h e use of arsenious oxide, which unlike s o d i u m t h i o s u l p h a t e , is a p r i m a r y s t a n d a r d a v a i l a b l e in a high degree of p u r i t y 9a,las, is c e r t a i n l y to be preferred. T h e r e a c t i o n s m o s t p r o b a b l y can be r e p r e s e n t e d b y t h e following e q u a t i o n s : 2NH~ 9CS 9NtIu ~- I2

) (I-I2N 9C 9 S 9 S 9 C- Ntt~) 2HI

(HaN 9C 9 S 9 S 9C 9Ntis) 2ItI ---+ H~N. C- NI-I~ Jr S -]- I-I~N 9CN -}- 2I{I

II

NK

N

Ng

(2)

II

S

S (colloidal and finely divided) + 3 I2 -t- 4tt20 ~ (NK2" CN + K~O ~

(1)

I-I~SOa+ 6IiI

Ntt~. NI-I. CO 9NK~).

(3) (4)

Thus t h e final p r o d u c t s are u r e a a n d s u l p h a t e a n d for one molecule of t h i o c a r b a m i d e , 8 a t o m s of iodine are required. B u t ff t h e iodine solution is a d d e d to a t h i o c a r b a m i d e solution c o n t a i n i n g s o d i u m b i c a r b o n a t e , t h e o x i d a t i o n is incomplete, a n d t h e r e a c t i o n m i x t u r e becomes t u r b i d , p r e s u m a b l y due to t h e f a c t t h a t in t h e absence of sufficient a m o u n t of t h e o x i d a n t t h e finely d i v i d e d a n d colloidal e l e m e n t a l s u l p h u r i n i t i a l l y f o r m e d as shown in e q u a t i o n (2) above, gets c o a g u l a t e d a n d forms larger a g g r e g a t e s which escape c o m p l e t e o x i d a t i o n b y iodine. 27*

420

PBAXASH C~ANDRAGU~TA

t~d. 196

6. Oxidation with potassium iodate and periodate BA~eAT and SHARlVIA5 carried out amperometric titrations f o r estimating thiocarbamide by oxidation with excess potassium iodate in presence of HgC12. The excess potassium iodate was titrated against arsenious oxide and the dead stop end point unit employed was of the simple form introduced by FOULK and BAwI)]~ % Oxidation with potassium periodate was used for the volumetric determination of several organic compounds including thiocarbamide by BERKA and Z~KA x~ Thiocarbamide converts IOn- to I + preferably in N hydrochloric acid. SAND~Il~ ~reated 30--20 mg of sample containing thiocarbamide or its derivatives with a known excess of 0.1N perchloric acid in presence of 5--10 ml of hydrochloric acid (d = 1.18) and after 20--30 min determined the excess I I I 0 ~ iodimetrically.

7. Oxidation with hypobromite Thiocarbamide can be oxidised to SO~- ~- C0a2- -~ N by alkaline bromine and can be estimated in alkaline solution employing an excess of hypobromite19, a~. C]~A~.rs, SIoN and CAMPE19 have proposed the following procedure : To 50 ml of 0.1N hypobromite add 5 ml of 2N NaOH solution and 25 ml of 0.08N thiocarbamide solution. After 1 hour 5 ml of 20~ KI solution is added followed by 11 ml of 6N sulphurie acid and the liberated iodine titrated with l~a2S~O3 solution. Results are reported ~o agree with those of accepted methods to within 0.2~ .

8. Oxidation with iodine monochloride

~i~LiX and R ~ I 6 K A 18 carried out a potentiometric titration of thiocarbamide with iodine monochloride and reported that ~hiocarbamide was oxidised to formamidine disulphide in neutral to strongly acidic solutions. R ~ o ~ T 9~ and SI~GH and co-workers 109 applied the iodine monochloride method to thiocarbamide and some of its alkyl and aryl derivatives. 9. Oxidation with selenious acid The method is based on the reaction which Cakes place between thiocarbamide and selenious acid in acid solution in accordance with the following equation11% lua : 4CS(NI-I~)2~ H2SeOa -~ 2HX

(NH~--C--S--S--C--NH~),

II

Ir

NH

NH

2HX q- Se ~ 3H~0

i.e., one molecule of selenious acid oxidises four molecules of thiocarbamide with the production of a salt of formamidine disulphide. A known excess of a standardised selenious acid solution is added to the thio-

1963

Thiocarbamides. I. Thiourea

421

e a r b a m i d e solution, a n d t h e a m o u n t of selenious acid left u n u s e d is determ i n e d either i o d i m e t r i e a l l y 4 K I -1- I-I2SeO~ q- 2 t t 2 S 0 4 - + 2 K 2 8 0 ~ + Se -1- 3H.zO -b I2 or b y d i r e c t t i t r a t i o n w i t h s t a n d a r d alkali, using s o d i u m a l i z a r i n a t e as indicator. T h e m e t h o d is n o t v e r y suitable as on s t a n d i n g t h e salts of f o r m a m i dine disulphide formed, in d i l u t e a c i d solution, s l o M y decompose w i t h p r e c i p i t a t i o n of s u l p h u r a n d g e n e r a t i o n of t h i o e a r b a m i d e , which w o u l d r e a c t f u r t h e r w i t h t h e selenious a c i d : K2N--C--S - - ~~- - G - - N K I 92KX ---+ S q- NH2 9CS - NtIi q- H~N" ON + 2ttX

II

II

NK NI-I JosH162 r e p o r t e d t h a t t h e o x i d a t i o n of t h i o e a r b a m i d e w i t h a n excess of I-I2Se0 a b y boiling for a s h o r t t i m e in 3 N - - 5 N h y d r o c h l o r i c a c i d proceeds as follows: 5H2SeO a = 5Se + 5 I I 2 0 + 502 N H 2 9 CS 9 N I t 2 + 2 0 ~ -~ H 2 0 = CO(NH2) s if- H~SO~ 2NIte 9CS - NI-t 2 + 302 --> 2 N I i : C ( N H 2 ) 9 SOaIt. E l e m e n t a l selenium was w e i g h e d a n d t h e excess of tIaSeOa determ i n e d b y t i t r a t i o n w i t h t h i o s u l p h a t e . A s t r i c t c o n t r o l over HCI concent r a t i o n is n e c e s s a r y for a c c u r a t e results.

10. Oxidation with potassium/erricyanide JosI~I 6a also d e t e r m i n e d t h i o c a r b a m i d e w i t h a l k a l i n e ferricyanide. A c c u r a c y d e p e n d s t o a g r e a t e x t e n t on t h e order of m i x i n g t h e reagents. The following r e a c t i o n s are r e p o r t e d t o be involved.

I%(CN)~- + e ~ Fe(CN)~N H 2 9 CS 9

2 q- 8 0 I - I - - - 8e - + NI-Ig 9 CO 9 NI-I~ q- I-I2SO~ -}- 3 I-IzO or NI-I 2 9 CS 9 N H 2 ~ 8KaFe(CN)a.

11. Oxidation with chloramine-T CUTIKILL a n d A T m ~ s ~6 o b s e r v e d t h a t t h i o e a r b a m i d e undergoes oxid a t i o n to u r e a a n d s u l p h a t e b y a n excess of c h l o r a m i n e - T solution. I n this m e t h o d a n excess of e h l o r a m i n e - T s o l u t i o n is s h a k e n w i t h a solution of t h i o e a r b a m i d e , w h e n a w h i t e p r e c i p i t a t e , a p p a r e n t l y p - t o l u e n e sulphonamide, is f o r m e d a n d t h e s o l u t i o n c o n t a i n s sulphnrie acid. 4CI{3 9 CGI-I4 9 S02 9 NC1 N a q- It~O -+ 4 C I I a 9 C~I-I4 9 SOs 9 NH~ qq- 4NaCI q- 4 0 . CS(NJvIz) 2 @ 4 0 --> CO(NH2) z -Jr SO a. T h e a b o v e m i x t u r e is k e p t for some t i m e a n d t h e n acidified w i t h dil. sulphuric acid, a f t e r which an excess of K I solution is a d d e d a n d t h e

422

PRAK~S~CKiNDI%iGUPTA

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liberated iodine titrated with thiosulphatc. In actual practice one molecule of thiocarbamidc reacts with slightly less than four molecules of chloramine-T required by the above equation. The maximum amount of chloramine-T reacting was found to be 97 ~ of this amount. The method, however, is very sensitive to slight variations in the experimental conditions and the results are therefore untrustworthy. A~A~ASV~V~ has reported accurate results when the reaction is carried out in dilute sulphuric acid. But he reports that thiocarbamide requires only 7 moles of chtoramine-T, when the reaction is carried out in hot dilute sulphuric acid. Recently A ~ A ~ s ~ v ~ proposed direct titrations in acidic media with indigo cermine as indicator, for thiocarbamidc and a number of other organic compounds. 12. Oxidation with hydrogen peroxide%11,21,33,~l,5%~~ G9-71,1t~ The action of hydrogen peroxide on thiocarbamide in oxalic acid solution was investigated by STORC~112, who obtained a salt of the formamidine disulphide [HN:C(NI-I2) 9 S 9 S 9 C 9 (I~H2):NH] but was unable to obtain the free base. K~CTOg 5~ reported its decomposition into ammoninm chloride, sulphur, sulphuric acid and carbon dioxide by heating it with hydrogen peroxide in hydrochloric acid, while BAgNETTG in alkaline medium obtained a dioxide ~2N--C--SO~. H (amidino sulphuric acid). II NH

According to Bo~sIi~N ~, ff the pH of the solution is maintained at 7, hydrogen peroxide forms the dioxide. HsN- CS 9 NHz ~- 2I{s02 -> H~N" C:SO~ 9N H 2 -~ 2H20. While in presence of alkali with increasing concentration of H~02, urea and sulphate arc the final products ~l,v~ H2N. CS 9 NH~ ~- 4H202 ~- 2NaOH -+ CO(NH2)~ -{- Na~SO4 + 5It20. KITAMC~AT~71, employed the reaction for the micro-analysis of organic sulphur compounds. The procedure given by him is as follows: 0.1 mg tool. of sample is digested in a sealed tube with 40 ml of 0.1 N KOIt-solu~ion -? 40 ml of water ~- 20 ml of 0.1 M H202 solution. The S is thereby oxidised to S0~- which neutralises a part of the K O H and the excess is titratcd with 0.01 I~ hydrochloric acid to a methyl-red end point. ~EH~ and H E u ~ R ~ reported good results with thiocarbamide and its allyl derivative employing 30~ and estimating the sulphate formed gravimetrically as barium sulphate. The quantitative oxidation of thiocarbamide with alkaline H~O~ is usually employed for its determination in biological liquids viz., urine and

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423

blood 51. The details regarding the clarification, purification and processing etc., of biological liquids prior to estimation of thiocarbamide, however, cannot be included here. IL Complex formation with inorganic salts Thiocarbamide forms molecular compounds, often of great stability, with a wide variety of metallic salts, well known since the early days in the history of thiocarbamide and have been extensively investigated ever since. Complex compounds of thioearbamide with the salts of almost all the known metals have been investigated and the literature is too extensive to be briefly reviewed or cited here. Complexes of thioearbamide with mercury, copper and bismuth salts are of analytical interest. 1. Estimation with mercury salts 1 a. Estimation with mercuric nitrate. WrL~IA~S 125 determined thiocarbamide in the absence of thioeyanates by adding a measured volume of ammonium thiocyanate, nitric acid and iron alum to the thiocarbamide solution and titrating the above mixture against 0 . I N mercuric nitrate solution, until the red colour of the ferric thioeyanate just disappears, leaving the solution water clear. From the total volume of standard mercury solution used is deducted the equivalent of the ammonium thiocyanate added and the remainder multiplied by 0.00761. The thioeyanate solution is added only to give an indication of the end point. The endpoint in this method is quite sharp and the determination rapid. The method is based on the formation of a 1 : 1 molecular complex which is stable in water 1~ I n the presence of thioeyanates, thiocarbamide can be determined as follows : A portion of the solution (containing about 0.2 g of thiocyanate and thioearbamide in 200 ml) is taken, l0 m] of nitric acid and 2 ml of iron alum solution are added and the solution is titrated with 0.1N mercuric nitrate solution until the red colouration just disappears. Then to an equal volume of solution are added 10--15 ml of a 10~ CdSQ solution plus 10 ml of t0~ caustic soda solution and the mixture boiled for 10 rain, cooled and filtered through alkali resisting paper and washed thoroughly. The filtrate is acidified with dilute nitric acid and after adding 2 ml of iron alum solution again titrated with 0.1N mercuric nitrate solutioi1 as before. This gives the thioeyanate content. The number of ml of the standard mercuric nitrate solution used in this titration deducted from the total required for the thiocyanate and thiocarbamide together will give the quantity of thiocarbamide present when the difference is multiplied by 0.00761. The composition and stability of the complex compounds of Hg ~+ which exist in aqueous solutions of thiocarbamide and its derivatives has been studied polarographicMly by various workers 3~,59,n5. JENSOVSKY59 and TOROPOVA115 reported that amperometric titrations of IIg ~+ with thioearba,mide are possible.

424

PI~AKASI~0HANDRAGUPTA

Bd. 196

l b . Estimation with mercurous nitrate. Recently KI~s 66 determined thiocarbamide by the dead stop method by titration with HgNOa solution with the use of two Hg electrodes. He derived the following equation65:

]i = i / i l = [(A' ~- 1)/(]/~ - - 1) 2] [(y ~- 1)/2] 1 - - l/-1 - - 4 [ ( ~ '

- - 1)/(LJ' -~ 1)] 2

[yl(y -~ 1)~],

to express the intensity of the current as a function of the reagent added during a dead stop titration, when a reversible oxidation-reduction system is present. I n this equation ]i represents the ratio of the current i at a n y given stage of the reaction to t h a t i~ at the equivalent point. y represents the ratio (Coxid~tion) : (Creduction) ~ and A'represents the applied potential 65. The determination is based on the formation ~7 of Hg[CS(iNH2)2] +.

2. Estimation with copper sulphate BRADAla proposed a new method for the determination of thiocarbamide volumetrically, by titrating it with copper sulphate in dilute nitric acid medium at 30~ with bismuth nitrate as indicator. The presence of urea, a m m o n i u m sulphate and acetic acid does not interfere. B u t the method is not very suitable as variation in temperature leads to inaccurate results. III. Methods based on desulphurisation with heavy metals Numerous reagents effect desulphurisation of thiocarbamideSi,l~176 10s,lls,las. I n the majority of cases the desulphurisation process is proceeded b y the formation of intermediate additive compounds, the colours of which are usually masked by the colour of the metallic sulphide 2s.

1. Argentometric methods2S,89,11s, 12s The earliest method for the determination of thiocarbamide appears to be t h a t of VOLXA~D11s, in which a hot ammoniacal solution of the sample is titrated with standard silver nitrate solution. The reaction consists in the conversion of thiocarbamide into urea, and of silver oxide into silver sulphide, which is precipitated. The reaction m a y be represented as follows : 2AgNO s ~- 2NHdOH = At20 ~- 2NttdN03 ~- H20 At20 -~ CS(NH2)~ = Ag2S -~ CO(NH~)2. The end point is determined by withdrawing a sample of the mixture on a glass rod and mixing it with a drop of ammoniacal silver nitrate on a piece of filter paper, till no more blackening of the patch is observed. A precise location of the end point is obviously difficult.

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I n a modified p r o c e d u r e CUT~mL a n d ATones ~6 a d d a n excess of A g N 0 3 solution to t h e a m m o n i a c a l solution of t h i o c a r b a m i d e , acidify t h e s y s t e m w i t h nitric a c i d a n d a f t e r filtering t h e p r e c i p i t a t e d silver sulphide, t i t r a t e t h e u n r e a c t e d silver n i t r a t e w i t h s t a n d a r d t h i o c y a n a t e solution, using ferric a l u m as indicator. This m e t h o d has t h e d i s a d v a n t a g e t h a t t h e t h i o c a r b a m i d e m u s t be c o m p l e t e l y free f r o m t h i o c y a n a t e s . A c c o r d i n g to W ~ L I A ~ S 1~5, t h i o c a r b a m i d e w h e n d e s u l p h u r i s e d w i t h a silver solution, is n o t e n t i r e l y c o n v e r t e d into urea, b u t c y a n a m i d e is f o r m e d according to t h e e q u a t i o n : CS(NH~)2 + 2 A g N Q -[- 2 N I t ~ -+ C N . NH~ Jr Ag2S -k 2 (NH~)N03. WILLIAMS d e t e r m i n e d t h i o c a r b a m i d e in presence of chlorides a n d thioc y a n a t e s as follows: A portion of the solution eontainh~g thioearbamide is placed in a 400 ml beaker and 30 ml of sodium silver cyanide solution is added together with 40 ml of a 20% caustic soda solution. The solution is diluted to 200 ml and boiled for 10 to 15 rain. I t is then cooled and filtered, and the filtrate after the addition of a few drops of a 10~ solution of potassium iodide, titrated with 0.1N silver nitrate solution with agitation until a permanent opalescence occurs. 1 ml of 0.1N AgNO 3 solution = 0.0038 g of thiocarbamide. 2NaAg(CN)2 -k CS(NH2)2 q- 2 N a O t t --~ CN 9 N H 2 -k Ag2S Jr 4 N a C N + 2H~0 4 N a C N -k 2AgNO~ ~ 2NaAg(CN)2 q- 2 N a N Q . A p r e l i m i n a r y p r e c i p i t a t i o n of chloride ion as basic b i s m u t h chloride was used to efiminate interference from t h i s source. LAND• a n d SOUI~E~rK 74 d e t e r m i n e d t h i o c a r b a m i d e d u r i n g its m a n u f a c t u r e as follows: 0.2 g of the sample is dissolved in 50 ml of water and diluted with 100 ml of water. Silver nitrate solution is then added and 100 ml of 250/0 ammonia and 10 ml of 10~ potassium cyanide solution, stirred, diluted to 250 ml with water and filtered. The precipitate is ignited to silver and weighed. Ammonium thiocyanate, cyanamide, cyano-guanidine, urea, ammonium sulphate and ammonium carbonate do not interfere. A coulometric m e t h o d w i t h a c o n s t a n t c u r r e n t was d e v e l o p e d b y ~AKAI~ISIII a n d ](OBAYASHI ss for t h e m i c r o - d e t e r m i n a t i o n of t h i o c a r b amide. A solution of A g B r in aqueous a m m o n i a was a d d e d to a t h i o c a r b a m i d e solution a n d t h e l i b e r a t e d b r o m i d e e q u i v a l e n t was t i t r a t e d potent i o m e t r i c a l l y w i t h A g + ions g e n e r a t e d anodically. 1 m g a m o u n t s were s a t i s f a c t o r i l y d e t e r m i n e d w i t h a s t a n d a r d d e v i a t i o n of a b o u t 0.1 m g a n d t h e m e t h o d is r e p o r t e d to be a p p l i c a b l e to smaller a m o u n t s .

2. Desulphurisation with zinc LEsz a n d co-workers 75 carried o u t a n i n d i r e c t c o m p l e x o m e t r i c determ i n a t i o n of t h i o c a r b a m i d e :

426

PRAKASHCHANDRAGUPTA

Bd. 196

To the aqueous solution (ca. 0.2 g of thiocarbamide) add 20 ml of 0.0495 M Zn (N03)2 and 13 ml of 3N Na0H solutions and 2.5 g of hydroxyammoninm chloride. Boil the mixture for 20 rain, filter hot through a sintered glass filter (G4) and wash the precipitate with hot water. Neutralise the combined filtrates with 3 N hydrochloric acid, add ammonia buffer (p~ 10) and titrate with 0.0516 M EDTA solution with eriochrome black T as indicator. The error in the range 20--200 mg is reported to be of the order of =j=20/0.

3. Desulphurisation with cadmium K O ~ T S K I J 73 d e t e r m i n e d t h i o c a r b a m i d e i n m i x t u r e s c o n t a i n i n g e y a n a m i d e derivatives, cyanamide, sulphides a n d t h i o e y a n a t e s as follows : The sample containing 0.1--0.2 g of thiocarbamide is dissolved in 150 ml of water, acidified with acetic acid and 10 ml of 10 ~ cadmium acetate solution added; the mixture is filtered if any cadmium sulphide is formed. 50 ml of the filtrate is diluted with an equal volume of water and 20~ sodium hydroxide solution added slowly until Cd(OH)2 is formed and an additional 1--2 ml (excess) of NaOH solution are added. The solution is heated to 80~ C, stirred and allowed to stand for one hour. Then it is acidified with acetic acid until a perceptible odour of acetic acid appears; filtered through an ashless filter paper and washed with water. 50ml of 0.1N iodine solution and 5 ml of hydrochloric acid are added and the excess iodine is titrated with 0.1N thiosulphate in presence of starch. 1 ml of 0.1N iodine solution corresponds to 0.0038 g of thiocarbamide. Determination is reported to be accurate to within 2.80/0. B U D ~ I ~ S t ; ~ a n d co-workers 15 h e a t e d the c a d m i u m salt of ethylened i a m i n e t e r r a , e e r i e acid (EDTA) (0.25 M) with water soluble sulphides (or thiocarbamide) i n a n alkaline solution for 15 rain on a boiling water bath. The c a d m i u m sulphide precipitate was t h e n filtered, washed with distilled w a t e r a n d the E D T A liberated i n the c o m b i n e d filtrate a n d washings was t i t r a t e d with 0.05 M CaCI~ solution with m e t h y l - t h y m o l blue as indicator. S0~-, S~O~-, a n d S C N - do n o t interfere a n d the m e t h o d is reported to have a n error of ~ 0.30~

4. Desulphurisation with lead GU~TA 46 d e t e r m i n e d t h i o c a r b a m i d e gray/metrically b y desulphurising it with lead acetate a n d c o n v e r t i n g the lead sulphide formed into lead sulphate which was weighed as such. The procedure was as follows: The liquor containing thiocarbumide is desulphurised by heating with sodium plumbite im an alkaline solution of lead acetate containingsodium hydroxide in excess in an atmosphere of purified hydrogen at 40o--60~ C for 30 rain. The precipitated lead sulphide is quickly filtered, washed with acetic acid (1:1000), transformed into lead sulphate (via lead chloride) and determined gravimetrieally. IV. Aeidimetrie methods W e a k l y basic c o m p o u n d s which c a n n o t be t i t r a t e d i n aqueous solution can often be t i t r a t e d in n o n - a q u e o u s solutions. Especially i n acidic solv e n t s the a p p a r e n t basicity of a weakly basic c o m p o u n d is considerably increased. The possibility of using glacial acetic acid as a t i t r a t i o n m e d i u m

1963

Thiocarbamides. I. Thiourea

427

was first demonstrated by CObAlT and HALL ~3 in 1927, and later followed up by CObAlT, I-I~LL and WER~23,2~,ds,49, 5~ The titrations can be performed potentiometrically or visually. Their work was followed by various applications of glacial acetic acid as a titration medium for weak

bases. Very recently ALIcI~o ~ and BAYER and POSGAYs reported that thiocarbamide can be successfully estimated as a weak base by titration with perchloric acid in acetic acid medium in the presence of mercuric acetate. Crystal violet and gentian violet can be used as indicators but 0.1 ~ quinaldine red in glacial acetic acid was found to give sharper end-points. SKODI~7and KAI~KUZARK111~carried out potentiometric titration employing an antimony electrode for determining thiocarbamide and other weak bases in acetic acid or acetic acid ~-acetic anhydride medium with perchloric acid. V. Colorimetrie methods GROTE41reported a blue colour reaction for soluble organic compounds containing the groups -~ C - - S - - H , -->C--S--S--C+- and ~ C ~ S etc. when treated with a reagent obtained by treating Na2Fe(CN)sNO in NaHC03 solution with NH2 9 OK and then bromine. The reaction is sensitive and quantitative comparisons can be made with thiocarbamide in dilutions of 1 : 100,000 to 1 : 200,000. The blue colour developed with G~OTE'S above nitroferricyanide reagent has also been used to measure thiocarbamide in ultrafiltrates (through cellophane under pressure) of serum lv,2v. W z ~ E n l ~ - 1 3 1 applied the method for determining thiocarbamide in citrus peel constituents. CAMPBELL, LAnDGraVE and MO~GA~16 employed the reaction of thiocarbamide with HN02 in acid solution to form thiocyanic acid for estimating thiocarbamide in urine. The red colour developed by the addition of ferric chloride is measured with a green filter. DE I~ITIS and ZAcco 9v have described another method for the colorimctric estimation of thiocarbamide in serum, which is as follows : 1 ml of serum is mixed with 3 mI of water and 2 ml of dialysed Fe solution, shaken and filtered. Then to 3 m] of the filtrate, 0.1 ml of 5~ FeC13 solution is added and a stream of air containing NO (developed by mixing a 25~ solution of N~NO~with acetic acid) is passed until saturated. The orange re4 eolour developed is proportional to the content of thioearbamide. The error of the method is reported to be of the order of 5~ A spectrophotometrie method for the determination of thiocarbamide based on the formation of thiocyanie acid in the interaction between nitrite and thiocarbamide has been developed by HUTCHI~SO~~ and BOLTZ5s. The method is of interest as it can be applied to the colorimetric estimation of either nitrite or thiocarbamide with slight modifications.

428

PRAKAS]~CHANDI~AGUPT~.

Bd. 196

VI. Other miscellaneous methods KODAMA and co-workers 72 employed an extension of xanthydrol method 3~ for the determination of thioearbamidc : To the methyl alcoholic solution of thiocarbamide, a mixture of 1 part 2~ xanthydrol NeOH solution (containing xanthydrol in the ratio of 2--3 moles per mole of thiocarbamide in the sample) and 4 parts acetic acid are added and the reaction mixture stirred for 3 hours. The solution is allowed to stand over night and filtered through a glass filter. The precipitate is washed with methyl alcohol and water alternately, dried for one hour at 110~ and weighed as xanthydrylthiourea. If ammonium thiocyanate is also present in the sample it may be determined by adding 5 ral of dilute nitric acid (1 : 7) and 5 drops of ferric alum solution to the filtrate obtained above and titrating with 0.1 N silver nitrate. ] ~ I E ] ) ~ A ~ as and KAYA~A ~4 studied the catalytic action of several organic sulphur compounds, including thioearbamide on the iodinesodium azide reaction 2 NaN 8 + 12 -+ 2 N a I + 3 N 2. KAYAMA6a found that the catalytic action of thioearbamide is proportional to its concentration only when it is present in very small quantities. He studied the reaction by eolorimetry and azometry. The method is suitable for only micro-quantities of thioearbamide. Moreover, the determination can be carried out only with the help of an empirical curve obtained previously under the same conditions. The action of thiocarbamide in this case is not purely catalytic and is borne out by the fact that the sulphur of the thioearbamide molecule itself gets oxidised to sulphate during the course of the reaction. According to SuzuKI and KAWAGOE113, upto 0.02 mg amounts of thiocarbamidc can be determined by this method. II~D~z-GuTIE~ZSa, 54 studied the complex formation between thioearbamide and K2ligI a in alkaline solution, lie reports that when this complex is treated with potassium iodide, the S separates quantitatively as HgS. The sulphide thus obtained is filtered or separated by centrffugation, washed thoroughly and oxidised with a known excess of a standard B r J K B r solution. The excess of bromine can be determined iodimetrieally. A lengthy procedure has been given33, 54. MEDNOS and V ~ n o v A s4 carried out a polarimetric estimation of thiocarbamide in mixtures arising during its production. W~o~sK1133 reported that in 0.1 N ItClO,~ in water or methyl or ethyl alcohol, thioearbamide and related compounds can be titrated with 0.002--0.05 M t t g (OAc)2-aniline solution to the pale-yellow to violet change of p-dimethylaminobenzylidene-rhodanine. Hafides, SO32- and $2082- must be absent. GIz~zBcnoa0 reported that the oxidation of thiocarbamide in a copper sulphate or sulphuric acid electrolyte is irreversible and is essentially determined bey diffusion kinetics. He determined small quantities of thiourea in copper electrolytes with a rotating platinum electrode

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Thiocarbamides. I. Thioure~

429

(anode). P~OSENTHALEI~ s8 p r o p o s e d a b r o m i n e - a c i d i m e t r i c m e t h o d for t h e assay of several compounds including thiourea. Z~LENI~ 134 c a r r i e d o u t q u a n t i t a t i v e d e t e r m i n a t i o n s of t h i o c a r b a m i d e in f u n g u s e x t r a c t s b y a s p e c t r a l m e t h o d a n d r e p o r t e d t h a t b y m e a n s of a l i n e a r s p e c t r u m p r o v i d e d w i t h a q u a r t z m e r c u r y l a m p i t is possible t o d e t e r m i n e t h e p r e s e n c e o f 0.001 ~ o f t h i o c a r b a m i d e .

Summary A r e v i e w is g i v e n of t h e m e t h o d s of a n a l y s i s of t h i o u r e a a n d tile chemistry involved therein. Practical details are given where necessary, in o t h e r eases o n l y t h e p r i n c i p a l s a r e discussed. A n e x t e n s i v e a n d c r i t i c a l s u r v e y of t h e l i t e r a t u r e is i n c l u d e d .

Zusammenfassung E s w i r d eine i ) b e r s i c h t fiber die M e t h o d e n z u r T h i o h a r n s t o f f b e s t i m m u n g g e g e b e n . E x p e r i m e n t e l ] e E i n z e l h e i t e n w e r d e n in e i n i g e n F/~llen b e s p r o c h e n , i m f i b r i g e n w e r d e n n u r die G r u n d l a g e n d i s k u t i e r t . E i n e ausffihrliehe L i t e r a t u r z u s a m m e n s t e l l u n g w i r d g e g e b e n . The author wishes to thank Professor S. S. Jos~I, D. Se. (London), F.t~.I.C. (London) and Dr. 1%. H. SA~AS~iBVDgnY, D. Sc., F.R.I.C. (London), for their kind interest and invaluable help during the preparation of this manuscript. References i A~'a~ns~v, B. N. : Trudy Sverd]ovsk Selskok. Inst. 1, 361 (1957). -- ~ AFAXAS~V, B. N. : Zavodskaja Laborat. 15, 1271 (1949). -- a ALICI~O, J. F. : ~icrochem. J. 4, 551 (1960). -- a B).NE~:r:EE, S . N . : J. Indian chem. Soc. 86, 449 (1959). -5 BA~AT, M. G., u. B. SE~MA: Z. analyt. Chem. 157, 258 (1957). -- 6 B A ~ T T , E.: Proc. chem. Soc. 25, 305 (1909). -- J. chem. Soc. (London) 97, 63 (1910). -7 Biw~A_<~.: Ber. dtsch, chem. Ges. 6, 1373 (1873). -- s BAY~, I., u. E. PosoAY: Pharmaz. ZentralhMle Deutschland 100, 65 (1961). - - ~ BEILSTEII~ u. GEUTI~R: Liebigs Arm. Chem. 108, 99 (1858); 12~, 241 (1862). - - i 0 BERKA, A., u. J. Z:~Ki: Chem. Listy 50, 314 (1955). -- iiBo~sKEx, J.: Proe. Acad. Sci. Amsterdam 39, 717 (1936). -- i2 BO~SKE~, J. : l~ec. Tray. Chim. Pays-Bas 55, 1040 (1936). -- ia B~ADA, Z.: Anal. chim. Acta (Amsterdam) 3, 53 (1949). -- i4 BVC~ANAN, G. H., and G. BA~SKY: J. Amer. chem. Soc. 52, 195 (1930). -- 1~ BUD~NSK~, B., E. Vi~thKOV2 u. J. K6~Bn: Collect. czeehoslov, chem. Commun. 25, 76, 456 (1960). -- i~ C i ~ E L ~ , D., 1~. W. LANDGIgEBE and T. N. ~Io~r Lancet 1, 630 (1944). -- i~ CI~ShE~, L. C.: J. biol. Chemistry 152, 571 (1944). -- is 0 ~ K , J., u. J. I~I~I6KA: 'Chem. Listy 49, 1731 (1955). -- TM C~AEYs, H . S . , H. SIo~ et A. C ~ E : Bull. Soc. chim. Belgique 70, 455 ( 1 9 6 1 ) . - ~0 C~ies, A. : Liebigs Ann. Chem. 179, 139 (1875). -- ei CLAYS,A.: Bet. dtsch, chem. Ges. 7, 235 (1874). -e~ Coim~, M. E., and E. A. WEI~E~: Proc. chem. Soc. 29, 188 (1913). -- J. chem. Soc. (London) 103, 1221 (1913). -- ea CONA~T, J. B., and N. F. HALL: J. Amer. chem. Soe. 49, 3047, 3062 (1927). -- ~ CObAlT, J. B., and T. H. W~a~E~: J. Amer. chem. Soe. 52, 4436 (1930). -- ~ CO~NI~seu, E., A. Bvcly~, M. ~V~AxIhlu. C. ]). NENITZESeL': Acad. 1Re]?. Pop. Romine, Stud. Cercet. China. 7, 67 (1960). -- ~a CUT//[ILL, t~., and C. A~KI~S: J. Soe. chem. Ind. 56, 5T (1937). - - ~ DA_~owsKI, T. S.: J. biol. Chemistry 152, 201 (1944). -- ~s DEgN, W. M. : J. Amer. chem. Soc. 62, 3189 (1940). -~ D~sm~cz~, G. S., u. M. G. B x e i ~ : Z. analy~. Chem. 156, 276 (1957). -- s0 DI-

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