Glauert Mann and Walkanson Some Oxonols derived from Thio-oxindole. Part I. By R. H. GLAUERT,FREDERICK G. MANN and A. J. WILKINSON. [Reprint Order KO.5697.1 The symmetrical oxonol derived from thio-oxindole and three unsym- metrical oxonols containing this nucleus have been prepared and their sensitising properties determined. Two of the latter dyes show abnormal behaviour on heating undergoing isomerisation at their melting points. BIS-[~-(~ 3-DIHYDRO-3-OXOTHIO~APHTHEN)]METHISOXONOL (I) WaS first prepared by Friedlander and Kielbasinski (Bey. 1911 44 3098) who condensed thioindoxyl (I1 ; R = H) with its 2-formyl derivative (11; R = CHO) in the presence of sulphuric acid. It has subsequently been obtained by the reaction of thioindoxyl with chloroform and alkali (Friedlander and Risse Ber.1914 47 1919) with formic acid (Schwenk J. pr. Chem. 1921 103 103; Rodionov Bogoslovskii and Kazakova Izv~st.Akad. Nauk S.S.S.K. Otdel. Khim.Nauk 1948 536; Chem. Abs. 1949 43 2200) and with formamide (Hiinig Annalen 1951 574 99). It is also formed by the interaction of thioindoxyl with thioindoxyl-2-aldehyde anil (I1; R = 0CH:NPh) under acid conditions [Sveshnikov and Levkoev J. Gen. Chem. (U.S.S.R.) 1940,10,274]. Dyes of type (I)have been found C-OH co co CHR C=CH C C-OH (V) ‘s‘ ” to act as photographic sensitisers for the green portion of the spectrum (Brooker in Mees “ The Theory of the Photographic Process,” Macmillan London 1942 p. 990). In view of the marked sensitising action of certain rtterocyanines derived from thio-oxindole (Glauert and Mann J.1952 2135) it was of interest to prepare the isomeric oxonol (IV) containing two thio-oxindole nuclei and unsymmetrical oxonols of type (V) containing one thio- indoxyl and one thio-oxindole nucleus. We have prepared the bright red bis-[3-(2 3-dihydro-2-oxothionaphthen)]methin-oxonol (11’) by condensing thio-oxindole (I11; R = H) with its 3-formyl derivative (I11 ; 119551 Some Oxonols Derived from Thio-oxindole. Part I. R = CHO) in the presence of triethylamine. Thio-oxindole-3-aldehydeanil (111; R = *CH:NPh) failed however to react with thio-oxindole despite the use of a variety of conditions and the attempted preparation of (IV) from thio-oxindole and formamide was also unsuccessful although under comparable conditions thioindoxyl gives an almost quantitative yield of the dye (I) (Hunig Zoc.cif.). The oxonol (V; R = R' = H) was prepared by condensing thioindoxyl-2-aldehyde anil with thio-oxindole under acid or basic conditions it could not be obtained by the condensation of thio-oxindole-3-aldehyde with thioindoxyl or by that of thio-oxindole with thioindoxyl and formamide. The deep red crystals melt at 222-223" resolidify on further heating and remelt at 260-275"; the significance of this behaviour is discussed below. The symmetrical oxonol (IV) derived from thio-oxindole is markedly more soluble in common solvents than the unsymmetrical dye (V) or the thioindoxyl compound (I); moreover its absorption maximum 500 mp is at much shorter wave-length than that of (V) Amax.566 mp or of (I),Amax. 592 mp. These properties may reflect (a) the greater degree of steric hindrance in (TV) preventing coplanarity of the two nuclei (cf. Knott J. 1952 2399) and (b) the absence of ortho-quinonoid forms analogous to (IA) and (VA)-in bipolar structures such as (IVA) which must contribute to the resonance hybrid of (IV). The compound formed from (V; R = R' = H) by the action of heat is an isomer m. p. 283-284" its ultra-violet spectrum in dioxan shows I-. 370 mp and its infra-red spectrum shows no hydroxyl band. It is insoluble in aqueous alkalis but dissolves in hot ethanolic potassium hydroxide to give a yellow solution which on acidification yields a new compound m. p. 159",which in ethanol has Am=.356 mp and which contains a hydroxyl group (band at 3.06 p). This compound is reconverted at its melting point into the above isomer from which it appears on analytical evidence to be derived by addition of one equivalent of ethanol. Neither the compound of m. p. 283-284" nor that of m. p. 159"contains a thiol or a carboxylic acid group. A satisfactory explanation of the above results has not been found. It may be noted that Knott (Zoc. cd.) has observed a somewhat similar but readier isomerism in some oxonols derived from oxazolones and has suggested the spiran structure (VI) for the isomer of [2-benzylthio-4-thiaol-5-one] [2-phenyl4-oxazol-5-one]methinoxonol.It is un- likely that the isomer of (V; R = R' = H) has the analogous structure (VII) for this would not be expected to cause absorption at 370 mp and it also does not offer a satisfactory interpretation of the reaction with ethanolic potassium hydroxide.A further possibility that the isomer is the o-mercaptophenylthionaphthenopyrone (VIII) is precluded by the absence of a thiol group although such a compound would be expected to undergo ring opening with alkali with generation of hydroxyl group and ready recyclisation. The molecular weight of the isomer indicates further that it is not the disulphide corresponding to (VIII). The exact structures of the isomer and its derived product remain obscure and the small quantities available have prevented a fuller investigation. We have also prepared oxonols of type (V) with an ethoxy-substituent in either the Glauert Mann and Witkinson thio-oxindole or the thioindoxyl ring.The former dye (V; R = H R' = OEt) behaved like (V; R = R = H) undergoing isomerisation at its melting point ; the latter (V ; R = OEt R = H) however did not. As the effect of the ethoxy-group in the second case will probably be to suppress the ionisation of the hydroxyl group of the thioindoxyl ring the result suggests that ionisation of this group is the first stage in the observed isomerisation reaction. The attempted condensation of 6-chloro-4-methylthioindoxyl-2-aldehydeand thio- oxindole in boiling ethanol containing piperidine gave mainly 6-chloro-Pmethyl-2-(piper-idinomethy1ene)thioindoxyl (IX) contaminated with a small amount of a red dye presumably the required oxonol (asV).It was found moreover that the compound (IX) could be prepared by the direct reaction of the aldehyde and piperidine in ethanol. The fact that compounds of type (IX) can act as intermediates in the preparation of mero-cyanines from hydroxy-aldehydes in the presence of piperidine as well as in the preparation of oxonols has been shown by the preparation of the known merocyanine (XI) (Glauert and Mann Zoc. cit.) by the condensation of (X) and lepidine methiodide in boiling ethanol in the absence of a catalyst. The absorption and sensitising properties of the new oxonols are briefly summarised on p. 33. EXPERIMENTAL Thio-oxindole its 3-aldehyde and the aldehyde anil were prepared by Glauert and Mann's method (J. 1952 2127). Bis-[3-(2 3-dihydro-2-oxothzona~hthen)]methinoxonol (IV).-A solution of thio-oxindole-3-aldehyde (111; R = CHO) (0.5 g.) and thio-oxindole (0.42 g.1 mol.) in ethanol (10 c.c.) containing triethylamine (0.4c.c. 1 mol.) was boiled for 3 hr. under reflux and the solvent then evaporated. The residual red gum was stirred and washed with ether (4 x 10 c.c.) and then dissolved in a minimum of hot acetic acid. The oxonol (IV) slowly crystallised in red needles m. p. 162-163" when recrystallised from acetic acid (Found C,65.6; H,3-5. C,,HloO,S require C 65.8; H 3.2%) 12%. [2-(2 3-Dihyd~o-3-oxolhiona~hfhe~)] (V).-[3-(2 3-dih~d~o-2-o~othiona~hlhen)]melhinoxonoZs Equimolecular amounts of the appropriate thioindoxyl-2-aldehyde anil and the thio-oxindole dissolved in the minimum of boiling ethanol were treated with triethylamine (1 mol.).After 0-5-2 hours' boiling the dye was worked up as above ready crystallisation occurring on addition of the acetic acid. The oxonol (V; R = R' = H) formed red needles (36%) m. p. 222-223" when inserted at 2103,resolidifying on further heating to 230" and remelting at 260-275" (Found C 65-7; H,2.95. C,,H,,O,S requires C 65.8; H,3.2%). The use of a small quantity of hydrochloric acid as catalyst in place of triethylamine gave the same product. The oxonol (V; R = H,R' = OEt) formed clusters of red-brown prisms (43%) m. p. 179-181" when inserted at 165",resolidifying by 185" and remelting at 250-257" (Found C 64-5; H,4-3. C,,H1,O,S requires C 644; H 4.0%). A second sample melted only- when inserted at ca.195-200". resolidifying in 1 min. at this temperature and remelting at 250-257" (Found C 64.3; H 4.4%). The infra-red spectra of the two samples were indistinguishable. Condensation of 6-ethoxy(thioindoxyl) and NN'-diphenylformamidine in boiling ethanol (15min.) gave 6-ethoxy(thioinrZoxyI)-2-aZdehyde anil as orange-brown crystals m. p. 1U0,from cyclohexane (Found C 69.0; H 6-2. C,,H,,O,NS requires C 68-6; H 5.1%). The oxml (V; R = OEt ; R' = H) formed chocolate-coloured crystals (34%). m. p. 206",unchanged on further heating to 300" (Found C,64-5;H 4-2. C,,H,,O,S requires C,64-4;H,4.0%). Isomer of the Oxonol (V;R = R' = H).-The oxonol (570mg.) was heated in an oil-bath for 10 min. whilst the temperature was raised from 225" to 235".The dye melted with mild effervescence and some yellowish oil formed in the upper part of the tube. The residue r 19551 some Oxonols Derived from Thio-oxandoie. Part I. dissolved in hot glacial acetic acid (125 c.c.) on cooling deposited dark crystals (315 mg.) m. p. 270-273" which when recrystaked from the same solvent gave purple-brown crystals m. p. 276-278" (Found C 65-85; H 3.0%). A dark impurity was removed by chromat+ graphy of a benzene solution of the product on alumina and recrystallisation from ethanol then gave the isomer as pale fawn needles m. p. 283-284" (Found C 65.8; H 3.1% ; M cryoscopically in ethylene dichloride 300. C,,H,,O,S requires C 65-8 ; H 3.2% ; M 310). Solutions of the product in ethanol or benzene were fluorescent.A solution in dioxan showed 370 mp (E 23,900); 359 mp (E 18,500). The infra-red spectrum showed a carbonyl band at 5-78 p but no hydroxyl or thiol bands. This isomer (80 mg.) w-as boiled with potassium hydroxide (1 g.) in ethanol (20 c.c.) for 2 min. giving a yellow-brown solution which when cooled diluted with water (40 c.c.) and acidified with dilute hydrochloric acid gave a fawn-coloured precipitate. Recrystallisation from ethanol-water and then ethanol gave a compound as very pale yellow crystals m. p. 159" when inserted at 150" resolidifying and remelting at ca. 285" (Found C 64.2 64.3; H 4-6 4.6. C,,H,,O,S requires C 64.0; H 4.5%. C,,H,,,O,S requires C 64-2; 33,4.3%). The ultra-violet spectrum in ethanol showed 356 mp (E 13,500) and in ethanol containing a small quantity of sodium hydroxide 402405 mp (E 7380).The infra-red spectrum showed a hydroxyl band at 3-06 p and a carbonyl band at 5.91 p but no thiol band. Isomer of the Oxonol (V; R = H; R' = OEt).-The oxonol was heated for 10 min. at 200-230' and the product worked up as above giving very pale brown prisms with a dark reflex m. p. 262-263" apparently the isomer (Found C 64-0 63.9; H 3-45 3-7. C,,HI,O,S requires C 64-4 ; H 4.0%). In dioxan solution it showed &. 378 (E 28,900) 397mp (E 22,900). A ttempted Condensation of 6-Chloro-4-methylthioindoxyl-2-aldehyde with Thio-oximiole.-When an ethanolic solution of equimolecular amounts of the aldehyde thio-oxindole and piperidine was boiled under reflux for 6 hr. and cooled the precipitate consisted largely of grey-green lumps m.p. 191-194" contaminated with a trace of red material. Recrystal-lisation from aqueous acetic acid gave the dye (IX),m. p. 195-197' undepressed on admixture with the following authentic compound. 6-Chlovo-4-methyZ-2-(piperidinomethyletze)thioindoxyZ (IX) was formed readily when an ethanolic solution of 6-chloro-4-methylthioindoxyl-2-aldehydeand piperidine ( 1 mol.) was boiled for 6 hr. The product (58%) separated on cooling and gave yellow needles m. p. 200-202'. from ethanol (Found C 61.3; H 5-4; N 5-1. C,,H,,ONClS requires C 61.3; H 5.45 ; N 4.8%). Mixing an ethanolic solution of this compound with an ethanolic solution of 2 4-dinitro-phenylhydrazine containing some hydrochloric acid caused the slow deposition of the 2 4-dinitrophenylhydrazone of 6-chloro-Pmethylthioindoxyl-2-aldehyde,m.p. 257-258" undepressed on admixture with an authentic sample. 2-(Pi~cridinomethyle7)-4 5-benzothioindoxyl (X) similarly prepared (77%) from 4 5-benzothioindoxyl-2-aldehyde,formed sparkling yellow plates m. p. 190-191" (Found C 73.0 ; H 5.8 ; N 5-0. C2,H,,0NS requires C 73.2 ; H 5.8 ; N 4.7%). The infra-red spectrum showed a carbonyl band at 6.1 p and no :NH band. When an ethanolic solution of this compound and lepidine methiodide (1 mol.) was boiled for 7 hr. a deep green colour developed with deposition of the crystalline [2-(2 3-dihydro-3-0~0-4 5-benzothionaphthen)] [4-( 1 :4-dihydro-l-methylquinoline)]dimethinmerocyanine(XI) m. p. 285-287" unaffected on admixture with an authentic sample; it gave a turquoise-coloured ethanolic solution.Absm@on and Sensitisation Datu.-In the following Table columns 2 3 and 4 give the absorption maxima of the oxonols in ethanol 2-ethoxyethanol containing a small amount of methanolic sodium hydroxide and 2-ethoxyethanol containing a small amount of hydrochloric acid respectively. Column 5 gives the absorption maxima in a positive chlorobromide emulsion and column 6 the sensitisation range in this emulsion. Figures are in mp. Oxonol Absorption maxima Max. in emulsion Range (I) ........................... 592 587 482 600 470-655 (Iv)........................... 500 500 430 515 (470)-550 (V;R = R' = H) ...... 566 666 465 580 (465)-635 (V;R = H R' = OEt) 578 580 _. 565 460-630 (V;R = OEt R' = H) 490 512 550 482 600 (480)-645 In positive emulsions the semitising power of the first three oxonols decreases in the order (I)> (V; R = R' = H) > (rv),in agreement with the expectation on steric grounds; that 0 Arcus and Smyth Olefinic Additions with of (V; R = H R’ = OEt) is markedly less than that of (V; R = OEt €3’ = H).All show only low sensitisation in negative emulsions. We are greatly indebted to Imperial Chemical Industries Limited Dyestuffs Division for the above investigation of the absorption and sensitisation of the oxonols and to the Depart- ment of Scientific and Industrial Research for a grant (to .4. J. IY.). UXIVERSITY CHEMICAL LABORATORY, CLMBRIDGE. [Received. September Snd 1954.1