Adrenochrome semicarbazone

Addition products have been obtained from aminochrome derivatives such as the semicarbazone, with sodium bisulfite. Recently Correia Alves reported the preparation of a compound described as adrenochrome semicarbazone sodium sulfonate (m.p. >300°) by treating a solution of adrenochrome monosemicarbazone (90) in sodium carbonate solution with sulfur dioxide at 40° for several days192 this compound was apparently different from the substance (m.p. 227-228°) obtained in a somewhat similar manner by Iwao193-194 and may be comparable to the compound (83) (m.p. > 300°) previously described in a Belgian patent179 (see Section IV,F). Iwao established the structure of his compound as the sodium salt of epinochrome-3-sulfonic acid monosemicarbazone (93).193... 

ADRENOCHROME SEMICARBAZONE -- 3-hydroxy-l-methyl-5,6-indolinedione semicarbazone. 

NaOH added with stirring at 90° under Ng to an aq. suspension of 7-methyl- adrenochrome semicarbazone, boiled ca. 2-5 min. under N2 until effervescence ceases, cooled to 50° by addition of ice, dimethyl sulfate added dropwise, cautiously heated to 80°, and kept 5 min. at this temp. 6-methoxy-7,N-dimethylindole. Y 54%. F. e. s. R. A. Heacock and O. Hutzinger, Soc. 1965, 3902 phenols from quinone monosemicarbazones s. J. Thiele and W. Barlow, A. 302, 311 (1898). 

Adrenochrome monosemicarbazone (96) is not very soluble in aqueous solution and this sometimes creates a problem in preparing solution for clinical use. To overcome this problem by chemical means, attempts have been made to introduce solubilising groups into the molecule. It was found, for example, that when adrenochrome semicarbazone (96) was allowed to react with sodium bisulphite at 30 C for several days sodium l-methyl-5-semicarbazono-6-oxo-2,3,5,6-tetrahydroindole-3-sulphonate (Adona, AC-17, 97)[183, 184] was formed. On the other hand, when a solution of adrenaline was boiled under reflux with sodium bisulphite for 1 hour and the product oxidised and then treated with semicarbazide, a compound isomeric with (97) having the sulphonate group in the 2-position (AC-44, 98), was obtained [185, 186]. The synthesis of a compound described as sodium 1-methyl-2,3,5,6-tetrahydro-5-semicarbazido-6-hydroxyindole-3-sulphonic acid (99) has recently been claimed in a British patent [187]. The procedure followed was similar to that used by Tomino [18 in the synthesis of (98) and the validity of the structure proposed for (99) is therefore questionable. 

Chemical Name 3-Hydroxy-1-methyl-5,6-indolinedione semicarbazone Common Name Adrenochrome... 

Recently adrenochrome has been obtained (as its semicarbazone) by the air oxidation of synephrine [i.e. /9-hydroxy-/J-(4-hydroxy-phenyl)ethylmethylamine (5)] in the presence of potato tyrosinase.46 This overall reaction must involve an initial hydroxylation of synephrine (5) to give adrenaline (2), which is subsequently oxidized to adrenochrome (1). 

Adrenochrome methyl and ethyl ethers (8 and 9 respectively), first isolated by Hukki and Seppalainen as their semicarbazones,66 have now been obtained in crystalline form by oxidation of the corresponding catecholamine ethers with silver oxide in dry acetonitrile.65 A-Ethylnoradrenochrome (6) has also been prepared in crystalline form by the oxidation of N-ethylnoradrenaline in 90% methanol with the calculated quantity of iodic acid65 (cf. the preparation of adrenochrome by Macciotta67). Adrenochrome 08-acetate (3-acetoxy-epinochrome) (10) was obtained by the oxidation of acetyladrena-line [j3-acetoxy-j8-(3,4-dihydroxyphenyl)ethylmethylamine].68... 

The sodium bisulfite addition compounds must have a free (or potentially free) ketone-type carbonyl group, since they readily form derivatives with typical ketone reagents such as semicarbazide and 2,4-dinitrophenylhydrazine.174 Decomposition of these derivatives with alkali gives the corresponding adrenochrome derivatives e.g., adrenochrome monosemicarbazone would be obtained from the semicarbazone of the adrenochrome-sodium bisulfite complex.174 If one accepts Tse and Oesterling s formulation of the adrenochrome-sodium bisulfite complex, the semicarbazone would probably have a basically similar structure (i.e. 82). This type of structure is more... 

The syntheses of the monoxime [mono- or di-hydrate, m.p. 178° (decomp.)] and monosemicarbazone [m.p. 223° (decomp.)] of DL-adrenochrome have recently been described by Remizov.191 The majority of previous publications referring to these compounds have dealt with derivatives of adrenochrome prepared initially from L-adrenaline. The picrates obtained from the DL-oxime and dl-semicarbazone of adrenochrome were described as yellow powders, decomposing at 124 and 150°, respectively.191 Remizov also described the formation of highly colored complexes from the interaction of the DL-oxime and DL-semicarbazone with certain metal ions (e.g. Co++, Ni++, Cr+++ Fe++ and Fe+++).191... 

Contraindications None noted. Acts as a systemic hemostatic preventing capillary bleeding during injury. Adrenochrome causes chemically induced schizophrenia. Its semicarbazone does not. Supplier CS. 

Adrenochrome (3-hydroxy-l-methyl-5,6-indoline-dione) [54-06-8] M 179.2, m 125-130 (dec). It was crystallised from MeOH/formic acid, as red crystals of the hemihydrate, and stored in a vacuum desiccator. The mono-semicarbazone (Carbazochrome) [69-81-8] M 236.2, crystallises as orange-red crystals from dilute EtOH with m 203° (dec) and is haemostatic. [Heacock Chem Rev 59 181 1959, Beilstein 21 IIEIV 6434.]... 

The semicarbazone (134) was too water-soluble to isolate readily, but it was possible to isolate other derivatives of the aminochrome-thiol addition products of this type one such compound was the p-nitrophenylhydrazone of the addition product between adrenochrome and )S-mercaptopropionic acid which was readily obtained in pure crystalline form. The structure of this compound (135) was established by consideration of the microanalytical data and spectroscopic (u.v. visible, i.r. and n.m.r) properties. A total of five derivatives of this type have been prepared and fully identified (see Table 63) [249]. 

Adrenochrome itself is not sufficiently stable for pharmaceutical use, but the greater stability of a number of its derivatives, such as its mono-semicarbazone, permits them to be used therapeutically. Solubility is often a problem with these derivatives, however, and attempts are being made to solve this problem in two ways. Firstly, it is possible to solubilise the molecule chemically by the introduction of polar groups such as -SOjNa and secondly, by the use of solubilising agents, such as sodium salicylate (see p. 306). 

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