Ikrisimidaxolt-s w n h t t c d 11. Quaternary pyridinium salts are thus prepared by the bimolecular reaction of pyridine with an organic halide. If the proton reacted with the nitrogen, the shift should be toward the ultraviolet. Its formation from bemil and ammonia may proceed as in equation 1 , page 36. Thus attempts to prepare 9-dialkylaminoacridines from 9-alkoxyacridines and salts of secondary amines resulted in much hydrolysis to the 9-acridanones, a difficulty encountered with reactions in phenol solution. Methyl 4 or S -imidaaolecarboxylate. The first resolution was via the a,a'-bromocamphorsulfonic acid salts169;this has been 171 but also ~ 0 n f i r r n e d.
Burtlee, R, and Pyman, F. Basic Strength Iinidazole is a monoacidic base having the ability to form crystalline salts with acids. As the quantitative oxi'dation of an acridan to the acridine is easily carried out, this two-stage conversion is a very valuable, frequently used procedure. Bromination of Evoxanthine and Norevoxanthine The bromination of evoxanthine in methanolAois similar to that of melicopicine and melicopidine, in that addition occurs at positions 1 and 2. The methiodides of these alkyl pyridines and quinolines are more reactive,398as would be expected on electronic grounds, than the parent tertiary amines, toward electron-deficient centers ; it is, therefore, remarkable that 9,lO-dimethylacridinium iodide in contrast to the tertiary base is reported not to react with 4-dimethylaminobenzaldehyde, 4-nitrosodimethylaniline, and other compounds.
B B Two dcrivtrtivcs of 4 or 5 -aminoiinidaeole,namely 4 or 5 -yanidoimidazolc and 4 or 5 -urcidoimidazole, are of importance as hydrolytic products of tlic purine base guanine 42. It is of interest that the 1,4-isomeride exhibits a greater chemical stability than does the 1,5-compound. Rule, Gurney and Jackson, London, 1926, p. Sulfonic acidz7and chloro20substituents may also be responsible for failure under normal conditions. Methods of Preparation of Acridines 35 the proton needed to start the reaction. A final decision regarding evaluation of the structure of the imidazoles must await the establishment of the bond distances and bond angles, In analogy to other, more thoroughly investigated, heterocyclic ring systems, imidazole may be represented a8 a resonance hybrid with contributions from structures shown on p. Apart from a conversion of diacetyl to acetyl-methyl carbinol, no change indicating a loss of aroma was discovered.
The liistidine band iwnains prcicticdly stationary in tliis systeiii. The interaction of 2,2'-bipyridyl, 4,4'-dimethyl-2,2'-bipyridyl, 5,5'-dimethyl- 2,2'-bipyridyl, or l,l0-phenanthroline with aromatic or aliphatic α-haloketones, or with ethyl bromoacetate, gives high yields of 1-acylmethyl-2- pyridyl pyridinium salts. Rome , 58, 533 1968. Cold ferric chloride also oxidizes cold alcoholic solutions of I-, 2-, 3-, and 4-methylacridans to the acridines. The rate of formation of the aminoacridine was increased by increasing the acid concentration, but so also was the rate of hydrolysis of the chloroacridine to the 9-acridanone.
Its chemistry is similar in many ways to that of 9-acridanone, as will become apparent in the following review. A small number of acridines have also been obtained from dehydrogenation, cyclodehydrogenation, and other reactions that will be considered here. Treatment of N- 2, 4-dinitrophenyl pyridinium chloride 5a with hydroxylamine, followed by refluxing the resulted 5- 2, 4-dinitroanilino -2, 4-pentadienal oxime 6a in dioxane-water 4 : 1 gave pyridine N-oxide 7a in 87% yield from pyridine. A classical example is the compound 2,4 or, 2,5 -diphenylimidazole. U S S R ,17, 463 1944. Frkres, and Mayer, British Patent 137,214; French Patent 509,610 1919 ; U S.
Io7 9-Phenylaminoacridine may be prepared by the action of isocyanatobenzene on acridine 10-oxide in dimethylformamide, carbon dioxide being evolved a t room temperature. The'study of the acylation of imidazoles is complicated by the property of a number of these substances to undergo ring fission under the influence of scylating reagents and alkalis. Leipzig , 116, 350 1925. Most of those that are properly identified as acridinium salts will be considered in Chapter V. Most important among the salts is the sparingly solu- ble silver salt, which is precipitated when imidazole is brought into contact with ammoniacal silver solutions.
Schmidt, Organic Chemistry, 1st English ed. There is ample evidence 13,14,39 to substantiate the view, first expressed by Windaus 351, that the initial step represents a breakdown of the D-glucose molecule with the formation of methylglyoxal. The synthesis is not in general suitable for the preparation of asymmetrically substituted diaminoacridines, but 3-aminodiphenylamine N-phenyl-rn-phenylenediamine will give 3,6-bisphenylaminoacridine or 3-aminoacridine, according to the conditions. Formation from 2-Imldazolinea 2-Imidarolines have served as the starting niaterials for the prepasstion of I-mono- or 1,2-dialkylimidazoles 49. The Code method 70 for the biological estimation of histamine in blood involves the preparation of a trichloroacetic acid filtrate and hydrolysis with hydrochloric acid. Thus the mornent of I -methylimidazolc witen iiieasured in bctizenc solution is little dependent on the concentnrtion, in contrast to that, of iiiriclazolc ~vl~icli v:iric? When volatile acids are employed, sealed reaction vessels are essential. The lower melbing modification results from the condensation of a-aminobenzyl cyanide with bemaldehyde and also from the treatment of 2,6diphenyloxazole with ammonia 63 ,while the higher melting form is obtained from the reaction of benzamidine with m-bromoacetophenone or by the interaction of a-hydroxyacetophenone with benzaldehyde in the presence of ammoniacal cupric acetate 40,64.
The introduction of an electronegative substituent such as a nitro group into the 5 or 4 -position of a 4 or 5 -bromoirnidazole alters the behavior toward sulfite ion. This difficulty is overcome by the use of diazotized p-nitroaniline or p-hromoaniline. This reaction has preparative potentialities. The substance, or substances, giving the characteristic aroma to roasted coffee is as yet unidentified. Reasonable yields of products were obtained after refluxing the triphenylcarbinol in nitrobenzene for 15 to 30 min. N-Acylmethylpyridinium salts Ia—c were applied to some pyridine and quinoline N-oxides in the presence of acetic anhydride. Ferric chloride is undoubtedly the best reagent for the oxidation of aminoacridans.