A-methyl derivatives

Compounds related to benzene were obtained from similar plant extracts Eor example a pleasant smelling resin known as tolu balsam was obtained from the South American tolu tree In the 1840s it was discovered that distillation of tolu balsam gave a methyl derivative of benzene which not surprisingly came to be named... 

Preliminary IR spectral studies were said to suggest that pyrimidinones existed as pyrimidinols <50JCS3062) but this conclusion was promptly reversed <52JCS168) on better experimental evidence subsequent comparison with their N- and O-methyl derivatives showed that the pyrimidinones (39a R = H) and (40a R = H) along with their A-methyl derivatives (39a R = Me), (40a R = Me) and (40b R = Me) all exhibited vqo in the range 1600-1700 cm, whereas the methoxypyrimidines (39b R = Me) and (40c R = Me) showed no such absorptions <53JCS33l, 55JCS211). Closer analysis of the spectra for pyrimidin-4-one (40a R= H) showed that the ort/jo-quinonoid form (40a R = H) is the predominant tautomer (see Section 2.13.1.4). 

The melting point of indazole has been reported at various temperatures in the range of 145 to 149 °C. Indazole boils at 269-270 °C at 743 mmHg and 146 °C at 15 mmHg, can be readily sublimed on a water bath and is also steam-volatile. Its two A-methyl derivatives have similar melting points 1-methyl (106), m.p. 61 °C, 2-methyl (107), m.p. 56 °C, but they are easily separated by fractional distillation [(106), 120/15 (107), 141/15]. 

Diseleno acetals and ketals are cleaved more rapidly than their dithio counterparts a methyl derivative is cleaved more rapidly than a phenyl derivative. Methyl iodide or ozone converts diseleno acetals and ketals to vinyl selenides. ... 

A number of 5-sulfenylthiocarbonates have been prepared to protect thiols. A benzyl derivative, R =CH2Ph, is stable to trifluoroacetic acid (25°, 1 h) and provides satisfactory protection during peptide syntheses a r-butyl derivative, R = r-Bu, is too labile in base to provide protection. A methyl derivative, R =CH3, has... 

Anhalamine, C11H15O3N, occurs in microscopic needles, m.p. 187-8°. The hydrochloride, B. HCl. 2HjO, forms lustrous leaflets, m.p. 256-8° and the sulphate, Bg. H2SO4, colourless prisms the picrate has m.p. 234-6°. The base contains two methoxyl groups and one hydroxyl group. A dibenzoyl derivative, m.p. 128-9°, and a monobenzoyl derivative, m.p. 167-5°, are formed, the latter but not the former being soluble in alkalis. The methyl ether of anhalamine is identical with anhalinine, b.p. 130 0°/0-01 mm., m.p. 61-3°, and the A-methyl derivative is anhalidine, m.p. 131-3°. 

Both the 4- (38) and 6-(31) nitrimines are reduced with sodium boro-hydride to the corresponding y5-nitramine derivatives, e.g., (41)], which are methylated with methyl iodide and potassium carbonate. The A -methyl derivative is reduced in modest yield to the 5a-fluoride (43) with lithium aluminum hydride. 

Methylation of hydroxyquinazolines invariably produces a mixture of 0- and A -methylated derivatives. The A -methyl derivatives are, therefore, best prepared by unequivocal syntheses. 1-Methyl-2(1H)-quinazolinone (16) is not known. When o-aminobenzaldehyde is treated with methylisocyanate, 3-methyl-2(3i7)quinazolinone (17) is obtained. If this is heated in ethanol it dissolves and an alcoholate, presumably (18), crystallizes out, and this can be converted back to (17) by vacuum sublimation. Methylation of l-methyl-4(lH)Quinaz-... 

Alkylation of these mercapto compounds in alkaline solution gives only the S-methyl derivatives. Of the four isomeric A-methyl derivatives, the 4-thioquinazolines, (28) and (29), have been obtained from the corresponding oxo compounds with phosphorus pentasulfide but the corresponding 2-thio derivatives (30) and (31) are not known. However, derivatives of substance (31) with methyl replaced by... 

Ultraviolet spectra have long been used to study systems of this type. In 1889, comparison of the ultraviolet spectrum of 2-hydroxy-quinoline with those of its O- and A -methylated derivatives led... 

The isolation of two tautomers of 2,3,4-trihydroxyquinoline has been reported but one was later identified as the isomeric 1,2,4-trihydroxy compound 47. The fact that 2,3,4-trihydroxyquinoline is oxidized more slowly than its A -methyl derivative was considered to show that it existed in an oxo form. The product resulting from... 

Between 1951 and 1953 investigations by three English groups clearly demonstrated the preponderance of the oxo forms of pyrimidin-2- and -4-ones by comparing the ultraviolet spectra of these compounds with those of the N and 0-alkylated derivatives, The o-quinonoid form 91 (R = H) is favored by the evidence that A -methylation of the 6-methyl derivative of 89a does not cause a bathochromic shift in the ultraviolet spectrum (A -methylation of pyrid-4-one causes a bathochromic shift, but this is not observed for pyrid-2-one) The isomeric A -methyl derivatives of pyrimidin-4-ones [e.g., 91 (R = Me) and 90 (R = Me)] form similar cations (e.g., 92 and 93), and hence the equilibrium constant between... 

V NH band is present in the infrared spectra of both indanthrone and mono-A -methylindanthrone, (h) the infrared spectra of indanthrone and its mono- and di-A -methyl derivatives showed vC—O bands of approximately equal intensity, and (c) the ultraviolet and visible spectra of indanthrone and its A -methyl derivatives are similar. 

Comparison of the ultraviolet spectra of the parent compounds with those of both possible A -methyl derivatives shows that the structures (cf. 155) predominate in equilibria of type 155 156. ... 

If diazomethane is added slowly to an etheral suspension of benzo-l,2,4-triazin-3-one, the 0-methyl derivative (cf. 161) is obtained in good yield, but, if the solid benzotriazinone is added to an etheral solution of diazomethane, approximately 50% of the A -methyl derivative (or, according to a later report, 70% of a mixture of two isomeric iV-methyl derivatives) is formed. These facts have been interpreted to indicate that the benzotriazinone exists as such in the solid state, i.e., as 162, and partially tautomerizes to 161 in solution. Similar results have been reported and similar conclusions drawn for the related 1-oxide 162a. ... 

The trioxo formulation (190, R — H) of 2,4,6-trihydroxypteridine is supported by the fact that its ultraviolet spectrum resembles that of the A-methyl derivative (190, R = Me), the pyrimidine ring in the parent compound having been assigned the dioxo configuration by analogy. On the basis of ultraviolet spectral data, the trioxo con-... 

Tryptophan (15) and its substituted derivatives also react with aldehydes to give l,2,3,4-tetrahydro-jS-carboline-3-carboxylic acids (17), Acetaldehyde and benzaldehyde yield the expected products with the amino acid and its A -methyl derivative (abrine). ... 

Alkylation at the ind-N of l,2,3,4-tetrahydro-j8-carbolines has been carried out with alkyl halide after treatment with sodamide in the usual manner. Cyanoethylation of a p /r-V-substituted tetrahydro-jS-carboline in the presence of Triton B yields the corresponding 9-cyanoethyl derivative. Similarly, treatment of p / -V-methyl-l,2,3,4,4a,9b-hexahydro-y-carboline with sodamide, followed by benzyl chloride, leads to the ind-A -benzyl-substituted derivatives. l-Oxo-l,2,3,4-tetrahydro-j8-carboline yields the ind-A -methyl derivative directly with dimethyl sulfate.Prolonged treatment with sodium hydride, followed by methyl iodide, yields the 2,9-dimethyl derivative. Heating with sodium hydride in acetone followed by the addition of dimethyl sulfate gives rise to the ind-V-methyl derivative. ... 

As shown by an H NMR study (77BSB967), A-methyl derivatives of 5-mercaptoimidazole exist in the thione form 176a in chloroform. According to results obtained in (82KGS957), the zwitterionic form 176b should not be excluded from consideration for the compounds 176 (R" = CONH2, CSNH2). 

The proposed structure of 97 isolated from broiled sardines was confirmed by straightforward synthesis starting from5,6-diaminoquinolines. After reaction with cyanogen bromide it afforded the 2-amino-imidazo[4,5-/]quinolines 99 (R = H, Me), which was then converted into its 3-A-methyl derivative 100 by... 

At the same, time attempts to apply this approach to the synthesis of phenotel-lurazine and its A-methyl derivative using diphenylamine and A-methyldiphenyl-amine as starting materials failed [83JOM(251)223 85KGS757]. The parent phe-notellurazine 35 (M = NH, R = R = H) has been prepared in low yield (7%) by refluxing an acetic acid solution of 4-trichlorotellurodiphenylamine 39 (89H1007). 

TABLE I. Dependence of the Yield of Alkynylpyrazoles and Their A-Methyl Derivatives on the Composition of Diyne/Diazomethane Mixtures and Reaction Time [71CAS1731]. 

In general, the A -methyl derivative of a given compound absorbs at longer wavelengths than the O-methyl derivative. The intensity of a band which appears in aqueous solutions beyond the maximum absorption in alcohol and which is due to the absorption of the betainic species alone, is a measure of the tautomeric equilibrium. The pA"a value of the 2-methyl-hydroxyisoquinolinium chlorides increase in the order 4-hydroxy (4.93), 8-hydroxy (5.81), 6-hydroxy (6.02), 5-hydroxy (6.90), and 7-hydroxy (7.09 in water at 25 °C, respectively) (57JCS5010). Thus, 2-methyl-4-hydroxyisoqui-nolinium chloride is the strongest acid. The UV spectra of 2-methyl-isoquinolinium-5-olate (34) and 2-methyl-isoquinolinium-8-olate (39) were also presented (61BCJ533) and the formation of a quinoid structure of 2-methyl-isoquinolinium-6-olate (38) can also be detected by means of UV-spectroscopy. 

NMR investigations of A (l)-methyl 117 and A (5)-methyl 118 derivatives of 112 (R = H) revealed that they adopted a similar conformation as the parent 112 (R = H) (99T6759). Both A -methyl derivatives contain the methyl group in an axial position. All of them have a trans-ring junction. Whereas, cA-2/7,4//,9n//-dimethyl derivative 112 (R = Me) exists in a single conformation, its cis-2H,AH-trans-9aH diastereomer 119 is conformation-ally complex, consisting of al, 0 2, and fi anomers in equilbrium in D2O (OOJOC889). 

BF3 -OEt2. 2-(A-Ethoxycarbonyhnethyl-A-methyl), and A-cyanomethyl-A-methyl) derivatives 230 (R = COOEt, CN R = H) did not yield any tricyclic product (98JCS(P1)3327). 

Similarly, for 2-(p-substituted-anilino)benzothiazoles (180 181), the relative proportions of the isomeric A -methyl derivatives produced on reaction with methyl iodide in neutral solution has been related to... 

Quinoxalin-2-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

Ultraviolet and infrared spectroscopy indicate that quinoxaline-2,3-dione type structures are preferred to tlie tautomeric 3-hydroxy-quinoxalin-2 One or 2,3-dihydroxyquinoxaline forms. The light absorption properties (UV) of quinoxaline-2,3-dione have been compared with those of its NN -, ON-, and OO -dimethyl derivatives (79, 80, and 81), and also its N- and 0-monomethyl derivatives (43 and 82). The parent dicarbonyl compound and its mono- and di-A -methyl derivatives show very strong carbonyl absorption near to 1690 cm split into two peaks. 

The effect of solvents on the reactions of lactams with diazomethane can be pronounced saccharin gives only A -methyl derivative in benzene solution, but in ethereal solution up to 24% of 0-methyl saccharin is formed in the still more strongly polar solvent di-... 

---