Amino compounds, oxidation synthesis

One of the best methods of synthesis of isothiazoles is by direct oxidation of y- iminothiols (169) or their tautomers. The reaction is capable of many ramifications and is represented by the general equation shown in Scheme 27. The substituents represent a wide range of groups. Thus, iminothioamides (169 R = NH2) are oxidized to give 3-alkyl-5-aminoisothiazoles (170 = NH2), amidines (169 R = NH2) produce 3-amino compounds,... 

D. Miscellaneous.—A further study of the reactions of diphenyl-phosphine oxide with tetracyclone has confirmed that the reaction yields the oxide (30) under mild, basic conditions, and that the reaction is thermally reversible. The displacement of halogen from phosphorus by amino-compounds has been used in the synthesis of a number of aminofluoro-phosphine oxides (31), and of A-methyl-AA-bis(dichlorophosphinyl)-amine (32). ... 

T. Shono, Kagaku (Kyoto) 42, 642 643 (1987) Synthesis of Physiologically Active Amino Compounds using Anodic Oxidation as the Key Step". 

Further degradation of the methine and isomethine yields the same 3 4-dimethoxy-8-vinylphenanthrene [v], which can be oxidized, first to 3 4-dimethoxy-8-(a /3-dihydroxyethyl)-phenanthrene [vi] and finally to 3 4-dimethoxyphenanthrene-8-carboxylic acid [vn] [16, 66]. The latter has been converted via the 8-amino compound to 3 4 8-tri-methoxyphenanthrene [vm] [67], shown to be identical with an authentic specimen [68]. Two ethylphenanthrenes, not identical with 9-othylphenanthrene, are obtained by distilling [v] with zinc-dust [66]. Position 8 of the phenanthrene system was thus established as the point of attachment of thecarbon end of the side-chain in apomorphine. Position 9 as point attachment of the nitrogen was assumed on the basis of evidence derived from the chemistry of morphine and was finally proved by synthesis. 

Nucleophilic introduction of nitro functions seems to be confined to reactions of diazonium salts which offer a useful entry, particularly to 2-nitroimidazoles (from the diazonium fluoroborates see Section 3.02.7.1.6). This method, though, depends on the ease of synthesis, isolation, and stability of aminoimidazoles. The 4- and 5-amino isomers in particular are frequently unstable in air, and aminoimidazoles are usually made either by ring synthetic methods or by reduction of nitro compounds. Oxidation of amino groups to nitro is seldom a useful option. 

Numerous individual substances were detected only in Ru04 extracts e.g. di- to pentachlorinated benzenes, 4-chlorobenzoic acid and 2,4-dichlorobenzoic acid 24, hexachlorocyclohexanes (a-,P-,y- and 5-HCH) 22, a technical mixture obtained during the synthesis of lindane, and the plasticizers alkylsulfonic acid phenylesters 23. These plasticizers were recently identified in riverine sediments (Franke et al. 1998). Furthermore, nitro-substituted benzoic acid and alkylated phenols 24 were observed. The occurrence of aromatic nitro compounds as a result of the oxidation of anilines can be excluded due to the contemporary appearance of amino compounds, e.g. 4-aminobenzoic acid or N-ethylaniline. However, the origin as well as the emission pathway of these compounds is still unknown. 

Routes via o-aminophenylpyrroles present the most convenient syntheses of a wide variety of pyrrolo[l,2-a]quinoxalines. Thus reaction of the amino compound 6 with acetic anhydride in acetic acid gave the acetamido derivative which was cyclized with phosphoryl chloride to give the 4-methyl compound 7 (R = Me) in 56% yield. The 4-phenyl compound 7 (R = Ph) has been prepared similarly. An even more convenient synthesis of 4-aryl compounds is achieved by reaction of compound 6 with aromatic aldehydes to give the 4,5-dihydro derivatives These are readily oxidized to 4-arylpyrrolo[l,2-a]quinoxalines 9 with manganese dioxide. This approach may be carried out in one step by reaction of compound 6 with aromatic aldehydes (e.g., benzaldehyde) in the presence of cupric acetate. Reaction of the aminophenylpyrrole 6 with 90% formic acid gave pyrrolo[l,2-a]quinoxaline (7, R = H) directly in 98% yield. Pyrrolo[l,2-a]quinoxalines substituted in the l-position and the 7-position have also been prepared from appropriately substituted... 

A Michael adduct, reminiscent in structure of the first intermediate in the Gates synthesis of morphine, has been obtained as a catechol derivative en route to conversion to an indole. 3-Nitro-6-ethoxycarbonyl-1,2-naphthoquinone with ethyl acetoacetate in dioxan containing zinc chloride was refluxed for 5-10 minutes, allowed to stand for 20 minutes, the nitro compound reduced with zinc dust to the amino compound which cyclised after a final oxidation step to an indole,... 

The oxidation of aldose phenylosazones to aldos-2-uloses (osones) and the g.l.c. separation of the TMS ethers of the products have been examined in the cases of the D-f/ reo-pentose, D-arabino-, D-lyxo-, L-xy/o-hexose compounds, and two disaccharide derivatives. A new approach to the synthesis of ketonic carbohydrate derivatives involves the treatment of amino-compounds with sterically hindered quinones to prepare imines which rearrange as shown in Scheme 1 to give products which undergo hydrolysis to ketones. The method gave the 2- and 3-ulosides, respectively, when applied to methyl 2-amino-2-deoxy-a- and 3-D-glucopyranoside and methyl 3-amino-3-deoxy-j3-D-allo-furanoside. ... 

The 2-diazo-4,6-dinitrophenol (dinol, diazol, DDNP, DDNPh, or DADNPh) is the first-ever synthesized diazonium compound. Its synthesis is attributed to Griess [1] who prepared it by introducing nitric oxides into an alcoholic solution of 2-amino-4,6-dinitrophenol (picramic acid) [1,2]. Its explosive character was, however, first reported more than 30 years later in 1892 by Lenze [3]. 

Amides of 2-iodoxybenzoic acid (IBX-amides) 246 can be prepared by the dioxirane oxidation of 2-iodobenzamides 245 (Scheme 56) in the form of stable, microcrystalline soHds moderately soluble in dichloromethane and chloroform (2003ACE2194). This procedure has been used for the synthesis of the amides 246 derived from various types of amino compounds, such as esters of a-amino acids, esters of P-amino adds, and (R)-l-phenylethylamine. A single-crystal X-ray analysis of the phenylalanine derivative [246, R = (S)-CH(CH2Ph)C02Me] shows a close intramolecular contact of 2.571 A between the pentavalent iodine center and the oxygen atom of... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Hydroxyphthalazin-l(2//)-one is obtained in a smooth reaction between phthalic anhydride and hydrazine hydrate and this is again the starting compound for many 1-substituted and/or 1,4-disubstituted phthalazines. The transformations of 1,4-dichloro-phthalazine, which is prepared in the usual manner, follow a similar pattern as shown for pyridazines in Scheme 110. On the other hand, phthalonitrile is the preferential starting compound for amino- and hydrazino-phthalazines. The most satisfactory synthesis of phthalazine is the reaction between a,a,a, a -tetrachloro-o-xylene and hydrazine sulfate in sulfuric acid (67FRP1438827), alt iough catalytic dehalogenation of 1-chloro- or 1,4-dichloro-phthalazine or oxidation of 1-hydrazinophthalazine also provides the parent compound in moderate yield. 

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