Analogues of antipsychotic phenothiazines. 10-(β-dialkylamino) ethylaminophenothiazines

A series of 10-(β-dialkylaniino) ethylarninophenothiazines III was obtained by lithium alumi-um hydride reduction of 10-dialkylaminoacetylaminophenothiazines II. Compounds II were synthesized by intramolecular cyclization, via a Smiles rearrangement, of 2-nitro-2′-(β-dialkyl-aminoacetyl) hydrazinodiphenyl sulfides I and XI, which in turn were best prepared by condensation of the appropriate dialkylaminoacetic acid hydrochloride with the corresponding 2-nitro-2′-hydrazinodiphenyl sulfide in the presence of dicyclohexyl carbodiimide. Other attempted methods for the synthesis of compounds 1 are also described.     

10-(O,O-dialkylphosphonoformyl)phenoxazines and phenothiazines

Conclusions A number of new 10-(O,O-dialkylphosphonoformyl) derivatives of phenoxazine and phenothiazine were obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2624–2625, November, 1972.     

10-Alkenylphenothiazines. 2. Synthesis and mechanism of acidic hydrolysis of cis- and trans-10-2-phenylvinyl)phenothiazines

The addition of phenothiazine to phenylacetylene in super-base media proceeds regio- and stereoselectively and leads to the predominant formation of cis-10-(2-phenylvinyl)phenothiazine, which is completely converted to its trans-isomer at 200C. Kinetic analysis of the acidic hydrolysis of the cis- and transisomers has allowed us to assign to it an AS_E2 reaction mechanism, similar to the mechanism of hydrolysis of vinyl alkyl ethers.For Communication No. 1, see [1].Translated from Khimiya Geterotsicheskikh Soedinenii, No. 10, pp. 1420–1424, October, 1986.     

Tetracyclic phenothiazines. III. . Intermolecular hydride transfer in acid induced disproportionation of 1,2-dihydro-3-hydroxy-3H-pyrido[3,2,1-kl] phenothiazines

1,2-Dihydro-3-hydroxy-3H-pyrido[3,2,1-kl]phenothiazines and 1H-pyrido[3,2,1-kl]phenothiazines undergo acid catalyzed disproportionation with intermolecular hydride transfer to form pyrido[3,2,1-kl]phenothiazinium salts and 1,2-dihydro-3H-pyrido[3,2,1-kl]phenothiazines. Sodium borohydride reduction of 3-alkyl- or 3-arylpyrido[3,2,1-kl]phenothiazinium salts gives 3-alkyl- or 3-aryl-1H-pyrido[3,2,1-kl]phenothiazines. In the presence of a proton source, borohydride reduction of pyrido[3,2,1-kl]phenothiazinium fluoroborate or 3-chloropyrido-[3,2,1-kl]phenothiazinium perchlorate gives 1,2-dihydro-3H-pyrido[3,2,1-kl]phenothiazine, while 1H-pyrido[3,2,1-kl]phenothiazine is formed in aprotic solvents with pyridine present.     

2-, 10-, and 2,10-phosphorylated phenothiazines

Russian Chemical Bulletin -     

Phosphorylation of 10-(chlorocarbonyl) phenoxazine, 10-(chlorocarbonyl)phenothiazine,and their derivatives

Conclusions Some phosphorylated derivatives of 10-[(-hydroxyethyl)carbamoyl]phenoxazine and the phenothiazine derivative were obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2131–2134, September, 1979.     

Synthesis of 10-(substituted phenylhydrazonoacetyl)phenothiazines as possible anticonvulsants

Some 10-(substituted phenylhydrazonoacetyl)phenothiazines were synthesized as possible anticonvulsants. These compounds were investigated for their anticonvulsant activity and inhibitory effects on the oxidation of pyruvic acid by rat brain homogenates.     

Tetracyclic phenothiazines IV . Synthesis of 1,2,3,4-Tetrahydro-azepino [3,2,1-kl] phenothiazin -4-one

The synthesis of 1,2,3,4-tetrahydroazepine[3,2,1-kl]phenothiazin-4-one was accomplished by cyclization of phenothiazine-10-butanoic acid using phosphorus pentoxide and absolute ethanol. The title compound represents the first reported example of the azepino[3,2,1-kl]phenothiazine ring system. A vastly improved malonic ester-type synthesis of the precursor acid has also been developed.     

10-[N-(Dialkylphosphono and thiophosphono)glycyl]phenothiazines

Conclusions Eight new 10-[N-(dialkylphosphono and thiophosphono)glycyl]phenothiazines have been synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 170–171, January, 1969.     

Mass spectral fragmentation patterns of heterocycles. IV . Tetracyclic phenothiazines. IX. Electron impact promoted mass spectral fragmentation of pyrrolo[3,2,1-kl]phenothiazine

The mass spectral fragmentation patterns of pyrrolo[3, 2, 1-kl]phenothiazine ( 1 ) and its 1, 10-dideuterioderi-vative [2] are reported. The site of deuterium substitution in 2 was established by examination of its ¹³C nuclear magnetic resonance spectrum. The heteroaromatic stability of 1 to electron impact is exemplified by the occurrence of the molecular ion as the base peak and the formation of a reasonably intense M²⁺ ion. An intense M-1 ion is also observed. The more abundant fragment ions appear to result from sulfur ionization. Fragment ions arising from ionization of the nitrogen constitute only a small fraction of the total ion current. Proposed fragmentation pathways of 1 are supported by the detection of appropriate metastable ions, exact mass measurements, and electron impact spectrum of 2 .     

Tetracyclic phenothiazines. VII. Electron impact promoted mass spectral fragmentation of some pyrido[3,2,1-kl]phenothiazines

The mass spectral fragmentation pattern of a series of pyrido[3,2,1-kl]phenothiazines is reported. The major fragments are derived from the breakdown of the pyrido ring and substituents thereon. The 1,2-/2,3-unsaturated, unsubstituted and most of the 3-substituted compounds show the molecular ion as the base peak indicative of their relative stability toward electron impact. The genesis of the base peaks from the molecular ions of the 2,2-dithiophenyl substituted compounds probably involves a concerted expulsion of a neutral diphenyldisulfide molecule and hydrogen atom transfer from the 1-position to the 2-position in the pyrido ring. On the other hand, 2-thiophenyl substituted molecular ions lead to base peaks involving simultaneous ring opening of the pyrido ring, cleavage of phenylthiomethylene moiety as a radical and contractive ring closure to the pyrrole system. These two mechanisms appear to be diagnostic for distinguishing 2,3- versus 2,2-positional isomers. The McLafferty rearrangement takes place in the 2-thiophenyl and 2,2-dithiophenyl substituted compounds. The retro-Diels-Alder fragmentation of the pyrido ring occurs in varying degrees depending on the nature of the 2- and 3- substituents and also the presence or absence of unsaturation in the pyrido ring. In the 2-thiophenyl-3-keto compounds, thiophenyl group participation with 3-carbonyl carbon and oxygen atoms is observed in the genesis of some interesting ion fragments. The detection of metastable ions in the spectra of 1,2-dihydro-2-thiophenyl-, 1,2-dihydro-2,2-dithiophenyl-3-hydroxy-, and 1,2-dihydro-2,2-dithiophenyl-3-keto-3H-pyrido[3,2,1-kl]phenothiazines; and spectra of 1,2-dihydro-3-methyl-, 1,2-dihydro-2-carbethoxy-3-keto- and 1,2-dihydro-2-thiophenyl-3-keto-3H-pyrido[3,2,1-kl]pheno-thiazines at low voltage support major fragmentation pathways.     

CuI-catalyzed intramolecular cyclization of 3-(2-aminophenyl)-2-bromoacrylate: synthesis of 2-carboxyindoles

A new approach was described for the synthesis of substituted 2-carboxyindole using 3-(2-aminophenyl)-2-bromo-acrylates through a CuI-catalyzed intramolecular coupling. The reactions were mild, rapid and with good to excellent yields.     

Synthesis via pummerer intermediates. II.. Disproportionation reactions of 3-(methylsulfinyl)chromones and 3-(methyl-sulfinyl)quinolinones with hydrochloric acid

Sulfoxides ( 1 and 10 ) gave oxidation-reduction products when treated with 5N hydrochloric acid. 8-Methoxy-3-(methylsulfinyl)-4H-benzopyran-4-one (1) gave 8-methoxy-3-(methylthio)-4H-1-benisopyran-4-one ( 4 ) and 8-methoxy-3-(methylsulfonyl)-4H-1-benzopyran-4-one ( 5 ), whereas 1-melhyl-3-(methylsulfinyl)-4(1H)quinolinone ( 10 ) gave 1-methyl-3-(methylthio)-4(1H)-quinolinone ( 12 ) and 1-methyl-4(1H)-quinolinone ( 13 ).     

The dihedral angle of 2-(trifluoromethyl)phenothiazine

The structure of 2-(trifluoromethyl)phenothiazine, C₁₃H₈NSF₃, was determined by single crystal X-ray diffraction. The molecule crystallizes in space group P2₁2₁2₁, with a = 7.766(2), b = 5.957(1), and c = 23.499(5)Å. The final R value is 0.073. The CSC bond angle is 102.0°, the CNC bond angle is 124.8°, and the dihedral angle between the phenylene planes is 171.2(1)°. The hydrogen atom bonded to the nitrogen atom was located; it is on the inside of the butterfly angle and the S…N? H bond angle is 173.3°.     

Synthesis via pummerer intermediates. III. Rearrangements of 3-(methylsulfinyl)quinolinones, 3-(methylsulfinyl)cinnolinones, 3-(methylsulfinyl)chromanones and 3-(methylsulfinyl)chromones with acetic anhydride and with thionyl chloride

The reaction of 1-methyl-3-(methylsulfinyl)-4(1H)quinolinone ( 1 ) with acetic anhydride and thionyl chloride gave 3-[[(acetyloxy)methyl]thio]]-1-methyl-4(1H)quinolinone ( 2 ) and 3-[(chloromethyl)thio]-1-methyl-4(1H)quinolinone ( 3 ) respectively. 3-(Methylsulfinyl)-4(1H)cinnolinone ( 4 ) gave the corresponding products when treated under similar conditions. Treatment of 8-methoxy-3-(methylsulfinyl)-4H-1-benzopyran-4-one ( 11 ) with acetic anhydride and thionyl chloride gave bis addition vinyl Pummerer products 2,3-bis(acetyloxy)-2,3-dihydro-8-methoxy-3-(methylthio)-4H-1-benzopyran-4-one ( 12 ) and 2,3-dichloro-2,3-dihydro-8-methoxy-3-(methylthio)-4H-1-benzopyran-4-one ( 13 ), respectively.