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.     

Efficient oxidizing agents for determination of 2,10-disubstituted phenothiazines.

2,10-Disubstituted phenothiazines are the best drugs in psychiatry. Several methods for their analysis have been reported in the literature. The official methods are based on non-aqueous titration or spectrophotometry. Various oxidizing agents have been used for the spectrophotometric determination of 2,10-disubstituted phenothiazines, e.g. Ce(SO4)2, NH4VO3, K2S208, KIO4, KIO3, KBrO3, FeCl3, NaNO2, H2O2, chloramine T, p-benzoquinone, N-bromosuccinimide. Oxidation reactions of phenothiazines were also used for their determination by flow-injection methods.     

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.     

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.     

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.     

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.     

The Crystal Structure of (2 R, 7 S, 10 R)-2,10-diamino-5,5,7-trimethyl-4,8-diazaundecanenickel (II) perchlorate

The structure of the title compound, a tricyclic Ni(II) tetra-amine complex has been determined from analysis of photographic X-ray data. The crystal system is orthorhombic, space group P2₁2₁2₁, with unit cell dimensions a = 9.802, b = 8.998, c = 24.378 Å. The Ni atom is square planar coordinated. The six-membered chelate ring has a chair conformation. One of the five-membered chelate rings has a distorted gauche (λ) conformation with the methyl substituent in an equatorial position, the other has an unsymmetrical gauche (δ) conformation with the methyl substituent axial.     

5-phosphorylated furfural and 2-thiophenecarboxaldehyde derivatives

An easy synthetic pathway to 5-phosphorylated furfural and 2-thiophenecarboxaldehyde derivatives has been found, based on their hydrazones. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:461–470, 1998     

Tetracyclic phenothiazines. VI. Attempted pummerer cyclization of 10-(2-Keto-3-methylsulfinylpropyl)phenothiazine

The title compound ( 3 ), a β-ketosulfoxide prepared by a Claisen-type condensation of ethyl 2-(10-phenothiazino)acetate ( 4 ) with dimsyl carbanion, was subjected to a variety of catalysts in attempts to achieve a Pummerer cyclization to 1,2-dihydro-3-methylthio-2-oxo-3H-pyrido[3,2,1-kl]phenothiazine ( 2 ). Although the Pummerer rearrangement product, 10-(2-oxo-3-hydroxy-3-methylthiopropyl)phenothiazine ( 5 ), could be obtained in excellent yield under mild conditions, neither it nor the β-ketosulfoxide could be successfully cyclized under any of the conditions attempted. Instead, phenothiazine, 2-hyroxy-3-(10-phenothiazinyl)-2-propen-1-al ( 7 ), 3-(10-phenothiazinyl)-1,1-di(methylthio)propan-2-one ( 8 ), 3-(10-phenothiazinyl)-1-methylthiopropan-2-one ( 9 ) and 10-phenothiazinylformamide ( 10 ) were variously obtained.     

Mechanistic aspects of the bromination of 10-substituted phenothiazines

The addition of 1 and 2 molar equivalents of bromine to a series of 10-alkylphenothiazines, 1a-d (methyl, ethyl, n-propyl, and isopropyl, respectively), yields the corresponding 3-bromo- and 3,7-dibromo-10-alkylphenothiazines ( 11a-d and 12a-d , respectively). Evidence which supports the typical clectrophilic aromatic substitution mechanism is presented. Radical cations ( 12a-d^.+ ) arc produced when 12a-d are treated with 1 or 2 molar equivalents of bromine. Upon boiling in acetic acid these radical cations are converted predominantly to 1,3,7,9-lelrabromophenothiazine ( 5 ) and the parent 3,7-dibromo-10-alkylphenothiazine ( 12a-d ) with the evolution of hydrogen bromide. The 10-methyl radical ( 12a ) gives, in addition, 1,3,7-tribromo-10-methylphenothiazine ( 15 ). A mechanism if proposed for these reactions in which initial dealkylution of 12b-d^.+ to 3.7-dibromophenothiazine radical cation ( 13 ) occurs followed by reduction of 13^.+ by bromide ion to parent 3,7-dibromophenothiazine ( 13 ). Subsequent bromination of 13 by molecular bromine produced in the previous redox reaction yields 1,3,7-tribromo-( 14 ) and 1,3,7,9-tetra-bromo-( 5 ) phenothiazines. The small size of the methyl group allows 12a to be brominated at the 1-position prior to dealkylation. In addition to undergoing bromination at the 3- and 7-position, 10-isopropylphenothiazine ( 1d ) is oxidized to the radical cation 12e^.+ when treated with bromine. 10-Benzylphenothiazine ( 1e ), however, undergoes oxidation to radical cation 1e^.+ exclusively. This radical cation debenzylates readily at room temperature and is converted finally into phenothiazine.     

New routes to condensed polynuclear compounds—IX : Synthesis of 2,10-, 3,10- and 4,10-diazaphenanthrene

Synthesis of 2,10-, 3,10-, 4,10-diazaphenanthrene and some of their derivatives has been achieved through benzyne cyclisation of anils and reduced anils derived from o-chlorobenzaldehyde and the appropriate aminopyridines.     

N-phosphorylated imidazolium salts as precursors to 2- and 5-phosphorylated imidazoles and new imidazol-2-ylidenes featuring the PNCN unit

It has been experimentally proven that the reaction of 1- or 1,2-disubstituted imidazoles with diorganylphosphorus(III) halides proceeds via initial formation of N-phosporylated imidazolium salts. Treatment of these salts with strong bases results in phosphorylation of the parent imidazoles at the 2- or 5-positions, correspondingly. In a previous case, imidazol-2-ylidenes are formed as intermediates. With both N1 and N3 atoms bearing sterically demanding or/and π-donating groups, deprotonation of 1,3-disubstituted imidazolium salts with NaN(SiMe(3))(2) afforded new stable N-phosphorus-substituted Arduengo-type carbenes.     

1,4-Unsubstituted 2-phosphorylated vinylacetylenes as valuable phosphorus-containing dipolarophiles

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New camphor-derived sulfur chiral controllers: Synthesis of (2R-exo)-10-methylthio-2-bornanethiol and (2R-exo)-2,10-bis(methylthio)bornane

An efficient preparation of two camphor-derived controllers [(2R-exo)-10-methylthio-2-bornanethiol1b and (2R-exo)-2,10-bis(methylthio)bornane 2] potentially useful as a ligands or chiral auxiliaries in asymmetric synthesis is described. Both compounds have been prepared starting from (1S)-camphor-10-thiol 3. Alkylation of this thiol with sodium methoxide and methyl iodide afforded 10-methylthiocamphor 8. Conversion of 8 into the corresponding thioketone 9 with the Lawesson's reagent followed by the stereoselective reduction with DIBAL-H at low temperature yielded (2R-exo)-10-methylthio-2-bornanethiol1b in good yield. (2R-exo)-2,10-bis(Methylthio)bornane 2 could be obtained by alkylation of 1b with sodium methoxide and methyl iodide.     

The mass spectrometry of phenothiazines—I. 10-alkylphenothiazines

The fragmentation of six substituted 10-alkylphenothiazines is discussed. Predominant expulsion of OH, SO and O occurs from the molecular ions of 10-alkylphenothiazine-5-oxide derivatives, the relative extent depending upon the configuration of the 10-substituent. The simultaneous elimination of two OH radicals from the molecular ion of 10-alkylphenothiazine-5-sulphone derivative is also observed.     

Access to 14C-Ring labelled phenothiazines. Synthesis of 2-chlorophenolhiazine-5a,9-14C

Through the use of a recently reported ring expansion reaction, a new route to phenolhiazines has been developed suitable for the preparation of ring labelled derivatives. As an example, the preparation of 2-chloropheno thiazine-5a,9-¹⁴C ( 1 ) is reported. Condensation of cyclohexanone-2-¹⁴C with 2-amino-4-chlorothiophenol gave the spiro-2,3-dihydro-l, 3-benzothiazole 4 which was protected by acetylation ( 5 ). Treatment of 5 with sulfuryl chloride gave the tetrahydro-phenothiazine olefin mixture 6 and 7 which was directly converted to labelled 1 via treatment with DDQ in refluxing benzene followed by hydrolysis of the acetyl group.     

Unexpectedly facile isomerisation of [7,10-Ph2-7,10-nido-C2B10H10]2- to [7,9-Ph2-7,9-nido-C2B10H10]2-

The 2e-reduction of 1,12-Ph2-1,12-closo-C(2)B(10)H(10) followed by oxidation or metallation gives products that arise from [7,9-Ph2-7,9-nido-C(2)B(10)H(10)](2-), formed by unexpectedly facile isomerisation of the kinetic 7,10-isomer: the 4,1,6-MC(2)B(10) compounds which result are progressively isomerised to 4,1,8- and 4,1,12-isomers for M = {CpCo} but to an equilibrium mixture of 4,1,8- and 4,1,12-isomers for M = {(arene)Ru}.