Hemant K. Sharma

The Photochemical Irradiation of R3SiH in the Presence of [(η5-C5H5)Fe(CO)2CH3] in DMF Leads to Disiloxanes not Disilanes†

The ability of DMF to react with the hydrogen formed in this dehydrocoupling process to produce Me3N was used to rationalize such interesting chemistry. In our hands, the irradiation of the tertiary silanes R3SiH reported in reference [2] (e.g. Ph2MeSiH (1), PhMe2SiH (2), Et3SiH (3)) in the presence of the catalyst [FpMe] in DMF solution results in the high-yield formation of the corresponding disiloxanes R3Si-O-SiR3 and no apparent formation of the disilane. In our experiments, 130 mg samples of the tertiary silanes (Gelest) were irradiated in dry DMF (Aldrich) with 5 mol% of the catalyst [FpMe] in sealed NMR tubes at a distance of 3 cm from a 400 W low-pressure mercury lamp. The reactions were monitored by Si NMR spectroscopy. The reactions with 1, 2, and 3 behaved similarly, with the disappearance of the resonance of the starting silane (d = 17.5 ppm (1) in 48 h; d = 17.2 ppm (2) in 1.5 h; d = 0.5 ppm (3) in 10 h) along with the appearance of a single resonance associated with the formation of the corresponding disiloxane R3SiOSiR3 (d = 9.1, 0.6, and 8.4 ppm for the reactions of 1, 2, and 3, respectively). No resonances associated with the corresponding disilanes were observed, for example (Ph2MeSi)2 at d = 22.6 ppm or (PhMe2Si)2 at d = 21.5 ppm. Figure 1 illustrates this clean process for silane 1. The GC–MS analysis of the product of this reaction also confirmed the formation of the disiloxane and the absence of

Dehydrogenative Dimerization of Di‐tert‐butyltin Dihydride Photochemically and Thermally Catalyzed by Iron and Molybdenum Complexes

Dehydrogenative coupling of tertiary stannanes, R3SnH, catalyzed by a transition metal is known to produce distannanes, R3Sn SnR3, whereas a mixture of cyclic and linear oligoor polystannanes is obtained from the analogous dehydrogenative coupling of secondary stannanes, R2SnH2. [2–4] 1,2-Dihydrodistannanes are of significant interest as bifunctional model compounds to mimic the properties of polystannanes and they are excellent precursors for further derivatization. However, until a report by Uhlig et al. there were no well-defined methodologies for the synthesis of 1,2dihydrodistannanes. The Uhlig synthesis involves a two-step reaction sequence that starts with the reaction of tertbutylmagnesium chloride with tin tetrachloride in an overall yield of 2.5%. We now report the photochemical and thermal dehydrogenative dimerization of tBu2SnH2 (1) to tBu2HSn SnHtBu2 (2), catalyzed by the iron catalysts 3 and 4 and their molybdenum analogues 5 and 6.

Synthesis and spectroscopic studies on dibutyl-, tributyl- and triphenyltin esters of p-methoxy trans-cinnamic acid

One triphenyl, one tributyl, and two dibutyl esters of p-methoxy trans-cinnamic acid have been synthesized and characterized by IR, NMR (1H, 13C, 119Sn) and 119Sn Mossbauer spectral data. Spectroscopic data suggest that the carboxy-dibutyl distannoxane adopts a ladder structure containing five-coordinate tin atoms, while the dibutyltin bis(cinnamate) ester has a distorted six-coordinate trans-R2SnO4 structure. The tributyltin ester is a five-coordinated polymer in the solid state and is a four-coordinate monomer in solution. The corresponding triphenyltin ester is four-coordinate in the solid and in solution.

Identification, isolation and characterization of process-related impurities in Rizatriptan benzoate.

Three process-related impurities were observed in routine monitoring of the samples by HPLC. These impurities were identified by LC-MS. One of the impurities, Imp-3 [rizatriptan-2,5-dimer] was reported in literature. Other two impurities were isolated by preparative HPLC and characterized by NMR, Mass and IR. Pure impurities obtained by isolation were co-injected with Rizatriptan benzoate sample to confirm the retention times in HPLC. Structure elucidation of these impurities by spectral data has been discussed in detail. These impurities were identified as 4-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)ethyl)-1H-indol-1-yl)-4-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)ethyl)-1H-indol-2-yl)-N,N-dimethylbutan-1-amine [rizatriptan-1,2-dimer] and [4,4-bis-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)-ethyl)-1H-indol-2-yl)-N,N-dimethylbutan-1-amine [rizatriptan-2,2-dimer].

Crystal and molecular structure of 1,2;3,4-di-µ-o-aminobenzoato-OO′-1,3-bis(o-aminobenzoato-O)-1,2,4;2,3,4-di-µ3-oxo-tetrakis[di-n-butyltin(IV)]

The crystal structure of [{[SnBun2(O2CC6H4NH2-o)]2O}2] has been determined by single-crystal X-ray diffraction (298 K); space group P, a= 17.278(9), b= 15.890(9), c= 14.154(8)A, α= 71.80(9), β= 68.67(8), γ= 82.02(6)°, Z= 2, and R= 0.050 for 2 038 reflections [I > 3σ(I)]. This dimer incorporates two bridging, one effectively isobidentate, and one nearly unidentate carboxy groups. The Sn–O and C–O bond distances, OCO bond angles (non-bridging carboxy groups), 119mSn Mossbauer, i.r., and n.m.r. (1H, 13C, and 119Sn) spectral data reveal that one molecule, (I), in the dimer has one six-co-ordinate and one five-co-ordinate tin atom while the other, (II), has two six-co-ordinate tin atoms. This stannoxane is the first example of its kind so far reported.

A Validated RP-HPLC Method for theDetermination of Impurities in Montelukast Sodium

The present paper describes the development of a reverse phase chromatographic (RPLC) method for montelukast sodium in the presence of its impurities and degradation products generated from forced degradation studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of montelukast sodium was observed under acid and oxidative environment. The drug was found to be stable in other stress conditions studied. Successful separation of the drug from the process impurities and degradation products formed under stress conditions were achieved on an Atlantis dC18 (250 x 4.6 mm) 5 μm column. The gradient LC method employs solution A and solution B as mobile phase. The solution A contains aqueous 0.1% OPA and solution B contains a mixture of water, acetonitrile (5:95 v/v). The HPLC method was developed and validated with respect to linearity, accuracy, precision, specificity and ruggedness.

Synthesis and photolysis of the five possible isomeric phenyl-hexamethyltrisilyl-(cyclopentadienyldicarbonyliron) complexes: (η5-C5H5) Fe(CO)2 Si3 Me6Ph

Abstract Isomeric phenyl-hexamethyltrisilyliron complexes of the type (η 5 -C 5 H 5 )Fe(CO) 2 Si 3 Me 6 Ph, FpSi 3 Me 6 Ph ( I–V ) have been synthesized, characterized, and photolysed in an inert solvent. Separate photolyses of the linear Fp complexes, e.g. FpSiMe 2 SiMe 2 SiMe 2 Ph ( III ), result in the transient formation of intermediate isomeric 2-substituted trisilyl Fp complexes, FpSiMe(SiMe 3 ) (SiMe 2 Ph) ( IV ) and FpSiPh(SiMe 3 ) 2 (V) which photodeoligomerize to FpSiMe 3 and FpSiMe 2 Ph via the intermediacy of Fp disilyl complexes. The product distribution from the photolyses of the Fp complexes is in accord with a mechanism involving equilibrating silyl(silylene) iron complexes. The two branched silyl complexes, FpSiPh(SiMe 3 ) 2 and FpSiMe(SiMe 3 ) (SiMe 2 Ph), isomerize prior to formation of the disilanes whereas the linear trisilanes and disilanes do not interconvert.

Identification of oxidative degradation impurities of Olanzapine drug substance as well as drug product

Impurities found in stressed and stability studies of olanzapine (polymorphic form-I) [1-7] in both drug substance and drug product are described. These impurities are identified as 4-(4-methyl-1-piperazinyl)-3-hydroxymethylidene-1H-benzo[b][1,4]diazepine-2(3H)-thione (hydroxymethylidene thione) and (Z)-4-(4-methyl-1-piperazinyl)-3-acetoxymethylidene-1H-benzo[b][1,4]diazapine-2(3H)-thione (acetoxymethylidene thione). An oxidative degradation pathway of olanzapine, for the formation of these impurities, has been proposed.

The redox behaviour of ferrocene derivatives: III. Ferrocenylacyl complexes (η5-C5H5) Fe(η5-C5H4-COER3 E C, Si or Ge; R Me or Ph☆

Abstract The electrochemical behaviour of the ferrocenylacyl derivatives [FcCOER3] (E  C, Si or Ge; R  Me or Ph) is examined. One-electron oxidations to the substantially stable monocations [FcCOER3]+ occur at potentials significantly higher than that observed with ferrocene, but only minor differences hold within the series, independent of the nature of both E and R. In contrast the EPR spectra of the monocations for E  C show that the unpaired electron resides mainly on the iron, whereas for E  Si or Ge the electron density is essentially localized on the C5H4COER3 fragment.

Gradient RP-HPLC method for the determination of potential impurities in atazanavir sulfate.

This paper proposes a simple and selective RP-HPLC method for the determination of process impurities and degradation products (degradants) of atazanavir sulfate (ATV) drug substance. Chromatographic separation was achieved on Ascentis(®) Express C8, (150mm×4.6mm, 2.7μm) column thermostated at 30°C under gradient elution by a binary mixture of potassium dihydrogen phosphate (pH 3.5, 0.02M) and ACN at a flow rate of 1.0ml/min. A photodiode array (PDA) detector set at 250nm was used for detection. Stress testing (forced degradation) of ATV was carried out under acidic, alkaline, oxidative, photolytic, thermal and humidity conditions. In presence of alkali, ATV transformed into cyclized products and the order of degradation reaction is determined by the method of initial rates. The unknown process impurities and alkaline degradants are isolated by preparative LC and characterized by ESI-MS/MS, (1)H NMR, and FT-IR spectral data. The developed method is validated with respect to sensitivity (lod and loq), linearity, precision, accuracy and robustness and can be implemented for routine quality control analysis and stability testing of ATV.