Synthesis,characterization and antimicrobial activity of novel sulphapiperazine containing arylazopyrazoles

Mannich reaction of benzotriazole (1), ethyl-4-amino benzoate (2) and formaldehyde in ethanol afforded 4-(1H)-benzotriazoyl methyl amino benzoate (3), which on treatment with hydrazine hydrate results in the 4-(1H)-benzotriazoyl methyl amino benzoyl hydrazide (4). This compound on condensation with pre-prepared various ethyl-2-substituted phenyl hydrazono-3-oxobutyrates (6a–h), furnished 1-(4-((1H-benzo[d][1,2,3]triazol-1-yl) methyl amino) benzoyl)-3-methyl-4-(2-(4-(4-alkylpiperazin-1-ylsulfonyl) phenyl) hydrazono)-1H-pyrazol-5(4H)-ones (7a–h). All these compounds (7a–h) were characterized by spectral studies. The compounds showed significant antimicrobial activity against various bacteria and fungi.     

Photoinitiated polymerization of methyl methacrylate and methyl acrylate with 14C-labeled benzoin methyl ethers

Three ¹⁴C-labeled benzoin methyl ether (α-methoxy-α-phenylacetophenone) derivatives were utilized as photoinitiators in the polymerization of methyl methacrylate (MMA) and methyl acrylate (MA). The results of polymer end-group analysis are in accord with a mechanism of benzoin ether photocleavage into initiator radicals and dispute earlier labeling studies which were interpreted as evidence for copolymerization of excited-state benzoin ethers with reactive monomers. In MMA polymerization, the results indicate a preference for termination by disproportionation (～60%) and provide evidence for primary radical termination at 0.041M photoinitiator (optically dense solutions) in neat MMA. Evidence for chain branching by initiator radical hydrogen abstraction from poly(methyl acrylate) (PMA) is also presented. The benzoyl and α-methoxybenzyl radicals, produced on photolysis of benzoin methyl ether, appear to be equally effective in both initiation and hydrogen-abstraction processes. Quantum yields at 366 and 313 nm indicate the absence of a wavelength effect.     

Mechanisms of photochemical reactions of <Emphasis Type="Italic">para</Emphasis>-benzoquinones with thiols

The mechanisms of quinone reduction by thiols containing α-hydrogen atoms were established using chemically induced dynamic nuclear polarization effects. It was found that substituents in the quinone nucleus change the nature of the primary radical pair. In the photolysis of 2,6-dimethyl-1,4-benzoquinone (1), the radical pair consists of semiquinone and thioalkyl radicals, whereas in the case of 2,6-diphenyl-1,4-benzoquinone (2), the radical pair is composed of semiquinone and thiyl radicals. Quinone 2 is readily photolyzed with any thiol to give dibenzofuran derivative as the final products.     

Titanium-dioxide-mediated photocatalysed reaction of selected organic systems

The photocatalysed reaction of four selected organic systems, namely dichlone (1), 2-amino-5-chloropyridine (2), benzoyl peroxide (3) and 3-chloro perbenzoic acid (4), has been investigated in an acetonitrile/water mixture in the presence of titanium dioxide and oxygen. An attempt has been made to identify the products formed during the photo-oxidation process using the GC/MS analysis technique. The photolysis of dichlone (1) leads to the formation of phthalic anhydride (11) and 1H-indene-1,2,3-trione (10), whereas 2-amino-5-chloropyridine (2) gave rise to 2,2′-diamino bipyridyl (14), 2-pyridinamine (16), 2-hydroxy-5-chloropyridine (18), bipyridyl (19) and 2-amino bipyridyl (21). The photolysis of benzoyl peroxide (3) yielded a mixture of products such as benzoic acid (24), biphenyl (27), biphenyl-4-carboxylic acid (29) and benzoic acid phenyl ester (30). Two intermediate products, as 3-chlorobenzaldehyde (35) and hydroxyl added 3-chlorobenzaldehyde (33), have been identified in the case of 3-chloro perbenzoic acid (4). The products have been identified by comparing the molecular ion and mass fragmentation peaks of the products with those reported in the GC-MS library. A probable mechanism for the formation of the products has been proposed.     

Chemical polarization of nuclei. PMR spectra of decomposition products of dimethyl peroxydiphthalate

Chemical polarization of protons was observed in methyl benzoate formed during the thermal decomposition of dimethyl ester of peroxydiphthalic acid. The polarization pattern of methyl benzoate aromatic protons was very different in this case from that observed during the thermal decomposition of acetyl benzoyl peroxide. The unpolarized products formed from the methoxy radical, CH₂O and CH₃OH, were found in the mixture of decomposition products of this peroxide and were identified by means of PMR spectroscopy.     

Cyanoacetamide in heterocyclic chemistry: Synthesis,antitumor and antioxidant activities of some new benzothiophenes

Cyanoacylation of 2‐amino‐tetrahydrobenzothiophene‐3‐carboxylate ethyl ester with 3‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐3‐oxopropanenitrile afforded cyanoacetamide 2 . The later was utilized as key intermediate for the synthesis of 3‐substituted 2‐iminocoumarins 3 , 4 , 5 , 6 and acrylamides 7a , b via Knoevenagel condensation with 2‐hydroxy‐1‐naphthaldehyde; 2‐hydroxybenzaldehyde; 1‐nitrosonaphthalen‐2‐ol; 7‐hydroxy‐5‐methoxy‐2‐methyl‐4‐oxo‐4H‐chromene‐6‐carbaldehyde; 4‐dimethylamino‐benzaldehyde; and 4‐piperidin‐1‐yl‐benzaldehyde in EtOH/piperidine. The derivatives 7a , b did not afford the pyrazoles 8a , b upon treating with phenyl hydrazine. Furthermore, coupling of 2 with 4‐amino‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one and 4,6‐dimethyl‐1H‐pyrrolo[2,3‐b]pyridin‐3‐amine afforded the hydrazone derivatives 9 and 10 , respectively. The later derivative 10 was cyclized in acetic acid to afford the pyridopyrazolotriazine 11 . Finally, 2 was treated with dimethylformamide‐dimethylacetal (DMF‐DMA) to afford the dimethylaminoacrylamide 12 which underwent transamination with 4,6‐dimethyl‐1H‐pyrrolo[2,3‐b]pyridin‐3‐amine to afford the pyrazole 13 . Cyclization of compound 13 in acetic acid or pyridine was unsuccessful. The antitumor and antioxidant activities of the synthesized products were evaluated; several were found to exhibit promising antioxidant activities. J. Heterocyclic Chem., (2011).     

Photochemistry of β, γ-unsaturated ketones-V: The direct irradiation of some γ-phenyl β, γ-enones

The photochemistry of some members of the two series of γ-phenyl substituted acyclic β, γ-unsaturated ketones 1 and 2 upon direct irradiation with γ 310nm has been investigated, viz 1c–1h and 2b+2c.The alkyl substituted (E)-5-phenyl-4-penten-2-ones 1c–1h yield the corresponding 1,3-acyl shift products and (Z)-isomers, and 1g and 1h in addition two decarbonylated products. 2b only yields the (Z)-isomer and some benzaldehyde, but 2c yields the 1,3-acyl shift product, the ODPM product, three hydrocarbons formed by disproportionation of the allyl radical, and some benzaldehyde. The β-phenyl β, γ-UK 3a proved to be photostable. The 1,3-acyl shift products of 1c–1h result mainly from the singlet excited state in a cage radical process. The exclusive formation of the (E)-configuration of the 1,3-acyl shift product is explained in terms of conformational preference of the intermediate allyl radical. It is proposed that the formation of the (Z)-isomer proceeds from ¹T(π -π^*) which is populated according to

. Evidence is presented which supports the proposed mechanism.The β,γ-UK 2b containing a benzoyl moiety leads to a higher degree of (E)-(Z) isomerization than the corresponding 1d which has an acetyl moiety.The triplet energies of (E)- and (Z)-1h are 56 and ca 70 kcal/mol respectively.     

The benzoyl cation: The participation of isolated electronic excited states in the dissociation of molecular ions of the form [C6H5COX]+˙

The heat of formation of the benzoyl cation generated from [C₆H₅COX]⁺˙ is found to depend on X, while the heat of formation of the phenyl ion produced therefrom is, with one exception, independent of X. The excess energy of the benzoyl cation can be accounted for by an electronic excited state of the ion in the mass spectra of benzoic acid, benzaldehyde, benzamide, methyl benzoate and possibly benzophenone; the benzoyl cation is not excited in the mass spectra of acetophenone and benzoyl chloride.     

Enantioselective route to ferrugine and its methyl analogue via aldol deoxygenation

A simple enantioselective approach to ferrugine (2α-benzoyltropane) and its methyl analogue (2-acetyltropane) is reported. The four-step sequence uses an enantioselective aldol reaction of tropinone with benzaldehyde or acetaldehyde, combined with an aldol deoxygenation via tosylhydrazone reduction and oxidation of the side-chain hydroxy group. The final products, ferrugine and its methyl analogue, are prepared in 35% and 23% overall yields, respectively. Both enantiomers of the products (ee 90-99%) are accessible via the same route using either enantiomer of N,N-bis(1-phenylethyl)amine hydrochloride as the chiral reagent.     

Photochemistry of <Emphasis Type="Italic">N</Emphasis>-substituted salicylic acid amides

The products of photolysis of N-substituted salicylic acid amides, viz., 2-hydroxy-3-tert-butyl-5-ethylbenzoic acid N-(4-hydroxy-3,5-di-tert-butylphenyl)amide (1) and 2-hydroxybenzoic acid N-[3-(4-hydroxy-3,5-di-tert-butylphenyl)prop-1-yl]amide (2), in heptane were studied by optical spectroscopy and stationary and nanosecond laser photolysis (Nd: YAG laser, 355 nm). It was shown by the method of partial deuteration of amides 1 and 2 that they exist in both the unbound state and as complexes with intraand intermolecular hydrogen bond. Amides 1 and 2 are subjected to photolysis, which results in the formation of a triplet state and phenoxyl radicals RO? presumably due to the absorption of the second photon by the excited singlet state. The formation of radical products due to N–H bond ionization was not observed. The main channel of decay of the triplet state and radicals RO? is triplet–triplet annihilation and recombination (k _r ≈ 2.3?10⁸ L mol^–1 s^–1), respectively. The UV irradiation of compounds 1 and 2 leads to the excitation of the amide groups, and no formation of radical products due to N–H bond ionization was observed.     

Nitrogen photochemistry. Cocaine and its model compounds

The ultraviolet irradiation of the π → π* transition of cocaine, p-anisoyl-l-ecognine methyl ester, p-toluoyl-l-ecognine methyl ester benzoyl tropine and benzoylpseudotropine in methanol using a Corex filter produces the corresponding N-demethylated products. Formaldehyde is quantitatively produced. 1-Methyl-3-piperidyl benzoate and 1-methyl-4-piperidyl benzoate yield benzoic acid under the same conditions but no demethylated products. Phenylacetyl-l-ecognine methyl ester gives no demethylation during irradiaiton. The phosphorescence bands of cocaine and its model compound, methyl benzoate, have been shown to be strongly dependent upon solvent polarity suggesting charge transfer in the triplet state.     

Synthesis and characterization of oxime‐bearing hexakis(2‐formylphenoxy)‐phosphazene and its derivatives

Hexakis(2‐formylphenoxy)cyclotri‐phosphazene ( 2 ) was obtained from the reaction of hexachlorocylotriphosphazene ( 1 ) with 2‐hydroxy‐benzaldehyde. Hexakis(2‐[(hydroxyimino)methyl]‐phenoxy)cyclotriphosphazene (3) was synthesized from the reaction of 2 with hydroxlaminehydrochloride in pyridine. Hexasubstituted compounds 4, 5, 6, 8, 9 , and 10 were obtained from the reactions of 3 with methyl iodide, ethyl bromide, allyl bromide, propanoyl chloride, benzoyl chloride, and 4‐methoxybenzoyl chloride, respectively. Disubstituted product 7 was obtained from the reaction of 3 with chloroacetyl chloride. Pure and defined products could not be obtained from the reaction of 3 with acetyl chloride, benzyl chloride, and 2‐chlorobenzoyl chloride. The compounds were characterized by elemental analysis and IR, ¹H, ¹³C, and ³¹P NMR spectroscopy. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:791–797, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20350     

Deoxycholic acid degradation by a pseudomonas sp: Phenolic and neutral products

The microbial degradation of deoxycholic acid by Pseudomonas sp. MR108 was studied, and four products were isolated. Evidence is presented that one is the phenol 3,12β - dihydroxy - 9,10 - secoandrosta -1,3,5(10) - trien - 9,17 - dione (11) and that the other three are the neutral compounds 3aαH - 4α - [3' - propionic acid] - 5α - hydroxy - 7aβ - methyl - hexahydro -1 - indanone - δ - lactone (12), 12β - hydroxyandrosta -1,4 - dien -3,17 - dione (10), and 12α - hydroxyandrosta - 1,4 - dien - 3,17 - dione (7).     

When ethyl is infinitely different from methyl: double addition of lithiated dithianes to aromatic carboxylates revisited

Addition of lithiated alkyl dithianes to benzoyl chloride or methyl benzoate does not produce the expected product of double addition, alpha,alpha-bis(alkyldithianyl) benzyl alcohol, for alkyls larger than methyl. Instead, the first step intermediate, i.e. 2-benzoylated dithiane, undergoes an electron-transfer reduction by the second molecule of the dithianyl anion. This reduction is followed by the ring-opening mesolytic fragmentation of the dithiane ring in the ketyl anion radical and subsequent radical recombination yielding acetophenone-tethered thioortho esters 4, alpha-[3-(2-alkyl-1,3-dithiane-2-ylthio)propylthio]-alpha-alkyl-acetophenones. It appears that the Corey-Seebach bisaddition of lithiated dithianes to methyl benzoate is an exception rather than the rule in the alkyl dithiane series.     

α-Branched amines through radical coupling with 2-azaallyl anions,redox active esters and alkenes

α-Branched amines are fundamental building blocks in a variety of natural products and pharmaceuticals. Herein is reported a unique cascade reaction that enables the preparation of α-branched amines bearing aryl or alkyl groups at the β- or γ-positions. The cascade is initiated by reduction of redox active esters to alkyl radicals. The resulting alkyl radicals are trapped by styrene derivatives, leading to benzylic radicals. The persistent 2-azaallyl radicals and benzylic radicals are proposed to undergo a radical–radical coupling leading to functionalized amine products. Evidence is provided that the role of the nickel catalyst is to promote formation of the alkyl radical from the redox active ester and not promote the C–C bond formation. The synthetic method introduced herein tolerates a variety of imines and redox active esters, allowing for efficient construction of amine building blocks.

A mild method for the construction of α-branched amine derivatives is presented. SET processes between the Ni catalyst, redox active esters and 2-azaallyl anions generate azaallyl radicals and alkyl radicals that functionalize the alkenes.     

Studies in sesquiterpenes—L : 3-hydroxylongifolaldehyde,the elusive intermediate in the abnormal perbenzoic acid oxidation of longifolene

The isolation and stereochemistry of 3-hydroxylongifolaldehyde (4), the missing key-compound in the earlier proposed mechanism for the abnormal perbenzoic acid oxidation of longifolene is described. Rearrangement of hydroxyaldehyde (4) to hydroxyketone (6) during exposure to LAH is reported.     

Reaction of cholest-4-ene-3,6-dione with perbenzoic acid : Formation of novel oxetalactones

Oxidation of 1 with perbenzoic acid (p-toluene-sulphonic acid monohydrate as catalyst) provided novel oxetalactones 4 and 5 along with compounds 2 and 3. Treatment of 2 with perbenzoic acid yielded 4. A probable pathway for the formation of 4 from 1 involving the intermediacy of 2 has been suggested.     

New Protected Protecting Groups for the 5′‐Hydroxy Group of Deoxynucleosides by Use of 2‐(Hydroxymethyl)‐ and 2‐[(Methylamino)methyl]benzoyl Skeletons and Oxidatively Cleavable Tritylthio and (4‐Methoxytrityl)thio Groups

The new protecting groups 1a , b and 2a , b were developed for the 5′‐OH group of deoxynucleosides by utilizing the unique characters of the sulfenate and sulfenamide linkage. These new protecting groups have a 2‐(hydroxymethyl)benzoyl or 2‐[(methylamino)methyl]benzoyl skeleton whose hydroxy O‐atom or amino N‐atom was blocked with a tritylthio‐type substituent. They are removable by intramolecular cyclization following the oxidative hydrolysis of the tritylthio‐type substituents under mildly oxidative conditions (Schemes 3 and 6). Among them, 2‐{{[(4‐methoxytrityl)sulfenyl]oxy}methyl}benzoyl (MOB; 2b ) was found to be the most preferable for protection of the 5′‐OH function of deoxynucleosides. MOB can be introduced at the 5′‐OH groups of various deoxynucleosides without the protection of the 3′‐OH functions (Scheme 5). The applicability of the MOB group to a new oligodeoxynucleotide synthesis protocol without acid treatment was demonstrated by the solid‐phase synthesis of a tetrathymidylate (Scheme 8).     

Additions of functionalized α-substituted allylboronates to aldehydes under the novel Lewis and Brønsted acid catalyzed manifolds

The stereo- and chemoselectivity in the additions of four model α-substituted allylboronates to benzaldehyde was examined under the standard thermal (uncatalyzed) conditions and the novel Lewis and Brønsted acid-catalyzed conditions. With either of Sc(OTf)₃ or triflic acid as catalysts, an α-ethyl allylboronate, 1a, led to a surprising inversion of stereoselectivity that can be tentatively rationalized through subtle differences in the geometry of the allylboration transition state between uncatalyzed and catalyzed pathways. It was also found that the chemoselectivity of α-silyl reagents (1c and 1d) can be reversed upon use of a catalyst, providing allylsilation products instead of the allylboration product obtained from the thermal uncatalyzed reaction.     

Photochemical Reaction of Benzoin Caged Compound:Time-Resolved Fourier Transform Infrared Spectroscopy Study

The benzoin group caged compound has received strong interests due to its excellent photo-deprotection properties and wide use in chemical and biological studies. We used time-resolved infrared spectroscopy to investigate the photochemical reaction of the benzoin caged compound, o-(2-methylbenzoyl)-DL-benzoin under 266 nm laser irradiation. Taking advantage of the specific vibrational marker bands and the IR discerning capability, we have detected and identified the uncaging product 2-methylbenzoic acid, and two intermediate radicals of benzoyl and 2-methylbenzoate benzyl in the transient infrared spectra. Our results provide spectral evidence to support the homolytic cleavage reaction of C-C=O bond in competition with the deprotection reaction. Moreover, the product yields of 2-methylbenzoic} acid and benzoyl radical were observed to be affected by solvents and a largely water containing solvent can be in favor of the deprotection reaction.