Synthesis and antibacterial activity of certain quinoline and quinazoline derivatives containing sulfide and sulfone moieties

Some aryl and/or heterocyclic mercaptans were allowed to react with 8-quinolyl chloroacetate (II), 8-quinolinoxyacetyl chloride (IV) and 3-(2′-chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one (X) in dry benzene and/or sodium hydroxide in absolute ethanol to give corresponding 8-quinolyl-α-mercaptoacetate (V), 8-quinolinoxythioacetate (VI) and 3-(2′-arylmercaptoethyl)-2-methyl-4-(3H)quinazolin-4-ones or 3-(2′-heterocyclicmercaptoethyl)-2-methyl-4(3H)-quinazolin-4-ones (XIa-h). The mercaptans V and XI were subjected to oxidation with hydrogen peroxide/acetic acid mixture (1:2) to afford the corresponding sulfones VII and XII. The structures of the synthesized compounds were elucidated by spectroscopic (IR and ¹H-NMR) and elemental analyses. Some of these compounds were tested for their antimicrobial activities in comparison with tetracycline as a reference compound.     

Synthesis and antibacterial activity of thioglycolic amino acid derivatives and dipeptides containing the 2-methyl-3,4-dihydroquinazolin-4-one moiety

3-(2′-Chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one ( I ) was reacted with sodio (sodium thioglycolate) in dry dioxane and yielded compound II . By using thionyl chloride, this compound was converted to the corresponding acid chloride ( III ). The prepared acyl chloride ( III ) was allowed to interact with different α-amino acids such as Gly, L -Ala, L -B-Phe, DL -Asp, L -Glu, L -Thr and L -Val to give new amino acid derivatives ( IVa – g ). A selected C-terminal derivative of glycine ( IVa ) was converted into acid chloride ( V ). The acid chloride formed was reacted with L -Ala, L -B-Phe, DL -Asp, L -Glu, L -Thr and L -Val and yielded the new dipeptides VIa – f . The structures of the synthesized compounds were elucidated by elemental analysis and IR spectra. The prepared peptides were tested for their antimicrobial activities by comparison with tetra-cycline as a reference compound.     

Synthesis of 2-alkyl-3-methyl-2-cyclopentenones from carboxylic acids or methylketones

Various 2-alkyl-3-methyl-2-cyclopentenones were prepared via 2-alkyl-4-penten-2-ols serving as common intermediates from carboxylic acids or methylketones. For example, dihydrojasmone was prepared from heptanoic acid as follows: Grignard reaction of heptanoic acid (I) with allylmagnesium chloride gave 1-decen-4-one (II) and re-Grignard reaction of (II) with methylmagnesium iodide produced 4-methyl-1-decen-4-ol (IV). 4-Methyl-1,4-decanediol (V) was obtained by hydroboration of (IV). Oxidation of (V) with chromium trioxide gave 4-hexyl-4-methyl-4-butanolide (VI). Dihydrojasmone may be prepared by dehydration of (VI) with polyphosphoric acid. Several new 2-alkyl-3-methyl-2-cylopentenones were obtained by this method.     

2-(3,4-二氯苯基)-2,4-二氢-5-甲基-3H-吡唑啉-3-酮的合成及表征

本文以3,4-二氯苯胺为原科合成了3,4-二氯苯肼盐酸盐,再与乙酰乙酸乙酯环化,合成2-(3,4-二氯苯基)-2,4-二氢-5-甲基-3H-吡唑啉-3-酮.用红外光谱、熔点仪、高效液相色谱和核磁共振对产品进行了表征和检测.考察了盐酸用量、还原剂、反应温度、溶剂和后处理对转化率和纯度的影响.结果表明:选用氯化亚锡作还原剂,在低温和盐酸过量下有利于提高3,4-二氯苯肼盐酸盐的收率.选用V(乙醇)∶V(水)=6∶1为溶剂,75℃下反应4小时,以碳酸钠调节pH =7,2-(3,4-二氯苯基)-2,4-二氢-5-甲基-3H-吡唑啉-3-酮转化率为82.6％,熔点163～164℃,纯度述96％.     

Synthesis of some new diarylsulphides and diarylsulphones containing a quinazol-4-one moiety

4-Amino-4′-nitrodiphenylsulphide and 4-amino-2′-nitrodiphenyl sulphide ( I ) were smoothly condensed with 2-methyl-3,1-benzoxazin-4-one ( II ) to produce the corresponding 2-methyl-3-diphenylsulphidoquinazol-4-ones ( III ). 2-Styryl-3-diphenylsulphidoquinazol-4-ones ( IV ) were prepared by heating III with the appropriate aromatic aldehydes using piperidine as a basic catalyst. Compounds IV oxidised easily in a hydrogen peroxide-glacial acetic acid mixture to produce the corresponding sulphones ( V ). The constitution of some of the prepared products is discussed in the light of their infrared and ultraviolet spectra. The biological activities of some of these compounds were tested.     

Synthesis and antibacterial activity of some quinazolin containing oxadiazolin-5-thione moieties

Several new quinazolin-4-one containing oxadiazolin-5-thione moieties were synthesized and evaluated for their antibacterial activity. Esterification of 2-substituted phenyl-3-carboxyalkyl-methyl-3,4-dihydroquinazolin-4-ones (I) with absolute ethyl alcohol in the presence of sulfuric acid afforded the corresponding esters (II). Hydrazinolysis of (II) with hydrazine hydrate in ethanol gave the acid hydrazides (III). Refluxing (III) with equimolar amounts of potassium hydroxide and slight excess of carbon disulfide afforded the corresponding oxadiazolin-5-thione derivatives (IV). The thiones undergo Mannich reaction using a formaldehyde/secondary amines mixture whereby the 4-substituted amino-methyl derivatives (V) were obtained. Microanalysis, IR, NMR spectra were used to elucidate the structures of the newly synthesized compounds. All the designed compounds were tested for their antibacterial activity. The morpholino derivatives showed an encouraging antibacterial activity.     

Synthesis and antibacterial activity of some new diarylsulphides and diarylsulphones containing azetidin-2-one and/or diazetidin-2-onyl moities

Cyclonucleophilic addition of N-phthaloylaminoacid chlorides (II on 4-(N-ary-lideneamino)-4′-nitrodiphenyl sulphides (I) in dioxane and triethylamine afforded 4-(4″-aryl-3″-phthalylamino-2″-oxo-azetidin-1″-yl)-4′-nitro-diphenyl sulphides (III). Hydrazinolysis of III yielded 4-(4″-aryl-3″-amino-2″-oxo-azetidin-1″-yl)-4′-nitro-diphenyl sulphide hydrochlorides (IV). Condensation of IV with anisaldehyde using ethanol and piperidine as a basic catalyst gave 4-(4″-aryl-3″-anisylidine amino-2″-oxoazetidin-1″-yl)-4′-nitrodiphenylsulphides (V) in good yields. Interaction of V with chloroacetyl chloride in dioxane and triethylamine produced 4-(4″-aryl-3″-substituted β-lactamyl-2″-oxo-azetidin-1″-yi)-4′-nitrodiphenyl sulphides VI. Oxidation of IV, V and VI using hydrogen peroxide/glacial acetic acid mixtures gave the corresponding sulphones (VII), (VIII) and (IX). Sulphones of the type IX were obtained by unequivocal synthesis through interaction of sulphone-anils VIII with chloroacetyl chloride. The antibacterial activities of some of these compounds were determined.     

Reaction of amines with conjugated olefins using lithium naphthalenide in non-ethereal solvents

It was found that lithium naphthalenide can be prepared from metallic lithium cuttings and naphthalene in non-ethereal solvents, such as benzene–N,N,N′,N′-tetramethylethylenediamine (TMEDA) or benzene-N,N,N′,N′-tetramethyldiaminopropane (TMDAP), under ultrasonic irradiation. Secondary amines reacted with conjugated olefins, such as isoprene or myrcene, using lithium naphthalenide in such non-ethereal solvents to give allylic amines. The yields of products were higher than in the reaction using lithium naphthalenide in tetrahydrofuran. From diethylamine (I) and isoprene (II), a mixture of N,N-diethyl-3-methyl-2-butenylamine (IV) and N,N-diethyl-2-methyl-2-butenylamine (V) (IV:V = 79:21) was obtained in 77% yield, and from diethylamine (I) and myrcene (III), N,N-diethylgeranylamine (VI) and N,N-diethylnerylamine (VII) (VI:VII = 88:12) were produced in 72% yield. These terpenic amines, VI and VII, are used as starting compounds for the preparation of perfumery materials.     

Lasioderma chemistry sex pheromone of cigarette beetle (Lasioderma serricorne F.)

A chemical study of the sex pheromone of the cigarette beetle was carried out. Seven components were isolated from active fractions of column chromatography of the female extract, and their structures were elucidated by spectroscopic evidence and confirmed by synthesis to be (4S,6S,7S)-4,6-di-methyl-7-hydroxynonan-3-one (serricornin) (I), 2,6-diethyl-3,5-dimethyl-3,4-dihydro-2H-pyran (anhydroserricornin) (II), 4,6-dimethylnonan-3,7-dione (III), 4,6-dimethylnonan-3,7-diol (IV), 4,6-dimethyl-7-hydroxy-4-nonen-3-one (V), (2S,3R)-2,3-dihydro-3,5-dimethyl-2-ethyl-6-(l-methyl-2-oxobutyl)-4H-pyran-4-one (serricorone) (VI) and (2S,3R)-2,3-dihydro-3,5-dimethyl-2-ethyl-6-(1-methyl-2-hydroxybutyl)-4H-pyran-4-one (serricorole) (VII).These structural features suggested that the occurrence of these components might be related to the polyketide biosynthesis. The behavioral bioassay and BAG experiments revealed the biological role of each component in the copulatory behavior of this insect.     

Synthesis of 4,4′-aryldihydrazono-3-(3′-pyridyl)-2-pyrazolin-4,5-diones and 1-aryl-3-(3′-pyridyl)-4,4′-arylbisazo-5-aryliminopyrazoles and their application as disazo disperse dyes. Part II

3-(3′-Pyridyl)-2-pyrazoline-4,5-dione 4,4′(4,4′-biphenylenedihydrazone and p-phenylenedihydrazone) and its derivatives ( IIa-e, IIIa-e ) were obtained by the coupling reaction of tetrazotised benzidine and p-diamonobenzene with 3-(3′-pyridyl)-2-pyrazolin-5-ones ( Ia-e ). Similarly, bis-azo compounds containing pyrazole nucleous as, 1-aryl-3-(3′-pyridyl)-4,4′-arylbisazo-5-aryliminopyrazoles ( VIa-i and VIIa-i ) were prepared by the interaction of the corresponding chloro compound ( IV and V ) with aromatic amines. The compounds so obtained ( II, III, VI and VII ) are used as disazo disperse dyes for dyeing polyester fibres fast yellow-orange shades. Their fastness properties towards washing, rubbing, acid-alkaline perspiration and light were investigated.     

The synthesis of pyrazolo- and isoxazolo-[3,4-c]-pyrazole hemiazadicarbocyanine dyes

New substituted pyrazolo and/or isoxazolo-[3,4-c]-pyrazole hemiazadicarbocyanine dyes (IV_a-d, V_a-d, VI_a-d) were prepared via the synthesis of 4-arylidino-1-phenyl-3-benzoxazolium-2-yl-pyrazol-5-one (II_a-d) followed by their interaction with hydrazine hydrate, phenylhydrazine and hydroxylamine. Structures of the synthesised compounds were determined from analytical data and from spectra. The biological activity of IV, V and VI were tested against bacteria and fungi.     

Studies on the Vilsmeier-haack reaction. Part XIII: Novel heterocyclo-substituted 4,4′-bi-pyrazolyl dithiocarbamate derivatives

5-Imino-3-methyl-l-phenyl-2-pyrazoline-4-dithiocarbamic acid (I) underwent simultaneous formylation and dimerization reactions with the Vilsmeier reagent giving 4-[5′-imino-3-(1″-formyl-2″-dimethylaminoethenyl)-3′-methyl-1′-phenyl-1′H-pyrazolo-4′-dithiocarbamyl-2,4-dihydro-3-imino-5-methyl-2-phenyl-1-pyrazoline]dithiocarbamate (II) which hydrolysed with sodium hydroxide to give 4-[3′-(1″-formyl-2″-hydroxyethenyl)-3′-methyl-1-phenyl-1′-H-pyrazolo-4′-dithiocarbamyl-1′-pyrazoline]dithiocarbamate-5,5′-dione (IV). Treatment of II and/or IV with morpholine, piperidine, piperazine, hydroxylamine, hydrazine hydrate or phenylhydrazine afforded the corresponding dipyrazolo-4,4′-dithiocarbamate derivatives with different heterocyclic systems at the 3-position. The structures of these compounds were confirmed by microanalysis data, IR and ¹H-NMR spectrometry. All synthesized compounds have been screened in vitro against Gram-positive and Gram-negative bacteria, and fungi.     

强酸性离子交换膜催化合成5-乙氧羰基-4-(4-甲氧苯基)-6-甲基-3,4-二氢嘧啶-2(1H)-酮

在HF-101强酸性离子交换膜的存在下,由茴香醛、乙酰乙酸乙酯与脲一步合成了5 乙氧羰基 4 (4 甲氧苯基) 6 甲基 3,4 二氢嘧啶 2(1H) 酮。当茴香醛、乙酰乙酸乙酯与脲的摩尔比为1:2:5,乙醇作溶剂,4g离子交换膜,回流2h,产物收率达95 2%。同时研究了离子交换膜作为催化剂的重复使用情况。     

Distribution Studies of Actinides Using a Tetradentate Extractant, 4,4′-Nonanedioyl-Bis(2,4-Dihydro-5-Methyl-2-Phenyl-3H-Pyrazol-3-One)

Abstract

The extraction of Th(IV), UO₂(II), Am(III), and Eu(III) from aqueous acid by a tetradentate extractant, 4,4′-nonanedioyl-bis(2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one), H₂NDBP, has been studied and compared with two bidentate model compounds, 4-hexanoyl-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one, HHMPP, and 4-benzoyl-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one, HBMPP. The distribution coefficients of UO₂(II), Am(III), and Eu(III) were somewhat larger using H₂NDBP relative to the model compounds under the conditions studied. However, the Th(IV) extraction using H₂NDBP was greatly enhanced when compared to HBMPP or HHMPP. The distribution coefficient for Th(IV) from 0.5 M HNO₃ was 11.6 using 3.0 × 10^?3 M H₂NDBP compared with values of D < 0.01 using 3.0 × 10^?3 M HBMPP or HHMPP.     

强酸性离子交换膜催化合成二氢嘧啶酮药物中间体

在HF 101强酸性离子交换膜的存在下,由对羟基苯甲醛、乙酰乙酸甲酯与脲一步合成了5 甲氧羰基 4 (4 甲氧苯基) 6 甲基 3,4 二氢嘧啶 2(1H) 酮。当对羟基苯甲醛、乙酰乙酸甲酯与脲的摩尔比为1∶2∶5,乙醇作溶剂,3g离子交换膜,回流2h,产物收率达95.4%。同时研究了离子交换膜作为催化剂的重复使用情况。     

Aluminium exchanged Indian clay as an efficient reusable green catalyst for synthesis of 2, 3-dihydroquinazolin-4(1H)-one derivatives

Aluminium exchanged Indian clay (Al³⁺-ExIC) catalyzed synthesis of 2, 3-dihydroquinazolin-4(1H)-one derivatives in good to excellent yields has been reported. The catalyst has been characterized for its physico-chemical properties. Effects of solvent, molar ratio, amount of catalyst and reaction time on the yield of 2-phenyl-2, 3-dihydroquinazolin-4(1H)-one and recyclability of the catalyst have been investigated. Various 2, 3-dihydroquinazolin-4(1H)-one derivatives have been obtained in good to excellent yields.     

Synthesis of some new styryl oxazolophenoxazines

Reductive acetylation of 3-aminophenoxaz-2-one (II) gave 3-acetylamino-2-acetoxy-phenoxazine (IV). Thermolysis of (IV) gave 2-methyl-5H-oxazolo(4,5-b)phenoxazine (V). The styryl derivatives (VIII) were synthesised by condensation of (V) with aromatic aldehydes. Quaternisation of (V) was carried out giving (VII). Oxidation of (V) using SeO₂ gave 2-formyl-5H-oxazolo(4,5-b)phenoxazine (VI). Fragmentation patterns of certain of the products under electron impact are suggested.     

高速逆流色谱法分离纯化散斑竹根兰中的抗癌活性成分

采用高速逆流色谱法（HSCCC）,以正己烷-乙酸乙酯-乙醇-水组成二相系统作为固定相与流动相,对散斑竹根兰的抗癌活性部位进行了分离纯化。结果发现：以正己烷-乙酸乙酯-乙醇-水（体积比为1∶1∶1.1∶0.9）组成的系统可以从散斑竹根兰的抗癌活性部位中分离出其中的抗癌活性成分之一3-（4′-hydroxy-benzyl）-5,7-dihydroxy-6-methyl-8-methoxyl-chroman-4-one,纯度可达95%以上。     

Odor similarity between stress-inducing odorants in wistar rats

Odor similarity to the odor of 4-mercapto-4-methyl-2-pentanone (I) was measured on eight rats by generalization of a conditioned avoidance response tocis- andtrans-8-mercapto-p-menthan-3-one (II and III), 3-mercapto-3-methyl-2-pentanone (V), andt-amyl mercaptan (VI). Previously, these odorants had been found to induce stress in rats in an open-field situation. In the present experiment, rats generalized the avoidance response learned with I, for V, VI, and to a lesser extenttrans-isomer III, implying odor similarities;cis isomer II was discriminated. Odor similarity between mercapto ketone I and mercaptan VI is surprising since VI lacks the keto group.     

Synthesis and Antimicrobial Evaluation of Some Novel Bis-α,β-Unsaturated Ketones,Nicotinonitrile, 1,2-Dihydropyridine-3-carbonitrile,Fused Thieno[2,3-b]pyridine and Pyrazolo[3,4-b]pyridine Derivatives

The title compounds were prepared by reaction of 1,1′-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)diethanone (1) with different aromatic aldehydes 2a–c, namely Furfural (2a), 4-chlorobenzaldehyde (2b) and 4-methoxybenzaldhyde (2c) to yield the corresponding α,β-unsaturated ketones 3a–c. Compound 3 was reacted with malononitrile, 2-cyanoacetamide or 2-cyanothioacetamide yielded the corresponding bis[2-amino-6-(aryl)nicotinonitrile] 4a–c, bis[6-(2-aryl)-2-oxo-1,2-dihydropyridine-3-carbonitrile] 5a–c or bis[6-(2-aryl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile] 6a,b, respectively. The reaction of compound 6a with each of 2-chloro-N-(4-bromophenyl) acetamide (7a), chloroacetamide (7b) in ethanolic sodium ethoxide solution at room temperature to give the corresponding 4,4′-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis-6-(2-furyl)thieno[2,3-b]pyridine-2-carboxamide] derivatives 9a,b. While compound 6a reacted with hydrazine hydrate yielded the 4,4′-(5-methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis[6-(2-furyl)-1H-pyrazolo[3,4-b]pyridin-3-amine] 11. The structures of the products were elucidated based on their spectral properties, elemental analyses and, wherever possible, by alternate synthesis. Antimicrobial evaluation of the products was carried out.