The Synthesis of Some New Quinazolone Derivatives of Potential Biological Activity

The refluxing of 3-amino-6,8-dibromo-2-thioxo-2,3-dihydro-1H-quinazolin-4-one (5) with ethyl chloroformate and/or ethyl chloroacetate afforded compounds 6 and 7 . The reaction of 5 with ethyl bromobutyrate, chloroacetyl chloride, phenacyl chloride, and phenyl isocyanate yielded compounds 8 , 9 , 11 , and 12 . The coupling of 5 with (2,3,4,6-tetra-O-acetyl-α -D-gluopyranosyl)bromide( ABG ) in DMF at r.t. gave 3-amino-6,8-dibromo-2-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)thioxo-2,3-dihydro-1H-quinazolin-4-one ( 14 ). The deblocking of 14 in sodium methoxide gave 5 . 3-Amino-6,8-dibromo-2-methylthio-3H-quinazolin-4-one ( 16 ) was prepared by stirring 5 with methyl iodide in methanol. The treatment of 16 with hydrazine hydrate afforded 4 . The condensation of 4 with aldehydes furnished 3,5-dibromo-2-arylaminobenzoic acid hydrazide ( 18a–c ). The refluxing of 18a with acetic anhydride gave 3-(benzylideneamino)-6,8-dibromo-2-methyl-3H-quinazolin-4-one ( 19 ). Hydrazones 20a–f were prepared by the condensation of 4 with pentoses and/or hexoses. The acetylation of ( 20a–f ) with acetic anhydride gave the acetyl derivatives 21a–f .     

白藜芦醇类似物的合成

3,5-二甲氧基苄溴(4)与NaCN反应生成3,5-二甲氧基苄腈(5), 5经水解得到3,5-二甲氧基苯乙酸(6). 5与苯甲醛或取代苯甲醛发生Knoevenagel反应生成化合物2a～2d, 为Z式构型. 6与苯甲醛或取代苯甲醛发生Perkin反应得到化合物3a～3c, 为E式构型. 2a～2d和3a～3c均为白藜芦醇类似物. 给出了各步反应产物的IR, ¹H NMR, ¹³C NMR和MS数据, 讨论了影响反应的因素, 并给出了化合物2a～2d和3a～3c对乳腺癌细胞MCF-7、肺癌细胞H446、乳腺癌细胞231的体外生理活性和对正常肝细胞L02体外毒性的半致死浓度.     

Group-theoretical Foundations for the Concept of Mandalas as Diagrammatical Expressions for Characterizing Symmetries of Stereoisomers

Group-theoretical foundations for the concept of mandalas have been formulated algebraically and diagrammatically in order to reinforce the spread of the unit-subduced-cycle-index (USCI) approach (S. Fujita, Symmetry and Combinatorial Enumeration in Chemistry, Springer-Verlag, Berlin-Heidelberg, 1991). Thus, after the introducton of right coset representations (RCR) (H\)G and left coset representations (LCR) G(/H) for the group G and its subgroup H, a regular body of G-symmetry is defined as a diagrammatical expression for a right regular representation (C ₁\)G, which is an extreme case of RCRs. The |G| substitution positions of the regular body as a reference are numbered in accord with the numbering of the elements of G and segmented into |G|/|H| of H-segments, which are governed by the RCR (H\)G. By regarding each H-segment as a substitution position, the H-segmented regular body is reduced into a reduced regular body, which can be regarded as a secondary skeleton for generating a molecule. The reference regular body (or H-segmented one) is operated by every symmetry operations of G to generate regular bodies (or H-segmented ones), which are placed on the vertices of a hypothetical regular body of G-symmetry. The resulting diagram (a nested regular body) is called a mandala (or a reduced mandala), which is a diagrammatical expression for specifying the G-symmetry of a molecule. The effect of a K-subduction on the regular bodies of a mandala (or a reduced mandala) results in the K-assemblage of the mandala (or the reduced mandala), where the resulting K-assemblies governed by the LCR G(/K) construct a |G|/|K|-membered orbit, which corresponds to a molecule of K-symmetry. The sphericity of the RCR (or the LCR) is used to characterize symmetrical properties of substitution positions and those of stereoisomers. The fixed-point vector for each mandala (or reduced mandala) in terms of row view and the number of fixed points of K-assembled mandalas (or K-assembled reduced mandalas) in terms of column view are compared to accomplish combinatorial enumeration of stereoisomers. The relationship between a mandala and a reordered multiplication table is discussed.     

Investigation of the Addition of Benzenethiol to p-Chlorophenylphenylacetylene

The addition of benzenethiol to p-chlorophenylphenylacetylene results in the formation of a mixture of two pairs of diastereomeric (E)- and (Z)-1-p-chlorophenyl-2-phenyl-1-phenylthioethylenes (1 and 2) and (E)- and (Z)-1-p-chlorophenyl-2-phenyl-2-phenylthioethylenes (3 and 4). The configurations of these compounds have been established by ¹ H NMR studies, by their preparation from benzyl p-chlorophenyl ketone and p-chloro-benzylphenyl ketone, and by the oxidation of the thioethylenes 1, 2, 3, and 4 to the corresponding sulphonylethylenes 5, 6, 7, and 8, respectively.     

Acetoacetanilides in Heterocyclic Synthesis,Part 1: An Expeditious Synthesis of Thienopyridines and Other Fused Derivatives

3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulfonyl]phenyl}butanamide 1 reacts with arylidinecyanothioacetamide in refluxing ethanolic TEA to give the pyridinethione 2 rather than thiopyrane 4. Compound 2 reacts with α-haloketones to give the s-alkylated derivatives 7a–e. Compound 7a–e undergoes cyclization into thieno[2,3-b]pyridine derivatives 8a–e. The saponification of 8a gives the amino acid 9, which affords 10 when refluxed in Ac₂O. The treatment of 10 with NH₄OAc/AcOH gives 11. Compound II is also obtained when 8e is refluxed in Ac₂O. The reaction of 8a with hydrazine hydrate gives 12 and with formamide gives 13. Compound 13 also is obtained from the reaction of 8e with triethylorthoformate. The acetylation of 8a with Ac₂O gives the amide derivative 14, which, on treatment with aromatic amines, affords 15a–c. Compounds 15a–c are cyclized with H₂SO₄ to 16a–c. Compound 16 is obtained also from the acetylation of compound 8c, d by Ac₂O. Reactions of compound 8e with CS₂ in refluxing dioxane afford 17. The diazotization and self-coupling of 8e give the pyridothienotriazine 18. Finally, the chloronation of compound 13 with POCl₃ affords the chloride derivative 19.     

Kinetics and mechanism of formation of isomeric 1-methyl- and 2-methyl-5-vinyltetrazoles

The alkylation of 5-(β-dimethylaminoethyl)tetrazole (1) with dimethyl sulfate afforded 5-(β-dimethylaminoethyl)-1-methyltetrazole (2) and 5-(β-dimethylaminoethyl)-2-methyltetrazole (3). The exhaustive alkylation of compounds 2 and 3 at the terminal dimethylamino group gave 1-methyl-(4) and 2-methyl-5-(β-trimethylammonioethyl)tetrazole (5) methyl sulfates. The proton elimination from the α-methylene (with respect to the tetrazole cycle) groups of the quaternary ammonium cations of salts 4 and 5 by the action of a base leads to the corresponding zwitterions 4 ^± and 5 ^±, which in the rate-determining step undergo the cleavage of the nitrogen—carbon bond with the formation of 1-methyl-5-vinyl- (6) and 2-methyl-5-vinyltetrazole (7). The true constant of the transformation of zwitterion 4 ^± into tetrazole 6 is 21 times higher than that for the transformation of zwitterion 5 ^± into tetrazole 7.     

脱镁叶绿酸-a甲酯的1,3-偶极环加成及其叶绿素衍生物的合成

以脱镁叶绿酸-a甲酯(1)为起始原料, 利用其3-位乙烯基与重氮甲烷的1,3-偶极环加成反应, 得到3-位氢化吡唑取代的脱镁叶绿酸-a衍生物2, 通过热裂解使得3-位吡唑基开环并重排成环丙基. 碱性条件下, 所生成的3-环丙基取代的卟吩3脱甲氧甲酰基后转化成焦脱镁叶绿酸衍生物4. 选用重氮乙烷为另一偶极体与1进行1,3-偶极环加成反应, 则给出2-甲基环丙基取代的立体异构体卟吩5, 同样经过脱甲氧甲酰基处理, 得到焦脱镁叶绿酸衍生物6. 所合成新叶绿素衍生物2～6均经UV, IR, ¹H NMR及元素分析证明其结构.     

In quest of reversibility of Friedel-Crafts acyl rearrangements in the pyrene series

Friedel-Crafts acyl rearrangements in PPA of diacetylpyrenes (80–120 °C), dibenzoylpyrenes (80–200 °C), and bis(4-flurobenzoyl)pyrenes (80–120 °C) and Scholl reactions in AlCl₃/NaCl of dibenzoylpyrenes (140–200 °C) have been studied. The substrates were 1-AcPY, 2-AcPY, 1,3-Ac₂PY, 1,6-Ac₂PY, 1,8-Ac₂PY, 2,7-Ac₂PY, 1-BzPY, 1,6-Bz₂PY, 1,8-Bz₂PY, 1-4FBzPY, 1,6-4FBz₂PY, 1,8-4FBz₂PY. The mixtures of pyrene, 1-AcPY, 2-AcPY, 1,3-Ac₂PY, 1,6-Ac₂PY, 1,8-Ac₂PY, and 2,7-Ac₂PY were separated by HPLC. The following reversible intermolecular isomerizations were established: 1,6-Ac₂PY ? 1,8-Ac₂PY, 1,6-Bz₂PY ? 1,8-Bz₂PY, and 1,6-4'FBz₂PY ? 1,8-4'FBz₂PY, albeit not in high yields. The results substantiate Gore’s 1955 proposition that “The Friedel–Crafts acylation reaction of reactive aromatic hydrocarbons is a reversible process.” The isomerizations reported here differ from the few previously reported completely reversible intramolecular Friedel-Crafts acyl rearrangements. At ≥ 140 °C, in PPA and in AlCl₃/NaCl, 1,6-Bz₂PY and 1,8-Bz₂PY underwent a highly regioselective double Scholl reaction to give pyranthrone (3) and deacylations to 1-BzPy (and pyrene), followed by mono-Scholl reactions to give 8H-dibenzo[def,qr]chrysen-8-one (1), and 11H-indeno[2,1-a]pyren-11-one (2). The formation of 3 and not the expected tribenzo[a,ghi,o]perylene-7,16-dione (4) from 1,8-Bz₂PY indicates that 1,8-Bz₂PY has first undergone isomerization to 1,6-Bz₂PY. The present study confirms the linkage between Friedel-Crafts acyl rearrangements and the Scholl reaction.

     

Solution structure and equilibrium of new calix[4]resorcinarene complexes—prototype of molecular machines. NMR data

Association properties and molecular machine application of water soluble calix[4]resorcinarene (1) with two aromatic guests (2-naphthol (2) and 1,5-naphthalenediamine (3)) have been investigated by various NMR methods (chemical shift, nOe and diffusion measurements) in aqueous solution at different concentrations and pH range. In neutral solution 1 strongly associates with 2, while only moderately associating with 3. Increase in concentration causes an increase in the stability of 1 + 3 and 1 + 2 + 3 complexes and produces high order complexes. The decrease of pH does not have an influence on 1 + 2 association, but disrupts 1 + 3 assembly. 1 can be used for the separation of 2 + 3 mixture in aqueous solution at moderate concentrations. The pH dependency of the association properties of the 1 + 3 system makes these compounds prime candidates for pH-responsive molecular machines applications.     

Synthesis,Characterization, and Thermal and Antibacterial Studies of Diorganotin(Iv) Derivatives of Amino Acids

Abstract

Six diorganotin(IV) derivatives of α-aminoacids with general formulae [(CH₃)₂ SnAACl]₂ and [(CH₃CH₂CH₂CH₂)₂SnAACl]₂, where AA = L-alaninate, L-phenylalaninate, and L-isoleucinate, have been synthesized by reacting dimethyltin(IV) dichloride (M) and dibutyltin(IV) dichloride (B) with L-alanine (A) or L-phenylalanine (PA) or L-isoleucine (I) using acetonitrile as the solvent and designated as MA, MPA, MI, BA, BPA, and BI. These complexes have been characterized by elemental analysis, infrared (IR), ¹H NMR, ¹³C NMR, and ¹¹⁹Sn NMR spectroscopy. Thermal studies of all of the synthesized complexes were also carried out using thermogravimetric (TG) and differential scanning calorimetry (DSC) techniques. The thermal decomposition mechanisms were similar for MA, BA, MI, and BI and occurred in one step, while in compounds MPA and BPA, it occurred in two consecutive steps. The TG curves of MPA and BPA suggest the loss of the ligand (AA) in the first step, with probable formation of a tin oxide R₂SnO as an intermediate, and in the second step, free tin is obtained, similar to MA, BA, MI, and BI, in accordance with the stoichiometry of the related derivatives. The diorganotin(IV) complexes have also been screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. The minimum inhibitory concentration values of these complexes show enhanced activity.     

A new coumarin from the roots of Micromelum minutum

A new coumarin, minutuminolate (1), together with eleven known coumarins (2–12), was isolated from the roots of Micromelum minutum. The structures of these compounds were established on the basis of their 1D and 2D NMR spectroscopic data. Compounds 2, 5, 10, 11 and 12 showed cytotoxicity against KB cell line. In addition, compounds 2, 3, 4, 7, 11 and 12 also showed weak cytotoxicity against NCI-H187 cell line.     

Application of organolithium and related reagents in synthesis,Part XII. Synthesis of phenyl- and pyridylpyridopyridazinones and their derivatives

Summary The preparation of the pyridazinones10a,10b,11a,11b, and12a,12b from the ketoamides7,8, and9 and hydrazine hydrate is described. It was found that from ketoamides8b and9b in addition to the expected pyridopyridazinones11b and12b also aminopyridopyridazines14 and15 were formed and that ketoamide7b gave exclusively aminopyridopyridazine13. The pyridopyridazinones10b,11b, and12b were alkylated with alkyl iodides.

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Anwendungen von Organolithium und verwandten Reagenzien in organischen Synthesen, Teil XII. Synthese von Phenyl- und Pyridylpyridopyridazinonen und ihren Derivaten

Zusammenfassung Die Darstellung der Pyridazinone10a,10b,11a,11b und12a,12b aus Ketoamiden7,8 und9 und Hydrazinhydrat wird beschrieben. Es wurde festgestellt, daß aus Ketoamiden8b und9b außer den erwarteten Pyridopyridazinonen11b und12b auch Aminopyridopyridazine14 und15 enstanden und daß das Ketoamid7b ausschließlich ins Aminopyridopyridazin13 überführt wurde. Die Pyridopyridazinone10b,11b und12b wurden mit Alkyljodiden alkyliert.

     

Synthesis of canthine/erythrinane alkaloid analogs

The pentacyclic lactams9,11, and14 were prepared using a thermal condensation of tryptamine with symmetrical oxodiesters3 and4 as the key step. The formation of the ring E in the tetracyclic compounds5,6,8,10,12, and13 is strongly dependent on the ring size.

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Synthese von Analoga der Canthin/Erythrina Alkaloide (Kurze Mitteilung)

Zusammenfassung Die pentacyclischen Verbindungen9,11 und14 wurden durch thermische Kondensation von Tryptamin mit symmetrischen Oxodiestern3 und4 als wichtigster Reaktionsstufe dargestellt. Die Bildung des Ringes E in den tetracyclischen Verbindungen5,6,8,10,12 und13 ist stark von der Ringgröße abhängig.

     

AM1 study of conformations of oxocane and 1,3-dioxocane

Summary AM1 semi-empirical SCF MO calculations are reported for important conformations of oxocane (1) and 1,3-dioxocane (2). The boat-chair conformation of1 (BC-1) is found to be the most stable form, whereas the crown family conformation is calculated to be 3.7 kJ·mol^–1 less stable. The boat-boat form of1 is 15.9 kJ·mol^–1 less stable thanBC-1. The boat-chair conformation of2 (BC-1,3) is calculated to be the most stable form of 1,3-Dioxocane. The crown-family conformation and the boat-boat geometry of this compound are 4.2 and 8.3 kJ mol^–1 less stable thanBC-1,3.

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AM1-Rechnungen zu den Konformationen von Oxocane und 1,3-Dioxocan

Zusammenfassung Die wesentlichen Konformationen von Oxocan (1) und 1,3-Dioxocan (2) wurden mittels semiempirischer AM1-Rechnungen (SCF MO) untersucht. Die Wanne-Sessel-Konformation von1 (BC-1) ist am stabilsten; Konformationen aus der Klasse der Kronen sind um 3.7 kJ·mol^–1 energiereicher. Die Wanne-Wanne-Konformation von1 ist um 15.9 kJ·mol^–1 instabiler alsBC-1. Die Wanne-Sessel-Konformation von2 (BC-1,3) ist das stabilste Konformer von 1,3-Dioxocan. Kronenkonformationen und Wanne-Wanne-Geometrien sind um 4.2 und 8.3 kJ·mol^–1 energiereicher alsBC-1,3.

     

Reactivity of Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide towards some carbon electrophiles. A comparative study

Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide 2a, 2b have different relative reactivities towards some carbon electrophiles had been discussed.The Z-isomer underwent cyclization to give imidazole derivative 3 and triazine derivative 4, whereas the latter E-isomer does not undergo such cyclization. The reaction of 2a and/or 2b with 1,2-dibenzylidene hydrazine at different reaction conditions afforded the Schiff bases 6, 8 and the triazolidine derivative 9. Reactions of 2a, 2b with formic acid and phthalic anhydride gave the different cyclization products 10–14, respectively. The structures of all the new synthesized compounds were established from their IR, ¹H-NMR and mass spectra as well as elemental analyses.     

Cyclodesulfurization of Substituted Thiosemicarbazides into 1,3,4-Oxadiazoles via Hydrazonoyl Chlorides

Abstract

The reaction of thiosemicarbazides 1a–h with hydrazonoyl chlorides 2a–g at ambient temperature, in the presence of triethylamine yielded, in each case, two products. The structure of these compounds was confirmed as 1,3,4-oxadiazoles 14a–h and hydrazonothioates 15a–g. The structure of 15b was confirmed through single crystal X-ray diffraction. A mechanism was proposed for this cyclodesulfurization reaction.     

The Utility of Isothiocyanato Thiophenes in the Synthesis of Thieno[2,3-d]pyrimidine Derivatives as Possible Radioprotective and Anticancer Agents

The synthesis of novel thioureido derivatives 3, 8, and 10; biscompounds 7, 9, and 11; and tetracyclic compounds 5, 6, and 16 utilizing 5-isothiocyanato-3-methyl-thiophene-2,4-dicarboxylic acid diethyl ester 2 are reported. The structures of these compounds were confirmed by microanalyses and IR, ¹H NMR, and mass spectroscopy. Preliminary biological studies of some of the synthesized compounds showed promising radioprotective and anticancer activities.     

Hybrid-Density Functional Theory Study and Natural Bond Orbital Interpretation of the Conformational Behavior of 1,3-Dioxanyl, 1,3-Dithianyl,and 1,3-Diselenanyl Carbanions

Abstract

The effective factors on the conformational properties of 1,3-dioxanyl (1), -dithianyl (2), and -diselenanyl (3) carbanions have been investigated by means of the hybrid-density functional theory (DFT) (B3LYP/6-311+G**)-based method and natural bond orbital (NBO) interpretation. The results obtained showed that the axial conformation (i.e., the axial H atom attached to C₂) of carbanion 1 is more stable than its equatorial conformation. Contrary to the carbanion 1, the equatorial conformations of carbanions 2 and 3 are more stable than their corresponding axial conformations. The instability of the axial conformations of carbanions 1–3 increases from carbanion 1 to carbanion 2 but decreases from carbanion 2 to carbanion 3. The NBO analysis showed that the anomeric effect (AE) associated with the electron delocalization increases from carbanion 1 to carbanion 2, but decreases from carbanion 2 to carbanion 3. The calculated total dipole moment values of the axial conformations of carbanions 1–3 are greater than those of their corresponding equatorial conformations, but the calculated total dipole moment difference values between the axial and equatorial conformations decreases from carbanion 1 to carbanion 3. Consequently, the AE associated with the electron delocalization, but not the total dipole moment changes (i.e., Δμ_ax–eq), thus explaining the total energy differences between the axial and equatorial conformations of carbanions 1–3. The correlations between the AE, dipole moments, ΔG_ax–eq, structural parameters, and conformational behaviors of carbanions 1–3 have been investigated.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Solution and X-Ray Crystal Structures of the Di- and Tetra-allyl Ether of tert- utylcalix[4]arene

The di- and tetra-allyl ethers of tert-butylcalix[4]arene 1 and 2 have been prepared by alkylation of tert-butylcalix[4]arene with allyl bromide and K₂CO₃ using different reaction times. Solution ¹H NMR measurement of the di-allyl ether 1 and X-ray crystal structures of the complexes of 1 with chloroform (1a) or methanol (1b) indicate the cone conformation of 1 in which intramolecular hydrogen bonding can be maximized. The crystalline state conformers 1a and 1b are distorted in different grades depending on the solvent. While methanol is incorporated in the macrocycle, chloroform molecules do not occupy the cage. The solution ¹H NMR spectra of tetra-allyl ether 2 show the co-existence of the cone and partial cone conformation. The partial cone conformer of 2 was investigated by X-ray crystallography. In this compound hydrogen bonding is not existent. The conformer distribution is likely affected by steric and template effects.     

Synthesis and Antimicrobial Activity of Some New 1,3-Diphenylpyrazoles Bearing Pyrimidine,Pyrimidinethione, Thiazolopyrimidine,Triazolopyrimidine, Thio-and Alkylthiotriazolop-Yrimidinone Moieties at the 4-Position

1,3-diphenyl-1H-pyrazole-4-carboxaldehyde (1) reacted with ethyl cyanoacetate and thiourea to give the pyrimidinethione derivative 2. The reaction of 2 with some alkylating agents gave the corresponding thioethers 3a–e and 7. Thione 2 was cyclized to 5 and 6 upon a reaction with chloroacetic acid and with benzaldehyde, respectively. Thioether 3c was cyclized to 4 upon boiling with sodium acetate in ethanol, and 7 was cyclized to 8 upon boiling in an acetic anhydride-pyridine mixture. The hydrazino derivative 9 was prepared either by boiling 2 and/or 3a with hydrazine. The reaction of 9 with nitrous acid, acetylacetone, triethyl orthoformate, acetic anhydride, and carbon disulfide gave 10–14. The alkylation of 14 with ethyl iodide, phenacyl bromide, and ethyl chloroacetate afforded the alkythiotriazolo pyrimidinone derivatives 15a–c. The dialkyl derivative 16 was produced upon the treatment of 2 with two equivalents of ethyl iodide. Boiling 16 with hydrazine afforded the hydrazino 17. The reaction of 17 with nitrous acid, carbon disulfide, ethyl cyanoacetate, ethyl acetoacetae, and phenacyl bromide gave 18–22, respectively. Some of the newly obtained compounds were tested for their antibacterial and antifungal activities.