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.     

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.     

MECHANISM OF THE REACTION OF SOME STABLE HEMIMERCAPTALS WITH Secondary-AMINES: EVIDENCE AGAINST THE INTERMEDIACY OF A METHYLENESULFONIUM ION

Abstract

The reaction of the arenethiols 4a-b with formaldehyde and the sec-amines 5a-c gave the aminomethyl aryl sulfides 6a-d. The reaction of the hemimercaptals 3a-b with 5a in methanol gave 6a-b in high yield. In acetonitrile reaction media, 6b was obtained by the reaction of 3b with 5a which suggested that 7b was not an intermediate in the formation of 6b in methanolic media. The absence of 7b in methanolic media suggests that the methylenesulfonium ion 8b is not an reaction intermediate. The formation of 7b was observed in the reaction of 3b with methanol when catalyzed by the Lewis acid tetrafluoroboric acid diethyl ether complex. The experimental observations are best explained by a mechanism whereby 3a-b are in rapid equilibrium with 4a-b under the basic reaction conditions. Rapid reaction of the liberated formaldehyde with 5a leads to the normal Mannich reaction pathway. Consistent with this mechanism, the reaction of a mixture of 3a-b and 12 with 5a gave both 6a-b and 13.     

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.     

SYNTHESIS OF SOME NEW HETEROCYCLIC COMPOUNDS FROM BENZOPYRANO[2,3-c]PYRAZOL-3-ONE DERIVATIVES

The reaction of benzopyrano[2,3-c]pyrazol-3-one (1) with some active halo compounds, afforded compounds 4, 8 and 12, respectively. The cyanoethyl derivative 19 was synthesized and treated with active methylenes and sulfur or benzoylisothiocyanate and phenacyl bromide, to give compounds 24_a,b and 27. Compounds 25_a,b and 28 were obtained through the reaction of compounds 24_a,b with acrylonitrile or compound 27 with maleic anhydride. Thiation of compound 1 afforded the corresponding thio derivative 29. The reaction of 4-benzylidene-2-methyloxazolin-5-one with compounds 1 or 29 gave products 30_a,b , respectively.     

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 .     

Design,synthesis, and antimicrobial activity of fluorophore 1,2,3-triazoles linked nicotinonitrile derivatives

The synthesis and investigation of fluorescence and antimicrobial properties of a new series of 1,2,3-triazoles were described. Acetylenes 4a–c were resulted via alkylation of 2-oxonicotinonitriles 3a–c with propargyl bromide in base medium. [2?+?3] cycloaddition of acetylenes 4a–c with ethyl 2-azidoacetate, p-acetylphenylazide, and p-tolylsulfonylazide in the presence of Cu(I) afforded 1,2,3-triazoles 5a–c, 7a–c, and 9, respectively (via click reaction). The triazoles 5a–c were subjected to saponification process to give the acids 6a–c. The fluorescence and antimicrobial properties of triazoles 5a–c, 7a–c, and 9 were investigated and significant results were obtained.     

N-1-Naphthyl-3-oxobutanamide in Heterocyclic Synthesis: A Facile Synthesis of Nicotinamide,Thieno[2,3-b]pyridine,and Bi- or Tricyclic Annulated Pyridine Derivatives Containing Naphthyl Moiety

N-1-Naphthyl-3-oxobutanamide (1) reacts with arylidinecyanothioacetamide 2a–c in ethanol/piperidine solution under reflux to yield the pyridine-2(1H)-thiones 6a–c. Compound 6a reacts with α-haloketones 7a–e to give the 6-thio-N-1-naphthyl-nicotinamides derivatives 8a–e, which cyclized to thieno[2,3-b]pyridine derivatives 9a–e. The reaction of compound 9a with hydrazine hydrate and formamide gives the thieno[2,3-b]pyridine carbohydrazide derivative 10 and pyridothienopyrimidine derivative 11, respectively. Reaction of 9a with benzoyl isothiocyanate gave thiourea derivative 12. Compound 12, upon treatment with alcoholic NaOH, gave pyridothienopyrimidine 13. Saponifications of 9a gave the amino acid 15, which affords 16 when refluxed in Ac₂O. Treatment of compound 16 with AcONH₄/AcOH gave 17. Diazotization and self-coupling of 9b gave the pyridothienotriazine 18. Also, diazotization of the ortho-aminohydrazide 10 give the corresponding azide 19, which was subjected to Curtius rearrangement in boiling xylene to give imidazothienopyridine 20. Reaction of 10 with either formic acid or triethylorthoformate and phenyl isothiocyanate gave the corresponding pyridothienotriazepines 22 and 23, respectively. The interaction of 10 with acetylacetone furnished the pyrazolyl derivative 24. The structures of the synthesized compounds were established from their analytical and spectral data.     

Einige Neue N,S-Substituierte 2-Nitrodienverbindungen Aus Reaktionen Von Mono(p-fluorarylthio)substituierten Dienen Mit Aminen

2-Nitrodiene compound 1 was stirred with p-fluorothiophenol for a long time and compound 3 was obtained. Compound 1 gave bis(thio)substituted 2-nitrodiene compound 4 and tris(thio)substituted compound 5 with 2 moles of p-fluorothiophenol in the presence of NaOH in ethanol. The compounds 9a–g have been prepared from 8a–g and 3. Compound 7 was obtained from the reaction of mono(thio)substituted 2-nitrodiene with morpholine. Compound 3 gives 11a–d in the reaction with piperidines in CH₂Cl₂ (or ether). Compound 13a–b have been obtained from the reaction of compound 3 with primary amines 12a–b. Compound 3 gives 15 and 16 in the reaction with 2,5-dimethylpiperazine in CH₂Cl₂.

     

Studies on Spiroheterocycles,Part II: Heterocyclization of the Spiro Compounds Containing Cyclohexanone and Thiobarbituric Acid with Different Bidentate Nucleophilic Reagents

The reaction of thiobarbituric acid with different diarylidene ketones 1a–c yields the spiro compounds 2a–c. The diarylidene derivatives 3a–c are synthesized by the condensation of spiro compounds 2a–c with different aldehydes. A series of spiro heterocycles compounds 4a–l, 5a–l, 6a–l, 7a–l, 8a–l, and 9a–l are synthesized from the diarylidene compounds. The structures of the compounds are ascertained from their analytical and spectral data. Some of the compounds are screened for their biological activities.     

New N,S-Substituted Nitrobutadienes from Mono(Arylthio)Substituted Nitrobutadienes

N,S-Substituted nitrobutadienes 3a–g were synthesized from the reaction of the thiosubstituted derivatives 1a–g with thiomorpholine 2. The N,S-substituted nitrobutadienes 5a–g were obtained from the reaction of the thiosubstituted butadienes 1a–g with N-diphenylmethyl piperazine 4. The structure of butadiene 3c was elucidated by single crystal X-ray diffraction.     

Structural insight into the anion–water cluster: stabilised by alcohol and carboxylic acid containing tripodal ligand

A new flexible N-bridged, unsymmetrical, water-soluble tripodal ligand (L) bearing alcohol and carboxylic acid groups has been synthesised and its solid-state interaction with anions has been investigated. The fully deprotonated ligand encapsulates a sodium cation in a half cryptand bowl-shaped cavity (1). The chloride complex 2, contains a cyclohexane-like water cluster incorporating ligand OH groups. However, complexes with bromide and nitrate (3 and 4) are dimeric. Tetrahedral clusters containing two water molecules and two anions were found in complexes 3 and 4. Perchlorate complex 5 forms perchlorate–methanol adducts. Complex 1 forms a hydrophilic cation–water channel and complexes 2–4 form anion–water channels between the hydrophobic layers of the naphthalene moieties. Complexes 2, 5 and 3, 4 are isostructural in nature having similar packing structures.     

Chemo- and Regioselective 1,3-Dipolar Cycloaddition of 2-Diazopropane over 1,4-Benzoquinone: Synthesis of New Pyrazoloquinones

Abstract

1,3-Dipolar cycloaddition reaction of 2-diazopropane 1 with 1,4-benzoquinone 2 carried out at ?20 °C led to a minor mono-cycloadduct 4 and mixture of bis-cycloadducts 6 and 7. The same addition realized with 3H-pyrazole 7 at ?60 °C for 2 h yields a mixture of compounds 8 and 9 and results in O-alkylation. The reaction of 3H-pyrazoles 4 and 7 with dimethylsulfoxide and oxalyl chloride under Swern conditions led to pyrazolenines 11 and 12.     

Aqua substitution from mononuclear Pt(II) complexes with 2-(pyrazol-1-ylmethyl)quinoline non-leaving ligands

The rates of aqua substitution from [Pt{2-(pyrazol-1-ylmethyl)quinoline}(H₂O)₂](ClO₄)₂, [Pt(H₂Qn)], [Pt{2-(3,5-dimethylpyrazol-1-ylmethyl)quinoline}(H₂O)₂](ClO₄)₂, [Pt(dCH₃Qn)], [Pt{2-[(3,5-bis(trifluoromethyl)pyrazol-1-ylmethyl]quinoline}(H₂O)₂](ClO₄)₂, [Pt(dCF₃Qn)], and [Pt{2-[(3,5-bis(trifluoromethyl)pyrazol-1-ylmethyl]pyridine}(H₂O)₂](ClO₄)₂, [Pt(dCF₃Py)], with three sulfur donor nucleophiles were studied. The reactions were followed under pseudo-first-order conditions as a function of nucleophile concentration and temperature using a stopped-flow analyzer and UV/visible spectrophotometry. The substitution reactions proceeded sequentially. The second-order rate constants for substituting the aqua ligands in the first substitution step increased in the order Pt(dCH₃Qn) < Pt(dCF₃Qn) < Pt(H₂Qn) < Pt(dCF₃Py), while that of the second substitution step was Pt(dCH₃Qn) < Pt(dCF₃Qn) < Pt(dCF₃Py) < Pt(H₂Qn). The reactivity trends confirm that the quinoline substructure in the (pyrazolylmethyl)quinoline ligands acts as an apparent donor of electron density toward the metal center rather than being a π-acceptor. Measured pK_a values from spectrophotometric acid–base titrations were Pt(H₂Qn) (pK_a1 = 4.56; pK_a2 = 6.32), Pt(dCH₃Qn) (pK_a1 = 4.88; pK_a2 = 6.31), Pt(dCF₃Qn) (pK_a1 = 4.07; pK_a2 = 6.35), and Pt(dCF₃Py) (pK_a1 = 4.76; pK_a2 = 6.27). The activation parameters from the temperature dependence of the second-order rate constants support an associative mechanism of substitution.     

基于5-孟氧基-3-溴-2(5H)-呋喃酮的环丙烷合成方法研究:碳亲核试剂启动的不对称串联反应

研究碳亲核试剂(2a～2e)与手性合成砌块, 5-孟氧基-3-溴-2(5H)-呋喃酮的不对称串联反应, 分别得到不同结构的光学活性化合物3a～3d, 4, 5和6. 通过X射线晶体分析确认了它们的立体化学结构.     

Synthese Originale de 5-Aryl (ou 5-benzyl)-2[(1-Diethoxyphosphonyl)methyl]-1,3,4-oxadiazoles par Action du Phosphonomethylhydrazide sur les Imidates N-Acyles

The phosphonomethylhydrazide 2a reacts with N-acylated imidates 3a–d to give the corresponding 5-aryl (or 5-benzyl)-2-[(1-diethoxyphosphonyl)methyl]-1,3,4-oxadiazoles 4a–d after the elimination of ethanamide 5. Compounds 2a–e are prepared by the action of triethyl phosphonoacetate 1 with hydrazine and its derivatives. The structures of 1,3,4-oxadiazoles 4a–d and hydrazides 2a–e have been unequivocally confirmed by means of IR, ¹ H, ¹³ C, ³¹ P NMR and mass spectrometry.     

2-Amino-2-Deoxytetrose Derivatives. 2. Preparation from d-Glyceraldehyde Acetonide: A Reinvestigation

Abstract

A diastereomeric mixture of nitriles 1a,b was prepared by a Strecker synthesis from D-glyceraldehyde acetonide and benzylamine. The reported selective hydrolysis of the acetonide group of 1a could not be accomplished. Nitrile diastereomers 1a,b were carried forward as a mixture to amines 3a,b where the diastereomers were readily separable. The hydrochloride of 3a was transformed via sequential debenzylation, N-acetylation, reduction, and exhaustive acetylation to the 2-amino-2-deoxy-D-threose derivatives 5 and 6. The corresponding 2-amino-2-deoxy-D-erythrose derivatives 10a and 11 were prepared similarly from amine 3b.     

Synthesis of Some Bicyclic Thiazolopyrimidine Derivatives

Thiazolopyrimidine compounds 3(a–d) were synthesized by a simple one-pot condensation reaction of starting pyrimidine derivative 1 and 1,2-dibromoethane 2 in dimethylformamide. In a similar way thiazolopyrimidine compounds 5(a–e) were synthesized by reaction of 1 and 2-bromopropionic acid 4 in dioxane under reflux condition. The yields of products following recrystallization from ethanol were of the order of 70–80%.     

The Synthesis of Triazolothiadiazines and Thiadiazoles From 1,2-Bis-(4-amino-5-mercapto-1,2,4-triazol-3-yl)- Ethanol and Ethane

The reaction of DL-malic and succinic acids with thiocarbohydrazide afforded 1,2-bis[4-amino-5-mercapto-1,2,4-triazol-3-yl]-ethane derivatives 3a and 3b. The reaction of 3a,b with phenacyl bromide and benzoin afforded 1,2-bis-1,2,4-triazolo [3,4-b][1,3,4]thiadiazine derivatives 4 and 5. The carboethoxymethylation of 3a and 3b gave 6a and 6b, respectively, and their reactions with carbon disulfide and benzoylisothiocyanate gave the 1,2-bis-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole 7 and 9, and with p-nitrobenzaldehyde gave a Schiff's base and dihydrothiadiazole 8. The structures were confirmed by using ¹ H and ¹³ C NMR spectra. Selected members of these compounds were screened for antimicrobial activity.     

ORGANISCHE PHOSPHORVERBINDUNGEN 80 HERSTELLUNG VON TRIAZOLYLMETHYL-PHOSPHONATEN UND VON TRIAZOLYL-METHYLPHOSPHONIUMSALZEN UND DEREN VERWENDUNG IN DER WITTIG-HORNER REAKTION

Abstract

Attempts to prepare 1H-1,2,4-triazol-1-ylmethylphosphonates (4 and 5) by a Mannichtype reaction or by transesterification of 1-hydroxymethyl-1H-1,2,4-triazol 1 with tertiary phosphites failed. On the other hand 4 and 5 are obtained by a Michaelis-Becker reaction from 1-chloromethyl-1H-1,2,4-triazol 3 and sodium phosphites in high yield. The Michaelis-Arbuzov reaction is less suited for the preparation of 4 and 5. 3 is obtained in good yield as a water clear liquid, b.p. 52–54°C/0.2 torr, from the interaction of 1 with thionyl chloride followed by treatment with a base. On standing at 0° or 20°C it decomposes within hours and yields the unsymmetrical methylen-bis(triazol) 3a in addition to other products. However an acetonitrile solution of 3 is stable for months. Heating this solution with tertiary phosphines gives triazolylsubstituted phosphoniumsalts 6 to 8. The Wittig-Horner reaction with 4 to 6 gives the olefinically substituted triazols 9–12 as a Z/E mixture in high yield. Alkylation of 4 with methyl-and ethyl iodide gives the corresponding alkylated diethyl-1H-1,2,4-triazol-1-yl-ethyl-1-and-propyl-1-phosphonates 14 and 15 which on hydrolysis with HCI yield 1H-1,2,4-triazol-1-yl-ethyl-1-and propyl-1-phosphonic acids 17 and 18, respectively. Hydrolysis of 4 gives the unsubstituted 1H-1,2,4-triazol-1-ylmethyl-phosphonic acid, 16.