5,5,5-Trifluorolaevulic acid and some derived compounds

5,5,5-Trifluorolaevulic acid (II) has been prepared by the acidic hydrolysis of the Claisen condensation product (I) of ethyl trifluoroacetate and diethyl succinate. Dehydration of the acid (II) with phosphoric oxide gave 4-hydroxy-5,5,5-trifluoropent-3-enoic acid lactone (III). Reduction of either this lactone or the acid (II) with lithium aluminium hydride gave 5,5,5-trifluoropentane-1,4-diol (IV), from which 5,5,5-trifluoropenta-1,3-diene (VI) has been obtained by acetylation followed by pyrolysis.     

Condensation reactions of a comenaldehyde derivative

Condensation reactions of comenaldehyde methyl ether (I) with malonic acid, ethyl cyanoacetate, and cyanoacetamide to give β-(5-methoxy-4H-pyran-4-on-2-yl)acrylic acid (II), ethyl 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenoate (III), and 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenamide (IV), respectively, are described. Ultraviolet absorption spectra for 2-hydroxymethyl-5-methoxy-4H-pyran-4-one, I and II are presented.     

一叶秋碱全合成的研究-中间体α-羟酮的合成

α-羟酮是中枢神经药物叶 碱 合中的重要中间体。本文以不同路线合成了α羟酮, 并通过与天然降解物进行光谱对照确定了结构。     

The Reaction of Indole Magnesium Bromide with Ketones I. The Reaction of Indole Magnesium Bromide with Cyclohexanone

Indole magnesium bromide, produced by reacting indole with n-butyl magnesium bromide in ether, was reacted with cyclohexanone at ice or room temperature to yield 1-(indol-I-yl)-cyclohexanol (I), which is unstable and may be decomposed easily into indole and cyclohexanone in acidic condition. Indole magnesium bromide reacted with cyclohexanone in refluxing benzene or in anisole at 80°C, to form two products, 1-(indol-3-yl)-cyclohexanol (II) and 1-(indol-3-yl)-cyclohexene (III). (II) could be converted to (III) by heating (II) in phosphoric acid. Reaction of III with maleic anhydride gave a Diels-Alder adduct (IV). Reaction of indole magnesium bromide with cyclohexanone in anisole at 130°C yielded (III) and a trimolecular condensation product of cyclohexanone (V).     

Benzofurans. Improved syntheses of bufuralol, 7-ethyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran,and 1″-oxobufuralol, 7-acetyl-2-(2-tert-butylamino-1-hydroxyethyl)benzofuran

An improved laboratory scale synthesis of bufuralol ( 1 ) and 1″-oxobufuralol ( 4 ) was accomplished. The intermediate benzofurans were prepared via aromatization of 2,3-dihydrobenzofurans or by a one-step acidcatalyzed cyclization from 2,2-diethoxyethyl 4-bromo-6-ethyl-2-formylphenyl ether ( 23 ). Base-catalyzed cyclization of 3-(5-bromo-3-ethyl-2-hydroxyphenyl)-1.2-epoxypropane ( 16 ) provided the key intermediate, 5-bromo-7-ethyl-2-hydroxymethyl-2,3-dihydrobenzofuran ( 17 ). Selective functionalization of the C-2 and C-7 positions of the benzofuran ring system was accomplished to afford both 1 and 4 .     

Synthesis of nonactin (author's transl)]

Synthesis of Nonactin. The macrotetrolide antibiotic nonactin (I), containing four units of a C₁₀ hydroxy acid, has been synthesized starting from two adequately protected derivatives (III and IV) of nonactic acid (II). The 32-membered ring of the macrotetrolide is built up by a sequence of condensation and deprotection steps leading first to a product with two, and subsequently to one with four nonactic acid residues (VIII) which is then cyclized in the presence of Ag⁺-ions. Two reactions forming ester bonds have been developed to condense the hydroxy acids and to effect the final cyclization. In one the activation of the carboxyl group is achieved by conversion into the mixed anhydride with 2,4,6-trimethylbenzene sulfonyl chloride in pyridine. In the other the Ag⁺-ion induced reaction of a S-(2-pyridyl) hydroxy carbothioate is used to form the corresponding macrocyclic lactone. In the case of nonactin the ring closure is promoted by the coordinating effect of Ag⁺-ions present in the reaction mixture.     

Vitamin B6 analogs

4-Acetyl-3-hydroxy-5-hydroxymethyl-2-methylpyridine 5-phosphate (IV) was synthesized by oxidation of 3-hydroxy-5-hydroxymethyl-4-(-hydroxyethyl)-2-methylpyridine 5-phosphate (III) with chromic anhydride. Compound III was obtained by phosphorylation of 3-hydroxy-5-hydroxymethyl-4-(-hydroxyethyl)-2-methylpyridine with polyphosphoric acid (PPA). The UV and PMR spectra of the synthesized compounds were studied.See [1] for communication XIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 499–503, April, 1971.The authors sincerely thank Academician A. E. Braunshtein for his constant interest in this work, V. I. Ivanov and A. F. Vanin for their fruitful discussions, and K. F. Turchin and I. I. Chervin for kindly providing the possibility for obtaining the PMR spectra.     

Cyclization reactions of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole

The reaction of 3-hydrazino[1, 2, 4]triazino[5, 6-b]indole I with nitrous acid affords the azide III which could be cyclized with acetic anhydride to 10-acetyl-10H-tetrazolo[5′,1′:3, 4][1, 2, 4]triazino[5, 6-b]indole IIb . Cyclization reactions of I with acetic anhydride, ethyl chloroformate, carbon disulphide and aromatic aldehydes to the corresponding fused triazolo derivatives V–VIII are reported. On the other hand cyclization reactions of I with malononitrile, ethyl cyanoacetate, ethyl acetoacetate and acetylacetone to the corresponding condensed pyrazolino derivatives IX–XI are also reported. The reaction of I with α-dicarbonyl compounds to form mono and dihydrazones are reported. The structure of the compounds prepared and their cyclization mechanisms are reported.     

5-vinylisoxazole

Cycloaddition of fulminic acid to 1-butyn-3-ol gave a mixture of 5-α-hydroxyethylisoxazole (I) and 4-α-hydroxyethylisoxazole (II) in the ratio 9:1. By the dehydration of 1, 5-vinylisoxazole (III) was obtained. Compound III has also been prepared by cyclization of 4-penten-2-ynal as well as its diethylacetal with hydroxylamine hydrochloride; in both instances no isomers have been obtained. Compound III spontaneously polymerizes even at room temperature yielding a polymer still containing isoxazole rings.     

Preparation of alpha-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: use of glyoxylic acid hydrazone derivatives

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by beta-bromo alcohols. The resulting esters undergo radical cyclization to alpha-(2,2-diphenylhydrazino)- or alpha-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a beta-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 --> 30) so that an alpha-amino lactone can be generated by acid hydrolysis of the cyclization product.     

甾族化合物不对称合成的研究XV: 光学活性3-氧杂-A-失碳甾族化合物的合成

我们在寻找新的甾体口服避孕药的研究中,设计了A-失碳-3,9(10)-二烯-18-甲基甾体(1)作为全合成研究的目的物.前文已报道从5’-甲基呋喃二噻烷阴离子2b与消旋甾体CD环合成原3b的共轭加成,合成了两个新的消旋3-氧杂-A-失碳甾体4b和5b.本文报道     

合成(±)顺式-3-(二氯乙烯基)-2,2-二甲基环丙烷羧酸的新方法

本文报道两种从5-氯-3,3-二甲基戊酸乙酯(4)合成±)-顺式-3-(二氯乙烯基)-2,2-二甲基环丙烷羟酸(±)的方法.中间体4,4-二甲基-3,4-二氢-2-吡喃酮(3)是从化合物(4)经水解皂化,酸化和氧得到3,3-二甲基戊醛酸甲酯(6),再皂化得到3,3-二甲基戊醛酸(8),然后环化得到;或者由化合物4经苯基硫醚化,氧化得到8,然后环化后得到.     

Synthesis of 14-oxa-1,4,8,11-tetraazabicyclo[9.5.3]nonadecane(L1) and a spectroscopic and structural study of [Ni(L1)(ClO4)](ClO4) and of the macrobicyclic precursor diamide complex, [Ni(HL2)](ClO4); chloride substitution kinetics of the corresponding [Ni(III)(L1)]3+ species

The pentadentate ligand 14-oxa-1,4,8,11-tetraazabicyclo[9.5.3]nonadecane (L1) has been synthesized by the high dilution cyclization of 1-oxa-4,8-diazacyclododecane ([10]aneN(2)O) (1) with 1,3-bis(alpha-chloroacetamido)propane (2) and subsequent reduction of the diamide intermediate. The structure [Ni(L1)(ClO(4))](ClO(4)) (P2(1)/c (no. 14), a = 8.608(3), b = 16.618(3), c = 14.924(4) A, beta = 91.53(3) degrees converged at R = 0.050 (R(w) = 0.046) for 307 parameters using 2702 reflections with I > 2sigma(I). For the nickel(II) complex of the (monodeprotonated) precursor diamide ligand 14-oxa-1,4,8,11-tetraazabicyclo[9.5.3]nonadecane-3,9-dione (H(2)L2), [Ni(HL2)](ClO(4)) (Pbca (no. 61), a = 15.1590(3), b = 13.235(2), c = 18.0195(6) A), the structure converged at R = 0.045 (R(w) = 0.038) for 265 parameters using 1703 reflections with I > 3sigma(I). In the reduced system, the cyclam-based ligand adopts a trans-III configuration. The [Ni(L1)(ClO(4))](2+) ion is pseudooctahedral with the Ni-O(ether) 2.094(3) A distance shorter than the Ni-O(perchlorate) 2.252(4) A. The nickel(II) and nickel(III) complexes are six-coordinate in solution. Oxidation of [Ni(L1)(OH(2))](2+) with K(2)S(2)O(8) in aqueous media yielded an axial d(7) Ni(III) species (g( perpendicular) = 2.159 and g( perpendicular) = 2.024 at 77 K). The [Ni(L1)(solv)](2+) ion in CH(3)CN showed two redox waves, Ni(II/I) (an irreversible cathodic peak, E(p,c) = -1.53 V) and Ni(III/II) (E(1/2) = 0.85 V (reversible)) vs Ag/Ag(+). The complex [Ni(HL2)](ClO(4)) displays square-planar geometry with monodeprotonation of the ligand. The ether oxygen is not coordinated. Ni-O(3) = 2.651(6) A and Ni-O(3a) = 2.451(12) A, respectively. The Ni(III/II) oxidation at E(1/2) = 0.24 V (quasi-reversible) vs Ag/Ag(+) is considerably lower than the saturated system. The kinetics of Cl(-) substitution at [Ni(L1)(solv)](3+) are pH dependent. Detachment of the ether oxygen atom is proposed, with insertion of a protonated water molecule which deprotonates at a pK(a) more acidic than in the corresponding cyclam complex. Mechanistic implications are discussed.     

Metallacycloalkanes : II. Reactions of α,α′-bipyridyl-5-nickela-3,3,7,7-tetramethyl-trans-tricyclo[4.1.0.02,4]heptane

The title compound (II) underwent reductive elimination on treatment with maleic anhydride, tetracyanoethylene or triphenylphosphite to give 3,3,6,6,-tetramethyl-trans-tricyclo[3.1.0.0^2,4]hexane (III). With triphenylphosphite bi(2,2-dimethylcyclopropyl) (V) and 1-(2,2-dimethylcyclopropyl)-3-methyl-1,3-butadiene (VI) were also formed. Acidolysis of II with either HCl, malonic acid or methanol gave V. An intermediate complex α,α′-bipyridyl(phenoxy)-3-nickel-1,1′-bi-(2,2′-dimethylcyclopropyl) (VIII) was isolated by reaction of II with phenol. Methylene dibromide reacts with II to give III and 3,3,7,7-tetramethyl-trans-tricyclo[4.1.0.0^2,4]heptane (IV). With triethylaluminum and II complete exchange of the alkyl groups occurred and V was released on hydrolysis. Trifluoroborane diethyl ether and II gave 3,3,6,6-tetramethylcyclohexa-1,4-diene in a rearrangement-displacement reaction. The cyclodimerisation of 3,3-dimethylcyclopropene (I) to III catalysed by II and the fact that II can be recovered from the reaction mixture provides strong evidence for the intermediacy of metallacyclopentanes in these transition-metal-catalysed [2π + 2π] cyclo-additions.     

Mechanism of 1,4,5,8-naphthalene tetracarboxylic acid dianhydride hydrolysis and formation in aqueous solution

The study of highly conjugated, carbonyl-containing molecules such as 1,4,5,8-naphthalene tetracarboxylic dianhydride, III, is of interest since reactivity differences and transmission of electronic effects through the conjugated framework can be evidenced. The kinetics of hydrolysis of III in aqueous solution were determined from 5 M acid to pH 10. In basic solution hydrolysis of III yields, sequentially, 1,4,5,8-naphthalene diacid monoanhydride, II, and 1,4,5,8-naphthalene tetracarboxylic acid, I. The second order rate constant for alkaline hydrolysis is 200 fold higher for the first ring opening. The water-catalyzed hydrolysis of III yields a pH-dependent mixture of ionic forms of I and II. The rate constant for water-catalyzed hydrolysis of III is 25 fold higher than that for II. In concentrated acid the rates for reaching equilibrium (I, II and III) increase and III is the major product. The pK(a)s of I (3.24, 5.13 and 6.25) and II (3.05, 5.90) were determined by potentiometric, fluorescence and UV spectroscopy titrations and by quantitative fit of the kinetic and equilibrium data. The apparent, pH-dependent, equilibrium constants, K(EqII), for anhydride formation between I and II were obtained from the UV spectra. The quantitative fit of kinetic and equilibrium data are consistent with the assumption that anhydride formation only proceeds with the fully protonated species for both I and II and permitted the estimation of the equilibrium constants for anhydride formation, K(EqII). The value of K(EqII) (I <==> II) between pH 1 and 6 was ca. 5. Geometry optimization calculations in the gas phase of the reactions of III in alkaline, neutral and acid conditions, at the DFT level of theory, gave electronic distributions that were qualitatively consistent with the experimental results.     

5-(2,4-二氯苯氧亚甲基)-2-芳酰胺基-1,3,4-噻二唑的合成

研究了对1-(2,4-二氯苯氧乙酰基)-4-芳酰基氨基硫脲的酸催化环化, 它在酸催化下的环化是定向进行的, 环化途径是生成中间体后脱水而得到5-(2,4-二氯苯氧亚甲基)-2-芳酰胺基-1,3,4-噻二唑, 产物的结构经元素分析, 红外, 核磁以及质谱方法确证。     

Syntheses and Investigation of Some New Polyarylates and Copolyarylates. Part I

By the interfacial condensation of acid chlorides I, II, and III, respectively, with bifunctional phenols (IV-X), soluble or mold-able thermostable polyarylates were obtained. Similarly, copolyarylates were prepared from a mixture of the acid chlorides I + II or I + III. With bisphenol-A (VIII), soluble polymers are usually obtained. Methylene dichloride and/or carbon tetra-chloride-water systems were the best media for interfacial condensations, and the polymers formed showed the highest reduced viscosity values.

Polyester films are useful in many industrial applications because of their broad range of mechanical, optical, and electrical properties. The aromatic polyesters‐polyarylates-dominate the field of industrial polyester films [1].

Polyarylates prepared from dihydric phenols and purely aromatic dicarboxylic acid chlorides are highly heat resistant materials [2], but they are insoluble and nonmoldable [3]. However, by the introduction of ether linkages in the aromatic dicarboxylic acid moiety, soluble and/or moldable polyamides were obtained [4].     

Synthesis of Certain S-Triazole and s-Triazolo[3,4-B] 1,3,4-Thiadiazole Derivatives of Expected Pharmacological Activity

Reaction of the newly prepared 3-(2-thienyl)-4-amino-s-triazole-5-thione (I) with different alkyl kalides and aromatic aldehydes afforded the corresponding thioethers and arylidene derivatives (II and III), respectively. Attempt ring closure of (I) with acetic anhydride produced the unexpected triacetyl derivative (IV). The synthesis of certain 3-(2-thienyl)-6-substituted-s-triazolo[3,4-b] 1,3,4-thiadiazoles (V and VII) was described. IR, NMR and mass spectral analyses of the prepared compounds were discussed.     

Kinetics of anhydride formation in poly(acrylic acid) and its effect on the properties of a PAA-alumina composite

The kinetics of anhydride formation of poly(acrylic acid) (PAA) in porous PAA–alumina composites have been investigated by using a thermogravimetric technique (TGA). Three distinct reaction peaks at 200°C (I), 250°C (II), and 390°C (III) were identified in the dynamic TGA thermogram. These peaks were attributed to bound water removal (I), anhydride formation (II), and polymer degradation (III). The kinetics of the anhydride reaction were studied in a temperature range of 220–240°C and found to follow a second-order mechanism with an activation energy of approximately 38 kcal/mole. In addition, the bound water was found to inhibit the onset of anhydride formation. The degree of conversion to anhydride was correlated with the equilibrium swelling level attained by the composite in water.     

Synthesis and some transformations of bicyclic γ-lactones with a fused cyclopropane ring

Reductive cyclization of 4-hydroxymethyl-5,5-dimethyl(or pentamethylene)-2,5-dihydrofuran-2-ones by the action of sodium tetrahydridoborate gave bicyclic compounds in which the lactone ring is fused to a cyclopropane ring. Hydrolysis of the products with aqueous sodium hydroxide resulted in the formation of the corresponding disodium cyclopropane-1,1-dicarboxylates, which reacted with alkyl halides to produce the diesters. Acid hydrolysis of the fused systems was accompanied by opening of the cyclopropane ring with formation of 4-chloromethyl-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylic acid.