Construction of anomalously bent biphenyl structure using conformational properties of calix[4]amide

C_2v-symmetrical cyclic tetramers of aromatic amides were simply synthesized in moderate yield by condensation reaction of N,N′-dimethyl-1,3-phenylenediamine and isophthalic acid derivatives using dichlorotriphenylphosphorane. The calix[4]amides exist in 1,3-alternate structure with cis conformation of tertiary aromatic amides, which were shown to be a versatile scaffold leading to a bowl-shaped macrocyclic compound possessing a anomalously strained structure, a bent hinge angle between two aromatic ring planes of biphenyl moiety, via an intramolecular ligation reaction.     

Synthesis of new thiazole analogues of pyochelin, a siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. A new conversion of thiazolines into thiazoles

Three pyochelin analogues and their methyl esters all containing a thiazole ring have been synthesised from the same Weinreb amide key intermediate. One of these analogues called HPTT-COOH, a molecule released in the course of pyochelin and yersiniabactin biosynthesis, was efficiently synthesised using a new base induced conversion of the key compound 2′-(2-hydroxyphenyl)-2′-thiazoline-4′-(N-methoxy,N-methyl) carboxamide into 2′-(2-hydroxyphenyl)-2′-thiazole-4′-(N-methoxy,N-methyl) carboxamide.     

Spectroscopic studies and PM5 semiempirical calculations of new hydrazone of gossypol with 3,6,9-trioxadecylhydrazine

A new hydrazone of gossypol with 3,6,9-trioxadecylhydrazine (GHTO) has been synthesised and its structure has been studied by ¹H NMR, ¹³C NMR, FT-IR spectroscopy and PM5 semiempirical methods. The results have shown that the newly synthesised hydrazone exists in solution in the N-imine–N-imine tautomeric form, stabilized by several intramolecular hydrogen bonds among which the O₇H N₁₆ intramolecular hydrogen bond is the strongest. The structure of GHTO is visualized by the PM5 semiempirical calculations.     

The synthesis of 1-amino-2-hydroxy- and 2-amino-1-hydroxy-substituted ethylene-1,1-bisphosphonic acids and their N-methylated derivatives

A synthesis of 2-amino-1-hydroxyethylene-1,1-bisphosphonic acid 3 has been developed from N-phthaloylglycine via dimethyl 2-(N-phthaloylamino)acetylphosphonate 1. The preparation of the N-methylated and N,N-dimethylated derivatives 4 and 5 has been achieved by the reaction of 3 with formic acid and formaldehyde. The synthesis of 1-amino-2-hydroxyethylene-1,1-bisphosphonic acid 9 (R=R′=H) and its N-methylated and N,N-dimethylated analogues has been achieved by the reaction of phosphorus trichloride and phosphorous acid with the appropriate O-benzyl protected hydroxyacetamide, followed by catalytic hydrogenolysis of the protecting group.     

Spectroscopic and PM5 semiempirical studies of new hydrazone of gossypol with 3,6-dioxaheptylhydrazine

A new hydrazone of gossypol with 3,6-dioxaheptylhydrazine (GHDO) has been synthesised and its structure has been studied by FT-IR, ¹H NMR, ¹³C NMR as well as PM5 semiempirical methods. All the studies have provided clear evidence of the existence of GHDO in the solution in the N-imine–N-imine tautomeric form. The structure and the spectroscopic behaviour of this tautomer are discussed in details. It is shown the structure of GHDO is strongly stabilised by different types of intramolecular hydrogen bonds. In two of them the oxygen atoms of the oxaalkyl chains are also engaged. The strongest intramolecular hydrogen bond is formed between the O₇H proton and N₁₆ atom from the hydrazone group.     

Reagent for the detection and determination of N-active hydrogen

A colour-yielding reagent has been developed for sulphon-amides, acid amides, and other compounds containing N-active hydrogen. It consists of an aqueous pyridine solution of cyanide and either barbituric acid or 1-phenyl-3-methyl-2-pyrazolin-5-one and is applied after initial chlorination of the sample. Amounts down to 0.1 μg or less can be detected on TLC plates. The possibilities of quantitative determination have been investigated briefly.     

利用三中心氢键限制芳酰胺构象的核磁共振氢谱分析

设计并合成了9个可形成三中心氢键和6个可形成二中心氢键的N-芳基芳酰胺模型化合物, 基于它们在氯仿和二甲基亚砜(DMSO)中的一维核磁共振波谱, 系统地分析了羰基对βH和γH的去屏蔽效应. 将Δ(δ_βH)和Δ(δ_γH)的值结合在一起, 分析了三中心氢键对芳酰胺分子的构象限制效果, 发现N-(2-氟苯基)-2-氟苯甲酰胺、 N-(2-甲氧基苯基)-2-氟苯甲酰胺和N-(2-氟苯基)-2-甲氧基苯甲酰胺这3个N-芳基芳酰胺在酰胺基团的左右两侧都能展现出很好的构象控制效果, 因此认为这3种结构单元在构建折叠体方面具有更大的潜力. 此外, 本文还发现, 当NH与第二个氢键受体形成氢键时, 其和第一个氢键受体之间的氢键就被削弱了, 即在芳酰胺形成三中心氢键时, 2个氢键受体争相与NH形成氢键并取得了某种平衡.     

Synthesis of 2-oxazolines mediated by N,N′-diisopropylcarbodiimide

N-(β-Hydroxy)amides can be cyclised by reaction with diisopropylcarbodiimide (DIC) to give the corresponding 2-oxazolines in high yields. The reaction requires only very mild Lewis-acid catalysis (5 mol % Cu(OTf)₂) and can be accomplished with simple heating, or in very short reaction times under microwave irradiation.     

吡唑[1,5-a]并吡啶-3-羧酸衍生物合成方法的改进

以取代吡啶为原料,在羟胺-O-磺酸的作用下,得到取代的N-氨基吡啶的硫酸盐,再通过1,3-偶极环加成反应,与丙炔酸乙酯生成吡唑[1,5-a]并吡啶-3-羧酸乙酯衍生物,然后在质量分数30%的NaOH水溶液作用下水解成酸。 该方法将取代的N-氨基吡啶的硫酸盐直接投入到下步反应,省去传统方法中将硫酸盐转化为碘盐的步骤,解决了碘盐不易析出的问题,并将取代的N-氨基吡啶硫酸盐和丙炔酸乙酯分别用水和二甲基甲酰胺溶解后再混合,增加了原料和K₂CO₃在体系中的溶解性,提高了产率。 本文成功合成了6种化合物(4a~4f),产率为88%~93%,该方法条件温和,后处理简单,成本低,是适合大规模生产的新工艺。     

Synthesis and thermal decomposition of N,N-dialkoxyamides

N,N-dialkoxyamides 1c, a virtually unstudied member of the new class of anomeric amides, amides bearing two electronegative atoms at nitrogen, have been synthesised in useful yields directly from hydroxamic esters using phenyliodine(III)bis(trifluoroacetate) (PIFA). Infrared carbonyl stretch frequencies and carbonyl (13)C NMR properties have been reported, which support strong inhibition of amide resonance in these amides. Their thermal decomposition reactions in mesitylene at 155 °C proceed by homolysis to form alkoxyamidyl and alkoxyl free radicals in preference to HERON rearrangements to esters. The reactions follow first-order kinetics and for a series of N,N-dimethoxy-4-substituted benzamides, activation energies of 125-135 kJ mol(-1) have been determined together with weakly negative entropies of activation.     

The application of the sulphide contraction to the synthesis of some simple pyrrolidine alkaloids

The alkaloids (±)-hygrine, (±)-dehydrodarlinine, (±)-dehydrodarlingianine, and (±)-N-methylruspolinone have been synthesised by selective reduction of vinylogous amides formed by sulphide contraction of the salts prepared by reaction of N-methyl-2-thiopyrrolidone with the appropriate bromomethyl ketones.     

Synthesis and conversions of 2-substituted cinchoninic acid amides

Amides of 2-oxo- or 2-thiocinchoninic acid have been obtained by the reaction of substituted amides of 2-chlorocinchoninic acid with sodium acetate or sodium sulfide. The reaction of 2-thiocinchoninic acid amides with hydrazine hydrate or ethyl cyanoacetate leads to derivatives of 2-hydrazinocinchoninic acid or (4-carbamoyl-2-quinolyl)cyanoacetic ester respectively, which were also obtained from 2-chlorocinchoninic acid amides.Perm Pharmaceutical Academy, Perm 614600. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 697–700, May, 1997.     

Coulometric titration of iron by electrolytically generated bromine

Iron^II reacts with bromine more smoothly in acetic acid-sodium acetate medium than in sulphuric acid medium, producing a marked potential change at the end-point. The titration curves and the reaction velocities of the reaction have been studied with regard to various compositions of the electrolytic solution. It was found that iron^IIfrom 0.01 meq to 0.1 meq could be titrated coulometrically with less than about 1% error, if the electrolytic solution contained 0.1M potassium bromate, 1N acetic acid and 0.2N sodium hydroxide.     

Metal complexes of biologically important ligands: Synthesis of amino acidato complexes of Pd containing a C,N-cyclometallated group as an ancillary ligand

New amino acidato complexes of Pd^II of stoichiometry [Pd(C---N)(Aa)] (C---N=C,N-cyclometallated ligand, Aa = N,O-amino acidato ligand) have been obtained by reaction of [Pd(C---N)(acac)] (C---N=N,N-dimethylbenzylamine-C²,N (dmba) (1) or N,N-dimethyl(S--phenylethyl)amine-C²,N (S-dmphea) (2)) with glycine, chiral amino acids (alanine, phenylalanine and valine), and amino acid derivatives (N-acetylglycine and N-acetyl-,β-dehydroalanine) in MeOH. The compounds are characterized by IR, ¹H and ¹³C NMR. The geometry of these complexes has been unambiguously determined by NOE difference experiments and NOESY measurements.     

Comparative study of some synthesised and commercial fluorogenic substrates for horseradish peroxidase and its mimetic enzyme hemin by a flow injection method

Four 3,4-dihydroquinoxalin-2(1H)-one derivatives, i.e., 3,4-dihydroquinoxalin-2(lH)-one (DHQ), 3-methyl-3,4-dihydroquinoxalin-2(1H)-one (MDHQ), 3,4-dihydroquinoxalin-2(1H)-one-6-acid (DHQ-6-A) and 3-methyl-3,4-dihydroquinoxalin-2(1H)-one-6-acid (MDHQ-6-A), and N,N′-dicyanomethyl-o-phenylenediamine (DCM-OPA) were synthesised as potential substrates for horseradish peroxidase (HRP). Of these compounds DCM-OPA, DHQ and MDHQ can be prepared by very simple methods in a pure form in large quantities. Their properties for use as fluorogenic substrates for HRP and its mimetic enzyme hemin were compared with commercially available substrates, i.e., p-hydroxyphenylacetic acid (p-HPA), p-hydroxyphenylpropionic acid (p-HPPA), homovanillic acid (HVA) and tyramine, by a flow injection method. The results showed that DCM-OPA and MDHQ were the best among the five synthesised substrates and p-HPPA and p-HPA are better than HVA and tyramine. Substrates p-HPPA, p-HPA, DCM-OPA and MDHQ showed comparable ability for H₂O₂ detection in HRP and hemin catalysed reaction systems, with detection limits in the nmol l⁻¹ region. The stability of DCM-OPA is better than MDHQ, but both are stable for at least a month in a refrigerator.     

Chiral Non-racemic Bis(vicinal 1,2-Diamines): 4,5-Diamino-N-(3,4-diaminobutyl)pentanamide Tetrahydrochloride, N,N′-Bis[3,4-bis (t-butoxycarbonylamino)butyl]urea and N,N′Bis

The reaction of (R) or (S)-N⁴,N⁵-bis(t-butoxycarbonyl)-4,5-diaminopentanoic acid (6) with (R) or (S)-N³,N⁴-bis(t-butoxycarbonyl)-3,4-diaminobutylisocyanate (8) catalyzed by 4-dimethylamino pyridine (DMAP), leads to the synthesis of (R,R), (S,S), (R,S) and (S,R) isomeric amides (11 a — d) The addition of adipic acid monomethyl ester to (R) or (S) isocyanate, followed by saponification, acidification and subsequent reaction with the second molecule of (R) or (S) isocyanate allows isolation of the (R,R), (S.S) and the meso isomers of N,N′-bis[3,4-bis(t-butoxycarbonylamino) butyl]hexanediamide (17) Removal of protecting groups with HCl/EtOH affords chiral non-racemic molecules having two free vicinal diamine units.     

Synthesis of N-acyl-N,alpha,alpha-trialkyl and N-acyl-alpha,alpha-dialkyl glycines by selective cleavage of Ugi-Passerini adducts. Qualitative assessment of the effect of substituents on the path and yield of reaction

Several symmetric N-acyl-N,alpha,alpha-trialkyl glycine amides were synthesised by the Ugi-Passerini four-component reaction and subjected to selective cleavage with trifluoroacetic acid. In almost all cases it was possible to obtain the corresponding N-acyl-N,alpha,alpha-trialkyl and N-acyl-alpha,alpha-dialkyl glycines in fair to good yields directly from the reaction adducts. With some of the bulkier compounds our results show that the selectivity of cleavage is concentration dependent with respect to the acid, which suggests kinetically controlled processes. The isolation of a stable oxazolone as the product of some of the reactions seems to confirm that amide cleavage involves in all cases formation of an oxazolone-type derivative.     

Determination of fatty acid amides as trimethylsilyl derivatives by gas chromatography with mass spectrometric detection.

Fatty acid amides are a newly emerging class of compounds with biological activity. The amides are formed enzymatically in vivo. Analysis of fatty acid amides has been accomplished by gas chromatography coupled with mass spectrometry. Fatty acid amides required derivatization prior to analysis at high temperatures due to thermal instability. Trimethylsilylation of fatty acid amides has been accomplished under optimum reaction conditions. The limit of detection for the silylated amides is approximately 1 pmol, with the lowest detected level being 700 fmol for the lauramide derivative. Quantitation of fatty acid amide derivatives can be accomplished by monitoring m/z 59 or m/z M-71, the only two major fragments formed in the ion trap mass spectrometer with electron impact ionization. The smaller fragment is the result of a newly reported, McLafferty-type rearrangement; M-71 resulted from loss of an n-pentyl fragment. Either peak gave four-five orders of magnitude linear dynamic range. Numerous trimethylsilylamides from C7 to C20 were separated under standard conditions. Elution was linear with the number of carbons and was systematically affected by the number and position of the double bonds.     

Synthetic routes to 1,5-dihydro-5-oxo-4,1-benzoxazepines and to 5-oxooxazolo[3,2-a]quinolines

The literature concerning phenacyl anthranilate, N- phenacylanthranilic acid and phenacyl N-phenacylanthranilate is clarified. Phenacyl anthranilate is dehydrated to 1,5-dihydro-5-oxo-2-pheny 1-4,1-benzoxazepine by treatment with phosphoryl chloride; other examples of this reaction are described. A preparation of 4-methyl-5-oxo-2-phenyloxazolo[3,2-a]quinoline from N-phenacylanthranilic acid and propionic anhydride is reported.