4,5,6,7-Tetrachlorobenzo[d][1,3,2]dioxaborol- 2-ol as an effective catalyst for the amide condensation of sterically demanding carboxylic acids

[reaction: see text] 4,5,6,7-Tetrachlorobenzo[d][1,3,2]dioxaborole (4a) and 4,5,6,7-tetrachlorobenzo[d][1,3,2]dioxaborol-2-ol (4b) are effective catalysts for the dehydrative amide condensation between an equimolar mixture of carboxylic acids and amines. In particular, these catalysts are greatly superior to 3,5-bis(trifluoromethyl)phenylboronic acid (1) for the amide condensation of sterically demanding carboxylic acids. In contrast, 4c, which is prepared from a 1:2 molar mixture of B(OH)(3) and tetrachlorocatechol, is effective as a Lewis acid-assisted Br?nsted acid (LBA) catalyst for Ritter reaction.     

Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine as orally-active adhesion molecule inhibitors

Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.     

Synthesis of 1, 2-diazabicyclo [2.2.2] octane, 1, 2-diazabicyclo [3.2.1]-octane,and their derivatives

1, 2-Diazabicyclo [2.2.2] octane, its 6-methyl homolog, and 1, 2-diazabicyclo [3.2.1] octane are synthesized by a general method involving nitrosation of piperidine carboxylic acids, subsequent reduction to 1-aminopiperidine carboxylic acids, cyclization to 3-keto-1, 2-diazabicycloalkanes, reduction of the latter to 1, 2-diazabicycloalkanes. A number of 2-substituted 1, 2-diazabicyclo [2.2.2] octanes are synthesized.     

Electrocarboxylation of benzyl halides through redox catalysis on the preparative scale

The electrocarboxylation of benzyl halides to the corresponding carboxylic acids through homogeneous charge-transfer catalysis was investigated both theoretically and experimentally to determine the influence of the operative parameters on the yield of the process and on the catalyst consumption. Theoretical considerations, based on fast kinetics of redox catalysis, were confirmed by the electrocarboxylation of 1-phenyl-1-chloroethane catalyzed by 1,3-benzenedicarboxylic acid dimethyl ester performed at a carbon cathode under different operative conditions. We obtained high yields of the target carboxylic acid and experienced a low catalyst consumption by operating with optimized [RX]bulk/[CO2]bulk and [RX]bulk/[catalyst] ratios.     

Brønsted acidic ionic liquids and their zwitterions: synthesis, characterization and pKa determination

Imidazolium chlorides with one or two carboxylic acid substituent groups, 1-methyl-3-alkylcarboxylic acid imidazolium chloride, [Me[(CH2)nCOOH]im]Cl (n=1, 3), and 1,3-dialkylcarboxylic acid imidazolium chloride, [[(CH2)nCOOH]2im]Cl (n=1, 3), have been synthesized via their corresponding acid esters. Deprotonation of the carboxylic acid functionalized imidazolium chlorides with triethylamine affords the corresponding zwitterions [Me[(CH2)nCOO]im] (n=1, 3) and [[(CH2)nCOOH][(CH2)nCOO]im] (n=1, 3). Subsequent reaction of the zwitterions with strong acids gives the new imidazolium salts [Me[(CH2)nCOOH]im]X (n=1, 3; X=BF4, CF3SO3) and [[(CH2)nCOOH]2im]X (n=1, 3; X=BF4, CF3SO3), which exhibit melting points as low as -61 degrees C. The solid-state structures of two of the carboxylic acid functionalized imidazolium salts have been determined by single-crystal X-ray diffraction analysis. Extensive hydrogen bonding is present between the chloride and the imidazolium, with eight Cl.H interactions below 3 A. The pK(a) values of all the salts, determined by potentiometric titration, lie between 1.33 and 4.59 at 25 degrees C.     

Carboxylic acid clathrate hosts of Diels-Alder adducts of phencyclone and 2-alkenoic acids. Role of bidentate C-H ... O hydrogen bonds between the phenanthrene and carbonyl groups in host-host networks

Carboxylic acid host compounds (3) having a phenanthrene-condensed bicyclo[2.2.1]hept-2-en-7-one skeleton have been synthesized by the [4 + 2]pi cycloaddition of phencyclone (1a) with 2-alkenoic acids (2) and their inclusion behavior was investigated. The endo [4 + 2]pi cycloadducts (3) enclathrated alcohols and ethers besides aromatics and ketones. The X-ray crystallographic analysis of the inclusion compound (3ac-dioxane) of the endo [4 + 2]pi cycloadduct (3ac) of phencyclone and trans 2-butenoic acid (2c) indicated that dioxanes are located at the opposite side of the bridged carbonyl of the bicyclo[2.2.1]hept-2-en-7-one moiety, in which the O-H...O and C-H...O hydrogen bonds play an important role in the inclusion complex formation. Similarly, a pair of 3-pentanone molecules were included in the endo [4 + 2] pi cycloadduct (3ae) of 1a and cinnamic acid (2e). In both cases, the hosts are linked by the edge-to-face interaction between the phenanthrene and phenyl rings and the "bidentate" C-H...O hydrogen bonds between the phenanthrene-ring hydrogens and the bridged carbonyl or the carboxylic carbonyl group. The endo [4 + 2] pi cycloadduct (3bl) of tetracyclone (1b) and acrylamide (2l) also showed a wide-range inclusion behavior, in which alcohols are included by making a hydrogen-bond loop with the amide groups. The inclusion behavior of the carboxylic acid Diels-Alder hosts is discussed on the basis of the single crystal X-ray analysis, thermal analysis and semiempirical molecular orbital calculation data.     

1-[2-(2-hydroxyalkyl)phenyl]ethanone: a new photoremovable protecting group for carboxylic acids

[reaction: see text] A new photoremovable protecting group for carboxylic acids is introduced. The protecting group 1-[2-(2-hydroxyalkyl)phenyl]ethanone, HAPE, is used to protect various carboxylic acids. When photolyzed, the protected compound releases the acid in 70-85% isolated yields. The synthesis and the results of photorelease of the protected acids are presented here.     

A practical synthesis of isomerically pure 1,10-difunctionalized derivatives of the [closo-1-CB9H10] anion

The isomer-free [closo-1-CB9H(8)-1-COOH-10-I]- anion was prepared in four steps and 10% overall yield from B10H14. The key step is the skeletal isomerization of the [closo-2-CB9H8-2-COOH-7-I]- anion to a mixture of the 10- and 6-iodo derivatives of [closo-1-CB9H(9)-1-COOH]- formed in up to a 3:1 ratio. The carboxylic acid 4 was converted to the amine [closo-1-CB9H(8)-1-NH(2)-10-I]- using the Curtius reaction. The relative thermodynamic stability of each product was calculated at the DFT and MP2 levels of theory. The regioselectivity of electrophilic substitution in [closo-CB9H10]- derivatives was briefly investigated using the NBO population analysis of the MP2 wave function.     

Novel synthesis of benzalacetone analogues of naphth[a]azulenes by intramolecular tropylium ion-mediated furan ring-opening reaction and X-ray investigation of a naphth[1,2-a]azulene derivative

[reaction: see text] Benzalacetone analogues of naphth[1,2-a]azulene (8), naphth[2,1-a]azulene (13), and naphth[2,3-a]azulene (18) were synthesized from 2-(5-methyl-2-furyl)-1-tropylionaphthalene (7), 1-(5-methyl-2-furyl)-2-tropylionaphthalene (12), and 2-(5-methy-2-furyl)-3-tropylionaphthalene (17), respectively. The synthetic method is based on furan ring-opening reaction by the intramolecular electrophilic attack of a tropylium ion. Single-crystal X-ray work on the naphth[1,2-a]azulene derivative (8) revealed that its tetracyclic system exhibited deformation from planarity similar to that of benzo[c]phenanthrene (tetrahelicene). A centrosymmetric associated dimer structure, just like the molecules of carboxylic acids but via C=O...H-C hydrogen bonds, was found in the crystal. Reduction of bond-length alternation in the seven-membered ring was also found.     

Four New Alkaloids from the Fermentation Broth of Armillaria mellea

Four compounds with similar structures and UV spectra were isolated from the fermentation broth of Armillaria mellea by means of preparative HPLC. Their structures were established as methyl (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylate ( 1 ), (2S)‐1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]‐5‐oxopyrrolidine‐2‐carboxylic acid ( 2 ), 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]pyrrolidin‐2‐one ( 3 ) and 1‐[2‐(furan‐2‐yl)‐2‐oxoethyl]piperidin‐2‐one ( 4 ) on the basis of their 1D‐ and 2D‐NMR, and HR‐MS data. The absolute configurations of compounds 1 and 2 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) data. Additionally, four known compounds, 5 – 8 , were also isolated.     

Reactions with benzo[b]thiophene-2,3-diones I: Synthesis of 2,3-dihydroxy-2,3-diaryl(aralkyl)benzo[b]thiophene derivatives

Benzo[b]thiophene-2,3-diones ( 1 ) react with Grignard reagents to yield 2,3-dihydroxy-2,3-diaryl(aralkyl)benzo[b]-thiophenes ( 2 ). The latter compounds yield 3,3-diaryl(aralkyl)-benzo[b]thiophene-2-ones ( 3 ) by pinacolone rearrangement. Treatment of 3 by hot ethanolic sodium hydroxide solution yields the corresponding carboxylic acids by hydrolytic heteroring opening.     

Reaction of 2,3‐Dichloro‐1,4‐Naphthoquinone with 1‐Phenylbiguanide and 2‐Guanidinebenzimidazole

When 2,3‐dichloro‐1,4‐naphthoquinone (DCHNQ) ( 1 ) is allowed to react with 1‐phenylbiguanide (PBG) ( 2 ), 4‐chloro‐2,5‐dihydro‐2,5‐dioxonaphtho[1,2‐d]imidazole‐3‐carboxylic acid phenyl amide ( 4 ), 6‐chloro‐8‐phenylamino‐9H‐7,9,11‐triaza‐cyclohepta[a]naphthalene‐5,10‐dione ( 5 ) and 4‐dimethyl‐amino‐5,10‐dioxo‐2‐phenylimino‐5,10‐dihydro‐2H‐benzo[g]quinazoline‐1‐carboxylic acid amide ( 6 ) were obtained. While on reacting 1 with 2‐guanidinebenzimidazole (GBI) ( 3 ) the products are 3‐(1H‐benzoimidazol‐2‐yl)‐4‐chloro‐3H‐naphtho[1,2‐d]imidazole‐2,5‐dione ( 7 ) and 3‐[3‐(1H‐benzoimidazol‐2‐yl)‐ureido]‐1,4‐dioxo‐1,4‐dihydronaphthalene‐2‐carboxylic acid dimethylamide ( 8 ).     

Synthesis of phosphole-2,5-dicarboxylic acids via a [1,5]-shift of carbon dioxide around the phosphole nucleus

A new methodology for the synthesis of 1-P-functionalized phosphole-2,5-dicarboxylic acids is described. The carboxylic group is introduced through a two-step sequence which involves a preliminary attack of the phospholide unit onto CO(2) followed by a [1,5]-shift reaction of the CO(2)Li group around the phosphole nucleus. This approach was extended to the preparation of a new type of bidentate ligands. [reaction: see text]     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

The role of salicylic acid, L-ascorbic acid and oxalic acid in promoting the oxidation of alkenes with H2O2 catalysed by [MnIV2(O)3(tmtacn)2]2+

The role played by the additives salicylic acid, L-ascorbic acid and oxalic acid in promoting the catalytic activity of [MnIV2(O)3(tmtacn)2](PF6)2 (1(PF6)2, where tmtacn = N,N',N'-trimethyl-1,4,7-triazacyclononane) in the epoxidation and cis-dihydroxylation of alkenes with H2O2 and in suppressing the catalysed decomposition of H2O2 is examined. Whereas aliphatic and aromatic carboxylic acids effect enhancement of the catalytic activity of 1 through the in situ formation dinuclear carboxylato bridged complexes of the type [MnIII2(mu-O)(mu-RCO2)2(tmtacn)2]2+, for L-ascorbic acid and oxalic acid notable differences in reactivity are observed. Although for L-ascorbic acid key differences in the spectroscopic properties of the reaction mixtures are observed compared with carboxylic acids, the involvement of carboxylic acids formed in situ is apparent. For oxalic acid the situation is more complex with two distinct catalyst systems in operation; the first, which engages in epoxidation only, is dominant until the oxalic acid additive is consumed completely at which point carboxylic acids formed in situ take on the role of additives to form a second distinct catalyst system, i.e. that which was observed for alkyl and aromatic carboxylic acids, which yield both cis-diol and epoxide products.     

Syntheses of Three New Pyridyl Thienopyridine Ligands via the Hurtley Reaction

The tridentate pyridyl thienopyridines 5‐phenyl‐7‐(pyridin‐2‐yl)thieno[2,3‐c]pyridine ( L1 ), 7‐(pyridin‐2‐yl)‐5‐(thiophen‐2‐yl)‐thieno[2,3‐c]pyridine ( L2 ) and 5,7‐di(pyridin‐2‐yl)thieno[2,3‐c]pyridine ( L3 ) have been synthesized via the Hurtley reaction. L1 and L2 were synthesized by condensing 3‐bromothiophene‐2‐carboxylic acid with phenyl‐1,3‐butanedione and 1‐thienyl‐1,3‐butanedione respectively. L3 was synthesized by condensing 3‐bromothiophene‐2‐carboxylic acid with benzoylacetonitrile. Ring closure and a subsequent Negishi or Stille cross‐coupling afforded L1 , L2 , and L3 in an overall yield of 20, 3, and 6%, respectively.     

Substituted 2-aminonicotinamides in the synthesis of pyrido[2,3-d]pyrimidin-4(1H)-ones, 2,3-dihydropyrido- [2,3-d]pyrimidin-4(1H)-ones, and 11b,12-dihydropyrido- [2',3':4,5]pyrimido[2,1-a]isoindole-5,7-diones

The reactions of 2-aminonicotinamides with triethyl orthoformate, carboxylic acids chlorides, aldehydes, and 2-formylbenzoic acid were studied. As a result pyrido[2,3-d]pyrimidin-4(1H)-ones, 2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones, and 5,7,11b,12-tetrahydropyrido[2',3':4,5]pyrimido- [2,1-a]isoindole-5,7-diones were obtained.     

一个双螺旋配合物[Cd2L2(2,2'-bipy)2]n的合成、晶体结构与荧光性质

A flexible carboxylic ligand, l,4-benzenebis(thioacetic acid) (H2L), has been employed to assemble with Cd(Ⅱ) ions under hydrothermal conditions, generating a new complex [Cd2L2(2,2'-bipy)2]n (1). X-ray diffraction reveals the complex 1 possesses a self-assembly double helix structure deriving from [Cd2L2(2,2'-bipy)2] units linked by L2-ligands. A 3D infinite framework is constructed via π-π stacking of 2,2'-bipy. The photoluminescent properties in solid state were investigated.     

Stereoselective synthesis and antioxidant activity of azabicycloadducts derived from 9,10‐phenanthrenequinone

A facile synthesis of sprio{1‐aza‐bicyclo‐[3,3,0]‐6‐octene‐8,1′ ‐phenanthrene}‐2′‐ones has been accomplished by [3+2] cycloaddition of azomethine ylide (amy) generated from 9,10‐phenanthrenequinone and different secondary cyclic amino acids, namely, thiazolidine‐4‐carboxylic acid, L‐pyrrolidine‐2‐carboxylic acid (L‐proline), and piperidine‐2‐carboxylic acid (pipecolinic acid) with electron‐deficient dipolarophiles in 67%–79% yield. AM1 calculations have been performed to understand the stereochemical course of the cycloaddition. The products have been characterized by elemental analyses and spectroscopic techniques, namely IR, ¹H NMR, and ¹³C NMR spectroscopies as well as mass spectrometry. Some of the synthesized cycloadducts showed moderate antioxidant activity. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 20:379–392, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20562     

Carboxylic acid functionalized ortho-linked oxacalix[2]benzene[2]pyrazine: synthesis, structure, hydrogen bond and metal directed self-assembly

Cyclooligomerization of 2,6-dichloropyrazine 4 and benzyl 2,3-dihydroxybenzoate 5 under microwave irradiation resulted in a racemic pair of ester functionalized ortho-linked oxacalix[2]benzene[2]pyrazine 6, which was further transformed to the corresponding racemic carboxylic acid functionalized ortho-linked oxacalix[2]benzene[2]pyrazine 3. Both enantiomers of 3 adopt 1,3-alternate conformations with their two carboxylic acid groups pointing to opposite directions in the solid state. Enantiomers of 3 form a step-like one-dimensional supramolecular polymer via intermolecular hydrogen bond interactions between the carboxylic acids for crystals obtained in methanol. No hydrogen bonds were formed between the carboxylic acids for crystals of 3 obtained in pyridine and aqueous guanidine solutions; instead, intermolecular hydrogen bonds between the carboxylic acid groups of 3 and pyridine, as well as guanidinium ions were formed. Under metal-mediated self-assembly conditions, the pyrazinyl nitrogen atoms in 3 interacted with transition metal ions, such as Ag(I), Cu(II) and Zn(II), and resulted in the formation of four new metal-containing supramolecular complexes. Metallomacrocycles 7, 8 and 9 were formed by reactions of 3 with Ag(I) or Cu(II) ions by bridging two ligands 3 in the equatorial region via M-N coordination bonds. A one-dimensional coordination polymer 10 was generated by reaction between ligand 3 and Zn(II) ions, and a cage-based structure is presented in 10 by bridging of the cyclophane units by Zn(2+) ions via Zn-N and Zn-O bonds.