Solventless lactam synthesis by intramolecular cyclizations of alpha-iminoester derivatives under microwave irradiation

We have previously reported a new synthesis of amides from esters and amines under microwave irradiation, offering much higher yields than those achieved with conventional heating [1]. We have now extended these studies to the ring closure of neat iminoesters I2, I3 and I4-I6 to give five- and six-membered ring lactams L5, L6 and larger lactams L7-L9 (where I means imine and L means lactam), respectively, under both classical heating conditions and microwave irradiation.     

Benzindazoles from triketones of the indan series

In the reaction of 2-acetonyl-and 2-phenacyl-2-phenylindan-1, 3-diones with hydrazine hydrate, the five-membered ring of the indandione system isomerizes into a six-membered ring forming derivatives of 5-hydroxy-1H-benz[g]indazole. Derivatives of 3,4-(CO)-benzoylenepyridazine have been isolated as intermediates. The benzindazoles mentioned have been obtained by independent synthesis from the corresponding 2-acyl-1, 4-dihydroxynaphthalenes.For part I, see [1].     

Reactions of 5-mercaptoazoles and pyridine-2-thiones with acetylenic esters. Selectivity of the formation of novel fused thiazin-4-ones and thiazolidin-4-ones

A systematic study of the reactions of dimethyl acetylenedicarboxylate (DMAD) and methyl propynoate with 5-mercaptoazoles and pyridine-2-thiones has been carried out and as a result, a number of novel imidazo[1,5-b]thiazin-4-ones 6a,b, pyrazolo[1,5-b] thiazin-4-ones 15a-f, imidazo[1,5-b]thiazol-4-ones 7a,b and thiazolo[3,2-a]pyridines 21a-c have been prepared. The influence of the size of the ring of the starting "cyclic" thioamides on the size of the fused ring in the reaction products has been established. The preferred formation of a six-membered thiazine ring took place in the reactions of 5-mercaptoazoles. In contrast, the five membered thiazolidine ring is formed in reactions of pyridine-2-thiones. In both cases the product is a five-membered ring fused to a six-membered heterocycle.     

Hetarenes with a bridge nitrogen atom. 6. Ambident properties of the oxazolo[3,2-a]pyridinium nucleus in reactions with nucleophiles: Prediction and experiment

We have studied the problem of ambident opening of five-membered and six-membered rings of the heteroaromatic oxazolo[3,2-a]pyridinium cation. A quantum chemical SINDO1 calculation of the energies of isomeric adducts of this cation with nucleophiles predicts preferential formation of the C₉-adduct in the case of OH and SH ions with opening of the oxazole fragment, while for nitrogen-containing nucleophiles (NH₂, NMe₂) attack at the C₍₅₎ atom is also likely with opening of the pyridine fragment. We have experimentally observed that this cation undergoes opening of the five-membered ring in reaction with NaSH, opening of the six-membered ring in reaction with piperidine, and opening of both rings in reaction with ammonia.For communication 5, see [1].M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 397–402, March, 1997.     

Tetrarhena-heterocycle from the palladium-catalyzed dimerization of Re2(CO)8(μ-SbPh2)(μ-H) exhibits an unusual host-guest behavior

The six-membered heavy atom heterocycles [Re(2)(CO)(8)(μ-SbPh(2))(μ-H)](2), 5, and Pd[Re(2)(CO)(8)(μ-SbPh(2))(μ-H)](2), 7, have been prepared by the palladium-catalyzed ring-opening cyclo-dimerization of the three-membered heterocycle Re(2)(CO)(8)(μ-SbPh(2))(μ-H), 3. The palladium atom that lies in the center of the heterocycle 7 was removed to yield 5. The palladium removal was found to be partially reversible leading to an unusual example of host-guest behavior. A related dipalladium complex Pd(2)Re(4)(CO)(16)(μ(4)-SbPh)(μ(3)-SbPh(2))(μ-Ph)(μ-H)(2), 6, was also formed in these reactions of palladium with 3.     

Very strong C-H...O, N-H...O, and O-H...O hydrogen bonds involving a cyclic phosphate.

Very short C-H...O, N-H...O, and O-H...O hydrogen bonds have been generated utilizing the cyclic phosphate [CH2(6-t-Bu-4-Me-C6H2O)2]P(O)OH (1). X-ray structures of (i) 1 (unsolvated, two polymorphs), 1...EtOH, and 1...MeOH, (ii) [imidazolium](+)[CH2(6-t-Bu-4-Me-C6H2O)2PO2](-)...MeOH [2], (iii) [HNC5H4-N=N-C5H4NH](2+)[(CH2(6-t-Bu-4-Me-C6H2O)2PO2)2](2-)...4CH3CN...H2O [3], (v) [K, 18-crown-6](+)[(CH2(6-t-Bu-4-Me-C6H2O)2P(O)OH)(CH2(6-t-Bu-4-Me-C6H2O)2PO2)](-)...2THF [4], (vi) 1...cytosine...MeOH [5], (vii) 1...adenine...1/2MeOH [6], and (viii) 1...S-(-)-proline [7] have been determined. The phosphate 1 in both its forms is a hydrogen-bonded dimer with a short O-H...O distance of 2.481(2) [triclinic form] or 2.507(3) A [monoclinic form]. Compound 2 has a helical structure with a very short C-H...O hydrogen bond involving an imidazolyl C-H and methanol in addition to N-H...O hydrogen bonds. A helical motif is also seen in 5. In 3, an extremely short N-H...O hydrogen bond [N...O 2.558(4) A] is observed. Compounds 6 and 7 also exhibit short N-H...O hydrogen bonds. In 1...EtOH, a 12-membered hydrogen-bonded ring motif, with one of the shortest known O-H...O hydrogen bonds [O...O 2.368(4) A], is present. 1...MeOH is a similar dimer with a very short O(-H)...O bond [2.429(3) A]. In 4, the deprotonated phosphate (anion) and the parent acid are held together by a hydrogen bond on one side and a coordinate/covalent bond to potassium on the other; the O-H...O bond is symmetrical and very strong [O...O 2.397(3) A].     

Effect of the H-bonding on aromaticity of purine tautomers

Four tautomers of purine (1-H, 3-H, 7-H, and 9-H) and their equilibrium H-bonded complexes with F(-) and HF for acidic and basic centers, respectively, were optimized by means of the B3LYP/6-311++G(d,p) level of theory. Purine tautomer stability increases in the following series: 1-H < 3-H < 7-H < 9-H, consistent with increasing aromaticity. Furthermore, the presence of a hydrogen bond with HF does not change this order. For neutral H-bonded complexes, the strongest and the weakest intermolecular interactions occur (-14.12 and -10.49 kcal/mol) for less stable purine tautomers when the proton acceptor is located in the five- and six-membered rings, respectively. For 9-H and 7-H tautomers the order is reversed. The H-bond energy for the imidazole complex with HF amounts to -14.03 kcal/mol; hence, in the latter case, the fusion of imidazole to pyrimidine decreases its basicity. The ionic H-bonds of N(-)···HF type are stronger by ~10 kcal/mol than the neutral N···HF intermolecular interactions. The hydrogen bond N(-)···HF energies in pyrrole and imidazole are -32.28 and -30.03 kcal/mol, respectively, and are substantially stronger than those observed in purine complexes. The aromaticity of each individual ring and of the whole molecule for all tautomers in ionic complexes is very similar to that observed for the anion of purine. This is not the case for neutral complexes and purine as a reference. The N···HF bonds perturb much more the π-electron structure of five-membered rings than that of the six-membered ones. The H-bonding complexes for 7-H and 9-H tautomers are characterized by higher aromaticity and a much lower range of HOMA variability.     

Stereospecific Synthesis of Enantiopure [6]Helicene Containing a Seven-Membered Ring and [7]Helicene by Acid-Promoted Stepwise Alkyne Annulations of Doubly Axial-Chiral Precursors**

Enantiopure [6]helicene containing an embedded seven-membered ring and carbo[7]helicene (>99 % ee) with opposite helicity were simultaneously and quantitatively (>99 %) synthesized with a perfect stereospecificity through stepwise acid-promoted intramolecular alkyne annulations of doubly axial-chiral cyclization precursors. The helical handedness of the [6]- and [7]helicenes was fully stereocontrolled by the doubly axial chirality of the precursors as a result of complete axial-to-helical chirality transfer. The cyclizations proceeded in a stepwise manner; the first six-membered ring formation was followed by the kinetically controlled seven- or six-membered ring formation with or without helix-inversion of a [4]helicene intermediate generated during the first cyclization step, thus quantitatively producing enantiopure circularly polarized luminescent [6]- and [7]helicenes with opposite helicity.     

Synthesis of the [5-7-6] tricyclic core of guanacastepene A via an intramolecular Mukaiyama aldol reaction

[reaction: see text] A synthesis of the tricyclic [5-7-6] skeleton of guanacastepene A is described. The six-membered ring of guanacastepene A was constructed by a Diels-Alder reaction. After several functional group transformations, it was coupled to beta-iodocyclopentenone. Lithium dimethylcuprate conjugate addition followed by an intramolecular Mukaiyama aldol reaction furnished the desired [5-7-6] tricyclic ring system.     

Molecular level model for the agonist/antagonist selectivity of the 1,4-dihydropyridine calcium channel receptor

Summary Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxylate], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5-carboxylate], and Bay O 9507 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(4-nitrophenyl)-pyridine-5-carboxylate] were determined. The conformations of the 1,4-DHP rings of these activator analogues of Bay K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate] do not suggest that their activator properties are as strongly correlated with the degree of 1,4-DHP ring flattening as was indicated for members of the corresponding antagonist series. The solid state hydrogen bonding of the N(1)-H groups of the activators is not, unlike that of their antagonist counterparts, to acceptors that are directly in line with the donor. Rather, acceptor groups are positioned within ± 60 degrees of the N(1)-H bond in the vertical plane of the 1,4-DHP ring. Previously determined structure-activity relationships have indicated the importance of this N(1)-H group to the activity of the 1,4-DHP antagonists. Based on these observations, a model is advanced to describe the 1,4-DHP binding site of the voltage-gated Ca²⁺ channel and its ability to accommodate both antagonist and activator ligands.     

Cyclic homooligomers of furanoid sugar amino acids

Cyclic homooligomers of mannose-derived furanoid sugar amino acid 1 [H-Maa(Bn(2))-OH] were synthesized by using BOP reagent in the presence of DIPEA under dilute conditions that converted the sugar amino acid monomer directly into its cyclic homooligomers 3a and 4a. The glucose-based sugar amino acid 2 [H-Gaa(Bn(2))-OH] under the same reaction conditions gave a bicyclic lactam 5a as the major product. Cyclic homooligomers of 2 were prepared by cyclizing their linear precursors 6 and 7 leading to the formation of cyclic peptides 8a and 9a, respectively. Conformational analysis by NMR and constrained MD studies revealed that all the cyclic products, 3, 4, 8, and 9, had symmetrical structures. The deprotected cyclic trimer of Maa 3b displayed a conformation in which all the C=O and the N-H bonds of the molecule point in opposite directions. In the deprotected cyclic tetramer of Maa 4b, the COs and NHs were in the plane of the ring with the former pointing to outside and the latter inside the ring. The structure of the cyclic Gaa dimer 8b displayed an unusual six-membered intramolecular hydrogen bond between NH(i)() --> C3-O(i)()(-)(1) and a syn orientation between the C2-H and CO. In this molecule, the C2-hydrogens and the COs can be seen on one side of the ring while the NHs point to the other side. Addition of the bicyclic lactam 5b resulted in the influx of Na(+) ions across the lipid bilayer leading to the dissipation of valinomycin-mediated K(+) diffusion potential.     

Sensitivity of (1)J[C(1)-H(1)] magnitudes to anomeric stereochemistry in 2,3-anhydro-O-furanosides.

The magnitude of the one-bond coupling constant between C(1) and H(1) in 2,3-anhydro-O-furanosides has been shown to be sensitive to the stereochemistry at the anomeric center. A panel of 24 compounds was studied and in cases where the anomeric hydrogen is trans to the epoxide moiety, (1)J[C(1)-H(1)] = 163-168 Hz; and when this hydrogen is cis to the oxirane ring, ((1)J[C(1)-H(1)] = 171-174 Hz. In contrast, for 2,3-anhydro-S-glycosides, the size of the (1)J[C(1)-H(1)] is not sensitive to C(1) stereochemistry. Computational studies on all four methyl 2,3-anhydro-O-furanosides (5-8) demonstrated that (1)J[C(1)-H(1)] was inversely proportional to the length of the C(1)-H(1) bond. A previously reported equation, which relates C(1)-H(1) bond distance and atomic charges to (1)J[C(1)-H(1)] magnitudes, could be used to accurately predict the J values in the alpha-lyxo (5) and beta-ribo (8) isomers. In contrast, with the beta-lyxo (6) and alpha-ribo isomers (7), this equation underestimated the size of these coupling constants by 10-20 Hz.     

Synthesis, structure, and electrochemical properties of a family of 2-(arylazo)phenolate complexes of ruthenium with unusual C-C coupling and N=N cleavage

Reaction of 2-(4'-R-phenylazo)-4-methylphenols (R = OCH3, CH3, H, Cl, and NO2) with [Ru(dmso)(4)Cl2]affords a family of five ruthenium(III) complexes, containing a 2-(arylazo)phenolate ligand forming a six-membered chelate ring and a tetradentate ligand formed from two 2-(arylazo)phenols via an unusual C-C coupling linking the two ortho carbons of the phenyl rings in the arylazo fragment. A similar reaction with 2-(2'-methylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl2] has afforded a similar complex, in which one 2-(2'-methylphenylazo)-4-methylphenolate ligand is coordinated forming a six-membered chelate ring, and the other two ligands have undergone the C-C coupling reaction, and the coupled species is coordinated as a tetradentate ligand forming a five-membered N,O-chelate ring, a nine-membered N,N-chelate ring, and another five-membered chelate ring. Reaction of 2-(2',6'-dimethylphenylazo)-4-methylphenol with [Ru(dmso)(4)Cl2] has afforded a complex in which two 2-(2',6'-dimethylphenylazo)-4-methylphenols are coordinated as bidentate N,O-donors forming five- and six-membered chelate rings, while the third one has undergone cleavage across the N=N bond, and the phenolate fragment, thus generated, remains coordinated to the metal center in the iminosemiquinonate form. Structures of four selected complexes have been determined by X-ray crystallography. The first six complexes are one-electron paramagnetic and show rhombic ESR spectra. The last complex is diamagnetic and shows characteristic 1H NMR signals. All the complexes show intense charge-transfer transitions in the visible region and a Ru(III)-Ru(IV) oxidation on the positive side of SCE and a Ru(III)-Ru(II) reduction on the negative side.     

N,N′-二[3-氯-5S-(l-孟氧基)-2(5H)-4-呋喃酮基]-1,4-丁二胺的合成及晶体结构(英文)

合成了N,N′-二[3-氯-5S-(l-孟氧基)-2(5H)-4-呋喃酮基]-1,4-丁二胺,并通过IR,1H NMR,MS和X射线单晶衍射对其进行了表征.X射线单晶衍射结果表明:标题化合物的不对称结构单元中包含一个平面的呋喃酮环和一个椅式的环己烷环,四个手性中心.标题化合物通过N—H…O分子间氢键作用实现空间堆积.     

Synthesis of pyrrolo[1,2-a]quinoxalines by 1,3-dipolar cycloaddition reaction. An additional reaction mechanism via an aziridine intermediate

The reaction of the 2-substituted 6-chloroquinoxaline 4-oxides 1a or 1b with 2-fold molar amount of methyl propiolate resulted in the 1,3-dipolar cycloaddition reaction to give 8-chloro-1,3-bismethoxycarbonyl-4-(piperidin-1-yl)pyrrolo[1,2-a]quinoxaline 4a or 8-chloro-1,3-bismethoxycarbonyl-4-(morpholin-4-yl)pyrrolo-[1,2-a]quinoxaline 4b , respectively. Compound 4a or 4b was transformed into 8-chloro-3-methoxycarbonyl-4-(piperidin-1-yl)pyrrolo[1,2-a]quinoxaline 5a or 8-chloro-3-methoxycarbonyl-4-(morpholin-4-yl)pyrrolo[1,2-a]-quinoxaline 5b , respectively. The structure of 4a,b was confirmed by the NOE measurement among the C₁ -H , C ₂-H and C ₉-H proton signals of 5a,b . An additional reaction mechanism was proposed for the ring transformation of isoxazolo[2,3-a]quinoxalines into pyrrolo[1,2-a]quinoxalines.     

Alkylierung der 3-Acyl-thio- und -dithio-carbazinester-Gruppierung ?CO?NH?NH?CS?YR

3-Benzoyl-thiocarbazic acid O-methyl ester 7a and 3-benzoyl-dithiocarbazic acid methyl ester 7b are methylated, in presence of alkali, at the SH group of 1a , the ene-thiol tautomer of 1 , to give the 3-benzoyl-isothiocarbazic acid O, S-dimethyl ester 8a and the 3-benzoyl-isodithiocarbazic acid dimethyl ester 8b resp., which clearly differ from the N-methylated compounds 11a and 12a or 11b and 12b prepared from the two N-methyl benzohydrazides 9 and 10 resp. (melting points, thin-layer chromatography and NMR. spectra). The previously reported [1] ring closure of 3-(ω-chloroalkanoyl)-thiocarbazic acid O-alkyl esters and -dithiocarbazic acid alkyl esters can be interpretated as an intramolecular auto-alkylation of ? CO? NH? NH? CS? YR: the 3-(chloroacetyl)-compounds 2 are S-alkylated (enethiol form) to the six-membered thiadiazinones 4 , but the 3-(3-chloropropionyl)-compounds 3 are N-alkylated to the pyrazolidinones 6 , the five-membered ring being preferred in the latter case to the seven-membered ring 5 which would be formed by S-alkylation. Hence the position of alkylating attack depends on the size of the ring to be formed. As a consequence, starting from 3-(4-chlorobutyryl) compounds 13 , an alternative between the two N-alkylation products 14 (five-membered ring) and 15 (six-membered ring) would be expected. On the contrary however, a combination of 1,3,4-thiadiazole ring closure and chlorine elimination predominates, giving the 5-(3-hydroxypropyl)-1,3,4-thiadiazoles 16 . This reaction may proceed via the butyrolactone intermediates 18 and could therefore be interpreted as O-alkylation followed by rearrangement.     

Synthesis of oligoenes that contain up to 15 double bonds from 1,6-heptadiynes

This paper reports the synthesis of polyene oligomers ("oligoenes") that contain up to 15 double bonds that are identical to the "all five-membered ring" species formed through cyclopolymerization of diisopropyldipropargylmalonate. The oligoenes contain an isopropylidene unit at each end. The isolated oligoenes range from the "dimer" (a pentaene, (E)-di-1,2-[1-(2-methyl-propenyl)-4,4-di-iso-propyl-carboxy-cyclopent-1-enyl]-ethene (3b2)) to the "heptamer" (3b7, a pentadecaene). Oligoenes 3b2, 3b3, 3b4, 3b5, and 3b7 were prepared through Wittig-like reactions between aldehydes and the appropriate monometallic Mo alkylidene or bimetallic Mo bisalkylidene species whose alkylidene is derived from an identical five-membered ring monomeric unit. Compounds 3b2, 3b4, and 3b6 were prepared through McMurry coupling reactions of aldehydes. A representative aldehyde (the "monomeric" aldehyde) is diisopropyl-3-formyl-4-(2-methylprop-1-enyl)cyclopent-3-ene-1,1-dicarboxylate (2b), McMurry coupling of which yields 3b2. A heptaene that contains a six-membered ring in the central unit also was prepared in a Wittig-like reaction involving a bimetallic Mo alkylidene; this species is a model for oligoenes that contain both six-membered and five-membered rings. X-ray structures of two bimetallic species that are employed in the synthesis of the oligoenes are reported.     

Correct Structure of a Condensation Product C6H12N4O4 from Hydrazine,Formaldehyde and Hydrogen Peroxide

The compound mentioned in the title is shown by X-ray analysis to be 1, 2, 7, 8-tetraaza-4, 5, 10, 11-tetraoxatricyclo [6.4.1.1^{2, 7}] tetradecane, contrary to previous suggestions. The torsion angle about the peroxo bonds in the seven-membered rings in 100°, close to the value in hydrogen peroxide, which would not be possible in a six-membered ring.     

Reactions of Substituted Ethyl 1,2,3,4,4′,5′-Hexahydrospiro-[naphthalene-2,5′-pyrazole]-3′-carboxylates with Halogens

Substituted ethyl 1,2,3,4,4′,5′-hexahydrospiro[naphthalene-2,5′-pyrazole]-3′-carboxylates react with chlorine or N-bromosuccinimide to give spirocyclic substituted 3-halo-4,5-dihydro-3H-pyrazoles which lose nitrogen molecule on heating with formation of substituted spirocyclic 1-halocyclopropane-1-carboxylates. Heating of the title compounds with bromine in acetic acid results in opening of the spiro-fused six-membered ring to afford ethyl 4-aryl-5-[2-(2-carboxyphenyl)ethyl]pyrazole-3-carboxylates.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1058–1063.Original Russian Text Copyright © 2005 by Molchanov, Korotkov, Kopf, Kostikov.     

Investigations in heterocyclic chemistry

With the acid condensation of diarylglycolic benzylanilides as an example, it has been shown that the predominant formation of a fivemembered ring rather than a six-membered ring takes place even in the case where the internal structure of the anilide permits the simultaneous formation of both rings. It has also been shown that it is possible to determine the size of the ring formed on condensation from the UV and IR spectra, and the presence of hydrogen bonds in the arylamides of diarylglycolic acids and the formation of the lactim form and of the quatenary ammonium salt of the base of 3, 3-diphenyloxindole in solutions of sodium ethoxide and concentrated H₂SO₄, respectively, have been confirmed.For part XLIII, see [17].