Photochemistry synthesis. Part 2: Enantiomerically pure polyhydroxy-1,1,3-triarylpropan-2-ols

A new method to open the heterocyclic ring of flavan-3-ols via photolytic cleavage of the ether bond, with stereoselective trapping of the intermediates with phloroglucinol to obtain phloroglucinol grafted derivatives of flavan-3-ols, was developed. Photolysis of catechin and epicatechin, respectively, in the presence of phloroglucinol yielded the enantiomeric (1S,2S)- and (1R,2R)-1,3-di(2,4,6-trihydroxyphenyl)-1-(3,4-dihydroxyphenyl)propan-2-ols, respectively. The absolute configuration at C-1 and C-2 was determined by electronic circular dichroism (experimental and calculated) and these results confirmed that the trapping mechanism is controlled by the C-3 configuration of the flavan-3-ol.     

Lewis acid-catalyzed cascade reactions of arylmethylenecyclopropanes with 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers

Arylmethylenecyclopropanes 1 can react with 3-methoxy-1,3,3-triarylprop-1-yne 2 or 1,1,3-triarylprop-2-yn-1-ol 2-OH to give the corresponding functionalized methylenecyclobutene, cyclobutane, and cyclopropane derivatives in the presence of Lewis acid BF3.OEt2 under mild conditions. A plausible Meyer-Schuster rearrangement mechanism has been proposed.     

Lewis acid catalyzed cascade reactions of diarylvinylidenecyclopropanes and 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers

The reactions of vinylidenecyclopropanes 1 with 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers 2 in the presence of a Lewis acid selectively produce 4-dihydro-1H-cyclopenta[b]naphthalene derivatives 3 or 1,2,3,8-tetrahydrocyclopenta[a]indene derivatives 4 depending on the substituents on the cyclopropane. Good to high yields are obtained under mild conditions. A plausible cascade Meyer-Schuster rearrangement and Friedel-Crafts reaction mechanism has been proposed. Moreover, novel functionalized methylenecyclobutene derivatives 5 could also be obtained in moderate to good yields under similar conditions when strongly electron-donating methoxy groups were introduced into the benzene rings of 2.     

Practical ways from aldehydes to 2-chloro-1,1,1-trifluoro-2-alkenes and 2-chloro-1,1-difluoro-1-alken-3-ols

A reagent system CF₃CCl₃/Zn(>2 mol)/Ac₂O transformed aldehydes to 2-chloro-1,1,1-trifluoro-2-alkenes exclusively, whereas CF₃CCl₃/Zn(>2 mol)/AlCl₃(cat.) converted aldehydes into 2-chloro-1,1-difluoro-1-alken-3-ols.     

Stereoselective synthesis of 2-aryl-4-en-1-ols,promising synthons for the preparation of oxygen heterocycles

Reactions of arylacetic acids with N-methoxymethanamine afford corresponding Weinreb amides which at alkenylation with methallyl and prenyl bromides in the presence of (Me₃Si)₂N^–Na⁺ form unsaturated amides ArCHRCONMe(OMe) (R = CH₂CMe=CH₂, CH₂C=CMe₂). Amides readily react with BuLi and BnMgCl to give ketones ArCHRCOR' (R' = Bu, Bn). A stereoselective reduction of the latter with LiBH(s-Bu)₃ leads to a quantitative formation of syn-isomers of 2-aryl-4-en-1-ols.     

New titanium imido synthons: syntheses and supramolecular structures

Reactions of Ti(NMe(2))(2)Cl(2) with a wide range of primary alkyl and arylamines RNH(2) afforded the corresponding 5-coordinate imido titanium compounds Ti(NR)Cl(2)(NHMe(2))(2) (R = (t)Bu (1), (i)Pr (2), CH(2)Ph (3), Ph (4), 2,6-C(6)H(3)Me(2) (5), 2,6-C(6)H(3)(i)Pr(2) (6), 2,4,6-C(6)H(2)F(3) (7), 2,3,5,6-C(6)HF(4) (8), C(6)F(5) (9), 4-C(6)H(4)Cl (10), 2,3,5,6-C(6)HCl(4) (11), 2-C(6)H(4)CF(3) (12), 2-C(6)H(4)(t)Bu (13)). The compounds 1-13 are monomeric in solution but in the solid state form either N-H...Cl hydrogen bonded dimers or chains or perfluorophenyl pi-stacked chains, depending on the imido R-group. The compound 13 was also prepared in a "one-pot" synthesis from RNH(2) and Ti(NMe(2))(4) and Me(3)SiCl. Reaction of certain Ti(NR)Cl(2)(NHMe(2))(2) compounds with an excess of pyridine afforded the corresponding bis- or tris-pyridine analogues [Ti(NR)Cl(2)(py)(x)](y) (x = 3, y = 1; x = y = 2), and the structure of Ti(2)(NC(6)F(5))(2)Cl(2)(mu-Cl)(2)(py)(4) shows pi-stacking of perfluorophenyl rings. Reaction of Ti(NMe(2))(2)Cl(2) with cross-linked aminomethyl polystyrene gave quantitative conversion to the corresponding solid-supported titanium imido complex. This paper represents the first detailed study of how supramolecular structures of imido compounds may be influenced by simple variation of the imido ligand N-substituent.     

Synthesis of New 3-Phenoxypropan-2-ols with Various Heterocyclic Substituents

1-Phenoxy-3-piperidinopropan-2-ol, 1-(5-methyl-1,3-benzothiazol-2-ylsulfanyl)-3-phenoxypropan-2-ol, 1-(2-hydroxy-3-phenoxypropyl)azepan-2-one, 1,1′-(6-chloro-1,3-benzothiazol-2-ylimino)bis(3-phenoxypropan-2-ol), 1-(1,3-benzothiazol-2-ylsulfanyl)-3-phenoxypropan-2-ol, 1,1′-(piperazine-1,4-diyl)bis(3-phenoxypropan-2-ol), and 1,3-bis(2-hydroxy-3-phenoxypropyl)barbituric acid were synthesized by condensation of 1,2-epoxy-3-phenoxypropane with the corresponding amines and thiols.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 70–72.Original Russian Text Copyright © 2005 by Mesropyan, Ambartsumyan, Avetisyan, Galstyan, Arutyunova.     

2-Nitrosobenzothiazoles: useful synthons for new azobenzothiazole dyes

Novel azobenzothiazole dyes have been synthesized by condensation of 2-nitrosobenzothiazole and 6-nitro-2-nitrosobenzothiazole with aniline, anthranilic acid, 3-hydroxymethylaniline, 2-, 3- and 4-chloroaniline, 4-fluoroaniline, 4-iodoaniline or 4-nitroaniline. The new synthetic approach described is advantageous over the classic diazotization process commonly used for the preparation of related disperse dyes, since the presence of an electron-donating group at the para-position, or equivalent, of the coupling component is no more a pre-requisite for the success of the condensation reaction.     

Reactions of 1,1,1-trihalo-3-nitrobut-2-enes with enamines derived from cycloalkanones. Rearrangement of trifluoromethylated 1,2-oxazine N-oxide into 1-pyrroline N-oxides and stereochemistry of the products

1,2-Oxazine N-oxides derived from (E)-1,1,1-trifluoro-3-nitrobut-2-ene and cyclohexanone enamines underwent spontaneous rearrangement with ring contraction to give 1-pyrroline N-oxides. Reactions of (E)-1,1,1-trifluoro(trichloro)-3-nitrobut-2-enes with N-cyclopent-enylmorpholine resulted in a series of novel CX₃-containing nitroalkyl enamines and g-nitro ketones; the stereochemistry of the synthesized compounds were studied by NMR spectroscopy and X-ray diffraction.     

BF3·OEt2-catalyzed intermolecular reactions of arylmethylenecyclopropanes with (E)-1,1,3-triarylprop-2-en-1-ols

BF₃·OEt₂-catalyzed intermolecular reactions of arylmethylenecyclopropanes with (E)-1,1,3-triarylprop-2-en-1-ols produced the corresponding triene compounds, alcoholic derivatives or cyclobutane derivatives in moderate to excellent yields under mild conditions.     

A New and Facile Synthesis of Chroman-3-ols, 3,4-Dihydro-2H-[1]-Benzopyran-3-ols

o-Allyl phenols react with m-chloroperoxybenzoic acid (m-CPBA) in dry chloroform to give chroman-3-ols in a single step in good yields (93–96%).     

New isomeric N-substituted hydrazones of 2-, 3-and 4-pyridinecarboxaldehydes

Eighteen compounds unknown in the literature, N-(E)-stilbenyloxyalkylcarbonyl- and N-(E)-stilbenyloxyalkylcarbonylaminoalkylcarbonyl-substituted hydrazones of 2-, 3- and 4-pyridinecarboxaldehydes have been prepared. The stereochemical behavior of these compounds in dimethyl-d₆ sulfoxide solution has been studied by ¹H-nmr technique. The E geometrical isomers and cisltrans amide conformers have been found for N-substituted-hydrazones 1–16 .     

New reaction for the preparation of ethers of 1,1,1-trinitropropan-2-ol

Conclusions On reacting trinitromethane with vinyl acetate in a medium of different alcohols the ethers of these alcohols with 1,1,1-trinitropropan-2-ol are obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2566–2568, November, 1969.     

New Synthesis of 1,1,1-Tricarboalkoxy Derivatives: Masked 1,1-Diesters

During a synthetic project, it became necessary to mask the acidity and the nucleophilicity of the 1,l-dicarboalkoxy group in the presence of an aldehyde group. It became evident to us that the l,l,l-triester group would be the functionality of choice for this purpose.     

Synthesis of some new esters of 1-n-butyl-2, 5-dimethyl-4-ethynyl (ethyl)-and 1-allyl-2, 5-dimethylpiperid-4-ols

The following are synthesized: 1-n-butyl-2e, 5e-dimethyl-4e-ethynylpiperid-4a-yl benzoate ( isomer), 1-n-butyl-2e, 5e-dimethyl-4a-ethynyl (ethyl) piperid-4e-yl o-chlorobenzoate ( isomers), 1-allyl-2e, 5e-dimethylpiperid-4e-yl o-chlorobenzoate ( isomer).     

New solvates of the drug naltrexone: protonation,conformation and interplay of synthons

Naltrexone [systematic name: (4R,4aS,7aR,12bS)‐3‐cyclopropylmethyl‐4a,9‐dihydroxy‐2,4,5,6,7a,13‐hexahydro‐1H‐4,12‐methanobenzofuro[3,2‐e]isoquinolin‐7‐one] is an important morphine‐related drug used for combating alcoholism and opioid dependence. Of the eight crystal forms of naltrexone known thus far, only one exists in the neutral form and it crystallizes as a monohydrate. We have isolated the naltrexone free base as two new solvate forms, i.e. the ethyl acetate 0.33‐solvate, C₂₀H₂₃NO₄·0.33C₄H₈O₂, (I), and the diethyl ether hemisolvate, C₂₀H₂₃NO₄·0.5C₄H₁₀O, (II). While just one solvent molecule is present in the asymmetric unit of each solvate, there are three drug molecules (Z′ = 3) in ethyl acetate solvate (I) and two (Z′ = 2) in diethyl ether solvate (II). In (I), one of the three crystallographically independent drug molecules is present with its cyclopropyl group disordered over two sets of positions, as is the whole diethyl ether solvent molecule in (II). In all known forms, including the title forms, the naltrexone molecule exhibits the same conformation of the fused rings. The only conformational variability of naltrexone is in the cyclopropylmethyl group. Two conformations can be found around the bond connecting this group to the N‐heterocycle, which is directly related to drug protonation. We have calculated, at the B3LYP/6‐31G** level of theory, the minimum energy conformations of protonated and neutral naltrexone molecules for a chosen torsion angle about this bond. The lowest energy conformers depend on the protonation state and are in agreement with those found in the solid state. Within the cyclopropylmethyl group, the bond joining the methylene C atom to the cyclopropyl fragment also evidences conformational variability. In the literature, there are two well defined conformations around this bond. A third cyclopropyl conformation around this second bond is observed in the title solvates. Concerning the supramolecular features of the previously reported crystal structures, only one classical hydrogen bond between naltrexone molecules and one C(8) homosynthon is known, pointing to the robustness of this synthon and the difficulty in disrupting it. New R₂²(7) and C₂²(10) homosynthons are found in both (I) and (II), suggesting that their occurrence derives from crystallization of the neutral drug from nonpolar solvents.     

Psilocin analogs. 1. Synthesis of 3-[2-(dialkylamino)ethyl] -and 3-[2-(cycloalkylamino)ethyl] indol-4-ols

The synthesis of four dialkyl and three eyeloalkyl analogs of psilocin (4, R - CH₃), a hallucinogenic principle found in certain fungi, is described. The synthetic route involves four transformations starting with 6,7-dihydroindol-4(5H)one: (1).     

2-Amino-1,1,3-tricyanopropene in Heterocyclic Synthesis: Novel Synthesis of Thiopyran Pyridinethiones and Nicotinonitrile Derivatives

2-Amino-1,1,3-tricyano-3-bromopropene was obtained from bromination of malononitrile dimer, 2-amino-1,1,3-tricyanopropene with N-bromo-succinimide (NBS). The reactions of this bromo derivative with sodium hydrogen sulfide and thioglycollic acid afforded thiophene and thiopyran derivatives respectively. A novel synthesis of pyridinethione and nicotinonitrile derivatives by using 3-amino-4,4-dicyano-3-butenethioamide as starting material are reported and the synthetic potential of the method is described.     

Studies on peroxycompounds—XXVI: “SN2”-type decarbethoxylation of o-benzoyltartronates and benzoyloxycyanoacetates. New synthons for 2-hydroxycarboxylic esters and aldehydes

Diethyl O-benzoyl-R-tartronates 1; RH, C₂H₅, Ph undergo S_N2-type dealkylation and subsequent CO₂ elimination at 175–190°C in anhydrous or wet DMSO, with or without inorganic salts as catalysts giving the corresponding 2-benzoyloxyesters 2. Ethyl 2-benzoyloxy-2-benzylcyanoacetate 4 also undergoes decarbethoxylation (140°C, DMSO or wet DMSO) giving 6 in small yields (1–6%). The best yields of 6 (82%) were found when pyridine was the solvent and LiI the catalyst.