Synthesis of l-aminohomohistidine (l-Ahh)

A short synthesis of l-aminohomohistidine (l-Ahh), which starts from readily available δ-hydroxy-l-lysine is described. The embedding of the basic guanidino moiety in the aromatic imidazole lowers the basicity of the side chain to a pK_a of 8.3. It is proposed that l-Ahh may be employed as an arginine-mimetic in medicinal chemistry.     

Synthesis of 1-indanones by intramolecular Friedel-Crafts reaction of 3-arylpropionic acids catalyzed by Tb(OTf)3

Intramolecular Friedel-Crafts acylation reaction of 3-arylpropionic acids was efficiently catalyzed by Tb(OTf)₃ at 250 °C to give 1-indanones. Even deactivated 3-arylpropionic acids with halogen atoms on the aromatic ring can be cyclized in moderation to good yields.     

Enantioselective addition of phenylacetylene to aldehydes catalyzed by a d-glucosamine-derived sulfonamide-titanium complex

We present the synthesis of β-hydroxy sulfonamides derived from d-glucosamine and their application as ligands in titanium tetraisopropoxide promoted enantioselective addition of phenylacetylene to benzaldehyde and selected aromatic and aliphatic aldehydes. The N-3,5-bis(trifluoromethyl)benzenesulfonamido-d-glucosamine derivative was chosen as the most efficient ligand for this addition. The reaction is highly enantioselective for several aromatic aldehydes and enantiomeric excesses up to 92% were obtained.     

d-Phg-l-Pro Dipeptide-derived prolinol ligands for highly enantioselective Reformatsky reactions

Optically pure N-aminoethyl prolinol derivatives 3a-c have been prepared from the dynamic kinetic resolution of N-(α-bromo-α-phenylacetyl) proline ester 1 in asymmetric nucleophilic substitution and subsequent reduction. The peptide-derived prolinols are tested as chiral ligands in the asymmetric addition of Reformatsky reagent to aromatic aldehydes. Chiral ligand 3c has been shown to be effective to produce enantioenriched β-hydroxy esters 5a-j with up to 98% ee.     

Five-membered heterocycles. Part III. Aromaticity of 1,3-imidazole in 5+n hetero-bicyclic molecules

The aromaticity (in the form of HOMA index) of 1,3-imidazole ring and its bicyclic derivatives was studied on the basis of statistical data from Cambridge Structural Database and X-ray investigations performed by authors. As a starting point, aromaticity of the 1,3-imidazoles with exocyclic X substituent at C2 (XN, O or S) was calculated. Subsequently, the HOMA index was calculated for various 5+n bicyclic skeletons with N, O, and S as endocyclic heteroatoms in the second ring. For the isolated 1,3-imidazole ring, aromaticity depends on exocyclic substituent at C2 and decreases in sequence N, S, O. For bicyclic derivatives it was found that both rings are aromatic and coplanar in very few molecules (17% of investigated ones), and positive charge—located on endocyclic heteroatom—increases the aromaticity. For remaining compounds, presence of sp³ carbons excludes possibility of aromatic ring existence.     

Adsorption of aromatic compounds from solutions in <Emphasis Type="Italic">n</Emphasis>-heptane by modified nanoporous silica

The adsorption of anisole, anthracene, benzoic acid, benzene, naphthalene, phenanthrene, phenol, and carbon tetrachloride from dilute solutions in n-heptane on the modified nanoporous silica sorbents, Silasorb C18 and Phenyl-Silasorb, at 298 K is investigated by developing liquid chromatography. The Henry law constants and Helmholtz energy of adsorption for these aromatic compounds are calculated from their retention values. The adsorption isotherms of the aromatic compounds are calculated from their chromatographic peaks with allowances made for longitudinal smearing. A correlation is made between the Henry law constants calculated from the retention values of the aromatic compounds and from their adsorption isotherms. The influences of the surface modification of the silica adsorbents and the molecular structure of the aromatic compounds on their elution from the chromatographic column with n-heptane as the eluent are discussed. Contributions of functional groups in the molecules of the aromatic compounds to the Helmholtz energy of adsorption on different surfaces are estimated.     

<Emphasis Type="Italic">peri</Emphasis>-hydroxy acenaphthoyl compounds

Reactions of peri-hydroxyacenaphthaldehyde and its O-methyl derivative with amines, aryl methyl ketones, and malononitrile gave the corresponding Schiff bases, chalcones, and arylidenemalononitrile. The latter underwent heterocyclization on heating in trifluoroacetic acid to produce 2-oxoacenaphtho[5,6-bc]-oxepine-3-carbonitrile. The condensation of 5-acetyl-6-hydroxyacenaphthene with aromatic aldehydes afforded chalcones, their mixtures with heterocyclization products, or 2-arylacenaphtho[5,6-bc]oxepin-4-one, depending on the substituent in the aromatic ring.     

Gas-Phase Chemistry of Benzyl Cations in Dissociation of <Emphasis Type="BoldItalic">N</Emphasis>-Benzylammonium and <Emphasis Type="BoldItalic">N</Emphasis>-Benzyliminium Ions Studied by Mass Spectrometry

In this study, the fragmentation reactions of various N-benzylammonium and N-benzyliminium ions were investigated by electrospray ionization mass spectrometry. In general, the dissociation of N-benzylated cations generates benzyl cations easily. Formation of ion/neutral complex intermediates consisting of the benzyl cations and the neutral fragments was observed. The intra-complex reactions included electrophilic aromatic substitution, hydride transfer, electron transfer, proton transfer, and nucleophilic aromatic substitution. These five types of reactions almost covered all the potential reactivities of benzyl cations in chemical reactions. Benzyl cations are well-known as Lewis acid and electrophile in reactions, but the present study showed that the gas-phase reactivities of some suitably ring-substituted benzyl cations were far richer. The 4-methylbenzyl cation was found to react as a Brønsted acid, benzyl cations bearing a strong electron-withdrawing group were found to react as electron acceptors, and para-halogen-substituted benzyl cations could react as substrates for nucleophilic attack at the phenyl ring. The reactions of benzyl cations were also related to the neutral counterparts. For example, in electron transfer reaction, the neutral counterpart should have low ionization energy and in nucleophilic aromatic substitution reaction, the neutral counterpart should be piperazine or analogues. This study provided a panoramic view of the reactions of benzyl cations with neutral N-containing species in the gas phase.     

Rotational equilibria in 2-aryl-n-propanols, 2-aryl-n-propyl methyl ethers and 2-aryl-n-propyl acetates. Trends consistent with a CH---O hydrogen bond

An ¹H-nmr study of rotational isomerism in the title compounds reveals an increasing population of ?auche aryl/OMe and gauche aryl/OCOMe conformations as electron donor groups on the aromatic ring are replaced by electron withdrawing groups.     

<Emphasis Type="Italic">N</Emphasis>-Allyl-substituted aminomethylene-1,1-bisphosphonates in 1,3-dipolar cycloaddition reaction with aromatic nitrile <Emphasis Type="Italic">N</Emphasis>-oxides

A reaction of N-allyl-substituted aminomethylene-1,1-bisphosphonates with aromatic nitrile N-oxides was used to obtain new aminomethylenebisphosphonates with one or two 3-arylisoxazoline rings at the nitrogen atom. NMR spectroscopy studies showed that the bisphosphonates with two isoxazoline fragments in the molecule exist in solution as a mixture of two diastereomers.     

C-trifluoroacylation - a convenient route to carboxylic acids

Trifluoroacetic anhydride will trifluoroacylate reactive aromatic and heterocylic nuclei without the aid of a Friedel-Crafts catalyst. The resulting trifluoromethyl ketone undergoes hydrolysis to yield the corresponding carboxylic acid. This provides a very simple route to aromatic and heterocyclic carboxylic acids.     

(E)-1,2-Difluoro-1-iodo-2-trialkylsilanes—A useful synthon for the addition of the [IFCCF] unit to activated electrophiles

Fluoride ion catalyzed reaction of (E)-IFCCFSiR₃ with activated aromatic aldehydes and ketones and activated perfluoroaromatics, such as pentafluoropyridine and perfluorotoluenes, transfers the [IFCCF] unit to the activated electrophiles to stereospecifically provide (E)-1,2-difluoro-1-iodosubstituted derivatives. Aluminum chloride catalyzed reaction of (E)-1,2-difluoro-1-iodo-2-trialkylsilanes with alkyl or aryl acyl halides gives the corresponding (E)-1,2-difluoro-1-iodoketones stereospecifically in excellent yield. The vinyl iodide product formed via this methodology could be coupled (with Pd(0)) catalysis to provide an entry to a polyfunctionalized derivative.     

Dilactams. Synthesis of nonsymmetrical dibenzodiazocinediones

We report the first examples of nonsymmetrical dibenzodiazocinediones, mono-, di-, tri- and tetra-substituted in the aromatic rings including a benzo pyridino diazocine, by a new short method without the requirement of protection. The procedure involves conversion of an anthranilic acid to its sulfinamide lactone followed by direct heating with a different N-alkylanthranilic acid.     

Carboxymethylalginic acid ethyl ester and its reactions with <Emphasis Type="Italic">N</Emphasis>-nucleophiles

Esters of carboxymethylalginic acid have been prepared; their acylation activity in the reactions with aromatic amines and aromatic carboxylic acids hydrazides have been studied.     

Effective syntheses of quinoline-7,8-diol, 5-amino-l-DOPA, and 3-(7,8-dihydroxyquinolin-5-yl)-l-alanine

A modification of the Baeyer-Villiger reaction allows the conversion of aromatic 2-hydroxy-3-nitroketones and aldehydes into 3-nitrocatechols, which can be reduced to 3-aminocatechols. Reaction of the latter with acrolein yields quinoline-7,8-diols under exceptionally mild conditions. This new reaction sequence was successfully applied to the synthesis of the title compounds.     

Cheap thiamine hydrochloride as efficient catalyst for synthesis of 4<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">b</Emphasis>]pyrans in aqueous ethanol

Preparation of pharmaceutically active 2-amino-4H-pyran derivatives has been achieved using cheap thiamine hydrochloride as catalyst. A wide range of aromatic aldehydes easily undergo condensation with malononitrile and several kinds of 1,3-cyclohexanedione under mild condition to afford the desired product with good purity in excellent yield. This protocol has various advantages as a simple, clean, and environmentally benign three-component process.     

Synthesis of <Emphasis Type="Italic">o</Emphasis>(<Emphasis Type="Italic">m</Emphasis>)-carborane-containing azomethines

A method of preparative synthesis of o(m)-carborane-containing azomethines via the condensation of o(m)-carboranyl-C-methylene-4-formylbenzoates with aliphatic, cycloaliphatic, and aromatic amines was developed.     

Direct asymmetric aldol reaction co-catalyzed by l-proline and isothiouronium salts

An efficient, simple, and highly selective protocol for the direct asymmetric aldol reaction between cyclohexanone and aromatic aldehydes using l-proline as a chiral catalyst is reported. Catalytic amounts of achiral isothiouronium iodide salt 1d have been used for the first time as a co-catalyst for this reaction, which proved to be an excellent catalyst, producing good to excellent yields (up to 93%) with good stereoselectivities (up to 93:7 dr and 99% ee). These aldols are formed under solvent-free catalytic system, inside a standard laboratory refrigerator, and without stirring.     

A convenient synthesis of unsymmetrical secondary amines. Insitu formation of unstable formaldehyde imines.

The monoalkylation of aliphatic and aromatic primary amines can be accomplished by the reaction of organolithium or Grignard reagents with N-(cyanomethyl) or N-(aminomethyl) derivatives.     

Direct asymmetric aldol reactions catalyzed by l-proline-2,4,6-trinitroanilide

Direct aldol reactions of several aromatic aldehydes with ketones using l-proline-2,4,6-trinitroanilide catalyst 2d were conducted. Under optimized conditions, high enantioselectivity (99% ee), regioselectivity (up to 95:5), and diastereoselectivity (up to 98:2) were achieved.