New liquid-crystalline isothiocyanates with high clearing points,low viscosities and strong nematic character

Abstract

Bi-, tri- and tetra-ring liquid-crystalline compounds with an isothiocyanate group in the terminal position of the molecule and with an ethylene group in the central position have been synthesized. Phenyl, cyclohexyl, bicyclo[2,2,2]octyl, 1,3-dioxane and pyrimidinyl were used as the ring systems. Their transition temperatures and melting enthalpies have been determined. The relationship between the order of the rings in the molecule and the clearing points and melting points of the compounds is discussed. It is shown that these compounds are valuable components of liquid crystal mixtures, since they effectively raise their clearing points yet only have a small effect on the viscosity.     

2,2′-Bis(arylamino)-1,1′-biaryls as Building Blocks for the Synthesis of Dibenzo[d,f][1,3]diazepines,Dibenzo[d,f][1,3]diazepinones,and Dibenzo[c,e][1,2,7]thiadiazepine 6-Oxides

The iron-catalyzed oxidative C−C homocoupling of diarylamines affords 2,2′-bis(arylamino)-1,1′-biaryls which represent crucial synthetic building blocks for an access to a range of seven-membered heterocyclic ring systems. Reaction with paraformaldehyde, diphenyl carbonate, and diphenyl sulfite as efficient 1,1-dielectrophiles led to dibenzo[d,f][1,3]diazepines, dibenzo[d,f][1,3]diazepinones, and dibenzo[c,e][1,2,7]thiadiazepine 6-oxides. The synthetic procedures enable short and practical routes to these 1,3-diazepine derivatives under mild reaction conditions and with a high tolerance of various functional groups.     

Synthetic and Structural Studies of Cyclophosphathiazenes and their Adducts with Lewis Acids

Abstract

The reactions of (Me₃SiNR)PPh₂ (NSiMe₃) (R=H, SiMe₃) with (NSCl)₃ or S_xCl₂ (x=1, 2) provide improved preparative routes to mixed phosphazene-thia-zene ring systems, e.g. (Ph₂PN) (SN)₂, 1,3- and 1,5-(Ph₂PN)₂(SN)₂. The interaction of these heterocycles with protonic and Lewis acids, e.g. HBF₄, BCl₃, MeSO₃CF₃, has been investigated in order to determine the site of attack and the effect of adduct formation on the molecular and electronic structures of these ring systems. These reactions have been monitored by UV-visible and ³¹P NMR spectroscopies and the structures of crystalline adducts have been determined by X-ray crystallography. For example, the interaction of 1,3-(Ph₂PN)₂(SN)₂ with MeSO₃CF₃ gives a product in which the methyl group is attached to a nitrogen atom between phosphorus and sulfur. The resulting structural distortion in this and related adducts will be analyzed in the context of the electronic structures of mixed phosphazene-thiazene systems and their adducts with Lewis acids.     

1-Azaspiro Annelation: A Synthetic Approach to Naturally Occurring Heterocyclic Spiranes

The synthesis of 1-azaspiro[4, 4]nonans, -[4, 5]decanes and -[5, 5]undecanes has attracted considerable attention in recent years with special interest in natural products such as histrionacotoxin,¹ serratinine² and harringtonine.³ We have been investigating several synthetic approaches to these systems in hopes of developing one general approach to all such compounds. We were particularly interested in simplicity and chose to utilize a preformed, readily accessible, carbocyclic ring to which the spiro-heterocyclic or nitrogen containing ring would be attached. Illustrative of these general considerations was the approach shown in Scheme I.     

Facile Syntheses of ABC Ring Skeleton of Camptothecin and Related Alkaloids

Abstract

Facile synthetic approaches toward the preparation of ABC ring of camptothecin and related alkaloids starting from cheaper and readily available chemical reagents.     

Cleavage of Diethyl Chromonyl α-Aminophosponate with Nitrogen and Carbon Nucleophiles: A Synthetic Approach and Biological Evaluations of a Series of Novel Azoles,Azines, and Azepines Containing α-Aminophosphonate and Phosphonate Groups

A convenient synthetic approach leading to a series of novel substituted azoles, azines, and azepines linked to the α-aminophosphonate moiety was achieved. The methodology depends on ring opening and ring closure (RORC) of the chromone ring of diethyl chromonyl α-aminophosphonate 1 via its reaction with nitrogen nucleophiles such as primary amines and 1,2-, 1,3-, and 1,4-bi-nucleophiles in ethanolic sodium ethoxide. Also, treatment of compound 1 with some acyclic and cyclic active methylene compounds under the same reaction conditions afforded interesting novel isolated and fused pyridine systems bearing phosphonate groups at the α-position. The screening of antimicrobial activity for the synthesized compounds indicates that connection of pyrazole, oxazepine, and benzodiazepine rings with α-aminophosphonate moiety exhibited good antimicrobial effects. Also, evaluation of their antioxidant properties shows that the compounds having 1,5-benzoxazepinyl and 1,5-benzodiazepinyl units in combination with α-aminophosphonic diester moiety are the most powerful antioxidant agents.     

Stereoselective total synthesis of 4-((3S,5R)-3,5-dihydroxynonadecyl)phenol

A stereoselective total synthesis of 4-((3S,5R)-3,5-dihydroxynonadecyl)phenol has been accomplished in two different synthetic approaches. In the first approach, Prins cyclization has been successfully utilized to produce the anti-1,3-diol unit, which was further converted into a required syn-1,3-diol through Mitsunobu reaction. The side chain was constructed through cross metathesis and hydrogenation sequence. In the second approach, the chiral syn-1,3-diol was prepared by a sequence of reactions such as alkylation of 1,3-dithane with (R)-epichlorohydrin, ring opening of the epoxide with vinylmagnesium bromide, and 1,3-syn-reduction of the β-hydroxyketone with NaBH₄ in the presence of diethylmethoxyborane.     

Recent progresses in the synthesis of functionalized isoxazoles

Isoxazole is an important pharmacophore that is critical for biological activity. The isoxazole ring ranks 33rd in frequency among the 351 ring systems found in marketed drugs, thus suggesting a great deal of interest in the synthesis of functional isoxazoles. In recent years, various approaches have been developed for the synthesis and functionalization of isoxazoles. This comprehensive survey summarizes the recent new synthetic approaches to functionalized isoxazoles, with particular focus on the last three years with regard to the following reaction types: (1) 1,3-dipolar cycloaddition, (2) condensation, (3) cycloisomerization, and (4) direct functionalization.     

SOME REACTIONS OF 1,3-THIAZINE DERIVATIVES WITH ALIPHATIC DIAMINES

Abstract

A wide range of 2-substituted-5,6-dihydro-4H-1,3-thiazines (I) and tetrahydro-2H-1,3-thiazines (II) have been found to undergo a facile ring transformation reaction with aliphatic diamines to form the corresponding dinitrogen heterocycles (III) and (IV).     

Substituted Quinolinones,Part 12: Heterocyclization Reactions of 3‐(3‐Chromonyl)acryloylquinolinone with Some Bifunctional Nucleophiles

4‐Hydroxy‐1‐methyl‐3‐[E‐3‐(4‐oxo‐4H‐chromen‐3‐yl)acryloyl]quinolin‐2(1H)‐one (3) was smoothly obtained via a one‐pot aldol dehydration reaction of 3‐acetyl‐4‐hydroxyquinolin‐2(1H)‐one with 3‐formylchromone and was utilized to prepare miscellaneous triheterocyclic systems containing the quinolinone moiety. Both the α,β‐unsaturated ketone side chain and the γ‐pyrone ring in compound 3 were subjected to nucleophilic cyclization with certain 1,2‐ and 1,3‐bifunctional N,N‐, N,O‐, N,C‐, and O,C‐nucleophiles under different reaction conditions. Many pyrazolinyl‐, isoxazolinyl‐, pyrimidinyl‐, and pyridinylquinolinones bearing other six‐ or five‐membered heterocyclic systems have been conveniently synthesized using more than one synthetic route.     

A new synthetic method for the preparation of protonated-NHCs and related compounds

Protonated versions of N-heterocyclic carbenes (NHC,H⁺) are classically prepared by closing the ring through the introduction of the CH⁺ fragment. Here we report a totally different synthetic approach, which can be viewed as the addition of a 1,3-diazaallyl anion to a compound featuring two leaving groups (hereafter named “di-electrophile”). Using 1,3- and 1,4-dibromides, six- and seven-membered NHC,H⁺s have been prepared in good yields. Similarly, with 1,3,2-dioxathiolane-2,2-dioxide as a di-electrophile, imidazolidinium salts were obtained. To illustrate its broad scope of application, this synthetic route has been expanded to the preparation of protonated cyclic amino alkyl carbenes (CAACs) and amino thio carbenes, using 1-aza-allyl and 1,3-azathio-allyl anions, respectively.     

Beiträge zur Stereochemie der Additionsreaktionen an 3,4,5,6-Tetrahydropyridin-1-oxide. 3. Mitt.: Stereochemie der 1,3-Additionen an alkylsubstituierte 3,4,5,6-Tetrahydropyridin-1-oxide

4-tert-Butyl-3,4,5,6-tetrahydropyridine-1-oxide (1) and 6-Butyl-3,4,5,6-tetrahydropyridine-1-oxide (2) were selected to study the stereochemistry of 1,3-additions (nucleophilic additions) to these unsaturated six membered ring systems. Butylmagnesiumbromide, sodiumboronhydride and potassium cyanide were chosen as reagents. They added axially to1, but yielded mixtures of the two possible stereoisomeres with2.

     

Utilization of 2‐Chloronicotinonitrile in the Syntheses of Novel Fused Bicyclic and Polynuclear Heterocycles of Anticipated Antitumor Activity

Some of synthetic bicyclic and polynuclear heterocyclic compounds based on pyridine scaffold were tested as in vitro antitumor agents, and these compounds found to exhibit interesting activities. Fused heterocycles containing sulfur such as thienopyridine, pyridothiazine, and some related fused heterocycles as new ring systems were achieved. Bicyclic thienopyridine 6 and pyrido[3,2‐e][1,3]thiazin‐4(3H)‐one 7 exhibited good antitumor activities compared with 5‐fluorouracil.     

Highly efficient enantioselective synthesis of 1,3-disubstituted 2,5-diketopiperazine derivatives via microwave irradiation

Abstract

Chiral 2,5-diketopiperazine (2,5-DKP) derivatives have a broad range of biological activities in the medicinal field. The synthetic protocols of 1,3-disubstituted 2,5-DKPs via base-catalyzed cyclization of chloroacetamide have been reported. However, there are several drawbacks, such as an overly long reaction time, low to moderate yield, and racemization of the products. The sequence modified herein of 1,3-disubstituted 2,5-DKPs involves microwave-assisted cyclization. It increases yields and reduces reaction time. Furthermore, employing N-PMB protection prevents racemization, which frequently occurs in the base-catalyzed cyclization reaction. Consequently, the rapid synthetic method of enantiomerically pure 1,3-disubstituted 2,5-DKPs via microwave reaction was established successfully.     

6-(2-Haloethyl)-2,2-dimethyl-4H-1,3-dioxins: versatile haloethyl vinyl ketone equivalents for carbocycle construction

6-(2-Iodoethyl)-2,2-dimethyl-4H-1,3-dioxin has been prepared in five steps from ethyl acetoacetate. A variety of enolates were then alkylated with this iodide. The resulting 6-alkyl-4H-1,3-dioxins were either subjected to further transformations and/or heated (or subjected to a Lewis acid) to effect facile retrocycloaddition reactions. The resulting enones were found to smoothly participate in conjugate addition or olefin metathesis reactions to provide various carbocyclic ring systems. Collectively, these examples document the synthetic equivalency of dioxin 2 with iodoethyl vinyl ketone and, moreover, delineate a strategy for accomplishing the sequential reactions with nucleophiles at the β′, followed by the β electrophilic sites.     

Synthese und Reaktionsverhalten von 6-sec-Amino-1,3-thiazin-2-thionen

The title compounds3 have been prepared by ring transformation reactions of the isomeric 2-sec-amino-1,3-thiazine-6-thiones1 via ring-opening products2 and by special cyclocondensation reactions with thiocarboxamides8, and with iminium salts10, starting from 2,2-dichlorovinyl ketones6 in all cases. The pathways differ specifically in scope and limitations. On the other hand the intermediates2 react with alkylating agents to 2,6-di-sec-amino-1,3-thiazinium salts4, which are also available via alkylation of3 to 2-methylthio-1,3-thiazinium salts11 and aminolysis. Moreover,11 serve as useful precursors for other 1,3-thiazine derivatives by nucleophilic methylthio displacement (examples12).

     

Titanocene complexes of the N-methyl and N-phenyl-1,3-thiazoline-2-thione-4,5-dithiolates and 4,5-diselenolate ligands

Cp₂Ti(dithiolene) and Cp₂Ti(diselenolene) complexes containing the N-methyl-1,3-thiazoline-2-thione-4,5-dithiolate ligand (Me-thiazdt), the N-phenyl-1,3-thiazoline-2-thione-4,5-dithiolate ligand (Ph-thiazdt) and the N-methyl-1,3-thiazoline-2-thione-4,5-diselenolate ligand (Me-thiazds) have been synthesized. Three approaches have been developed in order to generate the dithiolene or the diselenolene ligands which were reacted with Cp₂TiCl₂ to form the corresponding heteroleptic complexes. Their X-ray crystal structures, UV-Vis absorption spectra as well as their redox properties, determined by cyclic voltammetry have been investigated and discussed. Variable-temperature ¹H NMR experiments have been performed in order to determine the activation energies of the chelate ring inversion.     

Synthetic approaches toward piperidine related structures: A review

Abstract

The current review covers explosive development of various synthetic approaches for piperidine scaffold and its analogues in the last few decades. The piperidine ring system is a key motif in many natural alkaloids and synthetic organic compounds. Further, piperidine moiety has gained significant consideration in drug discovery due to its wide range of therapeutic applications.     

SYNTHESIS,CHARACTERIZATION, AND BIOLOGICAL STUDIES OF NOVEL ISOXAZOLIDINES: 1,3-DIPOLAR CYCLOADDITION REACTIONS

ABSTRACT

1,3-Dipolar cycloaddition reaction of nitrones to olefins is of synthetic interest. In the present work, isoxazolidines have been synthesized in high yield via intermolecular cycloaddition of N-arylnitrone with monosubstituted olefins and are employed for biological evaluation.     

Straightforward Access to Pyrazine-(2,3)-diones through Sequential Three-Component Reaction

A novel protocol for the assembly of polysubstituted 2,3-dioxo-1,4,5,6-tetrahydropyrazines and 2,3-dioxo-hydro-1H-cycloalkyl[b]pyrazines has been developed by the sequential three-component reaction of primary aliphatic amines, 1,2-diaza-1,3-dienes (DDs) and oxalyl chloride. This synthetic sequence proceeds by initial aza-Michael addition of the amine to the azo-ene compounds and subsequent ring closure involving the oxalyl chloride. The ready availability of the starting materials as well as the high level of practicability of the reaction and work-up make this approach an attractive opportunity towards these uncommon systems.