Presence Of TiCl4 Research Articles

Claisen Self-Condensation of Lactones in the Synthesis of Ionizable Lipids.

The Claisen self-condensation of lactones can be carried out safely and efficiently under Mukaiyama conditions, in the presence of TiCl4 and triethylamine. The primary Claisen products can be elaborated to various derivatives or converted directly into dihydroxyketones. Such compounds are valuable educts for the synthesis of ionizable lipids for the delivery of nucleic acid therapeutics and can now be accessed through a concise, economical, scalable route that avoids more technically challenging reaction sequences.

Stereoselective Domino Semipinacol‐Schmidt Reaction: Diastereoselective Synthesis of 7 a‐epi‐(+)‐Lepadiformine C and Formal Synthesis of 7 a‐epi‐(−)‐Lepadiformine A

AbstractA concise approach has been developed for the diastereoselective synthesis of the azatricyclic core of (−)‐7 a‐epi‐lepadiformine A (8 a) and (−)‐7 a‐epi‐lepadiformine C (8 b) using stereoselective domino semipinacol‐Schmidt reaction as a key step. In presence of TiCl4, the oxaspiropentane‐azide derivatives underwent stereoselective domino cyclization to furnish the corresponding angularly fused azatricyclic cores in very good yields. Moreover, azatricyclic core of (−)‐7 a‐epi‐lepadiformine A has also been realized, in a stepwise manner, through the intramolecular Schmidt reaction of azido‐spirocyclobutanone intermediate. The synthetic utility of domino semipinacol‐Schmidt reaction is further shown in the diastereoselective synthesis of (+)‐7 a‐epi‐lepadiformine C (7).

Synthesis of 3-Acyloxyindolenines by TiCl3-Mediated Reductive Cyclization of 2-(ortho-Nitroaryl)-Substituted Enol Esters.

In the presence of TiCl3, the reductive cyclization of tetrasubstituted enol esters bearing a 2-(ortho-nitroaryl) substituent affords 3-acyloxy-2,3-disubstituted indolenines in good yields. A domino process involving the partial reduction of nitro to a nitroso group followed by 5-center-6π-electrocyclization, 1,2-acyloxy migration, and the further reduction of the resulting nitrone intermediate accounts for the reaction outcome. The so-obtained indolenines are converted smoothly to 2,2-disubstituted oxindoles via a sequence of saponification and semipinacol rearrangement.

Dihydrooxazine Byproduct of a McMurry–Melton Reaction en Route to a Synthetic Bacteriochlorin

A synthetic route to gem-dimethyl-substituted bacteriochlorins—models of native bacteriochlorophylls—relies on the formation of a dihydrodipyrrin precursor via a series of established reactions: van Leusen pyrrole formation, Vilsmeier formylation, Henry reaction, borohydride reduction, Michael addition, and McMurry–Melton pyrroline formation. The latter is the least known of the series. Here, the McMurry–Melton reaction of a 2-(6-oxo-2-nitrohexyl)pyrrole in the presence of TiCl3 and an ammonium acetate buffer formed the expected Δ1-pyrroline, as well as an unexpected polar, cyclic byproduct (a 5,6-dihydro-4H-1,2-oxazin-6-ol), each attached to the 2-methylpyrrole unit. Both species were characterized by single-crystal X-ray diffraction. The McMurry–Melton reaction is a type of intercepted Nef reaction (the transformation of a nitroalkyl motif into a carbonyl group), where both the Δ1-pyrroline and the dihydrooxazine derive from the reaction of the nitrogen derived from the nitro group upon complete or partial reductive deoxygenation, respectively, with the γ-keto group. The report also considers competing Nef and McMurry–Melton reactions, the nature of available TiCl3 reagents, and the use of ammonium acetate for buffering the TiCl3/HCl reagent.

Stereoselective synthesis of 2-deoxy-2-disubstituted ribonolactones through a TiCl4-mediated Evans-Aldol reaction

A convenient and novel route for the stereoselective synthesis of 3,5-Di-O-benzoyl-2-deoxy-2-chloro-2-C-methyl-ᴅ-ribono-γ-lactone 5a and its analogues is developed by an Evans-Aldol reaction in the presence of TiCl4. Starting from 2-chloropropionyl chloride, 5a is efficiently and regioselectively produced on a kilogram scale in an overall yield of 32% with an HPLC purity of 98% by area. In addition, this approach allowed an efficient synthesis of 3,5-Di-O-benzoyl-2-deoxy-2-fluoro-2-C-methyl-ᴅ-ribono-γ-lactone 5b in a total 20% yield.

Synthesis of Benzazepinoindole Derivatives via a One‐Pot Process of TiCl4‐Catalyzed Indole Alkylation/Pictet‐Spengler Cyclization

AbstractAn efficient synthetic approach involving indole alkylation/Pictet‐Spengler cyclization was developed to form benzazepinoindole derivatives. The reactions proceeded smoothly with indoles, 2‐aminobenzyl alcohols, and aldehydes in the presence of TiCl4 as a Lewis acid catalyst. The developed one‐pot protocol is operationally simple and tolerates various functional groups. Furthermore, this mild and practical tandem reaction provides a direct route to access benzazepinoindole‐containing natural products and bioactive compounds.

Control of Molar Mass Characteristics of Polybutadiene—a Component of Sticky Glue—by Physical Modification of the Catalytic System in Turbulent Flows

The computational experiments were carried out on the model of butadiene polymerization (toluene as a solvent) in the presence of TiCl4–Al(i-C4H9)3 catalytic system, physically modified in turbulent flows. It was shown that, the higher is the feed rate of reaction mixture into the tubular turbulent apparatus with diffuser-confuser design, and the larger is the ratio of the diffuser diameter to confuser diameter, and the greater is the diffuser opening angle, the lower are the number-average and mass-average molar masses of polybutadiene. These values of number-average and mass-average molar masses of obtained polybutadiene under upper conditions allows using it as a polymer component of sticky glue.

α-Imino Iridium Carbenes from Imidoyl Sulfoxonium Ylides: Application in the One-Step Synthesis of Indoles.

Imidoyl sulfoxonium ylides are presented for the first time as potential precursors to generate α-imino metal-carbene intermediates and applied in direct C-H functionalization reactions catalyzed by [Ir(cod)Cl]2 (4 mol %) to provide 2-substituted indoles (up to 70% yield) in just one step. This class of sulfur ylide is successfully obtained from imidoyl chloride and dimethylsulfoxonium methylide (23 new examples in 45-85% yield) or by imino group formation from the corresponding β-keto sulfoxonium ylides and anilines in the presence of TiCl4 as a Lewis acid (9 examples in 33-94% yield).

Practical direct synthesis of N-aryl-substituted azacycles from N-alkyl protected arylamines using TiCl4 and DBU

A novel transformation of N-alkyl protected arylamines and cyclic ethers into N-aryl substituted azacycles is described. Alkyl groups have been used for the protection of amines in organic syntheses. In this synthesis, N-alkyl protected arylamines were reacted with cyclic ethers in the presence of TiCl4 and DBU, crucial reagents affording five- and six-membered azacycles. In particular, utilization of the novel TiCl4/DBU-mediated reaction allows various N-alkyl protected arylamines such as N-methyl-, N-ethyl-, N-isopropyl, and N-tert-butyl arylamines to be readily converted into N-aryl substituted azacycles in high yields. This practical approach using various N-alkyl arylamines leads to the efficient preparation of azacycles.

TiCl4 mediated facile synthesis of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles

An efficient method for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles has been developed. Various hydrazides or thionyl hydrazides readily react with DMA derivatives in the presence of TiCl4 as a catalyst to afford the desired products. This protocol provides a simple and economical procedure that affords the target products with good yields and wide substrate scope.

Syntheses of chiral fused 4,5-diazafluorene–bis(nopinane) derivatives

Reaction of fused 4,5-diazafluorene–bis(nopinane) with tere-phthalaldehyde, benzophenone, ninhydrin or anthraquinone in THF in the presence of TiCl4 and pyridine results in a formation of new chiral condensation products, which exhibit solvatochromism and pleochroism. Crystal structure of the key products has been determined by X-ray crystallography, and unusual colour behavior has been explained by DFT calculations.

Intramolecular cyclization of polyfluoroalkyl-containing 2-(arylhydrazinylidene)-1,3-diketones

Refluxing of polyfluoroalkyl-containing 2-(arylhydrazinylidene)-1,3-diketones in dichloroalkanes in the presence of TiCl4 gives 3-acyl-4-polyfluoroalkylcinnolines as a result of Friedel-Crafts intramolecular cyclization with the participation of polyfluoroacyl and arylhydrazone moieties. 2-(Arylhydrazinylidene)-3-phenyl-1-polyfluoroalkylpropan-1,3-diones in the presence of CF3SO3H in dichloromethane at −20…−30 °C undergo the competitive cyclization with the participation of polyfluoroacyl and benzoyl groups to form 3-hydroxy-2-(arylhydrazinylidene)-3-polyfluoroalkylindan-1-ones. The heating of 2-(arylhydrazinylidene)-1,3-diketones in polyphosphoric acid at 115…120 °C resulted in 2-polyfluoroalkyl-1-(2-arylhydrazinylidene)ethan-2-ones. The tuberculostatic activity of the obtained cinnolines and indanone was found to be at the level of pyrazinamide or higher. It was established that these compounds do not inhibit cholinesterases and have rather weak inhibitory activity against carboxylesterase. A high antiradical activity was shown for indanone.

Formation of amides: one-pot condensation of carboxylic acids and amines mediated by TiCl4

A general procedure for the synthesis of amides via the direct condensation of carboxylic acids and amines in the presence of TiCl4 is reported. The amidation reaction was performed in pyridine at 85 °C with a wide range of substrates providing the corresponding amide products in moderate to excellent yields and high purity. The reaction proceeds with low yields when both the carboxylic acid and the amine are sterically hindered. The process takes place with nearly complete preservation of the stereochemical integrity of chiral substrates.

Assigning the stereochemistry of syn and anti β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters using GIAO 1H NMR chemical shift calculations

The stereostructure of β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters synthesized by Bellassoued et al. [J. Org. Chem. 2001, 66, 5054–5057] using Mukaiyama aldol reaction has been reassigned using density functional theory NMR 1H chemical shifts calculations. It is now concluded that the major diastereoisomer is syn and the minor is anti. Within this assignment, for all silyl esters, δHa(anti) > δHa(syn), δHb(anti) < δHb(syn), and 3JHa-Hb (anti) > 3JHa-Hb (syn). Since the experimental assignment was based on the stereostructure (E/Z) of the cinnamic acid obtained by elimination of trimethylsilyl 3-phenyl-3-(trimethylsiloxy)-2-(trimethylsilyl)propanoate in the presence of TiCl4 and on the assumption that this elimination is anti stereospecific in acidic medium, one arrives at the conclusion that the elimination of syn and anti β-trimethylsiloxy-α-trimethylsilyl alkanoic acid silyl esters is not anti stereospecific.

Decoupling and Functionalization of Coupled Polyisobutylene via Alkoxybenzene Quenching

During living polymerization of isobutylene, marginal conditions can lead to reaction of carbenium ions with exo-olefin and production of coupled polyisobutylene (PIB). When living PIB containing a coupled fraction is subjected to end-quenching with an alkoxybenzene compound in the presence of TiCl4, the coupling reaction is quantitatively reversed to form the two original chain ends, and the regenerated chains are observed to possess the desired alkoxyphenyl functionality. To demonstrate this phenomenon, various PIB samples were prepared to purposefully contain significant coupled fractions, from 10 to 55 mol %, by quenching living PIB with hindered nucleophiles under marginal conditions. The coupled fractions were quantified by 1H NMR and GPC. Coupled PIB samples were reacted with (3-bromopropoxy)benzene, methoxybenzene, or 4-phenoxy-1-butyl acrylate in the presence of TiCl4 and a source of protic catalyst. Various protic sources were found to be effective including externally added water, adventitious ...

Direct synthesis and phytotoxic activity of bicyclic-γ-lactones derived from 2,3-epoxycyclohexanone

A direct method for the synthesis of highly functionalized bicyclic-γ-lactones with three consecutive stereocenters has been developed from the reaction of the easily available 2,3-epoxycyclohexanone and different bis-(trimethylsilyl)ketene acetals in the presence of TiCl4. During reaction, a chlorine atom transfer from TiCl4 occurs as confirmed by single crystal X-ray crystallography. The phytotoxic activity of the synthetized compounds was evaluated, and it was found that these lactones interfere with the seed germination, root elongation, and seedling respiration of Amaranthus hypochondriacus and Solanum lycopersicum seeds being in some cases more potent than positive control Rival.

Studies towards C-3 functionalization of β-lactams using substituted allylsilanes

An effective and stereoselective synthesis of 3-(1′-methyl/phenylallyl)-3-phenylthio-β-lactams (3/4) using substituted allylsilane and Lewis acid is described. The reaction leads to the formation of a mixture of C-3 substituted allyl β-Lactams. However, these compounds on desulphurisation using tri-n-butyltinhydride and Raney Ni provide two separable diastereomers of the reduced product. In the presence of TiCl4, silanes such as crotylsilanes and cinnamylsilanes add efficiently at C-3 position of trans-3-chloro-3-phenylthio-β-lactams.

SF5-Enolates in Ti(IV)-Mediated Aldol Reactions

The F···Ti bonding in the transition structures determines high trans- and syn-diastereoselectivities for aldol reactions of SF5-acetates with aldehydes in the presence of TiCl4 in the non-nucleophilic solvent CH2Cl2. Such bonding is canceled in nucleophilic solvents where opposite cis-stereochemistry is observed. The potential of thus obtained stereoisomeric SF5-aryl acrylates as dipolarophiles in the preparation of SF5-containing heterocycles is demonstrated.

Improvement of rheological properties of invert drilling fluids by enhancing interactions of water droplets using hydrogen bonding linker

The conventional method to improve rheological properties of oil based muds (OBMs) by dispersing organoclays in continuous oil phase has generally been considered inefficient and deficient. This paper presented a new method to improve the rheological properties by using a hydrogen bonding linker (HBL) that can replace organoclay to enhance the interactions of water droplets through hydrogen bonding. Hydrogen bonding linker was synthesized by reaction of dimer acid and diethanolamine in the presence of TiCl4 as catalyst at 130°C, and characterized by FTIR. Emulsions with different concentrations of HBL were then characterized by bottle tests, focused beam reflectance measurements (FBRM) and rheological measurements. Experimental results show that optimum stability is achieved when the concentration of HBL is 2g/L. But when concentration of HBL exceeds 2g/L, the trend of instability is increasingly stronger because HBL leads to coalescence of water droplets. Emulsions with HBL demonstrate a more fragile gel structure and a stronger thixotropic behavior than emulsion without HBL. The application of HBL in an organoclay-free OBM shows that a higher yield point (YP), higher Gel strengths and a higher electrical stability (ES) were achieved in comparison with the conventional OBM.

Synthesis and Characterization of Mikanecic acid Diesters using NaH

Catalysts are used to make changes easier in the organic synthetic mechanism. Catalysts are involved in the process of chemical changes by reducing time and making it faster to get things done. Catalysts play a vital role in organic synthesis with a novel method for the synthesis of a terpenoid, Mikanecic acid diester. In this research we are using NaH to synthesis Baylis-Hillman adducts (alkyl-3-hydroxy-2-methylenepropanoates reacts with aldehyde with a variety of acrylates catalyzed in presence of TiCl4). Mikanecic acid diesters obtained from 1, 3-butadiene-2-carboxylate of (Diels-Alder type) self-dimerization occur in the presence of different catalysts. The yield which we obtained is in good ratio.