Heats of formation, bond dissociation energies, proton affinities, gas phase acidities, and pKa values in water, dimethyl sulfoxide, acetonitrile, and tetrahydrofuran were calculated for all hydrogen-containing halomethanes and methane using composite correlated molecular orbital theory at the G3(MP2) and Feller-Peterson-Dixon (FPD) levels. Notably, the G3(MP2) method was extended to include iodine-containing compounds. The calculated gas phase acidities generally agree with available experimental data within experimental error limits, often within ±4 kJ/mol; however, CH2F2 is a significant exception where theory and experiment differ by nearly 40 kJ/mol for the acidity ΔG. Aqueous pKa values range from 53.6 for CH3F to 28.0 for CHF2I. The latter's unexpectedly high acidity results from the CF2I- anion resembling a CF2 carbene interacting with an iodide anion. These computed values rationalize literature base choices for anion generation: trihalomethanes (pKa 28.0-34.2) are deprotonated by nonorganometallic bases (KOH, DBU, KOtBu), whereas less acidic dihalomethanes (pKa ≳ 38), particularly fluorodihalomethanes (pKa 42-49), require strong metal amides (e.g., LTMP, LDA), with LHMDS proving inadequate. An experimental CHBrCl2 case study corroborates these predictions, showing clean deprotonation with lithium amides compared to diminished efficiency with weaker bases due to competitive hydroxide addition. This work provides the most comprehensive high-accuracy thermochemical data set for the complete set of hydrogen-containing halomethanes.

The chromatographic purification on silica gel of complex mixtures can pose several issues for chemists (e.g. degradation or racemization). Switching to aluminium oxide as the stationary phase could be a strategically successful choice. Herein, some practical advice for its effective use is disclosed.

Though surprising – when compared with well‐established poly‐ fluoromethyl silanes (e.g., Ruppert‐Prakash reagent, TMSCF 3 ) – α‐ mono ‐fluoromethyl silanes are underrepresented motifs in chemical synthesis, having been – so far – reported no more than 2–3 examples. We propose herein the nucleophilic substitution on the silicon atom of chlorosilanes – with fluoromethyllithium (LiCH 2 F) – as a general strategy for their direct preparation. The procedure ‐ exhibiting remarkable dependance on steric elements across silicon – can be advantageously extended to prepare distinct IV‐row heteroatom‐centered analogues such as tin and germanium organometallics.

The constitutive low aromaticity of easily accessible 5-trifluoromethyl-1,2,4-oxadiazoles is explored to enable editing modification to the corresponding unprecedented gem-disubstituted 1,2,4-oxadiazolines. The operation proceeds via the nucleophilic addition of diverse carbon-centered nucleophiles with excellent regiocontrol (in almost all cases), thus selectively furnishing either the 2,5-dihydro or 4,5-dihydro isomers. The process, which also exhibits high chemocontrol, enables further derivatization of the intermediate anion with externally added electrophilic platforms. Calculations support the experimental evidence and identify intrinsic steric properties of the nucleophiles as a key factor controlling regioselectivity, thus rationalizing the non-optimal outcome observed in particular circumstances (i.e. LiCH2Br).

α-Fluoromethyl amides were prepared through the chemoselective nucleophilic addition of fluoromethyl-lithium to isocyanates.

Though surprising - when compared with well-established poly-fluoromethyl silanes (e.g., Ruppert-Prakash reagent, TMSCF3) - alpha-mono-fluoromethyl silanes are underrepresented motifs in chemical synthesis, having been - so far - reported no more than 2-3 examples. We propose herein the nucleophilic substitution on the silicon atom of chlorosilanes - with fluoromethyllithium (LiCH2F) - as a general strategy for their direct preparation. The procedure - exhibiting remarkable dependance on steric elements across silicon - can be advantageously extended to prepare distinct IV-row heteroatom-centered analogues such as tin and germanium organometallics.

Lupeol, a naturally occurring pentacyclic triterpenoid widely distributed in various medicinal plants, has attracted significant attention due to its diverse pharmacological properties. In this study, we report the synthesis and structural modification of 14 lupeol derivatives through selective functionalizations at C3 and C30 positions of the lupane skeleton, via the sequential chemoselective introduction of carbonyl moieties and the addition of organometallics. Emphasis has been given to the stereoselective alkylation at C3 using a range of carbanions, including organolithiums, organomagnesiums and organoindiums. The C30 position was modified through oxidative pathways to introduce several functionalities.

Carbonyl groups undergo the sequential installation of two nucleophilic elements, halomethyl and fluoride moieties. This formal gem-difunctionalization enables the preparation-under full chemocontrol - of vic-fluorohaloethanes by simply defining the C1 nucleophile, thus enabling access to all combinations of the four halogens.

The hitherto few explored α‐halomethyl amidine motif has been assembled through the addition of a lithiated (di)‐halomethane (i.e., carbenoid) to easily accessible N,N’‐diaryl‐substituted carbodiimides. Despite the inherent low electrophilicity of these heterocumulenes—as quantitatively determined in Mayr's previous studies—their sp‐hybridized carbon atom acts as a competent site of attack for these tamed nucleophiles. The overall high‐yielding transformation featuring a genuine chemoselective profile—as documented by using variously functionalized materials—is adaptable to the addition of dihalogenated carbenoids. Reaction products could be advantageously used in nucleophilic substitution sequences as well as in further functionalization of the nitrogen atoms due to the constitutive heteroallyl‐type skeleton.

As eco-friendly processes become central to modern organic synthesis, plant-based materials are emerging as attractive alternatives for both nanoparticle fabrication and catalysis. In this study, we explore the use of clove extract, a natural and renewable resource, for the green synthesis of copper oxide (CuO) nanoparticles and their subsequent application in organic transformations. Clove extract was employed to reduce copper chloride via a simple co-precipitation method under mild conditions, yielding CuO nanoparticles characterized by XRD, FTIR, and SEM-EDX techniques. These nanoparticles were then used as catalysts in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) to afford eugenol-based 1,2,3-triazoles in excellent yields. This dual use of clove extract exemplifies a sustainable approach that merges natural product valorization with efficient catalysis for triazole synthesis.

image [ 75‐62‐7 ] CBrCl 3 (MW 198.28) InChI = 1S/CBrCl3/c2‐1(3,4)5 InChIKey = XNNQFQFUQLJSQT‐UHFFFAOYSA‐N (used in the synthesis of trichloromethylated compounds; brominating reagent) Alternate Name : trichloromethyl bromide. Physical Data : mp 21 °C; bp 104.7 °C; d 2.01 g cm −3 . Solubility : soluble in benzene, chloroform, ethanol, and ether. Form Supplied in : colorless liquid; commercially available. Analysis of Reagent Purity : 1 H NMR, 13 C NMR, elemental analysis. Purification : the liquid is dried over CaCl 2 or K 2 CO 3 then fractionally distilled. Handling, Storage, and Precautions : avoid skin contact, wear suitable protective clothing, gloves, and eye protection. Do not breathe vapor. Use in a fume hood. Store in closed containers in a cool dry place. Toxicity rat LD 50 : 119 mg kg −1 . Incompatible with strong oxidizing reagents and strong bases.

The homologation of esters-in the presence of a lithium carbenoid-to thioesters, amides, and carboxylic acid is reported. By controlling the tetrahedral intermediate collapsing and promoting a series of rearrangements ultimately leading to a high electrophilic ketene, the subsequent incorporation of S-, N-, and O-nucleophilic elements furnishes the title compounds. Despite the coexistence of multiple (concomitant) equilibria and short-living entities, the protocol features remarkable chemocontrol and flexibility. Notably, the formal oxidation state of the final compounds is retained.

Modern organic synthesis continues to benefit from the flexibility of α-diazo carbonyl intermediates. In the context of homologation processes, the Roskamp reaction—first introduced in 1989—has become a valuable tool due to its selectivity and mild condition reactions for accessing important synthons amenable to further functionalization as β-keto esters. The fine-tuning of reaction parameters—including the nature of Lewis acids, solvents, and temperature—has enabled the development of catalyzed continuous-flow methodologies, as well as a series of asymmetric variants characterized by high transformation rates, excellent stereocontrol, and formidable chemoselectivity. This review aims to emphasize the attractive features of the Roskamp reaction and its applicability for addressing challenging homologation processes.

[594‐15‐0] CBr 3 Cl (MW 287.17) Density: 3.0 g cm −3 . Boiling point: 160 °C. Melting point: 55 °C. InChI = 1S/CBr3Cl/c2‐1(3,4)5 InChIKey = GKXZMEXQUWZGJK‐UHFFFAOYSA‐N Solubility : tribromochloromethane shows comparable solubility to other halomethanes in organic solvents; it is not soluble in water. Form Supplied in : tribromochloromethane is supplied in a pure form as a colorless to pale yellow solid. Handling, Storage, and Precautions : it is advised to store CBr 3 Cl at temperatures from 2 to 30 °C. Avoid contact with skin and eyes. Provide appropriate ventilation. Preparative Methods : tribromochloromethane can be synthesized by reacting bromoform (CHBr 3 ) with sodium hypochlorite (NaOCl), according to Burton's procedure. CHBr 3 is added to a solution of hypochlorite and the reaction mixture is stirred vigorously for 3 days at room temperature. The newly formed solid is washed with water over a Buchner funnel to obtain a crude mixture containing CBr 3 Cl, as the main product, and traces of CBr 4 , CHBr 3 , and CHBr 2 Cl. Finally, the product can be isolated by spinning band distillation. 1

[594‐18‐3] CBr 2 Cl 2 (MW 242.72) Density: 2.4 g cm −3 . Boiling point: 66 °C. Melting point: 38 °C. InChI = 1S/CBr2Cl2/c2‐1(3,4)5 InChIKey = IHUREIPXVFKEDT‐UHFFFAOYSA‐N Solubility : dibromodichloromethane is very soluble in common solvents. It is not soluble in water. Form Supplied in : dibromodichloromethane is supplied as a colorless to pale yellow solid. Handling, Storage, and Precautions : it is advised to store dibromodichloromethane at temperatures in the range 2–30 °C. Avoid contact with skin and eyes. Provide appropriate ventilation. Preparative Methods : the preparation of dibromodichloromethane can be accomplished by reacting carbon tetrachloride (CCl 4 ) with aluminum tribromide (AlBr 3 ) at reflux for 8 h, followed by distillation. 1

The chemoselective synthesis of trisubstituted alkenyl halides (Cl, Br, F, I) starting from ketones and aldehydes and lithium halocarbenoids is reported. Upon forming the corresponding tetrahedral intermediate adduct, followed by the addition of thionyl chloride, a selective E2-type elimination is triggered, furnishing the targeted motifs. The transformation takes place under full chemocontrol: various sensitive functionalities (e.g. ester, nitrile, nitro, or halogen groups) can be placed on the starting materials, thus documenting a wide reaction scope, as well as the application of the technique to biologically active substances.

A homologative process that enables vinylene insertions into organoboronates stereoselectively forms alkenyl boronates.

CH 3 Li · LiBr [332360‐06‐2] CH 3 Li · LiBr or Br · CH 3 Li · Li (MW 108.821) InChI = 1S/CH3.BrH.2Li/h1H3;1H;;/q;;;+1/p‐1 InChIKey = XLIKYFMMLMHLKL‐UHFFFAOYSA‐M (metalating agent, preparation of organolithium species, including carbenoids) Solubility : methyllithium lithium bromide complex shows comparable solubility to methyllithium in ethereal solvents in which both are usually supplied. Toluene exhibits sufficient solubility properties, but it can slowly undergo decomposition due to the activation of lithiation processes. MeLi–LiBr reacts exothermically with water and protic solvents. Form Supplied in : methyllithium lithium bromide is supplied as a complex solution (1.5 or 2.2 M) in diethyl ether; density 0.85 g mL −1 at 25 °C. Handling, Storage, and Precautions : it is advised to store MeLi–LiBr in an explosion‐proof refrigerator at temperatures <10 °C in order to minimize major hazards (corrosivity, pyrophoricity, and flammability) also because of the presence of flammable solvents. Due to air and moisture sensitivity, the reagent should be stored under an inert atmosphere. 1 Preparative Methods : a method reported by Parkins deal with the preparation of MeLi · LiBr starting from MeBr and Li metal. 2 Lithium lumps are flattened with a hammer to 1.5 mm thickness and cut into chips (2 × 10 × 1.5 mm) and then placed in a flask containing 800 mL of dry diethyl ether. Thereafter, the mixture is cooled at −25 °C and the flask is purged with dry nitrogen or argon (2 L min −1 during 1–2 min). Through a cooled dropping funnel, MeBr (104.4 g, 1.1 mol) is added and the appearance of turbidity and the increase of internal temperature are diagnostic for the beginning of the reaction. After the addition is complete, the reaction is kept at −15 °C under stirring for an additional hour and subsequently the temperature is slowly increased to 0 °C. The obtained solution is poured into the storage flask, which previously has been filled with inert gas. During the filtration, a fast stream of inert gas is passed through the reaction flask to preserve the solution from oxidative phenomena. After solvent filling and gentle swirling, the titration of the solution indicates approximately 1 M, which corresponds to a chemical yield of 90%.