Crystalline Reagent Research Articles

Vinyl Thianthrenium Tetrafluoroborate: A Practical and Versatile Vinylating Reagent Made from Ethylene.

The use of vinyl electrophiles in synthesis has been hampered by the lack of access to a suitable reagent that is practical and of appropriate reactivity. In this work we introduce a vinyl thianthrenium salt as an effective vinylating reagent. The bench-stable, crystalline reagent can be readily prepared from ethylene gas at atmospheric pressure in one step and is broadly useful in the annulation chemistry of (hetero)cycles, N-vinylation of heterocyclic compounds, and palladium-catalyzed cross-coupling reactions. The structural features of the thianthrene core enable a distinct synthesis and reactivity profile, unprecedented for other vinyl sulfonium derivatives.

2,3-Dimethoxyindolines: a latent electrophile for SNAr reactions triggered by indium catalysts.

2,3-Dimethoxyindolines (DiMeOINs) have emerged as a latent electrophile in indium-catalyzed SNAr reactions. They are easily obtained from commercially available indoles and allowed access to 3-substituted indoles. The reaction proceeds via SNAr reactions of in situ generated 3-methoxyindoles. Formation of C2-substituted indoles was also possible utilizing the C2-nucleophilicity of DIMeOIN. Our protocol is user friendly as DiMeOIN is a bench-stable easy-to-handle crystalline reagent.

Revisiting the Urech Synthesis of Hydantoins: Direct Access to Enantiopure 1,5-Substituted Hydantoins Using Cyanobenziodoxolone.

A method for the synthesis of enantiopure 1,5-substituted hydantoins was developed using a hypervalent iodine cyanation reagent (cyanobenziodoxolone, CBX) as a source of electrophilic carbon. Starting from inexpensive commercially available enantiopure protected amino acids, the method allowed the synthesis of various hydantoins without epimerization. Formation of hydantoins from dipeptides was also possible, but partial epimerization was observed in this case. This synthetic strategy is user friendly as CBX is a bench-stable easy-to-handle crystalline reagent and avoids conventional multistep protocols, thus allowing the facile synthesis of a library of chiral hydantoins.

Merging hypervalent iodine and sulfoximine chemistry: a new electrophilic trifluoromethylation reagent.

Electrophilic trifluoromethylation is at the forefront of methodologies available for the installation of the CF3 moiety to organic molecules; research in this field is largely spurred by the availability of stable and accessible trifluoromethylation reagents, of which hypervalent iodine and sulfoximine based compounds have emerged as two prominent reagent classes. Herein, we describe the facile synthesis of an electrophilic trifluoromethylation reagent which merges these two scaffolds in a novel hypervalent iodosulfoximine compound. This presents the first analogue of the well-known Togni reagents which neither compromises stability or reactivity. The electronic and physical properties of this new compound were fully explored by X-ray crystallography, cyclic voltammetry, TGA/DSC and DFT analysis. This solution stable, crystalline reagent was found to be competent in the electrophilic trifluoromethylation of a variety of nucleophiles as well as a source of the trifluoromethyl radical. Furthermore, the possibility of enantioinductive transformations could be probed with the isolation of the first enantiopure hypervalent iodine compound bearing a CF3 group, thus this new reagent scaffold offers the opportunity of structurally diversifying the reagent towards asymmetric synthesis.

Introduction of a Crystalline, Shelf-Stable Reagent for the Synthesis of Sulfur(VI) Fluorides.

The design, synthesis, and application of [4-(acetylamino)phenyl]imidodisulfuryl difluoride (AISF), a shelf-stable, crystalline reagent for the synthesis of sulfur(VI) fluorides, is described. The utility of AISF is demonstrated in the synthesis of a diverse array of aryl fluorosulfates and sulfamoyl fluorides under mild conditions. Additionally, a single-step preparation of AISF was developed that installed the bis(fluorosulfonyl)imide group on acetanilide utilizing an oxidative C-H functionalization protocol.

Thermochemistry of inorganic crystals at nonstandard conditions

Methodology for thermochemical evaluating reactivity of solid phases in nonstandard states is proposed, both amorphous and crystalline reagents being considered. The principal attention is paid to baroinduced states of solid reagents. Analytical expressions both for calculating baroinduced increments of thermochemical quantities and for linearized evaluating these quantities at polymorphic transformations are derived. The criterion for differentiation of activating and passivating pressure effects at solid-state transformations is advanced. The influence of crystal structure symmetry on its baroinduced reactivity is analyzed. Parameters for practical calculations are tabulated.

Naphthalene and Anthracene Cobaltates(1−): Useful Storable Sources of an Atomic Cobalt Anion

Reductions of CoBr(2) or cobaltocene by 3 equiv of potassium anthracene radical anion in tetrahydrofuran (THF) afford 60-80% yields of bis(anthracene)cobaltate(1-) (1), of interest as a readily accessible and quite labile source of spin-paired atomic Co(-). Although the unsolvated potassium salt of 1 is thermally unstable at 20 °C, the [K(18-crown-6)(THF)(2)](+) salt of 1 functions as a useful storable crystalline reagent for Co(-) in several reactions. Previously known classic cobaltates, [CoL(4)](-), for L = 1/2 (1,3-butadiene) (2), PF(3) (3), and P(OiPr)(3) (5), were obtained directly from 1 and structurally characterized for the first time. Anion 3 is noteworthy because it appears to possess the shortest known Co-P distance, av = 2.012(4) Å. Although the naphthalene analogue of 1 is not yet available as a pure substance, low-temperature reductions of CoBr(2) or cobaltocene by naphthalene radical anion in the presence of 1,5-cyclooctadiene (COD) afford variable yields (80-90% from CoCp(2)) of (naphthalene)(COD)cobaltate(1-) (10). Ready displacement of naphthalene in 10 by L = 1,3-butadiene, 2,2'-bipyridine, and COD occurs to give good yields of the respective [Co(L)(COD)](-), all of which have been structurally characterized. Both ligands in 10 are displaced by tert-butylisocyanide to afford [Co(CNtBu)(4)](-) (16), the first isolable and structurally characterized homoleptic alkylisocyanometalate. The molecular structure of 16 shows unprecedented bending of the isocyanides, av C-N-C = 137(2)°, for homoleptic isocyanide complexes.

Reagent‐Installed Capsule Network: Selective Thiocarbamoylation of Aromatic Amines in Crystals with Preinstalled CH3NCS

Crystalline reagent capsules were prepared by installing CH3NCS into networked molecular capsules. While the tight encapsulation completely prevented leaching of reagent molecules into the supernatant, introduction of amines into the interstitial pores triggered reagent delivery. As a result, enhanced substrate selectivity was observed in crystalline-state thiocarbamoylation (see picture; 86:14 in favor of 2- vs. 1-naphthylamine).

A new crystal engineering approach for the synthesis of {[K.18-Crown-6]I3}n as a nanotube-Like and recyclable catalyst for the chemoselective silylation of alcohols

Reaction of 18-crown-6 with KI in ethanol solution followed by addition of iodine (I2) afforded a unique triiodide salt with a nanotube-like structure ({[K.18-Crown-6]I3}n). It is shown that this reagent may be used for the chemoselective trimethylsilylation of alcohols. The synthesis of the crystalline reagent is a good example of crystal engineering. Reagent was recycled and reused.

Thionations Using a P4S10−Pyridine Complex in Solvents Such as Acetonitrile and Dimethyl Sulfone

Tetraphosphorus decasulfide (P(4)S(10)) in pyridine has been used as a thionating agent for a long period of time. The moisture-sensitive reagent has now been isolated in crystalline form, and the detailed structure has been determined by X-ray crystallography. The thionating power of this storable reagent has been studied and transferred to solvents such as acetonitrile in which it has proven to be synthetically useful and exceptionally selective. Its properties have been compared with the so-called Lawesson reagent (LR). Particularly interesting are the results from thionations at relatively high temperatures (∼165 °C) in dimethyl sulfone as solvent. Under these conditions, for instance, acridone and 3-acetylindole could quickly be transformed to the corresponding thionated derivatives. Glycylglycine similarly gave piperazinedithione. At these temperatures, LR is inefficient due to rapid decomposition. The thionated products are generally cleaner and more easy to obtain because in the crystalline reagent, impurities which invariably are present in the conventional reagents, P(4)S(10) in pyridine or LR, have been removed.

Preparation and Reactions of (β-Trifluoromethyl)vinyl Sulfonium Salt

(Beta-trifluoromethyl)vinyl sulfonium salt as a novel three-carbon fluorinated building block was conveniently prepared from easily available (beta-trifluoromethyl)vinyl sulfide and diphenyl iodonium salt in excellent yield. This easily handled crystalline reagent displayed two types of useful transformation involving aziridination and vinylation to afford the corresponding trifluoromethylated compounds in excellent yields.

Hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose as new crystalline reagent in the preparation of Amadori derived peptides

Abstract We established, that crystalline hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose is a new, convenient and stable reagent for solid phase synthesis of peptide derived Amadori products. The structure of the title compound was studied by X-ray analysis, NMR spectroscopy, and high resolution ESI-MS. The crystal structure indicated the existence of two symmetry-independent molecules that were not connected with hydrogen bonds. A comparison with previously reported 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose revealed, that these two compounds are isostructural.

Direct synthesis of trifluoromethyl decorated diphenylphosphites. Unusual non-bonded structural features in bis-[(2-trifluoromethyl)phenylphosphite: [2-(CF3)C6H4]2P(O)H

A direct, Grignard reagent-based route for the syntheses of [2-(CF3)C6H4]2P(O)H (1) and [3,5-(CF3)2C6H3]2P(O)H (2) has been developed and the isolation and characterization of these crystalline reagents is described. The crystal structures for 1 and 2 were determined and the structure of 1 reveals unexpected close non-bonded interaction between F-atoms of one CF3 group and the back-side of the central phosphorus atom.

The First Isolation of Crystalline Ethyl Bromozincacetate, Typical Reformatsky Reagent: Crystal Structure and Convenient Preparation

The highly reproducible preparation of ethyl bromozinc­acetate was achieved by a convenient procedure in which an excess amount of zinc powder was subjected to activation by chlorotri­methylsilane, followed by dropwise addition of ethyl bromoacetate. From the resultant solution of this Reformatsky reagent, crystalline ethyl bromozincacetate was isolated and its crystal structure was elucidated as its tetrahydrofuran-coordinated dimer (BrZnCH2CO2Et·THF)2 by X-ray crystal structure analysis. Although it had a dimeric structure similar to the tert-butyl bromo­zinc­acetate crystal, the two had different stereochemistry in the zinc-containing eight-membered ring (ZnCH2CO)2. The crystalline reagent obtained possessed satisfactory reactivity and stability for practical use. On the other hand, by preparing the tetrahydrofuran-free ethyl bromozincacetate in such solvents as 1,2-dimethoxyethane or cyclopentyl methyl ether, unintended crystallization could be successfully prevented.

Convenient Method for the Preparation of Carbamates, Carbonates, and Thiocarbonates

A convenient, rapid, and efficient method for the preparation of carbamates from amines with 1-alkoxycarbonyl-3-nitro-1,2,4-triazole transfer reagents is reported. Reactions of newly synthesized stable crystalline reagents with alkyl amines were completed in a few minutes without any additional base, and highly pure carbamates were obtained without chromatographic purification. These highly active reagents are also useful for the selective protection of nucleobases and preparation of carbonates and thiocarbonates.

N,N‘-Ditosylhydrazine: A Convenient Reagent for Facile Synthesis of Diazoacetates

A novel entry to the synthesis of diazoacetates is disclosed. A variety of diazoacetates were synthesized from the corresponding bromoacetates by treatment with N,N'-ditosylhydrazine in moderate to high yields. Ease of operation with the stable crystalline reagent as well as a short reaction time offer a useful alternative to the conventional methods.

Degradation of crystalline polyethylene glycol 6000 and its effect on assays for macroprolactin and other analytes

Objectives To determine why the incidence of macroprolactinemia was increasing in our laboratory. Design and methods Serum macroprolactin was detected by treatment with polyethylene glycol 6000 (PEG 6000). Results We compared results using freshly prepared solutions of PEG 6000 from various bottles of crystalline reagent and concluded that our stock had deteriorated. When decomposition was first suspected, the PEG 6000 caused a more complete precipitation of proteins, leading to poorer recovery of monomeric prolactin and false-positive macroprolactinemia, necessitating a 43-patient recall. After a further 6–8 months of decomposition, the PEG 6000 failed to fully precipitate macroprolactin, giving false-negative results. The PEG 6000 reacted strongly with Schiff's reagent (a test for aldehydes) throughout. Recoveries of several other analytes after PEG 6000 treatment were also affected. Conclusions PEG 6000 can deteriorate in the crystalline form, producing aldehydes and/or other compounds that denature serum proteins variably, causing false-positive or false-negative macroprolactin results.

Regioselective reaction of quinones with Reformatsky reagent: (BrZnCH 2CO 2Et·THF) 2

Reformatsky reactions of p-quinones with crystalline reagent (BrZnCH 2CO 2Et·THF) 2 were investigated and took place successfully, providing β-hydroxy esters in high yield. Notably, in the case of 2,6-disubstituted- p-quinones, regioselective Reformatsky reactions occurred to give corresponding β-hydroxy esters in good yields.

2‐(Prenyloxymethyl)benzoyl (POMB) as a New Temporary Protecting Group for Alcohols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

2-(Prenyloxymethyl)benzoyl (POMB) as a new temporary protecting group for alcohols

The 2-(prenyloxymethyl)benzoyl (POMB) group was introduced in high yields to hydroxyl functions using the crystalline reagent, 2-(prenyloxymethyl)benzoic acid, in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). 2-(Prenyloxymethyl)benzoic acid is readily available, in two steps, from phthalide in 65% overall yield. The POMB group can be cleaved, in two steps, by treatment with 2,3-dichloro-5,6-dicyanoquinone (DDQ) followed by intramolecular lactonisation of the resulting hydroxy ester induced by a catalytic amount of Yb(OTf) 3·H 2O. The reaction conditions are compatible with the presence of a number of protecting groups such as isopropylidene, benzyl, acetyl, chloroacetyl, benzoyl, levulinoyl, Fmoc and Boc groups.