Reaction of 5-oxo-2-phenyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-benzodioxaphosphepine with chloral. The synthesis and spatial structure of 5-carbaphosphatrane containing a four-membered ring

Phosphorylation of 2-hydroxyphenyl 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl ketone with dichloro(phenyl)phosphine gave 5-oxo-2-phenyl-4,4-bis(trifluoromethyl)-4,5-di-hydro-1,3,2-benzodioxaphosphepine. Heating of the latter initiated an intramolecular interaction of the P atom with the carbonyl group. Hydrolysis of the intermediate product yielded 3-hydroxy-2-oxo-2-phenyl-3-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-2,3-di-hydro-1,2λ⁵-benzo[d]oxaphosphole. The reaction was highly stereoselective (P_RC_S/P_SC_R). The reaction of the starting phosphepine with chloral proceeded highly stereoselectively (P_RC_SC_S/P_SC_RC_R) to give a 5-carbaphosphatrane derivative containing a four-membered ring, namely, 1-phenyl-3-trichloromethyl-10,10-bis(trifluoromethyl)-6,7-benzo-2,4,8,9-tetraoxa-1λ⁵-phosphatricyclo[3.3.2.0¹,⁵]decene. The trigonal bipyramid of the 5-carbaphosphatrane derivative is made up of the equatorial O atoms and the apical C atoms.     

Some syntheses using tetrakis(trifluoromethyl)dewar thiophene

Tetrakis(trifluoromethyl)Dewar thiophene ($\text{1}$) is found to be a good dipolarophile and dienophile. Therefore, $\text{1}$ reacts with any kind of azides to give 1,3-dipolar cycloadducts, which are transformed to tetrakis(trifluoromethyl)Dewar pyrroles ($\text{2}$), compounds of a new cyclic ring system. Further, $\text{1}$ reacts with cyclic or acyclic dienes to give Diels-Alder adducts. The adduct ($\text{3}$) of $\text{1}$ with butadiene was transformed to tetrakis(trifluoromethyl)cyclooctatetraene ($\text{4}$) by desulfurization, bromination and dehydrobromination, stepwise. Valence-bond isomerisation of $\text{4}$ will be presented.

     

Direct incorporation of A 6α(7α)-formamido group into penicillins and cephalosporins

6β(7β)-($\text{N}$-2,2,2-Trichloroethoxycarbonyl-$\text{N}$-trifluoromethanesulphonylamino) penicillins and cephalosporins have been converted into the corresponding 6α(7α)-formamido-6β(7β)-2,2,2-trichloroethoxycarbonylamino derivatives, by treatment with $\text{N}$,$\text{N}$-bis(trimethylsilyl) formamide and triethylamine.     

Perhalogenmethylmercapto-heterocyclen, (VII) [1] konkurrenzreaktionen elektronenarmer,substituierter aromaten um die halogenmethylmercapto- BZW. Chlorgruppe von Cl3-nFnCSCl in starken saeuren

Electron-deficient aromatics, such as 2,5-bis(trifluoromethylmercapto)thiophene ($\text{1a}$) or (trifluoromethylmercapto)benzene ($\text{8a}$), react with F₃CSCl in the presence of F₃CSO₃ as a catalyst to give mainly 3-chloro-2,5-bis(trifluoromethylmercapto)thiophen ($\text{3a}$) and 1-chloro-4- or 2-(trifluoromethylmercapto)benzene ($\text{10}$, respectively. This reaction competes with the one expected to result in 2,3,5-tris(trifluoromethylmercapto)thiophene ($\text{2a}$) and 1,4- and 1,2-bis(trifluoromethylmercapto)benzene ($\text{9}$,$\text{9′}$), respectively. Further reactions of deactivated aromatics with Cl_3-nF_nCSCl show that the chlorine substitution is in general catalysed by strong acids. Reaction mechanisms are proposed for both Substitutions. The Cl_3-nF_nCS group in aromatics exerts a -M-effect in the case of an attack of a positive ion, e.g. H^⊕, the well-known +M-effect in the case of reactions with positively polarized molecules, e.g. CF₃S^β+Cl^β-.     

Fluorocarbon derivatives of nitrogen. Part 11. Synthesis of some 2-(trifluoromethyl)imidazo[1,2-a]pyridines from trifluoroacetonitrile

3-(t-Butoxycarbonyl)-2-(trifluoromethyl)imidazo[1,2-$\text{a}$]-pyridine, prepared from trifluoroacetonitrile and pyridinium t-butoxycarbonylmethylide, reacts smoothly with trifluoroacetic acid to provide 2-(trifluoromethyl)imidazo[1,2-$\text{a}$]pyridine-3-carboxylic acid, which gives 2-(trifluoromethyl)imidazo[1,2-$\text{a}$]-pyridine when heated. 3-Cyano-2-(trifluoromethyl)imidazo[1,2-$\text{a}$]pyridine can be obtained $\text{via}$ treatment of trifluoroacetonitrile with pyridinium cyanomethylide, which is sufficiently reactive to effect nucleophilic displacement of fluorine from pentafluoropyridine under mild conditions [→pyridinium cyano(tetrafluoro-4-pyridyl)methylide].     

Reactions of mesomeric fluorocarbanions with acid anhydrides. Transformation of trifluoromethyl groups into fluorocarbonyl and perfluoroacyl groups

It was found that the reaction of mesomeric fluorocarbanions of the CF₃$\text{C}\text{θ}$XCOY type with benzoic anhydride leads to the loss of benzoyl fluoride and the formation of mesomeric carbanions of the FCO$\text{C}\text{θ}$XCOY type. In a similar reaction with perfluorocarboxylic acid anhydrides, besides a CF₃→COF transformation, further change of COF into COR_F is observed, leading to the formation of salts containing mesomeric anions of the R_FCO$\text{C}\text{θ}$XCOY type, which, upon acidification, give 1,1- -bis(perfluoroacyl)-2,2,2-trifluoroethanes CF₃CH(COR_F)₂ , tris- (perfluoroacyl)methanes (R_FCO)₃CH and bis(trifluoroacetyl)- acetic ester (CF₃CO)₂CHCOOMe. It has been shown that perfluoroalkyl groups in β-diketones and β,β′-triketones may hinder enolization despite their electron-attracting effect.     

The structures of 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles related to J147, a drug for treating Alzheimer's disease

J147 [N‐(2,4‐dimethylphenyl)‐2,2,2‐trifluoro‐N′‐(3‐methoxybenzylidene)acetohydrazide] has recently been reported as a promising new drug for the treatment of Alzheimer's disease. The X‐ray structures of seven new 1,4‐diaryl‐5‐trifluoromethyl‐1H‐1,2,3‐triazoles, namely 1‐(3,4‐dimethylphenyl)‐4‐phenyl‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₇H₁₄F₃N₃, 1 ), 1‐(3,4‐dimethylphenyl)‐4‐(3‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 2 ), 1‐(3,4‐dimethylphenyl)‐4‐(4‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 3 ), 1‐(2,4‐dimethylphenyl)‐4‐(4‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₆F₃N₃O, 4 ), 1‐[2,4‐bis(trifluoromethyl)phenyl]‐4‐(3‐methoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₈H₁₀F₉N₃O, 5 ), 1‐(3,4‐dimethoxyphenyl)‐4‐(3,4‐dimethoxyphenyl)‐5‐trifluoromethyl‐1H‐1,2,3‐triazole (C₁₉H₁₈F₃N₃O₄, 6 ) and 3‐[4‐(3,4‐dimethoxyphenyl)‐5‐(trifluoromethyl)‐1H‐1,2,3‐triazol‐1‐yl]phenol (C₁₇H₁₄F₃N₃O₃, 7 ), have been determined and compared to that of J147 . B3LYP/6‐311++G(d,p) calculations have been performed to determine the potential surface and molecular electrostatic potential (MEP) of J147 , and to examine the correlation between hydrazone J147 and the 1,2,3‐triazoles, both bearing a CF₃ substituent. Using MEPs, it was found that the minimum‐energy conformation of 4 , which is nearly identical to its X‐ray structure, is closely related to one of the J147 seven minima.     

2,3-Epoxyperfluoro-2-methylpentane in reactions with urea and thiourea

2,3-Epoxyperfluoro-2-methylpentane reacts with thiourea in protic (methanol, 2-propanol) and aprotic (dioxane) solvents, and also with urea in acetonitrile affording unexpected products: 1-(2,2,3,3,3-pentafluoropropionyl)-2-(2,2,2-trifluoro-1-trifluoro-methylethyl)isothiourea, and 1-(2,2,3,3,3-pentafluoropropionyl)-3-(2,2,2-trifluoro-1-trifluoro-methylethyl)urea respectively that result from the rearrangement of the intermediately formed ketone in the process of the intramolecular “haloform” cleavage. At the same time in dioxane the 2,3-epoxyperfluoro-2-methylpentane reacts with urea with the formation of a heterocyclic compound, 2-amino-4-pentafluoroethyl-5,5-bis(trifluoromethyl)-4,5-dihydrooxazol-4-ol. From 1-(2,2,3,3,3-pentafluoropropionyl)-2-(2,2,2-trifluoro-1-trifluoromethylethyl)isothiourea and Cu(OAc)₂ a stable fluorine-containing chelate complex was obtained.     

Alkaline hydrolysis of 2-(trifluoromethyl)imidazo[4,5-f] and -[4,5-h]quinolines

2-(Trifluoromethyl)imidazo[4,5-$\text{f}$] and -[4,5-$\text{h}$]quinoline have been prepared from 5(6),acetamido-2-(trifluoromethyl)benzimidazole and 7,8-diaminoquinoline respectively. These (trifluoromethyl)- quinolines like 2-(trifluoromethyl)imidazoles but unlike 2-(trifluoromethyl) benzimidazoles, undergo hydrolysis in dilute sodium hydroxide to give ultimately the corresponding imidazo[4,5-$\text{f}$] and -[4,5-$\text{h}$]- quinoline, respectively.     

Perhalogenmethylmercapto-heterocyclen,IX (perchlormethylmercapto)- und (perfluormethylmercapto)pyridine

Methods of substituting pyridine by perhalogenomethylmercapto groups are discussed. The side chain chlorination of 2-(methylmercapto)pyridine leads gradually to 2-(trichloromethylmercapto)pyridine hydrochloride ($\text{1a}$) and 2-(trichloromethylmercapto)pyridine ($\text{1b}$). Neither a direct reaction of pyridine with CF₃SCl nor the way over a Grignard reaction or a sulfenylcarboxylate lead to CF₃S-substituted products. Reactions of pyridine and bromopyridines with Hg(SCF₃)₂ yield 1:1-adducts ($\text{2a-d}$) only. Lithium tetrakis(1,2-dihydro-1-pyridyl)aluminate (LDPA) reacts with CF₃SCl to give 3-(trifluoromethylmercapto)pyridine ($\text{3}$); in addition a disubstituted product can be identified massspectroscopically. ¹H- and ¹⁹F-NMR-spectra are reported.     

Conformational analysis of trans-2,3-diaryloxy-1,4-dioxanes. A tool for discriminating between steric and electronic effects in the position of

The conformation of several $\text{trans}$-2,3-diaryloxy-1,4-dioxanes has been studied using ¹H NMR techniques. $\text{Trans}$-2,3-bis(4-nitrophenoxy)-1,4-dioxane and $\text{trans}$-2,3-bis(4-methoxyphenoxy)-1,4-dioxane have been found to be predominantly ( ≈98%) in diaxial conformation in CDCl₃). On the other hand, $\text{trans}$-2,3-bis(2,6-dimethylphenoxy)-1,4-dioxane exists in the same conditions as a 66:33 mixture of diaxial and diequatorial conformers. An explanation based on the fulfilment of the exo-anomeric effect is provided.     

Action of tert-butyl azidoformate on the conjugate bases of 1,2,3,4-tetrahydro-9H-carbazole and other indole derivatives

tert-Butyl azidoformate ($\text{2}$) reacts with the conjugate bases of $\text{3a}$, $\text{7a}$, $\text{9}$ (R¹ = R² = CH₃), and $\text{9}$ (R¹ = CH₃, R² = H) to give products [$\text{4}$, $\text{8}$, $\text{12}$, and $\text{14}$, respectively] in addition to the expected N-(tert-butoxycarbonyl)indole derivatives.     

Some reactions of 1,2,3,4,7,7-hexafluorobicyclo[2,2,1]hepta-2,5-diene: Thermolysis and attack by methoxide ion and by bistrifluoromethyl nitroxide

1,2,3,4,7,7-Hexafluorobicyclo[2,2,1]hepta-2,5-diene gave 1,2,3,4-tetrafluorebenzene in at least 73% yield when heated to 450°C in a sealed tube; the CF₂ bridge appeared, in part, as octafluorocyclobutane. Nucleophilic attack by sodium methoxide- methanol on the diene occurred exclusively at the CFCF bond, causing the formation of 1,2,4,7,7-pentafluoro-3-methoxybicyclo- [2,2,1]hepta-2,5-diene and a 1,4,5,6,7,7-hexafluoro-5-methoxybicyclo [2,2,1]hept-2-ene thought, on the basis of ¹⁹F nmr data, to be the 6-$\text{endo}$-F,5-$\text{exo}$-MeO isomer. Radical attack on 1,2,3,- 4,7,7-hexafluorobicyclo[2,2,1]hepta-2,5-diene by bistrifluoromethyl nitroxide took place at both olefinic sites, with a $\text{ca}$. 10:1 preference for the CFCF linkage; all three geometrical isomers of 5,6-bis(bistrifluoromethylamino-oxy)-1,4,5,6,7,7- hexafluorobicyclo[2,2,1]hept-2-ene were formed.     

Stable isobenzofuran endoperoxide and its use for oxidation of olefins ans aromatic compounds

1,3-Di-tert-butylisobenzofuran reacts with singlet oxygen with rate constant of 2.8 x 10⁹ M^?1 sec^?1 to give stable endoperoxide $\text{4}$. Thermolysis of the endopepoxide ($\text{4}$) in the ppesence of norbornene and naphthalene gave the corrpesponding epoxide and naphthols, respectively. Addition of Pd(OAc)₂ improved the yield of naphtols considepably.     

Nature of the catalytic cycle in iridium-complex catalysed hydrogenation of unsaturated alcohols

The $\text{endo}$ face specific reduction of $\text{endo}$-6-methylenebicyclo[2,2,2]octan-2-ol and $\text{endo}$-6-methy[bicyclo [2,2,2]-oct-5-en-2-ol with D₂ and iridium catalysts is accompanied by deep-seated isotopic redistribution through an intramolecular mechanism, although only two deuterium atoms are incorporated on average. Individual isotopomers of the product may be identified in the ¹³C N.m.r. spectrum at 125 MHz. and their ratio is generally consistent with a mechanism in which product is formed by breakdown of an alkyliridium trihydride. Iridium (and rhodium) catalysts part-isomerise the exocyclic olefin to its endocyclic isomer $\text{via}$ an Ir-allyl intermediate without incorporation of deuterium. The reduction of 3-methylcyclohex-2-enol is likewise accompanied by considerable scrambling, with isotopic enrichment occurring at C2, C3, C4 and C5 of the product, $\text{trans}$-3-methylcyclohexanol. Deuteration occurs exclusively on the hydroxyl-bearing face of the molecule.     

3-Bromo-2-(tert-butylsulfonyl)-1-propene. A multi-coupling reagent Part 1.

3-Bromo-2-(tert-butylsulfonyl)-1-propene $\text{4}$ is easily available in two steps from allyl-tert-butylthioether $\text{5}$ (70% overall yield). It reacts with a great variety of carbanions to give functionnalized α, β-unsaturated sulfones of type $\text{7}$ in high yields. A second nucleophile (lithium cuprates) can then be added to compounds $\text{7}$ to furnish functionnalized sulfones of type $\text{3}$ (Y=SO₂-tert-butyl).     

Mechanisms for reactions of halogenated compounds. Part 4.[1] activating influences of ring-nitrogen and trifluoromethyl in nucleophilic aromatic substitution

Rate constants have been measured for the reactions of ammonia with various fluorinated pyridines and diazines in aqueous dioxan at 25°. From the results the activating effects of ring-nitrogen (relative to CH) and of trifluoromethyl (relative to -H) have been determined. Ring-nitrogen activates the system at points $\text{ortho}$-, $\text{meta}$- and $\text{para}$- to the point of substitution, in the ratios $\text{ortho}$- 6.2 × 10⁴, $\text{meta}$- 8.5 × 10², and $\text{para}$- 2.3 × 10⁵. Similarly a trifluoromethyl substituent is activating by a factor of 2.4 × 10³$\text{ortho}$- and 4.5 × 10³$\text{para}$- to the point of substitution.     

Bis(tricarbonyliron) complexes of P-quinodimethanes: fragmentation and isomerisation under electron impact

EI mass spectra of $\text{trans}$-η⁴,η⁴-[3,6-bis(methylene)-1,4-cyclohexadiene]-bis=(tricarbonyliron) complexes $\text{1a}$, $\text{b}$ are reported. The fragmentation pathway is rationalized by assuming a rearrangement of the $\text{trans}$-bis(tricarbonyliron) complexes into the $\text{cis}$-isomers under electron impact.     

Inept-29Si NMR study of a TiCl4-mediated reaction of an enol silyl ether

Condensation of 1,3-bis(trimethylsiloxy)-1-methoxybutadiene ($\text{1}$) and 2-phenyl-2,2-dimethoxyethanal ($\text{2}$) under TiCl₄ condition gave the γ-hydroxycyclopentenone product $\text{3}$. The reaction was followed by INEPT²⁹Si NMR. Implication to the mechanism of the reaction was discussed.