Synthesis and Properties of Cadmium-containing Quinolinium and Pyrilium Salts

Consecutive treatment of methyl-substituted quinolinium and 2,6-diarylpyrilium perchlorates with sodium ethylate and equimolar amount of anhydrous cadmium(II) trifluoroacetate gives 2- and 4-methylenecadmium-containing salts of the above heterocyclic cations in 80-97% yields. The reactions of the cadmium-containing quinolinium and pyrilium salts with hydrochloric acid, acetic anhydride, mercuric trifluoroacetate, SnCl₂, and nickel(II) trifluoroacetate, resulting in substitution of the CdOCOCF₃ group by hydrogen, Ac, HgOCOCF₃, SnCl, and NiOCOCF₃, respectively, were studied.     

1,2,4-Trimethyl-1,2,4-triazolidine-3-thiones and 3,4-dimethyl-2-methylimino-1,3,4-thiadiazolidines

The reaction of aldehydes and ketones with 1,2,4-trimethylthiosemicarbazide in chloroform in the presence of CF₃COOH gives the corresponding 1,2,4-triazolidine-3-thiones, which in an excess of trifluoroacetic acid irreversibly and quantitatively recyclize to 2-imino-1,3,4-thiadiazolidine derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 403–407, March, 1992.     

Umwandlung von 6-Methylen-tricyclo[3.2.1.02,7]oct-3-en-8-onen mit Ameisensäure in kernmethylierte Phenylessigsäuren

In a preceding communication [5] it was shown that 1, 5-dimethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 2 ) and related tricyclic ketones are converted by strong acids (CF₃COOH, FSO₃H) into polymethylated tropylium salts with loss of carbon monoxide, e.g. the 1, 2, 4-trimethyltropylium ion 4 from 2 (Scheme 1). Under the influence of neat formic acid at 20°, 2 gives rise to ring-methylated phenylacetic acids, i.e. 2, 4, 5-trimethylphenylacetic acid ( 5 , main product) as well as smaller amounts of 2, 4, 6-and 2, 3, 5-trimethylphenylacetic acids ( 6, 7 resp.; Scheme 2). –On rearrangement of 2 in HCOOD, ca. 2 D-atoms are incorporated (formula d₂-5) into the 2, 4, 5-trimethylphenylacetic acid. The tricyclic 15 , containing 3 methyl groups, gives 2, 3, 5, 6-tetramethylphenylacetic acid ( 11 ; Scheme 4) with formic acid; the isomeric tricyclic 16 , 2, 3, 4, 5-tetramethylphenylacetic acid ( 12 ; Scheme 5). From 1, 2, 4, 5-tetramethyl-6-methylene-tricyclo[3.2.1.0^2,7]oct-3-en-8-one ( 17 ) one obtains pentamethylphenylacetic acid ( 14 ; Scheme 6). Similarly from 18 , a phenylacetic acid derivative, most probably 4-ethyl-2, 5-dimethyl-phenylacetic acid ( 19 ; Scheme 17), has been obtained. –In no case was the formation of α-phenylpropionic acid derivatives observed, not even from the tricyclic 23 containing six methyl groups. From the tricyclic ketone 2 in 70% formic acid a trimethyl-cyclohepta-2, 4, 6-triene-1-carboxyclic acid with partial formula 24 , besides 2, 4, 5-trimethylphenylacetic acid ( 5 ), is formed. 24 remained practically unchanged on standing in neat formic acid and thus does not represent an intermediate product arising by the rearrangement of 2 in that solvent. On standing in methanolic sulfuric acid, tricyclic 2 furnishes the two stereioisomeric methanol-addition products Z- 26 and E- 26 (Scheme 10); these are converted into the phenylacetic acids 5 , 6 and 7 by neat formic acid. The conversion of 2 and related compounds into ring-polymethylated phenylacetic acids, represents a novel and rather complicated reaction. In our opinion the reaction paths represented in Schemes 12 and 18 are responsible for the conversion of 2 into the trimethylphenylacetic acids, compound 40 representing a key intermediate. Analogous reaction paths can be assumed for the other tricyclic ketone transformations. The use of shift reagents in the NMR. spectroscopy and the high-resolution gas-chromatography of the corresponding methyl esters proved particularly important for the analysis of the reaction mixtures. The majority of the polymethylated phenylacetic acids were independently synthesised by means of the Willgerodt-Kindler reaction (chap. 3.2.), whose course is strongly influenced by methyl groups in the ortho-positions of the acetophenone derivatives employed.     

新型三环系稠杂环［1,2,4］-三唑并［1,5-a］［1］-苯并氮杂及［1,2,4］-三唑并［1,5-a］-喹啉的合成

α-四氢萘酮的乙氧羰基腙(1)经LTA氧化, 得到α-偶氮-α-乙酰氧基化合物2. 在AlCl3作用下, 化合物2脱去乙酰氧基产生重氮正离子中间体3, 再经与腈的1,3-偶极环加成、 ［1,2］-迁移扩环、 碱性水解和与苦味酸作用, 得到新型［1,2,4］-三唑并［1,5 a］［1］苯并氮杂苦味酸盐6a~6c. 以2,3-二氢-1-茚酮为底物, 采用相同的合成路线, 合成了1,2,4-三唑并［1,5-a］-二氢喹啉苦味酸盐12a~12c.     

Efficient rearrangement of epoxides catalyzed by a mixed-valent iron trifluoroacetate [Fe3O(O2CCF3)6(H2O)3]

The mixed-valent oxo-centered triiron(III, III, II) trifluoroacetate complex [Fe₂^IIIFe^IIO(O₂CCF₃)₆(H₂O)₃] was prepared by reacting anhydrous iron(III) chloride with boiling trifluoroacetic acid under nitrogen. The non-hygroscopic and readily available mixed-valent triiron trifluoroacetate complex was found to be an efficient catalyst for the regioselective rearrangement of epoxides. A number of carbonyl compounds formed via the rearrangement of epoxides could be obtained by a simple filtration of the reaction mixture through a short plug of silica gel.     

Concise total synthesis of phidianidine A and B

The shortest total synthesis of cytotoxic indole alkaloids phidianidine A and B is described. Rapid assembly of the 1,2,4-oxadiazole core from a novel N-hydroxyguanidine and the corresponding indole-3-acetic acid chloride led to formal syntheses of phidianidine A and B in only three steps from known compounds. Deprotection under standard conditions provided the trifluoroacetate salts of phidianidine A and B in quantitative yield.     

Complexation equilibria involving salts in non-aqueous solvents: ion pairing and activity considerations

Complexation of anions, cations and even ion pairs is now an active area of investigation in supramolecular chemistry; unfortunately it is an area fraught with complications when these processes are examined in low polarity organic media. Using a pseudorotaxane complex as an example, apparent K_a2 values (=[complex]/{[salt]_o?[complex]}{[host]_o?[complex]}) for pseudorotaxane formation from dibenzylammonium salts ( 2 ‐X) and dibenzo‐[24]crown‐8 ( 1 , DB24C8) in CDCl₃/CD₃CN 3:2 vary with concentration. This is attributable to the fact that the salt is ion paired, but the complex is not. We report an equilibrium model that explicitly includes ion pair dissociation and is based upon activities rather than molar concentrations for study of such processes in non‐aqueous media. Proper analysis requires both a dissociation constant, K_ipd, for the salt and a binding constant for interaction of the free cation 2 ⁺ with the host, K_a5; K_a5 for pseudorotaxane complexation is independent of the counterion (500 M ^?1), a result of the complex existing in solution as a free cation, but K_ipd values for the salts vary by nearly two orders of magnitude from trifluoroacetate to tosylate to tetrafluoroborate to hexafluorophosphate anions. The activity coefficients depend on the nature of the predominant ions present, whether the pseudorotaxane or the ions from the salt, and also strongly on the molar concentrations; activity coefficients as low as 0.2 are observed, emphasizing the magnitude of their effect. Based on this type of analysis, a method for precise determination of relative binding constants, K_a5, for multiple hosts with a given guest is described. However, while the incorporation of activity coefficients is clearly necessary, it removes the ability to predict from the equilibrium constants the effects of concentration on the extent of binding, which can only be determined experimentally. This has serious implications for study of all such complexation processes in low polarity media.     

Double- and triple-consecutive O-insertion into tert-butyl and triarylmethyl structures

[reaction: see text] The concecutive Criegee rearrangement reactions were studied for tert-butyl trifluoroacetate, triarylcarbinols, and benzophenone ketales with trifluoroperacetic acid (TFPAA) in trifluoroacetic acid (TFA). The formation of methyl acetate and methyl trifluoroacetate indicates that the consecutive double-O-insertion process has taken place for tert-butyl trifluoroacetate. The intermediate dimethoxymethylcarbonium ion was detected below 5 degrees C. A consecutive triple-O-insertion process has been observed for triarylmethanols and benzophenone ketals. A new high yield method of corresponding diaryl carbonates synthesis was developed.     

Synthetic procedure to pyrido[2,1-f][1,2,4]triazinium salt and related compounds

N-aminopyridyl ketone salts were reacted with formamide to yield heteroaromatic pyrido[2,1-f][1,2,4]triazinium salts. Upon storage of these products in the presence of water, formation of covalent hydrates have been observed. Reaction of the same starting compound with urethane yielded 3-chloropyrido[2,1-f][1,2,4]triazinium salt which readily reacted with secondary amines to afford 3-amino derivatives. An analogous ring closure reaction of 2-formylaminomethyl- and formaminobenzylpyridine allowed the synthesis of the partially reduced 3,4-dihydropyrido[2,1-f][1,2,4]triazinium compounds. The cyclization procedure was also applied for the synthesis of the related pyrimido[2,1-f][1,2,4]triazinium salt.     

Calix[4]arenes bearing a tropylium substituent as hosts for organic cations

Four novel calix[4]arenes bearing one cycloheptatrienyl substituent and two calix[4]arenes with one tropylium substituent at the wider rim were synthesized. Cycloheptatrienyl- and tropylium-calixarenes represent two states of a potentially photoswitchable calixarene host. The complexation of selected hosts with organic cations such as quinolinium, ammonium and tropylium ions was studied. It was found that the complexation of organic cations by the tropylium-substituted host was much stronger in CDCl₃ solution than by the related cycloheptatrienyl-host. Aryltropylium ions are bound by tropylium hosts. Accordingly, dimers of the host itself are formed both in CDCl₃ solution and in the gas phase. Because of the intramolecular charge transfer tropyliumcalix[4]arenes are qualified as chromogenic hosts. These undergo two acid-base equilibriums depending on the concentration and the solvent. Electronic Supplementary Material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

The perchlorate anion is more effective than the trifluoroacetate anion as an ion-pairing reagent for reversed-phase chromatography of peptides

The addition of salts, specifically sodium perchlorate (NaClO4), to mobile phases at acidic pH as ion-pairing reagents for reversed-phase high-performance liquid chromatography (RP-HPLC) has been generally overlooked. To demonstrate the potential of NaClO4 as an effective anionic ion-pairing reagent, we applied RP-HPLC in the presence of 0-100 mM sodium chloride (NaCl), sodium trifluoroacetate (NaTFA) or NaClO4 to two mixtures of synthetic 18-residue peptides: a mixture of peptides with the same net positive charge (+4) and a mixture of four peptides of +1, +2, +3 and +4 net charge. Interestingly, the effect of increasing NaClO4 concentration on increasing peptide retention times and selectivity changes was more dramatic than that of either NaCl or NaTFA, with the order of increasing anion effectiveness being Cl- < TFA- < C104-. Such effects were more marked when salt addition was applied to eluents containing 10 mM phosphoric acid (H3PO4) compared to 10 mM trifluoroacetic acid (TFA) due to the lesser starting anion hydrophobicity of the former mobile phase (containing the phosphate ion) compared to the latter (containing the TFA- ion).     

Field ionization mass spectrometry as a facile method for the study of the thermal formation of radicals

Electron impact spectra of thermolysis products of organic salts heated in the ion source of a mass spectrometer may give rise to organic ions corresponding to the cation of the salt. Field ionization mass spectrometry has been used as a facile method for detemining whether such an ion is due to ionization of the corresponding radical present in the gas phase, or to an electron impact induced fragmentation of a reaction product of higher mass. By comparison of the electron impact and field ionization spectra of a series of N-methyl pyridinium, tropylium and 1,2-dithiolylium salts it has been found possible to identify the radicals formed thermolytically, when present.     

Facile synthesis of 2,3,7,8-tetramethyl-2,2′-dipyrrin trifluoroacetate and its X-ray crystal structure

3,4-Dimethyl-1H-pyrrole-2-carboxylic acid was converted to 2,3,7,8-tetramethyl-2,2′-dipyrrin by the action of trifluoroacetic acid and ethyl orthoformate. A crystal of the dipyrrin was grown from dichloromethane-n-hexane and an X-ray crystallographic structure of its trifluoroacetate salt was determined. Correspondence: David A. Lightner, Department of Chemistry, University of Nevada, Reno, Nevada 89557-0020, USA.     

Synthesis of Substituted 1,2,4-Triazoles and 1,3,4-Thiadiazoles

The cyclization of 4-substituted 1-arylacetyl- and 1-aryloxyacetylthiosemicarbazides and also the potassium salt of (4-bromophenoxy)acetodithiocarbazinic acid in the presence of base gives the novel 3-arylmethyl- and 3-aryloxymethyl-5-mercapto-1,2,4-triazoles and, in the presence of concentrated H₂SO₄, the novel 5-substituted 2-arylmethyl- and 2-aryloxymethyl-1,3,4-thiadiazoles.     

Synthesis of derivatives of 1,2,4-triazin-3-thione and 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts from 1,2-dicarbonyl compounds and 4-substituted thiosemicarbazides

The reactions of methyl- and phenylglyoxal with 2,4-disubstituted thiosemicarbazides and of diacetyl with 4-monosubstituted thiosemicarbazides gave monothiosemicarbazones which were converted in trifluoroacetic acid into previously unknown 5-amino-2-acyl-2,3-dihydro-1,3,4-thiadiazolium salts. Diacetyl monosemithiocarbazones are cyclized to 5-methylene-1,2,4-triazin-3-thiones which are also obtained in the reaction ofdiacetyl with 2,4-disubstituted thiosemicarbazides. In particular cases the monothiosemicarbazones are converted into the corresponding 5-alkoxy-1,2,4-triazin-3-thiones in the presence of alcohols. The 3-thio-1,2,4-triazinium cations are formed from the 5-methylene- and 5-alkoxy derivatives in trifluoroacetic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1418–1425, October, 1992.     

Tautomerism of aza cycles: II. Synthesis and structure of 5-substituted 3-(2-hydroxyethylsulfanyl)-1<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazoles and their salts. Preference of the 1H,4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazolium tautomers

New complexing agents, potentially tautomeric 3-(2-hydroxyethylsulfanyl)-1H-1,2,4-triazole, its 5-methyl-and 5-phenyl-substituted analogs, and some their salts, were synthesized, and their structure was discussed on the basis of the ¹H and ¹³C NMR, IR, and mass spectra, X-ray diffraction data, and published data. In keeping with the rule formulated previously for N-unsubstituted 1,2,4-triazoles having dissimilar substituents, the synthesized compounds were found to exist as 3-(2-hydroxyethylsulfanyl)-5-R-1H-1,2,4-triazole tautomers (3-R_A-5-R_D-1H-1,2,4-triazoly). They are protonated at the nitrogen atom in position 4 of the triazole ring. The ¹H and ¹³C NMR spectra of these compounds in trifluoroacetic acid suggest the presence of two forms due to equilibrium between the neutral and protonated species. Analysis of the crystallographic data for the triazolium salts and published data showed preference of the 1H,4H-1,2,4-triazolium tautomer.     

Electrochemical fluorosulfation of organofluorine compounds

The scope of the review is: the application of fluorosulfonic acid as a solvent and reactant in the organic electrosynthesis, electrochemical behavior of various electrode materials in the fluorosulfonic acid and their effects on the anodic oxidation over wide potential range, the fluorosulfonic acid and its analogs’ adsorption during the anodic oxidation of organofluorine compounds, the effect of cathode material on the fluorosulfonic acid reduction and its influence on the products’ composition at this stage of the reaction. Results of preparative electrosynthesis (direct and indirect fluorosulfation of organofluorine compounds) are discussed, including the reaction mechanisms and the synthesis’ perspectives of the fluorosulfates thus obtained.     

Effect of trifluoroacetic acid on the reduction of disulfide bridges in peptides analyzed by fast-atom bombardment mass spectrometry

Some of the factors that influence the reduction of disulfide-containing peptides under fast-atom bombardment have been investigated using two neurohormonal peptides that include disulfide bridges in their structures. Deaminoarginine-vasopressin (DAVP) and arginine-vasopressin (AVP) have been analyzed as their acetate and trifluoroacetate salts. Results obtained in a thioglycerol matrix indicate that the peptides analyzed as their acetate salts are completely reduced under bombardment, whereas the trifluoroacetate salts show little evidence of reduction. Addition of trifluoroacetic acid to the acetate sample prior to bombardment inhibits reduction whereas addition after bombardment shows no effect on the reduction, thereby indicating the irreversibility of the process. Time-monitoring experiments conducted with the acetate salts of DAVP and AVP in common matrices such as thioglycerol, dithiothreitol + diethioerythritol, glycerol, hydroxyethyldisulfide and nitrobenzyl-alcohol demonstrate an important effect of the chemical nature of the matrix on reduction. In matrices containing thiol groups, the reduction is extensive, whereas it is almost suppressed in matrices such as hydroxyethyldisulfide and nitrobenzylalcohol. However, the addition of trifluoroacetic acid to all of these matrices essentially eliminates reduction and provides measured isotopic peak ratios that are in agreement with theoretically calculated values for these peptides.     

Correlation of the von Braun,Ritter, Bischler-Napieralski,Beckmann and Schmidt reactions via nitrilium salt intermediates

The Bischler-Napieralski dihydroisoquinoline synthesis from N-arylethyl-amides a formerly “one-pot” process was proven to occur via the imidoyl chlorides and the corresponding nitrilium salt. This led to the recognition of using other leaving groups better than chloride (e.g. trifluoroacetate, trifluoromethanesulfonate) and electrophiles better than phosphoryl chloride-POCl₄^? being an unfavorable counterion for the nitrilium ion. Previous facts about better yields with phosphorus pentoxide than phosphorus oxychloride were interpreted in the same light. The two-step process requires much milder conditions, 20–70° vs 110–205°. The “anomaly”, that is, the failure of 1,2-diaryl-ethylbenzamides to undergo cyclization as reported in literature was now rationalized in terms of fragmentation of the nitrilium salts into stilbenes, with formation of the conjugated π-system being the driving force for this product-controlled reaction. This, in fact, was now recognized as a reversal of the Ritter reaction which itself had been used in the synthesis of isoquinolines. The intermediate carbonium ion, from the nitrilium salt can, alternatively, undergo nucleophilic attack by an ionic halogen yielding products, expected from a von Braun reaction.Thus, correlation of the formerly unrelated Ritter, von Braun, Bischler-Napieralski, Beckmann and the Schmidt reactions has been established (Scheme 18) and a few other aspects of nitrilium salt chemistry such as elaboration of a modified Vilsmeier-Haack aldehyde synthesis via nitrilium salt intermediates and an attempt to synthesize compounds with the nitrilium group in a ring are discussed.