A convenient oxazole C-2 protecting group: the synthesis of 4- and 5-substituted oxazoles via metalation of 2-triisopropylsilyloxazoles

[reaction: see text] Metalation of oxazoles at the 4 and 5 position was achieved after regioselective C-2 silyl protection. Removal of the protecting group was then accomplished under mild conditions allowing for a straightforward preparation of C-5 monosubstituted and C-4,5 disubstituted oxazoles. The first practical C-2 protecting group of oxazoles has been demonstrated.     

Acylation of oxazoles by the copper-mediated reaction of oxazol-2-ylzinc chloride derivatives

C-2 acylation of oxazole derivatives is accomplished by reaction of oxazol-2-ylzinc chloride reagents with acid chlorides in the presence of cuprous iodide. O-acylated vinylisonitriles, which are the sole product from the corresponding reaction employing lithiooxazole, are not observed. The method accommodates substituted and unsubstituted oxazoles with a variety of acid chlorides.     

Prediction of electron ionization mass spectra of <Emphasis Type="Italic">О</Emphasis>-alkyl methylphosphonothionofluoridates

Electron ionization mass spectra of poorly studied toxic alkyl methylphosphonothionofluoridates and alkyl methylphosphonofluoridates are discussed. It is demonstrated that the compounds are decomposed in accordance with the general scheme of fragmentation of monofunctional organic compounds RX (X is a functional group), proposed previously. At the same time, noticeable differences between the corresponding mass spectra are found. The most important difference occurs in their alkene subspectra containing a peak of alkene ion [R–H]^+? and peaks of its decay products. A method was developed for the simulation of mass spectra of unknown alkyl methylphosphonothionofluoridates by transforming available mass spectra of their oxygen analogues.     

Chemistry of α-(benzotriazol-l-yl)alkylpyridines. Unusual nucleophilic attack at c-3a of the benzotriazolyl ring

Lithiation of 2-, 3- and 4-[α-(benzotriazol-l-yl)methyl]pyridines with butyllithium followed by reactions with electrophiles (alkyl halides, aldehydes, ethyl benzoate and diphenyl disulfide) gave the corresponding α-sub-stituted derivatives in good yields. Repetition of the reaction sequence allowed substitution of the second α-proton by an electrophile. 2-[α-(Benzotriazol-l-yl)-α-(phenylthio)pentyl]pyridine thus obtained gave an unusual attack of the Grignard reagents at C-3a of the benzotriazole system on treatment with arylmagnesium bromides.     

Direct fluorination of substituted pyridines

The direct fluorination of pyridines bearing alkyl, halogen, ester, or ketone functions has been employed to prepare the corresponding 2-fluoro-substituted pyridines.     

2-取代-4,5-双(α-呋喃基)噁唑的合成及发光性能的研究

以糠醛为原料, 经维生素B1 (VB1)催化合成糠偶姻. 糠偶姻与不同的酰氯反应生成糠偶姻单酯. 糠偶姻单酯在醋酸铵和醋酸作用下合成了新化合物2-取代-4,5-双(α-呋喃基)噁唑. 采用 IR, 1H NMR, MS和元素分析对目标产物进行鉴定和表征, 证实了其分子结构. 并对2-取代-4,5-双(α-呋喃基)噁唑进行了UV和荧光光谱测定, 对其进行了简单的发光性能的研究.     

Photodegradation of polyfluorene and fluorene oligomers with alkyl and aromatic disubstitutions

The stability of fluorene-based compounds and polymers, especially at the bridged C-9 position under photoirradiation and thermal treatment, has claimed wide attention. We report the electronic, vibrational, and MALDI-TOF mass spectral combined studies for the fluorene oligomers with alkyl and aromatic substitutions under UV-light irradiation. The low-energy emission and the formation of ketonic defects after degradation highly depend on the proportion of alkyl substitution. The oligomer with fully aromatic substitution shows good stability, but when the proportion of alkyl substitution increases, their photostability rapidly decreases. The mass spectra show not only the mass of the fluorenone-fluorene trimer but also another new degradation product with a large mass (pristine oligomer plus 14) from alkyl oxidation, which testify to the assistance of alkyl side chain during degradation. We propose that the degradation of fluorene is a radical chain process propagated by alkyl side chains, and then the different stability between alkyl and aromatic substitution can be well explained.     

Mass spectrometry in structural and stereochemical problems—CCXLIV : The influence of substituents and stereochemistry on the mass spectral fragmentation of progesterone

The complete high resolution mass spectra of progesterone (Δ⁴-pregnene-3,20-dione) and twenty-nine stereoisomers and alkyl substituted analogs have been analyzed with the aid of the recently developed computer program INTSUM. Progesterone analogs with “normal” configuration at the six chiral skeletal carbon atoms give rise to abundant ions corresponding to cleavage of the 1–2 and 3–4 bonds (ketene elimination), to cleavage of the 6–7 and 9–10 bonds (ring B cleavage), and to cleavage of the 13–17 and 15–16 bonds (partial ring D cleavage); these reactions are frequently followed by elimination of alkyl radicals. Alkyl groups at C-6 and C-10 exert a pronounced influence on the formation and fragmentation of the [M-ketene] ions. Reversal of configuration at C-10 increases the importance of ring B cleavage, whereas reversal at C-17 favors the partial cleavage of ring D. The fragmentation of 17-alkylprogesterones differs significantly from the general pattern, with acetyl loss (cleavage of the 17–20 bond) and partial ring D cleavage as the predominating reactions. Loss of ring D by cleavage of the 13–17 and 14–15 bonds is not an important reaction of progesterones. Direct interaction of the two ketonic functions was not observed.     

Local structure at the air/liquid interface of room-temperature ionic liquids probed by infrared-visible sum frequency generation vibrational spectroscopy: 1-alkyl-3-methylimidazolium tetrafluoroborates

The air/liquid interface of 1-alkyl-3-methylimidazolium tetrafluoroborates with the general formula [C(n)mim]BF(4) (n = 4-11) was studied using infrared-visible sum frequency generation (SFG) vibrational spectroscopy. The probability of the gauche defect per CH2-CH2 bond in the alkyl chain decreases as the number of carbon atoms in the alkyl chain increases. This observation suggests that the interaction between the alkyl chains is enhanced as the alkyl chain length becomes longer. The frequencies of the C-H stretching vibrational modes observed in the SFG spectra are higher than those of the corresponding peak positions observed in the infrared spectra of the bulk liquids. This shift is consistent with a structure in which the alkyl chain protrudes from the bulk liquid into the air. A local structure, which originates from the intermolecular interaction between the ionic liquid molecules, is proposed to explain these observations.     

Mass spectra of a series of 3-halo-2-oxazolidinones

The mass spectra of a series of 3-chloro and 3-bromo alkyl substituted 2-oxazolidinones have been investigated and compared with the mass spectra of the corresponding alkyl substituted-2-oxazolidinones. Fragmentation of the 2-oxazolidinone ring system has been found to be significantly influenced by: (1) the presence of an alkyl substituent, (2) the position, number and size of the alkyl substitutents, and (3)replacement of the N? H bond by N? CI and N? Br.     

Biotransformation of substituted pyridines with dioxygenase-containing microorganisms

A series of 2-, 3- and 4-substituted pyridines was metabolised using the mutant soil bacterium Pseudomonas putida UV4 which contains a toluene dioxygenase (TDO) enzyme. The regioselectivity of the biotransformation in each case was determined by the position of the substituent. 4-Alkylpyridines were hydroxylated exclusively on the ring to give the corresponding 4-substituted 3-hydroxypyridines, while 3-alkylpyridines were hydroxylated stereoselectively on C-1 of the alkyl group with no evidence of ring hydroxylation. 2-Alkylpyridines gave both ring and side-chain hydroxylation products. Choro- and bromo-substituted pyridines, and pyridine itself, while being poor substrates for P. putida UV4, were converted to some extent to the corresponding 3-hydroxypyridines. These unoptimised biotransformations are rare examples of the direct enzyme-catalysed oxidation of pyridine rings and provide a novel synthetic method for the preparation of substituted pyridinols. Evidence for the involvement of the same TDO enzyme in both ring and side-chain hydroxylation pathways was obtained using a recombinant strain of Escherichia coli (pKST11) containing a cloned gene for TDO. The observed stereoselectivity of the side-chain hydroxylation process in P. putida UV4 was complicated by the action of an alcohol dehydrogenase enzyme in the organism which slowly leads to epimerisation of the initial (R)-alcohol bioproducts by dehydrogenation to the corresponding ketones followed by stereoselective reduction to the (S)-alcohols.     

Stereochemical studies of substituted 6,7- benzomorphan derivatives by 13C and 1H NMR spectroscopy

The ¹³C NMR spectra of a series of 6,7-benzomorphan derivatives variously substituted at C-5 and C-9 by methyl and at C-3 by cyano, alkyl and aralkyl groups, together with certain 3-cyano, 3-allyl or benzyl congeners, are reported and chemical shift data analysed in terms of the configuration of isomeric pairs and compounds isolated as single diastereoisomers. Special attention is given to the consequences of γ-shielding interactions, the effects of the nitrogen lone-pair orbital and anisotropic shielding by the aromatic region of the molecule. Deductions of stereochemistry are supported by ¹H NMR data and the NMR features of the corresponding methiodide salts.     

Studies of oxazoles

Mercuration of oxazole derivatives is studied. As a result mono- and disubstituted mercury derivatives, hitherto not described in the literature, are obtained. The ability of the oxazole ring to undergo mercuration decreases in the order C-5>C-4 C-2. It is shown that phenyl-substituted oxazoles are mercurated solely, or mainly at least, at an unsubstituted carbon atom in the heterocyclic ring, actual phenyl substituents in the oxazoles remaining inert towards mercuration.     

Mass spectrometric determination of the configuration of the 4-substituted 1,2-dimethyl-4-hydroxydecahydroquinolines

The mass spectra of a number of the epimeric 1,2-dimethyl-4-alkyl-4-hydroxydecahydroquinolines (alkyl: C?CH, CH?CH₂, C₂H₅ and COCH₃) have been studied. The configuration at C-2 and C-4 in these molecules is proposed on the basis of the data obtained. Some aspects of the fragmentation pathways under electron-impact are discussed.     

Mass spectral studies on thiobenzoates and thioacetates

The mass spectra of O-methyl and O-ethyl thiobenzoates and their derivatives have been recorded together with those of the corresponding S-alkyl thiobenzoates. The direct fragmentations of the O-alkyl thiobenzoates are almost identical to those of alkyl benzoates and of S-alkyl thio-benzoates. Several important differences in rearrangements upon electron-impact can be observed between them, however. These are the migration of the alkyl group from the alkoxy oxygen to the thiocarbonyl sulphur and the migration of a hydrogen from the alkoxy group to the thiocarbonyl group. O-methyl and O-ethyl thioacetates behave similarly. The mass spectra of the thioesters obtained with low electron-accelerating voltages have also been studied.     

Electron impact mass spectra of 2-[acyl(alkyl)amino]oxazoles

The mass spectral behaviour of 2-methyl-N-butyl-N-(4-methyloxazol-2-yl)propanamide is characterized by cleavage of the acylamino substituents and the elimination of a hydroxyl radical. An understanding of this elimination has been obtained from the analysis of further 2-[acyl(alkyl)amino]oxazoles and the use of deuterium labelled compounds.     

Oxidation of Oxazolines and Thiazolines to Oxazoles and Thiazoles. Application of the Kharasch-Sosnovsky Reaction

Using a modification of the Kharasch-Sosnovsky reaction, the oxidation of oxazolines and thiazolines bearing a variety of 2-alkyl substituents (chiral and achiral) were smoothly oxidized to their corresponding oxazoles and thiazoles, respectively. The key feature involved in the successful implementation of this important oxidation was the use of a mixture of Cu(I) and Cu(II) salts to enhance the oxidation of the intermediate captodative radical, 24. The main limitation of this method was shown when the oxidation failed with oxazolines/thiazolines lacking the carboalkoxy group at C-4.     

Circular Dichroism of Some Isomeric Alkyl Pyridines

The UV. and CD. spectra of the optically active 2-, 3- and 4-(l-methylpropyl)-pyridines ( 1a , b , c ) and of the corresponding (2-methylbutyl)pyridines ( 2a , b , c ) have been investigated in hexane at RT. and at ?85°, in hexane/TFA and in aqueous HCl-solution. In 1c and 2c both the n → π* and the π → π* transitions are optically active, an n → π* transition being located above 265 nm. The position and the sign of the CD. bands are greatly influenced by the position and the nature of the alkyl substituent.     

Iodoarene-catalyzed one-pot preparation of 2,4,5-trisubstituted oxazoles from alkyl aryl ketones with mCPBA in nitriles

2,4,5-Trisubstituted oxazoles could be easily prepared in moderate yields by the reaction of alkyl aryl ketones, iodoarene, m-chloroperbenzoic acid, and trifluoromethanesulfonic acid in acetonitrile, propionitrile, butyronitrile, and isobutyronitrile, respectively. Here, reactive aryliodonium I(III) species is formed in situ by the reaction of iodoarene with mCPBA and trifluoromethanesulfonic acid, and the formed aryliodonium I(III) species reacts with alkyl aryl ketone to form β-keto aryliodonium species. This in turn, reacts with nitrile to form the corresponding oxazole. Iodoarene works as a catalyst. However, one equivalent of iodoarene is required because one equivalent of reactive aryliodonium I(III) species must be formed prior to the reaction with alkyl aryl ketone. Then, by introducing an ionic liquid group into iodoarene, to form ionic liquid-supported iodoarene, the isolation procedure of oxazole could be simplified. The addition of ethyl acetate to the reaction mixture, washing of the reaction mixture with aq NaHCO₃, removal of ethyl acetate, and extraction of the residue with ether provided oxazoles in moderate purity, and the residual ionic liquid-supported iodoarene could be reused in the same reaction.     

Transmission d'un effet stérique péri à travers un noyau hétéroaromatique—I : Synthèse et propriétés spectrales de dialkylimidazo [1,2-a]pyridines péri disubst1tuées

The regiospecificity of the condensation of 2-amino-pyridines and α-halo carbonyl compounds has been established and exists even in the occurrence of steric effects. Using this regiospecificity peri disubstituted imidazo[1,2-a]pyridines have been prepared. ¹³C and P NMR studies show profound differences between the spectra of peri disubstituted compounds and other disubstituted imidazo [1,2-a] pyridines. These differences have been interpreted in terms of peri steric effects; preferential conformations of the peri alkyl substituents are postulated.