Competitive formation of spiro and ansa derivatives in the reactions of tetrafluorobutane-1,4-diol with hexachlorocyclotriphosphazene: a comparison with butane-1,4-diol

Reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), in two stoichiometries (1:1.2 and 1:3) with the sodium derivative of the fluorinated diol, 2,2,3,3-tetrafluorobutane-1,4-diol, (2), in THF solution at room temperature afforded six products, whose structures have been characterized by X-ray crystallography and 1H, 19F and 31P NMR spectroscopy: the mono-spiro compound, N3P3Cl4(OCH2CF2CF2CH2O), (3), its ansa isomer, (4), a di-spiro derivative N3P3Cl2(OCH2CF2CF2CH2O)2, (5), its spiro-ansa (6) and non-gem cis bis-ansa (7) isomers and a tri-spiro compound N3P3(OCH2CF2CF2CH2O)3, (8). The tri-spiro derivative (8) was also formed in the reaction of the ansa compound (4) with diol (2) in a 1:3 ratio in THF at room temperature. The reactions of (1) with step-wise additions of (2) were also investigated at low temperature (-780C) to give the same range of products as at room temperature. The results of all reactions are compared with previous work on the reactions of (1) with butane-1,4-diol/pyridine mixtures and with the reaction of hexafluorocyclotriphosphazene, N3P3F6 (9), with the silyl derivative of the diol (2), (Me3SiOCH2CF2)2, in a 1:0.4 mole ratio in the same solvent, THF

Kryptoracemates

Racemic crystals normally crystallise in centrosymmetric spacegroups containing equal numbers of enantiomers. More rarely, racemates may crystallise in non-centrosymmetric space-groups having glide symmetry or, even more rarely, in space-groups devoid of a centre of inversion, having no rotary-inversion axes nor glide plane. The latter class of crystals form the subject of the present bibliographic review – a survey of kryptoracemic behaviour. The term kryptoracemic alludes to the presence of a hidden or non-crystallographic centre of inversion between two molecules that might otherwise be expected to crystallise in an achiral space-group, often about a centre of inversion. Herein, examples of molecules with stereogenic centres crystallising in one of the 65 Sohncke space-groups are described. Genuine kryptoracemates, i.e. crystals comprising only enantiomorphous pairs are described followed by an overview of non-genuine kryptoracemates whereby the crystal also contains other species such as solvent and/or counterions. A full range, i.e. one to six, stereogenic centres are noted in genuine kryptoracemates. Examples will also be described whereby there are more that one enantiomeric pair of molecules in the crystallographic asymmetric unit. A more diverse range of examples are available for non-genuine kryptoracemates. There are unbalanced species where in addition to the enantiomeric pair of molecules, there is another enantiomeric molecule present. There are examples of genuine co-crystals, solvated species and of salts. Finally, special examples will be highlighted where the counterions are chiral and where they are disparate, both circumstances promoting kryptoracemic behaviour

Effect of chain length on the formation of intramolecular and intermolecular products: reaction of diols with cyclotriphosphazene

The reactions of cyclotriphosphazene, N3P3Cl6 (1), in a 1:1.2 stoichiometry with the sodium derivative of seven diols [ethane- (2a), 1,3-propane- (2b), 1,4-butane- (2c), 1,5-pentane- (2d), 1,6-hexane- (2e), 1,8-octane- (2f) and 1,10-decane- (2g) diol] in THF solution at room temperature have been used to investigate the effect of chain length on the formation of reaction products. Although no new products were found for the reaction of 1 with diols 2a–c compared to those in the literature using other bases and solution conditions, the reactions of 1 with the diols 2d–g gave six different types of products, whose structures have been characterized by elemental analysis, mass spectrometry, 1H and 31P NMR spectroscopy; ansa compounds N3P3Cl4[O(CH2)nO], (5d–5g); single-bridged compounds N3P3Cl5[O(CH2)nO]N3P3Cl5 (6d–6f); double-bridged compounds N3P3Cl4[O(CH2)nO]2N3P3Cl4 (7d–7g, syn and anti) and triple-bridged compounds, N3P3Cl3[O(CH2)nO]3N3P3Cl3 (8d–f). Where suitable single crystals were obtained, X-ray crystallographic studies confirmed the structures of two ansa compounds (5d and 5f), one single-bridged compound (6e), and five double-bridged compounds (meso-anti for 7d, 7e, 7f and meso-syn for 7d and 7f). 31P NMR measurements of the reaction mixtures were used to quantify the formation of products for the reactions 1 with all the diols, 2a–g; it is found that, with increasing chain length of the diol, there is a decrease in the products formed by intramolecular reactions (spiro and ansa derivatives) and a concomitant increase in the amounts of products formed by intermolecular reactions (single-, double- and triple-bridged derivatives) of cyclophosphazene

Ansa isomer selectivity in the reactions of cyclotetraphosphazene with octafluorohexane-1,6-diol

The reaction of octachlorocyclotetraphosphazene, N4P4Cl8 (1), in three stoichiometries (1:1, 1:2 and 1:3) with the sodium derivative of the fluorinated diol, 2,2,3,3,4,4,5,5-octafluorohexane-1,6-diol (2), in THF solution at room temperature produced five products: the open chain compound N4P4Cl7[OCH2(CF2)4CH2OH] (3), the spiro compound N4P4Cl6[OCH2(CF2)4CH2O] (4b), the 1,5-ansa compound N4P4Cl6[OCH2(CF2)4CH2O] (4c), the cis-1,3;5,7-bis-ansa derivative N4P4Cl4[OCH2(CF2)4CH2O]2 (5a) and the 1,3;1,3;5,7;5.7-tetrakis-ansa compound, N4P4(OCH2(CF2)4CH2O)4 (6a). The structures were determined by elemental analysis, mass spectrometry, 1H, 19F and 31P NMR spectroscopies and for compounds 4c and 5a, where suitable single crystals were obtained, the structures were characterised by X-ray crystallography. It was found that the (PN)4 ring in compound 4c is in a slightly-twisted tub conformation but in compound 5a the first symmetrical crown conformation of the (PN)4 ring is observed. The results of all the reactions were compared with previous work on the reaction of hexachlorocyclotriphosphazene, N3P3Cl6, with the sodium derivative of the diol (2), in a 1:1.2 mole ratio in the same solvent, where intermolecular bridging reactions were preferred. The regio-selective formation of mainly ansa derivatives of the fluorohexanediol with cyclotetraphosphazene was rationalised in terms of non-bonded 1,3 and 1,5 P…P distances of the tetramer ring

Bridged cyclophosphazenes resulting from deprotonation reactions of cyclotriphophazenes bearing a P-NH group

Cyclotriphosphazene derivatives containing a P-NHR group in the side-chain react in the presence of a strong base to form stable intermolecular bridged products. Reaction of sodium hydride with mono-spiro cyclophosphazene derivatives having a P-NH group, N3P3Cl4[O(CH2)(3)NH], (1a) or N3P3Cl4[CH3N(CH2)(3)NH], (1b) leads to formation of bis-cyclophosphazenes bridged with an eight-membered cyclophosphazene ring in an ansa arrangement (2a, 2b) whereas reaction of sodium hydride with mono-amino cyclophosphazene derivatives [N3P3Cl5(NHR), R = n-hexyl, 3a; i-Pr, 3b; Ph, 3c] give bis-cyclophosphazenes bridged with a four-membered cyclophosphazane ring in a spiro arrangement (4a-c). In the latter reaction P-O-P bridged compounds (5a-c) were also obtained as a result of hydrolysis reactions associated with the amount of moisture in the solvent tetrahydrofuran. In addition, it was found that reaction of a mixture of cyclotriphosphazene with either mono spiro compound, (1a) or (1b), in the presence of sodium hydride lead to formation of the first examples of asymmetrically-bridged cyclophosphazenes (6a-b)

Single-, double- and triple-bridged derivatives of cyclotriphosphazenes with an octafluorohexane-1,6-diol

Reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), with the sodium derivative of the fluorinated diol, 2,2,3,3,4,4,5,5-octafluorohexane-1,6-diol, (2), in THF solution at room temperature afforded five products, whose structures have been characterised by 1H, 19F and 31P NMR spectroscopy: the mono-ansa compound N3P3Cl4[OCH2(CF2)4CH2O] (3); the single-bridged compound N3P3Cl5[OCH2(CF2)4CH2O]N3P3Cl5 (4), two double-bridged compounds N3P3Cl4(OCH2(CF2)4CH2O)2N3P3Cl4, (5-anti, 5-syn) and the triple-bridged compound N3P3Cl3(OCH2(CF2)4CH2O)3N3P3Cl3 (6). X-ray crystallographic studies confirmed the structures of the ansa compound (3), the double-bridged compound (5-anti) and the first example of a triple-bridged cyclotriphosphazene derivative (6). The results were also compared with those for reactions of (1) with analogous fluorinated shorter diols (1,4-butane- and 1,5-pentane-diols). It is found that on increasing the chain length of the diol, there is a decrease in the relative proportion of intramolecular reactions giving spiro and ansa derivatives and an increase in the amount of bridged cyclophosphazene derivatives via intermolecular reactions

Evaluation of the performance of maldi-tof ms and dna sequence analysis in the identification of mycobacteria species

Background/aim: Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is an alternative way of identifying mycobacteria via the analysis of biomolecules. It is being increasingly used in routine microbiology practice since it permits early, rapid, and cost-effective identification of pathogens of clinical importance. In this study, we aimed to evaluate the efficacy of phenotypic identification of mycobacteria by the MALDI-TOF MS MBT Mycobacteria Library (ML) 4.0 (Bruker, Daltonics) compared to standard sequence analysis. Materials and methods: A total of 155 Mycobacterium clinical and external quality control isolates, comprising nontuberculous mycobacteria (NTM) (n = 95) and the Mycobacterium tuberculosis complex (MTC) (n = 60), were included in the study. Results: Identification by MBT ML4.0 was correctly performed in 100% of MTC and in 91% of NTM isolates. All of the MTC isolates were correctly differentiated from NTM isolates. Conclusion: Based on our results, MBT ML4.0 may be used reliably to identify both NTM and MTC. © TÜBİTAK

Competitive formation of cis and trans derivatives in the nucleophilic substitution reactions of cyclophosphazenes having a mono-spiro P-NHR group

Nucleophilic substitution reactions of N3P3Cl4[NH(CH2)(3)NMe] (1) and N3P3Cl4[NH(CH2)(3)O] (2) with mono-functional alcohols (methanol, 2,2,2-trifluoroethanol, phenol) and a secondary amine (pyrrolidine) were used to investigate the relationship between the incoming nucleophile and the proportions of products with substituents that are cis or trans to the spiro NH moiety. The reaction products were characterized by elemental analysis, mass spectrometry, H-1 and P-31 NMR spectroscopy and the configurational isomers by X-ray crystallography. Six products have been characterised with the substituent cis to the spiro NH group for the alcohol (methanol, phenol) and pyrrolidine derivatives of both compounds 1 and 2, compared to just one derivative with the substituent trans to the spiro NH group, that for the pyrrolidine derivative of compound 2. For each reaction the relative proportions of cis and trans isomers were determined by P-31 NMR measurements of the reaction mixtures. It was found that the reactions of compound 1 with all three alcohols and of compound 2 with methanol lead to exclusive formation of isomers with the substituent cis to the NH moiety, whereas all other reactions lead to mixtures of cis and trans isomers in different ratios under standard reaction conditions. However, when crown ether is included in the reaction medium for the reactions of compound 2 with both 2,2,2-trifluoroethanol and phenol, it is found that only cis isomers are formed. All these results are rationalised in terms of the competition between at least two effects; the cis-directing effect by hydrogen bonding of the incoming nucleophile to the spiro N-H group already present on the cyclophophazene ring and the cis-directing effect of the sodium cation coordinating to the oxygen lone pairs of the P-O moiety of the spiro ring