Simultaneous determination of trimethylamine and trimethylamine N‐oxide in mouse plasma samples by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry

A method was developed that applies hydrophilic interaction liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode to separate and accurately quantify trimethylamine and trimethylamine N‐oxide in a single chromatographic run. This was achieved by converting trimethylamine to ethyl betaine, which is less volatile and hence results in greatly improved quantitation. Ethyl betaine also gives a similar response to trimethylamine N‐oxide using positive‐ion electrospray ionization mass spectrometry. It is readily separated from trimethylamine N‐oxide by hydrophilic liquid chromatography in a 5 min run and with improved peak shape compared to underivatized trimethylamine. Validation of the method yielded a limit of detection (S/N ≥ 3) of 0.5 ng/mL for trimethylamine and 0.25 ng/mL for trimethylamine N‐oxide. Method accuracies of 91.4–105.3% with precisions of 0.4–5.5% were obtained for standard mixtures over the range of 2.5–500 ng/mL. Recoveries measured for the extraction of trimethylamine and trimethylamine N‐oxide spikes into mouse plasma were both >90%. The method, which simultaneously measures trimethylamine and trimethylamine N‐oxide, was successfully applied to mouse plasma samples and could be adapted for use with other biological fluids.     

2-Phenyl-1-boraadamantane complexes. Crystal structure and use in the synthesis of cage compounds

Complexes of 2-phenyl-1-boraadamantane with trimethylamine and pyridine were studied by X-ray diffraction analysis. The 2-phenyl-1-boraadamantane adduct with tetrahydrofuran (1) was transformed to 1-hydroxy-2-phenyladamantane via a carbonylation—oxidation sequence. The intramolecular version of the organoborane reaction with organic azides was employed as a key step in the transformation of 2-phenyl-1-boraadamantane adduct (1) into 2-phenyl-1-azaadamantane (5).     

2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤的合成

报道了2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤(1)的合成, 通过对起始原料2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧甲基丁基)嘌呤(2)水解脱去乙酰基, 得到2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(3). 化合物3与三甲胺乙醇溶液在混合溶剂[V(THF)∶V(DMF)＝3∶1]中反应得到相应的氯化铵盐4, 然后与KF在DMF溶剂中反应, 得到化合物1. 产品经UV-vis, IR, ¹H NMR, ¹⁹F NMR和MS表征. 考察了反应温度、氟化试剂等因素对氟化反应的影响, 为6位含氟的嘌呤核苷类化合物的合成提供了一种直接、简易的新方法.     

2-Phenyl-1-boraadamantane complexes. Synthesis and intramolecular dynamics

The reaction of triallylborane with 3-phenylprop-1-yne at 135–140 °C followed by treatment of the reaction mixture with MeOH afforded 7-benzyl-3-methoxy-3-borabicyclo[3.3.1]non-6-ene (1) in 81% yield. Hydroboration of compound1 with a solution of BH₃ in THF yielded the tetrahydrofuran complex of 2-phenyl-1-boraadamantane (2). The reactions of trimethylamine or pyridine with compound2 afforded the trimethylamine (3) or pyridine (4) complexes of 2-phenyl-1-boraadamantane. respectively. Hindered rotation about the C(2)−Ph bond in adduct3 was observed by¹H and¹³C NMR spectroscopy. The activation energy of this process is 58.6 kJ mol⁻¹ (determined by 2D¹H−¹H EXSY spectroscopy).     

Untersuchungen von Reaktionsmechanismen durch Isotopenmarkierung,IV

It is shown by use of [2-¹⁴C]betaine that the formation of phenylmethylethers from phenoles and betaine takes place by methyl-group transfer from the trimethylammoniumgroup of the betaine. The formation of the by-products phenoxy acetic acid, trimethylamine and carbon dioxide is discussed.

III.G. Kollenz, Liebigs Ann. Chem.1978, 1666.     

A Green Procedure for the Oxidation of Benzyl Halides to Aromatic Aldehydes or Ketones in Aqueous Media

Green oxidation of benzyl halides to the corresponding aldehydes or ketones was achieved in aqueous media using trimethylamine N-oxide generated in situ from trimethylamine and H₂O₂. The yield of the reaction was excellent and the workup was simple.     

Diborane (4) derivatives via coupling of amine monobromocyanoboranes: Study of the bromination of amine cyanoborane and molecular structures of the amine dibromocyanoboranes

The first examples of diborane (4) compounds derived from amine cyanoboranes are described. A series of monobromo derivatives of amine cyanoboranes (A:BHBrCN), and dibromo derivatives (A:BBr₂CN), 1-7, were prepared. Lithiation of the monobromo derivative of trimethylamine cyanoborane, using n-BuLi, did not produce the C-lithiated intermediate Li⁺ [CH₂NMe₂BHBrCN]⁻, but instead the B-lithiated intermediate Li⁺ [Me₃NBHCN]⁻, was obtained. This intermediate, when allowed to react for 16 h, coupled with the un-lithiated trimethylamine monobromocyanoborane (Me₃NBHBrCN) and resulted in diborane (4) derivative formation as the 2LiBr complex. The same result was obtained when one equiv of the trimethylamine monobromocyanoborane was added to the reaction mixture 1 h after lithiation. Following the same procedure, novel diborane (4) derivatives of amine cyanoboranes were successfully obtained, 8-11, as their 2LiBr complexes from the monobromo derivatives of the corresponding amine cyanoboranes. Molecular structures of the trimethylamine dibromocyanoborane, 6, and the triethylamine dibromocyanoborane, 7, were determined using X-ray crystallography.     

Reactions of vinylidenediphosphonic acid with nucleophiles

It has been shown that heterocyclic amines can be added to the activated double bond of vinylidenediphosphonic acid to form adducts with betaine structures. Of aliphatic amines only trimethylamine reacts with vinylidenediphosphonic acid.For Part 4, seeIzv. Akad. Nauk, Ser. Khim., 1992, 2180 [Bull. russ. Acad. Sci., Div. Chem. Sci., 1992,41, 1709 (Engl. Transl.)].Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1590–1592, August, 1995.     

Reactions of indium phosphide cluster cations with ammonia and trimethylamine

Chemistry of indium phosphide clusters is studied using the powerful trapped ion cell techniques of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry in conjunction with an external cluster source and ion guide. The external source is capable of generating a wide range of cluster ions which the ion guide loads with high efficiency into the FTICR cell. The differential pumping of the ion guide allows for operation of the FTICR at requisite low pressure conditions while extracting clusters generated in a high pressure environment. Highly selective reactions of indium phosphide clusters are observed with ammonia and trimethylamine. Of all the In_xP⁺_y cluster sizes and stoichiometries studied, only the indium dimer ion reacts exothermically with ammonia. Thermalized In⁺₂ reacts by indium ion transfer to ammonia. Owing to its much higher basicity, trimethylamine is much more reactive. The smaller indium phosphide clusters react by indium ion transfer to trimethylamine. As the clusters become larger, however, the reaction probability decreases to zero.     

G protein-coupled receptor mediated sensing of TMA

A new approach for the detection of trimethylamine (TMA) using recombinant Xenopus laevis melanophores was developed. The cells were genetically modified to express the mouse trace amine-associated receptor 5 (mTAAR5), a G protein-coupled receptor from the olfactory epithelium, which conferred high sensitivity to TMA. A focused chemical screen allowed the discovery of additional, previously unknown stimuli of mTAAR5. The cell-based sensor demonstrated no sensitivity to trimethylamine N-oxide (TMAO), making it suitable for a convenient evaluation of TMA levels in fish tissue extracts. The developed gas measurement platform was able to detect TMA from 1 to 100 ppm within thirty-five minutes.     

Preparation and Characterization of Chitosan-Graphene Transducer Assembled via Vacuum Assisted Self-assembly (VASA) Method for Trimethylamine Sensing

A reduced graphene oxide/chitosan (rGO/Chi) nanocomposite film for chemoresistive trimethylamine sensing was prepared by solution-phase mixing and deposited on nylon membrane via vacuum assisted self-assembly (VASA) method. The film was analysed using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The electrical property of the prepared films were measured by four-point probe measurement. Using 0.40% volume fraction (v.f) it was exposed to trimethylamine vapour and its electrical resistance quickly changed. The composite film sensor exhibited linear range from 23 to 230mg/L (r²= 0.9774) and the calculated limit of detection was 20.56mg/L. It exhibited a repeatable response to trimethylamine gas.     

Oxidation of Organoboranes with Trimethylamine N-Oxide Dihydrate

Recently it has been reported that the commercialy available, easily handled trimethylamine N-oxide dihydrate is an effective oxidizing agent for organoboranes. An examination of the efficiency and reactivity of this reagent under various reaction conditions was conducted. Alkenes were hydroborated to the corresponding alkylboranes, and the subsequent oxidations to alcohols were carried out using a slight excess of trimethylamine N-oxide dihydrate. The product yields at different tiem intervals were determined by glpc analysis.The oxidation can be carried out in hydrocarbon as well as ethereal solvents. The rate of oxidation is proportional to temperature. Furthermore, long reaction times at moderate temperatures are not detrimental to yields. The rates of reaction of alkyl groups in the organoborane were determined to be tertiary > cyclic secondary > acyclic secondary > $\text{n}$-primary > branched primary > vinyl.     

Deposition of In2O3 nanofibers on polyimide substrates to construct high-performance and flexible trimethylamine sensor

Flexible trimethylamine sensor has been realized based on In₂O₃ nanofibers via electrospinning and a deposition technique. The web-like In₂O₃ nanofibers with high length-to-diameter ratios are benefit for gas adsorption and desorption. High trimethylamine sensing properties are observed. The sensors can detect trimethylamine gas down to 1 ppm at 80 °C with the response up to 3.8. Additionally, rapid response (6 s) and recovery (10 s) behavior can also be obtained. Good reliability and flexibility are observed in 100 bending/extending cycles. Our results open a new route to construct flexible gas sensors in practice.     

Preparation of TMS protected trifluoromethylated alcohols using trimethylamine N-oxide and trifluoromethyltrimethylsilane (TMSCF3)

A catalytic trifluoromethylation of aldehydes using trimethylamine N-oxide and trifluoromethyltrimethylsilane (TMSCF₃) is described. Aromatic, aliphatic and α,β-unsaturated aldehydes provided good to excellent yields of the corresponding trifluoromethylated products.     

Palladium‐catalyzed unstrained C(sp3)―N bond activation: the synthesis of N,N‐dimethylacetamide by carbonylation of trimethylamine

This work describes a highly efficient unstrained C(sp³)―N bond activation approach for synthesis of N,N‐dimethylacetamide (DMAc) via catalytic carbonylation of trimethylamine using a PdCl₂/bipy (bipy = 2,2′‐bipyridine)/Me₄NI catalyst system. A low Pd catalyst dosage (1.0 mol%) is sufficient for high selectivity (98.1%) and yield (90.8%), with a turnover number (TON) of 90.0 mmol of DMAc obtained per mmol of PdCl₂ employed under mild reaction conditions. The influence of reaction parameters such as catalyst precursor dosage, ligand type and promoter on activity is investigated. This work also discusses in detail the halide promoter's role in the reaction, and provides a plausible mechanism based on the intermediates methyl iodide and acetyl iodide. Analyses indicate that the carbonylation of trimethylamine may proceed through an active intermediate acetyl iodide formed by carbonylation of methyl iodide generated from the decomposition of the promoter Me₄NI under reaction conditions. The formation of acetyl iodide favors the cleaving efficiency of the inert unstrained C(sp³)―N bond of trimethylamine. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of aminimide monomers and polymers

A convenient and practical synthesis of trimethylamine acrylimide, 1 , starting from 1, 1, 1-trimethylhydrazinium p-toluenesulfonate, 3 , and 3-chloropropionyl chloride is described. The intermediate, trimethylamine 3-chloropropionimide, 2 , is easily transformed into 1 either through a single-step dehydrohalogenation or through a two-step process consisting of very facile thermal rearrangement to 1,1,1-trimethylacrylylhydrazinium chloride, 4 , and subsequent deprotonation. Two new polymerizable monomers, 5 , and 6 , containing aminimide functionality were synthesized from trimethylamine imine, 7 , and the appropriate vinyl oxazolones, 8 , and 9 . Synthesis of hitherto unreported trimethylamine chloroacetimide, 10 , which offers unique opportunities for incorporating water-solubilizing and alkali-stable aminimide functionality into a variety of structures through nucleophilic displacement, is also described.     

Effect of trimethylamine on the formation of anatase titania nanoparticles by gel-sol method

The anatase titania particles with controlled size and shape were prepared in large amount in the presence of trimethylamine (TMA) from the hydrolysis of a Ti-triethanolamine (TEOA) complex by gel-sol method. In the absence of TMA, ellipsoidal particles were obtained due to the anisotropic growth caused by the specific adsorption of TEOA onto the crystal planes parallel to the c-axis of a titania particle. TMA acted as a complexing agent of Ti(IV) ion to promote the growth of ellipsoidal particles and then inhibited the anisotropic crystal growth to produce ellipsoids of a low aspect ratio, rather than a shape controller to produce ellipsoids with a high aspect ratio. This may be explained in terms of the weak complexing between TMA (a tertiary amine) and Ti(IV) ion. The particle size was also controlled by seeding of anatase titania. Moreover, the seeding suggested that the rate-determining step of the gel-sol process was not the dissolution of the hydroxide gel, but the deposition of the monomeric precursor from the solution phase. Some cationic surfactants also promoted the particle grown to produce particles with a high symmetry in a similar way to TMA. The text was submitted by the authors in English.     

The synthesis and antitumor activity of metal complexes of amine–carboxyborane adducts

The amine carboxyborane metal complexes, tetrakis - μ - (trimethylamine – boranecarbo - xylato)acetonitrile dicopper(II) and bis-μ- (morpholine–boranecarboxylato)zinc(II) dihydrate demonstrated cytotoxic activity against human Tmolt₃, HeLa-S³ and MB-9812 cell growth.Tetrakis-μ-(trimethylamine–boranecarboxylato)-acetonitrile dicopper(II) and bis - μ - (morpholine – boranecarboxylato)zinc (II) dihydrate inhibited L₁₂₁₀ DNA, RNA and protein syntheses, with greatest inhibitory effects on DNA synthesis. The reduction in DNA synthesis correlates well with inhibition of de novopurine synthesis and the key enzymes involved in this pathway, i.e. IMP dehydrogenase and PRPP amido transferase. These compounds were also observed to induce DNA strand scission but did not appear to intercalate between base pairs of DNA, alkylate bases or cause cross-linking of the strands of DNA. Tetrakis-μ-(trimethylamine – boranecarboxylato)acetonitrile dicopper(II) also demonstrated the ability to inhibit L₁₂₁₀ DNA topoisomerase II activity. © 1998 John Wiley & Sons, Ltd.     

Demonstration of a convergent approach to UV-polymerizable lipids bisDenPC and bisSorbPC

Lipids containing UV-polymerizable diene moieties, such as BisDenPC 1 and BisSorbPC 2, have been extremely useful for the construction of micelles and lipid bilayers. The published syntheses have yielded lipids with only a trimethylamine head group. We have improved the syntheses of these monomers by a convergent method employing the Chabrier reaction of trimethylamine with a cyclic phospholane. This method can be extended to a variety of dialkylamine derivatives.     

Full Non-rigid Group of Sponge and Pina

The non-rigid molecule group theory (NRG) in which the dynamical symmetry operations are defined as physical operations is a new field in chemistry. Smeyers and Villa computed the r-NRG of the triple equivalent methyl rotation in pyramidal trimethylamine with inversion and proved that the r-NRG of this molecule is a group of order 648, containing a subgroup of order 324 without inversions (see J. Math. Chem. 28(4) (2000) 377–388). In this work, a computational method is described, by means of which it is possible to calculate the symmetry group of molecules. We study the full non-rigid group (f-NRG) of Sponge and Pina molecules with C ₂ and C _i point groups, respectively. It proved that these are groups of order 162 and 13122 with 54 and 3240 conjugacy classes, respectively. The character tables of these groups are also computed.