Trimethylamine -oxide

A mixture of 100 ml. of aqueous 33% trimethylamine solution and 600 ml. of 3% hydrogen peroxide is allowed to stand for 24 hours. If the odor of the amine is still apparent, another 100-200 ml. of hydrogen peroxide is added. After the amine odor has disappeared, the mixture is evaporated under vacuum and the residue is recrystallized from ethanol-ether mixture. The yield of trimethylamine oxide dihydrate, m.p. 96°, is around 95%. 

For dehydration 10 g. of the amine oxide dihydrate is placed in a 150-ml. flask which has a long, wide neck. Some boiling chips are added, and the compound is heated in an oil bath under a water pump vacuum of 10-12 mm. A calcium chloride tube is placed between the water pump and the flask. At an oil bath temperature of 120°, the amine oxide dihydrate melts and begins to bubble. The temperature is raised very slowly. After most of the water is off, the temperature of the bath is maintained at 140-150° for 10 minutes. A new calcium chloride tube is placed in the apparatus, and it is again heated under vacuum. At 180° sublimation starts, and anhydrous amine oxide collects in the neck of the flask. The mixture is held at a bath temperature of 190-200° for 1.5 hours to complete the sublimation. The yield of anhydrous trimethylamine oxide is around 95%. The material is extremely hygroscopic. A sample in a capillary tube melts at 208° after subliming around 180°. 

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Trimethylamine, CjH N, (CH3J3N. Colourless liquid with a strong fishy odour, miscible with water, m.p. — I24 C, b.p. 3-5°C. It occurs naturally in plants, herring brine, bone oil and urine. It reacts with hydrogen peroxide to give trimethylamine oxide and with ethylene oxide to give choline its commercial importance stems chiefly from this latter reaction. 

Trimethylamine oxide is normally available as a hydrate, and for the present preparation it is necessary to convert it to its anhydrous form. A convenient way of doing this is as follows. A solution of 45.0 g. of trimethylamine oxide dihydrate (supplied by Beacon Chemicals) is dissolved in 300 ml. of warm dimethyl-formamide and placed in a three-necked flask set up for distillation. At atmospheric pressure the flask is heated and solvent distilled off until the boiling point reaches 152-153°. Then the pressure is reduced using a water aspirator, and the remainder of the solvent is distilled. At the end of the distillation the temperature of the bath is slowly raised to 120°. The residual anhydrous trimethylamine oxide (30 g.) can be dissolved in 100 ml. of chloroform and may remain in the same flask for use in the present preparation. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

A coordinate covalent bond, represented by an arrow, is one in which both electrons come from the same atom that is, the bond can be regarded as being formed by the overlap of an orbital containing two electrons with an empty one. Thus trimethylamine oxide would be represented... 

The salt, formed from trimethylamine oxide and perchloric acid, explodes on heating, or under a hammer blow. 

Metabolism of trimethylamine oxide in fish muscle involves an enzyme-catalyzed oxidation-reduction reaction. The enzyme responsible for the conversion of trimethylamine oxide to trimethylamine is known as trimethylamine-W-oxide reductase. This enzyme acts on nicotinamide adenine dinucleotide (NADH) and TMAO to produce NAD+, trimethylamine and water (Fig. 13.13.1). TMAO acts as the oxidizing agent and is reduced, while NADH undergoes oxidation as the reducing agent. 

An alternate enzyme, trimethylamine-oxide aldolase, converts TMAO to dime-hylamine and formaldehyde, as written in Fig. 13.13.2. 

Figure 13.13.1 The reduction of trimethylamine oxide by nicotinamide adenine dinucleotide NADH.

Figure 13.13.2 Alternative reduction pathway of trimethylamine oxide to dimethy-lamine and formaldehyde.

Since the dipole moments of cyclopropenones are enlarged with respect to simple ketones and compare to other polar systems, e.g. trimethylamine oxide in Table 4, there seems to be evidence for considerable charge separation in the carbonyl group, which was expressed in terms of a cyclopropenium oxide contribution to the ground state. 

The cyclophane 35 is stable and remains unchanged upon heating to 300°C. The compound 35 is, however, readily oxidized at the Si-Si units by trimethylamine oxide in refluxing benzene, giving the cyclophane 36 containing three Si-O-Si bonds. 

Wolrath, H., Stahlbom, B., Hallen, A. and Forsum, U. (2005) Trimethylamine and trimethylamine oxide levels in normal women and women with bacterial vaginosis reflect a local metabolism in vaginal secretion as compared to urine. APMIS 113, 513-516. 

Cycloaddition (13,326).2 The azomethine ylide (a) generated with LDA from trimethylamine oxide adds stereoselectively to the dihydronaphthalenes 1 to provide the benzisoindoiines 2, of use as a-adrenergic agents in therapy. 

A comparative study of the analysis of aliphatic amines by GC-FID, GC-TSD and HPLC with refractive index detector (RID), using isopropylamine as internal standard, gave good results in all cases. Determination of trimethylamine oxide by HPLC with a pulsed amperometric detector was problematic136. 

Tribromamine oxide, 0291 Trimethylamine oxide, 1313 See FURAZAN N-OXIDES... 

Aside from the complications imposed by the oil in fish and the need to keep the catch cold, there is also a compound in fish called trimethylamine oxide (TMAD), which is converted to trimethylamine (TMA). Trimethylamine oxide is essentially an odorless compound which is ccxiverted by bacteria in and on the fish to the fishy tasting and smelling compound, trimethylamine. Retarding this conversion is one of the prime objectives of adequate cold storage of fishery products (3) (8). 

Bromination of lactone 386 followed by oxidation with trimethylamine oxide in DMSO resulted in rearranged 387 in poor, 7% yield (Equation (42) (2001H91)). 

The molybdenum-catalyzed cyclization procedure works well for a variety of homoprogargylic alcohols to afford the cycloisomeric 2,3-dihydrofuran compounds, as shown in Table I. The transformation was originally discovered with the reagent arising from reaction of molydbenum hexacarbonyl and trimethylamine oxide, but catalyst turnover and product isolation yields are significantly improved with the cunent procedure, which... 

Also, attempts to convert phosphine to PH3O using amine oxides, such as trimethylamine oxide and pyridine oxide, did not proceed to the result formulated in Eq. (19)... 

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