Tertiary amines, determination

Tertiary amines determination of primary plus secondary amines... 

Akzo Chemie Method VE/2.005 Fatty tertiary amines Determination of primary and secondary amine. 

Other impurities in commercial samples of N,N -diphenylethylenediamine are indicated by a direct titration in acetic acid (Fig. 3). Small amounts of aniline are present however, this does not account for the difference in inflection points. N,N -diphenylethylenediamine gives two inflection points when titrated in acetic acid, the first being very weak. Tertiary amine determinations in acetic anhydride would include other tertiary amines if present therefore, separations must be performed before titrating the 1,4-diphenylethylenediamine. 

For a tertiary amine determination, weigh a sample containing up to 1 meq of 1,4-diphenylpiperazine into a 150-ml beaker. Add 20 ml of acetic anhydride and heat for 2 hr on a hot plate at 70 C. Cool the sample, add 20 ml of acetic acid, and titrate with 0.1 N perchloric acid. 

For a characteristic titration of 1,4-diphenylpiper-azine from which the N,N -diphenylethylenediamine has been removed, weigh 0.2 g of sample in a 150-ml beaker. Add 40 ml of acetic anhydride and titrate with O.IN perchloric acid. One equivalent of amine per mole is titrated in the tertiary amine determination and two equivalents of amine per mole are titrated in the characteristic titration for 1,4-diphenylpiperazine. 

Recovery of 1,4-diphenylpiperazine from a N,N -diphenylethylenediamine sample, previously found to contain 13.75 of the compound, was 100.1 in the tertiary amine determination. Recovery from a precipitated sample was 98.07. ... 

Method 1. Treat 2 0 g. of the mixture of amines with 40 ml. of 10 per cent, sodium hydroxide solution and add 4 g. (3 ml.) of benzenesulphonyl chloi de (or 4 g. of p-toluenesulphonyl chloride) in small portions. Warm on a water bath to complete the reaction. Acidify the alkaline solution with dilute hydrochloric acid when the sulphonamides of the primary and secondary amines are precipitated. Filter off the solid and wash it with a little cold water the tertiary amine will be present in the filtrate. To convert any disulphOnamide that may have been formed from the primary amine into the sulphonamide, boil the solid under reflux with 2 0 g. of sodium dissolved in 40 ml. of absolute ethyl alcohol for 30 minutes. Dilute with a little water and distil off the alcohol filter off the precipitate of the sulphonamide of the secondary amine. Acidify the filtrate with dilute hydrochloric acid to precipitate the derivative of the primary amine. Recrystallise the respective derivatives from alcohol or from dilute alcohol, and identify them inter alia by a determination of the m.p. 

The free maleic acid content in maleic anhydride is determined by direct potentiometric titration (166). The procedure involves the use of a tertiary amine, A/-ethylpipetidine [766-09-6J, as a titrant. A tertiary amine is chosen as a titrant since it is nonreactive with anhydrides (166,167). The titration is conducted in an anhydrous solvent system. Only one of the carboxyhc acid groups is titrated by this procedure. The second hydrogen s dissociation constant is too weak to titrate (166). This test method is not only used to determine the latent acid content in refined maleic acid, but also as a measure of the sample exposure to moisture during shipping. 

Analytical methods iaclude thin-layer chromatography (69), gas chromatography (70), and specific methods for determining amine oxides ia detergeats (71) and foods (72). Nuclear magnetic resonance (73—75) and mass spectrometry (76) have also been used. A frequentiy used procedure for iadustrial amine oxides (77) iavolves titratioa with hydrochloric acid before and after conversion of the amine to the quaternary ammonium salt by reaction with methyl iodide. A simple, rapid quaHty control procedure has been developed for the deterrniaation of amine oxide and unreacted tertiary amine (78). 

Chemical Properties. Reactions of quaternaries can be categorized iato three types (169) Hoffman eliminations, displacements, and rearrangements. Thermal decomposition of a quaternary ammonium hydroxide to an alkene, tertiary amine, and water is known as the Hoffman elimination (eq. la) (170). This reaction has not been used extensively to prepare olefins. Some cycHc olefins, however, are best prepared this way (171). Exhaustive methylation, followed by elimination, is known as the Hoffman degradation and is important ia the stmctural determination of unknown amines, especially for alkaloids (qv) (172). 

Summary If the molecular weight is odd, then the compound contains an odd number of nitrogens. Fragment ions observed at even-mass numbers suggests the presence of nitrogen. The loss of ammonia is fairly common in nitrogen compounds and may not indicate exclusively that an amine is present. Chemical derivatization will easily determine if the unknown is a tertiary amine. 

Table 1). Further determinants of blocking potency are the membrane potential and the state in which the sodium channel is in (resting, activated, inactivated). The tertiary amine group can be protonated giving most local... 

In a study for precursor determination, we stem-fed individual Burley leaves with nicotine-2 - C or nornicotine-2 - C (29). Subsequently, the leaves were air cured, dried and analyzed for NNN and NNN- C. Recovery of the p-activity in the form of NNN- C amounted to 0.009% and 0.007%, respectively of the stem-fed label. This demonstrates that both alkaloids give rise to NNN. More importantly, it points to the fact that the tertiary amine, nicotine, which constitutes 0.5-2.6% of commercial tobaccos (26,27), is the major precursor for the carcinogenic tobacco-specific NNN, while the secondary amine, nornicotine is of lesser importance because it amounts to only 0.005-0.06% in tobacco (Figure 8). 

Direct Injection of Amines. In the course of developing methods for investigation of in vivo formation of NMOR and NPYR in rats treated with precursor amines and nitrite, it was necessary to determine the contamination levels of the amines by the nitrosamines. Spiegelhalder et al (32) reported the presence of nitrosamines in all secondary and tertiary amine samples which they examined, using vacuum steam distillation followed by extraction and GC-TEA determination. 

An alternative approach to increase the oxidation rate is the use of alkaline solutions, because bases enhance the reactivity of L-sorbose and weaken the adsorption strength of 2-KLG. Unfortunately, the rate enhancement at higher pH is accompanied by a drop in selectivity due to the poor stability of 2-KLG in alkaline solutions. To circumvent this problem, we have modified the platinum catalysts by adsorbed tertiary amines and carried out the oxidation in neutral aqueous solution [57], This allowed to enhance the rate without increasing the pH of the bulk liquid, which leads to detrimental product decomposition. Small quantities of amines (molar ratio of amine sorbose = 1 1700, and amine Pts = 0.1) are sufficient for modification. Using amines of pKa a 10 for modification, resulted in a considerable rate enhancement (up to a factor of 4.6) with only a moderate loss of selectivity to 2-KLG. The rate enhancement caused by the adsorbed amines is mainly determined by their basicity (pKa). In contrast, the selectivity of the oxidation was found to depend strongly on the structure of the amine. 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, facilitates lithiation53 by coordination at the lithium and promoting dissociation of aggregated structures. Kinetic and spectroscopic evidence indicates that in the presence of TMEDA lithiation of methoxybenzene involves the solvated dimeric species (BuLi)2(TMEDA)2.54 The reaction shows an isotope effect for the o-hydrogcn, establishing that proton abstraction is rate determining.55 It is likely that there is a precomplexation between the methoxybenzene and organometallic dimer. 

The structure of a copper(I) complex [Cu(L)][BPh4] (trigonal pyramidal three pyridyl groups in the trigonal plane and tertiary amine at the apex ligand as that in complex (4)) was also determined.29 The structure of complex [Cu2(L)(MeCN)2][BF4]2 (ligand as that in complex (179))169 and complex [Cu(L)][BPh]4 (ligand as that in complex (220)) 09 were also reported. 

Refaat et al. [24] used a spectrophotometric method for the determination of primaquine, and 16 other tertiary amine drugs, in bulk or in pharmaceuticals. The method involved the condensation of malonic acid with acetic anhydride in the presence of a tertiary amine in an aliphatic or a heterocyclic system. The condensation product is highly fluorescent and allows the spectrofluorimetric determination of the drug in the ng/mL ranges (Xcx = 415 nm and >.em = 455 nm). 

The dealkylative functionalization of tertiary amines 23 with electron deficient heteroaryl chlorides including triazinyl chloride 24 has been published <06TL2229>. Efficient and practical reaction conditions were determinated for a range of substrates. 

The plutonium concentration in marine samples is principally due to environmental pollution caused by fallout from nuclear explosions and is generally at very low levels [75]. Environmental samples also contain microtraces of natural a emitters (uranium, thorium, and their decay products) which complicate the plutonium determinations [76]. Methods for the determination of plutonium in marine samples must therefore be very sensitive and selective. The methods reported for the chemical separation of plutonium are based on ion exchange resins [76-80] or liquid-liquid extraction with tertiary amines [81], organophosphorus compounds [82,83], and ketones [84,85]. 

Aliphatic amines have been determined by a number of methods. Batley et al. [290] extracted the amines into chloroform as ion-association complexes with chromate, then determined the chromium in the complex colorimetri-cally with diphenylcarbazide. The chromium might also be determined, with fewer steps, by atomic absorption. With the colorimetric method, the limit of detection of a commercial tertiary amine mixture was 15ppb. The sensitivity was extended to 0.2 ppb by extracting into organic solvent the complex formed by the amine and Eosin Yellow. The concentration of the complex was measured fluorometrically. Gas chromatography, with the separations taking place on a modified carbon black column, was used by Di Corcia and Samperi [291] to measure aliphatic amines. 

The flow-cell design was introduced by Stieg and Nieman [166] in 1978 for analytical uses of CL. Burguera and Townshend [167] used the CL emission produced by the oxidation of alkylamines by benzoyl peroxide to determine aliphatic secondary and tertiary amines in chloroform or acetone. They tested various coiled flow cells for monitoring the CL emission produced by the cobalt-catalyzed oxidation of luminol by hydrogen peroxide and the fluorescein-sensitized oxidation of sulfide by sodium hypochlorite [168], Rule and Seitz [169] reported one of the first applications of flow injection analysis (FTA) in the CL detection of peroxide with luminol in the presence of a copper ion catalyst. They... 

NADH, containing a tertiary amine functional group, has been readily determined by Ru(bpy)32+ ECL. However the oxidized form, NAD+, containing an aromatic secondary amine group produces virtually no ECL signal. This had led to a variety of indirect enzymic methods of analysis, where the activity of the enzyme results in the conversions between NAD+ and NADH. These are discussed in Sec. 8. 

Since the order of increasing CL intensity for alkyl amines reacted with Ru(bpy)32+ is tertiary amines > secondary amines > primary amines, pharmaceutical compounds bearing a tertiary amine function (e.g., antihistamine drugs [99], anticholinergic drugs [100], erythromycin [101], and its derivatives [102]) have been sensitively determined after HPLC separation (Table 3). The method was applied to the detection of d- and L-tryptophan (Trp) after separation by a ligand-exchange HPLC [103], The detection limits for d- and L-Trp were both 0.2 pmol per injection. Oxalate in urine and blood plasma samples has also been determined by a reversed-phase ion-pair HPLC (Fig. 18) [104], Direct addition of... 

Amino acids labeled with DNS-C1 were determined using the Ru(bpy)32+ CL reaction after HPLC separation with a reversed-phase column [104, 105], DNS derivatives are expected to produce intense CL owing to their secondary and tertiary amino groups. The detection limit for DNS-Glu was 0.1 pM (2 pmol/ injection). Although underivatized amino acids could be detected by Ru(bpy)32+ CL, the DNS derivatives showed improved detection limits by three orders of magnitude [105], An approach to convert primary amines to tertiary amines was also reported [106], In this method, divinyl sulfone (DVS) was used for a cycloaddition reaction of primary amines (Fig. 19). The DVS derivatives after HPLC separation were sensitively detected (e.g., detection limits for propylamine and 3-aminopentane were 30 and 1 pmol, respectively). 

The above sequence mimics the proposed biosynthesis of Ervatamia alkaloids and in this context Thai and Mansuy (190) set out to determine whether an enzyme preparation would be able to promote the same transformation. By incubation of dregamine hydrochloride with a suspension of liver microsomes from a rat pretreated with phenobarbital (as a good inducer of P-450 cytochromes) in the presence of NADPH and 02, 20-epiervatamine (45) was formed together with the major metabolite Nl -demethyldregamine. It is well known that microsomal reaction on tertiary amines results in Af-oxide formation or N-deal-kylation. Thus it is likely that 45 was derived either from a rearrangement of dregamine JV4-oxide, catalyzed by the iron cytochrome P-450 or from one-electron oxidation of 30. 

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