Nitrogen alkaline hydrolysis

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Heliotrine, CigH2,05N, m.p. 125-6°, [ajn — 75° (CHCI3), yields a methiodide, m.p. 108-111°, and contains one methoxyl group, two hydroxyl groups and a tertiary nitrogen atom. On alkaline hydrolysis it forms heliotridine (p. 607) and heliotric acid (p. 613). In presence of platinic oxide it absorbs two molecules of hydrogen and affords, as scission products, heliotric acid and hydroxyheliotridane (p. 607). 

The corresponding [5,4-6]-compound (107) was prepared similarly and treated with methyl iodide to give a quaternary salt which was shown to have structure 108, because mild alkaline hydrolysis gave 3-acetamido-l-methyl-2-pyridone. Again, quaternization took place on the pyridine-nitrogen, which is different from the behavior of the corresponding 1,4-diazaindene mentioned above. 

Since the ring nitrogen at 3 is now comparable in reactivity to the amine at 4, acylation with one equivalent of 88 gives a mixture of products. The desired product, sulfaisodimidine (109), can be obtained by acylation with an excess of the sulfonyl chloride (140) followed by alkaline hydrolysis. The rate of saponification of the sulfonamide group attached to the ring nitrogen is sufficiently greater to cause it to be lost selectively. 

Example 1. Alkaline Hydrolysis of Nylon-6,6 in Isopropanol.9 Isopropanol (209 parts), 267 parts of water, 54 parts of 97% sodium hydroxide, and 100 parts of nylon-6,6 were charged to a 1-gal stainless steel autoclave. Under an atmosphere of nitrogen, the charge, which weighed 1060 g, was heated in the autoclave to 180°C for 1.5 h with constant agitation and then cooled. A clear two-phase liquid was obtained which had an alcoholic upper phase and an... 

Bilikova and Kuthan [87] developed a gas chromatographic method for the determination of submicrogram concentrations of Carbofuran (2,3-dihydro-2, 2,-dimethylbenzofuran-7-yl-methyl carbamate) in soils. Soil samples are mixed with methanol-water (80 20) and water samples are extracted with chloroform. After separation of the chloroform, and weak alkaline hydrolysis, derivatization is performed with l-fluoro-2,4-dinitrobenzene. The ester produced is isolated from benzene and cleaned up with acetone. The acetone extract is used to determine Carbofuran by gas chromatography with a nitrogen-specific detector. 

The nitrogen atoms of the twisted amides discussed on pages 107-108 are to a greater or lesser extent pyramidal, and incipient lone pairs electron density is thus available for reactions with electrophiles. The classic example is the cage lactam [57] first prepared by Pracejus (1959), which has an amide nitrogen with near normal amine basicity. Brown and coworkers have measured rates of alkaline hydrolysis of a series of anilides [58] and [59] with related structures and find that the rate increases with increasing divergence... 

Fig. 12 Dependence of the rate constant for alkaline hydrolysis for three amides [58] (x = 1, y = 2 x = 2, y = 1 and x = y = 2), and [59] on three different geometrical parameters the twist-torsional angle r (A), and the out-of-plane bending at the amide carbonyl (O) and nitrogen ( ) centres. [The geometrical...

Johnson and McCants (161) were the first to show that the alkaline hydrolysis of alkoxysulfonium salts, obtained by 0-alkylation of sulfoxides, proceeds with inversion of configuration at sulfur. This method was employed to interconvert (/ )- and (5)-benzyl p-tolyl sulfoxides 37 as shown in Scheme 21. In contrast to the hydroxide anion, the chloride, bromide, and iodide anions as well as the nitrogen atom of pyridine react with chiral ethoxydiarylsulfonium salts, not at sulfur but at the a-carbon atom of the ethoxy group, yielding the starting sulfoxide with retained configuration (284). On the other hand, the nucleophilic attack of the fluoride anion is directed at sulfur as in the case of the hydroxide anion (285). 

Several techniques have been described in the past for the analysis of VLCFA, pristanic acid and phytanic acid [1, 10]. In our hands gas chromatography-mass spectrometry (GC-MS) analysis after derivatisation with N-methyl-N-(tert-butyldi-methylsilyl) trifluoroacetamide (MTBSTFA), is a robust and reliable method for the quantitative analysis of VLCFA, pristanic acid and phytanic acid, especially when combined with stable isotopes for C26 0, C24 0, C22 0, phytanic acid and pristanic acid [13]. In order to allow measurement of the total pool of VLCFA, pristanic acid and phytanic acid, samples need to be subjected to both acidic and alkaline hydrolysis, followed by extraction into hexane. After the hexane phase is washed once more, the sample is dried under nitrogen followed by addition of pyridine and MTBSTFA and heating of the samples at 80°C. The sample is subsequently dried again under nitrogen and taken up in hexane, followed by GC-MS analysis. 

The ester function was determined by alkaline hydrolysis followed by precipitating the liberated acids as calcium salts. In the present work, samples of 1-1.5 grams were added to 50 ml. of 0.2N aqueous sodium hydroxide and refluxed with continuous stirring under nitrogen for 18-24 hours. After hydrolysis the samples were titrated to a pH of 9 with hydrochloric acid. Then 15 ml. of IN calcium acetate was added, and the sample was stirred rapidly under a stream of nitrogen for 1 hour. The suspension of calcium salt was filtered, washed with dilute base until free of excess calcium acetate as determined by titration with ethylenediaminetetraacetic acid (EDTA), and dried under a stream of nitrogen. Calcium was determined on the dried product. 

In order to gain some information on the degradation mechanisms, experiments with substances assumed to represent essential intermediates were undertaken. 2-Hydroxy-3-methoxy-5-methylbenzal acetone (XVII) is considered to play a dominant role in the proposed degradation mechanism when 6,6 -bicreosol is oxidized in alkaline solution although it could not be detected among the degradation products. The benzal acetone (XVII) was oxidized and underwent alkaline hydrolysis under our standard conditions. Alkaline hydrolysis in nitrogen atmosphere yielded rather small amounts of acetone (about 10% of theoretical amount). Oxidation yielded... 

Dog 53. Two preparations, of which the enzyme had been inactivated by alkaline hydrolysis, did not affect blood pressure or blood urea nitrogen. 

In general, the hydrolysis of amides requires conditions that are not compatible with the survival of several functional groups [10]. If the amide nitrogen is linked to an electron-withdrawing moiety, alkaline hydrolysis of the amide group is easier. Following this observation Martens and co-workers used 4-methoxy-2-nitrophenyl isocyanide 14 (or 2-methoxy-4-nitrophenyl isocyanide) as a convertible isocyanide for the preparation of Peptide Nucleic Acid (PNA) monomers [8a] (for another example, see Ref. [11]). The Ugi-4CR between isocyanide 14, carboxymethyl nucleo-... 

The USP XX limits for the nitrogen content of melphalan are 8.90—9.45% [25]. Several compendial assays are based on the determination of the chlorine liberated by alkaline hydrolysis (see 5.4). 

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