Sulfamates, hydrolysis

Acetamido-4-methyl-5-thiazolyl-sulfuryl chloride gives by hydrolysis the acid, which on heating with H2SO4 is reported to give the 2-sulfamic acid (337). 

Aqueous sulfamic acid solutions are quite stable at room temperature. At higher temperatures, however, acidic solutions and the ammonium salt hydroly2e to sulfates. Rates increase rapidly with temperature elevation, lower pH, and increased concentrations. These hydrolysis reactions are exothermic. Concentrated solutions heated in closed containers or in vessels having adequate venting can generate sufficient internal pressure to cause container mpture. An ammonium sulfamate, 60 wt % aqueous solution exhibits mnaway hydrolysis when heated to 200°C at pH 5 or to 130°C at pH 2. The danger is minimised in a weU-vented container, however, because the 60 wt % solution boils at 107°C (8,10). Hydrolysis reactions are ... 

Alkali metal sulfamates are stable in neutral or alkaline solutions even at boiling temperatures. Rates of hydrolysis for sulfamic acid in aqueous solutions have been measured at different conditions (Table 4) (8,10)-... 

Dilute aqueous solutions of sulfamic acid are stable for many months at room temperature but at higher temperatures hydrolysis to NH4[HS04] sets in. Alkali metal salts are stable in neutral and... 

This last reaction finds use in volumetric analysis. The use of sulfamic acid to stabilize chlorinated water depends on the equilibrium formation of A-chlorosulfamic acid, which reduces loss of chlorine by evaporation, and slowly re-releases hypochlorous acid by the reverse hydrolysis ... 

The susceptibility of the sulfamates to hydrolysis is intermediate with respect to procedures commonly used for extraction and manipulation of extracts. Quantitative hydrolysis of the pure sulfamate toxins can be accomplished (9) by heating at 100 C for 5 min in the presence of not less than 0.1 M free acid (pH 1 or below). Milder conditions appear insufficient (10). Figure 9 summarizes results from two separate experiments in which samples of nontoxic clam flesh, enriched with constant amounts of saxitoxin Cl (4), were acidified to differing final concentrations of HCl and heated for 5 min at 100 C. The difference between 0.1 M HCl, which would be sufficient for hydrolysis of the pure toxin, and the HCl concentration required to attain plateau toxicity, probably reflects the buffer capacity of... 

At the start, the sample containing 1 xmol of 6 has a toxicity of 230 mouse units. Epimerization to a mixture of Cl (4) and 6 will reduce the toxicity of the sample. At a ratio of 4 1 a )5, the decrease will be about 11-fold, to 21 mouse units. Hydrolysis of the original sample to the corresponding carbamate, GTX3 (5), would increase the toxicity of the sample 6-fold, to 1400 mouse units. Subsequent epimerization of the hydrolysate, 5, to a 4 1 mixture of the carbamates GTX2 (3) and 5 (or hydrolysis of the epimeric sulfamates 4 and 6 to the same mixture of carbamates) would then change the toxicity to 1,120 mouse units. 

Wagner, W.F. and Wuellner, J.A. (1952) Homogeneous precipitation of barium sulfate by hydrolysis of sulfamic acid. Anal. Chem., 24, 1031-1032. 

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

Up to this point, we have examined the hydrolysis of the S-0 bond in sulfates and sulfamates. In sulfamates (R-NH-S03), cleavage occurs at the... 

Kinetic studies of the hydrolysis of aryl Af-(methoxycarbonyl)sulfamates (350) are reported for the first time. The compounds are fairly strong acids with g>Ka = 0.5-2.4, and in acid both S-O and C-0 bond cleavages occur (Scheme 43). From an... 

This unusual process known as the W-method was discovered in Germany by Wolfram and involves the condensation of the potassium salt of sulfamic acid with formaldehyde to form the heterocycle (238) followed by treatment with nitric acid. The extreme sensitivity of (238) to hydrolysis means that nitrolysis has to be conducted under anhydrous conditions using sulfur trioxide or phosphorous pentoxide " dissolved in fuming nitric acid. The yield of RDX from the W-method is 80-90 %. 

Ammonium dinitramide has been synthesized from the nitration of ammonium sulfamate with strong mixed acid at -35 to -45 °C followedby neutralization of the resulting dinitraminic acid with ammonia. The yield is 45 % when the mole ratios of sulfuric acid to nitric acid is 2 1 and ammonium sulfamate to total acid is 1 6. The nitration of other sulfonamide derivatives, followed by hydrolysis with metal hydroxides, also yields dinitramide salts. ... 

In his meticulous exploration of methods for his thesis research, Proctor ( ) noted that the toxicity (MIP) of cell free extracts of Gonyaulax increased following heating at low pH. Hall (1,22) further explored this increase in potency, referring to it as Proctor enhancement, and demonstrated that it was primarily due to the hydrolysis of sulfamate to carbamate toxins. It was found that heating at 100 C for 5 minutes in aqueous HCl with a free acid concentration of 0.1 M is sufficient to insure complete hydrolysis and attain maximum MIP. 

Figure 5. Chromatography of an extract of Protogonyaulax clone PI07, showing the LC/TLC coordinates for the twelve saxitoxins. Conditions are as in ( ). Stippled bars in the TLC diagram (lower) show the coordinates of compounds not observed in this run. The toxicity profile (upper), shows the mouse intra-peritoneal potency of grouped fractions before (hatched area) and after (outline) hydrolysis of the sulfamates. Adapted from Ref. 22.

The sulfamate saxitoxins have very low potencies relative to their carbamate hydrolysis products. This relationship has been observed in every assay system tried, including the standard mouse bioassay (Figure 3), squid giant axon (1 ), frog sciatic nerve (16), mammalian brain (1 ), and single rat sarcolemma sodium channels incorporated into lipid bilayers (15). It seems unlikely that human oral potencies are an exception to this trend. 

In an assay that offers acceptable HOPi/ri ratios for the carbamates, potential HOP can be estimated by preparing the sample under conditions that insure hydrolysis of the sulfamates. Unfortunately, the conditions specified for sample preparation in the standard mouse bioassay are not sufficiently acidic to insure complete hydrolysis ( ). As currently employed in state monitoring laboratories, the mouse assay may substantially underestimate the potential HOP of samples containing the sulfamate toxins. 

At ordinary temperatures, sulfamic acid hydrolyzes slowly forming ammonium bisulfite. However, when heated it hydrolyzes rapidly forming sulfuric acid. Therefore nickel sulfamate should be prepared rapidly before any sulfamic acid hydrolysis occurs due to longer contact time with water. 

Synthetic heparinoid polymers such as polyanionic polyesters containing sulfamate and carboxylate groups were synthesized by hydrolysis of p(N chloro-sulfonyl beta lactam) [475]. These materials possess anti-coagulant activity (although lower than heparin) presumably due to the similarity of functional groups of this material and those found in heparin. 

The copper-free solution containing nickel, cobalt, ammonium sulfate, ammonium sulfamate, and some unsaturated sulfur compounds imdergoes an oxidation-hydrolysis step in an autoclave at 460°F under an air pressure of 600 psig. The unsaturated sulfur compounds are oxidized and sulfamate is hydrolyzed to sulfate. This step prevents the contamination of the fertilizer-grade ammonium sulfate with ammonium sulfamate and of the nickel with sulfur. The oxydrolyzed solution containing about 45 gm/liter Ni, 1 gm/liter Co, and 350 gm/liter (NH4)4S04 is ready for batchwise nickel recovery. 

Berglund showed that sulfamic acid derivatives are relatively stable under alkaline conditions which cause hydrolysis of A-acetamido groups. Jorpes, Bostrom and Mannson, utilizing these data, found that less than 10% of the total amino groups is liberated when a 0.2% solution of heparin in N sodium hydroxide is heated at 100° for 2 hours, whereas 55 % of that in chondroitinsulfate is released. 

Imidodisulfuric acid chloride forms colorless crystals which hydrolyze very rapidly in moist air they melt at 37°, boil at 115°/4 mm. and at 55°/0.03 mm., and have a refractive index ny> = 1.4948. The compound is readily soluble in organic solvents such as benzene or nitrobenzene. Hydrolysis in alkaline medium leads to imidodisulfate in acidic medium, sulfamic acid and sulfuric acid are formed. 

Anion or cation generation Anions can be generated slowly in solution to bring about homogeneous precipitation. Swift and Butler reviewed precipitation of the metal sulfides by use of thioacetamide or thiourea. PFHS of sulfides of cadmium, mercury, zinc, and nickel have been studied more recently by Swift and others. Phosphate can be generated by hydrolysis of triethyl phosphate, oxalate by hydrolysis of methyl oxalate, and sulfate by hydrolysis of diethyl sulfate or sulfamic acid. 

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