Sulfonyl isocyanates formation

Tertiary amines have been shown to react with isocyanates ia an analogous fashion to form ureas (41—43). Similarly, a2iridines (three-membered rings containing nitrogen) are found to react with isocyanates to yield cycHc ureas. Tertiary amines have also been shown to form labile dipolar 1 1 adducts with isocyanates reminiscent of salt formation. In contrast, formaldehyde acetal aminals form iasertion products with sulfonyl isocyanates (44,45). 

Addition of potassium chloride may be omitted if the chloro-sulfonyl isocyanate is free of sulfur trioxide. Otherwise, traces of sulfur trioxide will give rise to a yellow or brown coloration of the reaction mixture and to formation of small amounts of byproducts which, because of their emulsifying activity, may interfere with further processing. 

The intermediate sulfonyl isocyanate (107) reacts with the co-haloalcohols (108) to give N-carboxylsulfamates (109) which readily cyclise on treatment with triethylamine or sodium hydride to yield 2-oxazolidones (110) (Scheme 46). However, when (109) (Ar = Ph, X = Br) was heated with sodium hydride in boiling THF, the 2-oxazolidone (110) was not isolated, but rather the phenoxysul-fonylpiperidazine (111) (Scheme 46). The formation of the piperazine derivative (111) is believed to involve the initial formation of the 2-oxazolidone (110) which... 

Another case, in which the capture of a dipolar intermediate is reported, is the cycloaddition of an arene-sulfonyl isocyanate to a dialkyl-carbodiimide. One of the ultimate products is a 2 1 adduct, and it is suggested that an open dipolar species, the product of the first addition, adds a second molecule of isocyanate in a subsequent step. Formation of 2 1 adducts is regarded as strong evidence of cycloadditions with polar intermediates . 

Stereochemistry, substituent effects and activation parameters of most ketene reactions are consistent with a one-step cycloaddition polar effects of substituents and solvents, as well as the isotope effect, often require, however, that a fair amount of charge separation (that is, unequal bond formation) characterises the transition state. It has been kinetically proved that cycloadditions of enamines to ketenes can also proceed through a dipolar intermediate this is so for the reaction between dimethylketene and N-isobutenylpyrrolidine . In the latter case, the rate coefficient for the formation of the intermediate strongly depends on solvent polarity itacetonuriie/ cyclohexane = 560. Use of the Same criteria used for ketenes (as far as experimental data allow it) in the case of the 1,2-cycloadditions of fluorinated olefins results, instead, in the conclusion that a two-step biradical mechanism is operating. Results for 1,2-cycloaddition of sulfonyl isocyanates to olefins, cases (g) and (h) in Table 17, give indications of dipolar intermediates during the course of these reactions. 

The reversibility and thermodynamic control of product formation found for the high-pressure reaction between glycals and tosyl isocyanate indicated that the [2+2]cycloaddition of isocyanates to glycals could occur at atmospheric pressure under specific reaction conditions including an excess of isocyanate, as well as proper selection of solvent and substrates. Acyl isocyanates are generally less reactive in [2+2]cycloaddition reactions than sulfonyl isocyanates, except for trichloro- and trifluoroacetyl isocyanate 10,12 addition, acyl isocyanates are problematic because of the competitive formation of [4+2]cycloadducts, which are usually thermodynamically preferred over the [2+2]cycloadducts. 

Azides can undergo cycloaddition reactions with sulfonyl isocyanates as well. L Abbe et al. showed the formation of 4-sulfonyl-tetrazolin-5-ones that underwent thermolylically-induced decomposition and produced carbodiimides with the formation ofNa. ... 

Our trials showed that the phosgenation proceeds in a first stage through the readily and quantitative formation of the insoluble symmetrical sulfonyl urea (I) which reacts with butyl isocyanate to afford sulfonyl urea (II) and PTSI. The intermediate (II) reacts then, more slowly, with phosgene to give PTSI and regenerates butyl Isocyanate. The assumed mechanism is depicted in scheme 166 (Ref. 221). 

The parallel to the photochemistry of azides found in the arylimines is also observed on irradiation of 1,2,4-triazole 4-acyl-,129 133 4-sulfonyl-,81 and 4-carbamoylimines.133 In methanol the same products are generated as in the photolysis of the corresponding azides. Their formation is consistent with the mechanism given in Scheme 15 the AT-acyl- and sulfonyl-imines afford 1,2,4-triazole and a nitrene which yields the typical nitrene products 107a-d with methanol. Furthermore, carbamic esters (109) are formed, by addition of methanol to an isocyanate (108). These isocyanates can originate directly from the N-imine by a synchronous reaction or from the nitrene by a sextet rearrangement. Although irradiation of s-triazole... 

Isomannide (80) was the core for a hexahydrofurofuran library." Primary amines were loaded onto solid-support by reductive amination and acylated with bromoacetic acid to give bromides 79 (Scheme 7.16). Alkylation of bromides 79 on solid-support with isomannide (80) gave the solid-supported alcohols 81. A Mitsunobu reaction with phthalimide (82) proceeded to furnish amines 83 in excellent yield and purity after removal of the protecting group." " Support-bound primary amines 83 were converted to secondary amines by stepwise imine formation with aldehydes 84 and reduction with sodium borohydride." The hindered secondary amines 85 were acylated with acid chlorides, sulfonyl chlorides, isocyanates, and isothiocyanates to yield 87 after cleavage from solid-support. 

The acylation with acid chloride and the urea formation with isocyanate of intermediate resin 16 afforded other substituent groups onto 4-aminothiazole. Under microwave (MW) irradiation reaction with isocyanate and acylation reaction with acid chloride, R -substituted thiazole resin 19 was obtained. Following conversion of sulfonyl resin 19 to sulfonyl resin 20 (mCPBA/CH2Cl2), substitution reactions promoted by treatment with appropriate amines (R R" N diversity elements) furnished the 2,4,5-trisubstituted thiazoles 2 (29 examples 36-25% isolated yields from Merrifield resin 1, >95% purities, Table 10.1). 

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