Urethane, hydrolysis reactions

The above described adducts of the Isocyanates are cleaved on reaction with water to give ultimately an amine, CO2, and the active hydrogen containing progenitor. For example, the overall hydrolysis reactions of a urethane can be shown as ... 

The hydrolysis reaction is preferably carried out under alkaline conditions. Acid hydrolysis can lead to undesired side reactions and also incomplete reaction. Hydrolysis by water under pressure is also incomplete, especially in the case of aromatic polyurethanes. Alkaline hydrolysis in glass containers can give large amounts of silicate which interfere with subsequent analysis, and for this reason the use of steel or even nickel-coated steel containers is recommended. The hydrolysis of polyester urethanes yields the diamine from the diisocyanate, and the acid salt and glycols from the polyester. Hydrolysis of polyether urethanes yields the diamine and the polyether. If diamines are used as curatives then two diamines will be present in the hydrolysis products. 

Fluorenyl-based reagent 58 has been used for the attachment of mPEG of up to 40 kDa to proteins by means of urethane bond formation (Scheme 3.11). The fluorenyl moiety releases the native unmodified protein at a slow controlled rate by hydrolysis reaction, as is shown in Equation 3.29 [216]. Reagent 58 has been used in the reversible PEGylation of exendine-4 [216], human growth hormone, interferon a2 [217], enkephalin [218], atrial natriuretic peptide [219] and insulin [220]. 

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

Reaction of aniline derivatives with 4-chlorobutyroyl chloride followed by cyclization with sodium ethoxide and subsequent thionation promoted by sonication gave the corresponding A -arylpyrrolidine-2-thiones 126. Zinc-mediated condensation of diethyl bromomalonate with 126 using iodine as activator gave the vinylogous urethanes 127 whose cyclization with PPA gave the tricyclic compound 128 which upon hydrolysis afforded the acid 129 (96TL9403). 

Apart from the Important reaction leading to the formation of urethane groups, carbon dioxide can be released during curing by hydrolysis of the Isocyanate group, leading to the formation of urea groups (10). 

The formation of Intermediate compounds (e.g. carbamlc acid) Is not described in the model. So, the formation of urethane (reaction 1) and the hydrolysis of the isocyanate (reaction 2) are the rate-determining steps. 

The process proceeds through the reaction of pairs of functional groups which combine to yield the urethane interunit linkage. From the standpoint of both the mechanism and the structure type produced, inclusion of this example with the condensation class clearly is desirable. Later in this chapter other examples will be cited of polymers formed by processes which must be regarded as addition polymerizations, but which possess within the polymer chain recurrent functional groups susceptible to hydrolysis. This situation arises most frequently where a cyclic compound consisting of one or more structural units may be converted to a polymer which is nominally identical with one obtained by intermolecular condensation of a bifunctional monomer e.g., lactide may be converted to a linear polymer... 

Olsen and co-workers used a solution of nitronium tetrafluoroborate in acetonitrile for the V-nitration of acetamides and urethanes at —30°C. The following nitramides were obtained by this method V-nitroacetamide (13 %), V-nitro-2-chloroacetamide (55 %), V-nitro-n-butylacetamide (40 %), V-nitrobenzamide (53 %), ethyl V-nitro-n-butylcarbamate (91 %) and V-nitrosuccinimide (43 %). The low yield of V-nitroacetamide, a primary nitramide, is attributed to competing hydrolysis due to the release of tetrafluoroboric acid as the reaction progresses. The scope of the reaction is improved by moving to more basic solvents like ethyl acetate, 1,4-dioxane and trimethyl phosphate. ... 

The instability of primary nitramines in acidic solution means that the nitration of the parent amine with nitric acid or its mixtures is not a feasible route to these compounds. The hydrolysis of secondary nitramides is probably the single most important route to primary nitramines. Accordingly, primary nitramines are often prepared by an indirect four step route (1) acylation of a primary amine to an amide, (2) A-nitration to a secondary nitramide, (3) hydrolysis or ammonolysis with aqueous base and (4) subsequent acidification to release the free nitramine (Equation 5.17). Substrates used in these reactions include sulfonamides, carbamates (urethanes), ureas and carboxylic acid amides like acetamides and formamides etc. The nitration of amides and related compounds has been discussed in Section 5.5. 

Treatment of 2-lithiofurans with ethyl borate and hydrolysis of the resultant boronic ester yields 2(3//)-furanones (69AK(29)229). 2,5-Dimethyl-3(2i/)-furanone (358) has been prepared by a Curtius reaction on the ester (359) and acid hydrolysis of the intermediate urethane (360) (Scheme 97). This type of reaction has been used to synthesize muscarine and its stereoisomers (61QR153). 

For example, 2-bromoquinuclidine (80) does not form Grignard reagents and 2-aminoquinuclidine is so unstable that on hydrolysis of its urethans (81) under mild conditions ammonia is lost and polymers of dehydroquinuclidine are formed. The synthesis of 2-bromoquinuclidine (80) was achieved by the Borodin reaction,90 and the urethans (81) were obtained from quinuclidine-2-carboxhydrazide (82) by the Curtius reactions.142 The Curtius reaction with quinucli-dine-4-carboxylic acid derivatives gave 4-aminoquinuclidine (83).143 This compound (83) was also synthesized directly from quinuclidine-4-carboxylic acid by the Schmidt reaction. However, the first method is better, in spite of having more steps. 

Cyclization of side chain nitriles has found extensive use in the synthesis of benzocyclobutenes (70 n = 2),104 the versatile synthons which open on mild thermolysis to give o-quinodimethanes for inter- and intra-molecular [4 + 2] trapping.108 The nitrile group in (70) can be manipulated into a variety of functionalities for appending the dienophile portion. For example, in the synthesis of chelidonine, the nitrile (71) was converted, by hydrolysis followed by Curtius degradation and reaction of the formed isocyanate with benzyl alcohol, to a urethane (72). The latter was then condensed with a benzyl bromide to get the compound (73), which was elaborated further as shown in Scheme 14.109... 

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