Carbamates, hydrolysis preparation

Lithiated allylic carbamates (35) (prepared as shown) react with aldehydes or ketones (R C0R ), in a reaction accompanied by an allylic rearrangement, to give (after hydrolysis) y-hydroxy aldehydes or ketones. The reaction is called the homoaldol reaction, since the product is a homolog of the product... 

Analogues 249 (X = H, OH) of UDP-GlcNAc have been prepared as potential inhibitors of chitin synthetases. The synthetic route involved a C-allyl derivative of GlcNAc, which was elaborated by ozonolysis, Wittig reaction and coupling with the nucleoside, followed by hydrogenation or hydroxylation as appropriate. The corresponding amides were also prepared from 5 -amino-5 -deoxyuridine. Lipophilic amino acid methyl esters and methylamides have been coupled to 0-5 of AZT by carbamate links. The products showed anti-HIV activity, but this was not due to carbamate hydrolysis or to direct inhibition of reverse transcriptase, and the mechanism of action may be one not previously observed with nucleoside antivirals. ... 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

The Curtms rearrangement has been used to prepare 5-aminothiazole (11) (60.61), 4-methyl-5-aminothiazole. 2-chloro-5-aminothiazole (58), and 2.4-dimethyl-5-aminothiazole (62) (Scheme 11). Heating the corresponding azides yield carbamates that resist hydrolysis but react with acetic anhydride to give the 5-acetylaminothiazoles. 

The diphenylmethyl carbamate, prepared from the azidoformate, is readily cleaved by mild acid hydrolysis (1.7 N HCl, THF, 65°, 10 min, 100% yield). ... 

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. 

This ring system could be prepared by building either of the two heterocycles and then doing an annulation. Thus, cyclization of ethyl o-nitrophenylhydrazonocyanoacetyl carbamate 552 afforded 553. Reduction of 553 by the action of iron(II) sulfate gave 554, which on acid hydrolysis gave 558. Cyclization of o-aminophenyl derivatives 554 and 558 to 555 and 559, respectively, was effected (77CCC894) by treatment with acid. Phthalimido derivatives of 554 could also be cyclized to this... 

The mechanism of the polymerization of NCA with tertiary amine is still controversial. Mori and Iwatsuki claim that the true initiator is the primary amino group formed by hydrolysis of the NCA with contaminated water and that tertiary amine forms a complex with the NCA and accelerates the addition reaction37 . Harwood et al. confirmed the propagating carbamate by NMR in polymerization initiated with a strong base37 . The successive addition of NCA to the polymer end catalyzed with a strong base affords an alternative procedure for the synthesis of block copolypeptides. Block copolypeptides of poly(oxyethylene) were prepared by triethyl amine catalyzed polymerization of NCA in the presence of poly(oxyethylene)bis-eMoroformate38 . 

Early attempts to prepare 4(5)-aminoimidazole (25 R = H) from the carbamates (34 R = Me, Et) [obtained from the hydrazide (35) using the Curtius method] by either acid- or base-catalyzed hydrolysis resulted in failure (30JCS268). 

Strong acid hydrolysis of 1,2,6-thiadiazine 1,1-dioxides 239 or 240 results in ring contraction to afford the 1,2,5-thiadiazolinone 1,1-dioxides 241 in low yield <1996J(P2)293>. 3-Dialkylamino-2/7-azirines 242 suffer ring expansion with in situ-prepared iV-sulfonylamides 243 and carbamates to give both the 1,2,3-oxathiazoline 244 and the thiadiazoline 1,1-dioxide 245 (Equation 56). The oxathiazole 244 isomerizes quantitatively to the thermodynamically favored thiadiazoline 245 <1996J(P1)1629>. 

H. Bundgaard, A. Buur, V. H. L. Lee, Timolol Prodrugs Preparation and Hydrolysis Kinetics of A-Benzoyl Carbamate Esters of Timolol and Related Compounds , Acta Pharm. Suec. 1988, 25, 293 - 306. 

Fig. 9.8 presents another, more complex type of phosphate prodrugs, namely (phosphoryloxy)methyl carbonates and carbamates (9-26, X = O or NH, resp.) [84], Here, the [(phosphoryloxy)methyl]carbonyl carrier appears quite versatile and of potential interest to prepare prodrugs of alcohols, phenols, and amines. The cascade of reactions leading from prodrug to drug as shown in Fig. 9.8 involves three steps, namely ester hydrolysis, release of formaldehyde, and a final step of carbonate hydrolysis (X = O) or A-decar-boxylation (X = NH). Three model compounds, a secondary alcohol, a primary aliphatic amine, and a primary aromatic amine, were derivatized with the carrier moiety and examined for their rates of breakdown [84], The alcohol, indan-2-ol, yielded a carrier-linked derivative that proved relatively... 

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. 

Nitramine (161), the simplest member of the nitramines, can be prepared from ethyl carbamate (158) in three synthetic steps nitration of the latter with mixed acid or a solution of ethyl nitrate in concentrated sulfuric acid, followed by isolation of the resulting ethyl N-nitrocarbamate as the ammonium salt (159), hydrolysis with aqueous potassium hydroxide and subsequent acidification, yields nitramine (161). ... 

The nitration of the carbamate (55) with pure nitric acid, followed by hydrolysis of the product (56) and subsequent acidification, also yields EDNA (2). ° Acetylation of ethylenediamine, followed by nitration of the resulting product, N, A -ethylenebisacetamide (57), yields A, A -dinitro-A,A -ethylenebisacetamide (58), an explosive which also yields EDNA (2) ° on treatment with aqueous base followed by acidification. EDNA (2) has also been synthesized from ethyleneoxamide (169) the latter is prepared from the condensation of ethylenediamine with diethyloxalate. ... 

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. 

Solvolysis of Diels-Alder adducts provides a useful means of preparing a variety of nitrogen-containing compounds. For instance, the hydrolysis of A Cbz or A -Ts bicylic sulfonamides 44 and 112 with NaOH affords the homoallylic carbamate 113 and sulfonamide 114, respectively (Scheme 12) <2000TL3743, 2002TA2407>. Related hydrolysis reactions have also been reported with monocyclic 1,2-dihydrothiazine oxides <2004JOC7198>. 

Hydrolysis of the trimethylsilyl urethane (1 R=C02SiMe3), prepared by the action of trimethylsilyl iodide on the methyl carbamate (1 R = C02Me), with methanol at -78 °C yields the carbamic acid (1 R = C02H). On allowing a CDC13 solution of the carbamic acid to warm to room temperature, decarboxylation takes place to yield the deep red, highly unstable 1//-azepine (1 R=H) (80AG(E)1016>. 

J. Davy found ammonium carbamate to be soluble in alcohol of sp. gr. 0 829 and A. Basaroff found that it dissolves when heated with absolute alcohol in a sealed tube, and it crystallizes out again when the soln. cools. E. Divers also found that ammonium carbamate dissolves freely in aqua ammonia, and the system is cooled 100 parts of aqua ammonia dissolve 50 parts of the salt, and the soln. on standing furnishes crystals of normal ammonium carbonate but if the freshly prepared soln. be cooled to 0°, crystals of the carbamate are obtained, consequently ammonia retards the hydrolysis of the carbamate. 

A common method for the preparation of primary amines involves the hydrolysis of isocyanates or isothiocyanates.4 The latter react more slowly and more vigorous conditions are required. The reaction is catalyzed by acids or bases. In this case simple addition of water to the carbon-nitrogen double bond would give an N-substituted carbamic acid (3). Such compounds are unstable and break down to carbon dioxide (or COS in the case of isothiocyanates) and the amine ... 

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