Alkyl -substituted carbamates

Both mono- and dimeric iV-alkyl substituted carbamic acids have also been detected in solution [12, 18, 19]. At 293 K, under N2, the partial decomposition of the (BnNH3)02CNHBn salt, suspended in THF, was followed by IR... 

N-dealkylation results from an alkyl substitution on an aromatic molecule, which is one of the first places where microorganisms initiate catabolic transformation of atrazine, a xenobiotic molecule (Fig. 15.2). It is a typical example of a reaction leading to transformation of pesticides like phenyl ureas, acylanihdes, carbamates, s-tri-azines, and dinitranilines. The enzyme mediating the reaction is a mixed-function oxidase, requiring a reduced nicotinamide nucleotide as an H donor. 

Table 17), but cyclization of -substituted carbamates is highly selective (entries 2,4 and 5), presumably by insuring reversible formation of the intermediate prior to benzyl cleavage and steric interactions between the -substituent and the alkyl substituent favoring the axial orientation (equation 61). Cycliza-tions of this type, where R = H and Y = a-phenethyl, result in little asymmetric induction. However, the diastereomeric products can be separated and used for the synthesis of chiral nonracemic amino alcohol derivatives.164... 

The regioselective and enantiospecific allylic substitution of alkyl-substituted allyl benzoates and carbamates with (Me2PhSi)2Zn and Cul has been shown to occur by an oxidative addition - reduction elimination mechanism rather than an SN2 mechanism.16... 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

As discussed, conjugate addition reactions involving chiral y-alkyl-substituted unsaturated carbonyl derivatives usually occur with low levels of diastereoselectivity. In accord with this general trend, the benzyloxy and silyloxy derivatives 103 and 104 (Scheme 6.23) both reacted with a silyl cuprate in non-selective fashion, to give the conjugate adducts 108 and 109, respectively (entries 1 and 2, Tab. 6.3) [39]. Conversely, hi levels of diastereoselectivity were found for the corresponding carbamates, and even better results were obtained for carbonates, giving the anti esters 110-112 as the major diastereomers (entries 3-5) [39]. 

Potent antioxidant analogs of LA, exemplified by structures 362 and 363 <2003EJM1>, containing the W-alkyl-substituted morpholine ring and thioamide or thiocarbamate moiety, respectively, have also been developed and pharmacologically tested. In comparison to the structurally related amide or carbamate linker analogues, compounds 362 and 363 are more promising antioxidants. 

Alkyl carbamates 309 reacted with primary amines in the presence of DBU to give N-substituted carbamates 310 (82MIP2479209 82USP4336402). 

Synthesis of Alkyl iV-Cyano-iV-substituted Carbamates, Thiolcarbamates, and N, iV-Disubstituted Cyanamides... 

In summary, depending on reaction condition, we have described a novel and versatile direct synthesis of alkyl N-cyano-N-substituted carbamates or N,N-disubstituted cyanamides. The required intermediates can be prepared in good yields from cyanamide, carbon disulfidtj potassium hydroxide, alkyl or benzyl alcohols and alkyl or benzyl halides which are readily available and inexpensive. 

More classical approaches to the 2-benzazepine system, in particular the 2-benzazepinone 23, have been reported by Le Digueiher et al. The first was based on (5)-phenylalanine carboxamide 20 via the protected acetoxy compound 21 and acid-catalysed cyclization to 22 A-alkylation and carbamate deprotection then afforded 23. The second, more general route, was based on N-Boc aminomalonate 25 and 2,2 -dibromo-o-xylene, and then steps via 26 and 27. Yields were fair to moderate. The benzazepinone 23 was converted into the N-substituted derivatives 24, which were potent and specific farnesyl transferase inhibitors such compounds are of interest as potential anti-tumour agents <04BMCL767>. 

DIM Dimitrov, P., Jamroz-Piegza, M., Trzebicka, B., and Dworak, A., The influence of hydrophobic substitution on self-association of poly(ethylene oxide)-Z>-poly(n-alkyl glycidyl carbamate)s-6-poly(ethylene oxide) triblock copolymers in aqueous media. Polymer, 48, 1866, 2007. 

The 1 -alkyl substituted isoquinolines have been modified via the reaction between imines and ethyl chloroformate followed by trimethyl phosphite to form carbamate phosphonate intermediates that cyclize into isoquinolines in the presence of Lewis acid. ... 

This reaction was first reported by Riemschneider in 1949. It is an acidic transformation of alkyl or aryl thiocyanates into thiocarbamates and is known as the Riemschneider reaction. In this reaction, when thiocyanates are treated with concentrated sulfuric acid, the corresponding thiocarbamates are obtained. In parallel, when thiocyanates are treated with concentrated sulfuric acid in the presence of alcohol or olefin, the corresponding A -substituted carbamates are yielded. The alcohols or olefins that are stable in the presence of sulfuric acid, including isopropyl alcohol, cc-butyl alcohol, r-butyl alcohol, cyclohex-anol, isobutylene, and camphene aU are suitable for this reaction, whereas low-order alcohols such as methanol and ethanol do not react with thiocyanate to give the corresponding A -substituted thiocarbamates. hi addition, the benzyl thiocyante and some ortho-substituted phenyl thiocyanates cannot be transformed into the corresponding thiocarbamates under these conditions because they are sensitive to sulfuric acid. Some unsuitable thiocyanates are o-carboxyl, o-methoxy, o-nitrophenyl thiocyanates, and o-methyM-amino phenyl thiocyanate. ... 

While alkyl substituted piperidines have low levels of SRTD activity, the amides, carbamates, and ureas are much more active compounds (Table 2). The 4-fluorophenylurea, Compound 10, has the highest SRTD activity of any compound in the diaminoquinazoline area. The substitution patterns on the aniline and benzo portions of the molecule were reinvestigated with the more active group in Position 4, but the structure-activity relationships were found to be the same as for the 4-cyclohexylamino compounds as described in Figure 1. 

This approach has been used to efficiently assemble 3-vinyl indoles 13 with alkenes (Scheme 6.20) [28]. It was observed in this case that the nature of the nitrogen substituent influences the ability to trap the 3-palladated indole, with carbamates providing the highest yields. The elimination of HX from the palladium after P-hydride elimination creates a Pd(0) complex that is unable to mediate subsequent cyclizations. As such, co-oxidants, such as stoichiometric copper(II) salts, are used in this reaction to regenerate the palladium(II) catalyst. However, by modifying reaction conditions, Lu has found that the addition of excess LiBr can inhibit P-hydride elimination, and instead allow the formation of the reduced product (Scheme 6.21) [29]. This not only allows access to 3-alkyl substituted indoles, but also eliminates the need for stoichiometric oxidants. 

Tosylimino)phenyl-X -iodane, another iodine(III)-based reagent, also facilitates the conversion of a large variety of amides such as 16 into the corresponding isocyanates 17, which are suitable precursors for the synthesis of methyl carbamates 18 as shown in Scheme 6 [6]. The reaction proceeds in very good yields with a variety of electron-rich and electron-poor aryl-substituted amides as well as bulky alkyl-substituted amides. Although no conversion was observed when a 2,4,6-trimethylphenyl substituent was present, the authors successfully synthesized isopropyl Af-(4-methylphenyl)carbamate and ferf-butyl iV-(4-methylphenyl)carbamate by treatment of the corresponding isocyanates with suitable alcohols. 

Scheme 30 shows two alternative pathways to end up with the same mono-substituted carbamate resin 203. The first possible strategy is to form an activated carbonate derivative and to substitute it by a primary amine. The second approach uses isocyanates 202 which are added to the free alcohol functionality on the solid support. Further reaction of the resulting resin with alkyl halogenides 204 leads to twofold substituted carbamates that are released in the presence of primary or secondary amines 206 and... 

Bach, T. and Schrbder, J., The Paterno-Biichi reaction of a-alkyl-substituted ene carbamates and benzaldehyde. Synthesis, 1117, 2001. 

The salts of alkyl xanthates, A/,A/ -di-substituted dithio-carbamates and dialkyidithiophosphates [26] are effective peroxide decomposers. Since no active hydrogen is present in these compounds, an electron-transfer mechanism was suggested. The peroxide radical is capable of abstracting an electron from the electron-rich sulfur atom and is converted into a peroxy anion as illustrated below for zinc dialkyl dithiocarbamate [27] ... 

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