4-Nitrophenyl chloroformate

The nitric oxide donor SIN-1 13 (Section 5.03.12) reacts with 4-nitrophenyl chloroformate to give the N-acylated product that also acts as a potent nitric oxide donor. Further derivatives with trypanocidal activities may be prepared by transesterification with various alcohols <2003JHC943>. 

Examples of this behaviour are shown in Table 7 where k+ is related to reaction of substrate fully bound to a CTAX micelle and k to reaction in an anionic micelle of SDS. The ratio k+/k is consistently larger than unity for hydrolyses of open chain anhydrides, diaryl carbonates and aryl chloroformates. In addition hydrolysis of 4-nitrophenyl chloroformate is slightly faster in cationic micelles than in water. Spontaneous hydrolyses of N-acyl triazoles are also inhibited less by cationic micelles of CTABr than anionic micelles of SDS (Fadnavis and Engberts, 1982). 

With respect to the reduced water concentration (1), it seems as if all but one of the hydrolysis reactions following the mechanism shown in Scheme 10 are retarded in micellar solutions (the exception being the hydrolysis of 4-nitrophenyl chloroformate la in cationic micelles ) and the lower water concentration in the micellar Stern region (estimated to be 45 mol dm for and 33 mol dm for SDS ) will... 

The synthesis of pyrazolidine-2-carboxylic acid containing peptides is carried out following the standard procedures established for azaamino acid peptides as described in Section 10.4. Accordingly, l-(/< rt-butoxycarbonyl)pyrazolidine (which is the equivalent of 2-azaproline tert-butyl ester) is treated with 4-nitrophenyl chloroformate to generate (/ert-butoxy-carbonyl)pyrazolidine-2-carboxylic add 4-nitrophenyl ester.1 60 This active ester is then used... 

Importantly, TV-carbamoyl derivatives of primary amines obtained from photolabile benzoins exist in varying proportions as cyclic hydroxyoxazolidinone tautomers. Therefore, the preparation of TV-carbamoyl derivatives of benzoins is applicable only for secondary amines and TV-alkylated amino acids. 244 At basic pH unsymmetrical benzoins, such as 3,5-dimethoxybenzoin, their mixed carbonate and carbamate derivatives, tend to equilibrate to the isomeric forms. Nevertheless, in TFA and aqueous solutions at pH 8 the structural integrity is fully maintained. 244 Preparation of 3,5-dimethoxybenzoin-derived carbamates of secondary amines and amino acids can be mediated by either CDI/methyl triflate in ni-tromethane 246 or 4-nitrophenyl chloroformate/DMAP in dry THF. 244 ... 

To a THF (15 mL) soln of (l-pyrenyl)methanol (3.07 g, 13.2 mmol) and 4-nitrophenyl chloroformate (3.21 g, 16.0 mmol), pyridine (1.3 mL) was added dropwise at 0 °C. The mixture was stirred at 0 °C for 1 h and then at rt for 2 h. The solvent was distilled off and the residue dissolved in CH2C12, washed successively with 1M HC1, 4% NaHC03, H20, and sat. NaCl, then dried (Na2S04). After removal of the solvent, recrystallization of the crude product from CHCI s/hexanes gave 4-nitrophenyl 1-pyrenylmethyl carbonate yield 4.79 g (91%) mp 130 °C. 

Carbamoyl chlorides, CDI, 4-nitrophenyl carbamates, and the compounds used to prepare them, e.g. phosgene and 4-nitrophenyl chloroformate, are toxic. 

Amines can be linked to polymeric alcohols as carbamates. Carbamate attachment of amines can be achieved by reaction of isocyanates with alcohol linkers, or by treatment of alcohol linkers with phosgene [339,427,428] or a synthetic equivalent thereof, followed by exposure to the amine (Figure 3.26). The reagents most commonly used for the activation of alcohol linkers are 4-nitrophenyl chloroformate [69,429-436] and carbonyl diimidazole [427,437-440], The preparation of support-bound carbamates is discussed in Section 14.6. 

A solution of 4-nitrophenyl chloroformate (43.0 g, 231 mmol, 5.5 equiv.) in DCM (200 mL) was added dropwise over a period of 0.5 h to a stirred suspension of Wang resin (45.0 g, 42.3 mmol) in DCM (600 mL) and pyridine (52.0 mL, 644 mmol, 15 equiv.). After completion of the addition, the mixture was stirred at room temperature for 3 h, and then filtered, lire resin was washed with DCM (5 x 300 mL) and then added portionwise to a stirred solution of piperazine (38.2 g, 444 mmol. 11 equiv.) in DMT1 (600 mL.). which led to an increase in the tempera-hue of the mixture and a color change to yellow-orange. The resulting mixture was shaken at room temperature for 13 h, then liltered, and the resin was extensively ashed w itli DMF. DCM, methanol, and finally with further DCM. After drying in aii, about 15 g of resin-bound pipera/ine was obtained. 

As alternatives to 4-nitrophenyl chloroformate, carbonyl diimidazole [100-102] or di-A-succinimidyl carbonate [103,104] can be used to convert polymeric alcohols into alkoxycarbonylating reagents suitable for the preparation of support-bound carbamates. Polystyrene-bound alkoxycarbonyl imidazole is less reactive than the corresponding 4-nitrophenyl carbonate, and sometimes requires heating to undergo reaction with amines. Additional activation of these imidazolides can be achieved by N-methylation (Entry 9, Table 14.7). 

Enantiomerically pure aminoalcohols, which are readily available by reduction of a-amino acids, can be converted into alkoxycarbonylating reagents suitable for the solid-phase synthesis of oligocarbamates (Figure 16.26). Particularly convenient alkoxycarbonylating reagents are 4-nitrophenyl carbonates, which can be prepared from alcohols and 4-nitrophenyl chloroformate, and which react smoothly with aliphatic primary or secondary amines to yield the corresponding carbamates. 

Solvolysis rates of isopropenyl chloroformate, CH2=C(Me)0C(0)Cl, were shown to be very similar to those for 4-nitrobenzoyl chloride in mechanism and reactivity.29 Stepwise mechanisms were observed in the aminolysis of aryl chloroformates by a series of substituted quinuclidines - which were more reactive than isobasic secondary alicyclic amines.30 The pH-independent hydrolysis of 4-nitrophenyl chloroformate in MeCN-H20 mixtures proceeded via a cyclic transition state containing the ester and two water molecules.15 Solvolyses of 2-furancarbonyl chloride in most... 

A preparatively useful approach to the enantiomerically pure antihypertensive agent (R)-SQ 32,926 was disclosed by Atwal et al. (Scheme 4.13) [169]. In the first step, the 1,4-dihydropyrimidine intermediate 38 is acylated at N3 with 4-nitrophenyl chloroformate followed by hydrolysis with HC1 in THF to give DHPM 39. Treatment with (R)-a-methylbenzylamine provided a mixture of diastereomeric ureas from which the (R,R) isomer 40 was separated by crystallization. Cleavage with TFA provided (R)-SQ 32,926 in high enantiomeric purity. Similar strategies have been used to obtain a number of pharmacologically important DHPM derivatives in enantiomerically pure form [169, 186, 187]. 

More useful is the conversion of dextran with ethyl chloroformate or 4-nitrophenyl chloroformate carried out in DMF/IiCl to give the corresponding carbonates [356]. Analysis of the total carbonate content and the content of 4-nitrophenyl carbonate moieties during the course of the reac-... 

More recently, thiolated dextran was synthesised by modification of dextran with 4-nitrophenyl chloroformate in DMSO/pyridine in the presence of DMAP at 0 °C yielding a carbonate (content 6%), which can be substituted with cystamine. Subsequent reduction yields the thiolated dextran containing between 1 and 4% thiol moieties (Fig. 57) [370]. 

Ethyl 2-chloro-2-formylacetate Barium hydroxide octahydrate Lithium aluminum hydride 4-Nitrophenyl chloroformate Phosphorus pentasulfide Methylamine... 

Another interesting modification of glass surfaces was introduced by Beier and Hoheisel.23 They synthesized a flexible, dendritic linker system that enables covalent immobilization of oligonucleotides and PNAs with high loading capacity in a controlled manner. This method facilitates the modulation of surface properties such as hydrophobicity and charge. The synthesis of the linker system involves two consecutive reactions an acylation of surface-bound amine groups with acid chloride (4-nitrophenyl-chloroformate or acryloylchloride) and subsequent reaction with an amine. A bis-amine results in a linker system, while a polyamine produces a dendritic structure (Fig. 14.3). Because polyamines possess primary and secondary amine... 

Scheme 3.2.4 shows the synthetic route employed for the synthesis of linker-head intermediate 14 from half-sided Boc-protected amine 13 [28], via urea formation, mediated by 4-nitrophenyl chloroformate with 1-Cbz-piperazine, followed by hydrogenation of the Cbz group with palladium on carbon. 

Nitrophenyl chloroformate activation. The reaction of polysaccharides with chloroformates forming reactive carbonate derivatives has often been used to link bioactive compounds, such as affinity ligands and enzymes, onto polysaccharide matrixes. It was reported that upon reaction with ethyl chloroformate cyclic carbonate as well as ethyl-carbonate structures are formed (9-13). Activation with N-succinimi-do chloroformate (14), 2,4,5-trichloroformate (14) and 4-nitrophenyl chloroformate (14, 15) reportedly led to the introduction of pending carbonate moieties. 

Recently we have reinvestigated (16) the activation of dextran with 4-nitrophenyl chloroformate (VII). The content of the 4-nitrophenyl carbonate groups in activated dextran can be easily determined... 

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