Carbamate, formation

Ethyl carbamate, C2HyN02, is developed naturally during the fermentation of alcohoHc beverages. It also appears in foods such as bread and yogurt. Since ethyl carbamate is not easily distilled, its formation most likely involves a distillable precursor. The mechanism of ethyl carbamate formation probably involves cyanate produced from the oxidation of cyanide or from urea-based compounds in the beer. Cyanate reacts with alcohol to form ethyl carbamate as follows ... 

Benzyloxycarbonyloxy)phenyl]dimethylsulfonium methyl sulfate, NaOH, H20,51-95% yield. " This is a water-soluble reagent for benzyloxy carbamate formation. Analogous reagents for the introduction of BOC and Fmoc were also prepared and give the respective derivatives in similar high yields. 

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

An interesting reaction ensues when the intermediate synthetic precursor (65) to synthon 60 is heated with phenylenediamine. The reaction can be rationalized as involving initial enamine-imine formation (66), followed by intramolecular attack on the ester carbonyl groups resulting in carbamate formation (67), which carbamate undergoes intramolecular trans-amidation to give urea 66. Other scenarios can be proposed and defended, but the net result is formation... 

Among the different chemical reactions usable to synthesize polymeric materials by step polymerisation are esterification, amidation, nucleophilic aromatic substitution and urethane (carbamate) formation. Polymerisation... 

TEA) is known only over the range of temperatures between 0° and 50 °C and the equilibrium constant for carbamate formation is known only at 18 °C for MEA and DEA. 

In a typical experiment the isocyanate (0.006 moles) was reacted with 1.5 g of the polysaccharide in 150 ml of a 5% LiCl/ N,N-dimethylacetamide solution at 90°C under nitrogen for two hours. The appearance of a strong infrared absorbance at 1705 cm l was an indication of carbamate formation. The derivatized polymer was isolated as a white powder by precipitation of the reaction solution into a nonsolvent such as methanol. Alternatively thin films were cast directly from solution the lithium salt could be removed by rinsing with acetone. Figure 1 illustrates the reaction of cellulose with phenyl isocyanate. 

Bartoschek S, Vorholt JA, Thauer RK, et al. 2000. N-carboxymethanofuran (carbamate) formation from methanofuran and CO2 in methanogenic archaea. Thermodynamics and kinetics of the spontaneous reaction. Eur J Biochem 267 3130-8. 

After selective cyclic carbamate formation, the 3 -OH can be selectively protected using THP (Scheme 4.14). The 5-OH was then glycosylated with a thiofuranose, creating a ribostamycin analog, 78. However, compound 78 was... 

Scheme 10.2 A plausible mechanism for vinylic carbamate formation.

Silver fluoride/palladium(ll)-assisted cyclic carbamate formation from tm-butyldimethylsi-lyl (S )-( )-4-chloro-l-(2-methylpropyl)-2-butenylcarbamate to provide a 15 1 mixture of the 1,2-amino hydroxy system (for assignment, sec p 470)121. 

Alcohols. These yield suitable derivatives by ester or carbamate formation. (—)-(l ,4/ )-Cam-phanoyl chloride is an especially useful reagent15 7, as demonstrated by the following examples. The absolute configuration of the isoprene iron tricarbonyl complex 6 was determined from the X-ray structure determination of (1R,45)-camphanoate 4, the precursor of 6158. 

Methyl Carbamate Formation via Modified Hofmann Rearrangement Reactions Methyl N-(p-Methoxyphenyl)carbamate. 

Phosphate and bicarbonate ions are important substrates for many enzymatic processes and as such have regulatory functions. Bicarbonate controls the key enzyme of photosynthesis, ribulose bisphosphate carboxylase, by carbamate formation (Fig. 13-12). Chloride ions activate amylases and may affect the action of "G proteins" that mediate hormone actions. Other observed effects of ions are too numerous to mention. 

In some initial studies [45], Saegusa and coworkers reported the synthesis of methylurethanes by the reaction of copper) I) -carbamates with methyl iodide. H ere, the carbamate formation occurred only in the presence of a bulky o-donor ligand,... 

Further alkylation of the lithium (Z)-enolate of 25 with methyl iodide gave 26, introducing the C16 stereocentre (3 1 dr) and completing the carbon backbone. Oxidation at Cl and carbamate formation gave 27 which underwent a chelation-controlled reduction at C17 (30 1 dr). Finally, global deprotection completed the synthesis of discodermolide (1), with an overall yield of 4.3% achieved over 24 steps in the longest linear sequence. 

The Heat Recycle Urea Process (HRUP) was developed by Urea Technologies in the 1970 s and is now offered by Monsanto Enviro-Chem. This process is shown in Figure 11.5. In this process ammonia, recycled carbamate and about 60% of the make-up CO2 feed are charged to the top of an open-ended reactor coil at 3200 psig (220 bar). Ammonium carbamate is formed within the coil, exits the coil at the bottom and flows up and around it. The exothermic heat of carbamate formation in the coil drives the endothermic dehydration of carbamate to urea on the outside of the coil. This isothermal reactor design allows the conversion rate to reach 77%. The reactor has a uniform temperature profile that eliminates corrosion in the bottom of the reactor112. 

To monitor tumor response to capecitabine therapy noninvasively, Zheng and co-workers, from the Indiana University School of Medicine, developed the synthesis of the fluorine- 18-labeled capecitabine as a potential radiotracer for positron emission tomography (PET) imaging of tumors.28 Cytosine (20) was nitrated at the C-5 position with nitric acid in concentrated sulfuric acid at 85°C, followed by neutralization to provide 5-nitrocytosine (27) in moderate yield. This nitro pyrimidine was then carried through the glycosylation and carbamate formation steps, as shown in the Scheme below, to provide the 6/s-protected 5-nitro cytidine 28 in 47% for the three-step process. Precursor 28 was then labeled by nucleophilic substitution with a complex of 18F-labeled potassium fluoride with cryptand Kryptofix 222 in DMSO at 150 °C to provide the fluorine-18-labe led adduct. This intermediate was not isolated, but semi-purified and deprotected with aqueous NaOH in methanol to provide [l8F]-capecitabine in 20-30% radiochemical yield for the 3-mg-scale process. The synthesis time for fluorine-18 labeled capecitabine (including HPLC purification) from end of bombardment to produce KI8F to the final formulation of [18F]-1 for in vivo studies was 60-70 min. 

When primary aliphatic isocyanates that show the lowest reactivity compared to secondary or aromatic isocyanates are used in combination with hydrophilic (pre-) polymers, crosslinking may be performed in aqueous solution without the use of additional crosslinkers. At neutral pH, hydrolysis of isocyanates to carbaminic acid with subsequent decarboxylation yields amines. These amines react much more rapidly than water with isocyanates, resulting in crosslinking if the functionality per macromolecule is more than two [43], This crosslinking reaction can be quenched by adjustment of the pH value. At pH values above 10, carbamate formation is faster than decarboxylation, whereas at pH values below 3 an almost quantitative protonation of the formed amino groups results in the formation of ammonium. In both cases, chemical crosslinking is prevented. 

Dynamic Capture of Carbon Dioxide via Reversible Ammonium Carbamate Formation... 

Fig. 11 (a) C02 capture by reversible ammonium carbamate formation, (b) Example of linear solid oligomer formed upon reaction of 2-hydroxy-l,3,5-benzenetrialdehyde and at least 3 equiv. of diethylenetriamine in the presence of C02... 

This situation, which is due to the thermodynamic properties of the reactants and products, is further aggravated by the fact that the carbamate-to urea conversion reaction is much slower than carbamate formation. This makes it necessary to operate in two steps ... 

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