Carbamate intermediate

Cp derivatives (Scheme 185) to form -oxo-bridged dimeric complexes. The stabilities of the Af,0-bound carbamate intermediates depend mainly on the cyclopentadienyl ring substituents, but there is also a small dependence on the nature of the length of the (dimethylamino)alkyl chain for the C5H4Me systems. ... 

Figure 3.13 CDI reacts with hydroxyl groups to form an active imidazole carbamate intermediate. In the pres ence of amine-containing compounds, a carbamate linkage is created with loss of imidazole.

Figure 15.13 Tween 20 can be activated with CDI using its hydroxyl groups to create an amine-reactive imidazole carbamate intermediate that then can be used to coat a carbon nanotube. The result is an activated nanotube that can be used to couple proteins and other amine-containing molecules.

The hydrogenation of C02 in the presence of amines to give dialkylformamides has been carried out directly in an IL/scC02 system. In this case, the ionic liquid was shown to play a dual role [74]. It is an effective solvent for the ruthenium phosphine catalyst and at the same time allows a distinct phase distribution of the polar carbamate intermediates and the less polar products formed during the conversion of C02. As a result, the selectivity of the reaction can be increased over conditions where scC02 is used as the sole reaction medium. 

A second route to nonracemic /-oxygenated allylic stannanes utilizes an enantioselective deprotonation of allylic carbamates by BuLi in the presence of (—)-sparteine. The configurationally stable a-lithio carbamate intermediate undergoes enantioselective S/,-2 reaction with Bu3SnCl and Mc SnCI (Scheme 28)65. Once formed, the /-carbamoyloxy stannanes can be inverted by successive lithiation with. s-BuLi and stannation with R3SnCl (Scheme 29)65. The former reaction proceeds with S/.-2 retention and the latter by Sf2 inversion. Nonracemic allylic carbamates can also be used to prepare chiral stannanes. Deprotonation with. s-BuLi TMEDA proceeds stereospecifically with retention (Scheme 29)65. 

Pechiney (2) A process for making urea from ammonia and carbon dioxide. The ammonium carbamate intermediate is handled and heated as an oil slurry. 

Figure 2. Equations showing the reaction between an JN-chlorosul-fenyl-IJ-methy 1 carbamate intermediate (or corresponding I -chloro-sulfinyl-N-methylcarbamate) and different nucleophilic agents.

Finally, Inanaga s contribution to the development of chiral 4-dialkylaminopyrid-ine based catalysts for enantioselective acyl transfer relied on the use of C -symmetric 4-PPY derivative 36 (Fig. 7) [130]. This compound was obtained in an enantiopure form by selective cleavage of a carbamate intermediate using Sml, and allowed the KR of various. yec-alcohols with selectivity factors ranging from y = 2.1 to 14. 

The amino group of 463 is transformed initially into carbamate compounds by treatment with several isocyanates. The carbamate intermediates were readily cyclized in base to give dihydrothieno[3,2-4]pyrimidines 464 (Equation 173) <1996MI597, 1995JOC1461>. 

Union Carbide also patented a phosgene-free process for making hexamethylene diisocyanates [40] (Scheme5.5). In this later process, 1,6-hexanediamine was reacted with dry-ice, trimethylchlorosilane, and trichlorophenylsilane to form a halosilyl carbamate intermediate and then converted to the corresponding diisocyanate. However, it should be noted that trichlorophenylsilane used in this process is on the EPA s Extremely Hazardous Chemicals List (40 CFR Part 355, Appendix A). 

First the bicarbonate ion is activated (step 1). The activated carbon is subject to nucleophilic attack by ammonia, leading to a carbamate intermediate (step 2). Finally, in a reaction similar to step 1, a second phosphoryl group is transferred to carbamate to form carbamoyl phosphate (step 3). 

The alcoholysis of urea affords stepwise acyclic carbonates through the formation of an alkyl carbamate intermediate (Scheme 7.2). The reaction of urea with alcohols to carbamate is exothermic, whereas the subsequent reaction-carbamate to carbonate-is endothermic. Thus, the ideal gas free energy, AG, is positive for the latter step, which means that a low yield of carbonates would be expected [12],... 

Carbamate intermediate 7 derived from aminothiophenes 1 and ethyl chloroformate were converted into 3-substituted thieno[2,3-d]pyrimidine-... 

As shown in Figure 5, the coupling reaction between an amino acid and an N-carboxy-a-amino acid anhydride is performed at alkaline pH but the resulting carbamate intermediate is decomposed at acidic pH in order to give the dipeptide and allow further reaction leading to polyamino acids. Polymer formation is performed most frequently at neutral pH since the half-life of the intermediate carbamate is very short (see Figure 6). 

A novel and versatile solid-phase synthesis of pyrimido[4,5- fJpyrimidine-2,4-diones has been reported <03S1739>. The key step is the reaction of the support-bound pyrimidine with isocyanates, involving formation of a carbamate intermediate, followed by a base-catalyzed intramolecular ring closure to give the polymer-bound pyrimidopyrimidines which are used in subsequent reactions providing 1,3-disubstituted 7-amino derivatives. 

The reaction of ( , )-2,4-octadecadienyl carbamate with thionyl chloride in pyridine at 15 "C yields only one stereoisomer of the corresponding dihydrothiazine 5-oxide via an /V-sultinyl carbamate intermediate which undergoes intramolecular Diels-Alder reaction with complete stereoselecti vity 96. 

A key carbamate intermediate during the total synthesis of pancratistatin was prepared via the Curtius rearrangement of the corresponding carboxylic acid by S. Kim et a. The isocyanate intermediate was rather stable and was converted to the desired carbamate in 82% overall yield by treatment with NaOMe/MeOH. 

Scheme 18. Cyanate-epoxy reaction via carbamate intermediate (Fyfe et al.)...

Hydrolysis of the galactosyl unit of 52 would produce a bis-carbamate intermediate. After release of C02, the resulting para-aminobenzylcarbamate, known to undergo spontaneous 1,6-elimination (52) under mild conditions, should lead to free doxorubicin (2) and another molecule of C02. Synthesis of prodrug 52 involved initial condensation of 2,3,4,6-tetra-O-acetyl-a-D-galactopyranose (49) with para-tolyl isocyanate in DMF to afford carbamate 53. Benzylic bromination of 53 to 54 was followed by solvolysis into primary alcohol 55. Activation of 55 to 56 was achieved by use of 4-nitrophenyl chloroformate. Further condensation of 56 with doxorubicin (2) in DMF gave 57 which was finally deprotected by transesterification to yield prodrug 52 [63]. 

The selective acylation of the amino group on G-1 of the 2-deoxy-streptamine moiety is, however, generally difficult for 3, 4 -dideoxynea-mine (187), ribostamycin (50, see p. 131), and lividomycin A (18, see p. 120), it has been achieved through a cyclic carbamate intermediate. 

D structures with the following assumptions. The carbamate intermediate is assumed to be tetrahedral with normal C-0 bond lengths... 

R = Me2C=CH-CH2-CH2) with hydrazine hydrate leads to carbamate intermediates, which undergo cyclization to give 5-hydroxy-5.6-dihydro-4/f-l,3,4-oxadiazin-2(3//)-ones 311. The thermal dehydration of 311 gives 1,3,4-oxadiazin-2(3//)-ones 312 <2003CHE1057>. In contrast to the case with hydrazine hydrate, the reaction of aromatic hydrazines with l,3-dioxolan-2-ones 310 provides 3-arylamino-4-hydroxyoxazolidin-2(3//)-ones 313. 

Fig. 6.12 In situ IR data acquired during reduction of a Weinreb amide. The loss of starting material and subsequent formation of a carbamate intermediate may be followed.

Total Synthesis of Woodward s Carbamate Intermediate Deslongchamps, 1985 (Scheme 6) [74]... 

One gram of TMS-capped silica was treated with 15 mL of 0.25 M TMSI in dry acetonitrile at 70° C for a period of at least 12 h. Temperatures of less than40°C (which were sufficient to deprotect systems based on one benzyl carbamate per imprint molecule) did not show appreciable deprotection of material 1. Given the treatment necessary to achieve carbamate deprotection, it is important to emphasize that the TMSI procedure does not change the connectivity of the silica framework, as ascertained by studies on model crystalline materials such as a high-silica zeolite faujasite [42]. Following TMSI treatment, the silica was filtered and washed with acetonitrile, methanol, saturated aqueous sodium bicarbonate, methanol, and acetonitrile. The purpose of the aqueous treatment was hydrolysis of the silyl carbamate intermediate as shown in Fig. 6b-c. 

Carbonates can be described as diester derivatives of carbonic acid, formed by condensation with hydroxyl compounds. However, carbo q lic acids do not possess the necessaiy reactivity to synthesize such products. Therefore bifunctional reactive molecules such as phosgene or carbonyldiimidazoles like N,N -carbonyldiimidazole (CDI) and disuccinimidyl carbonate (DSC) are commonly used (Scheme 1.13). These compounds readily react with nucleophiles to form stable conjugates. They react with hydro)q l-containing molecules to form the amino-reactive carbonate or carbamate intermediates. These intermediates react in a subsequent step with primaiy amines to form stable carbamate bonds (aliphatic urethanes). The reaction is usually carried out in alkaline media (pH 7-9) and in the absence of competing amino and... 

Bisphenoi A Diphenyl carbonate Terephthaloyl chloride intermediate, polacrylate resins Hydroxypropyl carbamate intermediate, polishes Coconut acid Tallow acid Triethanolamine intermediate, polyacrylates Dimethylaminoethyl acrylate intermediate, polyamide derivs. Cyclocarboxypropyloleic acid intermediate, polyamides Ethyienediamine Pyromellitic acid intermediate, polyarylates Bisphenoi A... 

The Mitsunobu reaction can be used in the preparation of carbamate esters as well (e.g., 234). The reaction proceeds via an in-situ carboxylation of an alkylamine with CO2, followed by an 0-alkylation with an alcohol in the presence of TPP/DEAD. Yields are typically in the 80-90% range. A solid-supported version in which Fmoc-(I)-phenylalanine is tethered to Wang resin via an ester has also been reported. In situ deprotection with a tertiary amine to yield an 0-ammonium carbamate intermediate in the presence of primary aliphatic alcohols and PBuj/ADDP leads to the formation of the corresponding carbamates the carbamates are typically obtained in 40-80% yield with variable purity after TEA cleavage from the resin. 

A method for the preparation of halosilyl carbamates and isocyanate involves direct synthesis from amines via halosilyl carbamate intermediates [277]. A primary amine is converted to its carbamic acid salt, which is then treated with a silane containing > 2 halogen atoms bonded to Si. Gentle heating of the resulting halosilyl carbamate gives the isocyanate. In an alternative (exchange) procedure, the carbamic acid salt is treated with any halosilane to form a silyl carbamate, which is trans-silylated. 

Ammonia and nitric acid have been selected as process examples in this book and are treated in detail in Sections 6.1 and 6.4, respectively. Urea is produced industrially by reaction of ammonia and CO2 via the intermediate product ammonium carbamate ([H2N-COO][NH4]). While the formation of the carbamate intermediate is exothermic and quantitative under the applied reaction conditions (200 °C, 250bar), urea forms from the intermediate by liberation of vater in a slightly endothermic equilibrium reaction. Existing process technologies differ in their ways of carbamate decomposition as well as ammonia and CO2 recycling. State-of-the-art urea plants produce up to 1.700 tons of urea per day and are often linked to ammonia plants as CO2 is a by-product of NH3 production from natural gas. 

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