Carbamoyl, intermediate

The condensation of isocyanate esters with diguanides proceeds in an entirely comparable manner, providing a corresponding series of s-triazin-2-ones (i.e. substituted ammelines) 378). However, since loss of water from carbamoyl-intermediates [e.g. RNHCONH C( NH)NH C( NH) -NH2] occurs much less readily than loss of hydrogen sulphide from their thiocarbamoyl-analogues, melamines are not formed in this reaction 378). The production of adducts from phenyl isocyanate and tetra-. 

Sensitive to oxidation and hydrolysis forms alkylating and carbamoylating intermediates. Half-life of 117 minutes at 25°C and neutral pH.2 Solubility below 0.05 mg/mL in water, 0.1 N sodium hydroxide, 0.1 N hydrochloric acid or 10% ethanol 70 mg/mL in absolute ethanol.1... 

There is no doubt that most of the mono- and polynuclear metal carbonyls react with liquid NH3 via nonisolable carbonyl carbamoyl intermediate complexes in which the acid amide group —CONH2 is directly bound to the transition metal. For the reaction of Mn2(CO)10 with liquid NH3, we have been able to show that, at -78°C, quantitative formation of ciJ-Mn(CO)4(NH3)—CONH2 and HMn(CO)5 occurs (105) according to the following reaction ... 

Tri-n-propylcarbazoyllithium 102 is another type of carbamoyl intermediate (of type mb), which is prepared at — 78 °C by reaction of the corresponding hydrazine 101 with n-BuLi and CO (Scheme 26)82. This intermediate has been trapped with different electrophiles to provide the corresponding products 103. 

Conversion of the carbamoyl intermediate 4 to the bicyclic end product 5 To a solution of 1.00 g (2.50 mmol) of the carbamoyl compound 4 in 30 mL of acetone, 10 mL of sat. aq Na2CO, are added and the mixture is stirred vigorously for 0.5 h. After the reaction is complete, the mixture is diluted with Ctt2Cl, washed with H20 and sat. NH4CI, dried over MgS04, filtered and concentrated under reduced pressure to afford an amorphous, pale yellow solid. Crystallization from acetone/hexane gives analytically pure product yield 0.96 g (96%). 

However, the next stage turns out to be extremely slow. Despite the fact that histidine can still act as a basic catalyst, water finds it difficult to attack the carbamoyl intermediate. This step becomes the rate determining step for the whole process and the overall rate of hydrolysis of physostigmine compared to acetylcholine is forty million times slower. As a result, the cholinesterase active site becomes bunged up and is unable to react with acetylcholine. 

On the contrary, scheme 2 is accepted for systems working under drastic conditions and in heterogeneous phase. In these cases, the reduced form of catalyst undergoes oxidative addition by amine and produces an imine-complex, leading to the carbamoyl intermediate by subsequent CO insertion into the M-N bond [laj. 

However, an alternative mechanism similar to that described in scheme 2, that considers the oxidative addition of aniline to the Rh° finely dispersed on the support, cannot be completely excluded. The evolution of carbamoyl intermediate to DPU should occur still via iodoformamide. The last mechanism could be also operative in the reductive carbonylation of nitrobenzene, when aniline is necessary for its conversion. In this case, the reaction could be better considered as an oxidative carbonylation process in which the nitrobenzene is playing the role of the oxidant in place of the oxygen. It has been ascertained that under these conditions the carbonylation occurs with the stoichiometry of reaction (11) [14], different from the one reported in reaction (4). 

The first NMR ( C, P) characterization of a carbamoyl intermediate (52) has been described in the related reaction of pyrrolidine with trans-[Pd(COPh)-(CO)(PMe3)2]Bp4. The O-protonated carbamoyl structure (53) was supported by an X-ray structural analysis of its O-alkylated analog. 

Kim KD, Lee SM, Cho NS, Oh JS, Lee CW, Lee JS (1992) Palladium-catalyzed N,AT-diphenylurea synthesis from nitrobenzene, aniline, and carbon monoxide. Part 3. Evidence of carbamoyl intermediate. J Mol Catal 75(1) L1-L6... 

Oligomers of phosgene, such as diphosgene [503-38-8] (COCl2)2, have found use in the laboratory preparation of isocyanates. Carbamoyl chlorides, A[,A/-disubstituted ureas, dimethyl- and diphenylcarbonates, and arylsulfonyl isocyanates have also been used to convert amines into urea intermediates, which are subsequendy pyroly2ed to yield isocyanates. These methods have found appHcations for preparation of low boiling point aUphatic isocyanates (2,9,17). 

Reaction of w-methylpiperazine with phosgene affords the carbamoyl chloride (170). Treatment of this intermediate with diethylamine affords the antiparasitic agent diethyl carbamazine (171)... 

Rh(OEP)H reacts with CNR (R = Me, n-Bu,) to give the adduct Rh(OEP)-(H)CNR (which has no parallel in CO chemistry) which then slowly transforms to the formimidoyl insertion product, Rh(OEP)C(H)=NR. The dimer Rh(OEP))2 reacts with CNAr (Ar = 2.6-Cf,H3Mc2) in aqueous benzene to give the carbamoyl product. Rh(OEP)C(0)NHAr (characterized by an X-ray crystal structure) together with the hydride, which it.self reacts further with the isocyanide. This is suggc.sted to form via a cationic carbene intermediate, formed by attack of HiO on coordinated CNAr in concert with disproportionation to Rh(III) and Rh(l). 

In many cases, the racemization of a substrate required for DKR is difficult As an example, the production of optically pure cc-amino acids, which are used as intermediates for pharmaceuticals, cosmetics, and as chiral synfhons in organic chemistry [31], may be discussed. One of the important methods of the synthesis of amino acids is the hydrolysis of the appropriate hydantoins. Racemic 5-substituted hydantoins 15 are easily available from aldehydes using a commonly known synthetic procedure (Scheme 5.10) [32]. In the next step, they are enantioselectively hydrolyzed by d- or L-specific hydantoinase and the resulting N-carbamoyl amino acids 16 are hydrolyzed to optically pure a-amino acid 17 by other enzymes, namely, L- or D-specific carbamoylase. This process was introduced in the 1970s for the production of L-amino acids 17 [33]. For many substrates, the racemization process is too slow and in order to increase its rate enzymes called racemases are used. In processes the three enzymes, racemase, hydantoinase, and carbamoylase, can be used simultaneously this enables the production of a-amino acids without isolation of intermediates and increases the yield and productivity. Unfortunately, the commercial application of this process is limited because it is based on L-selective hydantoin-hydrolyzing enzymes [34, 35]. For production of D-amino acid the enzymes of opposite stereoselectivity are required. A recent study indicates that the inversion of enantioselectivity of hydantoinase, the key enzyme in the... 

Figure 34-7 summarizes the roles of the intermediates and enzymes of pyrimidine nucleotide biosynthesis. The catalyst for the initial reaction is cytosolic carbamoyl phosphate synthase II, a different enzyme from the mitochondrial carbamoyl phosphate synthase I of urea synthesis (Figure 29-9). Compartmentation thus provides two independent pools of carbamoyl phosphate. PRPP, an early participant in purine nucleotide synthesis (Figure 34-2), is a much later participant in pyrimidine biosynthesis.

Diazonium salts couple to hydroxy-substituted vicinal triazoles (101) with subsequent rearrangement of the hydroxy arylazo compounds (102) to the carbamoyl tetrazole (104).170 An open-chain intermediate (103) has been proposed.169 This rearrangement is similar to that of the benzoyl... 

Although the Capdevielle reaction for one-pot conversion of aldehydes to nitriles is a very convenient and widely applicable synthetic procedure, 3-substituted furoxans appear to be susceptible to rearrangement when substitutions with amine nucleophiles are attempted, even under relatively mild conditions (Scheme 29) <1999JOC8748>. The formation of the final product 107 in this reaction was explained via phenyl abstraction by carbamoyl radical cation from the second molecule of intermediate product 106 < 1999JOC8748>. 

Due to the electron-demanding carbamoyl substructure on the nitroso hydrazine intermediates 129 the oxidative process that initiates the NO-release is much slower than with the active sydnonimine metabolites. The elimination of HNO from the nitroso intermediates and the subsequent oxidation to NO cannot be completely ruled out for this type of compounds. In vivo, an alternative, possibly thiol mediated route for the NO formation plays a role in the activity [147]. In this reaction the formation of nitrosothiols as unstable NO precursor intermediates is the most likely process. 

The metal-promoted processes follow a general mechanistic route, involving the intermediate formation of an alkoxycarbonyl- or a carbamoyl-metal species from the reaction between MX2, CO and NuH (NuH = alcohol, phenol or amine), followed by nucleophilic attack by Nu H (Nu I I = alcohol, phenol or amine) (Scheme 26). 

An isocyanate intermediate may also be involved in the selenium-catalyzed process, which starts with the formation of carbonyl selenide from the reaction between selenium and CO, followed by nucleophilic attack by NuH (Scheme 28). When NuH = primary amine, the resulting RNH(CO)SeH intermediate may eliminate H2Se to give the isocyanate, which then reacts with Nu H to give the final product (Scheme 28, path a). Alternatively, oxidation of Nu(CO)SeH by 02 may lead to a bis(carbamoyl)diselenide species, which is attacked by NuH (Scheme 28, path b). 

Under appropriate conditions, alcohols and amines can undergo an oxidative double carbonylation process, with formation of oxalate esters (Eq. 34), oxamate esters (Eq. 35) or oxamides (Eq. 36). These reactions are usually catalyzed by Pd(II) species and take place trough the intermediate formation of bis(alkoxycarbonyl)palladium, (alkoxycarbonyl)(carbamoyl)palladium or bis(carbamoyl)palladium complexes, as shown in Scheme 29 (NuH, Nu H = alcohol or amine) [227,231,267,293-300]. 

The urea q de, like the dtric add cyde, acts catalytically. Small quantities of the intermediates are sufficient to synthesize large amounts of urea from aspartate and carbamoyl phosphate. The cyde occurs partially in the mitochondria and partially in the cytoplasm. 

The two conditions can be distinguished by an increase in orotic add and uracil, which occurs in ornithine transcarbamoylase deficiency, but not in the defldency of carbamoyl phosphate synthetase. Orotic acid and uracil are intermediates in pyrimidine synthrais (see Chapter 18). This pathway is stimulated by the accumulation of carbamoyl phosphate, the substrate for ornithine transcarbamoylase in the urea cycle and for aspartate transcarbamoylase in pyrimidine synthesis. 

The carbamoyl group is transferred to the serine hydroxyl in the enzyme, but the resultant carbamoyl-enzyme intermediate then hydrolyses only very slowly (minutes rather than microseconds), effectively blocking the active site for most of the time. The slower rate of hydrolysis of the serine carbamate ester is a consequence of decreased carbonyl character resulting from resonance stabilization, as shown. 

Only a few important representatives of the non-proteinogenic amino acids are mentioned here. The basic amino acid ornithine is an analogue of lysine with a shortened side chain. Transfer of a carbamoyl residue to ornithine yields citrulline. Both of these amino acids are intermediates in the urea cycle (see p.l82). Dopa (an acronym of 3,4-dihydroxy-phenylalanine) is synthesized by hydroxyla-tion of tyrosine. It is an intermediate in the biosynthesis of catecholamines (see p.352) and of melanin. It is in clinical use in the treatment of Parkinson s disease. Selenocys-teine, a cysteine analogue, occurs as a component of a few proteins—e.g., in the enzyme glutathione peroxidase (see p.284). 

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