From carbamates

OS 30] [R 30] [P 22] The feasibility of generating a cation pool, i.e. of performing multiple reactions with various reactants, by means of electrooxidative micro flow processing was demonstrated [66,67]. The micro reaction system was consequently termed cation flow . By this means, various C-C bonded products were made from carbamates, having pyrrolidine, piperidine, diethylamine and trihydroisoquinoline moieties. These carbamates were combined with various silyl enol ethers, yielding nine products. 

Preliminary efforts to examine the mechanism of C-H amination proved inconclusive with respect to the intermediacy of carbamoyl iminoiodinane 12. Control experiments in which carbamate 11 and PhI(OAc)2 were heated in CD2CI2 at 40°C with and without MgO gave no indication of a reaction between substrate and oxidant by NMR. In Hne with these observations, synthesis of a carbamate-derived iodinane has remained elusive. The inability to prepare iminoiodinane reagents from carbamate esters precluded their evaluation in catalytic nitrene transfer chemistry. By employing the PhI(OAc)2/MgO conditions, however, 1° carbamates can now serve as effective N-atom sources. The synthetic scope of metal-catalyzed C-H amination processes is thus expanded considerably as a result of this invention. Details of the reaction mechanism for this rhodium-mediated intramolecular oxidation are presented in Section 17.8. 

Carbamates act similar to organophosphates by interfering with nerve system enzymes. They are derived from carbamic acid, H NCOOH, and share many of the properties of organophosphates (Figure 18.9). The carbamate known as carbaryl (commercial trade name is Sevin) was synthesized in 1956 and has been used extensively since that time. Carbaryl s advantages are that its toxicity to mammals is low and it kills a broad spectrum of insects. It is widely used in a number of household lawn and garden products. Other common carbamates include aldicarb (Temik) and carbofuran (Furadan). 

Carbamates such as carbaryl are derived from carbamic acid. 

HF-pyridine reagent, however, can also be used for the hy-drofluorination of alkenes,7 alkynes,7 cyclopropanes,7 and diazo compounds,8 the halofluonnation of alkenes,9 the preparation of fluoroformates from carbamates,10 the preparation of a-fluorocarboxylic acids from a-amino acids,11 and as a deprotecting reagent in peptide chemistry.12 Examples of the hydrofluonnation of alkenes with HF-pyridine are given in Table II. 

Carbamate esters also produced 2-oxo compounds, e.g., the esters of 3-aminopropanol88 and of 3-halogenopropanol.87 A few compounds have thus been prepared from carbamates, e.g., 20, with an aromatic substituent88 [Eq. (10)] or a heterocyclic one.89 Ethyl 7V-(3-hydroxy-propyl) urethanes cyclize to 2-oxo compounds with sodium methoxide.78 An interesting novel approach was to react an A-(chloromethyl)-carbamate with olefins to yield 2190 [Eq. (11)]. 

S -Methylxanthates 62 derived from the same alcohols 50 are thermally less stable than the corresponding carbamates 57. They decompose during their synthesis according to two competitive elimination pathways, ft C—H and ft C—Si (3/2) eliminations14 (Scheme 12), giving rise to a lower metallole yield than from carbamates 57. 

Carbamate pesticides are used as (1) insecticides, (2) fungicides and (3) herbicides. Insecticides are generally derived from carbamic acid fungicides, from thiocarbamic acid. The herbicide carbamates are a more complex class of compounds. Tables 21 and 22 list some commercial carbamate pesticides in approximate order of decreasing toxicity. It should be noted that the relative classification of highly and moderately toxic is no measure of the relative carcino-, muta- or teratogenicities of these carbamates, since it is based solely on acute LD q data (Morgan, ref. 20). 

On the other hand, a similar activation has been found to be practically possible when carbamates or amides instead of amines themselves are used as the starting materials. The a cation formed from carbamates and amides is sufficiently stable to be trapped by nucleophiles in solution 17). 

Dihydrothieno[3,4-d]pyrimidin-3(l//)-ones 337 were synthesized by a four-step reaction sequence starting from carbamates 310. The latter were selectively reduced with lithium aluminum hydride and then oxidized with activated manganese(IV) oxide to give aldehydes 334 in one-pot. Condensation of compounds 334 with ethanolamine in refluxing ethanol afforded the Schiff bases 335, which were reduced with sodium borohydride to... 

Figure 8. Comparison of UV and fluorescent tracings from carbamate chromatogram (15 ng)...

To complete this series of heterocumulene syntheses from carbonic acid derivatives, we here present the acid- and base-catalyzed alcohol elimination from carbamic acid esters (C, Figure 8.10) and the condensation of aniline and carbon disulfide to phenylisothiocyanate (F,... 

Yoshida et al. reported that generation and online detection of highly reactive carbocations from carbamates were accomplished by integrating an electrochemical microreactor with an FTIR spectrometer [57]. They also demonstrated that both the carbocations and nucleophiles could be generated using the paired electrochemical flow system to give the coupling products in reasonable yields (Scheme 4.42) [58]. 

OPs and carbamates have different receptor activities in the mammalian nervous system. OPs have effects on muscarinic and nicotinic receptors and can cause neurological effects in the CNS (Levy-Khademi et al., 2007). Carbamates are thought to cause only parasympathetic muscarinic effects with limited nicotinic and CNS effects (Sofer et al, 1989). However, there are case reports in children that have revealed the presence of CNS effects with carbamate exposures (de Tollenaer et al, 2006). One pediatric case series stated that the signs and symptoms from carbamate poisoning were indistinguishable from OP exposures, with severe CNS depression with stupor and coma occurring in eight cases (Sofer et al, 1989). 

In order to avoid decomposition of the cycloadduct, acetals have been subjected to the cycloaddition with a number of acylnitroso derivatives. The reaction proceeds with total regio- and stereoselectivity and the best yields in the cycloadduct 13 formation were obtained starting from carbamate-like derivatives66,67. 

Chiral oxazolidones are readily prepared from carbamates of a-amino esters by reduction with NaBHa-Lil in refluxing THF. Note that imides (A-acyloxazolidinones) are reduced to alcohols, therefore the reduction represents a method for recovery of both chiral products and auxiliaries. ... 

As above, the driving force for both reactions is ammonia removal. Both reactions (10a) and (10b) are catalyzed by a combination of a weak Lewis acid and a weak Lewis base, such as equimolar amounts of A1(/-Bu)2H and PPh3. These bifunctional catalysts reduce the formation of by-products from carbamate decomposition. The above reactions could be carried out in two separate steps or in one pot when in the presence of tin(IV) compounds as catalysts for the second reaction. 

Starting from carbamates of type 5, N-methylamines (16) could also be prepared by reduction with LiAlH4 according to Scheme 7. Although the yield varied from moderate to high, the compounds were obtained in high purity [26]. 

The reactivity of these prodrugs varies considerably. Whereas most of them are activated enzymatically, others are activated nonenzy-matically, as discussed in the following paragraphs. Enzymatic hydrolysis followed by chemical breakdown is another possibility (e.g., carbamic acids formed from carbamates). 

Figure 15.3 Urea and sulfonamide synthesis from carbamate derivatized oxime (19), thiophenol (16) and Wang (4) resins.

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