Carbamate moieties

The increased use of IV-methyl carbamate insecticides in agriculture demands the development of selective and sensitive analytical procedures to determine trace level residues of these compounds in crops and other food products. HPLC is the technique most widely used to circumvent heat sensitivity of these pesticides. However, HPLC with UV detection lacks the selectivity and sensitivity needed for their analysis. In the late 1970s and early 1980s, HPLC using post-column hydrolysis and derivatization was developed and refined with fluorescence detection to overcome these problems. The technique relies on the post-column hydrolysis of the carbamate moiety to methylamine with subsequent derivatization to a fluorescent isoindole product. This technique is currently the most widely used HPLC method for the determination of carbamates in water" and in fruits and vegetables." " ... 

The sense of diastereoselectivity in the dynamic kinetic resolution of 2-substi-tuted / -keto esters depends on the structure of the keto ester. The ruthenium catalyst with atropisomeric diphosphine ligands (binap, MeO-biphep, synphos, etc.) induced syn-products in high diastereomeric and enantiomeric selectivity in the dynamic kinetic resolution of / -keto esters with an a-amido or carbamate moiety (Table 21.21) [119-121, 123, 125-127]. In contrast to the above examples of a-amido-/ -keto esters, the TsOH or HC1 salt of /l-keto esters with an a-amino unit were hydrogenated with excellent cwti-selectivity using ruthenium-atropiso-... 

The results and discussion section is divided into two parts. The first part deals with direct laser flash photolysis of the MDI-PUE polymer and appropriate small molecule models. The transient spectra generated by direct excitation of the polyurethane are interpreted by consideration of the primary photochemical reactions of the carbamate moiety. The second part describes results obtained by production of a radical transient species which is capable of abstracting labile hydrogens from the polyurethane. This latter procedure represents an alternative method for production of the transient species which were obtained by direct excitation. 

For MDI based polyurethanes we have provided evidence for formation of a diphenylmethyl radical by direct excitation (248 nm) of the carbamate moiety as well as hydrogen abstraction by a tert-butoxy radical which is produced by excitation (351 nm) of tert-butyl peroxide. The diphenylmethyl radical readily reacts with oxygen. A proposed mechanism which accounts for the production (direct or indirect) and subsequent reaction with oxygen of the diphenylmethyl radical is shown in Scheme IV. The hydrogen peroxide product depicted in Scheme IV has been previously identified by FT-IR (7) we have simply provided a plausible mechanism for its formation. 

Future work will be concerned with quantitative measurement of hydrogen abstraction rates of labile hydrogens in the carbamate moieties of several aromatic diisocyanate based polyurethanes. It is expected that experimental conditions will alter significantly the hydrogen abstraction rate. Emphasis will also be placed on measurement of transient intermediates in polyurethane films. Finally, extensive laser flash photolysis experiments will be conducted on polyurethanes based on both 2,A-toluenediisocyanate and 2,6-toluenediisocyanate. Preliminary data suggest that the placement of the methyl substituent can alter the nature of the transient intermediates formed. 

The favorable effect of the introduction of a carbamate moiety into the cinchonan selectors was already proven by the prototype cinchonan carbamate CSPs (type I and type II) (Figure 1.9) [30], which showed enhanced enantioselectivities and a widened application range as compared to the CSPs with native cinchona alkaloid selectors and those reported earlier in the literature. 

On and/or in bean plants, aminocarb degrades with the carbamate moiety remaining intact. Methylcarbamate derivatives identified include the 4-methylamino, 4-amino, 4-methylformamido, and 4-formamido analogs (Abdel-Wahab et al., 1966). 

The reaction between a phosphoramidothioate and N-chlorosulfenylcarbamate described in Figure 2 has been applied to methamidophos. In Figure 2, the reaction was used to derivatize a toxic me thyIcarhamate ester by a non-toxic phosphora-midothioate however, in the case of methamidophos the reaction was used to derivatize a toxic phosphoramidothioate with a nontoxic carbamate moiety. The IJ-alkoxycarbonyl-IJ -alkylamino-sulfenyl derivatives of methamidophos thus prepared, where R... 

The results of a comparative metabolism study of an aryl-sulfenyl derivative of carbofuran [2,2-dimethy1-2,3-dihydro-benzofuranyl-7 -methyl-N-(2-toluenesulfenyl)carbamate] in the house fly and white mouse Indicated the selective action of this compound to be a consequence of different metabolic pathways in insects and mammals (12). The arylsulfenyl group on the carbamate moiety allows the mammal to carry out metabolic reactions leading to less toxic products which are rapidly conjugated, while the toxic parent methylcarbamate is formed in the insect. 

High insecticidal activity is not restricted to symmetrically substituted, N -thiodlcarbamates and subsequent work revealed a number of unsjmunetrlcal thlodlcarbamates with excellent insecticidal activities (24,25,26). In these cases, only one of the two carbamate moieties is represented by an insecticidal methylcarbamate. Table IV provides typical toxicological data for some of these derivatives (24). 

Lee and Matsuda modified a segmented polyurethane film with a dithio-carbamate moiety and then initiated the polymerization of (ethylene glycol) methacrylate and N,N-dimethylacrylamide [35]. The resulting films were hy-drophihc and were shown to inhibit adhesion of platelets. Such films could be useful as anti-coagulant substrates for devices implanted in vivo. 

Improved heat-resistant UV compositions for optical fiber applications These compositions are nonurethane UV cure compositions that have neither carbamate moieties nor long-chain poly(alkylene oxide) soft segments and exhibit inherently better thermal stability measured by thermogravimetric analysis (TGA) than typical coatings for optical fibers based on urethane acrylate oligomers. 

Since all members of the benzimidazole anthelminthics except thiabendazole contain a benzimidazole carbamate moiety, attempts have been made to produce antibodies recognizing this structure (19). Most successful was an approach in which a carboxylated analogue of albendazole was used as hapten and coupling to the carrier protein was performed using (V-hydroxysuccinimide and morpholi-noethyl isocyanide in the presence of dimethylamino pyridine. 

The ring closure of amino alcohols with C02 to yield cyclic carbamates, was achieved under mild conditions (atmospheric pressure of C02, room temperature), in acetonitrile as solvent and in the presence of triethylamine as the base, using more easily available reactants, such as P(III)-derivatives (Ph3P, (PhO)3P, n-Bu3P, (MeO)3P) and haloalkanes (CC14, CC13CC13) [76]. According to the proposed mechanism, the active species is a phosphonium adduct of the used P(III)-compound with the haloalkane, which activates the intermediate carbamate formed from amino alcohol and C02 at the carbamic moiety to produce a transient species which cyclizes to the final product (Scheme 6.12). 

The transfer of a carbamate moiety to epoxides is a suitable entry into carbamic esters of 1,2-diols. Yoshida and Inoue reported tbat tbe reaction of Ti(NMe2)4 with C02 and 1,2-epoxycyclohexane, followed by hydrolysis of the reaction mixture, afforded tra s-2-hydroxycyclohexyl N,N-dimethylcarbamate [77a], This reaction was the first example of transfer of a carbamate group from a metal carbamate to an epoxide (Scheme 6.13). 

The transfer of a carbamate moiety to olefins has been documented only in very few cases, using activated unsaturated substrates. For example, Yoshida and Inoue reported the selective (100%) formation of 1-ethoxyethyl N,N-dialkylcarbamate esters by the reaction of C02 (5 MPa) with ethyl vinyl ether and secondary amines R2NH (R = Me, Et) in the absence of any catalyst (Equation 6.11) [85]. 

In another approach, where the 2-methyl carbamate moiety was replaced by a more lipophilic group such as SC02R, SCONR R2 or S(CH2) C02R etc. [33] more soluble compounds were generated. Surprisingly, the resulting compounds exhibited a complete loss of antifilarial activity. It is evident from these studies that the carbamate moiety is an essential pharmacophore for antifilarial activity. 

The in vivo metabolism of capecitabine (1) to the active tumor cytotoxic substance 5-fluorouracil (5) is now fairly well understood. When capecitabine is administered orally it is delivered to the small intestine, where it is not a substrate for thymidine phosphorylase in intestinal tissue, and so passes through the intestinal mucosa as an intact molecule and into the bloodstream. When 1 reaches the liver, the carbamate moiety is hydrolyzed through the action of carboxylesterase enzymes, liberating 5 -deoxy-5-fluorocytidine (5 -DFCR, 10). DFUR is partially stable in systemic circulation, but eventually diffuses into tumor cell tissue where it is transformed into 5 -deoxy-5-fluorouridine (5 -DFUR, 9) by cytidine deaminase, an enzyme present in high concentrations in various types of human cancers compared to adjacent healthy cells (although it is present in significantly lower levels in the liver). Within the tumor, 5-... 

The reactions of electrophilic animation displayed little if any stereoselectivity (Table 3.10, entries 1 to 6). The chromatographic separation of the diastereomers was generally quite difficult. The menthyl and bomyl carbamate moieties in products 99a and 99b proved to be very stable and difficult to remove, even with prolonged reflux in 6 M HC1 or concentrated HBr, and the corresponding a-hydrazino acids could not be obtained in reasonable yield. However, the isobomyl 99c analogues were readily hydrolyzed. 

Unequivocal structural proof of l,l,4,4-tetramethyl-l//,4//-thieno[3,4-c]thiophene (see Scheme 19) was obtained by X-ray crystallographic analysis (80TL3617). Methyl iV-vinyl carbamate adds benzonitrile oxide to yield a mono- or bis-adduct, depending upon the experimental conditions. The syn stereochemistry of the bis-adduct (10) has been elucidated by an X-ray structure determination which showed that the carbamate moiety orients its NH above the isoxazolidine ring and toward the oxygen of the syn-oxadiazolinic ring (NH------O is 3.08 A) <80JCR(S)4341>. 

Molecules a, b, c, in Fig. 12.8 manifest the same structure of the carbamic moiety as rivastigmine, but their phenolic part is modified, with regard to both the distance of the amine from the aromatic ring, and the exact N-substituents. This led to compounds that, beside their central ACh E-blocking activity remindful of rivastigmine (albeit at a higher dose), also possess a new pharmacological feature. 

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