Methylation derivatizing

Bei der Reduktion von 2-Oxo-2,3-dihydro-indolen liegen die Ausbeuten iiber 80% d.Th. Das 3-Methyl-Derivat ergibt z. B. quantitativ 3-Methyl-indol (Skatol) Aus den Isatinen erhalt man die entsprechenden Indole in 45-80%iger Ausbeute. Isatin selbst liefert 72% d.Th. Indol. Zur Herstellung von 3,3-Bi-indolen aus den entsprechenden Lactamen s. Lit.4. 

Dieses ist iin Gegensatz zu den ersten Gliedern der Reihe von Alkyl-Derivaten, etwa dem Meso-Methyl-Derivat, wiederum kein Sensibilisator. 

A- [(Acy loxy )methyl] derivatization was also examined for its potential to improve the biological stability of peptides. For example, the peptide-like model A-[(benzyloxy )carbonyl]glycine benzylamide (8.171, R = H) was de-rivatized to a few N-/Yacyloxy)methyl] derivatives whose chemical and enzymatic hydrolysis was investigated [225], The results compiled in Table 8.13 indicate a fast chemical hydrolysis, the mechanism of which is depicted as Reaction b in Fig. 8.21. Enzymatic hydrolysis also occurs in human plasma, resulting in short half-lives, with the exception of the pivaloyl analogue. 

Additional experiments were performed to examine the role of the molecular size of the host enantioselectivity. Since the methyl groups in methylated jS-CD orient themselves toward the center of the cavity, it is expected that decreasing the extent of methyl derivatization in jS-CD from 21 (the permethylated jS-CD) to 14 methyl groups increases the effective size of the cavity." " As a matter of fact, the enantioselectivity of valine (kolkL = 0.32 with 21-methyl j8-CD) increases to W l = 0.18 with 14-methyl jS-CD. No significant effect of the cavity size is observed with the smaller alanine. 

Benzolsulfonsaure-allylester und sein 2-Methyl-Derivat reagieren mit primaren Aminen wie z.B. 1-Amino-hexan oder Anilin in Aceton in Gegenwart von Kaliumcarbonat unter Bildung tertiarer Amine, z.B. Diallyl-hexyl-amin, Bis-[2-methyl-2-propenyl]-hexyl-amin, N,N-Diallyl-anilin und ahnlichen Aminen2. 

Die (Condensation von 1,3-Dioxo-cyclohexan und seinem 2- bzw. 4-Methyl-Derivat mit primaren Oder sekundiiren Aminen fuhrt zu l-Amino-3-oxo-cyclohexenen, diesich nach IsolierungmittelsQuccksilber(IT)-acetat zu 3-Amino-phenoIen oxidieren lassen2. 

Monosaccharides of glycopro- DaisoGel silica, in-column teins(as l-phenyl-3-methyl- derivatized by 5-pyrazolone derivatives) octadecyltrimethoxysilane or... 

Methylation derivatization also has been successfully used for the transmethylation of esters and carbonates. For an ester, the reaction can take place by the following mechanism ... 

Im Rahmen der Herstellung von (—)-7 -Methyl-dihydrothebainon(lll) wird das Chlor-Derivat I durch Zink in waCrigcr Ammoniumchlorid-Losung zum Methyl-Derivat II reduziert2 ... 

In practice, thermochemolysis of organic matter mainly produces esters of aliphatic and aromatic acids, methyl esters of aliphatic alcohols and phenols, and a variety of other methylated derivatization products. " Thermochemolysis is particularly suitable for the analysis of fatty acids associated with organic matter matrix which are evolved as methyl esters when TMAH is employed. 

Detection and quantitation of THC in human tissue has been accomplished by Kudo et al. [44] using methylation derivatization and deuterated standards. The LODs were 1 ng/g using El and SIM. A unique method has been developed for detection of A -THC, A -THC, CBD, and CBN in saliva requiring minimal... 

Lenk T J, Hallmark V M, Rabolt J F, Haussling L and Ringsdorf H 1993 Formation and characterization of self-assembled films of sulphur-derivatized poly(methyl methacrylates) on gold Macromolecules 26 1230-7... 

There are ill-defined limits on EI/CI usage, based mostly on these issues of volatility and thermal stability. Sometimes these limits can be extended by preparation of a suitable chemical derivative. For example, polar carboxylic acids generally give either no or only a poor yield of molecular ions, but their conversion into methyl esters affords less polar, more volatile materials that can be examined easily by EL In the absence of an alternative method of ionization, EI/CI can still be used with clever manipulation of chemical derivatization techniques. 

Monobasic acids are determined by gas chromatographic analysis of the free acids dibasic acids usually are derivatized by one of several methods prior to chromatographing (176,177). Methyl esters are prepared by treatment of the sample with BF.—methanol, H2SO4—methanol, or tetramethylammonium hydroxide. Gas chromatographic analysis of silylation products also has been used extensively. Liquid chromatographic analysis of free acids or of derivatives also has been used (178). More sophisticated hplc methods have been developed recentiy to meet the needs for trace analyses ia the environment, ia biological fluids, and other sources (179,180). Mass spectral identification of both dibasic and monobasic acids usually is done on gas chromatographicaHy resolved derivatives. 

In addition to providing fully alkyl/aryl-substituted polyphosphasenes, the versatility of the process in Figure 2 has allowed the preparation of various functionalized polymers and copolymers. Thus the monomer (10) can be derivatized via deprotonation—substitution, when a P-methyl (or P—CH2—) group is present, to provide new phosphoranimines some of which, in turn, serve as precursors to new polymers (64). In the same vein, polymers containing a P—CH group, for example, poly(methylphenylphosphazene), can also be derivatized by deprotonation—substitution reactions without chain scission. This has produced a number of functionalized polymers (64,71—73), including water-soluble carboxylate salts (11), as well as graft copolymers with styrene (74) and with dimethylsiloxane (12) (75). 

Isomer separation beyond physical fractional crystallization has been accompHshed by derivatization using methyl formate to make /V-formyl derivatives and acetic anhydride to prepare the corresponding acetamides (1). Alkaline hydrolysis regenerates the analytically pure amine configurational isomers. 

For more specific analysis, chromatographic methods have been developed. Using reverse-phase columns and uv detection, hplc methods have been appHed to the analysis of nicotinic acid and nicotinamide in biological fluids such as blood and urine and in foods such as coffee and meat. Derivatization techniques have also been employed to improve sensitivity (55). For example, the reaction of nicotinic amide with DCCI (AT-dicyclohexyl-0-methoxycoumarin-4-yl)methyl isourea to yield the fluorescent coumarin ester has been reported (56). After separation on a reversed-phase column, detection limits of 10 pmol for nicotinic acid have been reported (57). 

In an alternative approach, the desired 2-methyl-l,4-naphthoqurnone is derivatized to form a water-soluble and commercially important sodium... 

The GBR resin works well for nonionic and certain ionic polymers such as various native and derivatized starches, including sodium carboxymethylcel-lulose, methylcellulose, dextrans, carrageenans, hydroxypropyl methylcellu-lose, cellulose sulfate, and pullulans. GBR columns can be used in virtually any solvent or mixture of solvents from hexane to 1 M NaOH as long as they are miscible. Using sulfonated PDVB gels, mixtures of methanol and 0.1 M Na acetate will run many polar ionic-type polymers such as poly-2-acrylamido-2-methyl-l-propanesulfonic acid, polystyrene sulfonic acids, and poly aniline/ polystyrene sulfonic acid. Sulfonated columns can also be used with water glacial acetic acid mixtures, typically 90/10 (v/v). Polyacrylic acids run well on sulfonated gels in 0.2 M NaAc, pH 7.75. 

Table 1.6.1. Epoxidation of 2-methyl-2-propene-l-ol benefieial effeets of eatalytie reaetions and derivatization.

In general, 2-substituted allylic alcohols are epoxidized in good enantioselectivity. Like glycidol, however, the product epoxides are susceptible to ring opening via nucleophilic attack at the C-3 position. Results of the AE reaction on 2-methyl-2-propene-l-ol followed by derivatization of the resulting epoxy alcohol are shown in Table 1.6.1. Other examples are shown below. 

Over the years the literature is filled with examples where the initial characterization was incorrect. One example is illustrated below. In 1940, Sethna and Shah presumed that they synthesized coumarins 42 and 43 from a reaction between P-orcacetophenone (44) and its 4-0-methyl ether 45 under standard Kostanecki-Robinson conditions, respectively. Three decades later Bose and Shah synthesized coumarin 43 via another route and concluded that the initial assignment made by Sethna and Shah was incorrect. After the Bose and Shah findings were published, Ahluwalia and Kumar concluded that the Sethna and Shah products were actually chromones 46 and 47 based on proton NMR data and chemical derivatization. Despite these shortcomings, the Kostanecki-Robinson reaction remains an effective method for formation of both coumarins and chromones. 

In a study by Stresser and co-workers, the effect on tumor modulation by 227 has been investigated. HPLC on liver extracts from Fisher 344 rats revealed two major compounds, 3,3 -bisindolylmefliane (133) and a linear trimer, together with a < l(KX)-fold lower content of 4 in comparison with the two major substances. The HPLC isolate was derivatized with /V-methyl-/V-bis(trifluoroacetamide) that, upon MS detection, gave a compound identical to /V,W -ditrifluoroacetylindolo-[3,2-()]carbazole. The content of 4 in this system was estimated to be 0.(XKX)13% of the total dose of 227 given. Thus, it was concluded that the beneficial effect of oral distribution of 227 is due to the total content of derivatives formed (95MI5). 

Recently, multidimensional GC has been employed in enantioselective analysis by placing a chiral stationary phase such as a cyclodextrin in the second column. Typically, switching valves are used to heart-cut the appropriate portion of the separation from a non-chiral column into a chiral column. Heil et al. used a dual column system consisting of a non-chiral pre-column (30 m X 0.25 mm X 0.38 p.m, PS-268) and a chiral (30 m X 0.32 mm X 0.64 p.m, heptakis(2,3-di-(9-methyl-6-(9-tert-butyldimethylsilyl)-(3-cyclodextrin) (TBDM-CD) analytical column to separate derivatized urinary organic acids that are indicative of metabolic diseases such as short bowel syndrome, phenylketonuria, tyrosinaemia, and others. They used a FID following the pre-column and an ion trap mass-selective detector following the... 

Figure 15.8 shows the multidimensional GC analysis of urinary aeids, following lyophilization and derivatization by methyl ehloroformate. In this figure, ehromatogram (a) shows the eomplexity of the urine matrix and the need for a seeond separation dimension. A heart-eut is taken over a small range at about 45 min. The... 

Figure 15.8 Multidimensional GC-MS separation of urinary acids after derivatization with methyl chloroformate (a) pre-column cliromatogram after splitless injection (h) Main-column selected ion monitoring cliromatogram (mass 84) of pyroglutamic acid methyl ester. Adapted from Journal of Chromatography, B 714, M. Heil et ai, Enantioselective multidimensional gas chromatography-mass spectrometry in the analysis of urinary organic acids , pp. 119-126, copyright 1998, with permission from Elsevier Science.

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