1.5- Dimethyl-5- barbituric

The Pd(0)-catalyzed transfer of the allyl moiety to dimedone [23], morpholine [22], or N,N -dimethyl barbituric acid [27] resulted in the completely selective cleavage of the Aloe group, whereas the numerous other protecting groups and the glycosidic bonds,... 

One of the most reactive 1,3-dicarbonyl compounds used in the domino-Knoevenagel-hetero-Diels-Alder reaction is N,N-dimethyl barbituric acid 2. It has been shown that the fairly stable products can easily been transformed into other compounds via a reduction of the urea moiety with DIBAL-H [20]. Thus, reaction of 30 with DIBAL-H at 78 °C led to 46, which can be hydrolyzed to give 47 (Scheme 5.9). In a similar way, 48 was transformed into 50 via 49 and 12 to 52 via 51. The obtained compounds containing a lactone and an amide moiety can again be further transformed using DIBAL-H followed by an elimination. In this way, dihydropyran 54 is obtained from 50 via 53 as one example. 

Scheme 5.9. Transformation of cycloadducts with N,N-dimethyl barbituric acid.

Fig. 5.4. Products of the domino-Knoevenagel-hetero-Diels-Alder-hydrogenation sequence of a-amino acids with N,N-dimethyl barbituric acid.

The necessary amino aldehydes are accessible from widely available amino acids and amino alcohols. In addition to N,N-dimethyl barbituric acid shown in Figure 5.3, other 1,3-dicarbonyl compounds can be employed, such as cydohexane-1,3-diones or coumarines (Figure 5.5). 

The first step of the domino process again was the laccase-catalyzed oxidation of catechol 25 to o-quinone 26, which reacted through Michael addition with N,N-dimethyl barbituric add 31 to yield the intermediate 32. This compound underwent a further oxidation followed by cyclization through two Michael additions. Finally, laccase-catalyzed oxidation provided polycyclic dispiropyrimidinone 35 in excellent yield of 90% (Scheme 9.7). Recently, the same authors reported the synthesis of... 

Four years later, Palasz showed the catalyst-free reaction in aqueous suspension without acetonitrile to be mostly cis-selective at ambient temperature [31]. The reactions of 1,3-dimethyl barbituric acid 61 or thiobarbituric add 65 with... 

Methyl 2-benzoylamino-3-dimethylaminopropenoate reacts with barbituric acid or its 1,3-dimethyl derivative to give a pyranopyrimidine 118 (89JHC1273). 

Hayon447 to absorb in this UV region. Similar measurements have been made for a number derivatives of uracil (5,6-dihydro, 1-, 3-, and 6-methyl, 1,3-dimethyl-, and 5-aminouracil, orotic acid, barbituric and isobarbituric acids also see similar measurements448 on 5-bromouracil and its iV-methyl derivatives), thymine itself and its derivatives (5,6-dihydro, 2-methylthymine). In the case of cytosine, Hayon447 has very tentatively suggested that species 47 and 48 are obtained on pulse radiolysis of the solution at pH 5.5, and 49 at pH 13.3. 

A brief comment should be made concerning the technique of "on-column" methylation. This is a technique wherein a methylating agent is injected along with the drug into the gas chromatograph whose temperatures initiate and complete derivatization. Trimethylanilinium hydroxide is the most commonly employed reagent and has been used to form the 1,3-dimethyl derivatives of barbiturates which do not form stable TMS derivatives (29). 

Skinner et al. (55) used GC/MS in their analyses of barbiturates. Samples were methylated (1,3-dimethyl derivatives) on-column using trimethylanilinium hydroxide. The analysis was conducted on 3% OV-1 on Gas Chrom Q. Temperature was programmed from 120 to 220°C at 10°C/min. 

Thiamylal see Barbiturates Thiopental see Barbiturates Thioridazine see Antidepressants Tranquilizers Thiothixene see Tranquilizers Thorazine see Tranquilizers 3-(2-dimethylaminoethyl)-indole see Dimethyl-tryptamine (DMT)... 

This reaction has been applied to a great number of carbonyl compounds, e.g., cyclopentanone,27 1,3-cyclohexanedione,36 5,5-dimethyl-l,3-cyclohexanedione,S5 1-acenaphthenone,24,25 1,3-indane-dione,35 1,3-phenalanedione,85 86 sodium salts of 3-aryl-3-oxo-propanals,39 2,3-dihydrobenzo[6]thiophen-3-one,40 sodium benzoyl-acetate,41 benzoylacetonitrile,29 30,88 ethyl cyanoacetate,30 35 cyano-acetanilide,30 barbituric acid,35 rhodanine,35 jV-phenylrhodanine,37 and iV-methylenebenzothiazoline.37... 

Alkylated barbituric acids, 6-chloro-a-methylcarbazole-2-aceticacid, 1-phenylethanol, 1-phenyl-1-propanol, dimethyl, 3,4,5,6-pentafluoro-benzyl alcohol, l-(2-naphthyl)-ethanol, 1 -(p-biphenyl)-ethanol Chirasil-Dex coated column, 0.15 pm... 

Methyl derivatives were used by Martin and Driscoll [509] they were prepared by treatment with dimethyl sulphate and applied to the analysis of barbiturates in serum, as follows. A 2-ml volume of a saturated solution of sodium dihydrophosphate and 10 ml of diethyl ether were introduced into a test-tube containing 2 ml of serum. The test-tube was closed and shaken vigorously for 30 sec, centrifuged for 1 min, then 7 ml of the extract were transferred into another test-tube and the ether was removed in a stream of air in a water-bath. The residue was dissolved in 2 ml of methanol with 10% of water (v/v), saturated with potassium carbonate, and 0.1 ml of dimethyl sulphate were added and the mixture was heated in a water-bath at 60°C for 4 min. At this temperature methanol was removed in a stream of air (3 min) and the residue was extracted into 1.5 ml of -heptane with the addition of 1 ml of 1 M acetate buffer (pH 6). A 1 -ml volume of the n-heptane extract was transferred into a small test-tube, evaporated carefully in order that losses of the derivatives might be avoided, and dissolved in 100 (A of acetone (containing an internal standard if necessary) 5 jul were analysed on a column packed with 5% of SE-30 at 175°C. 

The utility of the highly soluble 6-cyclodextrin derivatives (soluble polymer and dimethyl-6-cyclodextrin) in RPTLC is illustrated in the separation of barbiturates. The lipophilicity of a barbiturate or any guest decreases when included in a cyclodextrin-cavity. Therefore its mobility is modified in reversed phase thin layer chromatography. With this simple and rapid method, the stability of a complex can be estimated empirically (Table II). The "b" value of the following equation is characteristic for the complex stability (in water ethanol =4 1 solution, R determined at 5 different cyclodextrin concentrations for 21 barbiturates) ... 

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