1.1.3.3- Tetraethoxypropane

The best way to make pyrimidine in quantity is from 1,1,3,3-tetraethoxypropane (or other such acetal of malondialdehyde) and formamide, by either a continuous (58CB2832) or a batch process (57CB942). Other practical ways to make small amounts in the laboratory are thermal decarboxylation of pyrimidine-4,6-dicarboxylic acid (744), prepared by oxidation of 4,6-dimethylpyrimidine (59JCS525), or hydrogenolysis of 2,4-dichloropyrimidine over palladium-charcoal in the presence of magnesium oxide (53JCS1646). 

Tetraethoxypropane is available from Kay-Fries Chemicals, Inc., New York 16, New York, or from Distillation Products Industries, Rochester 3, New York, and may be used without further purification. 

The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and urea derivatives was first described by Evans2 and was later improved by Hunt, McOmie, and Sayer3 for the preparation of 2-mercapto-4,6-dimethylpyrimidine. Burness4 employed 3-ketobutyraldehyde acetal in this procedure to give 2-mercapto-4-methylpyrimidine. 2-Mercaptopyrimidine has been prepared from 1,1,3,3-tetraethoxypropane and thiourea by variations of this basic method 3 6 6 as well as by the reaction of 2-chloropyrimidine with thiourea 1 or sodium hydrosulfide.8... 

Condensation, of oxalyl chloride, with di- -alkylanilines, 41, 3 with dimethylaniline, 41, 1 of 1,1,3,3-tetraethoxypropane with thiourea to give 2-mercaptopy-rimidine, 43, 68... 

Tetraethoxypropane, condensation with thiourea to give 2-mercaptopyrimidine, 43,68... 

The fully aromatic and unsubstituted pyrimido[ 1,2-6 ]pyridazinium perchlorate (171) has been prepared by the condensation of 3-aminopyridazine (170) with 1,1,3,3-tetraethoxypropane in the presence of polyphosphoric acid. The product was precipitated from the reaction mixture by treatment with perchloric acid and ice. Several alkyl, aryl and halogenated derivatives of this ring system have also been prepared (71JOC2457). 

TMP, sometimes referred to as malonaldehyde bis(dimethyl acetal), is an acetal ofmalon-aldehyde. In the presence of an acid solution, this chemical is hydrolyzed, and malonaldehyde is liberated. Consequently, TMP or its ethyl analog, 1, 1,3,3-tetraethoxypropane, can be used in the construction of a TBARS standard curve. 

TMP is also referred to as malonaldehyde bis(dimethyl acetal). 1,1,3,3-Tetraethoxypropane, or malonaldehyde bis(diethyl acetal), can be substituted for TMP. Stock and working solutions are prepared as for TMP. 

If polyamide is exposed to an authentic malonaldehyde source, i.e., vapors from acidified 1,1,3,3-tetraethoxypropane, intense fluorescence excited at 360 nm is produced, initially in the 430 nm range, and broadening rapidly to 440-450 nm. 

Concentrated hydrochloric acid (20 mL) is added to a vigorously stirred solution of 100 mL (0.34 mole) of 1,1,3,3-tetraethoxypropane [malonaldehyde bis-(diethyl acetal)] in 100 mL of distilled water. To this is added, dropwise, 17.5 mL (0.34 mole) of bromine. ( Caution. Use a fume hood.) The coloration of the bromine disappears immediately if the dropping rate is sufficiently slow. No increase in temperature is observed. 

Pyrimidine, mp 22,5°C, bp 124°C, is a water-soluble, weak base that forms a sparingly soluble complex with HgCl2. Pyrimidine is prepared by condensation of 1,1,3,3-tetraethoxypropane with... 

Vinylethylether, ethyl orthoformate and BF3-ether complex were purchased from Fluka Chemie AG, Switzerland. 1,1,3,3-Tetraethoxypropane was purchased from Aldrich Chemical Co., USA and was also prepared in our laboratory. Anhydrous sodium carbonate, urea and hydrochloric acid were purchased from Qualigens Fine Chemicals. Fuming nitric acid was obtained from Ammunition Factory, Khadaki, Pune. 

In a three-necked round bottom flask equipped with a pressure equahzer dropping fimnel fitted with a calcium chloride tube at the top, a mixture of 10 g (0.067 mol) ethyl orthoformate and 0.09 ml of BFa-ether complex was given to which 3 g (0.42 mol) vinylethylether was added dropwise during 15 min at a temperature below 45 °C. After the addition, the mixture was stirred constantly at 33 °C for 1 h. This was followed by the addition of 0.3 g sodium carbonate and the stirring was continued for an additional 3 h at room temperature. The precipitate was filtered and the filtrate was fi actionated in vacuum in the presence of a small quantity of sodium carbonate as an acid quencher to yield 2.5 g (85 %) 1,1,3,3-tetraethoxypropane, b.p. 90 °C at 800 Pa. The product was characterized by spectral data and elemental analysis. 

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