3-Ethyl-l-pentyne

Ethyl-l-pentyn-3-ol added dropwise with stirring and ice-cooling to a mixture of excess coned. HCl, 0.5 mole of calcium chloride, 0.4 mole of CuCl, and some copper bronze powder, stirring continued 1 hr. at 0-5° 3-chloro-3-ethyl-l-pentyne. Y 83%.— This procedure gives higher yields and purer products than previous methods. F. e. s. G. F. Hennion and A. P. Boisselle, J. Org. Chem. 26, 725 (1961). 

In order to produce this alkane, the starting alkyne must have the same carbon skeleton as this alkane. There is only one such alkyne (3-ethyl-l-pentyne, shown below), because the triple bond cannot be placed between C2 and C3 of the skeleton (as that would make the C3 position pentavalent, and carbon cannot accommodate more than four bonds) ... 

Grignardization of 1-butynyl magnesium bromide with acetaldehyde and subsequent treatment of the resulting alcohol with PCI5 yields 2-chloro-3-pentyne. Now, ethyl (l-methyl-2-pentynyl)-eyanoaeetate is obtained therefrom by its condensation with ethyl cyanoacetate in the presence of sodium ethylate. Further condensation of the resulting produet with allyl bromide gives rise to ethyl-(l-methyl-2-pentynyl) allylcyanoaeetate. Condensation with N-methyl urea and subsequent neutralization with NaOH produees methohexital sodium. 

To a mixture of 50 ml of dry THF and 0.050 mol of l-tert.-butoxy-2-pentyne (prepared by ethylation of HC-CCH O-tert.-Ci,H9 in liquid ammonia was added 0.055 mol of butyilithium in about 35 ml of hexane in 10 min at -30°C. After stirring for 20 min at -25°C the solution was cooled to -50°C and 0.06 mol of methyl iodide was added in one portion, followed 10 min later by 50 ml of water. The aqueous layer was separated and extracted twice with diethyl ether. The solutions were dried over magnesium sulfate and concentrated in a water-pump vacuum. 

The irradiation of 2,5-dimethylfuran in the presence of mercury vapor gave a complex mixture of products. Carbon monoxide and propene were removed as gaseous products. Then, cis- and rran.s-l,3-pentadiene, isoprene, 1,3-dimethylcyclopropene, 2-pentyne, 2-ethyl-5-methylfuran, hexa-3,4-dien-2-one, 1-methyl-3-acetylcyclopropene, and 4-methylcyclopent-2-enone were obtained (Scheme 8) (68JA2720 70JA1824). The most abundantproduct was the cyclopentenone 19, the second was the 1,3-pentadiene 12, while the third product was the cyclopropenyl derivative 18. 

The reaction of 77 with alkynes has further been elaborated for the synthesis of substituted phthalonitriles 81. An alternative for the synthesis of these compounds is the cycloaddition reaction of 77 with enamines followed by a retro-Diels-Alder loss of N2 and elimination of the amine (Scheme 16). Generally, more forcing reaction conditions are required and lower yields are obtained in reactions with alkynes than in reactions with enamines, for example, 4-ethyl-5-methylphthalonitrile is obtained in 51% yield from 2-pentyne (xylene, 150°C, 18 days) and in 73% yield from 4-(l-ethylprop-l-en-l-yl)morpholine (CHCI3, 70°C, 7 days) <1998T1809>. The mechanism of the reaction with enamines has been studied in detail. This revealed a [1,5] sigmatropic rearrangement in the cyclohexa-2,4-dien-1-amine intermediates formed after the loss of N2 <1998T10851>. 

A very efficient, stereospecific synthesis of DL-ribose was based26 on the use of l,l-diethoxy-5-(tetrahydropyran-2-yloxy)-2-pentyn-3-ol as the substrate. Catalytic hydrogenation of this alkyne to the cts-alkene was accompanied by cyclization, to give 2-ethoxy-2,5-dihydro-5-(tetra-hydropyran-2-yloxy)furan (35). cis-Hydroxylation of the double bond in 35 was effected with potassium permanganate, yielding the ethyl DL-ribofuranoside derivative 36, which was hydrolyzed to DL-ribose. 

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