Two-phase system leads to thioalkylation
2-Phenylbutyronitrile
R.SCM·
Flash vacuum thermolysis a route to very reactive compounds
C2H5 2-Phenyl-2-thioalkylbutyronitrile
Κβ^} 1,2,3,4-Tetrahydro1,4-epoxynaphthalene
thiocyanate
°-1,orr
M vCH-C H* X
Isobenzofuran
Alkyl-3-chloromethylsulfide
Old synthetic routes gain new attention Despite the general notion that devel opment of chemical innovations pro ceeds at a rapid rate, many findings lie untouched for a number of years before their utility becomes recognized. Two instances of such a time lag came to light at the 1st International Confer ence on Organic Synthesis last month at the new campus of Université Catholique de Louvain in Louvain-laNeuve, Belgium. One of these findings is a route to carbanions and halocarbenes, avoiding the use of the usual proton-abstracting reagents. The other is flash vacuum thermolysis as a means of making very reactive chemicals. They are basically simple and hold considerable promise in preparative organic chemistry, both at bench-scale and commercial production levels. The two-phase system leading to carbanions and halocarbenes, species that are fundamental to organic synthesis and of key importance in the pharmaceutical and fine chemicals industries, is a development of Dr. Mieczyslaw Makosza, director of the Institute of Organic Chemistry at the Tehnical University of Warsaw, Poland. Although he first published an account of the method in the Polish chemical literature several years ago, it has only recently caught the attention of research workers elsewhere, and many of the more than 300 conference attendees learned details of the development for the first time. Using aqueous sodium hydroxide in the presence of a quaternary ammonium compound, Dr. Makosza and his colleagues are able to replace such proton-abstracting agents as butyl lithium, sodium azide, and potassium tertbutoxide. Besides being costly, these chemicals are sensitive to air and water and are dangerous to work with. "Our system is cheaper, simpler to operate, and gives exceptionally high yields of product," Dr. Makosza claims. A typical use of the method is in synthesis of l,l-dichloro-2-phenylcyclopropane from styrene and chloroform. These reactants, which together with a small amount of a quaternary ammonium compound constitute the organic phase of the two-phase system, are stirred with a highly concentrated
aqueous solution of sodium hydroxide. The base promotes proton abstraction from the chloroform, with formation of the corresponding trichloromethyl anion/quarternary ammonium cation ion pair. The ion pair migrates to the organic phase where it splits into quaternary ammonium chloride and dichlorocarbene. The dichlorocarbene reacts immediately with the styrene to yield the cyclopropane derivative. At the end of the reaction, the two phases are allowed to settle out and the organic solution is removed and treated to recover the product. A more recent example of the use of the system, cited by Dr. Makosza, is in the thioalkylation of a variety of carbanions. For example, the 2-phenylbutyronitrile readily interacts with an alkylthiocyanate to yield the corresponding 2-phenyl-2-thioalkylbutyronitrile. Similarly, chloroform can be converted to alkyltrichloromethylsulfide. The other technique just gaining widespread attention is flash vacuum thermolysis, which is essentially controlled pyrolysis, says Dr. Ulfert E. Wiersum of Akzo's research laboratories in Arnhem, the Netherlands, where pioneering studies on the technique have been under way for the past several years. But a much greater degree of selectivity of the pyrolysis products is possible because the organic substrate is exposed to high temperatures for only a very short time. "New highly reactive intermediates and interesting chemical species can now be made and isolated for the first time," Dr. Wiersum claims. "The technique is also a convenient method for synthesis of novel compounds, a fact that until quite recently hasn't been generally known." According to Dr. Wiersum, the system opens the way to preparation of many compounds that haven't been made previously or that are difficult to make by alternative means. He cites as examples isobenzofuran, fulveneallene,' and sulfene. Sulfene (CH2SO2), which is the sulfur analog of ketene (CH2CO), is so reactive that it has existed only as an intermediate in solution and couldn't be isolated and characterized. Dr. Wiersum has succeeded in making sulfene by flash
vacuum thermolysis of iV-sulfonylmethyl phthalimide. Recently, Dr. Paul de Mayo at the University of Ontario used the technique to make the chemical from methylsulfonyl chloride. Dr. Wiersum and his associates, Dr. Henk Hageman and Dr. Wim Mijs, have developed a simple apparatus that could be scaled up for commercial use, they say. To make isobenzofuran, for instance, they place 1,2,3,4-tetrahydro-l,4-epoxynaphthalene in a 50-ml. round-bottom flask connected to a vacuum pump. When the pressure in the system is lowered to about 0.1 torr, the naphthalene compound sublimes into a heating region maintained at 650° C. There it dissociates quantitatively into isobenzofuran and ethylene. The products pass on to a liquid-nitrogen-cooled trap where the isobenzofuran condenses in a high state of purity. A modification of the system can be used for dimerizing such compounds as α,α-dichlorobenzylcyanide or benzotrichloride. The dimers are of practical interest because they belong to a new class of polymerization initiators, but conventional preparative methods lead to mixtures that are hard to purify. In .the case of o;,a-dichlorobenzylcyanide dimerization, the monomer starting product vaporizes under a pressure of 20 torr and passes to a heating zone maintained at 500° C. Benzylcyanide radicals formed in the pyrolysis zone dimerize. But because the conversion rate is low, the chemicals emerging from the zone are condensed and recy cled to the flask. Dimer yields of up to 90% are possible, depending on the na ture of the starting monomer. Dr. Wiersum notes that several groups besides his own are now taking a close look at the utility of flash vacu um thermolysis. At Amoco's chemical research laboratory in Whiting, Ind., for example, Dr. Ellis Fields and Dr. Seymour Meyerson are focusing atten tion on the technique as a means of studying chemical radical processes. Similar studies are being performed by Dr. E. Hedaya at Union Carbide, Tarrytown, N.Y., and by Dr. Curt Wentrup at the University of Lausanne, Switzerland. And at Iowa State Uni versity, Dr. Walter Trahanovsky is using the system as a means of synthe sizing such compounds as methylenecyclobutenone from furfurylbenzoate. Sept. 23, 1974 C&EN
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