Sulfur Replaces Sugars7 Ring Oxygen 5-Thio-D-glucopyranose acts as competitive inhibitor for natural D-glucose in fruit flies 145TH ACS
NATIONAL
The Purdue group, under Dr. Roy L. Whistler, has replaced with sulfur the ring oxygen in D-glucose, D-fructose, D-xylose, D-ribose, and 2-deoxyD-ribose. Nuclear magnetic resonance spectra have shown that the α-D-xylose analog, like natural α-D-xylose, exists in the CI chair conformation [/. Org. Chem., 28, 1730 ( 1963 ) ]. This analog, like other sugars containing sulfur as the ring hetero atom, has an exceptionally high optical rotation. The sulfur-ring glycosides hydrolyze rapidly, although solvolysis of the glycosyl halides in methanol proceeds slowly [/. Org. Chem., 28, 1567 (1963)]. The high rate of glycoside hydrolysis is due to the extensive protonation of the exocyclic oxygen
MEETING
Carbohydrate Chemistry
Modified sugars with sulfur in the ring may have useful activity in living systems. At least one sulfur analog— 5-thio-D-glucopyranose—has bacterio static activity and acts as a mild com petitive inhibitor for natural D-glucose in fruit flies and Escherichia coli, ac cording to scientists at Purdue Uni versity. Syntheses of modified sugars with sulfur in the ring were first reported independently by three different lab oratories [Troc. Chem. Soc, 417, 418 (1961); JACS, 84,122 (1962)].
Preparation of Thio Derivatives Involves Displacement with Thiabenzylate Anion
T0SYL-0-CH2
0CH2SCH2
H2
"SCH20
OH 0 I 0-C-CH* I * CH3
0 I 0-C-CH* 3 I CH*
HSCHi CH30H
OH
I O-C-CH3
CH: 70
C&EN
OH
y\ H +
SEPT.
16,
1963
OH
H-OCH:
OH
caused by the inductive effect of the ring sulfur releasing electrons to it. Slow solvolysis of the sulfur ring glycosyl halide results in part from poor resonance stabilization of the carbonium ion at C-l resulting from the loss of the halogen. The exotic sugar analog with se lenium as the ring hetero atom has also been made, in the methyl D-xyloside configuration. As expected, this glycoside is heat sensitive and hydrolyzes even faster than the sulfur an alog. Methyl 5-thio-L-arabinopyranoside has also been prepared, according to Purdue's Roger M. Rowell. The standard route involves displacement of a p-toluenesulfonyloxy group at C-5 with thiabenzylate anion and re duction with sodium in liquid am monia to the mercaptan [/. Org. Chem., 27, 3897 (1962)]. This, in acidic methanol, gives the expected glycoside and a considerable amount of the disulfide of methyl β-L-arabinofuranoside. The amount of disulfide accompanying glycoside formation varies in different sugar structures de pending on the reactivity of the mercapto group. Use of the KoenigsKnorr reaction and methanethiol makes possible the preparation of methyl 1,5-dithiol-D-xylopyranoside, in which sulfur atoms replace both the normal ring oxygen and the exocyclic glycosidic oxygen. Oxidation of the sulfur ring sugars seems to produce oxides and sulfones which are not yet fully described, Mr. Rowell adds. Purdue biochemists have also pre pared 5-deoxy-6-thio-, 6-deoxy-6-thio-, and 5-deoxy-5-thio-4-glucosides, ac cording to Gary W. Earl. Again, the standard preparation route was used. The role of sulfur in possible septanoside ring formation is also being investigated by Dr. Whistler and his co-workers. The effect of the mercapto group upon the size of the ring pro duced in the methyl D-glucosides formed in acidic methanol is not fully characterized, Mr. Earl says. How ever, 5-thio-4-glucose under conditions normal for formation of furanosides produces mainly six-membered rings, indicating the preference for sulfur to enter the sugar ring. And 6-thio-Dglucose has little tendency to form a septanoside ring. However, 5-deoxy6-thio-D-glucose is more flexible and may produce somewhat more septano side.
Initial Brookfi'eld Viscosity vs. Shear Rates 60 PHR PLASTÎCIZER (LOW SHEAR RATE)
20 +
mm
Λ9Ϊ
Initial Severs Viscosity vs. Shear Rates 60 PHR PLASTICIZER ( HIGH SHEAR RATE)
610P
250 RPM
375
500
625
750
875
1000 ,1125
SHEAR RATE-SEC' 1
OPTIMUM PLASTISOL PROCESSING \ I
\
\
+ EXTRA VALUES
Τ i i
Ί 4 'ΪΛ »!
!
i
ALFOL® alcohol phthalates, as primary plasticizers in vinyl plastisols, give { ; ; ;_jl Overall viscosity control + Outstanding end-product properties J; : :H:!
n-
\ ! Optimu'm-plastisol processing depends chiefly upon ; floW "characteristics. Confirming favorable production experience, laboratory tests prove that straight-chain . phthalates made from ALFOL alcohols control viscosity , better than other commonly used plasticizers. And as a p[us value;'the ALFOL esters provide excellent low-temî pêraturè ;përfqrmance, low volatile loss, and long-term ι retention «of flexibility—at welcome cost savings over ex, pensive syste rps.J J J " , ; „ • Processors using* fluid vinyl plastisols—for molding, ; spread and reverse-roll coating, dipping, and sprayinggain extra benefits when they use ALFOL phthalates. These plastisol processors can formulate more directly toward end properties and worry less about viscosity and air-release problems, ι , .. .... Τ_Ί
i -J ! I.
; TYPICAL PLASTiSO^LJAPgUpATIONS
Fabric coating—upholstery ; !
; ; '
Foam sheeting—car coats, handbags ί Dip coating—wire baskets, gloves, strippable coatings • Molded—dolls, toys, footwear, mechanical goods
I I
Phthalate esters made from ALFOL 610 or ALFOL 810—straight-chain synthetic alcohols—yield significantly. lower initial and aged viscosities than DOP or DIDP. This means better flow and improved shelf life. Also, the. ALFOL phthalates offer these viscosity benefits at high as well as low shear rates. In the high-shear range, Severs rheometer readings show considerably lower dilatancy (increasing viscosity with increasing shear rates) for the ALFOL esters, in ad dition to their regularly lower viscosity. On the other hand, DOP and DIDP produce rapid increases in viscosity as rate of shear rises. And in the low-shear range, Brookfield results verify that ALFOL plasticizers consistently give lower viscosity than DOP or DIDP. Interested in plasticizers that will improve your plasti-"" sol processing? Ask your supplier for straight-chain plas- ! ticizers made from ALFOL alcohols. And fill in the cou pon below for helpful information. (Bulletins AL-9 and AL-14 contain specific data on plastisols.)
„Standardize on Straight-Chain ALFOL Alcohol esters I. I U-ŒCJ""; for your G-P plasticizers
Jliir
FILM&; SHEETING * PLASTISOLS · EXTRUSIONS · CABLE JACKETING HIM-M-I-
~ Conoco Petrochemicals COMTlW'ipfAi'o'lLCOIUiP'iSV" PETROCHEMICAL DEPARTMENT
> LCC
630 Fifth Avenue, New York 20, ΝΎ. · 212 JUd$ôn 6-2510
CONOCO PETROCHEMICALS, 6 3 0 Fifth Avenue, New York 2 0 , N.Y. Please s e n d m e t h e following Technical Bulletins: • D D Π
--.--:
AL-9 ( P h t h a l a t e Plasticizers) Π AL-12 (Esterification) _ . . . ' _ ."17 AL-10 ( L o w - T e m p e r a t u r e Performance) . Π AL-13 (Epoxy Tallates) \ \ AL-11 (ALFOL Alcohol Derivatives) .« _ - . Π A L - 1 4 ( T o m o r r o w ' s G-P Plasticiz Also, I have a p r o b l e m : ' "
Name *~ Company Address
Artist's conception of 150 metric tons/day S.S.V. Ammonia Plant at Koeping, Sweden if'
Lummus engineering and constructing ammonia plant in Sweden Aktiebolaget Svenska Salpeterverken Awards 150 Metric T o n s / D a y P l a n t at Koeping Lummus is now engineering and will construct a 150 metric tons/day anhydrous ammonia plant at Koeping, Sweden as part of Aktiebolaget Svenska Salpeterverken's current overall expansion program. The plant, scheduled for completion in 1964, will use fuel oil as feedstock and employ the Shell Gasifica tion Process for synthesis gas generation. It will produce both refrigeration and commercial grades of ammonia, as well as carbon dioxide to be used in the manufacture of urea, complex fertilizers and liquid carbon dioxide.
The Aktiebolaget Svenska Salpeterverken unit is among several ammonia plants recently put on stream or under construction by the world-wide group of Lum mus companies. The others range from 110 to 225 tons/ day, variously utilize natural gas or fuel oil as feedstock, and are located in Victoria, Texas, Salamanca, Mexico, and Sevilla, Spain. For hydrogen production, ammonia and other ni-, trogen or fertilizer products—consult Lummus.
ENGINEERS: Investigate a career in our expanding international operations. Contact your nearest Lummus office.
THE LUMMUS COMPANY
3 8 5 Madison Avenue, New York 1T, N.Y.
Offices and subsidiaries: N e w a r k , W a s h i n g t o n , D. C , H o u s t o n , M o n t r e a l , L o n d o n , Paris, The Hague, Madrid, Milan, Bombay, T o k y o , Sydney, Caracas, Rio de Janeiro. Engineering Development Center: N e w a r k . ARC H I T E C T / Ε NG ΙΝ Ε Ε RS A N D C O N S T R U C T O R S 72
C&ΕΝ
FOR INDUSTRY
AND GOVERNMENT
Dihalophosphoranes Convert ROH to RX Reaction works with variety of alkyl and aryl hydroxyl compounds, gives high yields without side reactions 145TH
ACS
NATIONAL
MEETING
Organic Chemistry
Dihalophosphoranes are useful rea gents for converting a wide variety of alcohols and phenols to the correspond ing organic halides, according to Dr. G. A. Wiley of Syracuse University, Syracuse, N.Y. They give high yields of primary and secondary halides and do not induce rearrangements, even with neopentyl compounds. The classical reagents for making organic halides from hydroxy compounds-HX, PX 3 , PX 5 , POX 3 , and SOX2—have many important applica tions, Dr. Wiley says. But none are completely general for making pri mary, secondary, tertiary, and aryl hal ides. Difficulties often encountered are rearrangements and other side re actions, such as the formation of ole fins, isomers, or inorganic esters. Thionyl chloride and phosphorus tribromide have a broad range of applica tions; but even these cause trouble in certain cases, he adds. Over the past 10 years, English scientists have developed some rea gents, of the type ( C 6 H 5 0 ) 3 P R X , that are fairly general. They react cleanly with primary, secondary, and tertiary alcohols, and do not rearrange neo pentyl compounds. Dr. Wiley points out, however, that one product of the reaction is always phenol. Thus, with aromatics, the reaction works well only for phenols that are more reactive than· phenol itself, such as those with electron-attracting groups. The dihalophosphoranes, R 3 PX 2 , have been known for some time. They are easy to prepare by treating ter tiary phosphines with halogens. They have seen only limited use for making alkyl or aryl halides. Their similarity to the successful Landauer-Rydon re agents developed in England prompted the current study by Dr. Wiley and co-workers, R. L. Hershkowitz, B. M. Rein, and B. C. Chung. Key Advantage. The main feature that distinguishes the dihalophos phoranes is that they contain only
two replaceable groups, the right num ber to produce clean ROH-to-RX con version. One reason for side reactions with some other reagents is that they contain more than enough such groups. With R 3 PX 2 , the absence of phenol as a coproduct extends its use fulness in making aryl halides. Most of the work done so far by Dr. Wiley's group has been with R 3 PBr 2 , where R is η-butyl or phenyl. Generally, the triphenyl analog is more reactive. Reaction temperature for alkyl bromides is below 50° C , while the aromatic compounds require temperatures around 200° C. The preferred solvent is dime thy If or m amide, although acetonitrile can be used in some cases—that is, where the product is not too soluble in acetonitrile-water mixtures involved in the workup, or where it can be readily distilled from the acetonitrile. For most alkyl halides, the pro cedure is simple. The halogen is added slowly to a mixture of the al cohol and tri-n-butyl- or triphenylphosphine in dimethylformamide, gen erating the dihalophosphorane in situ. The solvent and product are vacuum distilled off together and the alkyl halide separated by dilution of the dis tillate with water. This method usu-
This General Reaction . . . R3PX2 + ROH ^ [R 3 P + —0—R' X - ] + HX - > R 3 P = 0 + R'X
Gives These Results with (C, H ) PBr2 ALCOHOL n-Butyl I so butyl sec-Butyl tert-Butyl Neopentyl Cyclopentyl Cyclohexyl a-Phenethyl Ethyl lactate PHENOLS Phenol p-Chlorophenol p-Nitrophenol p-M et hoxy phenol
Yield of bromide (%)
91 89 90 49 79 84 88 79 75 92 90 60 59
ally gives the bromide in high yield with no measurable impurities. The reaction works just as well when the alcohol is added to preformed dihalo phosphorane. For aryl halides, there is a slightly different procedure. The appropriate phenol is added after the dihalophos phorane is formed and the solvent is removed. Pyrolysis of the mixture, followed by distillation, gives the aryl halide. Yields of alkyl bromides ranged from 75 to 9 3 % . An exception was tert-butyl bromide, which was ob tained in 49% yield. This is also the only case where appreciable amounts of side products were obtained (25% of higher boiling substances). tertButyl chloride, however, was formed in 90% yield from dichlorotriphenylphosphorane. The yield of cyclohexyl bromide was 8 8 % , while the yield of neopentyl bromide was 79% using the triphenylphosphorane, and 9 1 % with the tri-n-butyl derivative. In the lat ter two products, there was no trace of side products. For the four phenols studied, yields ranged from 59 to 92%; there was no attempt to find the opti mum conditions. An advantage of this method for halobenzenes is that the problem of position isomers, com mon in electrophilic substitutions, does not arise. The Syracuse group is also studying the possibility of using dihalophosphor anes to induce substitution of other nucleophiles for the hydroxyl of al cohols. Preliminary results indicate that this idea is feasible. R 3 PC1 2 plus R O H in the presence of bromide or iodide ions, for example, produces ex clusively R'Br or R'l, respectively. Similarly, thiocyanates and isothiocyanates can be formed when thiocyanate ion is added. Cyanide ion not only fails to yield alkyl cyanide, but also inhibits formation of alkyl halide. Dr. Wiley believes this may be due to the tendency of cyanide to coordinate strongly with metals like phosphorus. He is still looking into the possibility of using other groups in this applica tion. Work is also going on to determine the kinetics and stereochemistry of the basic reaction between dihalophos phoranes and alcohols, and to isolate reaction intermediates. A plausible intermediate, Dr. Wiley conjectures, is R 3 PX(OR'), possibly as the quasiphosphonium salt. But, he adds, there is no clear evidence on the structure of such substances. SEPT.
16,
1963
C&EN
73
