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Attempted hydroformylation of triacetyl-D-glucal Cameron, Christina Janet 1955

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ATTEMPTED HYDROFORMYLATION OF TRIACETYL-D-GLUCAL by CHRISTINA JANET CAMERON B.A.  A THESIS SU3MITTED IN PARTIAL FULFILMENT OF THE ;  REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN THE DEPARTMENT OF CHEMISTRY  We accept t h i s thesis as conforming to the standard required from candidates for the degree of Master of Science  Members of the Department of Chemistry  THE UNIVERSITY OF BRITISH COLUMBIA JULY 1955  1  SUMMARY  T r i a c e t y l - D - g l u c a l , an unsaturated sugar has been prepared and submitted to the hydroformylation reaction, which i s the addition of carbon monoxide and hydrogen to an unsaturated compound at high pressure and temperature.  A cobalt catalyst i s generally used, i n t h i s  case, cobalt acetate tetrahydrate. The mixture of products obtained was separated by column chromatography and d i s t i l l a t i o n .  The main products are probably  triacetyl-D-deoxyglucose obtained by the addition of water to the starting m a t e r i a l , 1,2-hydroglucal obtained by hydrogenation of the s t a r t i n g m a t e r i a l , a small amount of the t h e o r e t i c a l hydroformylation compound and varying amounts of the s t a r t i n g m a t e r i a l .  ACKNOWLEDGEMENT I wish"to thank Dr. A. Rosenthal for his assistance during "the course of this work. I also wish t o acknowledge the financial assistance received from The University of B r i t i s h Columbia, and from the National Research Council.  TABLE:OP CONTENTS  SUMMARY . . '  ...  INTRODUCTION"  . . . .. . . . . . .  HISTORICAL INTRODUCTION .. ..  '.. ..  .  /  .  v  fr .  .  IK".  1  '.. .. '.. .. '.. * .. '.. .. .. .. .. '.. .. . 3  EXPERIMENTAL.. ... .. .. .. .- .... .. .. .. .. .. .. .. .. .. H .. .. .. .. .. ., .. .. 1® Preparation of 2,3,4,6-Tetraacetyl-D-glucopyranosylbromide Preparation of 5,4,6-Triacetyl-D-glueal .. •• .. .-  .. .. 18  .. .. ..  Hydroformylation of 3,4,6-Triacetyl-D-glucal .... .. ..  . 18  .. .. .. . .19  Chromatographic Separation of the Products of Hydroformylation  20  D i s t i l l a t i o n of the Products of Hydroformylation .. .. .. ., . ... 22 A n a l y s i s of the Products of Hydroformylation  .. .- ... .-.. '.. .. . 25  Deacetylation of the Products of Hydroformylation .- .. .. . . ... • 2J DISCUSSION  .. '.. .. ......'.. .. .. .......... .. .. '., .. .. '•. .. .. .. .. '.. .. 29  BIBLIOGRAPHY ....... .......... ........ .. ........ .. .. .... .. .. .. .. 39  - 1 -  INTRODUCTION Relatively few sugars containing a branched-carbon skeleton are known. Digitoxose and streptose are found i n natural products. Isosaccharin and a series of heptoses derived from the cyanohydrin addition to fructose have been synthesized.  Since digitoxose and streptose  are both derived from medicinally important natural products (digitoxin and streptomycin), i t i s possible that synthetic branohed-ohain sugars could have some pharmaceutical  value.  The method of synthesis used i n this work i s by means of the oxo, or hydroformylation reaction, using 3, 4, 6-triacetyl-D-glucal as the starting material:  HC  ACOCH  HC H  CO + Hg  H|  HCOAc  HC-CHO  AcOCH  0 Go(CH C00) .4H20 3  I  2  f  HC— CH OAc 2  I I I I  i-  HCH  HC-CHO  AcOCH  0  HCOAc HC HgCOAc  CHrjOAc HC  The reaction might well be expeoted to yield two interesting new heptoses as represented by the above equation, both containing an anhydride ring, and a new aldehyde group. No heptoses of this type are known. Some 1, 2-dihydrotriacetyl-D-glucal might also arise by hydrogenation. carried  The reaotion was %out i n the presence of an equimolar amount of ethyl  ortho formate, thus momoethyl and d i e t h y l acetalsr could also be formed, giving r i s e to further products. The method of synthesis also affords an opportunity ing hydroformylation,  of study-  which has-been applied to many unsaturated com-  pounds, but not to a carbohydrate containing an ethylenic  linkage.  Such a reaction, requiring high temperature and pressure,  i s unusual  i n carbohydrate chemistry. T r i a c e t y l - D — g l u c a l was  subjected to the hydroformylation  and the products separated by chromatography and by The  process  distillation.  structure of any branched chain sugars produced' were to be  studied by means of the following reactionst: 1. )'deacetylation to the free sugar 2. ) oxidation to the lactone of the corresponding aldonic acid J.) reduction of the lactoner-to the lactone of an a l i p h a t i c a c i d , whose hydrazide could be prepared and compared to that of a known compound..  - 3HISTORICAL INTRODUCTION The "Oxo" Reaction The addition of carbon monoxide and hydrogen to an olefinic bond, under the influence of a cobalt catalyst, i s known as the MoxoH reaction* CHO H H  £ - 0 = ^ 3 :  ? I/  c  f  R + H 9 + CO  3 *  2  R - 9 - C - R H H  I  +  CHOH  I  1  ,  R - G- C- R II The normal products are saturated aldehydes ( I and I I ) containing one more carbon than the original olefin.  Since the reaction can also be  described as the addition of an atom of hydrogen and a formyl group to an olefinic bond, i t i s also known as hydroformylation.  The term "oxo"  i s sometimes used to refer specifically to a two-stage process i n whioh the aldehydes are reduced to alcohols.  The reaction i s carried out at  1 0 0 ° to 2 0 0 ° C . , and at combined pressures of carbon monoxide and hydrogen of 100 to 200 atmospheres. A related reaction i s the older Fischer - Tropsch process ( 6 2 ) i n which a mixture of carbon monoxide and hydrogen i s hydrogenated at high temperature and pressure to form hydrocarbons.  Oxygen containing  compounds had been detected i n the products ( 5 9 ) , but were never i n vestigated.  The actual discovery of the "oxo" reaction i s attributed to  Roelen ( 5 2 ) ( 6 5 ) . While attempting to extend the scope of the Fischer-  Tjropsch process by the addition of o l e f i n s to the feed gas, Roelen produced aldehydes which were- subsequently reduced to alcohols f o r i n d u s — r i a l use. Alcohols have also been used as a s t a r t i n g material, to preare alcohols containing one more carbon atom. I n t h i s instance the process i s c a l l e d homologation (4j5). Orchin and co-workers (4^)  found  appreciable amounts of hydrocarbon i n the f i n a l product when hydrogen and carbon monoxide were used i n the r a t i o of two to one. However, aldehydes are the main products when carbon monoxide and hydrogen are used i n equal quantities. Pino (48);has observed that increased y i e l d s of aldehydes may be- obtained by the addition of ethylorthoformate which w i l l by acetal formation, prevent polymerization and reduction of these aldehydes. The hydroformylation reaction has been applied to a v a r i e t y of unsaturated compounds i n which the double bonds are not conjugated, f o r example ( l ) (2) ,£ 5): o l e f i n s , a l l y l ethers,- unsaturated esters, unsatJ;  urated alcohols, and some heterocyclic compounds. I f the reaction i s applied to a conjugated system, simple hydrogenation u s u a l l y r e s u l t s (4j)»  except i n the case of o( ^-unsaturated esters. When the main products of hydroformylation are aldehydes  isomeric forms are obtained, i f no rearrangements  two  occur during the  reaction. Some simple generaliziions were formulated by Keulmans  (52)  to a s s i s t i n the prediction of the composition of the mixture:: 1.) straight chain o l e f i n s i n general y i e l d 60 - 40 percent straight chain aldehydes, and 40 - 60 percent branched  - 5 chain aldehydes. 2. ) addition to a tertiary carbon does not occur. 3. ) addition to a carbon adjacent to a tertiary carbon i s hindered. 4. ) addition of a formyl group adjacent to a quaternary carbon does not occur. 5. ) addition i s not hindered by an isolated tertiary carbon. Further, Adkins (2) noted that where the starting material contained a terminal double bond, the formyl group was added to the unsubstituted carbon as shown by the following equation: H ,C0 2  R - GH = CH  —  2  - GH  R  2  - CH  2  - CHO  The rule was reversed where R was phenyl, or o< -naphthyl. a large group n - Gj^,  Where R waa  n - C16H35, or (CH )8C0 CH5, complex mixtures 2  2  were produced which have been attributed to shifting of the double bond before l^droformylation, thus forming many products.  Since the reaction  mechanism i s not f u l l y understood, the structure of the products cannot usually be predicted with any accuracy. Natta and Beati (40) have made a study of the kinetics of the production of methyl formyl stearate from methyl oleate by hydroformylation.  H - C - (GH ) 2  2  - GH  OHC - G - (CH )  3  2  j|  2  - CH  J  H - C - (CH )7C0Me 2  *  HO;.- (CH^TCOMe  H  H - C - (CH )  3  2  I  2  - CH  I  and other  ' OAC - 9 - (CH ) C0Me 2  H  3  7  isomers.  - 6Th« reaction was found to be unimolecular at 100° to 150°C, and at pressures above 70 atmospheres. The reaction velocity was found to be solely dependent on the concentration of olefin, and did not vary between 70 and 210 atmospheres of combined carbon monoxide and hydrogen pressures, presumably because the gases were present i n such excess that their concentrations were essentially constant.  The following mechanism has been  postulated (65): \  /  C =C  /  \  + CO —  C  \  V  /  -C  + Ho —  'I  \  D  H  - C  l  A  '  X  H  X)  Keulemans and Kwante (32) suggested a free radical mechanism i n which G% H  and H» attack the double bond. Eoelen (65) believed that the reac-  tion mechanism involved the formation of a cobalt carbonyl*  Subsequently,  Adkins (l) and Orchin (67) both postulated that the reaction did not occur by heterogeneous catalysis, as the use of a solid catalyst suggested, but by homogeneous catalysis after the formation of dicoba.lt octacarbonyl during the reaction.  Both workers were able to show independently that  this compound was i n fact a catalyst for the reaction. Orchin (67) proposed the following mechanism: 2Co + 8C0 -^==? [cfo(C0) ] 4  |Co(C0) ] 4  2  J?jL  2  2Co(C0) C0H 3  2 ~*—J 125 atm. H  4Co(C0) C0H + 4CH2 = CHg 3  4CH CH CH0 + ^©(CO)^ 4 3  2  Some support for a mechanism of the type above i s afforded by studies of the reduction of alcohols to alkanes under hydroformylation conditions.  - 7 Wender and Orchin (43) have postulated a carbonium ion mechanism for the reduction involving cobalt carbonyls, and have produced experimental evidence i n i t s support. The catalyst f i r s t used by Roelen (65) i n hydroformylation was similar to the one used i n the Fischer-Tropsch process, and probably consisted of 30 percent cobalt, two percent thorium oxide, and two percent magnesium oxide suspended on 66 percent kieselguhr.  Catalysts of this  type are called insoluble, or Fischer-Tropsch type catalysts and are used almost exclusively i n industrial processes, many of which are patented (27). Smith and co-workers (59) used a catalyst which was composed of cobalt oxide, manganese oxide and cupric oxide suspended on various unreducible carriers, for example, diatomite brick.  Shexnalder (54) has used s i l i c a  hydrogel impregnated with salts of cobalt, thorium and copper. Finely- divided cobalt suspended on kieselguhr, prepared by the reduction of cobalt oxide mixed with kieselguhr, may also be used as a catalyst (41) (53). Pino (48), Parker (46) and Natta (40)(42) have employed a variety of cobalt ( l i ) salts:  cobalt stearate, oleate napthe-  nate, acetate, molybdate, oxide and iodide.  The effectiveness of a l l  these catalysts i s probably due to the formation of dicobalt octacarbonyl during the reaction. Adkins (l) has prepared crystalline dicobalt octacarbonyl from Raney cobalt and from Harshaw Chemicals Company Co 100 powder. Wender and Orchins (66)(67)(68) subsequently prepared dicobalt octacarbonyl, under conditions similar to those used i n the oxo reaction, from a carried  variety of cobalt salts.  The reaction was^oufe i n benzene, and the  preparation stored i n solution was estimated to contain 0.21 grams of dicobalt octacarbonyl per m i l l i l i t r e . A solution of dicobalt octacarbonyl may be analysed by means of the following reactions (43)(61): |Co(C0) ] 4  2  + 2I  2|Co(C0)+  3 I  > 2CoI +8C0  2  2  2  Hi(o-phenanthroline) Cl 3  2  > 2CoI +8C0 +21" 2  +2Co(G0) 1-=». Ni(o-phenanthroline) Jco(C0^| + 2C1~ 4  3  2  Equations 1.) and 2.) are used to determine the total dicobalt octacarbonyl and the carbonyl anion.  Equation 3.) gives the concentration of the anion  alone, and thus, by difference, the concentration of dicobalt octacarbonyl may be determined. It i s useful to study the electron structure of dicobalt octacarbonyl i n considering the mechanism of the oxo reaction (43).  The outer  orbitals of cobalt are 3d , 4s . By acquiring nine more electrons, cobalt may attain the structure of krypton.  Since cobalt tetracarbonyl has been  shown by cryoscopic studies to exist i n dimeric form, and i s paramagnetic, i t must attain the rare gas structure by receiving two electrons from each of four carbon monoxide molecules, and by sharing a pair between the two cobalt atoms. The dimer may then dissociate i n a cation and an anion, and the cation can react with Lewis bases, for example: 3JCo(C0) ] + 12 C H N 4  2  5  2Na + [Co(CO)^  2  [00(00)4]  2  5  * 2 Co^HglOe -j- [06(00)4] + 800  ;  2  t.)  > 2Na ][Co(C0)4]  + R - CH = C H - ^ R - CH - CH - Co(Cof + £co(C0) ]" 2  2  4  4  ^  The  Glycals Two types of unsaturated sugars which should undergo hydroformy-  l a t i o n are glycoseens and glycals ( 4 7 e ) . The double bond may be found i n other positions on the chain, though the 1,2 position i s commonest i n glycals. sugars In:the case of glucose derivatives, both of these unsaturated have been prepared from the intermediate 2,3>4,6-tetraacetyl-&-D-glucopyranosyl bromide commonly known as acetobromoglucose. The ^ - f o r m s of the halogeno sugars are produced almost: exclusively by most methods of synthesis,  though fischer (18) was able to produce the  S—form by the  action of dry hydrogen bromide on pentaacetyl-^x-D-glucopyranose. Acetobromoglucose has been prepared from either c< orjS pentaacetyl-D-gluco— pyranose by the action of hydrogen bromide i n acetic acid  12")(16)  or d i r e c t l y from D—glucose by the action of hydrogen:bromide i n acetic arihyiUJu-uu  (4)  anhydride ( 4 ) . An early method of prepartion was the addition of a c e t y l bromide to glucose (17)(50)i.Due acetobromoglucose  to the l a b i l i t y of the halogen atom,  i s unstable unless very pure ( 4 ) , and pentaacetyl  D—glucopyranose, and 2,3,4,6-tetraacetyl-D^-glucopyranose are common side products of any  reaction.  Fischer (18)(19)(21) prepared t r i a c e t y l - D - g l u c a l by/ shaking acetobromoglucose  with a mixture of zinc dust and f i f t y percent acetic  a c i d . He was attempting to prepare a t e t r a a c e t y l derivative of s o r b i t o l , but obtained instead an unsaturated compound which formed a dibromide and reduced Fehling}s solution. H e l f e r i c h and co-worker»: (26) have shortened the procedure for the preparation of t r i a c e t y l - D - g l u c a l from glucose by not i s o l a t i n g the intermediate acetobromoglucose. Fischer was not able to c r y s t a l l i z e the deacetylated form but  - 10 proposed the following structure (21): K>H  'G  1  H0GH HCQH HC—  <Q  CH 0H 2  Subsequently Bergmann (5) obtained crystalline D-glucal by deaoetylation of triacetyl-D-glucal with ammonia i n anhydrous methanol.  Staoey (44)  and co-workers have used sodium alkoxides i n anhydrous solution for deaoetylation. Fischer (21) reduced the non-crystalline deaoetylation products i  with palladium sponge i n aoetic acid and obtained crystalline hydroglucal for which he proposed the following structure: CH 0H 3H2  OCH  HI  HCOH  Q  HC I  CH 0H 2  The triacetate of the reduced compound was also prepared, but could not be crystallized, and was isolated as a syrup by high vacuum d i s t i l l a t i o n (20).  Deaoetylation with aqueous barium hydroxide yielded the free  hydroglucal i n crystalline form. Bergmann, Fischer and Schotte subsequently proposed a new structure for triacetyl D-glucal (22):  - 11 -  I I  0  AcOGH HGOAc  I  KG CHcOAc This struotvire was shown to he correct, by a series of reactions involving the double bond. An unstable dibromide and stable dichloride were prepared.  Oxidation with ozone yielded triacetyl-D-arabonio acid and triaoetyl  arabinose.  The only experimental observation incompatible with the new  structure was the reduction of Fehling's solution by triacetyl-D-glucal, but Bergmann and Schotte (5) were able to show that, when pure, glycals do not have reducing properties.  Finally, since the asymmetric centre at  the f i r s t carbon i s 3&st, epimeric pairs of aldoses should yield the same glycal, and i t has been shown that D-mannal i s identical with D-glucal. The double bond of a free or acetylated glycal undergoes two important addition reactions (47b), besides the formation of dihalogen compounds. F i r s t l y , a deoxy sugar, i s formed by treatment of a glycal with dilute sulphuric acid and barium carbonate (47b) (6) (58).  11  HCOH  HCOSO3H 0  + H 30 2  0  4  HGOH  HCOH  BaCOg H0 2  CH  2  HCOH  Secondly, a glycal i s reacted with perbenzoic acid to form normal aldoses (5)(36)(37)(47b).  D-Glucal yields mannose, but triacetyl D-glucal forms  triacetyl D-galactose (36)(37). Similarly free D-galaot&i reacts to form  - 12 -  D-talose, while the acetylated form y i e l d s t r i a c e t y l D-galactose (36)(37). The suggestion has "been made (36) that the t h i r d carbon i s unsubstituted, the o r i e n t a t i o n o f the free hydroxyl d i r e c t s addition by formation of an oxide r i n g .  Thus, unsubstituted g l y c a l s when reacted with perbenzoic a c i d  form aldoses with the hydroxyl groups on carbons two and three on the same side of the r i n g . o  A rearrangement of t r i a c e t y l - D - g l u o a l was observed by Bergmann (10), who found that a new compound was formed by b o i l i n g t r i a c e t y l Dg l u c a l with water f o r 15 minutes.  The compound was named diacetylpseudo-  g l u c a l , and assigned the following structure: HCOH  I I I  HC  HC  HCOAc HgOOAc HC Hydrolysis of diacetylpseudoglucal with barium hydroxide y i e l d e d two more compounds ( l l ) which were named i s o g l u c a l and protoglucal, and assigned structures:  I  GH  3  (3=0  I  CHO CH  CH  I  HCOH 0-  f2 I  HCOH  CHOH  -CH H  CHo—  isoglucal  protoglucal  Q>  - 13 I s h e l l (28) has proposed a mechanism f o r the formation of pseudofjlucal from t r i a c e t y l D-glucal. HC  CH  II  HCH  H  CH  I  TJH  I I  +  AcOCH  H0 2  I*  -OAc  HC  I  r  HCOAc  HCOAc HC 5H OAc 2  mi HCOAc HC-  CH OAc  CH OAc  2  2  I s b e l l was unable to propose a carbonium i o n mechanism f o r the formation of i s o g l u c a l and protoglucal on hydrolysis of diacetylpseudoglucal.  Deoxy and Anhydride Sugars A deoxy sugar i s one i n which a hydroxyl group has been replaced by a hydrogen, usually i n the 2 or 6 p o s i t i o n .  Those found i n nature most  commonly contain a 6-deoxy group such as fucose, rhamnose and digitoxose (which i s also a 2-deoxy sugar)(30)(47b). constituent of some nucleic acids.  ' &-#eoxyribose i s an important  ' 2>-lleoxy sugars have been prepared  from g l y c a l s as shown previously (6), by treatment with d i l u t e sulphuric a c i d and barium carbonate. Sugars containing a 1, 5 anhydride r i n g are usually classed as derivatives of polyhydric alcohols. are  Examples of naturally occurring ones  s t r y c i t o l ( l , 5 -D-mannitan) and p o l y g a l i t o l ( l , 5 -D-sorbitan) (47b).  1, 2 -Dihydro-D-glucal, obtained by hydrogenation of D-glucal i s a 1, 5anhydride compound.  - 14 Branched-Chain Sugars Branched-chain sugars are very rare, and most of those known are of natural o r i g i n .  Apiose (47f)(56) occurs i n the glycoside a p i i n which  i s found i n the leaves o f parsley. HOCHr,  I2 COH - CH(OH) - CHO  HOCH  2  Apiose Hamamelose (47c)(55) occurs i n hamamelitanin found i n the bark o f the shrub Hamamelis v i r g i n i c a . H CGH 2  HOC - CHO  I  CHOH  I  CHOH  I  CHgOH Hamamelose A branched-chain hexose containing two aldehyde groups occurs i n streptomycin (47g). CHO CHOH C(OH) GHO CHOH  I  CH  3  Streptose Regna, Hochstein, Wagner and Woodward (5l) have studied the structure o f the sugar mycarose found i n the a n t i b i o t i c magnamycin.  By degradation  studies they have shown the new sugar to be a deoxy sugar branched at  - 15 carbon three: HO - CH CH,2 HO f CH,-)CH,  HOCH CHCH  3  myoaroae A branohed -chain sugar acid has been synthesized by the alkaline degradation of maltose. (53) Isosaccarinic acid i s found among the products, and the lactone of this acid, isosaccharin, may be reduced to a noncrystalline branohed-chain aldose: (17) COOH  0=0  I  CH 0H - COH  CHgOH - COH  !H  CE 2  2  2  CHOH  !  ^2  I  CH2OH - COH  CH I CH 0H  CH  2  CHCH 0H 2  2  CH 0H 2  lactone (isosaccharin)  isosaccarinic acid Schmidt and Weber-Molster (57) have prepared a series of branchedchain sugar acids by cyanohydrin addition to D-fructose, D-xyloketose and D-araboketose.  In the case of the two acids produced by cyanohydrin addi-  tion to D-fructose the configurations were thoroughly studied. Woods and Neish (72) have employed the branched-ohain sugars obtained by cyanohydrin addition to D-fructose to prepare other branchedchain sugars.  By periodate oxidation of the lactose of the seven carbon  acid 4-C-hydroxymethyl-L-xyluronic acid was obtained. Reduction of the  -16  -  lactone and aldehyde groups of t h i s product with Raney n i c k e l and: sodium: amalgam yielded 2-Or-hydroxymethyl-D-rxylose.- Reduction of 4-G-^ydroxymethyl-L-xyluronic acid with sodium borohydride yielded noncrystalline 4-S-hydroxymethyl-D-arabinose'«. Staeey and co-workers (60) have synthesized a branched r  chain a l t r o s e s d e r i v i t i v e by the a c t i o n o f d i e t h y l magnesium, on me&hyl-2,5-anhydro-6-o-benzylizene-ec-D-fflannoside» diethyl ^ magnesium  CH2.OH  hydrolysis ^  H/ \H HO St  \H,OH 01 H  5-ethyl-D-altrose The structure of the branched chain sugar, apiose, has been elucidated by the following reactions ( 4 7 f ) ( 5 5 ) : (  H00H  HOCH  a  I 6(OH) - 0H0H- OHO  Ba(lOl  HOOH^  I 0(0H) * OHOH - COOH  HI  HOOH H-C HO - OH HC  I  - OOOH  3  5-methyl butyric acid  S i m i l a r l y 1-methyl v a l e r i c acid was- produced from hamamelose i n 5 . 5 to 5 percent y i e l d  ($$)t  - 17 -  HgCOH  HO - C - CHO I  CHOH i CHOH  CH5  Ba(lO) 2 >  HI —5»  P  I  CHgOH K i l i a n i (53)(54) reduced isosaccharin,  H C  _ coOH  I CH,  CH2 CH3 1-methylvaleric a c i d the lactone of isosaccharinic  a c i d with hydriodic a c i d and red phosphorous to oc-methylvalerolactone i n order t o indicate the p o s i t i o n of the hydroxymethyl group.  -  18  -  EXPERIMENTAL Preparation of 2. 5, 4, 6-Tetraacetyl-D-glucopyranosyl bromide The preparation was done according to the method of B a r c z a i Martose (4) with no modifications, except that h a l f quantities were used f o r convenience  i n handling the solutions.  The product  crystallized  r e a d i l y and 90g. (0.219 mole) of 2, 3, 4, 6-tetraacetyl-D-glncopyranosyl bromide was obtained from 50g. (0.28 mole) of D-glucose; y i e l d 78$;  m,p.  86-7°C. I f the preparation was allowed to stand f o r one day i n the presence of l i g h t and moisture, decomposition occurred as evidenced by a darkened color. Preparation of 5, 4, 6-Triacetyl-D-glucal o  The preparation was done according to the method of Fischer (20) with s l i g h t modification. Acetobromoglucose (90g.; 0.22 mole) was dissolved i n 900 ml. of 50% aqueous a c e t i c acid.  For convenience  i n handling, t h i s s o l u t i o n was  divided into two solutions of 450 ml. each.  Zinc dust (90g.) was added  to each batch, and both were shaken vigorously on a mechanical shaker f o r two or three hours.  The zinc dust was removed by f i l t r a t i o n , and the  solutions recombined, and evaporated at 10-20 nun. pressure, and at 40°C. to about one t h i r d of the t o t a l volume. f r i g e r a t o r , the zinc s a l t s c r y s t a l l i z e d .  On cooling overnight i n a r e A f t e r f i l t r a t i o n , the s o l u t i o n  was extracted several times with ether, and the combined extracts, about 500 ml., were n e u t r a l i z e d with sodium bicarbonate, washed with water, drieU over anhydrous magnesium s u l f a t e , and treated with decolorizing carbon. A f t e r f i l t r a t i o n the s o l u t i o n was evaporated at 10-20 mm.  pressure, and at  40^3. to a thick, c o l o r l e s s syrup which was inoculated with a seed c r y s t a l  - 19 -  and placed i n a r e f r i g e r a t o r .  The seed c r y s t a l was obtained from a pre-  vious batch which had c r y s t a l l i z e d spontaneously.  In about seven days  complete c r y s t a l l i z a t i o n had occurred; y i e l d 44.8g. (.165  mole; 67.2$).  A f t e r one r e c r y s t a l l i z a t i o n from 95$ ethanol the product had the follow20 ing constants; nup. 54-55°C. (uncor.), [ « 1 - 19.5° (C.3.02,95$ ethanol), 20 D which decreased to [ ©<'] - 13.2° (0.1.46,95$ ethanol). A f t e r three D r e c r y s t a l l i z a t i o n s F i s c h e r (20) reported a r o t a t i o n of - 13.02°, r i s i n g to - 15.2° on the seventh r e c r y s t a l l i z a t i o n . 18 reported a r o t a t i o n of | «=K  •  |  Danilov and Gakhokidze (16)  - 14.4°(25$ a l e ) .  D  On one occasion when the solution was allowed to stand i n the cold a f t e r f i l t r a t i o n o f the zinc s a l t s , 3, 4, 6-triacetyl-D-glucal cryst a l l i z e d ^ Hiowever, on concentration and extraction, more product  was  obtained, hence t h i s was not considered to be a f e a s i b l e method of i s o l a t i n g the product. Hydroformylation of 3, 4. 6-Triacetyl-D-&lucal 3, 4, 6-Triacetyl-D-glucal was tceaited with carbon monoxide and hydrogen according to a modification of the procedure of Pino (48), Adkins and Kresk ( l ) ( 2 ) , and Wender and co-workers (66). Reagents:Benzene was p u r i f i e d by treatment with several batches of s u l phuric a c i d , followed by d i s t i l l a t i o n over calcium chloride. Cobalt ( i l ) acetate tetrahydrate (Harshaw Chemicals Co acetate 101), supplied by the Harshaw Chemical Company of Cleveland, Ohio &>2), was used as catalyst a f t e r drying over phosphorous pentoxide. Table I shows the experimental r e s u l t s f o r hydroformylation of triacetyl-D-glucal.  The following i s a d e s c r i p t i o n of run I I , which  exemplifies the procedure used.  - 20  -  Triacetyl-D-glucal (4.30g., 0.0158 mole), cobalt acetate t a t r a hydrate (0.25g. 0.0009 mole), e t h y l orthoformate (0.034 mole) and 35 ml. of p u r i f i e d benzene were placed i n the glass l i n e r of a high pressure hydrogenator,  leaving a void of 264 ml. i n the bomb.  Carbon monoxide  was introduced to a pressure of 780 p . s . i . , followed by hydrogen to a t o t a l pressure of 1570 p j s . i . , both pressures measured at 17°C. mechanical rocker was started and the temperature  The  was raised to 100°C.  over a period of two hours, and maintained f o r a t o t a l of seven hours. The maximum pressure observed was 1950 p . s . i . room temperature  On cooling overnight to  the pressure was 1530 p . s . i . , corresponding to a drop of  40 p . s . i . (theor. 41.8  p.s.i.).  The gases were released, and the solution washed i n t o a f l a s k with benzene, f i l t e r e d and evaporated at 10-20 a syrup.  mm.  pressure and 40°C. to  The syrup was pale yellow i n c o l o r and started to c r y s t a l l i z e  as soon as evaporation was complete, m.p.  43-45°C. (uncor.), y i e l d 4.73g.  The product reacted with 2, 4-dinitrophenylhydrazine. Chromatographic Separation of the Products of Hydroformylation The product obtained from the hydroformylation of t r i a c e t y l D-glucal was chromatographically fractionated according to the procedure of Wolfrom and co-workers (70). Magnesol (2Mg0.5Si02) ( I 4- ) was dried overnight i n an oven at 100 C., and mixed with c e l i t e (No. 532, Johns-Manville) (31), i n a r a t i o of f i v e to one by weight; by shaking the mixture i n a large g l a s s bottle with a t i g h t f i t t i n g l i d .  The mixture was screened mechanically through  a 200 mesh per inch screen, and stored i n large brown b o t t l e s .  -  2 1  -  A tapered glass column (30 x 5.5 cm) was packed with 175g. of the prepared adsorbent using a reduced pressure of 740 mm.  The f i n i s h e d  column was moistened with 50 ml. of benzene, followed immediately by 850 mg. of the hydroformylation product dissolved i n 15 ml. of benzene. chromatogram was developed with 350 ml. of benzene. extruded and a i r dried f o r 12 hours.  the top of the column, and one 20 mm. from the top of the column.  The column was then  A streak of 1% potassium perman-  ganate i n 2.5N NaOH located two zones; one 80 mm.  115 mm.  The  broad, extending from  broad, extending from 95 mm.  to  The column was cut i n segments, and  the part of the column which had been sprayed was removed with a s c a l p e l and discarded.  Each zone was extracted with a volume of 500 ml. of  chloroform, followed by further extraction with 500 ml. of acetone.  From  the upper zone 450 mg. of sugar was recovered, and from the lower zone 200 mg.,  making the t o t a l recovery 76%.  The f r a c t i o n s from the upper and  lower zones were each r e c r y s t a l l i z e d , once from ether, twice from ethanolwater, and twice from e t h y l acetate-petroleum ether ( b o i l i n g range 40°60°C.) to form colorless, needle-like c r y s t a l s with constant melting points. The material from the upper zone reduced Fehling's solution i n 15 seconds 24 and had the following constants: m.p. 76.5°-78.5°C. (uncor.), J~ © C 1 +• D 100°(C 0.179, 95% ethanol).  The material from the lower zone d i d not r e -  duce Fehling's solution or take up bromine and had the following constants; 23." 5 m.p. 5l°-52°C.(uncor.) [ o< J - 5.7°(C 1.34, 95% a l e ) . A mixed D' melting point with t r i a c e t y l - D - g l u c a l was  45°-49°C.  Infra-red analysis of the compound melting at 51°-52°G. appears i n Figure 1 (p. 2.$  .).  - 22 -  Anal:  Upper zone - Calcd. f o r G H 0 : C, 54.23; H, 7.51; CHgCO, 1 7  34.32. MV Pound:  2 8  9  376.  C, 55.56; H, 7.07;  CH C0, 34.0. 3  Lower zone - Calcd. f o r GI'^±Q0 : 7  MKT 350 (cryoscopic).  C, 52.59; H, 5.60;  CH C0, 47.09. 3  JOT 274. Pound:  C, 52.81; H, 6.05;  CHgCO, 47.27.  MV  270.  D i s t i l l a t i o n of the Products of Hydroformylation A p o r t i o n (l2.05g.) of the syrup from hydroformylation VII (see Table l ) was d i s t i l l e d under high vacuum (0.05 mm.)  y i e l d i n g thick  syrups which ranged i n c o l o r from yellow to orange going from lower to higher b o i l i n g f r a c t i o n s .  The residue remaining i n the d i s t i l l a t i o n f l a s k  was charred and polymerized.  A f t e r standing i n a vacuum desiccator over  phosphorus pentoxide f o r periods ranging from eight hours f o r the lower b o i l i n g f r a c t i o n s , to two weeks f o r the higher b o i l i n g f r a c t i o n s , crys t a l l i z a t i o n was complete.  The crude products were r e c r y s t a l l i z e d from  ethanol (95$)-water and from e t h y l acetate-petroleum ether to form c o l o r l e s s , needle-like c r y s t a l s with constant melting points of 51°-52°C. and 112°-113°C.  The crude y i e l d of the compound melting at 51°-52°C,  was 3.29g., and t h i s f r a c t i o n was found to be i d e n t i c a l with that obtained chromatographically.  The higher melting compound (7.60g.) r a p i d l y r e -  duced Fehling's solution, gave a negative bromine test, and the following 20 23.5 rotations: [ ] + 90.0°(C 0.806, CHC1 ) and [©<] + 115.0° D D 3  (ale,  C Q.267).  Anal:  Calcd. f o r C  Pound:  1 2  H  1 8  0 : C, 49.64; H, 6.26; 8  C, 49.45; H, 6.28;  274 (exaltone).  GH C0, 54.7. MW 3  CH C0, 44.53 W 3  344 (camphor), 351  290. (benzene),  - 25 A summary of the separation of the products of hydroformylation by d i s t i l l a t i o n and by chromatography i s given i n Table I I . Analysis of the Products of Hydroformylation 1. )  The molecular weights were determined cryoscopically  using benzene. 2. )  Carbon, hydrogen and a c e t y l determinations were done by  Weiler and Strauss ('"64), and by Manser (39). 3. )  Infra-red analysis was done by Dr. R. Wright (73).  Deacetylation of Products Obtained from Hydroformylation of T r i a c e t y l D-Glucal. The products of hydroformylation which had been separated by d i s t i l l a t i o n and by chromatography were deacetylated according to the method of Overend, Shofizadeh and Stacey (44), a modification of the Zemplin method (75). A sample (0.4g.) of the sugar acetate melting at 51°-52°C. was dissolved i n 4.2 ml. of anhydrous methanol to which f r e s h l y cut sodium metal (  0.005g.) was added.  The f l a s k was sealed and allowed to stand  at room temperature f o r 48 hours.  The s o l u t i o n was treated with s o l i d car-  bon dioxide, and on addition of acetone an inorganic p r e c i p i t a t e , probably sodium acetate, appeared.  The p r e c i p i t a t e was removed by f i l t r a t i o n  and the remaining solution was evaporated under reduced pressure y i e l d i n g a syrup (0° lOg., y i e l d 50$).  After standing i n a vacuum desiccator over  phosphorus pentoxide f o r one month no c r y s t a l l i z a t i o n of the syrup occurred. No uptake of bromine by t h i s syrup could be observed. An o p t i c a l rota20 t i o n was taken on the dried syrup, [ ] + 12.0°(C 0.584, water).  - 24 -  F i s c h e r (21) reported a r o t a t i o n  [ ^ ]  + 1 6 . 3 1 ° (water) f o r crysD  t a l l i n e hydroglucal. A further sample (l.2g.) was dissolved i n 7.5 ml. o f anhydrous methanol to which f r e s h l y cut sodium metal was added. the  A f t e r 48 hours,  s o l u t i o n was treated with two i o n exchange resins; Amberlite IR120  (23) and Duolite D5683 (14) and evaporated to dryness under reduced pressure to a syrup; y i e l d 0.40 g., 62$. S i m i l a r l y 1.18 g. of the sugar acetate melting a t 112°-113°C. was deacetylated and taken to a syrup; y i e l d 0.40g., 65$.  - 95 -  I  .  40.00  1—  3250  i  i  2500  1900  i  i  1700  1500  :  1  1J00  i  5100  A Infra red spectmmof triacetyl-D-glucal. , 3 " n . 11 • 11 compund A, m.p. 51-52 0 G t. . . . compound 0, m.p. 112-113 C. D " . " " . " . compound A, deaeetyla*ed. E " ' ".. " compound 0, -deacetylated.  ' II  11  Figure I  i  1  900 cm".'  TABLE I IHDROFORMILATION RESULTS  TriacetylD-glucal  I  II  III  IV  Vol. of Cobalt Acetate beni4H 0 :-. zene 2  0.83g. 0.0030mol.  0.5g.  4.30g. 0.0158mol.  0.25g.  12.85g. 0.0472mol.  0.75g.  6.80g. 0.0250mol.  0.33g.  ethyl orthoformate  initial combined gas pressure (p.s. i . )  maximum pressure (p.s.i.)  1 theorpressure e t i c a l drop drop (p.s.i.) (p. s. i . )  maximum temperature.  3 time f o r reaction  55  40  35ml. 5.0ml. 0.034mol.'.  1500  1720  110°C.  lhr. a t 100-110°C.  35ml. 1.0ml. 0.0061mol  1570  1950  105°C.  6hrs. at 100-105°C.  45ml. 3.0ml. 0.018mol.  1545  2240  150°C.  5hrs. at 90-100°C.  130  45ml. 8.0ml. 0.048mol.  1490  1910  112°C.  9hrs. at 110-112°C.  50  8.07  41.8  121  69.2  product  yellow syrup crystallized in. p. 45-47°C. yellow syrup partially crystallized nup. 43-45°C.  brown syrup partially crystallized m.p. 41-51°C. brown syrup partially crystallized m.p. 38-44°C,  TABLE I (cont.)  TriacetylD-glucal  VII  2  Vol. of benzene  ethyl orthoformate  initial combined gas pressure (p.s.i.)  maximum pressure (p.s.i.)  maximum temperature.  3 time f o r reaction  0.33g.  35ml. 8.0ml. 0.048mol.  1600  2010  100°C.  5hrs. at 100-1IO°C,  6.43 g. 0.0253mol.  0.35g.  35ml. 8.0ml. 0.048mol.  1550  2100  125°G.  6hrs. at 100-125°C  20. l g . 0.0738mol.  1.08g.  55ml. 13.2ml. 0.081mol.  1550  2000  115°C.  6hrs. at 100-115°C  V 6.32g. 0.0232mol.  VI  Cobalt Acetate .4H 0  theorpressure e t i c a l drop drop (p. s.i.) (p. s. i . )  80  '59.4  leak in bomb.  65.0  2 50  155  product  yellow syrup partially crystallized m.p. 32-36°C. deep orange syrup. orange syrup  1.  Assuming hydroformylation occurs.  2.  Due to mechanical d i f f i c u l t i e s , i t was necessary to introduce and expel, and reintroduce gases i n s t a r t i n g reaction. The solution appeared to have undergone a change before reaction.  3.  Temperatures not constant i n some runs due to poor thermostatic control.  - 28 -  TABLE I I PRODUCTS OBTAINED PROM HYDROFORMYLATION OF TRIACETYL-D-GLUCAL  reaction  method of separation  products obtained  composition of mixture i  III  IV  V  chromatography  chromatography  chromatography  a. c r y s t a l s m.p.76.5-78.5°C.  a. 57.3$  b. c r y s t a l s m.p.51-52°C.  b. 16.8$  a* c r y s t a l s m.p.51-52°C.  a. 58.0$  b. syrup  b. 10.0$  a. c r y s t a l s m.p.51-52°C.  a. 63.0$  b. syrup  b.  8.6$  VI  distillation  a.  a. 78.0$  VII  distillation  a. c r y s t a l s m.p.51-52°C.  a. 25.6$  b. c r y s t a l s m.p.ll2-113°C.  b. 49.0$  - 29  -  DISCUSSION  In the preparation of the starting material, triacetyl-Dglucal, from acetobromoglucose according to the methods of Barczai Martose ( 4 ) and Fischer ( 2 0 ) , i t was observed that acetobromoglucose is very unstable, and that the best overall yields are obtained i f acetobromoglucose i s converted to triacetyl-D-glucal immediately. In fact, by the method of Helferich and co-workers ( 2 6 ) , acetobromoglucose need not actually be isolated. Crude triacetyl-D-glucal, or material which has been recrystallized only once, tends to darken and polymerize in the presence of light, moisture and traces of acid, and will in fact form a brittle, black material after standing for some weeks in the presence of light and air. After three recrystallizations triacetyl^3~glucal i s quite stable and may be stored in ordinary sample bottles at room temperature for some weeks. If stored in the cold, the material is of course much more stable. The experimental procedure for hydroformylation was taken from that of Adkins and Kresk  (1,2),  and Wender and Levine  (66),  using cobalt  acetate tetrahydrate as suggested by Pino (AS). In this work pressures of 100 to 150 atmospheres of the gas mixture were employed and temperatures from 1 0 0 to 1 5 0 ° CI, as i t was thought that temperatures above 1 5 0 ° C would favor decomposition of the sugar and reduction of any aldehyde formed to an alcohol. Natta ( 4 0 ) has employed pressures of 7 0 to 210 atmospheres in the hydroformylation of methyl oleate, and Parker ( 4 6 ) has employed tern-  30 -  peratures as high as 210° C in the hydroformylation of various alkenes. Pressures as high as 300 atmospheres are found in some industrial processes. Pressures greatly in excess of 2000 p.s.i. were avoided because the bomb had not been used at more than 1800 p.s.i. and 100° C for some years, and although i t was subsequently tested to 4500 p.s.i. in the cold, the maximum safe pressure at 100° C was unknown. The time for the reaction was chosen arbitrarily because no pressure drop could be observed at the maximum temperature and pressure. Since carbon monoxide and hydrogen form an extremely non-ideal gas mixture, i t could not be determined whether or not the maximum theoretical pressure, calculated on the basis of the pressure of the gases originally introduced, was ever attained at the maximum temperature.  As a consequence,  the bomb had to be completely cooled before any pressure drop could be measured. It i s possible that most of the reaction occurs instantaneously because no pressure drops were observed at the maximum temperature and pressure. This suggestion i s supported by the following observation. On introducing the gases, carbon monoxide was always added first, followed by hydrogen, in order to lessen the possibility of hydrogenation.  A  slight drop in the pressure of the carbon monoxide was always observed immediately after i t had been introduced. It was originally supposed that this drop was due to a small leak in a valve, however, on one occasion when the carbon monoxide had been introduced, and had subsequently  - 31 -  to be expelled because of mechanical difficulties, the solution was observed to have taken on a yellow color and bubbles could be observed. According to Adkins and Kresk the starting pressure i s that observed after both gases have been introduced, and the mixture rocked for one minute*  In this  work the total gas pressure observed was always slightly less than the total pressures of the gases originally introduced* Obviously the experimentally observed pressure drop could therefore be less than the true one.  The  accuracy of this observation was further impaired by the fact that the gauge scale was marked in divisions of 10 p.s.i. It can be seen from Table 1 that the experimental pressure drop was in some cases greater and in some cases less than the theoretical pressure drop. Run 111 is of particular interest because the observed pressure drop was 130 p.s.i., as compared to the experimental theoretical drop of 121 p.s.i. A compound was found in the products of this run which was not isolated in any other case. The discrepancy between the two may perhaps be explained by the error introduced by the gauge, and by the amount of gas taken up by the catalyst. It may be significant that in Run 111, a high concentration of sugar was employed, and a temperature of 150° c was reached during the reaction. The catalyst selected, cobalt acetate tetrahydrate, had been used by several other workers (67,48) in the hydroformylation of olefinic compounds. It was supplied as a sample by the Harshaw Chemicals Co. of Cleveland, Ohio (25). The chromatographic separation of the products was carried out according to the method of Wolfrom and co-workers (69, 70). Columns of  - 32  the type designed f o r extrusion chromatography were packed with the dry c e l i t e and magnesol mixed i n a one t o f i v e r a t i o .  I t was found that the  smaller columns could be packed with the dry adsorbent quite r e a d i l y , but the largest size  5.5 x 30 cm. were more d i f f i c u l t t o pack because  the packing tended to form channels and cracks. Wet packing was found to be more r e l i a b l e f o r the size of column.  The packing to be placed i n the  column was s t i r r e d vigorously with s u f f i c i e n t benzene t o make a mixture which could be poured e a s i l y i n t o the column.  I f the mixture was too  t h i c k , a i r bubbles were entrapped, and i f too t h i n the time required t o pack the column was g r e a t l y increased.  The solvent was removed from the  packing using s l i g h t l y reduced watgg pressure of 720-740  mm.  The products of hydroformylation were separated on the column using benzene as a developer.  The column was extruded and the separated  products i s o l a t e d by extraction of the adsorbent with chloroform and acetone.  Removal of the solvent yielded syrupy products which were p u r i -  f i e d by several r e c r y s t a l l i z a t i o n s .  The r e s u l t s of chromatographic separ-  ation of several runs are shown i n Table I I . In the separation of the products of hydroformylation by high vacuum d i s t i l l a t i o n , no exceptional amount of decomposition took place during most of the d i s t i l l a t i o n .  The material remaining i n the f l a s k was  charred, however, because of the very high bath temperature required t o r a i s e the vapor temperature to 150° C.  The syrups d i s t i l l e d , e s p e c i a l l y  the l a t t e r f r a c t i o n s , were so t h i c k that no condenser was used i n most cases, and i f the equipment necessitated the use of a condenser, i t was  33 -  f i l l e d with hot water and wrapped i n aluminum f o i l .  The syrups obtained  by d i s t i l l a t i o n of the products o f hydroformylations VI and VII (see Table II) c r y s t a l l i z e d slowly and a f t e r several r e c r y s t a l l i z a t i o n s yielded compounds having melting points of 51° - 52° G. and 112° - 113° C. The analysis of the acetylated compound melting at 51° - 52° C.  Tod^o D  - 7.19°  (c 1.05, ale.) agrees c l o s e l y with that of e i t h e r  t r i a c e t y l - D - g l u c a l or l,2-dihydro-3,4,6-triacetyl-D-glucal  (Found. C,  52.81$; H, 6.05$, CH3CO, 47.27$, Theor. f o r C^RieDy: C, 52.54$; H, 6.62$; CH3CO 47.09$.  Theor. f o r C^H-^Or,, C, 52.94$; H, 5.94$; CH3CO, 47.42$;  Fischer (14) has prepared l,2~dihydro-3,4,6.-triacetyl-D-glucal i n nonc r y s t a l l i n e form by the reduction of t r i a c e t y l - D - g l u c a l with palladium sponge i n a c e t i c acid, followed by d i s t i l l a t i o n of the product. of + 3 3 . 9 3 ° - 35.55° a l e . was reported f o r t h i s product.  A rotation  No constants f o r  the c r y s t a l l i n e compound have been found elsewhere i n the l i t e r a t u r e . A l though the infra-red analysis of the compound melting at 5 1 ° - 52° C. shows the presence of a double bond by absorption at 1600 cm.-l (see Figure 1 p. 25), the uptake of bromine by t h i s compound i s very s l i g h t .  Moreover  a small depression of melting point i s obtained when t h i s compound i s mixed with t r i a c e t y l - D - g l u c a l ,  The rotation of c r y s t a l l i n e hydroglucal obtained  by Fischer (14) was + 1 6 . 3 1 ° , while that of the deacetylated syrup obtained i n t h i s work was + 1 2 ° .  Therefore the c r y s t a l l i n e material obtained must  be a mixture of t r i a c e t y l - D - g l u c a l and  l,2-dihydro-3,4,6-triacetyl-D-glucal,  having a greater proportion of the hydrogenated  product.  The s i m i l a r i t y of  the two compounds might render further separation d i f f i c u l t .  - 34 -  The analysis of the acetylated compound melting at 112°-113°C. i s as follows: C, 49.76£; H, 5.62gj o f triacetyldeonyglucose i s  :  GR3OO7  46.9??. The theoretical analysis  C, 49.64$; H, 6.26#j  CH3OO  44.51#« The melt-  ing point of the f u l l y acetylated derivitive of the compound obtained i n this word i s 93-94° C , compared to 91° C. reported by Stacey and co-workers -ot.-D-2-deoxyglocose.  (44) for tetraacetyl  Bergmann (6) reported triacetyl-2-deoxyglocose as an intermediate in the production of 2-deoxy-D-glucose from triacetyl-D-glucal, but did not crystallize the acetylated deoxy sugar. The product obtained by deaoetylation of the compound melting at U2 -113° C. was a syrup, which could not be shown by paper chromato0  graphy to consist of more than one component. The rotation of this syrup was •+- 5.95° as compared to 4*4-6.59° obtained by Bergmann (6), for the crystalline compound. The presence of a compound containing a free hydroxyl i s i n dicated by the reduction of Fehling's solutions, and infra red absorption at 3500 cm." . It i s probable that compound melting at 112°-113°C. i s a 1  mixture consisting of triaeetyl-D-deoxyglucose contaminated with compounds of higher acetyl value. The analysis of the compound melting at 76.5°-78.5° C. agrees most closely with the theoretical analysis of the diethylacetal compound which should be produced by hydroformylation and subsequent reaction with ethylorthoformate.  Found (ave.) C, 55.67#j H, 7.14/S; CH3OO, 34.<#j M.W.  356. Theor. for C H gOQ: C, 54.39#, H, 7.48£j CH3CO, 34.3??; M.W. 376. 17  2  35  -  Unfortunately such a small amount of t h i s compound was obtained i n pure form that further work could not be done to study the structure of the compound. A number of experimental f a c t o r s must be considered i n attempting to determine why hydroformylation d i d not occur t o any appreciable extent, except perhaps i n Run I I I , Table I I ( p . ^ S ) » sidered i s the c a t a l y s t .  The f i r s t to be con-  Cobalt acetate tetrahydrate i s not. i t s e l f a  catalyst f o r hydrogenation, but cobalt hydrocarbonyl, formed from dicobalt octacarbonyl i n the presence of hydrogen w i l l act as a hydrogenation  cata-  lyst. 2 HCo(CO)  Since considerable hydrogenation  P  occurred i n every hydro-  formylation, i t may be assumed that the required hydroformylation c a t a l y s t , dicobalt octacarbonyl, does form under the reaction conditions employed. Unused cobalt acetate tetrahydrate remained i n the r e a c t i o n mixture, hence a s u f f i c i e n t amount was used. The second f a c t o r to be considered i s the e f f e c t of temperature. From consideration of Tables I and I I , i t would appear that there i s a c r i t i c a l temperature between 125°  C. and 150°  C,  at which hydroformylation  occurs, even though the amount of the desired product formed i s small even when a temperature of 150°  C. i s attained (see I I I  , Table I ) . No work  has been found i n the l i t e r a t u r e comparing the reaction temperature required t o hydrogenate an e l e f i n i c bond under the influence of a cobalt c a t a l y s t ,  -36  and the temperature same c a t a l y s t .  required t o hydroformylate the same bond, using the  The absence of any studies on t h i s subject i s probably  because the production of hydrogenated m a t e r i a l , under experimental cond i t i o n s s i m i l a r to those used i n t h i s study, has been considered t o be i n s i g n i f i c a n t by other workers. Hydrogenation i s theraodynamically favored over hydroformylation but i t has been found that (43) hydrogenation of an o l e f i n i c linkage only begins to compete with hydroformylation when the double bond of the system i s conjugated to another unsaturated system.  Adkin's observation of a  number of compounds containing conjugated systems which f a i l e d to undergo hydroformylation, substantiates t h i s generalization.  Triacetyl-D-glucal  contains no conjugated system, hence there must be some other reason hydrogenation i s favored and hydroformylation i s hindered.  why  I t may be that  the formation of.an unknown intermediate i s s t e r i c a l l y hindered by the r i n g form of the compound, or by the s t e r i c e f f e c t of f u l l y substituted hydroxyls. The formation of triaeetyl-2-deoxy-D-glucose normally occurs by treatment of triacetyl-OQglucal with d i l u t e sulphuric a c i d , thus e f f e c t i n g the addition of water across the double bond.  In considering, as a s p e c i f i c  case Run VII (Table I I ) , i t i s seen that 64 percent of the product i s triacetyl-2-deoxy-D-glucose.  The amount of water present i n the catalyst  i s 0.024 moles; and the amount of sugar present i s o,o738 moles.  The amount  of water present i n the gases must, therefore, be of considerable importance. Moreover, the amount of cobalt hydrocarbonyl formed must be able t o exert a c a t a l y t i c e f f e c t i n the addition of water t o the double bond.  Though t h i s  - 37 1 \  compound i s only detected i n Run VII (Table I I ) , i t was doubtless present in varying amounts i n the products of each hydroformylation. may have been prevented i n chromatographic numerous decompisition products.  Its isolation  separation by the presence of  Since the d i s t i l l a t i o n of run VI  (Table  II) was not. as complete as that of run VII (Table I I ) , the deoxy sugar probably remained i n the undistilled residue. Some suggestions regarding future hydroformylations of triacetylD-glucal may be made. F i r s t , to inhibit the formation of hydroglucal, a greater proportion of carbon monoxide might be employed. No studies were found i n the literature where a partial pressure of carbon monoxide greater than that of hydrogen was used, probably for reasons of economy, since, as discussed previously, the amount of hydrogenated product found by other workers i s usually insignificant anyway. Second, to prevent the formation of triacetyl-2-deoxy-glucose, the water must be removed from the system. One means of producing anhydrous conditions would be by the addition of a non-reactive desiccant whose hydrate i s stable at 150° C , for example magnesium sulphate.  The desic-  cant could be added to the reaction mixture, the bomb charged, and rocked for two or three hours before heating i s started.  A second method of re-  moving water from the system, would be to dry the gases before charging the bomb. Obviously, the mechanical d i f f i c u l t i e s involved i n such a procedure, when pressures of 100  to 150  atmospheres are employed, are enor-  mous. A series of reactions might be done using more carbon monoxide,  - 38  and a desiccant, at 125°  -  to 150° C ,  and at 2000 t o 2500 p . s . i .  products could be most r a p i d l y separated by d i s t i l l a t i o n .  The  The crude  f r a c t i o n s so obtained could be f u r t h e r p u r i f i e d by chromatographic separation, and r e c r y s t a l l i z a t i o n .  An i n t e r e s t i n g point i n considering  the reaction mechanism would be to determine what changes have taken place i n the reaction mixture immediately a f t e r the a d d i t i o n of carbon monoxide. Mien suitable conditions f o r hydroformylation are found the structure of the sugar produced could be determined by the following series of reactions:  deacetylation to the free sugar, oxidation to the  lactone of the aldonic a c i d and reduction to the lactone of an o i i p h a t i c a c i d , the hydrazide of which could be compared t o that of a known compound. Though the seven carbon sugar was found i n only one run, i t i s hoped that t h i s work w i l l remove some of the d i f f i c u l t i e s i n future attempts to hydroformylate t r i a c e t y l - D - g l u c a l , and w i l l be an addition to the e x i s t i n g knowledge of the oxo r e a c t i o n .  - 39 -  BIBLIOGRAPHY  1.  H. Adkins and G. Kresk, J . Am. Chem. S o c , 70, 383 (1948).  2.  H. Adkins and G. Kresk, i b i d , 71, 3051 (1949).  3.  H. Adkins and R. W. Rosenthal, ibid, 72, 4550 (1950).  4.  M. Barczai-Martose, F. Korosy, Nature, 165. No. 4192, 369 (1953).^  5.  M. Bergmann, H. Schotte, Ber., 54B. 440 (1921). C. A. 1£, 2420 (1921).  6.  M. Bergmann, H. Schotte and W. Lechinsky, Ber., ?5B. 158 (1922). C. A. 12, 2118 (1922).  7.  M. Bergmann, M. Kobel, H. Schotte, E. Rennert and S. Ludewig, Ann. 4^4, 79 (1923).  C . A. 18, 380 (1924).  8.  M. Bergmann, Ann. 4 J & , 223 (1925).  9.  M. Bergmann and W. Breners, Ann. 4J7, 54 (1929).  C. A. 19, 2478 (1925).  C. A. 22, 3670 (1929). 10.  M. Bergmann, W. Freudenberg, Ber. 64B. 158 (1931).  11. M. Bergmann, L. Zervas and J . Engler, Ann. 508. 25 (1933). C. A. 28, 1666 (1934). 12.  W. W. Binkley and M. L. Wolfrom, Sugar Res. Found. (N.Y.) S c i . Rept. Ser. No. 10, (1948).  13.  W. W. Binkley, W. L. Shilling and M. L. Wolfrom, J . Am. Chem. Soc. 72, 4544 (1950).  14.  Chemical Process Co., Redwood City, California, U.S.A.  15.  J . K. Dale, J . Am. Chem. Soc. 3_8, 2187 (1916).  - 40 -  BIBLIOGRAPHY (continued) 16.  S. N. Damilov and A. M. Gakhokidze, J . Gen. Chem. (U.S.S.R.) 6, 704 (1936).  17.  C. A. 2 2 , 6333 (1930).  E. Fischer and H. Fischer, Ber. 43_, 2521. C. A. 4^ 3234 (1902).  18.  E. Fischer, Ber. 44., 1898 (1911).  C. A. 5_, 3265 (1911).  19.  E. Fischer and C. Gach, Sitzb, kgl. preuss. Akad., 311  (1931).  C. A. 8, 73 (1914). 20.  E. Fischer, Ber. 47, 196 ( 1 9 H ) .  C. A. 8, 1121  21.  E. Fischer, Ber. 49_, 584 (1916).  C. A. 10, 1532  22.  E. Fischer, M. Bergmann and H. Schotte, Ber. 53B. 509 (1920).  23.  Fisher Scientific Supplier Ltd., Vancouver.  24.  M. Gehrke and F. X. Aichner, Ber., 6QB, 918 (1927).  25.  Harshaw Chemicals Co., Cleveland, Ohio.  26.  B. Helferich, E. N. Mulcahy and H. Ziegler, Ber. 87_, 233 (1954).  27.  Henkel and Cie. G. m.b.H. B r i t . 668, 557, March 19, 1952. C. A. 4J7, 1 U  (1914). (1916).  (1953).  28.  H. S. Isbell, J . Res. Natl. Bur. Standards, 3_2, 45 (1944).  29.  H. S. Isbell and W. W. Pigman, J . Res. Natl. Bur. Standards, 22, 397 (1939).  30.  B. Iselinand Z. Reichetun, Helv. Chim. Acta., 27, 1146 (1944). C. A. 3Jt, 4846 (1945).  31.  Johns-Manville Co., New York, N.Y.  41 -  BIBLIOGRAPHY (continued) 32.  A. K. Keulmans, A. Kwantes and ^h. Van B*vel, Rec. Trav. Chim.,  67, 298 (1948). 33.  H. K i l i a n i , Ber. 18, 631 (1885). B.C.A., 744 (1885).  34.  H. K i l i a n i , Ber. 18, 642 (1885). B.C.A., 745 (1885).  35.  H. K i l i a n i , Ber. 5JB, 75 (1922). C. A. 16, 2102 (1922).  36.  P. A. Levene and A. L. Raymond, J . B i o l . Chem., 88, 513 (1930).  37.  P. A. Levene and A. L. Raymond, J . B i o l . Chem., 9j3, 63I (1931).  38.  P. A. Levene and T. Mori, J . B i o l . Chem. {£3 , 803 (1929).  39.  A. Manser, Zurich, Switzerland.  40.  G. Natta and E. Beati, Chimi e Industrie 27, 80 (1945).  C. A. 41, 706 (1947) 41•  G. Natta, P. Pino and E. Mantica, Gazz. Chim. I t a l . , 80, 680 (1950).  C. A. 46, 904 (1952). 42.  G. Natta and P. Pino, Chimi Industrie, 63_, 467 (1950).  C. A. 4 J , 5883 (1953). 43.  M. Orchim, Hydrogenation of Organic Compounds with Synthesis Gas, Advances i n C a t a l y s i s V, p. 385, Academic  Press Inc., New York, (1953). 44.  W. G. Overend, F. Shafezadeh and M. Stacey, J . Chem. Soc., 738 (1950).  45.  W. G. Overend, M. Stacey and J . Stanek, J . Chem. S o c , 2841 (1949).  46.  P. F. Parker, U.S.  47.  ¥ . W. Pigraan and R. M. Goepp, Chemistry of The Carbohydrates,  2,597,096; A p r i l 29, 1952. C.A. 47, 141 (1953).  Academic Press Inc., 1948, (a) 8, (b) 129 (c)  168, (d) 352, (e) 369, (f)' 471, (g) 474.  - 42 -  BIBLIOGRAPHY (continued) 48.  P. Pino, Gazz. Chim. I t a l . , 81, 625 (1951).  49.  C. B. purves and A. S. Perkin, Can. J . Chem., 3JL, 227 (1953).  50.  C. E. Redemann and C. Niemann, Organic Synthesis, XXII, 21. John Wiley and Sons Inc., New York, 1942.  51.  P. R. Regna, T. A. Hochstein, R. L. Wagner and R. B. Woodward, J . Am. Chem. Soc. 75_, 4625 (1953).  52.  0. Rochen, U.S. 2,327,066. Aug. 17 (1943).  53.  S. K. Rhattacharyya and B.C. Subla Ras, J . Sci. Ind. Research (India), 1L3, 80 (1953). C. A. 47, 2690 (1953).  54.  J . Schexnailder, U.S. 2,500,210. C. A. 44, 4607 (1950).  55.  0. Th. Schmidt, Ann. 476. 250 (1929).  56.  0. Th. Schmidt, Ann. 483. 115 (1930).  57.  0. Th. Schmidt and C. C. Weber-Molster, Ann. 515. 43 (1934).  58.  P. Shoriugun and Makarav-Zembyanskii,  C. A. 2^, 2118 (1930). C. A. 25_, 920 (1931).  Ber. 66B, 387 (1933).  C. A. 27, 2674 (1933).  59.  D. F. Smith, C. B. Hawk and P. L.  Golden, J . Am. Chem. S o c ,  £2, 3221 (1930).  60.  M. Stacey, J . Chem. Soc. 3308 (1953).  61.  H. W. Sternberg, I. Wender and M. Orchin, Anal. Chem., 24, 172 (1952).  62.  H. H. Storch, N. Golumbic and R. B. Anderson, he Fischer-Tropch T  and Related^ Syntheses. 441. John Wiley and Sons Inc., New York, 1951.  - 43 -  BIBLIOGRAPHY (continued). 63.  Choji Zanaka, B u l l . Chem. Soc. Japan, £, 214 (1930).  C. A.  24_, 5026 (1930). 64.  G. Weiler and F. B. Strauss, Oxford, England.  65.  I . Wender and M. Orchin, U.S. Bureau of Mines Report Invest., 4270 (1948).  66.  I . Wender, R. Levene and M. Orchin, J . Am. Chem. S o c , 72, 4375 (1950).  67.  I . Wender, H. Greenfield and M. Orchin, J . Am. Chem. S o c , 731 2656 (1951).  68.  I . Wender, S. Metlin&and M. Orchin, J . Am. Chem. Soc. 73_, 5704 (1951).  69. M. L. Wolfrom and J . V. Karabinos, J . Am. Chem. S o c , 66, 9 0 9 (1944). 70.  M. L . Wolfrom, S. M. O l i n and W. J . Polglase, J . Am. Chem. S o c , 72, 1724 (1950).  71.  M. L. Wolfrom and J . M. Sugihara, Ann. Rev. Bichem.,  72.  R. J . Woods and A. C. Neish, Can. J . Chem., 31, 471 (1953).  73.  R. Wright, B.C. Research Council, Vancouver.  0  1£, 71 (1950).  


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