substitution of acyclic sugar acetals: rate of perchloric acid catalyzed acetolysis of...
TRANSCRIPT
SUBSTITUTION OF ACYCLIC SUGAR ACETALS RATE OF PERCHLORIC ACID CATALYZED ACETOLYSIS OF 2,3,4,5,6-PENTA-0-ACETYL-n-
GLUCOSE DIETHYL DITHIOACETAL AND I,Z,~,~,~,~-HEXA-O-ACIITYL-D-GLUCOSE S-ETHYL MONOTHIOACETtlL
S o n ~ ~ . \ s 11. KURIII.\R.\ .IUD EDG.\R P.\GI; P.\IN,I ER
Depnit~ilerzt nJ Cller~iistfy, Unzvers~ty of CalzJnrntn, Dav~s, Cnl$or?~in
Received February 2, 1966
ABSTRACT
The rate constants for the perchloric acid catalyzed subst i t~~t ion ol one ethylthio group 01 ~,~,4,5,6-penta-O-acetyl-~-ficose diethyl dithioacetal (Va) and the acetoxy group bonded to CI of 1,2,3,4,5,6-hexa-0-ncetyl-D-glucose S-ethyl monothioacetal (VIa) have been ~neasured when the substrates were dissolved in solutions of acetic acid and acetic anhydride. ?'he rate- determining step is interpreted to be the dissociation of the substrate c o n j ~ ~ g a t e acid to give a carbonium-sulfonium cation. The rate constants indicate that acyclic sugar derivatives are substituted faster than cyclic (pyranose) derivatives, and that a n acetosy group is substituted faster than an ethylthio group.
Acetals dissolved in mixtures oi acetic acid and acetic anhydride \\-hich contaiil a strong acid give substitution products \vhich arise by cleaving either C-0 bond of the substrate. The product has a C-OAc bond in place of the C-0 bond cleaved. Thus mcthyl 2,3,4-tri-0-acetyl-P-arabinoside (I) gave both I1 and I11 \vhen the acid \\-as zinc chloride or 0.16y0 sulfuric; and gave the C l gem-diacetate (I\'), a product \\-hich required cleavage of both the C1-OCI13 and C1-0 ring bonds of I , when the catalyst \\-as 4y0 ssulfuric acid (1).
Poly-0-acetyl diethyl dithioacetals of the comnzon monosaccl~arides behave in much the same n7ay. Pirie (2) dissolved dithioacetals (V) in acetic anhydride which contained 1.8 Msulfuric acid, and isolated products (Cl gem-diacetates (1'11)) for~ned by subs t i t~~t ion after cleavage of each ethylthio group. Sinlilar to the observation of A,Iontgomery ef nl. (1) \\-hen I \\-as the substrate, acids a t lo~v concentration catalyze a fast substitution of one
H SC?MS I3 SC?Hj H OAC \ /
Cl \ /
+ CI \ /
+ CI / \ R SC?Hs
/ \ R 0-%c
/ \ R OAc
v VI VII
SCtI-I group of 1' to give VI (3). The products of a single substitutio~l by an acetoxy group (11, 111, and VI) are diastereonleric pairs (1, 3). Strong acids in acetic acid epimcrize to give equilibrium mixtures. A Cl-OAc bond is broken in the process. gem-Diacetates are acetolysis products fornled by cleavage of a C1-OCI-Is bond (of 111) or a C1-SC2FIs bond (of VI). The rate of substitution of the illoiloacetals (I11 and VI) to give gem- diacetates is several powers of 10 slo\\-er than the rate of substitution of the acetals (I and
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1774 CAN:\Dl.X.U JOGRSAL O F CllEMlSTRY. VOL. -1-1, 1900
IT) or the rate of epimerization of the monothioacetals. Since relative rates difler so greatly, the reaction can be quenched after the initial fast substitution of \', so that good yields of ~nonothioacetals are obtained (3, 4). When dilute perchloric acid was the catalyst, we were unable to isolate a gem-diacetate \\-hich would sho\\i that the substitution VI -+ VII tool; place.
We cannot find in the literature rate constants for the substitution of dithioacetals or for the substitution (at C1) of a single acyclic sugar derivative. We therefore measured concentration changes \\:hen 2,3,4,j,6-penta-0-acetyl-~-glucose diethyl dithioacetal (Va) \\.as converted into 1,2,3,4,5,6-hexa-0-acetyl-D-glucose S-ethyl monothioacetal (VIa). To compare the rate of acetoxy substitution of an acyclic sugar urith that of a pyranose,
[31 Va - L71a (a: + p)
\'Ia has been prepared with 14C-acetoxy a t C1 and reaction [4] follo\ved by measuring the loss of 14C from the substrate. The experiinental conditions for reactions [3] and [4] \\-ere
H Oflc* H OXc
\C/ + rZcOH + 'C/ + -;\c*OH / \
I< S C J I , / \
l i SC2I-I,
a:-VIa V I a (a: + P )
those previously used to obtain data for a comparison ol inversion and substitution rates of pyranose pentaacetates. Lemieux et al. ( 5 ) demonstrated, by measuring 14C-acetoxy exchange of pentaacetates, that substitution rate constants inay be much larger than inver- sion rate constants.
KO studies coillparable to those on the hydrolysis of oxygen acetals (6-9) have been reported on the hydrolysis of sulfur acetals. I-Iydrolpsis rates of many a-halo thioethers (10-12) have, ho\vever, been i~~easured. Bord\\:ell et al. (12) gave convincing evidence that the rate-determining step for the solvolysis of a-halo thioethers is the forination of a
\ + sulfonium ion ( C--SR) by a unimolecular ionization analogous to the formation of the / - \ oxoniu~n ion ( c?-OR) \I-hich Keu-th and I3hillips (13) proposed to explain the solvol- / -
ysis of a-haloethers. Dissociation of an acetal conjugate acid to give the above oxonium ion is the rate-deter~nining step \\-hen acetals are hydrolyzed by acids (6-9). Based on the similar behavior of the a-halo derivatives and the experimental observatioil that thio- acetals are hydrolyzed under the same conditions as oxygen acetals, we believe that the rate-determining step for the substitutioil of our substrates is a first-order dissociation of the substrate conjugate acid to give a sulfoniun~ ion.
The conjugate acids of the dithioacetal (V) and inonothioacetal (VI) give the same sulfonium ion by the mechanism proposed. The former \\ill be used to illustrate the steps silo\\ n in eqs. [3] to [7] (R = AcOCH2-(CFIOAc)4-). Both substrates have an acetoxy group in a position to give anchimeric assistance, but \\-e \\-ill limit our exaillple to the cationic species \\-ithout neighboring acetoxy particip a t ' lon. C
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KURIIIARA A S l ) PAISTICR: SUBSTITUTIOS O F AC1;TAIS
Since a new asymmetric carbon is foi-riled by the s~~bst i tut ion of the dithioacetal, the product is a pair of diastereomers. Both isoillers (called a and P : the absolute configuration a t C1 is not known) were obtained from three sugar dithioacetals (3, 4). 'The diastereomer composition given by dithioacetals under conditions \\;hereby the monothioacetal product is stable may be different from that given under conditions (such as the presence of per- chloric acid) \\.hicl~ give an equilibrium between the diastereomeric pairs. When, holvever, the substrate is the glucose dithiodiacetal, the product composition a t epimeric equilibrium
is alniost identical with the composition obtained by substitution under conditions \\-liereby the substitution product is stable (3). 'The rate measurement on the glucose dithioacctal is then not complicated bl. consecutive reactions, so that k , + ko can be ignored.
RESULTS
Rased on the steps given for the substitution \\-e liave described, the rate (V is now written as RSCz[-Is) is given by
[s] rate = k[(RSCaH5)f-I+].
Substrate conjugate acid concentration is dependent upon the equilibri~um
11 we considcr that perchloric acicl is completely dissociated in acetic acid,' the concen- tration of substrate conji~gate acid is given by eq. [ I l l .
I317 eq. [I I] the rate constant I\ ill be first order with respect to perchloric acid. Provided that II1 is small, the first-order constant \\-ill varj- as l/[XcOI-I]. The data in 'Table I show that the rate constant is first order \\-it11 respect to acid, as observed \\,lien perchloric acid anomesizcd glucose pentaacetatcs (13) in mixturcs of acetic acid and acetic anlij-dride.
'Koltllolf c171d Billckellsleilz (27) giz'e ex-pcrill~elztal evidence tlzat perchloric acid i s ha l j iolzized ( to iotl p a i ~ s ) in acetic acid , i.e. HCI0.t = AcOH!-'- -ClO.i-. I?1cl~ldillg nlt additional lerln for z~~tdissociatcd p e r c l ~ l o ~ i c acid alzd colasideli~1.g clcet,ic acid a s n diirzer does ?tot lend lo a Irr0i.e z~sejzrl eqzcnlioz thart eq. [ll].
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CANADIAh- JOURh-.AL O F CI-IEMISTRY. VOL. I4. 1966
TABLE I
Rate constants for the co~lversio~l of 0.0806 ll[ dithioacetal (Va) into mo~iothioacetal (VIa) in acetic acid plus 4% acetic anhydride
a t 25"
We have no measure of the relative basic strength of the solvent acetic acid and the substrate. Unless IC1 (eq. [9]) is large, the concentration of AcOI-Iz+ is greater than that of (RSC211j)I-I+ because the concentration of solvent niolecules is in large excess. If the KI[RSC2Hb] term in the denominator (eq. [I I ] ) is sillall coinpared with the [AcOI-I] term, the rate constant should increase when the concentration of acetic acid is reduced by increasing the substrate concentration, and also when part of the acetic acid is replaced by an aprotic solvent. The solubility of the substrate (molecular weight = 496) is great enough to reduce the acetic acid concentration to one-half the concentration a t dilute substrate concentrations. Concentrated solutions become so colored soon after the addition of perchloric acid that the reaction cannot be followed polarinietrically. The rate was measured a t different conceiltrations of acetic acid by replacing part of the acetic acid ~yith metliylene chloride. Qualitatively, the rate constant (Table 11) increased as required by eq. [I l l , provided that the KI[RSC21-Is] term can be neglected.
TABLE I1
Rate constants for the conversion of dithioacetal (Va) into 1-acetosp monotl~ioacetal (VIa) in l n i s t ~ ~ r e s of acetlc acid and methylene chloride a t 25'
k/[I-I C1o.l] AcOI3
(70 by volume) [H ClO.,] (46) hobs. ( I I ~ ~ I I - ~ ) Observed Calculated
XOTB: Tlic substrate concentration was 0.31 .)I, The acetic acid contained n small amount of acetic an- hydride to ensure the absence of water.
While exploring synthetic procedures for tlie preparation of poly-0-acetyl 1-acetoxy-S- ethyl monotliioacetals of sugars from the diethyl dithioacetals, we observed that tlie substitution rate was faster in acetic acid -acetic anhydride (equal volullle mixtures) than in acetic acid alone. To determine lvhether the rate \\-as influenced by solvent com- position in the same way as anornerization (13) of glucose pentaacetates (also a substitu- tion process), we ~lleasured the rate in iilixtures of the tn-o solve~lts (Table 111).
.A plot oi sonic of these rate constants and anomerization rate constants measured in tlie same solve~lts sho~vs ho\v much the relative iliagnitude of the rates is illfluenccd by the ratio of acetic acid to acetic anhydride.
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I;UIIIII.lIL\ .lSD PAINTER: SUBSTITUTIOS OF ACETALS
TABLE I11 IZarc coli,LaliL, ior lie coiivcrsio~i of (!.OSOG .1! dirhiwilcetal (Va) i~ i ro 1-accrosy
mo~~orhioaccral (VIa) in aceric a c ~ d - acetlc anhytlritle rnisturcs ar 25"
Ac20 (% by volume) [I<CIO,] (A[) kobu. (min-I) kob,./[I-IC1041
Rate constants (averages of two or more ~neasurements) for the substitution of V a in acetic acid plus 4y0 acetic anhydride with 0.0083 114 perchloric acid a t each of three temperatures are as follows.
Temperature 15" 25' 35" kabs. (min-I) 4.84X10-3 1.50X10-2 3.49X10-2
These data give: AI-I+ = 16.6 1.3 ltcal/mole ; AS* = - 10.5 4.4 e.u. First-order rate constants for the substitution of the acetoxy group of 1,2,3,4,5,6-
hexa-0-acetyl-D-glucose l-14C-acetoxy-S-etl~yl nlonothioacetal (reaction [4]) are given in Table IV.
TABLE IV Rate c o n s t a ~ ~ t s for the acid-catalyzed acetoxy exchange of monothioacetal (a-VIa) in acetic acid and acetic
anhydride a t 25"
- 1 ~ 2 0 (% by volume) [Substrate] (M) [ H c l o . ~ ] ( M ) ka~,a. (min-') kob,./[HC1O 11
4 0.093 2.04X 4,29XlO-? 210 50 0.081 2.40X10-i 1.39 X 10-I 503
DISCUSSION
Provided that the K1[RSC21-Is] term in eq. [ I l l is small compared \\-it11 the [AcOII] t c r~n , the calculated rate constants will be first order with respect to perchloric acid and \\-ill vary as l/[XcOI-I]. The rate constant for the substitution of the dithioacetal is first order ni th respect to acid in all solvent mixtures tested. Replacing part of the acetic acid u it11 the non-basic solvent methylene chloride produces an increase in the rate constant 11 hich follows eq. [ I l l until about one-half the solvent volume is non-basic solvent. At higher volumc fractions of non-basic solvent, the rate constants become progressively larger than predicted by eq. [I]]. The effect of lnethylelle chloride on the rate constant is almost identical with that observed when the reaction is the substitution of the acetoxy group of glucose pentaacetate (15).
Replacing a given volume of acetic acid by acetic anhydride resulted in a greater rate increase than replacing the same volume by metllylene chloride. This result is surprising. Even though K z > K l , acetic anhydride must be a base in our solutions; if it is a very \veal<
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CANADIAN JOURNAL O F CHEMISTRY. VOL. 44, l D G G
E ACETIC ANHYDRIDE BY VOLUME
FIG. 1. Effect of solvent cornpositiorl on the acetolysis rates of V a (0) and glucose pentaacetate (0).
base, eq. [ l l ] should be obeyed. The rate constants calculated from the experimental data increased much faster mlleil tlie solvent fraction of acetic anhydride increased than was predicted by eq. [I]].
The data plotted in Fig. 1 sho~v that the substitution of the dithioacetal increases much faster than the substitutioil of the pyranosyl acetoxy as the ratio of acetic anhydride to acetic acid increases. The rate constant increases faster than a measured acidity function (HO) (1G) in the solvent mixture, and the rate constant for dithioacetal substitution, u~llike anomerization, reaches a maximum near 90% acetic anhydride. At this solvent com- position, acetic acid (in acetic anhydride) is almost co1npletelj7 dissociated to inonoiller (16). Apparently the ratio o f f substrate conjugate acid to f* becomes larger (at higher acetic anhydride concentration) when the substrate is the dithioacetal than when the substrate is glucose pentaacetate. One difference in the two reactions should be noted: acetoxy, p res~~mably from acetic acid, is consumed when thioacetals are substituted but not when acetoxy substitutes for acetoxy in the anomerization step. With the solvent composition where the rate constant begins to decrease, acetic acid should not be limiting because the ratio ol acetic acid to substrate is approxinzately 23.
Since the rate of acetoxy substitution of fl-glucose pentaacetate is larger than the
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GUKlIl.\K.\ :\ND P A l S Tblc. SUBSTlTUTlOS O F .\CET-\I,S 177'3
anomerization rate (based on experimental data (5, 17) the factor is \\,ithill the range 11.4 to 15.5), the differences bet~veen the rate constants for the t\vo substrates plotted in Fig. 1 are larger than the differences bet\\-een the substit~ition rate constants. At concentrations of acetic anhydride greater than 50%, the relative substitution rates of the t \ \o substrates are uncertain because 14C-acetoxy exchange has not been measured for glucose penta- acetate in solutions which have acetic anhydride as the major component.
The available data do not perinit an unqualified decision about which substrate, the one giving the oxoni~~nl ion or the one giving the sulfonium ion, \\rill be substituted by the faster rate. Solvolysis of a-haloethers indicates that oxygen is the better electron donor: the oxonium cation is inore stable than the sulfoni~in~ cation. Relative solvolysis rates (10, 11) measured in dioxane-\\rater were: a-chloromethyl ether/a-chloro-S-methyl ether =
1-2 X lo4. The difference in the n~ethanolysis rate of a-haloethers \\-it11 oxygen or sulfur in a pyranose ring (1s) was i~luch less: 2,3,4-tri-0-acetyl-a-xylopyranosyl bromide/2,3,4- tri-0-acetyl-a-xylothiopyranosyl bronlide = 40.
A comparison of the rate constants for the acid-catalyzed substitution of oxygen I I
acetals \\-it11 those for acetals 11-hich have both sulfur and oxygen (-S-C-0-) reveals I
data \\.hich places in doubt the relative donor capacity of sulfur and oxygen. I-Iorton ancl I-Iutson (19) state that "1-thioglycosides are inore resistant to acid hydrolysis than their glycoside analogs". i\/Iethyl and ethyl oxygen xylosides and glucosides \lrere hydrolyzed only 2-3 tiines faster than their sulfur analogues (IS, 20). When, however, sulfur \\.as in the pyranose ring, the acetal \\;as substituted faster than when oxygen \\;as in the ring. A'lethyl P-xylothiopyranoside \vas hydrolyzed nearly 30 times faster (by acid catalysis) than inethyl P-xylop~~ranoside (IS). The Lelvis acid aluminiuill chloride cleaved a C-0 bond of dioxolanes but not a C-S bond of dithiolanes (21).
The data in 'I'able V summarize the acid-catalyzed substit~ition rate constants of di- and mono-acetal substrates in solutions of acetic acid and acetic anhydride. The sub- strates are poly-0-acetyl derivatives of glucose (both acyclic and pyranose), and in all cases an acetoxy group from the solvent substitutes for one of the groups bonded to the anoineric carbon. To aid the comparison, some of the rate constants for substitution in the 1: 1 solvent mixture have been recorded as the value estimated, had perchloric acid been the c a t a l y ~ t . ~
'The data in Table V show that, \\-hen measured in equal voluillcs of acetic acid and acetic anhydride, acetoxy bonded to C1 was substituted 36 times faster than methoxyl when oxygen in a pyranose ring \\-as the electron donor. Acetoxy was substituted only 4 times faster than ethylthio when sulfur bonded to C1 in the acyclic substrate \\7as the electron donor. When measured in acetic acid with 4% acetic anhydride, acetoxy \vas substituted 116 tiines faster than ethylthio. I t is teinpting to say that acetoxy is the better leaving group (as acetic acid), but the concentration of substrate coiljugate acids
I 0 [-Y-C-XIH+, \\.here Y = 0 or S and X = CI-130, C21-15S, or CI-I3C0, is dependent
I upon equilibria \\re cannot measure.
The data (Table V) she\\, that, when the leaving group was the same, acyclic derivatives were substituted faster (about 190 times) than pyranose derivatives. Rate differences
2Botlt szlbstitutio?t and i?u:ersion rate constants ltazle bee?? calcl~lated for tlte sz~lfzlric acid calalyzcd reactions of glzlcose pentaacetntes zolten ~neaszlred i n tlte 1:1 sohelrf (17). Int~crszon rate co?tsta?tts Jbr llte snitre substrate haea been calcztlnted froiiz n zeas~rre i~~en l s w i th boll^. szrlf~rric clmd pcrchloric acids ,i?t nz ix t~lres of acetic acid ajzd acetic anllydridc (15). For the 1:l ~ ~ t i . ~ t i ~ r e k,b,./[I-ICIO.I] = S.~~,I,~./ /H?SO.II.
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Acid-catalyzed substitution of di- and mono-acetals in acetic acid and acetic anhydride solutions
kohs . (min-')/[acid] (d l ) 0 Group >
substituted % Ac2O Calculated z Substrate by acetoxy by volu~ne Catalyst Experi~nental for 11CI04 Reference s
0 z @-Glucose pentaacetate CI-I3CO 0 I-Ips04 0. lo!) 17 u
0 2,3,4,5,6-Penta-0-ncetyl-~-&cose diethyl C
dithioacetal C2I-1,s 4 IlClO4 1 .S1 1.81. $1 'l'h is worl; 1,2,3,4,5,6-hexa-0-acetyl-D-glucose S-ethyl 0 >
monothioacetal CH3CO 4 HCIO4 210 210 This worl; r
0 0 %
@-Glucose pentaacetate CISJCO 50 I-IS04 O.8G5 3.03* 17 n n T -
@-Glucose pentaacetate CI-I~CO 50 1-1 zSOa 0.87 3.05" 5 m 0
z - @-Glucose pentaacetate CI-I~CO 50 HCIO, 3.19 3.19t 3
n $1 V
CM3CO .":
or-Glucose pentaacetate 50 IIzS04 0.0102 0.0353* 5 n S
CIS~CO V
or-Glucose pentaacetate 50 I-I~SOI 0.0084 0.0204" 17 .r i\/Iethyl2,3,4,6-tetra-O-acetyl-@-gI~1coside CHIO 50 HzSOa 0.024 22 6-
CI-I 3 0 50 HzSOr 22 6
Methyl 2,3,4,G-tetra-O-acetyl-or-gI~1coside 0.015 + 2,3,4,5,6-Penta-0-acetyl-D-glucose diethyl w
CzI-IsS 50 IlClOr 130 0
dithioacetal 130 'This work a
1,2,3,4,5,6-Hexa-0-acetal-D-glucose S-ethyl 0 monothioacetal CH3CO 50 IlClO4 563 563 This work
*3.5lr,~~./[I-I?S011. tAnornerization rate constant for M HClOl X 14C-acetoxy excl~a~~ge/in\~ersionrate in 1 :1 soloe~lt. C
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ICURIIIAR.~ ASD P.\ISTEK: SUBSTITUTIOS OF .ACETXLS 1751
caused bj- the relative conjugate acid conceiltrations of these substrates seem to be unliliely. The differences are not those expected if the relative rates are solely dependent upon oxygen or sulfur as electron donors. We attribute the rate constant differences to steric factors in the step leading to the cationic intermediates VIII and IX. To attain the
planar carbonium ion VIII requires eclipsiilg of more bulky groups (~vhich are staggered in the substrate conforiller of lowest energy) than is required to form IX. The potential energy difference (ground state -+ carbonium ion) caused by steric factors must be less for our acyclic substrates than it is for pyranose substrates. The activation energy (E,) is smaller when the reaction is the substitution of glucose dithioacetal by acetoxy than when the reactioil is the substitution of glucose pentaacetate by acetoxy (23, 24). The activation energy for the hydrolysis of thioglycosides (20) is slightly larger than that for oxygen glycosides.
In case the substitution a t C1 is anchimerically assisted, a conforination with the acetoxy group a t Cz t r a m to the group substituted (X in X) is energetically favored when the substrate is an acyclic derivative (V or VI). When, however, the substrate is a 2,3,4,6- tetra-0-acetyl /3-glucopyranose derivative, the conformer with the group a t C1 trans- diaxial to the acetoxv group a t Cz has all polar groups axial, so that this conforiller is far less stable than the conformer (the major species) which has all polar groups equatorial.
EXPERIMENTAL
;Icetic acid was purified by partial freezing, and displacing the melt with dry nitrogen. This step was repeated 3 tinles on the solid. Acetic anhydride (99.670 pure, a s determined by the supplier) was purified in the same way to remove the small amou~i t of acetic acid.
Perchloric acid in acetic acid or acetic anhydride was prepared by dissolving silver perchiorate (dried a t 110 "C) in the solvent and by gassing the solution with dry hydrogen chloride to precipitate silver chloride. Excess 113-drogen chloride was removed by a stream of dry nitrogen. The perchloric acid concentration was measured by titration with potassium acid phthalate (25).
'The dithioacetal substrate was dissolved in solvents with the coinpositions listed in the tables, and the flasks containing the solutions were placed in a co~lstant-temperature bath. When the bath temperature was reached, a measured volume of perchloric acid in acetic acid was added and the solution poured into jaclieted polariilletcr tubes held to \\-ithill f 0.1" by circulating water from the consta~lt-teinperature bath. Rotation uras rneasiired until equilibrium was reached. Rate constailts were calculated fro111 the equation
1 , 2 , ~ , ~ , 5 , C ; - H e r a - O - a c e t ~ ~ ~ - ~ - & c o ~ e l-llC-Acetory-S-elizyl ll/lanotizioacetal 'I'he preparation of a-1,2,3,4,5,6-hexa-0-acetyl-D-glucose S-ethyl monothioaceta1 (Via) froin the dithio-
acetal (Vu) by a modification of the method of ii'olfrom et al. (14) has been described (3, 4). The source of 14C-acetosy used to label Vla was acetic acid-1-I.T obtained by distilling the solverit from a
solution of sodium acetate (0.41 g containing 1 mcurie of 14C) in 100 cc of acetic acid plus 5y0 acetic anh>.dride. 'The 14C-acetoxy group was incorporated by a n exchange reaction with unlabeled substrate (VIa). VIa
(6 g) was dissolved in 20 cc of acetic acid-l-'.'C which was 4y0 in acetic anhydride, perchloric acid was added to give a concentration of 2.44 X lop4 i l f , and the reaction mixture was allowed to stand for 48 h a t 24'. The reaction was the11 quenched by neutralizing the perchloric acid with anhydrous sodium acetate. The excess acetic acid was removed in nacrco, the resulting solid material was extracted with 100 cc of hot methyl- enc chloride, and the solution was filtered to remove suspended sodium acetate. Removal of the solvent a t reduced pressure gave a white crystalline residue. Two recrystallizatio~~s from %yo ethanol yielded 3.04 g, 111.p. 103-104', of labelled Vla.
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1782 CAKXDIAS JOURNAL OF CIIliMISTRY. VOL. 41, 1966
Kinetics of Ace1o.l-y Erclza?zye One gram of labeled VIa was dissolved in each of the solvents listed in 'Table IV. These solutions \\rere
placed in a constant- ten~perat~~re bath kept a t 25 f 0.1". ISerchloric acid catalyst was added until the con- ce~~ t ra t ion given in Table IV was reached, and a t 5 inin intervals 5 cc aliquots were removed and q u e ~ ~ c h e d in 5 cc of acetic acid saturated with sodium acetate. 'The acetic acid in each sanlple was removed hz vaclio and the resulting solid was extracted with 30 cc of chloroform. The chloroform estract was urashed 3 times with 30 cc portions of water. Crystalline material was obtained after final rcnloval of the chlorofor~n a t reduced pressure. This material was assayed by the technique of liquid scilltillation counting in a Pacl;ard Tri-Carb liquid scintillation spectrometer.
The scii~tillation fluid consisted of 60 g of naphthalene, 4 g PPO (L,5-diphenyloxazole) (scintillatio~~ grade), 0.2 g POPOP (1,4-bis-2-(5-phenyloxazolyl)-benze11e) (scintillation grade), 20 cc ethylene glycol, and 100 cc methanol made up to a volume of 1 1 with dioxane (26). The samples assayed were each 0.1000 g i ~ l ~ d were dissolved in 20 cc of the scintillation fluid. Low-potassium vials were used. The experimental data for a run ill acetic acid and first-order rate constants calculated a t the time intervals listed are given in Table \'I.
Acid-catalyzed loss of '"C activity from C1-1:tbelecl VI in acetic acid
Activity Time (min) (mcurie/mole) 102k,t,,. (min-')
'The first-orcler rate collstants recorded in Table IV \\,ere estimated from the slope of the line obtained by plotting log (at - a,), whereol = activity, against time.
T o be confident that the exchange is specific for CL-OAc, we dissolved glucose heptaacetate in a solution containing acetic acid-1-'"C and added perchloric acid (2 X 151). 'The count of the heptaacetate isolated \\.as 64 c.p.nl./O.l g (count of blank was 41 c.p.m./O.l g). -% satnplc of S-ethyl monothioacetal treated in the same \\ray save 10 635 c.p.m./O.l g-.
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