JOURNAL
`
`0P
`
`THE CHEMICAL SOCIETY
`
`TRANSACTIONS
`
`IL
`
`ommfttu of uhtftaliEn
`BiwwN LL
`Ltv MD YRS
`IL
`RLMsAY CflLL
`IUU3
`F.KS
`DVN8TAL MA K8
`Scorr
`THORP CJ3 LLD FItS
`Wru1uAt
`Wy flSc KRS
`Tirigw DSc F.RS
`LAND LL.ft LItS
`IL McLri LIL8
`Mui DM U4.D KKS
`
`Sir
`
`tnr
`MokaN DSe
`
`GaurAwAy
`
`1903
`
`VoL LIIL
`
`OURNEY
`
`LONDON
`JACKSON 10 PAPZRNOSTR ROW
`1903
`
`Breckenridge Exhibit 1011
`Breckenridge v. Research Corporation Technologies, Inc.
`
`

`
`PURDIE AND IRVINE
`
`TIlE ALKYLATLON OF SUGARS
`
`1021
`
`proportion of nitrous acid or nitrogen peroxide by means of
`phenylcnediamine reaction doubtless
`to some
`owing
`secondary
`reaction
`
`the
`
`$urnmary
`
`Nitric acid of 96 per cent and sulphuric acid of 98 per cent con
`centration show definitely marked characteristics analogous alihough
`cases strictly parallel as regards certain properties more
`nob in all
`especially density contraction and electrical conductivity also in the
`by ourselves and
`case of the former refractive indices as investigated
`the latter chemical
`in the case of
`reactivity boiling point vapour
`pressure and to
`less degree viscosity and capilla.rity as investigated
`by Knietzsch
`The precise constitution of acids having these critical concentrations
`remains at prose ut matter for further inquiry
`
`J.The Alkylation of Sugars
`By TixolAs Puiwi FR.S and Jns
`IRVINE Ph.D D.Sc
`researches on the synthesis of glucosidos
`Ii
`the course of
`the earlier
`frequently made to prepare alkyl ethers of
`attempts were no doubt
`the sugars Berthelot Awi CF4m Phy 1860
`80 103 by
`heating cane sugar with caustic potash and ethyl bromide obtained
`substance which he describes as
`diethyiglucosan ether Practically
`the only methods of alkylating sugars at present known
`however
`are those of Fischer Ber 1803 20 2400 1805 28 1145 and of
`Koenigs and Knorr Ber 1901 34 957 in the former process
`the
`on the sugar in
`alkylation is effected by the direct action of alcohol
`is duo to the
`the presence of hydrochloric acid whilst
`the latter
`the acetohalogen or acetonitro4leriv-
`and
`interaction
`of
`alcohol
`removal of
`ative and subsequent
`the acetyl groups by hydrolysis
`with alkali By these methods as is well known only one of
`the
`is etherified and the products are of
`carbinol groups of
`the sugar
`glucosidic nature Alkyl ethers of
`sense
`the sugars in the stricter
`of the term that is to say ethers which retain the aldehydie or ketonic
`the parent sugar and resist the action of hydrolysing
`properties
`of
`The main purpose of
`agents are however so far unknown
`the
`the preparation and investigation of corn
`following research was
`potmds of this class
`In alkylating the esters of optically active hydroxy-acids we found
`that the object could be attained when other methods bad failed as in
`the case of malic lactic and tartaric esters Trans 1809 75 163 483
`1901 79 957 and of mandelic esters McKenzieTrans 1899 75 763
`
`

`
`1O2
`
`PLJRDIZ AND IRVINE TflE ALKYLATION 01 8JGARS
`
`iodide and the application of
`by employing dry silver oxide and alkyl
`this method has been much extended since then by
`Lander
`Trans 1903 83 414 and earlier papers
`Provided
`the oxidis
`the silver oxide could be obviated it seemed not im
`ing effect of
`the sugars might lend themselves to this resctioi attd
`probable that
`the above-mentioned cias
`that we might thus obtain alkyl ethers of
`Alkylated
`sugars should be compounds of considerable interest
`completely alkylated hexose such as pentamethyl glucose should be
`in three stable forms
`capable
`of existing like pontaacety1glucose
`Of
`in structure and stereoisomeric
`those two should be glucosidic
`1120
`corresponding with the well4tnown
`penta-acetylglucosos
`and 131 the relations of which as a- and $-derivatives in the sense
`have
`been recently
`of Fischers nomenclature
`of
`the glucosides
`and Knorr bc cit and by Fischer and
`established by Koenigs
`Armstrong Be 1901 34 2885 The third isomeride structurally
`from the other two should possess the properties of an
`different
`ordinary a.ldehyde Among the penta-a.cetylglueoses Tanrets eom
`13 268 melting at 86 probably
`pound BtL Boc chirn 1895
`represents this form although its aldehydie properties do not so far
`appear to have been denitely proved
`In their behaviour
`towards hydrolytic agents however the alkyl
`ated sugars should differ from the corresponding acyl derivatives The
`are readily hydrolysed with production
`of
`the
`penta-acy1
`glucoses
`The pentamethyl glucose of a.ldebydic
`structure on
`parent sugar
`these agents whilst the
`the other hand should resist the action
`of
`corresponding glucosidic isomerides should lose on hydrolysis only one
`It seemed to us
`methyl group and yield
`tetrametbyl glucose otber
`interesting to ascertain how far
`this kind
`sugar derivative of
`Adopting Fischers view of the
`exhibits the properties of an aldose
`the derivative referred to might
`structure of
`the alkyiglucosides
`stable constitution represented by one or other of
`possibly possess
`the following formulie
`CIROCHOMeOHOMeOHOllOllOMoCHOMe
`IL CHOHCHOMeCHOMeCHOHOMeOllOMo
`
`tautonierie and
`or like the parent glucose the substance might be
`Few acyl derivatives of this class
`the functions of both forms
`exhibit
`appeared to have been prepared and on account of their ready hydrolysis
`they would not ho convenient
`further interest
`for investigation
`the above type
`attaches to the tetra-alkyl aldose and ketose ethers of
`It
`improbable that they might lend themselves to the synthesis
`is not
`throw some light
`study of which might
`of alkylatod disaccharides
`on the constitution of the common natural sugars of
`this class
`Although bouzoin Lander be cii and salicylaidebyde
`Irvine
`
`

`
`PUIIDLE AND IRVINE THE ALKYLATION OF SUGARS
`
`1tJ23
`
`by
`
`Trans 1901 79 668 can be ethorified the latter almost quantita
`tvely by means of silver oxide and alkyl
`iodide the method proved
`inapplicable to the reducing sugars When silver oxide was added to
`mixture of glucose dissolved in methyl alcohol and methyl
`iodide
`vigorous reaction ensued and when
`the alkyating
`large excess of
`agent was u.sed
`product soluble in ether but having an acid
`react
`tion was obtained On attempting to distil
`this much decompoititn
`occurred and the only substance isolated was methyl oxalate When
`iodide was employed in
`similar reaction the product was also
`ethyl
`acid and an analysis of
`the silver reidues showed
`that only 45 per
`cent of
`taken was converted
`the silver oxide
`into iudide the
`remainder having been reduced
`The reaction
`to the metallic state
`kn attempt
`complex one
`was evidently
`to alkylate kevulose
`this method was also unsuccessful
`To avoid oxidation it was evidently requisite that
`the aldebydic or
`the sugar should be masked and instead of glucose
`ketonic group of
`therefore we used Iisehers easily accessible methylglucnside Methyl
`iodide was employed throughout our experiments as previous ex
`perience with tartaric esters had shown that
`the slower action of
`the
`the occurrence
`scope for
`iodides gave
`of oxidation which
`higher
`resulted in the production of oxalates in considerable quantity
`The methyiglucoside in methyl alcoholic solution reacted readily with
`found to be
`of silver oxide and was
`iodide in the presence
`methyl
`The product
`nearly proof against the oxidising action of
`the latter
`consisting of mixture of methyl ethers of
`the glucoside was
`neutral viscid syrup soluble in ether having no action on Feblings
`vacuum
`8olution and distilling without decomposition in
`The solu
`bility in organic solvents and the volatility
`these compounds as
`of
`was to be expected increase with the number of the xnothoxyl groups
`in the molecule and it was found possible therefore to isolate
`present
`the main constituent
`This
`the mixture by fractional distillation
`of
`substance which proved to be
`trimethyl methyiglucoside boils at
`187170 under 17 mm pressure and is readily bydrolysed by dilute
`syrup which reduces Feblings solution
`hydrochloric acid giving
`is shown in the succeeding
`that
`three of
`the
`It
`paper
`vigorously
`the hydrolysis the
`four methoxyl groups are retained throughout
`Attempts to obtain
`hydrazone
`t.rimethyl glucose
`product being
`or osazone from this compound having failed evidence
`of
`its aldose
`nature was sought by oxidising it with bromine water according to
`Kilianis method
`The process gave an almost neutral syrup an
`analysis of which after distillation gave
`figures approximating to
`those for trimethyigluconalactono The lactonic nature of
`the compound
`was confirmed by titration with alkali and by the gradual change in
`rotation of
`its solution
`the optical
`As stated above the main product of
`
`the methylation when it
`
`is
`
`

`
`1024
`
`PURDLE AND IRVINE TUE ALKYLATION OF SUOAPS
`
`is
`
`The
`
`carried out
`in methyl alcohol
`trimetbyl methylglncoside
`the terminal primary
`remaining liydroxyl probably that of
`last
`the chain alkylates more slowly than the others
`earbinol group of
`Even when the alkylating agent was used in considerable excess the
`This is
`tetramethyl derivative was produced in very small quantity
`partly due to the fact which is videut
`from the abundant production
`the process that
`in the course of
`of dimethyl ether
`the alkylation
`extends to the solvent alcohol and that much of
`the alkylating agent
`is thus lost Complete alkyla.tion of the glucoside can however be
`the fact
`that
`the trimethyl znethyl
`effected by taking advantage of
`Such
`solution
`glucoside is readily soluble in methyl
`iodide
`tetra
`reacts readily with silver oxide and under
`these
`conditions
`neutral comparatively mobile
`methyl metbylgiucoside
`is obtained as
`17 mu pressure and showing no
`145 under
`liquid boiling at 144
`action on Feblings solntion
`On hydrolysing this compound with dilute hydrochloric acid the
`glucosidic methoxyl only is removed and
`tetramethylated glucose is
`decomposition at 182185 under
`produced which
`distils without
`20 mm pressure and gradually solidifies by recrystallising from warm
`is obtained in long needles melting at 8183 The com
`ligroin it
`pound reduces both Fehlings solution and ammoniacal silver nitrate
`To
`on warming and has undoubtedly
`the structure of an aldose
`from the isameric triniethyl methyl
`indicate this and to distinguish it
`glucosido referred to above it may be named tetrametbyl glucose
`Although the substance reacted with phenylhydrszine attempts to
`procure from it an osazone or crystallised hydrazone were not success
`ful hut evidence of its nature was procured as before by Kilianis
`The product was an acid
`process of oxidising aldoses to aldonic acids
`oil soluble in ether but dissolving completely in water only on heating
`the substance dried at 100 in
`vacuum showed it
`to be
`Analysis of
`This conclusion was confirmed by the
`tetramethyl gluconolactone
`barium salt prepared from it also by its behaviour on
`analysis of
`neutralisation and by the gradual diminution in specific rotation shown
`by its aqueous alcoholic solution
`glucose was obtained as stated by hydrolysing tetra
`Tetramethyl
`methyl a-methylglucoside With the idea of ascertaining whether
`the
`methyl group lost in hydrolysis could be re-introduced by our method
`of alkylation and if so whether
`this would result in the reproduction
`the initial compound or an isomerido the crystalline tetramethyl
`of
`iodide and treated with silver oxide
`glucose was dissolved in methyl
`The product was
`neutral oil distilling without decomposition at
`124127 under mm pressure which after
`months deposited
`crystals melting at 4243 AnalysIs of
`the crystalline substance
`showed it
`reduced ammoniacat
`pontamethylated
`glucose it
`
`to be
`
`

`
`PURDIE AND IRVINE TUE ALKYLATION OF SUGARS
`
`1025
`
`tetranietbyl
`
`silver nitrate but did not
`reduce Fehlings solution even on boiling
`isomeric and not identical with tetra
`is however
`That
`the substance
`character its
`is proved by its crysbafline
`methyl a-inethylglucoside
`lower boiling point and its different optical activity
`Of
`the three
`pentamethyl glucoses alluded to in the introduction it must be either
`fl-methylglucoside or the pentamethyl glucose of aldehydic
`test made with our
`As
`showed
`no
`structure
`first preparations
`action on Fehlings solution after warming with dilute aqueous hydro
`chloric acid we concluded
`the substance was the latter compound
`that
`On repeating the experiment on
`reduc
`second preparation however
`The amount of material at our
`tion of this solution was observed
`disposal being too small for further investigation the structure of
`the
`compound must remain in doubt
`for the present
`Its laworotiatory
`power favours the view that it
`is the /3-glucoside
`Examination of
`the oil which deposited the crystals just described
`showed that
`It
`it probably contained tetramethyl a-methylglucoside
`reduced Fehlings solution only after being hydrolysed and the product
`of hydrolysis yielded minute quantity of crystals which from their
`melting point seemed to be impure tetramethyl glucose
`It appears
`this compound two of
`therefore that by the methylation of
`the three
`peutametbylated
`glucoses are produced
`Adopting Fischers formula for methyiglucoside
`and omitting the
`product of hydrolysis of the tirimethyl derivative the following scheme
`the compounds described
`represents the relations of
`
`C1I2O1JUHOHC1ICHOllCflOMe
`
`aMothy1glueosido
`
`OHOHCHOMe OIFCIlOMe2CIFQMe
`
`Trimethyl amethylglueosidc
`
`CHOMeCHON eOIFOllOMe2O IFOMe
`
`oJ
`
`Tetnunethyl arnethy1glucoside
`
`Cli2OMeOIIOMe 0HOH Ol
`
`Tetramethyl glucose tn Si83
`
`CH2OMeCHOMeCiOllCHOMe2CO2H
`
`Tetramethyigluconic
`
`acid
`
`0112OMe4J11OMe4iH OIFOMe2CO
`
`Tetvtmetbylgluconolaetone
`
`Penta.methylatcd
`
`glucose
`
`tn 4243
`
`

`
`1026
`
`PURIME AND IRViNE T1E ALKYLATON Or SIJOARL
`
`the glucose derivatives de
`With regard to the optical activity of
`scribed in this and the succeeding paper all arc dextrorotatory except
`the abovemeutioned
`glucose which is lievorotatory
`pentamethylated
`The specific rotations recorded later were determined for the most part
`in dilute solution and are therefore
`to con8idcrable experi
`subject
`It must also be stated that
`mental error
`the resuibs obtained in
`the same substance were not concordant
`different preparations
`of
`The figures quoted below however suffice to show that it
`is the methyl
`group in the glucosidic position that chiefly affects the optical activity
`the conversion of glucose into glucoside causing in each case
`great
`increase in the dextrorotation whilst
`the introduction of methyl
`groups to form true ethers whether
`in the glucose or the glucoside
`much less marked effect
`produces
`
`Solvent
`
`52G
`792
`
`157
`50
`1405
`
`Methyiglucoside
`Primethyl methyiglucoside
`
`1120
`CH4O
`O2HCO
`IIO
`C2110
`i.I1
`Tetramethyl methyiglucoside
`The discordant observations of optical activity exhibited more par
`ticularly in different preparations of tri and tetra..methyl ametbyL
`glucosides may be accounted
`itnpuritie as the
`for by the presence of
`fractionation of such viscid liquids was necessarily attended with much
`difficulty or they may be due to partial conversion of
`the compounds
`into isomerides by intramolecular rearrangement during the repeated
`The activity of
`these two substances
`iodide
`treatments with methyl
`was not
`impaired by redistillation
`We have formulated the tn- and tetra-nietbyl glucoses on the basis
`formula commonly used for the parent sugar
`It is
`the aldehydic
`of
`of course probable that
`to tautomerie
`these compounds are sublect
`is worthy of note in this connec
`change like glucose itacli although it
`tion that we obtained no distinct evidence of multirotation in the case
`of either compound We hope to make
`thorough examination of the
`this point of view and in par
`crystalline tetramethyl
`glucose
`-mothyl
`to ascertain whether on hydrolysis tetriunetbyl
`glucoside yields the same compound as the corresponding
`a-glucosldo
`or
`stereoisomenide
`of som interest
`Our
`the
`in support of
`evidence
`results supply
`The
`formula adopted by Fischer
`for his alkylgiucosides
`lao cit.
`this formula has been amply verified by sub
`general correctness of
`sequent research but positive evidence with respect
`to the position
`Fiscbers view
`of
`the ring is still
`the oxygen coupling of
`lacking
`that the oxygen is linked to the y-carbon atom is mainly based on the
`
`lucose..
`
`TriLnetbyl glucosu
`
`Tetrametliyl glucose
`
`ticular
`
`front
`
`

`
`PUItDIE ND flWINE TILE ALKYLATION OF SUGARS
`
`1027
`
`fact that benzoylcarbinol benzoin and glyeolaldehyde Bsr 37 30
`3055 do not yield derivatives of
`gineosidic nature and that the group
`COOJFOH therefore does not suffice for the formation of glucosides
`the ethylene oxide type was up
`The alternative linkage that of
`ported by Marchieweki and hi arguments in favour of
`this formula
`were replied to by Fischer
`Lobry do Bruyn and Ekenstein however
`Ber 1895 28 3078 consider
`that
`the interconversion
`of glucose
`lvutoe and mannose by the action of alkalis lends
`to
`support
`Marchiewekis view The fact that our tetramethylgluconie acid forms
`lactone shows that its one unmethylated carbinol group is that
`in
`the rposition it
`follows necessarily that in the tetramethyl methyl
`glucoside from which the acid was derived and consequently also in
`is the carbon atom which is united
`the parent methylglucoside it
`with the oxygen of
`the ring Fischers formula is thus confirmed
`show that metbyifruetoside behaves
`Preliminary experiments
`like
`glaeoside and yields when completely metbylated
`the corresponding
`syrup boiling without decomposition
`tetrametbyl motbyifructoside
`at 132136 under 10 mm pressure The method of alkylation has
`also been applied satisfactorily to acetone
`rhamnoside
`to
`According
`Fischers formula Bar 1895 28 1150 the substance contains two
`unetherifled secondary carbinot groups By carrying out
`the alkyl
`in acetone and then in methyl
`stion first
`iodide solution the hydroxyl
`of both groups is methylated with the production of dimethyl acetone
`rbamnosido
`The
`substance is an oil of pleasant odour disUlling
`readily at 1l5_I18c under 11 mm pressure The introduction of the
`the sign of
`rotation the compound
`methyl groups changes
`being
`the results obtained with
`detailed description of
`hovorotatory
`later communication
`the fructoside and rhamoside will be given in
`Our method of alkylation can also be applied to bioses
`In the case
`of maltose as was to be expected the reaction is complicated by the
`occurrence of oxidation and we have not been able as yet to isolate
`Cane sugar however
`in
`the products
`pure state
`any of
`gives
`results of some interest
`It was
`to be expected
`that
`this sugar
`owing to the absence of
`in its composition
`free aldehydic groups
`readily to the reaction on the other hand the very
`would lend itself
`slight sohthility of the substance in all solvents in which the process
`The solubility
`can be carried out seemed an insurmountable diilloult.y
`sugar in organic solvents however
`of
`increases as the methylation
`proceeds and we found accordingly
`that by repeated alkylations
`in aqueous methyl alcohol and then in dry alcohol
`syrup
`first
`iodide was produced and the mehylation
`entirely soluble in methyl
`In this manner
`was therefore completed in the latter solvent
`neutral oil was finally obtained which showed
`no action on
`The product of hydrolysis was
`it was hydrolysed
`solution until
`
`

`
`1028
`
`PUIIflLE AND IRVINE TR ALKY1ATLON OF SUOARS
`
`The crystalline
`time partly crystaIlised
`viscid liquid which after
`subtance when purified by recrystallisatiozt from ligroin was recog
`nised by its melting point and by analysis to ho identical with the
`The un
`from glucose
`tetramethyl
`glucose
`previously prepared
`the oil no doubt contains the corresponding
`cryst.allisable portion of
`lawuloso which may possibly be isolated by distiUatiou
`derivative of
`or othorwbe
`Fischer Ber 1893 26 2104 after developing the constitution of
`that
`the alkyiglucosides concludes
`the complex car bohydrates probably
`the formula suggested by
`similar structure Modifying
`Tollens Ber $3 16 923 ho accordingly
`represents the constitu
`tion of cane sugar as follows
`CIIOH CCHOII CJJOHCllCHOll
`
`possess
`
`CIICEOH011OH0HCHOH0112011
`
`and Perkin has recently shown Trans 1902 81 185 that this vluw
`is corroborated by the magnetic rotation of
`the sugar
`The fact just mentioned that uietbylated cane sugar and methyl
`aled methylgiucoside give on hydrolysis the same tetramethyl glucose
`proves that the constitution and linkage of the glucose group of
`the
`This coupled with
`biose is the same as that of
`the simple glucoside
`the evidence given above of
`the constitution of
`glucose
`tetramethyl
`furnishes conclusive evidence at least so far as the glucose half of
`the
`the correctness of Fischers formula
`molecule is concerned of
`
`Trirnet/qil a-MethyljleicosiZe
`
`The a-methylglueoside used was prepared by Fischers method 1oc
`Ci the yield of product obtained in
`165487 being 73 per
`cent of
`the weight of glucose used
`The method of alkylation finally adopted was as follows the dry
`silver oxide mok was added to the mixture of methyl
`iodide 10
`mel dissolved in six to seven times
`mole and metbyiglucoside
`The methyl
`iodide was kept
`its weight of pure methyl alcohol
`in
`the oxide during the process and to obviate precipitation of
`excess of
`the glucoside it was added in several
`instalments each addition being
`The action
`amount
`the oxide
`followed
`by the corresponding
`of
`which was started after each addition by slightly warming the mixture
`then allowed to proceed spontaneously and flually completed
`was
`water-bath under
`by beating for sonic time on
`reflux condenser
`
`

`
`PU1UM AND IttVflE TilE ALKYLATION OV sJQAfl4
`
`1029
`
`The silver
`
`been filtered off and washed with hot
`residues having
`the filtrate was evaporated to dryness and the residual
`methyl alcohol
`syrup was then extracted with ether the alkylated products being thus
`removed
`The
`and any unaltered
`ethereal
`glucoside precipitated
`extract dried with anbydrous
`sodium sulphate and then evaporated
`viscid syrup which was distilled on
`graphite bath under
`left
`The total distillate boiling at 157165 under 14
`reduced pressure
`mm pressure amounted to about half
`the weight of glucoside taken
`167-V 170
`After severa1 fractional distil1ations
`liquid boiling at
`under 17 mm pressure was collected which was analysed with the
`following results
`O1999 gave O3728 002 and 01506 I120 05079 1i837
`OHO requires
`5085
`847 per cent
`
`That the substance was not merely mixture of different alkylated
`that the same liquid oi constant boil
`products is proved by the fact
`ing point was obtained in other experiments when different propor
`and even when
`the a.lkylating agent were
`tions of
`the
`used
`glucoside employed was
`crude syrupy mixture of
`the a- and fl-forms
`In the latter preparation
`better method of
`isolating the product
`was apparently employed because combustions
`of successive distilla
`tions gave the following results
`C5084 ll86L IL C5087 H858
`As the various methylated derivatives
`do not differ very much in
`elementary composition the motboxyl was determined by Zeisois
`method
`04704 gave 14864 Ag 0H5O5013
`L2480 Ag 0II050.04
`O3292
`C6H50200H34 requires 0H0 b254 per cent
`determination of
`the molecular weight of
`the substance by the
`cryoscopic method in aqueous solution gave 209 the calculated value
`being 236
`The substance
`is therefore trimethyl a-niethylglucoside
`When warmed it
`colourless fairly mobile liquid but on cooling it
`viscid syrup which after the lapse of
`becomes
`year shows no sign of
`crystallising The substance has
`slightly sweet taste it
`is soluble
`iU water alcohol and ether and has no action on Fehlings solution
`solution gave
`Observations of
`the specific rotation in alcoholic
`11
`1586 t4 199 hence
`1258
`solution
`1268t
`An
`e.c of this to 15 c.c gave
`obtalnod by diluting
`The quantity of substance
`used in these determinations was too large
`totter result
`is recorded in the succeeding paper
`An observation
`inud higher specilie rotation is recorded in the
`showing
`succeeding paper
`
`is
`
`is
`
`

`
`1030
`
`PURDIE AND IRVINE THE ALKYLATION OF 8UOARS
`
`the pure liquid made at 300
`observation of the specific rotation of
`30/t
`being manipulated gave
`as to admit of
`the substance
`7566l05
`1298
`ll656
`When the alkylating agent
`is used in the proportion given above
`little or no unchanged glucoside is left and the undistilled residues
`and less volatile fractions consist of mono- and di-metbylated deriva
`tives the percentage of carbon in which is raised by repeated alkyl
`ation When
`is used the
`larger proportion of alkylating agent
`It was
`more volatile tetramothyl ether is produced in small quantity
`however extremely difficult
`even by repeated alkylatAon to extend
`the process beyond the trimethyl stage so long as any methyl alcohol
`The further examination of
`was present
`this compound is described
`in the succeeding paper
`
`TetrameL41 aMeh1ucoiü
`On alkylating again some of
`the lower methylated ethers from the
`than methyl
`the use of other solvent
`previous experiments without
`iodide we found that
`the final distilled troduct which was compara
`much lower boiling point than the trimethyl ether
`tively mobile had
`and its composition approximated to that of
`tetraniethyl methyl
`The
`same process was
`therefore
`to the pure
`applied
`glucoside
`trimnethyl ether the following experiment being quoted as an example
`the method employed
`very large ezcess of alkylating agent
`of
`was used the quantities taken being 18 grams of trimethyl ether
`nioL reckoned
`118 grams of methyl
`iodide
`as methylglucoside
`10 mols and 90 grams of dry silver oxide mols The ether was
`the total amount of
`iodide and then half
`dissolved in half
`the oxide
`was added in small quantities the mixture being heated after each
`The action was feeble and when the rest of
`addition
`the alkylating
`material had been similarly added the mixture was heated
`for some
`filtering and
`The
`hours on
`water-bath
`liquid obtained after
`extracting the silver residues with ether was dried with anhydrous
`On distilling
`sodium sulphate and evaporated
`the residual neutral
`oil 10 grams were collected whiob boiled at 144152 under about
`20 mm pressure and fractionation yielded 62 grams boiling steadily
`at 144145 under 17 mm pressure The results of analysis and of the
`methoxyl determination in two different preparations were as follows
`01794 gave 03480 002 and 01426 HO 08290 ll8$3
`0l63 1120 05259 US67
`02144
`04134 002
`06484AgL 011O62ll
`01378
`01822
`O8494 AgL C1i306154
`011O requires 0528O 1J880
`C10 620
`
`01I.O00H requires
`
`

`
`PURDIE AND lRVflE PilE ALICYLATION OF U1AR8
`88 CT1O 81O4
`
`Analysis of
`third preparation gave
`per cent
`
`5245
`
`1031
`
`about
`
`is unnecessary to isolate the tn
`In preparing this compounds
`methyl ether
`The crude syrup containing the latter obtained from
`the alkylation in methyl alcohol solution may be alkylated after drying
`vacuum in methyl iodide solution in the manner described
`by heatingin
`above
`the les volatile fraetion8 are again alkylated the yield is
`If
`the glucosido taken
`per cent of
`colourless neura1 syrupy liquid
`Tetramethyl a-inetbylglucoside
`is soluble in water alcohol acetone
`burning taste it
`possessing
`ether and methyl
`iodide and has no action on Feblings solution
`the specific rotation made on different preparations
`Determinations of
`The
`results as mentioned
`discordant
`in the introduction
`gave
`following observations were made in
`tube
`
`it
`
`is
`
`dciii
`
`In ethyl alcoboL
`
`11
`
`Water
`
`54233
`50O90
`50O5
`
`l386
`14O8
`l363
`
`1278
`1405
`
`The solutions did not exhibit multirotation and the optical activity
`was but slightly altered by redistilling the substance
`The specific rotations of
`the two preparations
`in the form of pure
`liquids were
`7O0 2O/411QO6
`lO5
`128.10
`lO54 77.50 d20/4i1025 14CH3
`The specific rotation of
`the liquid substance is nearly the same as
`is considerably lower
`iu alcoholic solution in aqueous ohution it
`
`T8fra.rn4thyi Glucose
`
`To prepare this subhtance
`is boiled
`tetrametbyl a-methylglucoside
`per cent squeous hydrochloric acid for half an hour and the
`with
`dark coloured solution is then neutralised with sodium hydroxide and
`As evaporation
`of
`the product
`evaporated
`part of
`proceeds
`hydrolysis separates as an oil and must be removed by extraction
`with ether
`The
`on complete evaporation
`residue
`is boiled
`left
`and sodium chloride having
`with alcohol
`been
`the
`filtered off
`The residual syrup is then extracted
`alcoholic liquid is evaporated
`with boiling ether which ieaves the greater portion of
`the colouring
`matter undissolved the ethereal solution to which is added the solution
`containing the above-mentioned oil after being decolonised with animal
`and dried with sodium sulphate is completely evaporated4
`charcoal
`The residue is
`pale yellow oil consisting mainly of
`tetrametbyl
`
`

`
`1O3
`
`PURDIE MU IRVINE TILE ALKYLATLON
`
`OF SUGARS
`
`is
`
`To separate tbese
`glucose and unaltered tetramethyl methylgiucoside
`the mixture may be extracted with boiling ligroin which dissolves the
`In the latter
`it may be distilled
`former or
`case the unaltered
`first after which the thermometer rises
`glucoside ether passes over
`quickly when the
`viscid
`collected
`as
`tetrametbyl
`glucose
`mm pressure and slowly
`liquid boiling at 1S21S5 under
`This less volatile distillate contains1
`crystailising in long needles
`from which
`considerable quantity of uncrystallisable oil
`however
`the crystals have to be separated by means of
`porous tile
`the tile with
`substance
`is obtained
`by extracting
`of
`quantity
`ether evaporating and extracting the residual syrup with boiling
`ligroin When
`in
`rocrystallised from
`this liquid it
`is deposited
`needles melting at 8l83u The
`beautiful
`of
`tufts
`radiating
`compound was 35 per cent of
`the weight
`the recrystaibsed
`yield of
`taken
`of tetramethyl mothylglucoside
`two different preparations and methoxyl deter
`The analysis of
`muination wore made with the following results
`01705 gave 03165 0Q2 and Ql344 1120 CtiO63 I1869
`06137 AgL CI10527O
`Ol537
`U3578 002 and O1460 1120 C5O48 llSi9
`IL cr19s3
`01250 HQO 05092 H862
`Ol612
`03010 003
`847
`5O85
`CIOH0C requires
`06H$02OCll34
`01130 524 per cent
`
`further
`
`requires
`
`bitter
`
`The substance has
`taste and is neutral to litmus it
`is readily
`soluble in all ordinary organic solvents but sparingly so in ligroin
`Fehlings solution is reduced on boiling and ammoniacal silver nitrate
`The
`solution becomes yellow and
`on gently warming
`aqueous
`finally brown on boiling with dilute alkali a.nd with znaphthol
`and
`behaves
`concentrated sulphuric acid Molisch reaction the sub8tance
`like glucose
`Observations of
`
`rotation gave the following results
`the specific
`in alcohol 12 c50083
`783hence
`c5Ol83 8ll hence
`in water
`After 24 hours the obaerved
`this solution rose by
`rotation of
`O22 the specific
`becoming 8300 24 hours later
`rotation
`thus
`the reading appeared to be constant
`Thecompound therefore exhibits
`very slight extent if at all
`the property of multirotation to
`Trimethyl glucose and phenylhydrazine readily interact in molecular
`proportions with the production
`of an oil
`insoluble in water very
`soluble in alcohol ether and benzene
`The substance
`could not be
`made to orytalliso but as indicated below it
`bydr
`
`78.2U
`808
`
`is doubtless
`
`

`
`FURIME AND IRVINE THE ALKYLATION OF SUQARS
`
`1033
`
`When the pure base and
`the niethylated sugar wore mixed in
`slight coloration
`ethereal solution in the proportion indicated only
`ensued which was not much Increased when the solution was heated
`Reaction bad however
`sealed tube
`occurred as the oil
`at
`in
`which was left on evaporating
`the ether after having been washed
`with dilute acetic acid had no action on Fehlings solution When
`the base was added to the sugar derivative
`dilute acetic acid soluti
`of
`in the same proportions as before the latter dissolved at once and tho
`The interaction of
`solution subsequently deposited
`light yellow oil
`minute quantity of
`the substance was evidently complete
`as only
`khough
`phenyihydrazine acetate was found in the aqueous layer
`the oil after having been washed with water had no action whatso
`ever on Fehlings solution oven on boiling yet
`it nevertheless
`that
`contained both the sugar and hydrazine
`residues was proved by the
`positive results obtained on applying the eisel
`test for methoxyl and
`the ordinary test
`for nitrogen
`Attempts to recover
`the methylated
`by decomposing the compound with benzaldehydo or with
`glucose
`behaved
`towards
`fuming hydrochloric acid were unsuceessful
`but
`the latter reagent
`hydrazone as the product of
`like
`once reduced Fehlings solution in the cold
`
`the action at
`
`it
`
`Terarneth2lgiuconic Acid
`
`Tetramethyl glucose is readily converted into this acid by the action
`of bromine water
`The oxidation was carried out according to the
`method of Kiliani and Kleexnann Ber 1884 17 1298 for the pro
`used being
`paration of gluconic acid the quantities of material
`43 grams
`106
`grams of bromine and
`of
`tebramethyl glucose
`215 grams of water
`The bromine was added gradually with frequent
`shaking and after 15 hours the small qusutty of this element
`left was
`boiled off the hydrobromic acid was then removed with silver oxide and
`the dissolved silver by means of sulphuretted hydrogen The residue left
`in order to remove some barium
`on evaporation was dissolved in ether
`salt formed from traces of barium carbonate contained in the silver
`oxide and the ethereal solution after being treated with anhydrous
`sodium su