THE STEREOCHEMISTRY OF THE CATALYTIC HYDROGENATION of compounds containing an a s m e t r ic CARBON ATOM
By TERENCE JOHN HOWARD
A T hesis submitted to the University of London for the Degree of Doctor of Philosophy in th e Faculty of Science
The Organic Research Laboratories, Battersea College of Technology, Sept. i 960 London, S.W .ll. ProQuest Number: 10804653
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ABSTRACT OF THESIS
4-Phenyl pen t-3-en-2--one has been prepared by the
reaction of dimethyl cadmium with j3~methylcinnamoyl chloride, and its structure confirmed by a haloform degradation to trans - Q - methylcinnamic acid.
Reduction of the ketone with aluminium isopropoxide
gave (i)-4“Pbenylpent-3-en~2~ol, characterised by the preparation
of the 3J-a-naphthyl and R-4-diphenylyl-carbamates. On catalytic hydrogenation (-)-4“-phenylpent-3-en-2--ol gave a mixture of the two
diastereoisomeric racemates of (-)~4~phenylpentan-2-ol in which a
new centre of asymmetry has been generated at C^. On vapour-phase
chromatography the two racemates separated§ from the chromatogram
the ratio in which they are present has been determined, and hence
the degree of asymmetric synthesis calculated and found to bes
( i ) 50$? (ii) 57$• By oxidation the original centre of asymmetry
at has been removed to yield (~)-4“Pbenylpentan~2-one•
The stereochemistry of the hydrogenation is discussed.
(+) -a-Pinene has been hydrogenated over a Raney
nickel catalyst to give almost exclusively (+)-ci s~pinane, and the
stereochemistry of this hydrogenation is also discussed.
The possibility of purifying (+)-a-pinene by the
technique of progressive freezing has been examined. 3
(-)- (3 -Raphthylmethylcarbinol has been hydrogenated over a platinum oxide c a ta ly s t, and over a ctiv e and s ta b iliz e d Raney nickel catalysts. In all cases a mixture of isomers of 1,2,3,4- tetrabydro-2-ethylnaphthalene and 1,2,3,4-tetrahydro-6-ethylnaphthalene was the exclusive* or predominating, product. In the hydrogenation with a stabilized catalyst a small quantity of a tetrahydro-p - naphthylmethylcarbinol was isolated, and the presence of two isomeric
2-ethyldecalins was also detected.
The hydrogenation of |3-naphthylmethylcarbinyl acetate, and of the methyl ether, produced in each case, exclusively, a mixture of the two isomeric ethyltetralins»
p-Cymene has been acetylated to give a mixture of two acetyl cymenes in which 2-acetyl-p-cymene predominates. Aluminium isopropoxide reduction gave a mixture of two cymyl alcohols, the hydrogenation of which, under various conditions? gave in all cases an isomeric mixture of ethylcymenes, generally as the major product.
With a stabilized Raney nickel catalyst a small quantity of the menthyl alcohols was obtained, and vapour-phase chromatography showed that hydrogenation had produced a mixture of four diasterio- isomeric racemates of the menthyl alcohols, which were present in unequal amounts, indicating that an asymmetric hydrogenation had occurred. The stereochemistry of the hydrogenation is discussed. ACOOWLEDGMEUTS
The work described in this Thesis was carried out in the
Organic Chemistry Research Laboratories of the Battersea
College of Technology under the supervision of Dr. C.L. Arcus.
The author wishes to express his sincere thanks to Dr. Arcus for his constant help and encouragement throughout the work.
Thanks are also due to Dr. J .R. Haresnape and Mr. D.H. Desty of The B ritish Petroleum Company Research Centre9 Sunbury-on-
Thames3 for the use of a vapour-phase chromatograph. PREFACE
The work described in-this Thesis has been divided
into four parts, each dealing with the hydrogenation of a
different compound. Each part is complete in itself and
contains two sections^ in one section the experimental results
are given, and in the other the interpretation of these results is discussed. The whole is preceded by an introductory review of catalytic hydrogenation. 6
C d M T S
Title of Thesis 1
A b stract 2
Acknowle dgmen t s 4
P reface 5
THE MECHANISM AND STEREOCHEMISTRY OP CATALYTIC HYDROGENATION
Introduction 12
Historical Survey 12
Steric Interaction between Substrate and Catalyst 30
Optical Activity and Catalytic Hydrogenation 35
Conclusion 44
PURPOSE OP THE V/ORK 45
PART 1
DISCUSSI0N_0P RESULTS
R eaction Scheme 49
4-Phenylpent-3-en-2-one 49
The geometrical configuration of 4-pbenylpent-3-en~2-one 53
4-Phenylpent-3-en-2-ol 54
The catalytic hydrogenation of 4-pbenylpent-3-en-2-ol 56
The oxidation of 4“Pb©nylpentan-2-ol 58
The stereochemical course of catalytic hydrogenation of
4-phenylpent-3-en-2-ol 59
Conclusion 65 7
Preparation of ethyl bromoacetate 67
Preparation of ethyl p-methylcinnamate ■ 67
Preparation of j3-methylcinnamic acid 69
Preparation of (3-methyl cinnamoyl chloride 70
Preparation of 4-pbenylpent-3-en-2-one 70
4-Phenylpent-3-en-2-one semicarbazone 72
4-Phenylpent-3-en-2-one 2?4~&initrophenylhydrazone 73
Oxidation of 4~pbenylpent-3-en-2-one with
sodium hypochlorite 73
Preparation of 4-pbenylpent-3-en-2-ol 73
l-Methyl-3-phenylbut-2-enyl N-a-naphthylcarbamate 'JS
1-Me thy 1-3-phenyl but-2-enyl N-4-diphenylylcarbamate 76
Preparation of Raney Nickel W-3 catalyst 76
Hydrogenation of 4-pbenylpent--3-en-2-ol I 77
Oxidation of 4-pbenylpentan-2-ol I 79
4-Phenylpentan-2-one semicarbazone 83
Hydrogenation of 4-pbenylpent-3-en-2-ol II 84
Oxidation of 4-pkenylpentan-2-ol II 85
PART 2
DISCUSSI0N_0P RESULTS
(+)-a-Pinene 90
The catalytic hydrogenation of (+)-a-pinene 93
The purification of (+)-a-pinene by progressive freezing 100
Conclusion - 103 8
Greek (+)-a-pinene 104
Hydrogenation of (+)-a-pinene 105
Purification of (+)-a-pinene by progressive freezing 109
PART 3
Introduction to Parts 3 and 4 111
^SCUSSIOE^OP RESCJLTS
The attempted hydrogenation of p-naphthylmethylcarbinol 113
The attempted hydrogenation of p-naphthylmethyl-
carbinyl acetate 116
The attempted hydrogenation of p-naphthylmethyl-
carbinyl methyl ether 117
Further attempted hydrogenations of (3-naphthylmethyl~
c arb in o l 118
Conclusion 120
Preparation of (3-naphthylmethylcarbinol 121
Hydrogenation of j3-naphthylmethylcarbinol
I, Using a stabilized Raney Uickel catalyst 122
Identification of the low-boiling products of hydrogenation 123
1. Examination of the hydrocarbon product 124
2. Examination of the alcoholic product 124
Preparation of (3-naphthylmethylcarbinyl acetate 126
Hydrogenation of (3-naphthylmethylcarbinyl acetate 127 9
Preparation of p-naphthylmethylcarbinyl methyl ether 128
Hydrogenation of (3-naphthylmethylcarbinyl methyl ether 130
Hydrogenation of p-naphthylmethylcarbinol
II. Using an active Raney Uickel W-3 catalyst 132
III. Using Adam’s platinum oxide catalyst 133
PART 4
DISCUSSI0I\r_0P RESULTS
Introduction 137
The preparation of 2-(p-cymyl)methylcarbinol 137
The hydrogenation of the cymyl alcohol 140
The stereochemical course of catalytic hydrogenation of
2-(p-cymyl)methylcarbinol and 6-(m-cymyl)methylcarbinol 142
Further attempted hydrogenations of the cymyl alcohol 145
Conclusion 146
E M m A L
Preparation of 2-methyl-5-isopropylacetophenone 147
Preparation of 2- (p-cymyl)methylcarbinol 148
a-(2-p-Cymyl)ethyl H- 4-diphenylylcarbamate 151
Preparation of 2-(p-cymyl)methylcarbinyl hydrogen phthalate 151
Preparation of 2-(p-cymyl)methylcarbinyl acetate 152
Hydrogenation of 2-(p-cymyl)methylcarbinol
I. Using a stabilized Raney Uickel catalyst 153
a - ( 2~p-llenthyl)ethyl H- 4-diphenylylcarbamate 156 10
Hydrogenation of the cymyl alcohol
II. Using a Raney Hickel ¥-3 catalyst of low activity 156
III. Using an active Raney Uickel W-3 catalyst 158
Vapour-phase chromatography
Experimental conditions 163 GENERAL INTEODUCTI ON
Tlie Mechanism and Stereochemistry of
Catalytic Hydrogenation 12
INTRODUCTION
The use o f a s o lid c a ta ly s t i s e s s e n tia l in many modern industrial syntheses* Without the use of such catalysts many processes would require such extremes of pressure, or temperature, that they would no longer he economically feasible. For this reason the study of heterogeneous reactions has attracted much attention*
Nevertheless knowledge of the mechanisms involved is s till far from complete. This is not surprising when it is .remembered that in a heterogeneous system all the problems associated with a homogeneous reaction are present plus the added problems due to the introduction of a surface.
There is however one heterogeneous system, namely catalytic hydrogenation and the closely allied exchange reaction, for which a mechanism accounting for most observed experimental facts can be postulated. A survey of the work carried out in this field fo llo w s.
HISTORICAL SURVEY
Present-day knowledge of the mechanism of catalytic hydrogenation dates mainly from the work of Farkas, Faikas, and Rideal
(Proc. Roy. Soc., 1934? A? 146? 630). Prior to this date it was generally assumed that catalytic hydrogenation of olefinic linkages simply involved the addition of a molecule of hydrogen across the double bonds this postulate being based on the observation that in such hydrogenations predominantly cis products were obtained. 13
Farkas? Farkas? and Rideal (loc. c it.) suggested? however? that in view of the fact that chemi-adsorbed hydrogen on catalytically active metallic surfaces is in the atomic form? it would seem possible that the reaction was considerably more complex than the simple one postulated. This they attempted to show by investigating the hydrogenation of ethylene with the then recently discovered heavy hydrogen isotope deuterium. They observed that two reactions took places; the expected addition reaction which could be represented as
0 H + D _ v CJI„D0 2 4 2 ^ 2 4 2 as well as a hitherto unobserved exchange reaction
°2E4+B2 ^ ¥ ? + “
H o riu ti, Ogden? and P olanyi (T rans. Faraday S oc.,
1934? 30^ 663.)? stimulated by the discoveiy of an exchange reaction with ethylene? carried out sim ilar woik with benzene and observed that this also underwent an exchange reaction. Horiuti? and Polaryi
(ib id ? I I 65)? using ethylene as their model? suggested a possible mechanism for hydrogenation and exchange. They postulated that in itially ethylene was chemi-adsorbed by opening of the double bond and reaction of the two carbon atoms of the double bond with two suitably positioned Hi atoms in the catalyst. The exchange reaction then took place as follows - ♦ „ i v s H H • \X - H H tf Xv \ y V > \ \ X 'H l- D -HiX •'/ Hi -D MX i V- i '» j< N » » i i X. I I X! ;X \X s ''• // Hi- ; D ~ H i\ D Hi / \ ! x V t A H II t X •X' H H rxt V ' X » i \ - v ‘X H alf hydrogenated state
/ I H D H D ! x X J \/ X H i _v H’ -Hi X V/\ X; ... •X ■ ✓ .< * //A / v » / / ■ !x / H i ,C D- H iX /\ ■ '/; t /\ • \ x H H H H -»X X Final replacement state
Hydrogenation could also "be readily explained hy this mechanism as a side step in the above replacement reaction^ the hydrogenated product being obtained by the attack of a second deuterium atom on the half hydrogenated state. y \ !\" I \ / A ; X ! \ A / /V D »Ni ' A ■D Ml 'C' I X /V * o A * . \ H H »CN/ i -X Half hydrogenated state Final hydrogenated state
It is important to note that an essential feature of this mechanism is that hydrogenation results from the independent approach of two hydrogen atoms. Hie Horiuti and Polanyi mechanism, known as the associative mechanism* owing to the fact that ethylene undergoes associative chemi-adsorption, did not however meet with universal approval.
Farkas, Farkas, and Hi deal @?roc. Roy. Soc.? 1934?
^"9 146s 630) in their in itial paper on the hydrogenation and exchange reactions of deuterium with ethylene had very tentatively suggested that exchange might take place via an adsorbed vinyl . ra d ic a l ' f II Jf- ■H / j/iTilfhTillfmuiJ and that hydrogenation appeared to involve simultaneous addition of two hydrogen atoms from the same hydrogen molecule. 16
Farkas and Farkas in a series of papers,
Trans. Faraday Soc., 1937? 33? 678 . ( l ib id 1937? 33, 827. (2 ib id 1937? 33j 837- (3' J . Amer. Chern. S o c., 1938, _60j 22. (4 ,
further examined the problem and proceeded to elaborate and confirm
their previously expressed views on exchange and hydrogenation.
In their opinion these two reactions were independent of one another
and took place by different mechanisms. The exchange reaction
taking place via dissociative chemi-adsorption of ethylene^i^9 ^ ^ 9
H J H' ^ c ^ C' vH h C2HA -» » / + • 4 ' -r.-rSx-* r.-.rr-.- / //m u mu ill m m D I * iriWm
while hydrogenation involved the simultaneous addition of two
hydrogen, atoms of one catalytically activated hydrogen molecule to
an ethylene molecule in the ,Tadsorption layer”. This postulate was based on the observation that while para-hydrogen, in the absence of ethylene,, would undergo rapid conversion on a Pi or Fi catalyst, this
same conversion wras strongly inhibited in the presence of ethylene although hydrogenation was proceeding. Since para-hydrogen conversion
takes place by dissociation of the molecule, followed by recombination 17
of the atoms so formed, and since this did not occur in the hydrogenation of ethylene, it would appear that the two hydrogen atoms of one molecule are taken up hy ethylene* on the surface of the catalyst, before they have any chance to evaporate and re combine with each other or other atoms*. The simplest explanation for such behaviour is that both atoms of the same molecule are taken up simultaneously by the ethylene.
It is interesting to note that Vavon (Bull. Boc. cliim. France, 192?, 4? 41,? 1253) in one of the earliest suggested mechanisms for hydrogenation had expressed sim ilar views to those of Farkas and Farkas. lie noted that in the hydrogenation of conjugated double bonds by nascent hydrogen, hydrogen readily added
1$4« In catalytic hydrogenation, however, each double bond invariably hydrogenated separately. He explained this by saying that hydrogen in the nascent state consists of atoms, which can attack conjugated double bonds independently, whereas catalytically activated hydrogen consists of deformed molecules, which add as such to double bonds. The same view of catalytic hydrogenation was also expressed by Bourguel (ibid, 1932, 4? 5i? 253)*
According to these mechanisms hydrogenation should result in cis-addition of hydrogen. Thus hydrogenation of cis- an<^ trans-ethylene derivatives should lead to, respectively, rneso and racemic products regardless of whether or not these products are the thermodynamically most stable. 18
Thus in general s-
X I X H Y \/ V,/ C cie-addition 0 II I c H, c /\ S f \ X Y X H Y
ci s-compound meso-product
X Y X H Y X -H .Y \/ V./ C c ois-additiori I! I I c XT c "2 / / \ /' Y X Y H X Y H X
trans-compound racemic-produc t
Bourguel (loc. cit.) pointed out that apparent * trans-addition of hydrogen was probably due to isomerisation taking place on the catalyst subsequent to hydrogenation, and not to in itial trans-addition of hydrogen.
Faikas and Farkas (3) in a survey of the literature showed that the bulk of experimental evidence would support their mechanism of hydrogenation, and that the few apparent exceptions could be accounted for by isomerisations of the type suggested by
Bourguel. Support for their mechanism was derived largely from the work of Ott, Behr and Schroter (Ber., 1928, 61 .j 2124) who showed that ; 10
OH -C-COO*" Pd or Ei 3 If _ Meso-product CEL-C-COO
Ea salt dimethyl maleic acid
CEL-C-COCT Pd o r E i . 3 lf Racemic product O O C -C -C E -j j ■» Ea salt dimethyl fumario acid
CH-.-C-CrH- 3 It 5 Pd or Ei CH^-C-C^H- Meso-product 3 6 5 * cis-dimethyl stilhene
Pd o r Ei Racemic product C6H5- ° - CH3 trans-dimethyl stilhene
von W esseley and Welleha (Ber.., 1941? Z4> TTT) confirmed the work carried out on the two dimethyl-stilhenes and reported two further reactions again in accordance with cis-addition of hydrogen. 20
Pd Racemic product E0'
trans-die tkyl-stilboe strol
■01;
Pd Racemic product MeO
However, Greenhalgh and Polanyi (Trans. Faraday
Soc., 1939? 3£s 520) were quick to point out that the cis-addition observed by Farkas and Farkas was in no way proof of the simultaneous addition of two hydrogen atoms. They showed that the associative mechanism of Horiuti and Polanyi, which involves consecutive addition of two hydrogen atoms, w ill also account, equally satisfactorily, for cis-addition. 21
Rn R_ R. R R, R0 R. R R R_
XC = C y 1 v \ /c-——T-C 2 ^/ 2 h1 V \/2C-**— n c / 2 x X ^ [ I — p ( X Rp i | H d M* ----- Hi--~~ -.Ui*.-.. /////////innm m ji n tuni a H2
\ f 2 H 1 \/ \/ 0 — C I f •H H
It can "be seen that the optical configuration of the half hydrogenated
state is not destroyed hy free rotation about the carbon-carbon axis
and if breaking of the catalyst bond and substitution by hydrogen 1 2 occurs by the same sterj.c mechanism for both H and H , which is the
most reasonable assumption to make, the final product is the
experimentally observed cis-addition product.
A further point in favour of the associative mechanism
is that it will readily explain cis-trans isomerism and double bond migration, which often occur simultaneously with hydrogenation. For
example, the catalytic hydrogenation of ethyl oleate to ethyl stearate
is accompanied by side reactions leading to the formation of isomers
of ethyl oleate, namely the trans isomer ethyl elaidate, and structural isomers in which double bond migration has occurred. Furthermore,
Moore (j. Soc. Chem. Ind., 1919? 38^, 3217) has established that these isomerisations only take place during hydrogenation, and they must,
therefore, be closely associated with this process. Greenhalgh and ... 22
Polanyi showed that these isomerisations could in fact he predicted as logical side reactions in hydrogenation via the associative mechanism. II H H H H i I \ I I \ i y ■CH, GH2
/////////// ///h iti
// H
/ 1 - - h h ffnfi H ! i c — c I H 4Ti Hi7 7 -Mr * * ( U n i in m m u
-H -H
H H H H GH H 2 \ t I 1 C c — c I H H ch ; H Fi*.* Ji* -.--Wi, /(niiiii nf if d ji (iff f u It f! f i /
H ■CH H I 2 \ f C — ! H H ch ; H c is - tr a n s double bond migration isom erism 23
The above isomerisations cannot “be explained
satisfactorily by the dissociative mechanism of Farkas and Farkas
and in view of this inadequacy it would appear difficult to maintain it, particularly since these isomerisations arise as a natural
consequence of the associative mechanism.
Conn and Twigg (P ro c. Hoy. S oc., 1939? .A, 171 9 70)
obtained further evidence for the associative mechanism by investigating the exchange reaction between ethylene and deutero-
ethylene. If the dissociative mechanism is correct the exchange
should occur through dissociation followed by recombination, but if
the associative mechanism is correct no exchange should occur since
the presence of hydrogen is vital for the formation of the half hydrogenated state. No exchange was found to take place thus
confirming the associative mechanism.
The next mechanism to be put forward for catalytic hydrogenation was proposed by Rideal and Twigg (Proc. Roy. Soc.,
1939, A, VJ2j 55) , who favoured a modified form of the associative mechanism. They observed that both exchange and hydrogenation were of the same kinetic order, being of first order with respect to hydrogen pressure, and that the equilibrium ^H3) was inhibited by ethylene indicating that the concentration of chemisorbed atomic hydrogen during reaction was very small. This led them to suggest that in both reactions the in itial rate determining step involved reaction of a Van der Waal*s adsorbed hydrogen molecule 24
with an associatevely adsorbed ethylene molecule. This v/ould produce in the case of hydrogenation a non adsorbed ethane molecule obtained by molecular addition of a Van der Waal’s adsorbed hydrogen molecule.
This hypothesis of molecular addition they considered to be supported by the evidence put forward by Farkas and Farkas ( 3 ) for cis-addition.
Twigg and Rideal (Trans. Faraday Soc., 1940? 36? 533) added further weight to their argument by examining the packing of ethylene molecules on a nickel surface. Their calculations showed that ethylene could pack so closely on a nickel surface that the surface could be completely covered by ethylene so that no sites were left open for the equilibration. This is in agreement with their experimental findings.
The problem as to whether catalytic hydrogenation involves the independent or simultaneous addition of two hydrogen atoms was f in a lly s e t tle d by Twigg (D iscu ss. Faraday S o c., 1950? §j
152). He pointed out that if ethylene is hydrogenated with an equimolar mixture of hydrogen and deuterium the addition of single atoms would produce ethane of composition s
i ch3-ch 3 + J- ch3-c h 2d + i ch2d -c h 2d whereas simultaneous addition of a pair of atoms from one molecule would give a mixture of s
i CH -G H3 + CH2D -C H 2 D
Twigg found the former case to be true, showing unequivocally that addition of hydrogen to a double bond does not 25
take place in a single act3 but that the hydrogen molecule is first
split into atoms which then add one at a time. He proceeded to
suggest a mechanism for hydrogenation which would account for all
the following salient facts.
(i) The order of reaction is identical in exchange and hydrogenation
(ii) The energy of activation for exchange is greater than for hydrogenation.
(iii) Ortho-para conversion and the reaction H9IL 2HD are inhibited by ethylene. ' ^ ^
(iv) Hydrogen is dissociated into atoms before hydrogenation.
The scheme proposed was s~
. ; CH0 - CH„ C2tI4 I 2 I " l / l i i m i i i ch2 ~ c h 2 + .fV _lv ch2d _ c h 2d I 1 CH D ~ - -Hi-* - f yM * I I Hi^ * * •— Hi* -r. i* ///////////// 4
CHD + HD •*> =* *-Hi* •** * *»Ui* f ////////// Ethylene is first adsorbed by opening of the double bond. Adsorption of hydrogen then takes place by reaction of a
Van der Waal’s adsorbed molecule with an adsorbed ethylene molecule.
Since exchange and hydrogenation have different energies of activation this step ( 3 ) cannot be the rate determining one. As both reactions 26
have the same kinetics hoth must proceed from the same adsorbed state and therefore reaction 4 controls exchange and reaction 7 hydrogenation-
Although the above scheme will explain hydrogenation it is necessary to include one further equation to adequately explain the allied exchange reaction. Reactions 3 and 4 would suggest that during exchange between ethylene and deuterium the hydrogen returned to the gas phase has the composition HD* whereas experimentally it is shown to be largely This can only be explained by postulating an additional and faster reaction 5 which virtually suppresses 4«
/l/mnm/ // //"//
Thus 1*2 and not HD will be returned to the gas phase. These steps can be shown to,explain all the features of the exchange and hydrogenation reactions of ethylene.
There remains one final mechanism* the most recent th a t o f Jen k in s and R id eal (J» , 1955? 2490* 2496) to be d isc u sse d .
It differs considerably from that of Twigg in that hydrogenation comes about as a result of collision between a gaseous (i.e. non adsorbed) ethylene molecule and two adsorbed hydrogen atoms. Their work was based on an earlier observation of Beeck* Smith* and Wheeler
(Proc. Roy. Soc.* 1940, A, 177? 62 ) that the ratio of hydrogen to ethylene adsorbed on a Hi surface was 2s1* and who concluded that 27
ethylene was th erefore adsorbed on 4 s i t e s . I t v/as suggested th at ethylene was dissociatively chemisorbed to an acetylenic complex and two chemisorbed hydrogen atoms. CH == CH C2H4 + 4 Nl ^ ITi Hi-— * 2 M , /f (fll/lti Hi However, to explain the hydrogenation Beech (Discuss. Faraday Soc.,
1950 ? 8? 118) found it necessary to assume that some ethylene was also associatevely adsorbed.
Jenkins and Hideal in order to clarify the position regarding the adsorption of ethylene on a Hi surface, and its mode of hydrogenation, carried out a systematic examination cf the behaviour of ethylene, alone, and in the presence of hydrogen, on I surfaces.
Their results indicate that ethylene does not in fact undergo associative adsorption but on the contrary is dissociatively and irreversibly adsorbed to an acetylenic complex and chemisorbed hydrogen. They found that in the final state the surface is 80$ covered by these acetylenic complexes, 10$ by hydrogen on double sites, and 10$ by hydrogen on single sites. They conclude that hydrogenation occurs through reaction between gaseous ethylene and chemisorbed hydrogen on the 10$ of double sites. Adsorption of more hydrogen on the vacated sites w ill then take place permitting further hydrogenation to occur.
The following mechanism is proposed. To explain the fact that in the initial stages of exchange the hydrogen gas leaving the surface is almost pure hydrogen, and not HD as indicated, they suggest that the exchange reaction rate
(reaction 2) is much faster than the rate of desorption 3? so that all the adsorbed deuterium w ill have exchanged with hydrogen (in ethylene) before desorption, thus producing pure Hg.
The introduction of the Rideal mechanism complicates the picture regarding exchange and hydrogenation since, like the
Twigg mechanism, it w ill also explain all the major features associated with these two reactions. However, until a more critical examination of the Rideal mechanism has been made, most workers favour a Twigg type of mechanism in which the olefin, prior to addition of hydrogen, undergoes associative chemisorption on the c a ta ly s t.
The above survey has been restricted solely to a study of ethylene. This is due to the fact that the majority of 29
work carried out on the mechanism of catalytic hydrogenation has
heen done with this system.- The reason for this is that various
■ side reactions, such as double bond shift, which can occur in more
complex systems, cannot occur in ethylene and therefore the basic
hydrogenation reaction is not obscured by other side reactions.
Several other systems have been examined, notably
propylene by Toyama (Rev. Phys. Ghem. Japan, 1940? 14,? 8 6 ), and the
n-butenes by Taylor and JDibeler ( J . Phys. Chem. 1951? 55? 1036).
Their kinetics were shown to be sufficiently similar to that of ethylene
for it to be clear that reaction must take place by a basic mechanism
similar to that postulated for ethylene.
There remains one further point to be clarified.
According to the Twigg mechanism cis-addition of hydrogen may take
place in two ways? e ith e r by ad d ition o f hydrogen atoms to the o le fin
molecule from the side facing the catalyst or to the side facing away
from the.catalyst. Most workers accept the former possibility, and
the results of Blomquist, Liu, and Bohrer (j. Amer. Chem. Soc., 1952,
74? 3643) would support th is view . They found th at both c i s - and
trans-cyclononenes were readily hydrogenated. In the case of cis-
cyclononene (i) both sides of the double bond are equally accessible
and therefore adsorption of the olefin, and addition of hydrogen to
it, may take place from either side. On the contrary in the case of
tra n s-cyclono ne ne ( 11 ) one side of the double bond is completely
blocked by the rest of the ring, and therefore adsorption and addition 30
of hydrogen? can only take place from one side. Since this
adsorbed species adds hydrogen just as readily as the cis-
cyclononene it can only mean that hydrogen is adding to it from
the side facing the catalyst.
H-C H-C
'C-H
ci s-cyclononene trans-cyclononono I II
Steric Interaction between Substrate and Catalyst.
So far little attention has been paid to the part
played by the saturated portion of the molecule on the mode of
adsorption of the olefin. In the case of ethylene only the double bond need be considered, but in any more complex system the effect
of the rest of the molecule on the double bond must also be taken into account. For example in trans-cyclononene? due to the
nblockingM effect of the chain of seven methylene groups, only one
side of the double bond is exposed to the catalyst? and this adsorption
can only take place from one side.
The fact that the groups attached to the trigonal
carbon atoms of the double bond influence the ease of hydrogenation f has been appreciated fo r some tim e, and much work of a q u a lita tiv e 31
nature carried cut. Some of the earliest measurements were made by Lebedev, Kobliansky, and Yakubchik ( showed that compounds of the type HCEtCH^ were hydrogenated more rea d ily than o le fin s o f the type RCH=CHR/', Lagerev, and Abranov ( j . Gen. Chem o, UoS°S.R., 1938, 8_, 1682) and Lag©rev, and Babak ( ib id ., 1937 ? 7,? I66l) examined a series of isomeric olefins of the general formula and observed that the ease of hydrogenation decreased with increasing substitution about the trigonal carbon atoms. n-C0H_-CH=CH-CH-> > (CH0 )0-CH-CH=CH-CIL > CBL - .CH. 3 7 3 / 3 '2 3 / 3 vch ’3 CH. C JI_ CH., 5 V / 3 n-C .H--€H=CH„ > CH^C-CHaCH,,itr _ nrr nrr \ \> \ aC=CH-CH, n nrr nrr \ \ > n C„H u ^nrr~CH=C n / 4 9 2 / 2 / y S 3 / 2 5 N\ CH, CH, CH. j 3 U 3 K azanskii, and Tatevoysan (J . Gen. Chem., U .S .S .R ., 1939? 2j ^458 ) observed a sim ila r decrease when a simple t r i substituted ethylene was successively substituted by larger phenyl groups. ✓ ° * x . ■ / H3 . . . /C6H5 C H ,-C H = C ) CH,-CH=C )CH,-CH=C )C,H,--C&.C 3 y / 3 / 3 \ & 5 y C2H5 C6H5 C6H 5 °6H5 Thus the la rg er, and more numerous, become the substituents around the double bond the slower becomes the rate of 32 hydrogenation- Consequently,, it would appear that these substituents exert a certain hindering effect on the adsorption of the olefin. Linstead, Doering, Davis? Levine, and Whetstone ( j . Amer. Chem* S o c., 1942? 6£? 1895)? ^ exam ination o f the stereochemistry of catalytic hydrogenation of diphenic acid and phenanthrene derivatives, concluded that the adsorption of an organic molecule on a catalyst is affected hy stereochemical considerations* Thus the ease of hydrogenation of large molecules appears to depend mainly on the ability of the molecule to find an area on the catalyst which.has sufficient'size, suitable spacing of the metallic atoms, and s u ffic ie n t fla tn e s s to accommodate i t . The o le f in i s adsorbed on this site in such a way that there is the minimum of hinderanee between the catalyst and substrate, i.e ., that side of the molecule which conforms most closely to a plane becomes adsorbed on the catalyst. Finally cis-addition of hydrogen takes place to the molecule from the side facing the catalyst so that all the hydrogen atoms appear on the same sid e . The concept of catalyst hinderance, introduced by Linstead et al., appears to be a determining factor in many hydrogenations, as shown by the results of Varon, Adkins, Linstead, and o th ers. Vavon (D u ll. Soc. chim ., ( 4 )? 1926, 39,668) found that the hydrogenation of substituted hydroaromatic ketones gave predominantly cj-s-aloohols. 33 0 H-V*OH •R In the ketcne sterio hinderanee can occur "between the catalyst and the group R, and adsorption w ill most readily take place with the group R inclined away from the catalyst, so that the entering hydrogen on C^ takes up the ois-position with respect to that on C^. f Catalyst hinderance can also account for the discovery of Adkins, Waldeland, and Zartman ( 1933? 4234) that substituted diphenyls of the type in which there is restricted rotation about the double bond, w ill not undergo hydrogenation. This can be accounted for by the fact that the molecule, due to its very form, cannot attain a planar configuration, and therefore adsorption and hence hydrogenation are inhibited. Another example of interest is an observation made by Linstead and co-workers on which their hypothesis of catalyst hinderanee is partly based. One-sided addition of hydrogen to the octahydro-phenanthcol I could give rise equally to II or III* Experimentally however only III is obtained? and the simple postulate of one-sided addition is unable to account satisfactorily for this single product. 12 OH OH OH I I I I I I Linstead considers the determining factor here to be one of catalyst hinderance. I can be adsorbed on the catalyst in two ways with the ring A pointing away from the catalyst? or towards it. V I I I In the latter case there w ill obviously be considerable hinderance between substrate molecule and catalyst , and it is reasonable to suppose that the former non hindering configuration ?/ill therefore be preferred. This is what is found experimentally. 35 V Optical Activity and Catalytic Hydrogenation Although optical activity has been widely used as a tool in the study of homogeneous reactions it has "been relatively little applied to heterogeneous systems. I t i s true th at many o p tic a lly a ctiv e compounds have been hydrogenated, but the great majority of these,hydrogenations have been of the type . a h \ * / ;CH C Ef x X where C=X represents any kind of unsaturated linkage. An example of this type of reaction is the hydrogenation hept-l-en-3-ol to give 3-heptanol, with no loss in optical purity. (Kenyon and Snellgrcve J 1925, 127» 1169 -) H E ’ P+ X ^ c4h?-c-ch = CH2 ------c4h 9 - c - c 2h5 CH. OH In such a case it is not the stereochemistry of addition to the double bond which is of importance, but rather the stereochemical consequences of this addition to the other parts of the molecule, and, as such, is of little interest in the field at present under investigation. Hydrogenations which are of particular importance 36 in a stereochemical and mechanistic investigation of catalytic hydrogenation are those resulting in asymmetric syntheses. These are lim ited in number, and? with one exception, r e s u lt in low degrees of asymmetric synthesis. The first partial asymmetric synthesis achieved by catalytic hydrogenation was carried out by Vavon and Jakubowicz (B u ll. See. chim ., 1933? ^3, 1111 )• They hydrogenated, using platinum black as catalyst, optically active esters of trans-S - methylcinnamic acid and obtained in every case, on saponification of the saturated ester, an optically active p-phenylbutyric acid. X- CH-> yCOOR CH3 , CH3 H / P t ^ CgH^-^-CH^-COOR _ ^ C6H5-Cf-CH2~COGH . CA H H H 6 5 An identical reduction to the above had previously been attempted by Cohen and W hitely ( ‘ J ., 1901, 70? 1305) using an aluminium-mercury couple but no asymmetric synthesis was achieved. Lipkin and Stewart (j ■ Amer. Chem.,Soc. 1939? 61, 3295) in a sim ila r experiment to th at of Vavon and Jakubowicz, reduced the hydrocinchonine salt of P-methylannamic acid, using platinum oxide as catalyst, and obtained on acidification of the saturated salt optically active {3 -phenylbutyric acid. An analogous experiment using the hydrocinchonine salt of (3 - (a -naphthyl) cinnamic acid also yielded an optically active saturated acid. In both cases the degree 37 of asymmetric synthesis was 8-9$? which compares with a maximum value of 20$ obtained by Vavon and Jakubowicz.. Lipkin and Stewart (ib id , 1939? 61, 3297) a lso report an asymmetric sy n th esis by reduction of p-methylcinnamic acid with d-glucose in alkaline solution in the presence of Raney nickel. The p-phenylbutyric acid obtained was only slightly optically active and indicated a degree of asymmetric synthesis of about 0. 5$ . Prelog and his co-workers (Bull. Soc. chim., 1956, 937 ) in an attempt to understand the steric course of Grignard addition reactions with optically active a-keto esters have re examined the work o f McKenzie (fo r bibliography, see P relog, H elv. Chim. Acta, 1953, 36, 308) R> R1 R-CO-COgR* RtMgX y R-C~C02R* „__ y R -C -C O g H OH (5h Prelog points out that since the configuration of the optically active alcohols used by McKenzie were not known the steric control exerted by the groups attached to the asymmetric c e n tre s in them could not be ascertained, and hence no conclusions on the steric course of the reactions could be reached. Prelog and his co-workers have therefore repeated McKenzie’s work using optically active alcohols of known configuration. They have found th a t 2 38 (1) The configuration of the resulting a-hydroxy acids was controlled by the steric hinderance of the groups attached to the asymmetric centre in the optically active alcohol nearest to the reacting carbonyl group* (2) In an alcohol ^R^C-OH if R1, R2, and B3 differed considerably in size then the degree of asymmetric synthesis would be high* Thus, by using the symbols L, M, and 3, as proposed by Cram and Elkafez (J . .Amer. Chem. S o c., 1952? 74j 5828 ) to represent the la r g e ? medium, and sm all groups, and assuming th at R’MgX w ill react with the most energetically favoured conformation of the a.-keto e s te r , that i s with the two carbonyl groups in one place and anti to each other, the following scheme was obtained. S R 4 i M-C-OH + HO-OC-CO-R HO-OC-C-OH 4 4 L /h R.! S 0 M ,S 0 \ / C ,„C ^R ^ \a y ^c « ^R 4 4 \r \0 y . \ co y xr ■\0 y \ X / II j t 'v Un * ST> tMn-T &¥ R * ii&A OMgX Attack by R’MgX takes place on the least hindered side, that is on the same side as the group S. Prelog (loc. cit.) has suggested that the rules applying to the above homogeneous process should also be applicable 39 to a catalytic hydrogenation, although this is a heterogeneous process and presents certain additional complexities not encountered in a homogeneous reaction. To verify this suggestion Prelog and Scherrer (Helv# Chim. Acta, 1959? 42? 2227) have hydrogenated a series of optically active esters cf trans-^-methylcinnamic acid, after the manner of Vavon and Jakubowicz, using optically active a lco h o ls o f known c o n fig u ra tio n . I h e ir r e s u lts , given "below, show Prelog’s prediction to he correct. Alcohol Sign $ Asymmetric Synthesis Sign of Product, > H-C-CH, (— ) 4-5 (-) I 3 OH H-C-CH (— ) 7-5 (— ) Mebv. DMe (+)' 13 (+) K.C-C-H (+) 27 (+) OH 40 'Ulus the steric course of the hydrogenation may he represented as S HOOC CH_ I* \ / " i 6 5 M-O-OE + C—C H-C-CH -C00H / \ I . H C.Hr CH. 6 5 V A M S O ISO \ / (I \ / If C O . H • C C ■ H ^ \ / \ / 4 \/\/ If 0 C f —H A, h 0 G ^ H II i C H-— C /\ H,C C fX H0C C X 3 6 5 3 . 6 5 As for the two carbonyl groups in the a-keto esters, the carbonyl group and the double bond in this case are also assumed to be anti to each other in the most energetically favoured conformation, and as before attack* this time by adsorbed hydrogen, takes place on the least hindered side. Occasionally in the heterogeneous process the rules appear to be contradicted. Prelog states that this can be explained by the fact that in the transition state of a catalytic hydrogenation the more remote parts of the optically active alcohol are capable of making a contribution to the steric control of the reaction. This is in contrast to the homogeneous process where only the asymmetric centre in the optically active alcohol nearest to the reacting carbonyl group is responsible for the configuration of the 41 final product. Thus it is the additional contributions in the heterogeneous reaction which are responsible for the apparent deviations from the rule. The low degree of asymmetric synthesis achieved in all the above cases is probably due to the fact that the reacting centre is separated from the asymmetric centre by the -CO-O- grouping. Duveen and Kenyon ( Bull Soc.c'him.? 1940? Mem.? 165) therefore attempted the reduction of an unsaturated linkage adjacent to an asymmetric centres it being reasonable to expect that under such conditions asymmetric induction would be at a maximum? and that therefore a high degree of asymmetric synthesis would be obtained. # H * I *1 * I J CH £ - CH(0H)CH^ Eane^ CH^ *CHicH(OH)CH-, ^ CH^ ^ 0 Hi x 0 0 X I I I I I The reduction of-1 was successfully carried out but all attempts to replace the hydroxyl group in II? so that the degree of asymmetric synthesis might be determined from the optical activity of III? proved unsuccessful. Arcus and Le Ba Loc (Le Ba Loc? Ph. D. Thesis, Lond., 1959) have re-examined the above reaction but attempts to remove the original asymmetric centre? this time by oxidation? again proved unsuccessful due to ring cleavage,.- Arcus and Smyth ( j .? 1955? 34) have however managed to carry out a hydrogenation In which the olofinic linkage is adjacent 42 to the asymmetric centre, and to assess the degree of asymmetric synthesis. This was found to be 7 far higher than that achieved in any other catalytic hydrogenation. C JBL-CH 4 9 j ch (oh )ch . ch (oh )ch . COCH 3 I II III (+)-3“Ethyl-hept-3-en-2-ol I was hydrogenated over Raney nickel to give the saturated alcohol II in which a new asymmetric centre was generated at The original centre of asymmetry at was then removed by oxidation and the resulting 3-ethyl~heptan-2-one III was found to be optically active. This means that addition of hydrogen to the imsaturated alcohol I has taken place from predominantly one side of the olefinic linkage, since were addition to take place with equal ease to either side of the double bond the final product would be optically inactive, and no asymmetric synthesis would have resulted. The authors consider that it is the asymmetric centre at 0^ which controls the mode of adsorption of the unsaturated alcohol on the catalyst so that it is adsorbed in one heavily preferred conformation. Cis- addition of hydrogen to the side of the molecule facing the catalyst therefore results in the alcohol being predominantly hydrogenated from one side. Thus asymmetric adsorption precedes, and leads to, asymmetric addition of hydrogen. It is suggested that this adsorption takes place hy interaction of the lone-pairs of the oxygen atom* as well as the it electrons of the double hond with the catalyst. * Arcus, Cort, Howard, and Le Ba Loc (J., i 960, 1195) have recently reported a further asymmetric hydrogenation of the above types 3-methyl-4-phenylbut-3-en-2-ol,IV, being hydrogenated over Raney Hi to yield a 22$ asymmetric synthesis. Ph CH ' / 3 f H CH(0H)CH'3 IV . . Compared with the previous example the low degree of asymmetric synthesis is somewhat surprising. However, work described in the present Thesis provides a further example of this type of hydrogenation which has yielded a 57 $ asymmetric synthesis. * The work reported here was carried out by Le Ba Loc, being part of a Thesis presented to the University of London for the Ph.D. degree^ the contribution of the present author, relating to the hydrogenation of a-pinene, is described later in the present Thesis. 44 CONCLUSIONS From the foregoing review it can he seen that catalytic hydrogenation is a process of considerable complexity, and that the exact mechanism of the reaction is still not fully understood. However, it is apparent that there are a number of basic features which are almost invariably present in any hydrogenation. These may be summarised as s- (1) Prior to addition of hydrogen both the hydrogen and the unsaturated molecule are adsorbed on the catalyst. ( 2) The mode of a d so rp tio n o f the o le f in i s c o n tro lle d by various steric factors, such as theMndering effect of a large groups in general the adsorption conformation which presents the double bond most closely to a plane being adopted. (3) Addition of hydrogen takes place via the independent approach of two hydrogen atoms? this hydrogen adding ois- to that side of the adsorbed molecule which faces the,catalyst• 45 HJRPQSE OF THE WORK In the preceding review it has "been shown that the majority of asymmetric syntheses achieved "by hydrogenation have been of the following type s Me COOR* Me Me "n. / J* * C * C v Ph-C-CH^-COOR v Ph-C-CH0-C00H / \ Ooat^ * 2 J 2 Ph. H H H However, more recently Arcus and co-workers (J.jl955; 34 and J., i960, 1195) have reported two asymmetric synthesis by hydrogenations of a different type. R1 R2 R2 R2 * H^cat. ^cjR gH Oxid. R1CH 0 ^ ______^ch.-Sh QxiA\ R 1 Gx1 - fa / \ # * 2 I ^ t H CH(0H)le *CH(0H)le COMe In both of the above schemes an asymmetric synthesis is achieved by the hydrogenation of an olefinic linkage, and there is no reported example of an asymmetric synthesis of either type in which the unsaturated centre is other than olefinic. It was therefore decided to attempt an asymmetric hydrogenation of the type reported by Arcus and co-workers, but in which the unsaturated centre was aromatic in character. 46 The two aromatic alcohols used for this investigation were j3 -naphthylmethylcarbinol I, and 2~(P-cymyl) methylcarbinol II. CH (OH )Me I II The hydrogenation of these two alcohols is reported in parts III and IV respectively. In “both of the asymmetric syntheses reported by Arcus and co-workers a new centre of asymmetry was produced at O y i.e. a to the original centre. The hydrogenation of 4-phenylpent- 3-en-2-ol (ill) is now reported in which a new asymmetric centre is generated at Q y (3 to the original centre s i Ph. H Ph X / \ * # .Cb C Sv GH-CH«-CH(0H )Me / V ^ / 2 Me CH(OH)le Me III On vapour-phase chromatography, the two diastereo- isomeric alcohols produced, on hydrogenation separated completely, and the degree of asymmetric synthesis has been determined from the chromatogram (. Part i). The stereochemistry of the hydrogenation is discussed. 47 Vapour-phase chromatography has also heen used to examine the extent of one-sided addition of hydrogen to (-)-a -pinene in the presence of a Raney nickel catalyst ( part II). The stereochemistry of the hydrogenation is discussed* The purification of organic compounds by zone melting or progressive freezing techniques has been reviewed? and the purification of (-f)-a -pinene by progressive freezing examined* PMT 1 Ph. V ^ C=CH-CH(OH)CH3 m/ 49 PISCUSSIOH R eaction Scheme Ph H Ph / \ = 0 N k \ y CH0 COCH. ch 3 3 o 4-Phe nylpent-3-en-2-one 4~Phenylpenta.n-2-one Ph H t Ha V y y — ^ gh - ch 9- ch (oh )ch 3 CH3 gH(OH )0H3 E p/m ^ CH. 4-Phenylpent-3~en-2-ol 4-Phe ny Ipent an-2~o1 4-Pheny lpent-3-en-2-one '4-Phenylpent~3~en~2~one was firs t prepared by Johnson and ICon ( j 1926, 2748) "by "the action of zin c methyl iodide on p - methylcinnamoyl chloride. Since then a number of alternative methods of p re p a ra tio n have been re p o rte d . Howard and Smith ( j . Amer. Chem. Soc., 3-943*6£? 165) have prepared the ketone by pyrolysis of 3-aceto- 4~phenylpyrazoline (i) obtained by reaction between diaaomethane and benaylideneacetone. Ph-CH-C-COCIL I H 4 Ph CH0H PhCH=sCHCOCH. — ^ ^ C = CHCOCH \ 2/ CH. 3 +ch 2h 2 50 A more recent method is that of Martin and Ebrmant (Bull. Soc. chim. France., 1957s 432) who prepared the ketone by hydrolysis of the enolic ether IV* which they had obtained via a series of re actions starting from ethyl viryl ether (il) and a-methyl styryl bromide (III). Ph 0C2H5 \ 0 e CHBr / ch 3 CH, III XI Br,. s k * ' OEt Ph Ph OEt I \ / C « CHMgEr + BrCH C = CH— CH ✓ CH- \ CHgBr CH3 CH^Br a l e ' KOH \ k Ph Ph OEt \ / C = CHCOCH- r4 H2S0, jC « CH* ✓ 3 hyd, / ch 3 CH. CH, IV However? of the various methods available for the preparation of 4-phenylpent~3-en-2-one that of Johnson and Kon is .the simplests it is applicable to large scale preparations and uses readil 3r available starting materials? namely? acetophenone ( v ) and e th y l brcmoacetate (VT). 51 Ph Ph ,^C » 0 + CHgBrCOOEt Zn y C^-C-CH^OOEt VII CH. OH o V VI P°C13 Ph H Ph X / X n C VIII / " \ X CH^ C00H ch 3 S0C12 M/ Ph H Ph H X ✓ X / / J3 « C\ ---- Zn ■ Me. y I C = C ^ ch 3 0001 ch 3 ooch A modified version of the Johnson and Kon method has been used in the present work:. It differs only from the above scheme in that in the final stage the zinc methyl iodide has "been replaced by dimethyl cadmium. Dimethyl cadmium is preferred because of its greater ease of preparation, the appreciably higher yields that it gives, and its lower reactivity towards the carbonyl group. The first step in the synthesis involved the preparation of the hydrozy-ester VII, which was obtained by means of a Reformatsky reaction with acetophenone and ethyl bromoacetate. The crude hydroxy-ester, without purification, was dehydrated with phosphorus oxychloride to the unsaturated ester VIII which on 52 hydrolysis yielded tran s-(3-methylcinnamic acid m.p.99-100°. Stoermer, Grimm, and Laage (Ber., 1917? £0? 959) report for the trans-acid m-p.98#5°# and have shown helow that the isomer with this melting point is unequivocally the trans-compound. The in itial yield of acid from the hydrolysis was somewhat low "because of the formation of a considerable amount of an oily "by-product. Johnson and Kon showed th i s to "be a m ixture o f th e {3Y~acid (p -p h e n y lv in y la c e tic acid), and the els- and trans- [3-methylcinnamic acids. By treatment of the oil with "boiling concentrated alkali a further quantity of the stable trans-3-methylcinnamic acid was obtained owing to the conversion of the less stable acids. The 4~pbenylpent-3~‘en-2~one was finally obtained by the action of dimethyl cadmium on the trans-6-methy 1- cinnamoyl chloride. The ketone was obtained as a yellow oil b.p. 127-130°/l2 mm. n ^ 1.5675 (Howard and Smith report b.p.l32-138°/l7 2*5 o / 20 mm., n ^ I . 5662. Martin and Hormant report b.p. 124 /8 mm., n^ I. 5492). Johnson and Kon isolated the ketone in the form of the semicarbazone and reported for the regenerated ketone b.p.133-136°/l2 mm., which solidified on standing forming large plates m.p. 100°. When attempts were made to ciystallise the yellow oil from the di methyl cadmium preparation, the ketone was deposited as pale yellow needle-like crystals m.p.37.5-38.5°* This melting point and crystal form are identical with those reported by Arcus and co-workers (j*,1960, 1195 ) for 3-methyl-4~phenylbut-3-en-2-one IX. 53 Hi OIL Ph H X S 3 X / . G = G C = Cv / x * x H COCH0 CIL COCH-j 3 3 3 IX X It was therefore feared that during the attempted preparation of X isomerisation had occurred at some stage to give the isomeric ketone IX. However., when a mixed melting point was carried out between the prepared ketone and an authentic sample of IX? the mixture melted immediately the two components were brought together? intimate mixing being unnecessary. Further proof that the prepared ketone ?/as 4-phenylpent~3~en-2~one X was obtained by its oxidation to trans-p - methylcinnamic acid, (see page 73 ) The yield of pure 4~piienylpent-3-en-2-one obtained from the dimethyl cadmium reaction was 50$? which compares fav o u rab ly with the 25$ yield of Johnson and Kon using zinc methyl iodide♦ The geometrical configuration of 4-phenylpent-3-en-2-one Oxidation of 4-pkenylpeni-3-en-2-one with sodium hypochlorite was found to yield P-methylcinnamic acid of m.p.99-100°. p-Methylcinnamic acid exists in two forms? a stable form of m.p. 98 .5°? an^ an unstable form? generally called allo-p - methylcinnamic acid?of m.p, 131.5°.(Stoermer? Grimm and Laage* Ber.? 1917 ? %Qj 959)« The allo-acid may be obtained by exposing the stable acid to ultra-violet light for 10 days? and when shaken with 54 concentrated sulphuric acid at -5° gives 3-methylindone. (Stoermer and Laage* ibid* 981)• CH H \ / .CH. X 3 +H2° COOH » 0 The allo-acid must therefore he the cis-isomer. Thus the p-methylcinnamic acid obtained by the oxidation of 4-pkenylpent-3-en~2-one is the trans-acid9 and the ketone must have the trans-configuration X. COCH. C = C X H 4-Phenylpent--3~en-2-ol 4-Phenylpent~3~en--2-ol was prepared by a Meerwein- Ponndorf-Verley reduction* with aluminium isopropoxide, of the ketone X. This alcohol is a crystalline solid* m.p,63-64°? and gave a H-a-naphthylcarbamate* m,p.96-97°j and a H-4-diphenylylcarbamate m.p.116.5-117°• Each of these compounds behaved as a single entity. The alcohol is concluded to be a single geometrical isomer* and of the trans-configuration (Xl) unaltered from that of the ketone. 55 CH ch (oh )ch . XI < Ph. Attempted vapour- phase chromatography of the alcohol was unsuccessful, owing to its decomposition on the column used. The appearance of two peaks (see Fig. 1, page 75 ) so soon after injection would indicate that the decomposition products are hydro carbons, as o:nygen-containing compounds are held hack by a trito ly l phosphate packing. It is possible that these compounds are trans- and cis_-4~phe]^lpenta-l,3-diene, formed by dehydration of the alcohol accompanied by isomerisation. Ph H X / ✓ 0 - CS . CH3 C&=CH2 ~> ch 3 ch (oh )ch 3 CHaaCH, When the alcohol was subjected to chromatography at 100° no decomposition occurred, but the alcohol was retained so long on the column that no positive trace was obtained. 56 The catalytic hydrogenation of 4-pb.er;ylpent-3"-en~2-ol 4"Pkenylpent-3--en~2-ol was hydrogenated over Raney Mi W-3 catalysts at a maximum temperature of 52°C? and a maximum pressure of 107 atmospheres? to give the saturated alcohol 4“Phenyl- pentan-2-ol h.p.118-119 /10-5 mm.,nt^ 1.5101 (Menitzescu, Gavat? and Gocora? B ar.? 1940? 73B9 233? re p o rt h .p o l2 4 -5 ° /l5 rum.) Theoretically the hydrogenation of (i)-4-phenyIpent- 3-en-2-ol could produce four diastereoisomeric forms of the saturated a lc o h o l. Ph Ph a CH - CH(0H)H© H2//l:?1 -v ^CH-CH2-CH(0H)Me ) (+ ).® .«® *.«o. (+ ) I (+) II ( • (+)...... (-) III )»..o«o..«. ) IV These four forms comprise two diastereoisomeric racemates namely (I + IV) and (II + III)? one of which should predominate over the other if an asymmetric addition of hydrogen has occurred. Vapour-phase chromatography showed the saturated alcohol to he a mixture' of two diastereoisomeric racemates? present in unequal amounts? indicating that an asymmetric hydrogenation had in fact taken place. To determine the degree of asymmetric synthesis 57 it is necessary to know the amount of each, racemate present, sinces- j, . . . ,, Excess of major over minor component „ % Asymmetric synthesis » —““— i -a—— 3 ——— , x 100 ' Total amount of major ana minor components These quantities may he readily calculated hy measuring the areas under the peaks of a vapour phase chromatogram of the alcohol, since for two diastereoisomeric racemates the areas under the peaks w ill he proportional to the amount of each racemate present. Therefores- ^ A , . ,, Area of major component - Area of minor component _ % Asymmetric synthesis » y ---- — —y— ——r—------y-—— — ■ x 100 ' 0 ^ Total area of major + minor components By using the ahove expression the first hydrogenation was found to have given a $0$ asymmetric synthesis- A second hydrogenation, carried out under identical conditions, gave a 57$ asymmetric synthesis. These figures are not the exact degrees of asymmetric synthesis achieved since a partial separation of the diastereoisomeric racemates was accomplished hy distillation. This was shown when the fractions of lowest and of highest hoiling points, obtained hy distillation of the crude alcohol from the first hydrogenation, were subjected to vapour phase chromatography - The low-boiling fraction indicated a 43$ asymmetric synthesis, and the high-boiling fraction a 53$ asymmetric synthesis. The apparent increase in the degree of asymmetric synthesis is due to a larger amount of the higher hoiling racemate being present in the higher hoiling fractions. However, the 58 low-boiling fraction constituted only about 5$ of tbe hydrogenation product, and the high-boiling about 10$, and calculation indicates that the percentage of asymmetric synthesis found for the main f r a c tio n ( 50$) does not deviate by more than 1$ from the correct value. Although a similar detailed chromatographic analysis was not carried out on the product of the second hydrogenation* it is probable that the true degree of asymmetric synthesis in this case also does not differ from that of the main fraction (57$) ^>7 more than 1$. Oxidation of 4~-phenylpentan~2'-ol The final step in the synthesis was the removal of the original centre of asymmetry at by oxidation. The method used was the same as that employed by Arcus and Smyth (J 1955? 34) 'to remove the asymmetric centre at Cg in (-)-3-ethylheptan-2-ol. The alcohol was dissolved in glacial acetic acid* and oxidised at 80° by the addition of chromic anhydride in glacial acetic acid. The ketone was obtained as a yellow liquid b . p . 116- 117 '°/ l 4 mm., n ^ 1 . 5048 , n ^ 1.5091*? semicarbazone m.p. 140-1410. (Colonge and Pichat, Bull. See. 0 him . Prance, 1949? 177 / « report b.p.l09°/ll mm., n ^ 1.5890? semicarbazone m.p.l37°» ITenitzescu and Gavat, Ann., 1935? 519? 260, report b.p.H3-115°/l3 mm., n ^ I . 5124? semicarbazone m.p.137°)° 59 The oxidation of 4-phenylpentan-2-ol9 which vapour-phase chromatography showed to he a mixture of two diastereoisomeric racemates9 should give rise to a single racemio modification of the ketone, as oxidation removes the original centre of asymmetry in the alcoholj and leaves the ketone with only the single induced asymmetric centre at C^. This was confirmed hy vapour phase chromatography which showed there to he a single component present. The stereochemical coarse of catalytic hydrogenation of 4-~phenylpent-3-en~2~olo Cis-addition of hydrogen to (i)-4-phenylpent- 3-en~2-ol (I and II) can give rise to four diastereoisomeric forms of 4“Pke^ lp ett'fca'n-2-ol (ill? IV 9 V9 and VI) s- 60 Me HO H H OH H H IV VI H H Me H H Me Ph Ph ^ Addition of hydrogen from above Me H. Me \ OH HO \ C C = 0 X II \ Ph. \ H Ph A d d itio n of hydrogen from "below i Me 4 Me I HO - H H 4 H - H III V H H - Me Me H Ph Ha The p a ir s ( i l l + v) 9 and (IV + VI) comprise two diastereoisomeric racemates., each racemate "being obtained "by addition of hydrogen to a different side of the double bond. If addition of hydrogen takes place with equal ease to either side of the double bond the two racemates will be obtained in equal amounts* and no asymmetric synthesis w ill result. 61 However, vapour-phase chromatography shows that one racemate predominates over the other to the extent of'3si, and therefore preferential addition to one side of the double bond must have occurred® The first possible explanation for this behaviour is that, because of the hindering effect cf one or more groups in the alcohol, there is steric hinderance between catalyst and substrate such that only one side of the double bond can be presented in a planar conformation to the catalyst® (Such as is the case with a-pinene, see page 99 ) That this explanation does not apply for 4-phenyl- peht-3-en~2-ol is shown by a study of the alcohol molecule with Catalin models, when it can be seen that either side of the double bond can be presented to the catalyst in an equally planar confoimation (A and B)® Ph H Ph. -Me X / / C = C X Me T f tH “ e Me C 0 » / X / \ * . HO ’H H a / NV HO VH A B Thus the dissymmetric addition of hydrogen cannot be due to the blocking of one side of tho double bond. The only 62 other possible explanation is that it is due to the original asymmetric centre at C^9 which must control the mode of adsorption of the alcohol on the catalyst such that one heavily preferred conformation is adsorbed* From examination of A and S it is observed that there is closer crowding of the methyl groups in B than in A? and hence it is probable that A is the preferred adsorption conform ation. Arcus and Smyth ( J . ? 1955? 34) have suggested that this adsorption of the alcohol takes place via interaction of the lone-pairs of the oxygen atom, as well as of the 7i electrons of the double bond, with the catalyst. I f adsorption is followed by cis-addition of hydrogen to the side of the adsorbed molecule facing the catalyst, the result will be predominantly one-sided hydrogenation of the alcohol. If the above arguments are correct the course of hydrogenation o f (-)-4-phenylpent-3~en~2-ol may be represented as s— 63 Ph Ph H * H H D * D* H I OH OH HA ( H Ph Me * ph \/ \/ c H Me B | B1 Me « ▼x \ h [ HO A. H \ H OH H. Ph Me\ / A A* \ . 0' Me \ H' OH H SJ/ Ph Me - H 0* H - H HO - H Since A and A* are the preferred conformations* the racemate CC* w ill he the one which predominates in a mixture of the two racemates CC! + PD!• v Vapour—phase chromatography showed that the racemate CC1 predominated over HD1 to the extent of about 3si? 6 4 indicating that the alcohol is three times more readily adsorbed in the A conformation than in the 13. The final oxidation stage cf the reaction?in which the original asymmetric centre at was removed,may he represented ass~ ) Ph Ph H Me me -■ H H H H - H H OH HO - K Me Jdd oxid >/ Ph Ph Me II E E 1 H H H CO * CO 1 1 Me Me Toxid ♦ 'to x id \ Ph Ph i * i ♦ II - Me Me — H I) * S ’ 4 H - H \ H — H HO ■itJ— H I H — OH i -4-r Me Me Thus oxidation should give a single racemate EE1, a result which is in accord with experimental finding. 65 CONCLUSION The catalytic hydrogenation of 4“Phenylpent-3-en~2-ol has heen carried out to give ( i ) a 50$? and ( i i ) a 57$? asymmetric s y n th e s is . This result is explained by the suggestion that initially the unsaturated molecule is adsorbed on the catalyst in a planar conformation$ the exact mode of adsorption being controlled by the asymmetric centre at Cg? such that one heavily preferred conformation is adsorbed. Adsorption is then followed by cis-addition of hydrogen to the double bond from the side facing the catalyst. hydrogenation thus results in predominantly one sided addition of hydrogen to 4-pbtenylpent~3~en-2~ol9 giving rise to an asymmetric synthesis. The mechanism proposed is in full agreement with present views of' catalytic hydrogenation* and provides further proof of the validity of these views. The asymmetric hydrogenations which have been investigated may be divided into two groups* those in which the ■ v. unsaturated linkage is separated from the asymmetric centre by a-CO-O-grouping* and those in which it is directly connected to it. The majority of hydrogenations are of the former type* and lead to low degrees of asymmetric synthesis* in general less than 20$. Since it is suggested that the asymmetric centre controls the mode of hydrogenation of,the alcohol it might he expected that in the second group* where it is adjacent to the reacting centre* the control it exerts would he greater and that therefore the degree of asymmetric hydrogenation would he higher. The first hydrogenation of this type* that of 3-ethylhept-3-en-2-ol hy Arcus and Smyth (J.* 1955? 34) yielded a 76$ asymmetric synthesis. A second sim ilar hydrogenation* that of 3~methyl~4“phenylhut-3-en- 2-ol hy Arcus et al. (J., I960* 1195)? gave a 21$ asymmetric synthesis* while a third example* the hydrogenation of 4-phenylpent- 3-en-2-ol reported in the present Thesis* yielded a 57$ asymmetric s y n th e s is . Thus* although only a few hydrogenations of this type have so far been carried out* the available evidence does indeed indicate that in general, when the asymmetric centre is adjacent to the unsaturated centre* a higher degree of asymmetric hydrogenation can be expected. 61 EXPERIMENTAL Preparation of ethyl bromoacetate Ethyl bromoacetate was prepared according to Org. S y n th ., 23^, 37* The y ie ld was 825 g <-9 b.p. 155-15 6° - (Org. Synth, report 8l8g., b.p. 154- 155°)* Preparation of ethyl 6 -methylcinnamate Clean zinc wool (65g«) was placed in a 1L., 3 neck, flask fitted with two reflux condensers, a stirrer, and a dropping funnel. Fifty ml. of a mixture of acetophenone (l20g.), ethyl bromoacetate (l35g*)? and benzene (200 m l.) were added, and the stirrer started. Reaction was initiated by warming on a steam-bath, and after removal of the steam-bath the remainder of the mixture added at such a rate that gentle refluxing was maintained. After the addition was completed, the mixture was warmed under reflux for a further hour, cooled, and hydrolysed by addition to ice cold 3^ sulphuric acid (500 ml.). The benzene layer was separated off, the aqueous layer extracted with benzene (3 x 100 ml.), and the combined benzene solutions dried over anhydrous magnesium sulphate. The above benzene solution, containing crude . A hydrozyester, was dehydrated to give the unsaturated ester by refluxing for lg^-2 hrs. with phosphorus osychloride (60 m l.). The cold solution was washed with water (2 x 100 ml.), the washings extracted with 68 ■benzene ( l x 50 ml.)? an& the latter washed with water (l x 25 m l.) . The combined benzene solutions were dried over anhydrous magnesium sulphate* benzene removed on a steam-bath* and the residue distilled at reduced pressure to give a pale yellow liquid- In all* six separate preparations were carried out as described* the results of which are tabulated below. P rep. b .p . 25 Y ield n P 1 152- 154°/20 mm. 1.5418 86 g . n2° 1.5441 5$?o 2 148-150° / l 8 mm. 1.5420 85g* 56?o 3 150-152°/21 mm. 1.5410 79g* 52/o 4 138-142°/l4 mm. 1.5405 95g* 62^ 5 142-145°/i6 mm. 1*5395 10 2g. 6lfo 6 136-139°/l2 mm* I. 54OO lOOg. 65fo Yields are based on ethyl bromoacetate. (.Johnson and Kon report b.p. 142-145°/l6 mm*? n^*^ 1.5451* Heilmann and Glenatt* Bull. Soc • ehim. France^ 1955? 1589 ? report b.p. 128~131°/8‘5 mm*> n^ 1*5453*) 69 Preparation of g-methylcinnamic acid Ethyl (3 -methyl cinnamate (295S’) was hydrolysed by heating under reflux for two hours with 5Ofo aqueous potassium hydroxide (150 ml.) and ethyl alcohol (900 m l. \ sufficient alcohol having been added to produce a homogeneous solution. The hydrolysis product was poured into water (lL), extracted once with light petroleum (b.p. 40- 60°, 200 ml.),and after removal of the bulk of the alcohol by distillation, cooled, and acidified with 3N hydrochloric acid. Acidification produced an oil, which on chilling partially solidified. The solid was filtered off, and recrystallised from light petroleum (b.p. 100- 120°) to give {3-methyl cinnamic acid (lllg.)m .p. 99- 100° . The combined oily cinnamic acid residues ( 85 g*) were treated with a sufficient excess of concentrated aqueous potassium hydroxide to give a clear solution, and the mixture refluxed for one and a half hours* The product was diluted, acidified, and filtered. The brownish solid was recrystallised from a mixture of benzene and light petroleum (b.p. 100- 120° ) and decolorized with charcoal to give a further quantity of the acid (44g„) m.p. 99-100°C. A second hydrolysis of the ethyl ester ( 243g.) yielded'p-methylcinnamic acid (l 04g») m .p. 99- 100° . TO Preparation of 6-me thy1cinnamoyl chloride |3-MetLylcinnamic acid (l54g«) was warmed with thionyl chloride (l70gv) on a water-bath for one and a half hours. The excess thionyl chloride was removed under reduced pressure on a steam-bath, and the residue distilled at reduced pressure to give a yellow liquid (l6lg., 94$) "b.p* 148°/22 mm. A similar preparation from the acid (lOOg.) y ie lded (3-m eth y lci nnamoy 1 c h lo rid e (10 2g., 90$ ) h . p . 150° / 25 mm. (Johnson and Kon report b«p„1327l8 mm.). Preparation of 4-phenylpent-3-en-2-one Methyl magnesium bromide was first prepared (Org. Synth., 38, 4l) "by the addition of methyl bromide (l75s°)? in ether (lL), to magnesium turnings ( 41g*)s> suspended in ether (500 m l.) . The resultant methyl magnesium bromide solution was cooled, and anhydrous cadmium chloride (173g« of approx. 95$ anhydrous cadmium chloride) added at such a rate that gentle refluxing was maintained (Org. Synth., 28^ 7 6 )° After completion of the addition, the mixture was stirred and refluxed for a further hour. At the end of this period a Gilman test was carried out to tesc for the presence of unreacted Grignard reagent. The test proved negative showing reaction to be complete. The ether was then distilled off until a dark viscous residue which almost prevented stirring remained. Senzene (400 ml.) was added, and distillation continued until another 150 nil. had been collected. 71 A second quantity of benzene (500 ml.) was added? and the mixture vigorously stirred to break up the cake in the flask- After the dimethyl cadmium solution had been heated to boiling? the acid chloride (lOOg.)? in benzene (200 ml-)? was added at such a rate that gentle refluxing was maintained- After addition was completed? stirring and refluxing were continued for a further hour. The reaction mixture was cooled? and decomposed by the addition of ice (approx. lOOOg.) followed by excess 3N sulphuric acid. The benzene layer was ran off, and the lower aqueous layer extracted with benzene (2 x 200 ml.)- The combined benzene solutions were washed with water (300 m l.)? 5$ NagCO^ solution (300 ml.)? water (300 ml.)? and saturated sodium chloride s o lu tio n (150 ml.)? and finally dried over anhydrous sodium sulphate. The benzene was removed on a steam-bath? and the residue distilled at reduced pressure to give a yellow oil ( 46g.) b.p. 13 9- 141°/2 0 mm? n ^ I . 5656? n ^ I . 5683 . When the distillate was chilled yellow needle-like crystals separated out. These were filtered off from the very viscous yellow oil in which they were suspended? and recrystallised from light petroleum (b.p. 60- 80 °) to yield the ketone as pale yellow c r y s ta ls (3 0 .5g»? 3 5^)m 0P** 37*5-38.5° Founds C? 82.55? Calc, for Cu H120 s C?82.45? H?7.55$- Considerable difficulty was experienced in the above preparation because the heavy sludges formed in the course of the reaction at times stopped the stirrer? and towards the end of the preparation only permitted very inefficient stirring. Therefore? in a second preparation of the ketone a very powerful stirrer was used so that efficient stirring was maintained at all times* The quantities of reagents used were also modified! methyl bromide (l75g.)? magnesium (42»5g*)? cadmium chloride (l8lg.) and (3-methyl- cinnamoyl chloride (l6lg.)« Experimental conditions were unchanged and the final product was a yellow oil ( 90g«) "b.p. 127-130°/l2 mm, 9 n ^ I . 5675 ? which crystallised rapidly on seeding. The crystalline material was removed hy filtration? and recrystallised from light petroleum (h.p.60-80°) to give the ketone ( 71 g*? 5®$) ni<,p• 37"5-38*5°* Owing to the close sim ilarity between the prepared ketone and the isomeric 3~methyl-4~Pkenyrbut-3~en-2-one a mixed melting point was carried out with an authentic sample of the latter. The mixture was found to melt immediately the two samples were added together? intimate mixing being unnecessary. 4-Phenylpent-3-en~2-one semicarbazone The ketone (0.2Cg.) was added to a solution of semicarbazide hydrochloride (0.20g.) and crystalline sodium acetate (0 .3 0 g .) d isso lv e d in th e minimum q u a n tity o f w ater? and alco h o l added until a clear solution was obtained. The mixture was heated on a steam-bath for ten minutes? diluted with water? cooled? and the product filtered off and recrystallised from aqueous alcohol. 73 The semicarbazone (0.25g*> 93 $) after one recrystallisation had m.p. 193 *5-194*5°? constant on fu rth er r e c r y s ta llis a tio n . 4-Fhenylpent-3-e n -2-one -29 4-dinitrophenylhydrazone Brady’s reagent (lO ml.) was added to the ketone (0.10g.), the mixture warmed on a steam-bath for five minutes,, allowed to stand over-night, and the product filtered off. The derivative ( 0 . 15g «9 72/0 after one recrystallisation from methyl alcohol had a constant m. p. 193.5-194° «> Founds 0,59*53 H,4»85? N,16.7. Calc, for IT s C, 60.0 $ H,4*75l F,l6.45$* Oxidation of 4-phenylpent~3~en-2-one with sodium hypochlorite The ketone (l.Og.) was added to a solution of sodium hydroxide (3«0g.) and sodium hypochlorite (27 ml. of 10$ solution) in water (73 ml.). The mixture was heated on a steam- bath for 20 min., refluxed (over a Bunsen) for a further 20 min., and sulphur dioxide bubbled through for the same length of time. The crude acid was filtered off, washed with water, and after two recrystallisations from light petroleum (b.p.100-120°) had constant m.p. 99-100°. Admixture with the previously prepared {3-methyl- cinnamic acid produced no depression in m.ps99-100°„ Preparation of 4-pbenylpent-3-en-2-ol Aluminium foil (lOg.) was dissolved in isopropyl alcohol (200 ml.) by warming on a steam-bath under reflux, reaction 74 "being initiated "by addition of a few crystals of mercuric chloride. The resulting grey solution was cooled slightly and 4-pbenylpent- 3~en~2~one (2 6g.) added. The mixture was heated under reflux for one hour* and then the acetone allowed to d istil off slowly. When all the acetone had "been removed? the remaining isopropyl alcohol was distilled off under reduced pressure. The viscous grey product was cooled and added to an excess of 31T sulphuric acid and ice to give the alcohol as a pale yellow solid. The alcohol was ether extracted? washed with 3$ sulphuric acid (2 x 100 ml.)? followed by2N sodium hydroxide (2 x 100 ml.)? and finally with water until neutral. The ether solution was dried over anhydrous potassium carbonate,and the ether removed by distillation on a steam-bath. The residue was recrystallised from light petroleum (b.p.100-120°) to give the alcohol (l7g*s 65$) as a white crystalline solid m.p.63-64°. A second preparation from the ketone (60g.)? Aluminium (23g»)? and isopropyl alcohol (450 ml.)? yielded the alcohol (37g.? 61$) with m.p.63-64°. The two batches were combined and recrystallised again from light petroleum (b.p.100-120°) to give a single stock m.p.63-64°? n^ 1.5521 (super-cooled). Founds C,8l*5» H,8.85* C11H14° reQ.ui res 0*81*45? H?8.70$. Attempts to vapour, phase chromatograph the alcohol r •ynrirMa~iniMynrii~tiii,t7^tifw*tfgttrtfvw.in,TrmMnirvMij-'',,w»f»’-‘*->ci::»r»,‘«,“t-a^r't»««i>1111 imi«iiuiuu»mwytani«wiiinnnnii.uuuucM«iuiwi - ...... --- ...... o - '...... • o 75 O n ...... - ...... — ...... - - ...... - - ...... - n O Vapour-phase chromatogram of 4--phenylpent-3-en-2--ol CO - ---•■• - • - - - CO VO...... - ...... - - ...... - .... - ...... - VO to F ig . 1 o 76 were unsuccessful owing to its decomposition on the column* Fig* I* (see discussion page 55 )• l-M ethyl-3-phenylbut-2-enyl If-ct^-naphthy 1 carbamate 4-fhenylpent-3-en-2-ol (l.COg.) was heated with 1-isocyanatonaphthalene (Q.95g») op a steam-bath for one hour. The product was dissolved in light petroleum (b.p.100-120°), and insoluble di-a-naphthyl urea (0.17g«) filtered off. After three recrystallisations from light petroleum (b.p.100-120°) the -naphthylcarbamate (0.'77g«) had constant m.p.96-97°» Founds C?79»4? H?6.15? 1ST,4.35* C22H21°2:W re^-uires c^79.7l H?6.4* 3M-25 l-Methyl-3-phenylbut-2-enyl N-4-diphenylylcarbamate 4-Fhenylpent~3-en-2-ol ( 0 . 90g.) was heated with 4-isocyanatodiphenyl (l.OOg.) on a steam-bath for one hour. The product was dissolved in light petroleum (t .p.100-120°)? and insoluble di-4-diphenylyl urea (0.l8g.) filtered off. After two recrystallisations from light petroleum (b.p.100-120°) the K-4-diphenylyl carbamate (l.03g.) had constant m.p»ll6.5-H7°« Founds C?80.1§ H,6-7 °9 U ,4 .1 . C24H23°2N reclu ir e s c ?8o -65$ H?6.5$ tt,3-9 Preparation of Raney Nickel W-3 Sodium hydroxide (l28g.) was dissolved in water (500 ml.) in a 2-litre conical flask fitted with a thermometer and a Hershberg-type stirrer. The flask was placed in a bath of cold running water, and when the temperature had fallen to 50° hi-Al a llo y ( 50- 50$? 100g.) added in Ig. portions., over a period of one hour? to the vigorously stirred solutions; the rate of addition + o "being controlled so that the temperature was maintained at 50-2 . Sudden rushes of foam following addition of portions of the alloy were collapsed by adding a few drops of ethyl alcohol. When all the alloy had been added., the solution was stirred at 50° f o r a f u r th e r 50 minutes., gentle warming on a water-bath being necessary. Following this the catalyst was washed 5 times by decantation with water and transferred to a 1-litre graduated cylinder. The catalyst was vigorously stirred with a paddle stirrer, and further washed by siphoning through water (15 l i t r e s ) by means of an off-set inlet tube opening at the base of the cylinder. The catalyst was allowed to settle, and the water decanted. The catalyst, after transfer to a conical flask, was washed by decantation with 96$ ethyl alcohol (3 x 150 m l.), followed by .29$ ethyl alcohol (3 x 150 ml.), and finally stored under 99$ ethyl alcohol. hydrogenation of 4-phenylpent-3-en-2-ol I 4-Bienylp9nt-3~en-2~ol (l5«00g.) was dissolved in ethyl alcohol (99$? 75 ml.) and hydrogenated over Haney nickel W-3 (about lg.) s- 78 Time Temp P ressu re Remarks atm. °C 11.00 14 100 System flushed twice with hydrogen (50 atm.) and filled to 100 atm. 11.40 14 100 Scirrer and heater switched on. 11.45 14 99 Immediate pressure fall to ' 99 atm. when stirrer started. 12.15 44 . 107 Heater switched off. 12.35 52 107 Maximum temp, and pressure. 15.55 34 100 17 -05 32 100 20.30 21 97 Pressure released. The ethanolic solution from the hydrogenation was filtered to remove the Raney nickel catalyst, the ethanol removed on a steam- bath. <, and the residue distilled at reduced pressure* 'Taction I h.p. H8-119°/l0.5 mm. n 2| 1.5090 0.77g II 119- 120° / l 0 .5 mm. 1.5100 ll» 5 7 g III 120- 121° / l 0 .5 mm. 1.5100 l*53g Residue - viscous, yellow 1.5190 0 .7 1 s Fraction II was redistilled* 79 Fraction IV Id. p. Il8°/l0.5 nun. 1.5098 1.01 g. V Il8-119°/l0.5 mm. I. 5IOI 6.02g. VI 119-120°/l0.5 mm. I. 5IOO 3-94g* Residue I .5096 0»42g. Fraction V. Founds C979*8§ H ,9.75° C alc, for C-^H^Os C9 80.45? H ,9 .8 $ . Fraction V was- subjected to vapour-phase chroma tography (Fig. 2 ) which showed there to he two diastereoisomeric racemates present and indicating a ^Ofo asymmetric synthesis. Fractions I and III were also chromatographed, indicating asymmetric syntheses of 43$ and 53$ respectively. (F ig . 3 ) . See also discussion page 57 Oxidation of 4~Phenylpentan~2-ol I 4-Phenylpentan- 2- o l ( 9 *06g.) was dissolved in glacial acetic acid (30 ml.) and heated with stirring in an oil hath at 80°. Freshly powdered chromium trioxide (6.55s*) suspended in glacial acetic acid (40 m l.) was added portionwise d u rin g 15 minutes, and the resultant green solution kept stirred at 80° for a further 15 minutes. The solution was cooled, poured into water (100 ml.), and extracted with light petroleum (h.p.40-60°, 2 x 50 m l.). The combined petroleum extracts were v/ashed with a saturated solution of sodium bicarbonate (3 x 50 ml.), followed by w ater (4 x 50 ml.), and dried over anhydrous magnesium sulphate. o 80 Os - - '• - - - • CO ...... - ...... Vapour-phase chromatogram of 4-phenylpentan~2-pl . ( Fraction V ) -______t^Ratio. A:B -_____ 1:3.02 CO.. F ig o~ 81 v o - ...... — ...... VO chromatograms of 4-phenylpentan-2^ol R atio A*:B CO Fraction III ■CO CO R atio A*:B* 1:2.52 F ra c tio n I Yapour-phase chromatogram of If-pheny Ip e n t an- 2- o ne -p 83 ■The light petroleum was removed on a steam-bath and the residual o i l ( 6 . 66g .?n ^ 1 * 5045) distilled at reduced pressure. Fraction I h.p. 113°/l2 mm. 1*5047 0.47g» II 113-115°/l2 mm, I .5047 4 *08 g . Ill 115-116C/l2 mm. I .5044 l-5 8 g . Residue 1*5043 »35g* Fraction II was redistilled. Fraction IV h.p. Il6°/l4 mm. n^ I .5050 0.47g* V 116-117°/14 nun, n2^ 1.5048 2-14g- 15 1.5091 D VI 1 1 7 « ll8 ° /l4 mm. n ^5 1-5047 ■ 1.26g. Residue r.£ 25 1.5045 n r-n/1r- F ra c tio n V. Founds C?8l.555 H 98»45° C alc..for C-qH-^Os C,81.455 H,8 . 7^0 Vapour-phase chromatography showed fraction V to consist very largely of a single component (about 9 9* 5$ ) w ith a small quantity of a second component (about 0.5$). (Fig. 4 ) 4-Bienyl~pentan- 2~one semicarbazone 4-Phenylpentan- 2-one ( 0 . 2Og.) was added to serni- carbazide hydrochloride ( 0 . 20g«) and crystalline sodium acetate (0.30g.) dissolved in the minimum quantity of water. Ethyl alcohol was added dropwil.se until a clear solution was obtained and the mixture warmed on a steam-bath for ten minutes. On cooling, 84 the semicarbazone crystallised out and after two recrystallisations from aqueous ethyl alcohol it ( 0 . 19g.) had constant m.p. 140- 141°* Founds U,18.8. Calc* for IT, 19*15 $ • Hydrogenation of 4-Hienylpent-3-en-2-ol II 4“Hienylpent- 3- e n - 2- o l ( l 5 °00g 0 was dissolved in ethyl alcohol (9975 ml.) and hydrogenated over Raney nickel W-3 (about lg .) under conditions as close as possible to those used for the first hydrogenation. Time Temp P ressu re Remarks oc atm. 11.00 14 100 System flushed twice with hydrogen (50 a tm .) . 11.30 14 100 Stirrer and heater switched on * 11.35 14 99 Immediate pressure fall to 99 atm. when stirrer started 12.10 45 105 Heater switched off • 12.25 52 106 Maximum temp, and pressure. 15.55 37 102 17.00 34 101 19.00 27 99 Pressure released> The hydrogenation product was filtered to remove Raney nickel? the ethanol removed on a steam-bath 5 and the residue distilled at reduced pressure. 85 25 Fraction I h.p. H7°/9-5 mm. nx D 1.5098 l.0 9 g . II U7-ll8°/9*5 mm. 1.5106 8 .08 g . III 118-119°/9«5 mm. 1.5107 2.7 8 g . Residue 1.5129 2.30g. Fractions II and III were combined and redistilled. 25 F ra c tio n IV h .p . n 0 . 60g . 115°/9 mm. D 1.5097 V 115-ll6°/9 mm. 1.5102 5-71g. 0 VI ll6-117°/9 mm. 1.5106 3 . 27g* Residue lo 5109 O.94g . A vapour-phase chromatogram of fraction V (fig. 5) indicated a 57«0$ asymmetric synthesis. Oxidation of 4-phenylpentan-2~ol II 4-Phenylpentan-2-ol (5*45g*) was dissolved in glacial acetic acid (20 ml.) and oxidised with freshly powdered chromium trio x id e (3.94g») suspended in glacial acetic acid (30 ml.)? u sin g conditions identical to those previously described (Page 79 ) Ihe crude 4-pbenylpentan-2~one was distilled at reduced pressure to- give three fractions. o o 86 C\ ON CO CO ■Vapour-phase chromatogram of 4”phenylpentan- 2- o l ( Fraction V ) R atio A:B VO 1:3.65 VO in m CO r'ig. 5 f 8 Z I 87 -p 88 Fraction X b.p., Il6°/l4 mm. I. 505O 0 .3 0 g . II H6-ll8°/l4 nun. 1.5048 3 . 26g. I l l Il8 -1 1 9 ° /l4 mm. I . 5043 0.45s* Residue I . 504I 0.33g* Fraction II was redistilled. fraction IV Id.p. 116-117°/l5 mm. n^ 1*5045 0.79g» V 117-ll8°/l5 mm. 1.5047 l*43g* VI I l8 ° /l 5 mm. I .5044 0 .6 3 g . Residue 1.5043 0.33g. Vapour-phase chromatography showed fraction V to he a single entity containing a trace of low "boiling impurity too low in quantity to he estimated. (Fig. 6) PMT 2 90 DISCUSSION (+)- g-Pinene. a-Pinene occurs widely in Nature, and is found in many of the essential oils derived from the Coniferae . It exists in hoth laevo- and dextro-rotatory forms* the sign of rotation and degree of optical purity depending on the source from v\rhich it is d e riv e d . (+) -a~Pinene of high optical purity may he readily obtained from Aleppo Pine (Pinus halipensis). Veze’s (Bull. Soc. chim. Prance* 1909? 932) records for a-pinene from this source h.p.l55-156°* n^ 1.4634? d^ O. 854 ? and [ a]^+48«4°? Chiurdoglu* Decot* and Mme Van Lancker-Prancotte (Bull. Soc. chim. beiges, 1954? 63, 7 0 ) re p o rt n ^ I . 466I, d^ 0.859? and [ a]^+48.0°. The view that (+)- a-pinene obtained from Aleppo Pine is of high optical purity is supported by the work of Thurber and T hielke ( j . Amer. Chem. Soc.* 1931* 52.? 1030) who o b tain ed (+)- and (-)- a-pinene of high purity by decomposition of the pure optically active pinene nitrosochlorides. They record for (+)-a-pinene n^ 1*4663* d^ 0.859* and [a] ^ +51«-14°* 91 The (+)- a -pinene obtained in the present work p r 2q gC from Pinus halipensis had n^ 1.4636* I. 466I , d ^ 0 .8 56, d ^ 0.859s [ct-] ^ +47 «78°j and b .p . 1560. These values are in good agreement with those quoted above* and indicate a high degree of p u r ity . Althougha -pinene contains two asymmetric carbon atoms* and can therefore theoretically give rise to two pairs of enantiomers* it does in fact exist in only one (+)- and one (-)- form. This is because it contains a four-membered bridge ring which necessitates, for stability of the molecule, a cijs-arrangement of the isopropylidene bridge group about the cyclohexene ring (P ig . A ). A. a -pinene 92 For a second (+)- and a second (-)- form of a-pinene to exist, the bridge group would bave to be connected trans-across the six-membered ring 5 an arrangement which would involve a degree of strain incompatible with a stable structure. Thus a-pinene can exist in only one (+)- and one (-)- form, and according to Fredga and Miettinen (Acta Chem. Scand., 1947? i? 371°)? who have related the steric configuration of (+)- a-pinene to that of (+ )-glyceraldehyde, the (+)- form must have the configuration shown in Fig. A. In Fig. A the cyclohexene ring is considered to lie substantially in the plane of the paper, with the iso- propylidene bridge pointing outwards. 93 The catalytic hydrogenation of (+)-a-pinene» Addition of hydrogen to (+)- a-pinene (i) can theoretically give rise to two diastereoisomeric forms of pinanes cis-pinane (ll)? and trans-pinane (ill). CH \ I l l H- /v y trans-pinane CH, (+)- a-pinene 0- II c rs-p in a n e CH, 94 Each pinane is obtained by addition of hydrogen to a different side of the pinene molecule. Cis-pinane ( i i ) is obtained by addition of hydrogen to I from below the plane of the paper, i.e . to the side of the molecule facing away from the isopropylidene bridge, while trans-pinane (ill) is obtained by addition of hydrogen to the opposite side of I, i.e . by addition of hydrogen from above the plane of the paper. Both cis- and trans-pinanes are known, but while the physical properties of cis-pinane are well established, those of trans-pinane are still in doubt. 95 ( 2 ) (4 ) c is-p in an e Lipp ^ F is h e r v ' Chiurdoglu ^ Schmidt v^ ' 20 I .4624 1.4628 n D 1.4624 0.857 0.857 O.857 a4 ? a25 0.853 4 [ c3d +23.08° -23.2° +23.H°at 20° b .p . 1 6 3 -4 % 20mm I 690 167-168° From a -p in e n e {3 -pinene a -p in e n e ci s-6 -pinene C a] -q +47*5° [ a ] D-2 1 .3 ° [a ] 15+48.0 trans-pinane nn1 D 7 ' 5 1.4595 20 1.4619 I .4608 I. 46I 8 n D d17-5 O.852 4 O.854 O.856 4 0.852 4 i 5? _ P» +I8.1°at 20° +23.83° i -1 6 .1 ° -18.1°at 30° t n p / 162-1/7 20mm 162.5-164° 165-I 66. 50 From a -p in en e 0 -p in en e a -p in en e trans-6 -pinene [ a ] D-3 8 .0 8 [ a ] D-2 1 .3 ° [a] ^+48.0° 96 (1) Lipp, Ber., 1923? 56^ 2098. ( 2) F is h e r, S tin so n and G o ld b la tt, «T. Amer. Chem. Soc*, 1953? 75? 3675. (3 ) Chiurdoglu, Decot and Mme. Van Lancker-Francotte, Bull. Soc. chim. beiges, 1954? 63j 70 . (4 ) Schmidt, Ber., 1947? §0, 520. The physical properties of cis-pinane can he considered to he reasonably accurate since a number of workers have obtained values in good agreement with one another. However, the values for trans-pinane are considerably less reliable, since it is unlikely that any of the samples of trans-pinane were in fact pure. Schmidt’s trans-pinane was undoubtedly impure as it was obtained from trans-6 -pinene which he knew to be impure. The same is true of bis cis-pinane which he obtained from cis-6 - p in e n e . Lipp’s trans-pinane was obtained by a Sabatier- Senderens reduction of a-pinene with a nickel catalyst at 220-230°. Under these conditions it is possible that some p-menthanes were also formed, and these would not be separated from the trans-pinane by distillation. Fisher (private communication) states that it is unlikely that the trans-pinane he and his co-workers obtained was actually pure, and that it probably contained small amounts of cis- pinane and the p-menthanes, all of which boil at about the same temperature. He also states that his own experience in trying to 97 separate the two pinanes, using a 100 plate Podbielniak column at 20 mm., would suggest the boiling points are closer together than those reported by Chiurdoglu et al., who report the separation of cis>and trans-pinanes by distillation through a 30 .plate column at atmospheric pressure. The boiling points of cis- and trans-pinanes reported by Lipp, and by Schmidt, support U sher's view. In conclusion it may be said that while the physical properties of cis-pinane are well established those of trans-pinane are much less reliable, and one can only say with certainty that the trans-isomer is lower boiling, and has lower refractive index? density, and optical rotation than the cis-isomer. In the present investigation a sample of (+)- a-pinene was hydrogenated over a Haney nickel W-3 catalyst at a maximum temperature of 107 °? and a maximum pressure of 103 atmospheres, to yield a product having the following physical properties for the main fraction? b.p. 166-167°? n^l.4^02, n ^ l. 4626, d^O .854? 20 25 o d^ 0.857? [&] ^+23 -02 . These values are in very good agreement with those quoted in the above table for cis-pinane, and indicate that hydrogenation has yielded almost exclusively the cis-isomer. This was verified by vapour-phase chromatography. A chromatogram having a single sharp major peak with a shoulder on the more volatile side was obtained. There were also two small low-boiling impurities present totalling less than 1$ of the specimen. It appears reasonable to ascribe the main peak to cis-pinane, and the 98 shoulder to an isomer? presumably trans-pinane, estimated to form ifo of the specimen. Although the boiling point of trans-pinane is only slightly lower than that of cis-pinane, it is possible that some separation of the isomers has been achieved by distillation? and that therefore the ratio of cis- to trans-pinane found for the main fraction is not the same as that for the hydrogenation as a whole. This possibility was examined by submitting to vapour-phase chromatography the immediately preceding fraction to the main fraction? which should contain a larger proportion of trans-pinane if any separation has occurred. The physical properties of this fraction were very close to those of the main fraction (see experimental results page 106 ), The chromatograms of the two f r a c tio n s were virtually identical? whence distillation has not resulted in appreciable separation of the cis- and trans-isomers. It can therefore be stated with reasonable certainty that hydrogenation has produced overwhelmingly cis-pinane with only a trace of trans- pinane (about 1$). This means that almost exclusively one-sided addition of hydrogen has taken place to a-pinene? and for cis- pinane to be the product this addition must have taken place to the side of the pinene molecule facing away from the isopropylidene bridge. Thus s- 99 CH. (+ )~ a -ppinene i CH. CH. CH. (+)-cis-pinane Theoretically 9 hydrogenation ofa-pinene would he expected to proceed preferentially through the adsorption conformation which presents the douhle-hond most closely to a plane. Examination of a -pinene shows that owing to the hindering effect of the isopro- pylidene bridge there is only one adsorption conformation in which the double bond can be presented in a planar conformation to the catalyst, i.e . that having the isopropylidene bridge remote from the surface. Adsorption of the pinene molecule in this favoured conformation, followed by cis-addition of hydrogen to the side of 100 the molecule facing the catalyst will produce cis-pinane? a result in accordance with experimental finding1. The purification of -pinsne hy progressive freezing. The purification of metals hy zone refining techniques is a well established metallurgical process. The method consists of causing a narrow molten zone to traverse a solid bar of the metal. In general the impurities become concentrated in the molten zone and are moved towards the tail of the bar? i.e. in the direction of zone movement. Zoning may be repeated as many times as is necessary to attain the required degree of purity? and the impure end of the bar discarded. Although zone refining was originally developed for the preparation of metals of very high purity? it can also be used for the purification of organic compounds? for the method is applicable to any crystalline substance that exhibits a difference in soluble impurity concentration in the liquid and solid states at the point of solidification. The degree of success that can be achieved depends on the difference between the solubility of the impurity in the liquid and solid phases? the larger is this difference the greater is the chance of zone purification. Since impurities usually lower the melting point of the material in which they are dissolved? they generally become concentrated in the molten zone. Impurities that tend to raise the melting point of the solvent, such as is the case with some alloys? are subject to a 101 reverse and much less efficient process? the moving molten zone becoming progressively purer. Applications of zone melting to the purification of organic compounds, which are solids at normal temperatures? have been reported by a number of workers* Thus? Herington? Handley and Cook (Chem. and Ind*? 1956? 292)? using a zoning method almost identical to that previously mentioned for metals? have reduced the concentration of anthracene dissolved in naphthalene from 0.2$ to 0.00002$ after seven passes. The same authors have also managed successfully to treat compounds which are liquids at room temperature by placing the apparatus in a refrigerator at - 25°? and passing a molten zone through the frozen material. Progressive freezing? in which a solid boundary advances into the liquid? is in theory superior to zone melting? for when molten material is permitted to solidify unidirectionally? at a rate sufficiently slow to permit solid state diffusion? a purer product should be obtained. This ideal condition is not achieved in practice? owing to the extreme slowness of solid state diffusion? but by controlling the rate of directional solidification it is possible to achieve a high degree of directional purification. Schwab and Wichers («X * Res. nat. Bur. Stand.? 1944? 32? 253) have used this method to purify benzoic acid^ by freezing twice and r e je c tin g 40$ they raised the purity from 99*91$ to 99*998$. Dickinson and Eaborn (Chem. & Ind? 1956? 959) have also successfully 102 used the progressive freezing method to purify liquids and low- melting solidso The method used was to place the liquid in a glass tube of 3 cm. diameter and to slowly lower the tube at a controlled rate into a freezing bath. Using commercial "Pure *1 benzene they found that after six passages, in which the top tenth of liquid was left unfrozen and removed each time, all impurities revealed by vapour-phase chromatography were removed. For liquids of much lower melting point, e.g. nitromethane m.p. ca«- 29°? th e sample was lowered at 1 cm./hr. into a dry ice~.acetone mixture. They found that the impurities (ca.4$) shown to be present in nitromethane by chromatography were completely removed in eight passages, one tenth being rejected each time. This technique of progressive freezing has now been used for the purification of •(..+)-a-pincnc (mop.^ 75 °) using a liquid air bath (ca.-190°). The rotations of the starting material, and the recrystallised, and rejected pinenes, indicate that a small but positive purification has been achieved. 103 CONCLUSION (+ )-a-Pinene has heen hydrogenated over a Raney Nickel W-3 catalyst to yield almost exclusively (+)-cis-pinane. This one-sided addition of hydrogen can he explained in terms of steric hinderance between substrate and catalyst. It is suggested that, owing to the hindering effect of the isopropylidene bridge, one side of the cyclohexene ring in a ^pinene is, in effect, blocked.. As a result a-pinene possesses only one adsorption conformation in which the double bond can be presented closely to a plane, i.e . that having the isopropylidene bridge remote from the surface. If adsorption is followed by cis-addition of hydrogen to the side of the adsorbed pinene molecule facing the catalyst, the product is cis-pinane. The proposed mechanism is in agreement with present views on catalytic hydrogenation, and provides further proof of the validity of these views. An attempt to purify (+)-a -pinene by the progressive freezing technique gave a small but definite increase in purity, indicating that purification by this method is possible, even at very low temperatures. 104 EXPERIMENTAL Greek (+ )-g-pinene The a -pinene from Aleppo Pine (Pirns halipensis) ^ C q was* as acquired, of a high degree of purity having a jJ+79 O^O, 25 1*4638• Purification was carried out hy fractionation through a h eated 20 cm. column packed w ith g la s s h e lic e s . Two hatches of the crude pinene were distilled. The r e s u lts o f one o f th ese d i s t i l l a t i o n s are given "below, showing general trends ohservahle in hoth cases. Fraction I h.p. I 55-I 560 n^51.4634 a,p 5+8l.53° (L^) I I 156 1.4636 +81.32 I I I 156 1.4636 +81.12 IV 156- 156.5 1.4637 +80.60 Fraction I was comhined with two other fractions of like "boiling point and rotation from the other distillation, and the comhined fractions redistilled. Fraction V h.p. 156° n ^ l .4636 d ^ O .856 a ^+81.75° 6^2 ) n^l-4661 d^00.859 [a ]2B5+47.78 VI 156 n251.4636 a ^5+8l.40(L}2) vii 156-156.5 1.4636 +81.03 105 Hydrogenation of (+)-q-pinene (+)-a -Pinene (100 g . ) 9 from fraction V, was hydrogenated in ether (200 m l.), in the presence of Haney Hi W-3 (3 g .)* Time Temp. > P ressu re A? Remarks °C atm os. I I « 15-30 16 99 Flushed twice with (50 atmos.) before filling to max. press. 16.20 15 -1 98 -1 Stirrer and heaters on. 17.00 61 +46 103 +5 17 4 0 95 +34 101 -2 18.00 107 +12 82 -19 19.25 107 0 61 -15 21.05 105 -2 61 0 Stirrer and heaters off. 15 50 Pressure released. The hydrogenated material was filtered to remove Haney Hi, the ether removed on a steam-hath, and the residue distilled. In the first distillation a single wide cut was taken. h.p. 166-169 mainly 168 ° 95«40g. This was redistilled. 106 Fraction I b.p. 166-168° n^l*4603 67»24g» II 169 1.4603 21.51g. Residue I .4609 4*67g» Fraction I was finally redistilled to give the following s- Fraction III b.p. 166° n25 D'1.4579 2.31s- IV 166 1.4600 5 *30g» V I 66-I 67 1.4602 42.75g* VI 167-168 1.4602 10.05g . Residue 1.4607 4*28g. . The fo llo w in g f u r th e r measurements were made %■ 20 F ractio n s *20 d25 ! 1 4 4 a ?D ? 1 C a f B5 IV 1.4623 0.857 0.854 +9-65° 0 .5 +22.61 V 1.4626 0.857 O.854 +39.33 2 +23.03 VI MM +39.76 2 Samples from fraction IV and V were subjected to vapour-phase chromatography (Figs. 7 and 3). 107 Vjapour-phase chromatogram : of (+)-cis-pinane (F ra c tio n IV ) ■4 Fijg. 7 108 Vapouif-phase chromatogram of | ( + )- c is - pinane j(Fraction V ) 109 Purification of (+)~g -pinene by progressive freezing. The s i l i c a tube S (le n g th 28 cm.* i n t . diam. 2 cm.) was filled to a height of 20 cm. with redistilled a-pinene (from fraction VI )* and lowered through a close fitting asbestos sheet A into liquid air, contained in a Dewar flask* at a rate of 2 cm. per hour* by means of a synchronous motor M. As soon as the silica tube broke the surface of the liquid* the a-pinene began to crystallize* and as the tube was lowered the solid front gradually advanced up the column of liquid pinene. When the so lid f r o n t was 2 cm. from the surface of the liquid, the motor was stopped* and the remaining liquid, com prising about l/lOth of the initial bulk* syphoned off. The crystalline a-pinene was allowed to melt, and the rotation of the two factions measured. 2^5 o Starting material a £+ 81.40 1, 2 Recrystallised a-pinene + 81*53 1,2 Rejected a-pinene + 20.33 1 , §• (+ 81.32 i f 1*2) This indicates that a small* but positive* purification of a-pinene has been achieved. 3~NAFHTHYLI,!ETHYIiCi\RBIN0L I l l imODUCTIOH TO PARTS III A IV The work described in these two sections was carried out prior to that in Parts I and II. The intention of this work was to carry out an asymmetric synthesis by hydrogenation of the two aromatic alcohols j3-naphthyImethyIcarbino1 (a ) and 2-(p-cymyl)methylcarbinol (b ). Thus 8- Me Me A •COCH. 3 B 112 However, it was found that in each case the alcohol underwent hydrogenolysis with the resultant destruction of the asymmetric centre at C^. Subsequent attempts, using different catalysts, varying reaction conditions, and different derivatives of the alcohols, were also unsuccessful. In most cases the picture was complicated by hydrogenatibn occurring simultaneously with hydrogenolysis. The resulting, often complex, products have been examined, and their nature is reported. 113 DISCUSSION The attempted hydrogenation of B~naphthylmetfcyloarblnol (3-Naph thy Ime thy lcarbinol was prepared by a Meerwein- Ponndorf-Verley reduction, with aluminium isopropoxi.de, of (3-naphthyl methyl ketone by the method of Collyer & Kenyon (J., 1940, 676 ). The hydrogenation of (3-naphthylmethylcarbinol was initially carried out with a stabilized Raney nickel catalyst, a maximum pressure o f 160 atm., and a maximum temperature o f 128 ° . The bulk of the hydrogenation product distilled continuously over the range 126-148°/24 mm* A single sharp high-boiling fraction was also obtained. This on redistillation had b.p. 156-158°/l7 mm . 9 20 n^ 1.5413? and on analysis was shown to be a tetrahydro- (3 -naphthyl- methylcarbinol. (Adkins and Billica, J. Amer. Chem. Soc., 1948? 70? 695 report b.p. 119-119*5°/2 mmjn^ 1 . 5484 )* The low-boiling distillate, on analysis, was found to be mainly hydrocarbon, and to contain only a small percentage of the expected alcoholic product 5 its composition was determined as fo llo w s . A sample of the low-boiling distillate was treated with 1 -isocyanatonaphthalene to remove the alcoholic material, and the remaining hydrocarbon isolated as a colourless liquid b.p. l08-110°/l3 mm.f n ^ I. 509O. The r e f r a c tiv e in d ex in d ic a te d th a t 114 this was a mixture of 2-ethyltetralin and 2-ethyidecalin. (Bailey, Smith, and Staveley, J., 195^? 273 report for 2-ethyl- 20 tetralin n^ 1-5294? and Adkins and Davis, J.A.C.S* ,1949?li?2955 report for 2-ethyldecalin n^ 1-4727)- Analysis showed the hydrocarbon to have a composition intermediate between that of 2-ethyltetralin and 2-ethyldecalin. The hydrocarbon mixture was further examined by vapour-phase chromatography. The chromatogram (Fig. 9 page 125) showed there to be four main components present. It would seem reasonable to ascribe peaks I and II to two isomeric forms of 2-ethyldecalin, possibly cis-ois-2-ethyldecalin A and trans-cis- 2-ethyldecalin B. ■Et E t A The other two major peaks. III and IV, are probably l,2,3,4-tetrahydro-2-ethylnaphthalene C and 1,2,3,4-tetrahydro-6- ethylnaphthalene D. E t •Et C D 115 The alcoholic portion of the low boiling distillate was "both characterised* and isolated from the hydrocarbon* hy oxidation and the preparation of a solid ketonic derivative, the 2,4~dinitrophenylhydrazone • B'ractional recrystallisation from glacial acetic acid of the crude 2,4-dinitrophenylhydrazone produced three crops of ciystals. The first crop had m.p. 257 - 258 °, indicating it to he the (3-naphthyl methyl ketone d e riv a tiv e * fo r which Johnson ( j . Amer. Chem. S o c ., 1953* 25.* 2720) reports m.p. 261-262°. This was confirmed hy analysis, and its presence shows that the hydrogenation product must have contained some unchanged (3-naphthylmethylcarbinol. The second crop of m.p.l95“‘200°* was unreacted 2,4-dinitrophenylhydrazine. The third crop, which was not obtained pure, had an indefinite melting point with the hulk of the material melting around 130°. It is possible that this crop contained some {3-decalyl methyl ketone derivative, since Dauhen and Hoerger ( J . Amer. Chem. S o c., 1951* J2j 1504) report this to have m.p. 134-135°• Thus the attempted hydrogenation of (3-naphthyl- methylcarhino1, with a stabilized Haney nickel catalyst, has resulted predominantly in hydrogenolysis with the production of a mixture of two 2-ethyltetralins and two 2~ethyldecalins. 116 Some hydrogenation of the carbinol did occur, as shown by the presence of a small amount of tetrahydro-13-naphthylmethylcarbinol, however, this constituted only about 10$ of the reaction product. The presence of a small amount of unreacted |3-naphthylmethylcarbinol was also detected, and it is possible that there might also have been present a trace of decahydro-13-naphthylmethylcarbinol. The attempted hydrogenation of {3-naphthylmethylcarbinyl acetate Owing to the ease with which |3-naphthylme thy lcarbinol underwent hydrogenolysis^the hydrogenation of a derivative of the alcohol was next attempted. (3-Naphthylmethylcarbinyl acetate, prepared by the method of Collyer & Kenyon ( j ., 1940, 676 ), was hydrogenated with an active Raney nickel W-3 catalyst. Over a period of two hours the temperature was gradually raised to 122°, during which time no uptake of hydrogen was observed. After heating at this temperature for a further two hours, without any change in pressure occurring, the temperature was raised to 132° when a marked fall in pressure took place. D istillation of the reaction product gave two fractions, a small low-boiling one containing acetic acid, and a large higher-boiling one b.p. 130-133°/l8 mm. containing all the remaining product of reaction. This was redistilled to give a main fraction b.p. 121°/3-5 mm., n^ 1.5270. (Bailey, Smith, and Staveley J., 1956, 273 * report for a mixture of ac- and ai^-2-ethyltetralin /*\ ocs b .p . IO 5-8 / I 3 mm0,n ^ 1-5294). Analysis confirmed this to be 117 2-ethyltetralin. Vapour^phase chromatography (Fig. 10 page 129 ) showed there to "be three components present. It would seem reasonable to ascribe peaks A and B to l,2,3,4-tetrahydro~2- ethylnaphthalene and 1,2,3,4-tetrahydro-6-ethylnaphthalene. The compound causing peak G is not clear, but the analysis figures would suggest that it is possibly isomeric with ethyltetralin. Thus the attempted hydrogenation of the acetate has resulted exclusively in hydrogenolysis, with the production of 2-ethyltetralin and acetic acid. The attempted hydrogenation of B -naphthylmethylcarbinyl methyl ether. The above ether, prepared by the action of methyl iodide on the potassium alkoxide, was hydrogenated with an active Raney $Fi W-3 catalyst, at a maximum temperature of 120°, and a maximum p re ssu re o f 152 atm. D istillation of the reaction product showed there to be only a single product present. The main fraction had b.p. ll6-ll8°/3-2 mm., n^ 1*5267. This is identical with the product obtained from hydrogenation of (3-naphthylmethylcarbinyl acetate, which was shown to be ethyltetralin. This was confirmed by vapourv phase chromatography (Fig. lOpage 129 )s a chromatogram almost identical to that from the hydrogenation product of the acetate being obtained. Thus the hydrogenation of the ether has also resulted in hydrogenolysis. 118 Further attempted hydrogenations of g-naphthylmethylcarbinol The first hydrogenation of the alcohol, using a stabilized Raney nickel catalyst, having been unsuccessful, a second hydrogenation was carried out using an active Raney nickel W-3 catalyst. A product having b.p* Il6-ll8°/l2 mm., n^p 1.5272 was obtained, which was identical to that obtained from both the acetate and the ether. Further confirmation was obtained by vapour-phase chromatography (Fig. 10 page 129 )• Thus, hydrogenolysis has again occurred. A final attempt at hydrogenation was made using Adam's platinum oxide catalyst. Although this is not as powerful a hydrogenation catalyst as Raney nickel W-3, with respect to the naphthyl nucleus, it does not promote hydrogenolysis as readily as does a nickel catalyst. Hydrogenation was in itially attempted at about 138°, but no uptake of hydrogen being observed, the temperature was gradually raised to a maximum of 205° while the pressure rose to a maximum of 168 atm.. Even under these drastic conditions only a small amount of hydrogen was absorbed, and heating was therefore stopped. The reaction product on distillation failed to give. 119 sharply separated fractions 9 hut distilled continuously over the range 148 - 165°/21 nm. A residue remaining after d istillatio n was found to he unchanged {3-naphthylmethylcarhinol, which was also deposited from all the fractions on standing. Vapour* phase chromatography showed that the only other product present was ethyltetralin. Thus the attempted hydrogenation of (3-naphthyl- methylcarhinol, with Adam's platinum oxide catalyst^ appears to result in hydrogenolysis to give ethyltetralin. 120 C0RCLUSI0R The attempted hydrogenation of (3 -naphthylmethyl- carhinol with a stabilized Raney nickel catalyst? an active Raney n ic k e l W-3 c a ta ly s t? and Adames platinum oxi.de c a t a l y s t ? re su lte d ? in every case? in hydrogenolysis* With Raney nickel W-3? the most active of these catalysts? the sole product was ethyltetralin? with Adam’s platinum oxide? possibly the least active of the catalysts? a large amount of j3-naphthylmethylcarbinol remained unchanged? * the material which reacted being converted to ethyltetralin by hydrogenolysis* Using a stabilized Raney nickel catalyst a mixture of products was obtained. This catalyst did not promote hydrogenolysis as strongly as did the other two catalysts? and •¥r although the major product was a mixture of ethyltetralin and 2-ethyldecalin? a small amount of tetrahydro-(3-naphthylmethyl- carbinol was produced. The attempted hydrogenations of two carbinol derivatives? the acetate and the methyl ether? were equally unsuccessful? the sole product being ethyltetralin formed by hydrogenolysis. • • • • * In every case the product referred to above as ethyltetralin was in fact a mixture of ac- and ar- 2-ethyltetralin ? i.e. 1? 2? 3? 4-tetrahydro~2-ethylnaphthalene and 1?2?3?4-tetrahydro- 6-ethylnaphthalene• 121 EXPERIMENTAL Preparation of (-)- 6 -Naphthylmethylcarhinol The alcohol was prepared hy reduction of {3-naphthyl- methyl ketone with aluminium isopropoxide hy the method of Gollyer and Kenyon (j*,1940, 676 ). P-Naphthyl methyl ketone (nup.53-54°? 170 £•) was reduced with a solution of aluminium isopropoxide (from Aluminium 60 g., propan-2-ol 1200 ml., and a trace of mercuric chloride as catalyst) hy heating under reflux for several hours on a steam- hath. Acetone produced during the reaction was allowed to d istil off slowly, and when the reaction was complete, excess propan-2-ol was removed hy distillation at reduced pressure. The viscous residue was cooled, and added to excess of 3N H^SO^ and ice. The product was filtered off, and recrystallised from light petroleum (h.p.60-80°) to give the alcohol (114 g*) as a white crystalline solid m.p. 71-72° (Collyer and Kenyon, loc. cit. report m.p.71-72°). A second preparation, using half quantities, yielded p-naphthylmethylcarhinol (57 g*) m.p. 72-73°* 122 Hydrogenation of (-)-* 6 -naphthylmethylcarbinol I. Using a stablized Raney nickel catalyst The alcohol (15 g .) was hydrogenated in ethanol (99$? 1 5 0 ml.) in the presence of Raney nickel catalyst (B.D.H. stabilized, ca.2 g.) Time , s, . A T P ressu re A p Remarks atm os. 11.30 31 128 Vessel flushed twice with before loading to 128 afrnoso Stirrer and heaters on. 12.10 70 +39 145 +17 13 .05 127 +57 160 +15 13.45 124 -3 160 0 14.30 125 +1 160 0 15.10 124 -1 158 -2 15.50 128 +4 156 '■ -2 16*30 124 -4 151 -5 Leak detected and fault r e c t i f i e d . - CO r-J 1 T O IT\ 17.00 122 -2 —1 0 Stirring and heating stopped. 1 21 —1 Pressure released. The hydrogenated material was filtered to remove Raney nickel, the ethanol removed on a steam-bath, and the yellow residue distilled at reduced pressure. 123 F ra c tio n I b.p. 126-128°/24 mm. n ^ I . 5HO 2.35 g* II 128-134°/24 mm. 1,5200 3.88 g . III 134-142°/24 mm. 1.5238 2.26 g. IV 142- 162°/24 mm. 0 .5 2 g . (chiefly 142-148) V 162-166°/2 4 mm. 1.5286 2.12 g . F ra c tio n V was redistilled. 20 F ra c tio n VI b.p. 153-156°/l7 mm. n p 1.5200 1.01 g . VII 156-158°/l7 mm. 1.5413 0.50 g . Fractions II, and VII, were tested with a head of sodium. Fraction II reacted slowly and incompletely, while fraction VII reacted rapidly to give a yellow resinous mass. Fraction VII. Founds C,82.2f Calc, for ^12^ 16^ (^e^ra^5r(iro“ £-naphthylmethylcarbinol)s C,8l.75l H,9*15$* Fraction II. Founds C,86.35f H,10.55? (whence 0,3.l) Calc, for C12Hl6 ( 2-ethyltetralin)s 0,89*95? H,10.05$. Calc, for 0^2^22 ( 2-ethyldecalin)s C,86.65? H,13.35$* Identification of the low-boiling products of hydrogenation Combustion analysis showed that the low-boiling material was chiefly hydrocarbon, and that there was only a small amount of oxygen-containing material, the expected alcoholic product, present. The hydrocarbon portion was isolated by removal of the alcoholic material, with 1-isocyanatonaphthalene, and identified by analysis and vapour-phase chromatography. The alcoholic portion 124 was characterised hy oxidation* and the ketonic products were removed from the unchanged hydrocarbon hy reaction with 2, 4-&initrophenylhydrazine. Examination of the hydrocarbon product Fraction II (2.50 g*) was heated with 1-isocyanato- naphthalene (2.20 g») on a steam-bath for one hour. On standing a small quantity of di-a -naphthyl urea separated out, and was filtered off. The filtrate was extracted with n~heptane (25 m l.) , washed with water (3 x 20 ml.), and dried over calcium chloride. The n-heptane was distilled off and the residue distilled at reduced pressure. The distillate on standing slowly deposited di- a-naphthyl urea, and this was repeatedly filtered off until precipitation ceased. The remaining filtrate was then re distilled to give a single fraction bop.l 08 --110° / l 3 mm., n ^ I . 509O. Founds C, 88.35? H, 11.05$* (Compare w ith fig u re s for 2-ethyltetral*in and 2-etbyldecalin given above). A sample was subjected to vapour-phase chromatography (Fig. 9)* 2 Examination of the alcoholic portion A quantity of the low-boiling distillate (2.50 g.) v/as shaken with glacial acetic acid (8 ml.) in an oil-bath at 80°, and powdered chromic anhydride (0.95 £•) added over a period of 30 minutes. The resulting green solution was poured into water, and extracted with ether (3 2: 10 m l.) . The e x tr a c t was washed w ith aqueous sodium carbonate, followed by water, and dried over anhydrous 125 M HIH 126 sodium sulphate. The ether was removed on a steam-bath, and the yellow residue shaken for 9 hours with an excess of a saturated solution of 2,4-dinitrophenylhydrazine in 2H hydro chloric acid. Ho solid derivative was obtained hut on standing a deep red organic layer separated out. This organic layer was run off, and n-heptane added, when the 2,4-dinitrophenylhydrazone Was precipitated as a very viscous red oil. The oily hydrazone was dissolved in boiling glacial acetic acid, and on cooling was deposited as a dark red crystalline solid. After two recrystal lisations from glacial acetic acid the 2,4-dinitrophenylhydrazone had constant m.p.257-258° (decomp.). Pound? H,l6.2» Calc* for ^18 ^ 14^4^4 ^ -ftaphthyl methyl ketone derivative)? H,16.0$. By Y/orking up the mother liquors a second crop, m .p . 195- 200°, of unchanged 2, 4-dinitrophenyihydrazine, was obtained. A third crop, orange in colour, of which there was only sufficient for a single melting point, was also isolated. This gave an indefinite melting point, with the bulk of the material melting at 130° (For the interpretation of the above results see discussion page 115 )• Preparation of 3 -naphthylmethylcarbinyl acetate (3 -Uaphthylmethylcarbinol (21.00 g.), pyridine (10.80 g.), and acetic anhydride ( 15.OO g.), were heated together on a steam-bath for one hour. The mixture was cooled, poured on 127 to crushed ice* and ether-extracted* The extract was washed with N hydrochloric acid* with IT sodium hydroxide* and with water until neutral* and then dried over anhydrous sodium sulphate. The ether was removed on a steam-bath, and the residue distilled at reduced pressure to give the acetate ( 19*00 g.) b.p. l88-l89°/l8 rum** 1*5729* (Collyer and Kenyon* J 1940* 676 report b.p. 172°/ 15 mm., n ^ 1°5753). Hydrogenation of S-naphthylmethylcarbinyl acetate The acetate (19*00 g.) was hydrogenated in ether (150 ml.) in the presence of Haney nickel W-3 catalyst (ca.l g.) Time Temp. AT P ressu re &P Piemarks °C atm os. 13.15 24 96 Vessel flushed twice with before loading to max. pressure. 14.05 25 •f*l 93 -3 Stirrer and heaters on. I 4 . 4O 76 +51 108 +15 15*15 122 +46 122 +14 15.50 119 ~3 121 -1 17*20 124 +5 121 0 19.15 132 +8 118 -3 21.00 132 0 118 0 Stirring and heating sto p p ed . 24 81 Pressure released. 128 The hydrogenated material was filtered to remove Raney nickel, the ether removed on a steam-bath,' and the residue distilled at reduced p re s su re . Fraction I b.p. below 130°/l8 mm. 4°20 g . II 130-133°A8 mm. n^ 1*5265 11*92 g. Fraction I smelt strongly of acetic acid, and when redistilled at atmospheric pressure gave a main fraction with b.p. 118° (Founds equiv., 60*8, Calc, for acetic acid? equiv., 60*05). Fraction II gave a negative result on testing for an ester, and was redistilled, giving a main fraction b.p* 12 1 °/l5 mm., n^5 1*5270 (Founds C,89*45? . H,10*0* Calc, for 2-ethyltetralins C,89*95? H,10.05$)° A sample of this main fraction was subjected to vapour-phase chromatography. (Fig. 10) Preparation of g-naphthylmethylcarbinyl methyl ether (3 -Raphthylmethylcarbinol (20 g.) was added in 1 g. portions to finely divided potassium ( 4*5 g«) in benzene (45 ml.) over a period of half an hour with, constant shaking. After the addition was completed, the mixture was refluxed for half an hour, and then cooled* Methyl iodide (16*5 g°) was added in 1 ml. portions, and the mixture finally refluxed for 40 minutes* The product was washed with dilute hydrochloric acid and water, and dried over anhydrous potassium carbonate. After removal of the benzene the residue was distilled at reduced ------O ------ 129 - O v - Vapour-phase chromatograms of the hydrogenation products from ( i ) (3-naphthylmethylcarbinyl acetate (ii ) (J-naphthylmethylcarbinyl^methyl . t.. ; ... ether . . (iii) naph thy line thylc arbinol F i g / 10 130 pressure. A single wide fraction was takenf it (16.25 g*) was heated on a steam-bath for 3 hours with phthalic anhydride (10 g»), and pyridine ( 5*5 £•)> convert any unchanged carbinol to the hydrogen phthalate. The mixture, after standing for one hour, was dissolved in ether, and washed with dilute hydrochloric acid, dilute sodium hydroxide, and water. The ethereal solution was dried over anhydrous potassium carbonate, and after removal of the ether the residue distilled at reduced pressure. The methyl ether ( 10.50 g.) had b.p. 148-150°/l6 mm.,n 25 1.5719* A second preparation was carried out exactly as described above„ The methyl ether (8.32 g.) had b.p. 148-151°/l6 mm., n25 1*5724 (Pounds 0,84-35? H J. 9 5. C alc, f o r C—H-.Os D 1J 14 0,83.85$ H,7 -$ .) Balfe, Kenyon, and Searle (j., 1951, 38 o) report b.p. 148 - 151°/18 mm., n ^ 1 * 5829 * Hydrogenation of B-naphthylmethylcarbinyl methyl ether The methyl ether (10*60 g.) was hydrogenated in e th an o l (100 ml.) in the presence of Haney nickel W.3 catalyst (c a .0 .5 g*)§- 131 Time Temp. A t P ressu re A p Remarks °C atm os. 18.30 18 118 Flushed twice with H^. Filled to max. pressure. Allowed to stand over-night. 10.45 12 -6 117 -1 Stirrer and heaters switched on. 11.45 104 +92 148 +31 12.15 120 +16 152 +4 13-50 120 0 150 -2 15 .OO 120 0 150 0 Stirring and heating . I stopped. 12 112 Pressure released. The hydrogenated material was filtered to remove Raney Hi, the ethanol removed on a steam-bath, and the residue distilled at reduced pressure. F ra c tio n I b .p . 116- 118 ° / l 2 mm. n2^ 1.5267 3.7 9 g II 118 - 123° / l 2 mm. 1.5262 3.53 g III 123~126°/l2 mm. 1.5260 1.04 g Residue 1.15 g Vapour-phase chromatography, (Pig. 10 ), the boiling points, and the refractive indices, all showed that the product was the same as that obtained by hydrogenation of {3 -naphthylmethylcarbiryl acetate, i.e., 2-ethyltetralin. Hydrogenation of 3 -naphthylmethylcarbinol II. Using active Raney nickel W-3 catalyst The previous hydrogenation of the alcohol, using a stabilised catalyst, having been unsuccessful, a second hydrogenation was carried out using an active catalyst• (3 -Naphthylmethylcarbinol (l5»0 g.) was hydrogenated in ethanol (150 ml.) in the presence of active Raney nickel W-3 catalyst (ca.l g.). The temperature was raised slowly, so that any sudden changes in pressure, indicating step-wise hydrogenation, might be observed. Time Temp. P ressu re 0 A T A p Remarks C atm os• 4.30 16 124 Flushed twice with Filled to max. pressure Allowed to stand over n ig h t 0 10.30 12 -4 122 -2 Stirrer and heaters switched on. 13.30 7.6 +64 145 +23 14.15. 83 +7 147 +2 15.15 94 +.11 150 +3 16.05 97 +3 149 -1 I 6.50 106 +9 15.0 +1 17 -.45 us +12 153 +3 18.30 126 +8 154 ■ +1 19.40 132 +6 156 +2 Stirring and heating stopped. 14 112 Pressure released. ' 133 The hydrogenation product was filtered to remove Raney nickel, the ethanol removed on a steam-bath, and the residue distilled at reduced pressure. D istillation showed there to he a single product present| the main fraction had b.p. Il6-ll8°/l2 mm., 25 n D 1 •5272. Vapour-phase chromatography (FiglO ) confirmed this to he 2-ethyltetralin. Hydrogenation of g -Haphthylmethy 1 carhino 1 III. Using Adam’s platinum oxide catalyst Preparation of the catalyst A mixture of chloroplatinic acid (l.O g .), water (3 ml#), and sodium nitrate (10 g.) was evaporated to dryness, hy warming gently over a Bunsen flame, while stirring with a glass rod. The temperature was then raised, over a period of 20 minutes, to between 500 and 550° during which time fusion took place with the evolution of brown oxides of nitrogen. The temperature was held at this point for 30 minutes to complete the fusion, and the melt allowed to cool. The mass was treated with water (15 ml.), and the brown precipitate washed twice by decantation. The precipitate was filtered off, washed on the filter until free from nitrate, and dried in a desiccator. The yield was 0*42 g. [3 -Haphthylmethylcarbinol (l5»0 g.) was hydrogenated in ethanol (150 ml.) in the presence of Adam!s platinum oxide catalyst (0.42 g.). Ho uptake of hydrogen was observed at lower temperatures, and the temperature was gradually raised to 205° • V K \' 134 ------ Time Temp. A t P ressure A p Remarks. °c atm os. i 14*45 21 102 Flushed twice with H F ille d to maximum p re s su re . 15.15 19 -2 99 -3 Stirrer started. 15.45 20 +1 99 0 Heaters switched on. 17.00 118 +98 128 +29 18.05 137 +19 136 +8 18.40 139 +2 137 +1 Heating increased. 19.20 149 +10 140 +3 20.25 165 +16 148 +8 21.20 172 +7 151 +3 Stirrer and heaters switched off. 13.45 21 98 Following day. Stirrer and heaters switched on 15 .45 176 +155 150 +52 16.15 203 +27 168 +18 16.22 205 +2 168 0 Heaters off. 16.50 181 156 Stirrer switched off. 21 98 Pressure released. 135 The hydrogenation product was filtered to remove Raney nickel, the ethanol removed on a steam-bath, and the residue distilled at reduced pressure. Fraction I b.p. 148-150°/21 mm. 1.5743 II 150-154°/21 mm. 1.5760 I I I I 54-I65°/21 mm. 1.5770 Residues crystalline In the above fractionation, distillation was continuous over the whole range 148-165°/21 mm., and fractions were therefore taken at random. Redistillation of Fractions I, II, and III, also failed to give any clear-cut fractions. On standing both low- and high-boiling fractions deposited unchanged $-naphthyl- methylcarbinol m.p. 65- 67 ° (without recrystallisation). The distillation residue was recrystallised once from light-petroleum (b.p. 60-80°) to give unchanged -naphthylmethylcarbinol m.p. 7 2 -7 3 °. Vapour-phase chromatography showed that the only other compound present was 2-ethyltetralin. CYMYLlSTHYLCiiRBINOL 137 DISCUSSION Introductions The interpretation of the results in this section is complicated "by the fact that it was not possible to carry out the chromatographic analyses until the experimental work had been completed. As a result it was not discovered until the work had been finished that the C3>myl alcohol which had been prepared was not a single entity* 2-(p~cymyl) methylcarbinol, but a mixture of two isomers. Experimental evidence had given no reason to believe that the alcohol was other than a single entity* and it was not until chromatographic analysis was carried out that it was found to be a mixture of isomers. It is endeavoured* in the following discussion, to evaluate and explain the results in the light of the chromatographic evidence. The preparation of 2-(p-cymyl)methylcarbinol This alcohol was prepared by a Meerwein-Ponndorf- Verley reduction, with aluminium isopropoxide, of the ketone 2-acetyl-p~cymene. The alcohol behaved as a single entity, distilling sharply at 100-102^1 mm., and gave a well defined N-4~ The ketone* 2-acetyl-p-cymene, was prepared as 138 described “by Allen (Org. Synth., Coll. Vol. II, 3), who obtained it by acetylation of p-cymene, with acetyl chloride, in the presence of aluminium chloride at -5 to +5°. It, also, behaved as a single entity, distilling sharply at 145-147°/30 mm., and had n^I.5183, n ^ l. 5168 . (Allen reports b.p. 155-157/30 mm. Lacourt, Bull. Soc. chim. beiges, 1929? 38_? 1? reports b.p. 124*2- 0 . 20 \ 5*2/12 mm., n ^ 1 . 5185 ). It gave a well defined semicarbazone, m .p. 146. 5- 147 °? for which Lacourt reports m.p. 147°* Thus on the basis of the above evidence the cymyl alcohol was assumed to be the single entity 2-(p-cymyl) methyl carbinol I. ch ( oh )m< However, vapour-phase chromatography (Big. 12 page 150) showed the alcohol, in fact, to be a mixture of two isomers, present in the ration of 7*0sl. The ketone was therefore examined by chromatography (B ig. 11 page 349) and also found to be a mixture. This was to be expected as it was unlikely that the aluminium isopropoxide reduction could be responsible for isomerisation of the magnitude detected in the alcohol. The interpretation of the chromatogram of the ketone is complicated by the fact that there are four peaks 139 present, and not the expected two. However it was found that hy varying the length of time that the ketone remained on the column the sizes of the peaks were also altered, indicating that some rearrangement or decomposition of the ketone takes place on the column. This is further supported hy the unsymmetrical shapes of peaks A and B, a feature often indicating a reaction taking place on the column. Thus it is possible that peaks C and D (present in the ratio of 4«0sl) are caused hy the two isomeric ketones which produce the mixture of two cymyl alcohols on re d u c tio n . It is suggested that the two isomeric ketones are 2-me thy1-5-i so pro pylac e to phe no ne II , and 2-m ethyl-4-isopropyl- acetophenone III. (Hereafter referred to as 2-acetyl-p-cymene and 6-acetyl-m-cymene respectively) ,COMe COMe This suggestion is based on the work of Nightingale and S hackelford ( J . Amer. Chem. S o c., 1956? !§.? 133) who rep eated the acetylation of p-cymene using Allen’s method, hut varied the temperature. They found that acetylation of p-cymene at temperatures not higher.than 5° (Allen recommends -5 to +5°) leads to a mixture of II and III in which III predominates^ the product yielding a 140 semicarbazone m.p. 168°, v/hich is the derivative of 6-acetyl-m- cymene III. $hen the reaction was carried out at -5 to -10° no semi-carbazone of III was isolated., the product under these conditions presumably being either exclusively, or predominantly, 2-acetyl-p-cymene II, semicarbazone m.p. 147°. In the present work the acetylation of p-cymene was carried out between the lim iting temperatures -10 to +5° 5 throughout the greater part of the preparation the temperature being kept below 0°. In accord with this, the melting point of the semicarbazone (m.p. 146.5-147°) prepared from the product, indicates that the predominant isomer was 2-acetyl-p-cymene II. It is therefore suggested that the predominating cymyl alcohol is 2-(p-cymyl)methylcarbinol IV, and that the minor lower boiling component of the mixture is 6-(m-cymyl)methylcarbinol V. i.CH(°H>fc ch (oh )m< IV V Hydrogenation of the cymyl alcohol The first hydrogenation of the cymyl alcohol was carried out with a stabilized Raney nickel catalyst. Ho uptake of hydrogen was observed at the in itial reactiort-temperature of 130° 141 and the temperature was therefore raised to 170°. At this temperature hydrogenation appeared to take place. D istillation of the reaction product showed there to he a mixture present. The hulk; of the product distilled continuously over the range 98-112°/l6 mm. § there was also a small higher "boiling fraction present* "b.p. 120- 128 ° / l 6 mm., which constituted ahout 10$ of the reaction product. Analysis showed the low-hoiling distillate to he almost exclusively hydrocarbon having a composition intermediate between that of ethylcymene and ethyImenthane* showing hydrogen- olysis to have taken place. Vapour-phase chromatography (Fig. 13(i) page 155) produced three sets of peaks. The two major groups of peaks* A and B, are produced hy an isomeric mixture of ethylcymenes (b ) and ethylmenthanes (a ). These multiple peaks are to he expected since the cymyl alcohol was a mixture. The reason for four peaks in the ethyl cymene hand is not evident* although it is possible that* as in the case of the acetyl cymenes, some rearrangem ent i s ta k in g p lace on th e column. The th ir d h ig h - boiling set of peaks* C* is produced hy the menthyl alcohols. These are responsible for the 1$ of oxygen found to he present* hy analysis* in the low-hoiling distillate. The small high-boiling product of hydrogenation was shown* hy analysis* to he chiefly menthyl alcohol* the expected hydrogenation product. The menthyl alcohol was characterised by 142 the preparation of a l\F-4~d.iphenylylcarhamate5 "but i t is not possible to say of which of the four isomeric menthyl alcohols this was the derivative. Vapour-phase chromatography (Fig. 13(ii) pagel55) produced two main sets of peaks. The low-boiling band B is produced by ethylcymenes. The major group of peaks (c \ C^9 C^, and C^) is produced by the menthyl alcohols. The stereochemical course of catalytic hydrogenation of 2-(p-cymyl )methylcarbinol and 6-(m-cym,yl )methylcarbinol Cis-addition of hydrogen to (i)-2-(p-cymyl) metbylcarbinol (P and Q) can give rise to four diastereoiso-meric 1 1 forms of 2-(p~menthyl)methylcarbinol R9 R and S9 S . 143 R R* HO H H OH A / HO' H H OH Q i i » i i i OH ♦ 1 Me S ! S HO OHH R R^ and S comprise two diastereoisomeric racemates? each, racemate "being obtained hy addition of hydrogen to a different side of the benzene ring. If addition of hydrogen takes place with equal ease to either side of the ring the two 144 raoemates w ill "be obtained in equal amounts, and no asymmetric synthesis will result. An argument exactly analagous to the above w ill apply to 6-(m-cymyl)metbylcarbinol. Thus hydrogenation of the two isomeric cymyl alcohols can give rise to a total of four racemates, and each of these will be present in different amounts if dissymmetric addition of hydrogen takes place. Vapour-phase chromatography (Fig. 13( ii) page 155) indicates that the four menthyl alcohols (C^, G*% C^, C^) are indeed present in different amounts, showing that in both cymyl alcohols hydrogen must have added preferentially to one side of the benzene ring, and that, therefore, an asymmetric hydrogenation has taken place. . Examination of the cymyl alcohols with Gatalin models shows that either side of the benzene ring can be presented in a planar conformation to the catalyst. The fact that addition does not take place with equal ease to either side of the ring must therefore mean that the asymmetric centre at controls the mode of adsorption of the alcohols on the catalyst, such that each alcohol is adsorbed, predominantly, in one preferred conformation. Cis-addition of hydrogen to the side of the adsorbed molecule facing the catalyst thus results in dissymmetric hydrogenation of the two alcohols. 145 Further attempted hydrogenations of the cymyl alcohol In an attempt to lim it the extent of hydrogenolysis, hydrogenation of the alcohol was attempted under a variety of experimental conditions. With an aged Raney nickel catalyst the main products of hydrogenation were ethylcymenes. The chromatogram (Fig. 14? page 157) also showed the presence of small quantities of ethylmenthanes and of two compounds of unknown composition (X and Y). Ro m enthyl a lc o h o ls ?^ere obtained# and a la rg e amount of cymyl alcohol remained unchanged. When hydrogenation was repeated with a freshly prepared active Raney nickel catalyst, bydrogenolysis again occurred with the production of ethylcymenes, and the two compounds of unknown composition mentioned above. In this hydrogenation the two unknown compounds (X and Y) comprised the greater part of the reaction product. Ho ethylmenthanes or menthyl alcohols were obtained? a small amount of the cynyl alcohols remained unchanged. 146 CONCLUSION Attempts to carry out an asymmetric synthesis hy dissymmetric addition of hydrogen to the cymyl alcohols have proved in the main unsuccessful? owing to the occurrence of hydrogenolysis and the resultant destruction of the asymmetric centres at „ In only one hydrogenation were any menthyl alcohols produced? and then they only constituted ahout 10$ of the reaction product. However? chromatography has shown that the proportions in which these menthyl alcohols were present must mean that they were produced hy dissymmetric addition of hydrogen to the cymyl alcohols. Thus an asymmetric synthesis has heen achieved hy hydrogenation. This is the only recorded example of an asymmetric synthesis achieved hy hydrogenation of an aromatic nucleus. The result is explained hy the suggestion that the asymmetric centre at controls the mode of adsorption of the aryl alcohol on the catalyst so that it is preferentially adsorbed in one of the possible conformations. Cis-addition of hydrogen to the side of the adsorbed molecule facing the catalyst thus results in preferential addition of hydrogen to one side of the benzene ring producing an asymmetric synthesis. • * • 147 EXPERIMENTAL Preparation of 2-methyl-l>-isopropylaoetophenone ( 2-Ac ety 1 -p - cyme ne ; Phis was prepared by a Friedel-Craft reaction, using the method of Allen (Org. Synth,, Coll. Vol. II, 3). A 3-L three-necked flask was fitted with a dropping funnel, a Hershberg-type stirrer, a low-temperature thermometer (range - 20° to + 20°), and a condenser, to the upper end of which was connected a gas trap for the disposal of hydrogen chloride evolved during reaction. A mixture of carbon disulphide (400 ml.) and anhydrous aluminium chloride ( 360g.) was placed in the flask, which was immersed in an ice-salt freezing mixture, and stirred until the temperature dropped "below -5°* A mixture of p-cymene ( 350gO and acetyl chloride (200 ml.) was then added at such a rate that the temperature never rose above 5°I through out the greater part of the addition the temperature was maintained between 0 and -10°. The mixture was allowed to stand over^-night, and poured on to crushed ice (2 kg.) to which concentrated hydro chloric acid (400 ml.) had been added. The mixture was extracted with ether (3 x 1 1 .), the extract dried over anhydrous calcium chloride, and the ether distilled off on a steam-bath. The residue was placed in a distillation flask provided with an 11 in ch 148 unpacked column and heated on an oil hath at atmospheric pressure 'until the temperature of the hath reached 210°. During this heating a small amount of unreacted p-cymene ( 26«5g.) distilled over* The remaining material was distilled at reduced pressure to give the ketone (33 5g*? 79 $) as a pale yellow oil? ho p. 145- 147 ° / 20 25 o 30 mm., n ^ 1.5183, n ^ 1.51685 semicarbazone mop. 146. 5-147 • A second preparation, with half quantities, gave ketone (l83g., 82 $) having "b.p. 143-145°/30 mm., n ^ 1.5174- Vapour-phase chromatography (H g .ll) shuhsequently showed the ketone to he a mixture of isomers. Preparation of 2-(p-cymyl)methylcarhinol Aluminium foil (ll3g.) was dissolved in isopropyl a lco h o l (2200 ml.) hy warning on a steam-hath under reflux, reaction heing initiated hy addition of a few crystals of mercuric chloride. The resulting grey solution was cooled slightly, and 2-acetyl-p- cymene (335g°) added. The mixture was heated under reflux for one hour, and then the acetone allowed to distil slowly. When all the acetone had heen removed the remaining isopropyl alcohol was distilled under reduced pressure. The viscous grey product was cooled, and \ added to an excess of 2B sulphuric acid and ice. The alcohol was extracted with ether, and the ether extract washed with 2B sulphuric a c id , 2B sodium hydroxide, and water. The ether solution was dried over anhydrous potassium carbonate, and the ether removed hy 149 90 Vapour-pha.se chromatogram of the]cymyl ketona 4atio C:D \ f 4 . 0:1 " 150 o\ • - • ...... CO------ . Vapour-phase chromatogram of the. cymyl alcohol R atio A:B Fig. 12 151 distillation on a steam-bath. The residue was’distilled at reduced pressure to give the aloohol ( 25%*? 1&?°) as a sweet smelling* pale yellow, viscous oil b.p. 100- 102° / l mm., n ^ 1 . 5150- (Founds 0, 81.35? H,10.05. gi 2Hi 8 ° c > 8 0 .85 ? H 10.15$). A sample was chromatographed (Fig* 12). See discussion page 137 a - ( 2~p~c.ym>yl )ethy 1 R-4-diphenyl.yl carbamate 2-(p-Cymyl)methylcarbinol (l.8g.) was heated with 4-i so cyanatodi phenyl (l.9g«) on a steam-bath for one hour* The product vra,s dissolved in light petroleum (b.p.100-120°) and insoluble di-4-diphenylyl urea(o.20g.) filtered off. After three recrystallisations from light petroleum (b.p.100-120°) the R-4~diphenylylcarbamate (2.20g.) had constant m.p.H4-115°- (Founds 0, 79-85? H, 7-55? N, 3*75- C^H^O^ requires C, 80.35? H, 7-3? Nf 3 .7 5 $ -) Preparation of 2-p-c.ymylmethylcarbinyl hydrogen phthalate 2-p-Cymylmethylcarbinol (ll.O g.), phthalic anhydride (8 .8 g.), and pyridine ( 4 »9g.) were heated on a steam-bath for three hours, and left to cool over-night. The homogeneous product was diluted with an equal volume of acetone, and acidified to Congo Red with 2H hydrochloric acid. The resultant oil was poured on to crushed ice, and stirred until it solidified. The crude hydrogen phthalate (l 9g-) had m.p. 63- 65°, and when dried under vacuum gave a colourless very viscous oil, which could not be induced to 152 crystallize. The oil was crystallised from a mixture of ether and light petroleum (b.p. 60-80°) to give the hydrogen phthalate as colourless rhombs of constant m.p. 85-87°® As before, drying of this material resulted in the formation of ah oil. (Founds equiv., 344° ^ 19^ 21^ 2 ° ^ ^ requires equiv., 326. C^H^O^-COOH. lH^O requires equiv., 344*) Thus it would appear that the hydrogen phthalate has lH^O of crystallisation, and that on drying this is removed to give the anhydrous hydrogen phthalate as an oil. Preparation of 2-(p-Cymyl) methylcarbinyl acetate Four preparations of the acetate were carried out. P rep. 1 P rep. 2 P rep. 3 P rep . 4 Alcohol 4«45 §• 445 £• 4.45 g . 4.45 g. P y rid in e 2 017 § • 2.17 g . 2.17 g. 2.17 g. A cetic 3.06 g . 3 .0 6 g . Anhydride A cetyl 2.16 g . 2.16 g . C hloride R eaction H t. 1 h r . Stand at 25° H t. 1 h r . Stand at 25° co n d itio n s a t 100° f o r 24 h r . a t 60° fo r 24 h r . Y ield 4*00 g . 3®35 g . 3.00 g . 3.4 2 g . b .p . 146-8°/l9 mm. 146- 8 ° / l 9 mm. 144-6°/l7 mm 151-3°/22 mm. 25 1.4940 1*4943 n D 1.4941 1.4944 The reaction product from each preparation was poured on to crushed ice, and ether-extracted. The ether extract 153 was washed with H hydrochloric acid, II sodium hydroxide, and water. The ethereal solution was dried over anhydrous sodium sulphate, the ether removed on a steam-bath, and the residue distilled at reduced, p re s su re . All four preparations were finally combined and re distilled with difficulty, owing to severe frothing occurring at the boiling point, to give a main fraction b.p. 147 ~148 ° / l 8 mm., n*£ 1.4934 (Founds C,77 *1? H ,9»0. ^ 3.4^ 20^2 requires C,76.35? H,9«15$•) Hydrogenation of 2-(p-cymyl)methylcarbinol I. Using a stabilized Haney Hickel catalyst The alcohol (l5«0 g*) dissolved in ethanol (150 ml.) was hydrogenated in the presence of a stabilized Raney nickel catalyst (B.D.H. stabilized Raney Hi). Time Temp. P re s s, Remarks A t °C atm os. A.P 10.15 22 100 Flushed twice with H Filled to 100 atmos. Stirrer and heaters on. 10.55 59 +37 115 +15 11.35 128 +69 138 +23 12.15 133 +5 140 + 2 13.15 133 0 140 0 Heating increased 13.55 170 +37 157 +17 14.35 171 +1 157 0 14.55 169 -2 178 + 21 Pressure raised to maximum 15.-55 171 +2 178 0 16.35 170 -1 178 0 Stirrer and heaters off 21 110 Pressure released 154 The hydrogenated material was filtered to remove Raney nickel, the ethanol removed on a steam-bath, and the residue distilled at reduced pressures I 98-102°/l6 mm. n^ 1-4759 2.69 go II 102~104° / l 6 mm. 1.4785 2.06 gc III 104- 108 ° / l 6 mm. I. 48 OO 1.28 go IV 108-112 °/l6 mm. 1.4798 1.55 g. V 120- l 28 ° / l 6 mm. 1.4759 1.79 g. chiefly 126-128°/l6 mm. All fractions were colourless. Fraction V was more viscous than fractions I to IV, and reacted much more rapidly and completely with a bead of sodium than did fraction I. Fraction II Founds C,86*2f H,12.6$ (By diff.0,1.2) Calc, for C12H18 ( 2“E'fcl]^1'’P“ cymene) C ,88.8f H 5II. 2 . C alc, f o r C]_2H24 (2-Ethyl-p-menthane) C, 85.655 H,14»35$» Fraction V Founds C,80.6f 33,12*7 * Calc, for C-^gH^O (2-(p-mentlayl) - methylcarbinol) C, 78.2^ H,13.1$. Calc, for (2-(p-cymyl)- methylcarbinol) 0,80.85? H,10.15$. Fractions II and V were subjected to vapour-phase chromatograpiiy (Figs. 13(i) & (ii))* Chromatography confirmed fraction II to be a hydrocarbon mixture, as indicated by analysis, and showed fraction V to be a more complex mixture in which the hydrogenated alcohol predominated. + • -T i ' ; l : -t T 1- : rv r ; Vapour-phase chromatograms of products from 1st, hydrogenation - of- cymyi aicohoi ~y*- (i). Fraction II (ii)Fraction V ■.TP ; lahd; C * Menthyl EEIt 156 J a ~(2-p-menthy 1) ethy 1 H-4~diphenylylcarbamate The fact that fraction V contained 2-(p-menthyl)- methylcarbinol was further confirmed by the preparation of the N-4-diphenylylcarbamate* :: A portion of fraction V (l.02 g.) was heated with 4-iso cy anatodiphenyl (l.OO g.) on a steam-bath for one hour. The product was dissolved in light petroleum (h.p. 100-120°) and insoluble di-4-diphenylyl urea (0.30 g.) filtered off. After three re- ciystallisations from light petroleum (b.p. 100-120°) the very soluble H-4~diphenylyl carbamate (0.06 g.) had constant m.p. 137*5- 138.5°. (Founds 0,79*1? H,8.5. reCLuires 0,79*3-5 H,8.75$) Hydrogenation of the c.ymyl alcohol. II. Using a Raney Hickel W-3 Catalyst of low activity. In this hydrogenation an aged sample of Raney nickel W-3 catalyst was used. Unlike freshly prepared Raney Hi W-3 this did not ignite spontaneously when exposed to air. The cymyl alcohol (20.0 g.) dissolved in ethanol (150 ml.) was hydrogenated in the presence of an aged Raney nickel W-3 catalyst (ca. lg.) Hydrogenation was in itially attempted at 100°C and a pressure of 135 atmos. Ho uptake of hydrogen took place, and the temperature was therefore raised to 170° while the pressure rose to 166 atmos. Although the uptake of hydrogen was still smaller than that required for hydrogenation further heating was Vapour-phase chromatogram of product from 2nd* hydrogenation 157 158 t considered unwise* and reaction was stopped. After removal of Raney nickel and ethanol from the reaction product* the residue was distilled at reduced pressure. Fraction I 120°/l7 mm. n^ 1*4247 1*11 g. II 120-130°/17 mm. 1.4956 5.69 g. Ill 130~144°/l7 mm. I .5063 11.98 g . Vapour-phase chromatography (fig. 14) showed fraction II to contain chiefly hydrogenolysis products and unchanged cymyl alcohol. Fraction III was found to he largely unchanged cymyl alcohol contaminated with small quantities of low-hoiling impurities. Chromatography also showed the presence in fraction II of two compounds of unknown composition (X and X). Hydrogenation of the cymyl alcohol.III. Using an active Raney Hickel W-3 catalyst. In view of the large amount of unchanged cymyl alcohol obtained in the preceding reaction* hydrogenation was repeated using a freshly prepared qyr ophoric Raney nickel W-3 c a ta ly s t. The cymyl alcohol (15*5 §•) dissolved in ethanol (150 ml.) was hydrogenated in the presence of an active Raney Hi eke 1 W-3 catalyst (ca. Ig.) 159 ...... i Time Temp. P re s s . Remarks A T atm os. A? 10.15 9 124 Flushed twice with H Filled to max. press. 10.45 8 -1 124 0 Stirrer and heaters on. 11.25 52 +44 138 +14 12.15 100 +43 160 +22 14.05 102 +2 162 +2 Heating increased. 15.45 139 +37 177 +15 17.50 I 64 +25 189 +12 18.15 166 +2 190 +1 Heating and stirring sto p p ed . 11 . 124 Pressure released The hydrogenation product was filtered to remove Raney nickel, the ethanol removed on a steam-hath, and the residue distilled at reduced pressure. F ra c tio n I 108~110°/l2 mm. n^5 1.4895 O.47 g . II 110- 114° / l 2 mm. 1.4907 5.91 g. III 114-ll8°/l2 mm. 1.4909 4.59 g* IV Il8-120°/l2 mm. 1.4926 2.13 g. Residue 1 ° 47 S • 160 T4 Xt l6 l Fraction II. Founds C 984 * H,10.7 (hy diff. 0,5•!$)• low percentage of oxygen (the saturated alcohol contains ca. 9t) indicates that hydrogenolysis has again occurred. Vapour-phase chromatography (Fig. 15) showed fraction II to he a mixture of ethylcymenes, and two compounds (X and Y) of unknown composition, only found to he present in small quantities in previous hydrogenations. Chromatography also showed there to he a small amount of unchanged cymyl alcohol present in fraction V. VAPOUR-PHASE CHROMATOGRAPHY (EXPERIMENTAL CONDITIONS) 163 Chromatograms, 1 to 6, 9j 10, and 12 to 15. Packings 20$ tritolyl phosphate on 72-100 mesh Celite 545* Columns 120 x 0 .4 cm.Temp., 150°. I n l e t p re ssu re s 33.8 cm, Hg. Outlet pressures atmospheric. Rate of flows ca. 30 ml./min. Carrier gass argon, with Lovelock ionisation detector. Chromatograms 9 7 and 8 . Packings 20$ trito ly l phosphate on 100-120 mesh Celite 545* Columns 120 x 0 .4 cm.Temp., 75°. I n l e t p re ssu re s 112.5 cm. Hg. Outlet pressures atmospheric. Rate of flows 41 m l./m in. Carrier gass argon, with Lovelock ionisation detector. Chromatogram, 11. Packings 20$ squalan© on 80-100 mesh Celite 545* Columns 120 x 0.4 cm. Temp., 155°. Inlet pressures 12 lbs./sq,.in. Outlet pressures atmospheric. Rate of flows ca. 60 ml./min. Carrier gass 75$ hydrogen and 25$ nitrogen mixture, with thermo-couple detector.