Professor:

THE AUST RALIM~ NATIO ld1L UN IV ERSITY

John Curtin School of ~·i edical Research

Annual Report 1966

De partment of r·1 edi cal Chemistry

STAFF

6/1967

A. Albert, B. Sc. (Sy d .), Ph. 0., D.S c . (Land.), F. R.A.C. I., F .A.A.

Reader:

D • J . B row n , rt; • S c • ( Sy d • ) , P h • D .. , D • S c • ( L o n cl • } , F • R • A • C • I •

Professorial Fellow:

D. D. Perrin, H.Sc.(LZ.), Ph .D.,D.Sc.(Lond.), F.R.I.C.,

F.R.A.C.I.

Senior Fellow:

E. Spinner, M.Sc.Tech., Ph. D.( Manc.), F.R. A.C.I.

Microanalyst (Fellow):

J o y c e E • Fi 1 des , B • S c • ( Sy d • } , .,J • S c • ~ P h • D • ( n i rm • ) •

Fellows:

W • L • F • r.., rm a r e g o , P h • D • ( L o n d • ) , F • R • I • C • ; G • B • B a r 1 i n ,

M.Sc.{Syd.), Ph.D.U .. N.U.), F. R. A.C.I. ; T. J. Batterham,

Ph.D.( N.S.N.) ( f rom October, previously Research Fellow).

Research Fellows :

N. W. Jacobsen, M .Sc.( W . A ust.)~ Ph .D.( A. N.U.) (resigned

Eovemb e r); V. S. Sharma, ;L Sc •• Ph.O.(Agra);, E. Kalatzis,

B.Sc.(Alex.), Ph.D.(Lond.); Vi . E. C. Biffin, Ph .O.(Lond.);

B. D. Batts, Ph.D.(Queensland); R. M. Hoskinson, Ph.O.(N.S. tL)

(commenced February); P. B. Ghosh, B.Sc.(Lond.), Ph.D.

(East Anglia, En9land) (commenced June).

Visiting Research Fellow:

J. J. McCormack, Ph. O.(Vale), U. S. National Institutes

of Health Postdoctoral Fellow (until May).

- 2 -

~esearch Assistants:

B. T. England9 B.Sc. (A.r:.u. )(from January} .

S v ea - fte et Ja as on, B • Sc . ( iL S • ~L ) ( fro~ ii ay ) .

Head Technician:

J . A. i''!aguire .

r:Es EARCH w .. i RK

Introduction

6/ 1967

riedica·1 chemistry is the stuay of chemical fa~11ilies in which

strong and highly selective bioloqical effects reside. It covers

(i) the organic chemical syntheses of these substances, their

analysis , ano th~ study of their chemical properties~ (ii) the

stu~y of their physical properties and atte~pts to correlate these

with molecular structure, and beyond this with biological properties,

and (iii) the inorganic co~~rdination chemistry of biologically­

active metal cations.

In this ~epartment the subject is being developed by (a) studies

of the teterocyclic chemistry of substances related to the nucleic

acid bas~s, especially the physical and organic chemistry of

pteridines, pyrimidinesi and purines, and (b) quantitative studies

of equ ilibria involving biologically-potent heav_y metal cations

with biologically-occurring ligancs.

Covalent hydration of B-azapurines (Albert)

Although 1 in 1965, no hydration could be detected in members

of the purine faMily, the 8-azapurines have now been found to have a

h i g h a f f i n i t y f o r \~a t e r , w h i c h t :i e: y a d d a c r o s s t h e 1 , 6 - do u b 1 e b o n d

(and hence elimincte it). This hyuration can be repressed by

inserting a methyl-group in the 6-position, where it offers the

expected steric and electronic hindrance~ but the similar effect

of a 9-metnyl group was unexpected and will be investigated further.

- 3 - 6/1967

Covale~t hydration has.considerable biological importance: the

presence of a hitherto unexpected alcoholic group must alter the

pattern of distribution in the body. Horeover hydration can produce

a substance which can serve as a depot for a more biologically active

substance if this is obtainable by gentle oxidation. Thus the

hydrated form of 2-amino-8-azapurine is readily oxidized in vitro to

8-azaguanine which is highly active against cancer in the rat, but

is eliminated too fast from the human body to be a useful drug.

The possibility that hydrated 2-amino-8-azapurine may act as a

precursor of 8-azaguanine is being teste rl for us by Dr. Chester Stock

in the Sloan-Kettering Institute (New York).

Nucleophilic additions in pteridines (Albert, McCormack)

The surprising ability of certain pteridines to add Michael

reagents, demonstrated here last year, has been extended to

2-aminopteridine which gives 2-amino-3,4-dihydro-4-substituted

pteridines with the following nucleophilic reaqents: sodium hydrogen

sulphite, dimedone, 4,6-dihydroxypyrimidine, barbituric acid,

2-thiobarbituric acid, nitromethane, an ~ even ethanol and methanol.

The oxidation of heterocycl ic hydrazines (Albert, Catterall}

In a comprehensive study of the best conditions for replacing

a hydrazine-group by hydrogen in heterocyclic compounds, two

reagents proved to be outstandingly reliable, (a) oxygen in the

presence of ethanolic alkali, and (b) aqueous cupric sulphate.

This replacement re action is useful for the synthesis of many

nitrogen heterocyclic substances required in medical chemistry,

and enough knowledge has now been obtained for the reaction to be

undertaken with more confidence than formerly.

Polymers of 2-aminobenzaldehyde {Albert, Yamamoto}

~1'. hen 2-aminobenzaldehyde is stored at room temperature, a

trimer is formed, whereas acidic conditions produce the salt of a

tetramer which is changed on neutralization, to another tetramer of

more complex structure. These substances do not have the simple

- lf -

constitution assigned to them in the literature, but ~re cage

mol&cules whose exact structures have no~ been determined by

physical methods (princi~ally ultraviolet, infrared, and proton

magnetic resonance spectrosco.y).

PvriMidines (Browr)

The quite special importance of the pyri~idines nucleus in

Nature is indicated by the new types of oyriMidine constantly being

discovered in ribonucleic acids (both transport and microsomal).

To increase knowledge of the chemistr· of this still imperfectly

understood nucleus, the following studies 4ere unrlertaken.

~u cleophilic displacements in pyrimidines

{Brown, Foster, Ford)

Aminolyses of 2- and 4-methoxy (or methylthio) pyrimidines

bearing C-methyl, 5-brorno-, or 5-nitro groups have oroved of value

for preparing the corresponding alkyl3minopyrimidines in the

absence of solvent. The rate constants indicate mild deactivation

by methyl groups, moderate activation by a bromo substituent, and

profound activation by the nitro 2roup.

Pyrimidine 2- and 4-sulp~ones and sul~hoxides have been found

to undergo facile reactions with nucleophiles. Rate constants for

their aminolysis indicate a sliqhtly greater reactivity than the

corresponding chloropyrinidines, and some 1c5 times the reactivity

of the t h i o et he r s from H h i c h t ·. e y \fJ ~re de r i v e d .

been extended to the purine series.

The rimroth Rearrangement

(Bro n, Paddon-row, England)

The work has

The facilitatino effect of electron-withdrawing ~roups on

Dimroth Rearrangement of l-alkyl-1,2-uihycro-2-iminopyrimidinas has

been further explored: 5-haln, 5-carba~oyl, or 5-cyano substituents

increase the rate in that order; so too does replacement of the

N-alkyl group by an allyl, 2 1 -hydroxyetllyl, benzyl ~ or

p-nitrobenzyl group. The introduction of a 5- or N-prop-2'-ynyl

group leads not only tc rapid Oimroth ~e&rrangement but 3lso to

,. -· 0 -

interesting isomcriz a tions in the side chain to yield

allenyl and prop-1'-ynyl deri •atives as well as bi cyclic

products .

Dimroth 2earranqement proceed~ rapidly and normally in

anhycrous secondary amines, e.1. diethylamine, but not in primary

~~ ines (abnormal ali~hatic products). \\'. o reaction occurs in

6/19f7

tertiary amines. This behaviour is consistent with the previously

postulated mechanism in aqueous media. ~earrangements of

1,4-dialkyl-1,2-dihydro-2-imincpyriri dines r roceed so very

sluggishly that hydrolysis tc the corres oond ing oxopyrimidines

overrides -the reaction. ~ hile the reason for this was being

sought by proton m-gnetic resonance techniques~ in collaboration

with Dr T. Batterham, a new an~ rapid (acid/base catalysed)

deutera tion of the 4-methyl roups in such molecules was discovered.

The "Christmas r.ea rrangement 11 ( Bro\<1n, Pa.ddon-R0\'1)

This reaction, first discovered in this Department in

December 1965, is exemplified by the is ome ri zation of 1-aryl (or

benzy1)-4-marcapto-1,2,3»5~7-penta-azaindene to 4-aryl(or benzyl)

amino-1-thia-2,3 ,5 ,7-tetra- aza inde ne . It has no ~ been s how n that

each rearrangement reach es an equilibrium (from eith e r component)

in the molten state or by boiling in an alcohol or other solvent.

In most cases the equilibriu~ constant favours the tniatetra-azaindene,

but in alkali the acidic mercapto compound is favoured. Electron-

withdrawing £-Substituents incre ase the rate of equilibration, and

a rectilinear plot is obtained for Hammett's sigma-values against

1og !f (rate of fission for tne penta-azaindene).

The Hilbert and Johnson RP.arrrtnaement (Brown, Lee)

The effect of substitution on the rate of thermal

rearrangement cf alkoxypyrimidines has been furt he r explored.

The measured rate differences are quite sm all with the exception

of that occasioned by a nitro qroup.

5-Nitropyrimidines (Brow n, Biffin, Lee)

Attempts to make 5-ni tropyri mi~i ne in many laboratories have

failed. Following t ne qcneral stucy of hydraz ino h eterocvcle ~,

- 6 -

~e ntiane~ aDovej 4,~-dihyora zino-5-ni t rooy ri m i~ine ~ as oxidized

by silver oxi de in methanol to ~ ive 5-nitropyrimidine in go od

yield . Its cat ion wa s covalently hydrated, t~e first ex am ple of

this phenomenon in a s in~le ring heterocycle . Similar reactions

have been used t o rn3ke r el ate~ co~po un ds .

rg uilibri ~ be t ween ~etal cations and organic

con olexino su0stances ( Pe rri n, S~arma, Sayce)

To t hrow rore light c~ Quantitative as,ects of ~etal-complex

f. /l 'JC7

e q u i i i b r i a. i n b i o 1 o a i c a 1 s y s t ems s a co m ;'JU t e r pro'} r a nn e :ia s been

developed for calcul3ting the concentrations of metal complexes

(including polynuclear, mixed, and hydrolysed species} in multi-metal

multi-ligand systemss by using the values of t1eir stability

constants . Su ch syste~s, also serve as mod els of me talloenzyme-

substrate interactio ns . Sta bili ty constants of su ch complexes

for several bi valent metal i ons with representative ligands have

been obtained from potentiometric me6s urene nts: calcu l a tions were

c a r ri e d o u t 1Ji t h a g e n er ;1 1 co r p u t er ;i r o g r a mm e i n to w h i c h 111 e re fed

the titrati 0n d~t~ and t ~e known const ants f0r complexes containing

only one tyoe of li gand . ~uantita tiv e equ ili bria unde r physioloqical

con~iticns be t~ een his t idi ne and bivalen t wetal ions, including

copper(II)s hav e been e luci date~ . Sul~h ur-containin g ligands

readily for r oolynuclear complexes ~ it ~ ~etal ion s: stability

constants of sone of these comrl~x es have been obtained. Ho~vev er

penicillamine, for steric reasons, forms only mcnonuclear complexes.

ra~ i d- reaction tec hn iaues ( Pe rrin, Buntinq}

Ionization constants have bPen fou~d for unstable hydrated

cations in the quinazoline, triazanaphtnalene, and ~-a zapurine

s er ies, a l . a t~e equi li briu m rrooortio ns and the kinetics, all by

~sing a ~ o d ifi eG Gritton-Chan ce type aoparatus with quartz capillary

reaction cell, s p~e ric al le nses, cat~ode tube display, and rapid­

repeat ph otogra~ hy .

. 7 - 6/ 195 7

~itrosation and deamination (Ferrin, Kalatzis)

Rates of hyarolytic deamination of neutral molecules of

9-a~ino-, 9-methylamino-, and 9-dimethylaminoacridine were found to

b e i n de p e n de n t o f t h e h .v c r o xy l i o n c o r. c . n t r a t i o n o f t ii e s o l u t i on .

The mech~nism of the 'iazotisation of 4-aminopyridine has been

elucidated . In acid solutions the resulting 4-pyridine diazonium

ion {like the corresponriing 2-isoMer nnj the ~-nitroso derivatives

of a- and y-metnyl~mino-~-heteroaromatic bases) readily undergo

nydrolysic:.

Carboxylate ion structure (Spinner and, in ~art, Kang)

Vibration-spectral studies of the bcn structure of the

carboxylate grouping have been continued. In crystalline sodium

formate t~e (time- and space-averaged) crystallographic site

symmetry of the formate ion is C~h' and the ionic sy~metry c2v;

if the local, short-term~ symmetry of the ion were the same as the

crystallographic symmetry, no crystal solitting of fundamental

vibration bands would be permitted. hctually the infrared band

of HC0 2Na at 13c6 cm.- 1 ~oes show cryst~l-splittinq, very

prominently after isotopic ciluti~n ~itn oco 2 ~a, and irrespective

of the precise ~ethod of crystallization of the s~ecimen or the

precise conditions of cxc.minati011 (disc or mull}.

If the co 2- grouping had c2v symmetry the two carboxylate

stretching fr~quencies would sho~ a roughly similar susceptibility

to intra- or intE·r-molecular environmental effects. f\ctually, in

benzenoi~ carboxyl~te ions the frequency rear lCCO cm.- 1 moves over

a range of 150 cm. -l ~ccordin1 to the polar effect of the substituent,

while that near 1400 cm.-l does ~ot vary with substitution, especially

in aqueous solution. In solid group I and group II metal salts of

substituted acetic acids. a reqular pattern of cation effects on

carboxylate stretching freque~cies is nor~ally observed, irrespective

of the substituent in t~e anion; exceptio~s attributable to crystal

packing effects are rate: replaceme t of a univalent metal ion by an

isoelectronic divalent one has little effect on the carboxylate

stretching frequency near 1600 cm.- 1,but raises thai near 1400 cm.- 1

considerably.

• 6/1967 - 8 -

Fine structure of pyridines (Spinner, Batts)

A study of d~uteratea and other substituted 4-pyri ones has

shown that there is no localized carbonyl stretching vibration

in these coMpounas; instead, mixed C=O/C=C stretchin~ occurs.

A vi ration-$pectra1 study of the bond structure of the

4-aminopyriaine cetion by means of ring deuteration, nitrogen

rieuteration an~ nitrogen methylation would make it appear that

this ion has an amidinium ion (pyridone-like) structure, and

not a pyridinium ion structure, or one intermediate betveen

the two. This is at variance with widely-held opinion based

on ionizction constants.

Vibrational assign~ents and vibrational ~ixing in some

pyridines anG pyridinium ions have been elucidated by ring

deuteration.

Physical properties of Gi- and Tri-azanaphthalenes

(P.rmcrego)

The infrared ana n.m.r. spectra of many families of di- and

tri-azanaphthalene (also 1,4,5,8-tetra-azanaphthalene) were stu~ied

to form a background of reference for conte~pleted synthetic work.

The difficult study of th2 (very small) proportion of hydrated

bases in the neutral species (mainly anhydrous) of twenty-eight

quinazolines was commenced.

5 - ;· 1 em b e red h e t e r o c y c l i c r i n g s ( B a r 1 i n )

Many 5-mem~ered heterocyclic nuclei of great biochemical

interest (e.g. imidazolc) contain two opposing influences.

Electron release by a singly bound nitrogen atom is opposed by the

electron attraction exerted by the doubly-bound nitrogen atom.

To evaluate the relative strength of these effects, the reactivity

of the bromine atom in a series of bromo-R-methyl-tetrazoles,

-triazoles and imidazoles with piperidine in ethanol was measured

by studying the kinetics of its reaction. The results showed,

by comparison with those obtained for 2-bromopyridine, that

from two to three doubly bound nitrogtn atoms were required in

azoles to overcome electron release froM the singly bound atom and

- 9 ~

reach the reactivity of 2-broMopyridine.

positional effects ~ere also Gbserved.

Some 1 a rg e

Kinetics of the methyl ulphonyl-grouP

as a l ea v i no g r o u p ( B a r l i n , k'. • V • 6 r c "' n )

A series of naw me ~ylsulphonyl-derivatives of pyridine,

pyridazine, pyrazinej quinolin~, isoq~~noline3 quinoxaline,

cinnoli~e and phthalazine have been prer~re~. A study of the

kinetics of replacement of the methylsulphonyl group by

methoxide ion in methanol showed that th2 methyl3ulphony1 group

is very reacily exchanged. ~herever direct comparisons were

possible, t~e ~ethylsulphonyl compounds were fou~d to be from

~O to 100 times ~ore reactive than t1e corres~onding chloro

co~pound. The ~ethylsulphonyl group in the above series of

co~pounds was founrl also to be readily replaced by hydroxide

ion) amraonia, methylamine, n-propylamine, hydrazine, sodium

hydrogen sulphide and sodium cyanide.

The sit( of orotonttion of azoles (Barlin, 6atterham)

The proton ~ag~~tic resonante spectra of various charged

spEcies of thirty five azoles were me~sured. This data

reveals the site of orotonation in imidazoles and

1,2,4-triazoles. Solv~nt effects were also examined.

Proton ·:aqnetic Resonance studies (BatteriP.m)

p.m.r. spectra of many families of nitrogen-heterocycles

have been determined and interpreted, during the year. The

f /1967

surprising observation was made that the pteridine cation, after

hydration in the Jj4-position, transfers th's water to the 7,8-.

and adds a second molecule in the 5,6-, positions (with Albert

and ~cCormack). The stereochemistry cf cobamide-mediated

hydrogen transfer in the biosynthesis of ~eoxyribonuc1eotides

has been decided (with R. L. P,lakley). See also above under

a rown.

- 10 - 6/1967

TEACHING AND OTHER ACTIVITIES

Of the Department's twelve scholars proceeding to the degree

of Doctor of Philosophy, thr2e satisfied their examiners during

the year: of these, two (iV;r . J. Smith and i1 r. R. V. Foster)

have taken up research 1 1ork in pharmaceutical industry and one

(Mr. J. G. Catterall) hi:s c. postdoctore.1 fellowship at the

University of Warwick, Coventry. T~ree other scholars

{t .. ir. ~1. Paddon-Rov1, Mr. I. G. Sayce~ :-1r. J. Bunting) have presented

their theses and are &~aiting examination. One new scholar

(Mr. G. B. Yeoh) commenced during 1966. One of the twelve scholars

(Mr. J. Bunting} holds a Commonwealth Postgraduate Awnrd, and

one (Mr. P. FGra) a C.S.I.R.O. Postgraduate Studentship.

Dr. E. Spinner arranged the Deoartment's programme of

seminarst which were ~~fd at fortnig ~ tly (sometimes weekly)

intervals. Dr. T. J. Batterham gave a course on Nuclear

Magnetic Resonance to the School in February and ~a rch.

The Department helped organize the Third Nat ional Convention

of the Royal Australian Chewical Institute including the Fourth

Australian Heterocyclic Symposium in Canberra (Aug. 15-18}. Papers

were presented by Ors. Brown (Chairman), Barlin, Batterham, Batts,

Kalatzis, Spinner, and ~essr5 . W. V. B ro~n, Bunting, England, Lee,

Paddon-Row, end Yamamoto.

Professor Albert spent eight months in the Nor thern Hemisph ere

on study leave, mainly as an Honorary Research Associate at

University College (six mont~s). He also visited Departments of

Chemistry ano Phurmacology in Istanbul, Bucharest, Cluj (Rumania},

Be 1 g rad e , Cat an i a , Rome , Mi l an ( one 111 on t h i n the I s t i tu to di

Fa rmacologia of the University), basel, Zurich, Hamburg, Kiel,

Stuttgart, MGnster, Bonn, Copenhagen, Stockholm, Paris, Vienna,

Philadelphia, Seattle, and Vancouver, then took part in the

9th International Cancer Congress (Tokyo) and visited Universities

in Tokyo, Sendai, f!a goya, Osaka, and Kyoto. He gave thirty

lectures in various centres cf research on selectively toxic agents.

Four Ph.D. theses we re examined, for other Universities,

by Gr. D. J. Brown .

- 11 - f. /1967

Specimens of substanc~s discovere1 in the Department have

been sent on request to Pr. P. Hand12r {Biochemistry Department,

Duke University, ··: .C.); f:. r. J. Jaco bus ( Di vision of ~·! edicinal

Chemistry, U.S. [iepartment of the f"rmy); Or. ~i. Gordon (Smith

Kline f-.. French, Philadelpria) ; Dr. f' . :?,huglir (Polan d); ~ r. Chester

Stock (Sloan-Ketterino Institute for Canc2r Fesea rc h ); Cr. ~ .

. Jacobson (Car.-ri~ge) · ~r . /\. R. Peac ocke (~·1 uf field !Jep arti:'lent of

Clinical Biochemistry, C:xford).

Large scale equipment was pu t at the ctisncs al of the

Biochemistry Department of t:.is sc;10ol for t~e processing of

nucle~tides; also the Canberra Fire qrigade used our large scale

plant for the dilution of conce~trate d sulrhuric acid . Absolute

and s.v.r. grades of a co~cl were routinel y purified for the whole

of the John Curtin School, thus re~ucino the cost from ~ 10.00 to

38~ per winchester bottle.

out for other Departments.

Fou r or~anic synt heses were carried

·n e lar e-scalt:: laboratory ~·i as in use

on 40 per ce11t of tl:e 11ro rkinq days of t:ie: yea r.

A computer of average transie~ts for th e enhancement of the

sensitivity of the Perkin-Elmer ,,lu nuc lear riagnetic resonance

spectrophotometer \''~ S P• s ta l e:.:! ir: DecE!mbe r. Tne determination

and interpret ation cf 1500 nuclear ~agneti c resonance spectra were

made of which 300 were for ot: e r Depa r tm ents in t his School.

Spectroscopic service ~ork in Dr . s, inner's se ction comprised the

determination of 227 ultraviol2t and 12 in f rar e~ spectra.

The Analytical Chemistry section of the Ceoa rtrnent carried

out 1943 microanalyses and micro -we ig hing s9 on 659 s am ples, for

the whole of t~e John Curtin Schoo19 r £p r esen tinq a 10 per cent

incr~ase over the average for t~e previous five years. and a

12 per cent increase over last ~ear . Ana lyses carried out for the

Inorganic Chemistry Unit of the Pesearch School of Chemistry

exceeded those for 1965 by 44 per cent. About 2.5 per cent of the

car bon, hydrogen, an~ nitro~en analy ses were completed on the new

- 12 - 6/1967

gas-chromatographic F. and M. Analyser which was installed in June,

but was out of service through a defect between early August and

November. This semi-automatic apparatus has proved particularly

useful for perchlorates and azides which often explode in the

furnace. At the request of the School Committee, thorough

analytical checks were applied to fifteen "Analytical Grade 11

chemicals of Australian manufacture, which were compared simultaneously

wi th the leading imported brands. It was found that the overall

quality of many of the local manufactured chemicals conformed to

the standards recommended by the American Chemical ·society

{Dr. Fildes and Miss Jaason).

During the year, the Perkin-Elmer Atomic Absorption

Spectrophotometer was used frequentl y by research members of other

Departments in this University {Biochemistry , Physical Biochemistry,

Experimental Pathology, Geography and Zoology); the Department of

Geography (Research School of Pacific Studies) has also been

helped with pH measurements.

PUBLICAT!Of'(S

ALBERT, A.

The Acridines, their Preparation, Physical Chemical and

Biological Properties , and Uses . 2nd Edition, revised and

enlarged. Edward Arnold Ltd. London, xii + 604.

ALBERT, A.

'3H-l,2,3,496-Penta-azaindenes ("8-Azapurines.") Part I.

Covalent Hydration~ Syntheses, and Reductions'.

J.chem.Soc. (B) 427.

ALBERT, A. 1 Purine Studies. Part IV. A search for Covalent Hydration

in 8-Substituted Purines. 1 J.chem.Soc. (B) 438.

ALBERT, A., BATTERHAM, T. J. and M cCOR~AC K, J. J. 1

1 Pteridine Studies. Part XXXIII. Equilibria between

3,4-hydrated and 5~6,7,8-dihydrated Cations'.

J.chem.Soc. (B), 11C5.

ALBERT, A. and McCORMACK, J. J. 1

'Pteridine Studies. Part XXXII. ~ucleophilic Addition Reactions

of 2-Aminopteridine•. J.cheM.Soc. (C), 11 17.

- 13 - 6/1967

ALBERT, A. and TRATT, K.

'The Rea rrange~ent of A~ino[1:2,3Jthiadiazolo[5,4 -~Jpyrimidines

to :~:ercapto -8- azao•Jrines, (:nd its Retrogression '.

Angei·Jandte Chemie (German ':d.) 78, 59C; {Internat.Ed.), _§_, 587.

'A Uew Route to t~e 7-~ethyl-~-fzapurines (1,2,3,4, 6-Pent~-

azaindenes). Cnem.Commun.Chcm.Soc. 243 .

fi. L S ER T , A • "' no Y Ml A!" ~q 0 , H •

'The Structures of the Anhydro-polyme rs of

2-Aminobenzaldehyde'. J.chem.Soc. (B) 95E.

ARhAREGO, W. L. F.

'f-1 and C- 3 Protonation of Indolizines'. J.chem.Soc. (B) 191.

AR~rnREGO, ,J. L. F., BARLP·l, G. B. and SPHH'Ef', E.

1 The Infra-red Spectra of some ~iaza- and Triaza-naphthalenes

and of 1~4,5,8-Tetraazanaphthalenc' . Spectrochim.Actall ..?_?_, 117.

AR~AREGO, ~ . L. F. and BfoTTERHA : , T. J.

'Proton Mag net ic Resonance Spe ctra of some Di- and Tri-

azanaphthalenes and ~itroisoquinolines'. J.chem.Soc. (B) 750.

A R '.') r E G 0 , w • l. F • ' B A TT E ~ ~. :>. ; ~ ' T • J . • s c H 0 F I E L [j ' K • 2

a n d

3 THEOBP.LD, R. S.

' I~ ea c t i ons of : , et ha z on : c Ac i d . Part V . Formation of

~uin~ zoli ne-3-oxides' . J.cne~.Soc. (C). 1433.

A R, iA R E G 0 , ~J • L • F • a n cl S . " I TH , J . I • C •

'Quinazolines. Part VIII . Electronic Effects in 2-Substituted

Quinazolines 1• J.chem.~oc. {C) 234.

BARLH~, G. B.

'Ionization Constants of Heterocyclic Substances. Part VIII.

1 , 3 , 5 - T r i a z a i n cl e n e s 1 • J . c h em • So c • ( B ) 2 8 5 •

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- 14 -

'Some Aspects of the Heterocyclic ~ ature of Pyrimidine'.

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f:/1967

'The Oimroth Rearrang e~ent. Part ~ II. Measurement of Equilibria

in Reversible Exanples fro~ the Pyrimidine Series. 1

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8ROlrn, D. J. C1nd FOSTEP, R. v.

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BRO k!~J, D. J. and FOSTER~ R. V.

'Pyrimidine Peactions. Part XIV. The Butylaminolysis of

Substituted f~ ethoxy~ and .,.l ethylthio-pyrimidines 1•

Aus t . ,J. C h em • li, 2 3 2 1 •

'The Dimroth P.earrangement. Part VI. The .~bnormal Behaviour

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- 15 - f./1967

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'Co mple x ForMation by Hydrolysed Copper(II) Ions in

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'The Vibration Spectra of t ~ e ~y d rochlorides of ~ ethyl

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' Vib r at io n- spectral Stu~ies of Compounds formea by the

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'Sp ectra l and Ionization Const ant Studies of Substituted

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1 The Spectra end Structures of the Cations and Ani ons of

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.. - 16 -

ALEE RT ;; A.

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'The r elative Electron-releasinq Po~er of a Singly Bound

6/1967

en d the Electro n-att rac t ing Po~ er of a ~o ubl y 8oun~ Nitrogen

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J.chem.Soc. (B).

GA R l I i: , & • B • a n d B J.l, TT E RH A i·i , T . J .

1The Proton Mag netic Re son a nce Spect ra of Some Azol~s· .

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'Kinet ics of Rea ctio ns i n Heterocyc les. Pa rt !I. Replacement

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of the ~r,eth ylsul phony1 Grau fro •·'l r~uinoline. Isoquinoline,

Quinoxal i ne, Cinnol"ne, and P~thalazine by ~e t ho xi de Jen.

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3 Ra W N S 0 t~ , C • l l

1 Cobamides and ~ ibo r. utl 2otide Red ucti on . Part IV.

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1~.'·.unz 1 s, E.

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· ~eactions of ~-Het~roaromat ic Bases with ~itrous ~ cid.

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PEr : H!, D. D. ~nd SAYCE, I. <1.

1

2

3

'~·

5

6

7

9

'Stability Ccns t ants cf Polynuclear ~e rc ~ ptcacetate Complexes

f •\I' k l I -.·• I l • - (·1) o h l c e a n c L. 1 n c • '-' • c n em • ~ o c • 11. •

Visiting ~ese3rch Fellow.

A member of the University of Exeter.

A mer:iber of t:1e 11 ristol College of Science an(! Technology.

Based on work done while a member of this Qepartment;

present address ~esearch School of Chemistry .

A member of the UnivC'rsity of Uppsala, s~1<:der ••

Journal issueci (backc'.ated) in 19t:6.

.!ember of staff of C.S.I. '.': .0. Canberra.

Visiting Fellow fr om Institut fur Orgarische Chemie,

Stuttgart, Germany.

f,iember of the Tec !in ic .~ l University, St 1.1ttqart~ Germany .

1 O B as e d o n 11 o r k do rr e •..,: h i1 e ?. ::1 e-., b e r o f t; i s Depa rt me n t (1 9 5 9 - 1 9 c 2 ) ;

present address ~niv1::irsi t_v cf · cl!:.•)ur::e .

1 1 ::ember of t:~e ;,.~t: p;-· rtr.ier•t rf Pioc:12r.:i~try.