Mesityl Semicarbazide

THESIS

PRESI=l;NTED FOR THE DEGREE

of

HASTER OF SCIEl~C"F: ~l.ND BONOTJRS.

UNIVERSITY. OF NEVJ ZEALAND,

1951.

Ci-!ERISTR1!'

~·i..

"

~-INDEX~.

~~-,.

Page"

A.

ABSTRACT OF THESIS

. . .

_{• • •} 1

B. INTRODUCTION

. .

0 • .,

. .

• 2

c.

PRESENT ~·iORK _•

.

_{• •}

l . semicarbazide

0 _{• • •}

.

.

_• 6

2. Preparation

.

_• 7

3. Pre para on of _•

.

9

4e mesity1 urea •

.

£:; on s of mesi

v o

llrea •

.

13

6. on of ty1~semi de

7. of carbazones.

.

_{• •}

8. Other _{• •}

.

.

20

9. Dis ells of sms for

reaction urea

hydrazine

.

_•

..

.

•

.

.

• 24

D. E_X?ERT11ENT.A1..:

.

_{• • • •}

. . .

on of mesidine

.

_{• •}

. .

_"

2o e:paration _{• •} 33

3. on of mes urea.

. .

_{• • •} 34

4. on s rnesi

urea.

.

.

_•

. .

£:; _{mesi 37}

....,.

6.

. .

• • •

..

. .

7. on semi s

.

_•

.

_• 42

8. ?repar on ni ureas.

.

. .

44

,.,. _{BIBLI OGRAP!ff.}

A. ABSTRACT OF THESIS.

1. Hesi tyl urea has been prepared and used for the success-ful preparation of mesi t:¢1.-semicarbazide.

2. A number of aldehydes and ketones have been characterised with mesityl-semicarbozide.

3. An examination has been made of the effect of basicity of certain primary amines on their reactivity with nitrourea. 4. A mechanism for the reaction of mesityl urea ~~th

B. INTRODUCTION.

During a literature search it was found that 4-(2:4:6 trimethylphenyl)-semicarbazide, (lviesityl-semicarbazide).

\'!Tas not knm·m.

-NH-CO-N".ti I~'i2

4 3 2 1

Semicarbazide itself and substituted semicarbazides are common reagents for characterising aldehydes and ketones. Mesityl-semicarbazide, if it could be prepared, might also prove of use in this respect, particularly as Sah1 and his co-workers have shown that the introduction of an aromatic group into the semicarbazide molecule gives derivatives melting over a wide range of temperatures. The introduction of a

tri-methylphenyl group into the semicarbazide molecule would give semicarbazones of high molecular weight and might enable ready isolation and identification of water-soluble aldehydes and ketones.

An examination of ·the methods available for the prepara-tion of substituted semicarbazides showed that substituted ureas were good intermediates, easily prepared, widely used, and stable. A further point of interest arose when it was found that mesityl urea, 2:4:6-trimethylphenyl-urea had not apparently been prepared. Pierron4 prepared 2:4:5-trimethyl-phenyl urea, m.p. 237°. Engel 2 reported a "monocumyl urean of which it seems he did not know the structure. Beilstein3 notes it as x:x:x-trimethylphenyl-u~ea indicating the unknown structure. Engel's starting material was a mixture of

3.

point and boiling nt as mesi

'

but then prepared his

subs urea (m.p. 227° decomposition) om the

?2""o ""''"'Llo (mesidine 0

~ ~ -C:G ... boili fraction of amines -233 ) •

Engel did prepare any derivatives of s urea and no

fur-ther i could be obtained. It appears most unlikely

however mesi urea, because it was found

duri the present work mesityl urea decomposes, without

melti at

The indeterminate nature of the substituted urea prepared

by 1 emphasises that any preparation of mesityl urea must

be guous and final product free from isomers.

Some of known methods commonly us for synthesis

of substi ureas

are:-me

(i) _{treating amine, glacial acetic acid, with}

potassium cyanate. (VJalther vllodk01.'17ski 5. )

(ii) amine hydrochloride and urea. (Organic

Syntheses6.) .

(iii) From the ne cyanic acid. (Hofmann·.) 7

(iv)

(v)

s

om clysis the

action of cyanogen

nitrourea

and Blanchard8.)

the substi

Blanchard prepared a number of

, prepared by

. 5

am~ne •

amine. (Davis

tituted ureas

(V) quently Sah his co-workers (loc.

.) applied method the eparation ortho- and

para-tolyl ureas

used by Sah9 as a me

of ct- B- ureas. It was also

for characterising primary amines.

Davis and Blanchard (loc. • ) demons effectively

that trourea

H

H

'N-C-N/ I,T,; .~ 0 n ,,~., i\i(.)2

ndearranges in aqueous s on to form an e

mix-*

Davis and Underwood22 de conversion

ammon-ium to urea as ea rearrangement • They

term reverse process as the dearrangeme and

equently us 11_{dearrangeme n to}

note any re-versible breakdown of urea or substituted ureas.

ture of cyanic acid and nitramide, but does not dearrange in nonpolarising solvents, nor in dry alcohols. They also showed that the 11_{dearrangementu is reversible, and that}

nit-rourea can be formed from cyanic acid and nitramide. An analogy is found in urea itself. '\4ohler 1 _{s classical}

trans-formation of ammonium cyanate into urea is regarded as pro-ceeding through the analogous intermediates, cyanic acid and ammonia, 1.vhich combine to form urea, rather than

by direct reaction between the ammonium and cyanate ions. The evidence for this is that the transformation proceeds thirty times as fast in ninety per cent alcohol as it does in water. OJalker and Kay10 .) VJalker and Hambly10 showed that the trans-formation is reversible, and at 100° there is an equilibrium mixture of urea and ammonium cyanate containing ninety five per cent urea and five per cent ammonium cyanate. Ammonium

cyanate exists in equilibrium wfuth ammonia and cyanic acid "vhich then combine to form urea ..

In nitrourea the nitro group appears to promote dearrange-ment so that the nitrourea is a source of free cyanic acid. If a very basic amine, such as methylamine, is introduced into a solution of nitro urea, the reaction of the amine with the cyanic acid proceeds so fast that cooling is required to mod-erate the reaction.

By this method Davis and Blanchard (loc. sit.) prepared a number of substituted ureas in good yield from the correspond-ing primary amines. The nitramide formed decomposes spontan-eously on heating, into nitrous oxide and water. Consequently on evaporating the solution to dryness the substituted urea can be obtained in a fairly pure state, particularly as mono-substituted ureas themselves do not dearrange readily. Davis and Blanchard also noted that the more basic the amine, the more readily it reacted, as instanced by methylamine which required cooling while less basic ones required warming. The

5.

mutual rei cements of their ctron-donating ct as a consequence mes is more basic than ar~

Davis and prepared urea good eld. It

was fore expe provided the t"lflO methyl

gr s in the positions interfere steri

mes urea mi be easily and in reasonable yield this me

Success on me urea by s method

could then followed by attempts to prepare mesi semi-carbazide by standard method refluxing with

hydrate.

If were available it was proposed carry out vmrk on the trourea reaction aring yields monosubsti d ureas from c amines of various basici es. The ortho-, meta-

o-arilines appeared be a s s, because

in ties varying ci It

be noted,

,

s are

in no case is a verv

" gh be cted. om a

son of dissociation constants, whi vwuld be ex-pe to refle the ct of the •

.!-m~_,ro group on amino

group, it was the meta- tro- ne should give

a tter ni

'

the

para-ni a of subs tuted urea than the

CHRISTCHURCH, N.Z.

C. PRESENT -vVORK.

( )

O

y·,·r·r

vrl':f_

V'

'

t;:f:l3

O'L1rea

O

G::-_..,~\)

' _/

+

0

-v.£1 .. :;

'"''..,.

~t..>i

'

7.

2. Prenaration o? Mesidine.

on of

sub-ctory. s

was by virtue the i r>.a te of the starting

mat-erial ch ~<'las apparently a e oi' isomers

tri-methyl- fore methods preparation of me

ng the formation omers, are n difficult

and ous to separate were used. A satisfactory starting

material lable was mesitylene (B.D.H.) b.p. 163°-1670. It

-was known could monovitrated satisfactorily12

the resulting ni o-mesitylene reduced mesidine .. 3,

p. 1160) standard methods for on o groups to

no groups.

mesi was after

removal c acid, by ng in an ethereal solution

alkali, crude omesitylene was puri by steam

dis on and equent ctional tillation. Both

s ons vJere in preparations mesidine

that crude o-mesitylene could be

re-duced ctly loss purity with considerable

increase overall eld.

Reduction .c> •

01.. r~ compounds is often by n and

hydrochloric s nitro-compounds it

is s advantageous to some al to faci the

on It was that using an c

tion nitro-mesitylene adding the concentrated

hydro-chloric a s , the on could smoothly easily

controlled. ss concentrated chloric d was

when the rea vJas , to mesidine ochloride

1,lhich is steam volatile. cohol unchanged

nitro-mesitylene were then by s dis on.

the s the mesidine was s stilled

and fur puf'ifi by fracti on. s method resulted

of mesidine. The propor oi'

8.

temperature was extremely small.

9.

3. Preparation of Nitrourea.

Urea comrner quali was nitrated by

concen-trated c acid to a solution urea. A saturated

solu-tion urea was found to the st yields excess

nitric was ensure cipitation of the urea

, whi almost oluble the presence of excess

nitric acid. culty was encountered in removing the

excess ic acid, by the tals an

ether-mu.ch was eliminated. purification

was cted by recrys zation om boiling

urea ate 1r1as ed in an oven at 50° thout apparent de-tion.

ni was by method Davis

Blanchard (loc. sit.), whi entailed careful on of

urea to concentrated c a ,

fol-lowed by pouri the onto ice, filtration and

subse-quent recrystallization from olute alcohols. Davis and

Blanchard yields nine cent or better using

mother liquors fur recrystallizations. Yields

tained the vmrk were less this. In this

connection noting statement Davis

Blanchard who that cient a present

prevent dearrangeme in al Some effervescence

oc in experiments during pre

ng possible de J. . +. vlon .. Another ctor whi may

have the the urea nitrate t have

10.

4. Prenaration of Mesityl Urea.

This was prepared by adding the mesidine to a saturated solution containing slightly more than one equivalent of nitrourea. Davis and Blanchard showed that the nitrovxea dearranges into cyanic acid and nitramide. The ni tramide decomposesspontaneously or on heating into nitrous oxide and water. Since substituted ureas can be prepared from amines and cyanic acid?, or amine salts and potassium cyanate 5 , it is extremely likely that the free cyanic acid from the nitro-uxea dearrangement is the attacking agent.

As Davis and Blanchard had stated that the reaction with very basic amines "vJas fast and that with less basic amines correspondingly slower it was expected that the mesidine would react more readily than aniline, which requires warming a little for the reactionto proceed reasonably quickly.

Hm.vever, after stirring a calculated quantity of mesidine in a saturated solution of ni trourea for t\velve hours there was no visible precipitate. The reaction flask was then trans-ferred to a 50° waterbath and the stirring continued. After half an hour a perceptible precipitate had formed. In two hours this was quite dense. Observations under controlled

conditions·in no way indicated that mesidine reacted more readily than aniline. Apart from considerations on the position of the equilibrium for the reaction between cyanic acid and the various amines, a factor which may have affected any tendency, for the formation of mesityl urea to proceed any faster than pehnyl urea, was the relative solubilities of the two amines. Mesidine was noticeably less soluble than aniline and consequently the concentration of mesidine in solution would be lower than that of aniline. This factor, it may be noted, would also affect any comparison between the relative reactivities of aniline an~ the nitranilines (to be discussed later) but should not affect a comparison of yields within the nitroaniline series since they have roughly the

ll.

the pure mesi tyl urea ~r;ere difficult to compare under identical conditions because of their different solubilities. Phenyl urea was shown to be much more soluble than mesityl urea in both alcohol and watere On qualitative observations alone therefore mesidine and aniline appeared to possess roughly the same reactivity in this reaction.

Mesityl urea was added to a saturated solution of nitro-urea containing slightly more than one equivalent and the mix-ture stirred vigorously in a 50° waterbath for about thirty six hours. (50° was chosen primarily because Davis and Blanchard stated that nitrourea could be recrystallized at this tempera-ture from ~r;ater \'IIi thout decomposition and also because Sah9 recommends this temperature.) Yields of mesi tyl urea \rJere about sixty per cent of theoretical and were somev;hat less than were expected. This may have been due to the nature of the precipitate of mesityl urea, which was of a flo~ulent type that could easily occlude droplets of mesidine, thus prevent-ing attack by the cyanic acid. Yields 1vere not reduced by lossess of cyar~c acid by evaporation, because addition of further quantities of nitrourea during the sitrring did not alter the yields appreciably.

Purification of the mesityl urea was effected by

re-cyrstallization from absolute ethyl alcohol. It 1vas far too insoluble to recrystallize from water and even in boiling alcohol the solubility was only two per cent CvJ/V). Evapor-ation of the alcoholic mother liquors yielded further (small) quantities of mesityl urea, brown in colour. This could be purified by recyrstallization. Evaporation of the water from the original reaction flask resulted in only extremely small quantities being recovered. This precipitate was so impure that such recoveries were abandoned.

The pure mesityl urea did not melt. Decomposition com-menced at 250°, became appreciable at 258° (with visible

shrinkage), to give a sublimate and solid residue which finally sublimed at 320°.

s cro Kj method ch co stent results. Calculated _• '"""'t 20: _;o trogen.

Found~ 15.60% gen.

Me tyl urea is s in methyl alcohol, ethyl

alcohol s a bulky cipi of fine

white s on recrys on se solvents. It

slightly s chloroform, toluene hot , but

5. Preparation o£ Acetvl Derivative of Mesityl Urea.

ace derivative was prepared adding acetyl chloride to a cooled s on of mesi urea in pyridine.

The dine and excess mesityl urea were removed, after reaction was , by means of concentrated hydro-chloric The pyridine forms the hydro and mesityl u~ea dissolves concentr acid.

ace was recrystallized e

alcohol a constant ng and analysed ni ogen content. (Semimicro

culated _{c12 H16} Found:

eldhal.)

.7%

ogen. 12.6% Ni ogen. heating acetyl

Attempts to acetylate along, or heating th mixtures fai

ace c acid - ace c ap~ydri

Attemuted Preparation of Benzoyl Derivative.

Repeated attemp us the Schotten-Baumann method, and by heati mesi

me

urea vii benzoyl chloride alone, gave no result. urea v1as recovered

A ttemuted Ni trosa tion. One

method was cooled s

was to trosate tyl urea. add a calculated amount of sodium tri

of mesityl urea glacial acetic acid. mesi urea was recovered.

ons Fis clhfelder of

The to a

Only

ni o=

N-phenyl-urea troso-N- thylphenylurea (mesi urea) that osating nt would probably be

restri the bulky ortho me groups in

14.

6. Prenaration of Mesitvl-Semicarbazide.

First attempts to prepare this were by refluxing, for

thirty hours, equimolecular quanti ties of 50/50 ('vJ!'if), hydrazine hydrate, and mesityl urea, with sufficient absolute ethyl

"'

alcohol to take all the mesityl urea into solution. Ow-ing probably to the dilution of the hydrazine hydrate, mesityl-semicarbazide was not isolated in any significant quantities.

Therefore equimolecular quantities of mesityl urea and hydrazine fi.ydrate, together vli th an equal weight of alcohol as a solvent, were placed in two sealed tubes and heated in an

0

oven at 110 for seventeen and twenty nine hours respectively. Apart from a strong smell of ammonia in the latter there was no evidence that any appreciable quantities of mesityl semi-carbazide had been formed.

The stochiometric equation for the reaction bebveen hydra-zine and a substituted urea shows that ammonia is a reaction

product:-H H H

I 1 I

R-N- 9,-NH2+Jilli2l'ffi2 --~ R-N- S-N-l\Jti2+:Nli3

0 0

Therefore a quantity of mesityl urea was refluxed with a 2:1 (V/V) mixture of ethyl alcohol and 50/50 hydrazine hydrate, sufficient quantity being used to eventually take all the mesityl urea into solution. ~~mania was detected (by its odour and by litmus) coming from the top of the reflv~ con-denser, and this was taken as a criterion of the progress of the reaction. ~Jhen the evolution of ammonia had ceased, or considerably diminished, the reaction was considered complete. In this way, after seventy two hours refluxing, good yields were obtained. Increasing the time of refluxing further did not increase the yields.

15.

stirring briskly. The dense white precipitate formed was filtered and \,vashed well with distilled water. After this stage both products were treated in the same way. The mass was disolved in boiling alcohol, allowed to cool a little and an excess of concentrated hydrochloric acid added.

The-hydrochloride was precipitated immediately as a dense pearly-white mass. After filtration the mesityl-semicarbazide

hydro-chloride was dissolved in the minimum amount of distilled

water, the solution again filtered and the filtrate subsequent-ly carefulsubsequent-ly neutralized to litmus with 4N caustic soda. The solution \vas then stirred for about an hour and a half, after which time the precipitation of the mesityl-semicarbazide was

complete. Hhichever method of isolation of the original pre-cipitatB was used, the ultimate yields of mesityl-semicarbazide were the same.

Further purification for analysis was by recrystallization from boiling absolute alcohol (solubility 2.5 gms. per 100 ml. of alcohol). For the preparation of semicarbazones the

mesi tyl-semicarbazide was converted to the hydrochloride "l.vi th-out further purification.

Yields were 80-85% of theoretical after the above purifi-cation process, as compared yields of

4-m-nitrophenyl-semi-carbazid~

of 36%, and of 4-phenyl-semicarbazide of 34-37%

(Ref. 6, p. 439) quoted for other preparations from hydrazine and the corresponding substituted urea.

The mesityl-semicarbazide shrinks visibly with decomposi-tion at 220°. At 304° it finnaly melts with decomposition.

Attempts to analyse mesityl-semicarbazide by a semimicro Kjeldhal method were unsuccessful. A semimicro Dumas method16 using a modified Poth21 generator as a source of carbon dioxide gave consistent and satisfactory analyses.

Found:

16.

and , but insoluble cold water ether.

Preparation of' 4-Eesityl-Semicarbazide Hydrochloride.

excess of concentrated hydro c acid vras d to a warm, saturated, c solution the semicar

Pre of ochloride was immediate.

v!as fi , washed alcohol

fied recrystalli om boiling (

determine the hydro vras a mono

0-, a ;_0-,;eighed ty v.ras ti th alkali a

17.

7. Formation of' Semicarbazones.

An excess of the aldehyde or ketone was added to an aqueous-alcoholic solution of 4-mesityl-semicarbazide

hydro-chloride buffered to approximately pH 4.5 with sodium acetate since Conant and Bartlett24 showed that the maximum rate of formation of simple semicarbazones takes place at approximately pH 4.5. The solution was warmed on a water bath for half an hour if the formation appeared to take place readily. In other cases much longer heating \·Jas required to complete the reaction. One experiment \vi th an unbuffered solution of mesityl semicarbazide hydrochloride (using acetone) gave no precipitate after heating for fifteen minutes in contrast to a further experiment where the acetone was added to a \>Jarm. solu-tion of the hydrochloride buffered (with sodium acetate) to pH 4.5 giving an imn1ediate precipitate.

The lo\ver aldehydes and ketones reacted most readily giving voluminous precipitates. On the other hand cyclic ketones or ketones where the substituents were rings gave in many cases, little or no precipitate after prolonged heating. Acetophenone gave a precipitate after heating for a short time, "~:Jhile benzo-phenone camphor and cyclohexanone gave no appreciable precip-itate after prolonged refluxing using either alcohol-water or glacial acetic acid as solvent.

only, after prolonged refluxing.

Benzil gave a m.onoderivative

Owing to lack of time no quantitative work was done on yields. However 0.4 gm. of the reagent was sufficient to

give enough of the substituted semicarbazone for recrystalliz-ation to a pure state and for subsequent micro analysis. As 4-mesityl-semicarbazide hydrochloride readily gave voluminous precipitates, particularly with the lower aldehydes and

Alcohol is necessary as a solvent with s aldehydes ketones. In many cases

me point after st recrys ation d

con-s on subsequent re stallizations.

croanalyses of mesityl- c:ar ones were carr

out Otago sity.

Semi car bazones.

Descrintion l'1elting Point

Ace needles 0

c.

thyl-ketone

c ..

Ace none

Benzil (Mons der.) needles

Description Helting Point needles

need:J_es d

Pr onaldehyde te needles

te needles d

llov.r s

n needles

(d :::: melts composi ti

benzophenone, cyclohexanone camphor no carba-zones could be is d.

eler and olonged 11ras

nee-in order camphor-4-m- trophenyl- carbazone,

prepare corresponding to

benzo-without culty.

ityl-semicar hydro is qui for

char a sing the aldehydes ketones. It gives a

reas spread me ng points the s are

ins and _• on

has developed so the be easily

wi yields The quoted are average

of products high of Several

were for s and, was

19.

either re in yields a s time

20.

8.

s c. sit~) that

reactiv-ity n nes ourea with creasing

basici the amine. nee Davis Blanchard prepared phenyl urea in 98% yie , it would expected

th c ssociation constants than

react th (to corre

s ti tu ted urea) , 1-vhile nes ~nTi th dis so stants aniline

prepare. Class I.

Methylamine Ethylamine

Ethylene

Dimethyl ne Diethyl ne Aniline

Class II.

m-amino-azobenzene Class III.

a-toluidine p-tolui

E-nap Class TV.

m-ni ni o-ni trani m-nitr -ni o-nitrani ne

become i ngly

Yields of substituted urea

80% I

78%

88%

65%

98%

Yields of substituted urea

Yields Yields not

Yields of substituted urea (This thesis)

20y;

ce none

Solubility (25° C.)

nes ivOUld

sub-on csub-on- con-cult to

(25°

c.)

5.0 X 10 -4 5.2 X 10

3

.

4 _- X 10

8.5 X 10 -5

5.2 X 10 -4

5 .. 2 X 10 -4

6 X l ,..._-... u

{25° " \ \ ' - ' • )

(25°

c.)

-9

1.48xl0

2.0 x lo-1 0

4 .. 0

1 ., _o..l.. X lO-l 2

10-Class I sts a

ed and

by c dis so

= 3.4 X 10-4

=

4.6

s I sts the (loc. sit.)

ori nal ""vere

s I I is an amine

su

the yields constants

-10

X 10 .

s

corresponding Sah

u.reas ..,.,-('o_

Y- ...

are ose d range

his

ureas. sh or can tracts available.

~;vhi s

ob-yie the small

s lm.v s ty the ne.

gures for its s vrere

Class e ic sso

cons and ve s .., ..Ll .

in pre Comparison of ss

shO\JtTS no on

cons does a

sngge icity

cing the lds.

Comparison of sso on constants for

para- s ads to the

they be the same reactivi

amino-azobenzene s cannot be

cause of conditions and methods

of , but on seems

is a more factor some supp from a son

s

thems s, ;;..rhere om most

solu-.;..•

vl be isolated.

the 0 in the or

out as a factor ch

c acid and o- ne<O

s and r ty

w·ere stirr in a

sat-on a at r:

'"-'.

re in the on of tarry Since

are attached by c , they vlere table as solvents~

Isolation trophenyl ureas was cult

s amount

nitro-s prenitro-sent, a cedure 1vas 1>\!hich i removal of the excess nitroanilines washing with e

( _{tituted ureas are nerally ins ether) and}

the pre co nee ochloric

.recrys from ethyl

The conclusion can be drawn the comparison s and Blanchard's results and those in this the

basicities amines do some part in

ties \,vi The the yields

nes of vJidely basicities are the same

as in Class I, from the s show a

i

deviation ( in a narrower range of bas-s), sugges effect of i ty in reduci

is most the case basi cities.

changes icity reduce markedly. In the reaction en an amine c acid,

atom of is c and the

of the be expected

that more readily the of the amine

re-is, the more formed.

H

+

H

H :a:

l

I

R-N-C-Iil II \ 0 H

(C)

the addi on (

ue

-J...i H i R-N-C=~-H

rl

-0-I{

more basic the i tion)

)

(B)

is

o-23.

a proton ans (A) could

s structure (C) a subs urea, or

\ 1"'11 • ..,

9. Possible Mechanisms for the Reaction between Mesityl-u~ea

and Hvdrazine.

The stochiome c e on for reaction

hydra-zine mesi urea cates cular quantities

mi expe to mesityl and

in e cular ties.

and mesityl- car are formed

reaction.

mechanisms for s reaction are possible:

(l) first mechanism proposed is via dearrangeme of

subs urea into an isocyanate and

by attack the mole on ei ocyanate

or on one of pr

R-I\J=

subse

H

I

R-N-0

(2) second mechanism is a

attacking the

of

e

s

no

ntly

it:-Stj2

hydra-th taneous

as

-H

+tl

T1i2

NH

I

R-NH-C + NH3

25.

(1) The evidence in support of the dearrangement mechan-ism is as follows:

Davis and his co-workers11' 22 consider that urea is

con-verted to ammonium cyanate through the following steps.

H

₂

H-C-l'lliz~ HNCO+Nn

₃

~ NH₄ 9 CNO e

A. monosubstituted urea, they suggest, dearranges in tvJO modes corresponding to the "OOssi ble methods of preparation22.

RNH

2+HNCO ~ RliJ:FJ:CONH

2

~ RNCO+NH3

The supporting evidence they quote for this type of mechanism is as follows. On heating phenyl urea, ammonia and aniline can be detected by their odours and the cyanic acid by silver nitrate. The aniline which is formed by one mode of

de-arrangement combines vii th the phenyl isocyanate formed by the other to form sym-diphenyl urea.

Assuming iscyanates are formed, these are knowfi to react

livi th water and they are known to react vigorously ltli th

prim-ary alcohols. (Ref. 1, p. 55.) In the first case amines or sym-disubstituted ureas may be formed.

H

H,_O I

RNCO --=-J. (R-N-COOH) ---7 Rl\in~ + CO?

~ ~

H H

I

I

RNCO ~ R-N-C-N-R II

~

and in the second case urethanes are formed.

H

I

RNCO + R OH ---1t- 3.-N-C-0-R

II

0

Since both alcohol and \~\Tater are present during the formation of mesityl-semicarbazide it could be postulated that

either (i) the isocyanate itself is attacked by hydrazine

or (ii) the unstable carbamic acid is attacked by hydra:tine (iii) the urethane is attacked by hydrazine.

Of these (i) and (iii) seem to be the most likely inter-mediates. (iii) is actually a method used for preparation of semicarbazides. ( R _{_,eJ...} ..o

u,

·:> _{p. 378.)}

s his t~

S l.l.OC.

cyanate is esent as s because

those from iso

of course, theory

the discuss of mechanism

could ce absence of

of , Tyabji, cates

and a aryl isocyanate tuted

should (

cyanate water an

tolyl urea was formed.) The high

carbazide (80-85% cati

probably side on., No

\vere during s

iso

this rea on, aw~onia must also

t .. ) assume oducts

s. be the same isocyanate. and +· ( reaCvlOn no substi

of me cate

26.

an iso-are not, during ons indi-\rJa ter substi-ureas iso-di-o-_l semi-there is ous side oducts ons.

as a st s in

mesityl urea \rJater, re

aqueous-alcohol even a

aqueous-tion no ctedc

This mechanism es an ins ty of me tyl urea

mole is experimen work.

urea can be

de compos on a11.d can led_ concentrated a and

alkalis change.

second me is a nucle c

sub-sti ch is se order 2). The

mole-cule the carbon and amino is

elim-inated as ammonia. ( p. 2..!f.. this thesis. )

s mechanism explain the yields,

lack side and steady on of

ammonia the rea on. It n the

results d by s Underwo 22 heated

27.

cy3.nic acid and aniline. ?henyl urea can be prepared from cyanic acid and aniline.

C .... H,..1\f.tL-, + HNCO ~ C~HrN"rlCONH₉

~ 0 G 0 0 ~

If this step were reversible as is the case with many such reactions, on heating dry phenyl urea, the reaction 1-TOUld tend to go to the left because the equilibrium would be upset by the elimination of cyanic acid as a gas. The free aniline present could then attack the remaining phenyl urea with con-sequent elimination of ammonia,

f6H5

H-l'J-H

I

0 H -\TH 0 · ,-H·

..;6 -sk.L~ ~_,_\j ~2

Is

e

?6H5

NH + T~Jn₃

I

c

_6H5-NH-C

II

0

by analogy \vi th the

Sn

2 mechanism favoured here for the forma-tion of mesityl-semicarbazide. The important point is that Davis and Underwood's results can be explained without post-ulating that free isocyanates are present.

A kinetics study would give further evidence. If the order of the reaction ~eJas determined and it proved to be first order, then these would be two possibilities:

(i) The unlikely dearrangement mechanism might be cor-rect and the actual dearrangment step, i.e., the rate step, taking place much more slowly than the reaction between the isocyanate (or one of its products) and hydrazine.

(ii) Mesityl urea might not react in the form usually written, but in its tautomeric form analogous to that existing for urea itself (as proved by the preparation of the 0-methyl derivative 14 .)

H

-i

R-N-C-NJI?.

R

~

u

3.-N=C-NH?. I ~

0

I

28.

The rate of transformation into the tautomeric form could be the rate step, and subsequent reactions fast. On general considerations this does not appear to be likely either.

A second order reaction could also apply to tvw possible mechanism. s ..

( . l 1., The dearrangement step might be very fast so that if

a fraction ~of the urea dearranged the concentration of the isocyanate vmuld be O((urea) and the

rate = R.o(..( urea). (hydrazine )_ ',vhere ~ is a constant

d.. is the fraction of u.rea dearranged.

The reaction would then be second order. This again appears unlikely on the evidence given earlier.

(ii) It could point to theS'n 2 mechanism.

A comparison of the rate of the mesityl isocyanate-hydra-zine reaction vd th that of the mesi tyl urea-hydrazine reaction taken in conjunction with the determination of the reaction orders, should be sufficient to decide which mechanism is correct or whether a single mechanism can be allocated.

The fact that a simple Sn 2 mechanism appears to explain adequately the results obtained from qualitative experiments on mesityl urea, and the high yields (with lack of obvious side products) for the formation of mesityl-semicarbazide iB no way indicates that this may be the only mechanism involved in the formation of substituted semicarbazides in general. Lower yields obtained for the preparation of other substituted semicarbazides may be due to the fact that with different

substituents other mechanisms may be involved in which com-peting reactions, described for the proposed dearrangement mechanism, play an important part. Alternatively it may just indicate that the substituents in substituted ureas influence the stability, leading to losses by hydrolysis. An example

f

is phenyl urea, which on boiling with water gives the NN -disubstituted urea, aniline, carbon dioxide and a~~onia,

v1hereas mesi tyl urea is stable under these conditions.

was on by

semi car

2:4-hydrate.

v.ras

zide : seventy- hours) as compar th the the same compound (by

29.

2:4-and hydrazine

hours required and c e h/10, '-'J .from 2:4-dini urea and ne hydrate. does not that method (of using N-subs N I tro-ureas) 1t~ould be of neral cation the ation of

semicarbazides cause t's cates

tration of monosubsti aromatic ureas,

re t on the ti amino

D. EXPERIJV1ENTAL .

l. PreParation of .r~J.esidine.

In pre work me tylene was nitrated the me detailed c Synthese , and the trome tylene

isolated .. reduced tin chloric

as de belov.r .. yield the conver of

mesi tylene was 60% of the ore yield.

For the to mesi the

yield was therefore approximately 40%$ following modified cedure elim-on of the ni tromesi tylene v.ras

yields mes ne ranging theoreti ) for the conversion of mesitylene mesidine.

Modified Procedure: Me (B. • ) was fractionated

the ction within range colle and

used.

40 g. mesi and 60 g. acetic anhydride were pla a eked r bottomed flask, ~rli th a mechani stirrer, a dropping and a thermome _"'ell.

flask was placed a bath of ice and the con-tents cooled to A mixture 31.5 g. fuming nitric a ' 20 g. glacial ace c acid 20 g. acetic

was placed dropping funnel. acetic

c acid been previously pr by

cau ous adding fuming c acid the acetic acid

-ace c alli~ydride mixture while ning temperature

0

20 • m J.. stirrer was started

dropping funnel so that

contents the rea flask was

tion took

the op on \'1/as removed. om the ice

It was then to

the e in the temperature of

bebveen forty

reaction

to s hvo s.

allowed remain at reaction

800 g ..

aqueous mercial e

ual ni orne tylene. four 30 • portions aqueous tv-as

tion vJas ansferred

e

temperature n cooled and

extra ethereal s 10 •r-!f1

-.l.Ojo S

a 1 l. r

ten s .. The ed slmvly on to

ing The

with • of com-v1as added resid-on v,ras with hydroxide the

The e solu-ttomed Claisen flask and the e disti over a s am bath.

To omesitylene 50 g. of tin,

50 ml .. and of abs alcohol were added.

200 ml. concentrated vJere added

'0

continual shaking, the addi on ing such

that ature flask was ca.:; .•

of on, ne hydro could

be seen s ng te After the

hydro c acid was the \vas gently over a

steam l any- pieces , which failed to

diss

The contents of flask were steam

the dis ss and ss ( 2-3

sL

disti ;_r;as dis

s

co~mercial caus c soda then added cautiously

until cipitate flask

conte \l'lere then s stilled. mesidine came over

as a ch se

sti The s tillation 1:-1as un the

dis was free drops \>.I as

The mes a funnel tl1.e

aqueous extra th 3 X 100 • portions

commer-cial e ch vlere to the me

Solid commer caus c potash were added

ethereal to remove any sent ethereal

solution mesidine a filter

The mesi ne ·,,;as .i-~ _t..nc!"' - - to a 100 ml. s

flask • .!-1

\All vfl a condenser, dis over a free At first one or tvro ops of ether came over.

The then rose and at

232-but had

The mesidine was a clear, yellmv- oil , when stored, in a~ air-ti t bottle, a dark board,

could t, scolouration, s \>J'eeks.

Yield 34.8 g. or 77% ( ed on mesi ne).

A fur tion a 74%

2. Preuaration of Nitrourea.

(a) Prenaration of urea nitrate.

A so on of co11lll1er cial urea was by s i 200 g. ml, of stilled To \'IT ere

400 ni c urea ni

separ-a ted mixture was chilled !"!

and

'-'·

through a Buchner l~ cipi was 1:Jashed ml. of 3:1 ether-al mixture remove excess

nitric then recrys ce from

The urea te 1rras stored in a glass bottle mon thout

356 g. or

(b) Prenaration of nitrourea by the method of Davis and Blan-chard.

200 g. urea ate were in portions

to . of ates c a (s.g. 1.84) contained

in a 1r1hi ch ~;vas _tted a stirrer

im-mersed in a of ice salt.

below The about

rr1inutes. After ate was complete,

mixture -v1as al stand one before

iN"i agi on one litre finely ice.

The ni ourea,

was then and suction prolonged

effe a par crystals. The t crys

were dis sol boi alcohol. solution was

on, d, crys

with a m..L., of alcohol air- ed .. Some effervescence was i,vhen crystals were added the

ling (See p. 9 of s thesis.)

crys in ly-t,rhi te s and tvas

used fur purifi on (c.f. and

34.

3. Preparation of Mesitvl Urea.

A 1500 ml. flask containing one litre of distilled water 1-vas placed in a vJater bath at 50° and fitted with a mechanical

stirrer. To this was added 25 g. of nitrourea and the con-tents stirred until the ni trourea 1.o1as dissolved. 20 g. of mesidine 1•rere then added. After about half an hour a

per-ceptible precipitate had formed. After several hours the white precipitate had become bulky and flocculent and acculli-ulated near the surface in spite of vigorous stirring. The stirring was continued for 36 hours.

The flask 1o1as then removed from the vJater bath, the con-tents chilled and filtered with suction. Addition of further quantities of nitrourea to the filtrate did not result in any appreciable quantity of precipitate being formed. The pre-cipitate of mesityl urea was washed well with distilled water and dried in an oven at 110° C. without apparent decomposition.

Yield 17.7 g. or 67% (Average 6350.

The mesityl urea was recrystallized three times from boiling alcohol (solubility 2.% (VJ/V) ) •

Evaporation of the aqueous filtrate from the reaction flask yielded very small quantities of impure mesityl urea, brmvn in colour. Such recoveries were abandoned. By evap-oration of the alcoholic mother liquors rather larger quan-tities of mesityl urea were recovered.

The pure product did not melt, but at 250° decomposition commenced, and at 258° decomposition became appreciable with visible shrinkage, leaving a solid residue which finally sub-limed without melting at about 320°.

Solvent Dioxan

lvlethyl alcohol Ethyl alcohol

Chloroform Toluene l'la ter Ether

Concentrated hydrochloric acid

Concentrated alkali

Cold

slightly soluble

n 11

II i1

n n

u n

insoluble

n

(as .for

35.

Hot soluble

!I

It _{(2% -vJ/V)}

slightly soluble

rl u

.,

Tt

insoluble dissolves

water)

Mesityl urea gave bulky, white needles on recrystalliza-tion .from dioxan, ethyl alcohol and methyl alcohol.

Analysis.

Calculated for C10H14N20, Found (Semimicro Kjeldhal),

Calculated .for c₁₀H

₁₄

N

₂

0~

Found (Mr. A. D. Campbelll ₇

rJ/ 15.73%' 15.70%' 15.65%' C% H% 67.42 7.86 67.17 7.67

Nitrogen Nitrogen

Net ;o

36.

4. Preparation of N-Mesityl-N -Acetyl Urea.

0.5 g. of mesityl urea was added to 5 ml. of pyridine and the mixture cooled to 0° C. 1 ml. of acetyl chloride was added drop by drop with stirring. A vigorous reaction took place and a white mass was formed in the test-tube. Concen-trated hydrochloric acid was added carefully and the mixture stirred well. This dissolved the excess mesityl urea and pyridine. The remaining white crystals were filtered with suction and washed three times with concentrated hydrochloric acid.

The acetyl derivative was recrystallized three times (to constant melting point) from a 50% ethyl alcohol-water mixture. N-mesityl-N -acetyl urea forms fine white needles

on recrystallization from boiling alcohol-water; these melt at 212°.

The acetyl derivative was analysed for nitrogen content by a semimicro Kjeldhal method16 •

Calculated for C12H16N202, Found,

12.7% Nitrogen 12.4%, 12.6%, 12.6% Nitrogen Attempted Benzoylation of Mesityl Urea.

Attempts to benzoylate mesityl urea by the Schotten-Baumann method and by a method analogous to that used for acetylation, gave no result.

Attempted Nitrosation of Mesityl Urea.

0.7 g. of mesityl urea was dissolved in 7 ml. of glacial acetic acid. 0.2 g. of finely powdered;.sodium nitrite 1>1as slowly added in small portions to the solution with constant shaking. The temperature was kept just above the freezing point of the acetic acid. After the addition of the sodium nitrite was completed the solution was shaken for about twenty minutes and then poured into 50 ml. of distilled water. Only mesityl urea was recovered.

Note: The expected product was N-nitroso-N-mesityl urea since N-nitroso-N-phenyl urea can be obtained by this method.

5. Preparation of Mesityl-Semicarbazid.e.

6 g. of mesi urea, 15 hydrazine hydrate 50/50 ml. of ethyl alcohol were placed in a 250 ml. round- ttomed flask, fitted to a reflux condenser by means

a ground glass joint which was ghtly greased -vli th

si cone grease. The flask was placed. an electrothermal heating

that the

ammonia could.

with a simmerstatt and adjusted so e refluxed steadily. After about an hour

de cted ( its odour is ng from the top of condenser.

by litmus paper) After about 48 hours most of the solid had. disappeared.. Shortly afterwards a solid separated, forming irregular roundish masses. The refluxing was continued until the a~uonia comi from top condenser had considerably shed or ceas This took seventy- hours or longer. After reaction was considered to comple the flask was removed.

Two alternative methods of isolation were

used:-(a) contents flask were allowed to cool, when the mesityl-semicarbazide separated out as a solid white crys

ne mass. The mass was broken up, transferred to an evapor-ating dish and dried over a steam _• The dry mass weighed

6.5 gms. This mass was then broken and \>lashed with stilled ·water.

(b) The alternative method vlas to pour the contents of the reaction flask into 200 distilled water, 1.rhile stirring vigorously. The dense precipitate was filtered wi suction

cobol and washed 1-1ell distilled water to remove

excess

From stage th yields were purified the same procedure. There was no percepti difference in

mate yields.

"vJi

:,vas trans

drying moist, crude mesityl-s to a beaker and dissolved

amount ethyl alcohol (300

carbazide , it 1varmi in the

concen-38.

c acid f'or three • of

alco-The ochloric v:as cau ous1y

first Jch t a

dense e s

'"as filtered ed over pump

9 -vrhi1e s 11 a 1000 . beaker ted

s mesi senli car

ated, aqueous on, 800 o of s being re

solu on 1,ras fil care to

cau.st:ic s and s one

hours. A bulky, pre

grad formed. ~;v-as filtered suction washed

th s On

caus c s by no more

cip-itate was formed. The mes ir: an

oven ..,.,00 ..LJ... composi on.

5. 5 g. or 1n s ons yields vJere

con-siste the

s semi \vas re talli

e

further

ca-~Jhen was in a

comp melting

vli th vis took ce at

304° but

s d re decomposi on.

analysis mesityl-s carbazide

me was not successful. nature the

necess to i a on

the

con-sis , vlere mar value.

.76%

+- '710

_c

_p

Se

u s ~ .L .,

15 .. 9 2.73 .,53

$2 754 .~

6., 0

~2 15 757 60 21 ..

Calculated 62.,18 7.,77 .76

62 ..

s order decreasing s

a s

Solvent

ox an s ble soluble

al

cohol (2. )

Chl more s ble

Toluene

soluble

VJater

ins

car f'ine, s on

om me alcohol, e

40.

6. Preparation of' Nesitvl-semicaY'bazide Hydrochloride.

Hesityl..,.semicarbazide hydrochloride was prepared by diss-olviLg 2.5 g. of mesityl-semicarbazide in 100 ml. of absolute alcohol, and adding 25 ml. of concentrated hydrochloric acid. The hydrochlorde \Alas precipitated immediately. The solution was then chilled and recrystallized three times from 50%

aqueous-alchol, the mesityl-semicarbazide hydrochloride form-ing fine white needles.

The hydrochloride did not melt, but decomposed at 300°. To determine '"hether the mesi tyl-semicarbazide behaved as a monoacidic base, a weighed quantity of mesityl semicarbazide hydrochloride vJas titrated (as a salt of strong acid and a weak base) with standard caustic soda solution using a Cambridge pH-meter.

Determination of the Composition of lvlesitvl-Semicarbazide Hydrochloride.

0.3518 g. of the hydrochloride was dissolved in 300 ml. of distilled lrJater and titrated against standard caustic soda

( 0. 05958N) • The usual procedure was followed for standardisa-tion of the glass electrode against the incorporated standard cell.

The pH was read directly. Results.

ml. of caustic soda added

o.oo

3.10

5.00 3.41

9.00

13.00 3.89

15.00 17.00

19.05 4.31

19.50 20.00

20.50 4.47

m1. OT caustic soda added

21 .. 00

21. 4.

m1~ of caustic soda added

35.00 .. 4 () v

11 ..

Or.,

• v 4.65

40.00

.. oo

.76

23 .. 00

point graph .3

25.3 • of 0 .. caus

=

25.3 x 0.05958 equi 1000 3

= 1. x 10- equivalents~

= 0.3518 eauivalents

229.5 ~ ?

= 1. X 10-3

The shape semi carbazide

hydro as the of a base a s

on that it behfWes as anything

~·:

~

·,_,_:.:.;..p

+l--'----' -- : :c::!

' ' ' -, -1

~I

:·:·.::~,_

-!+i-++-H

~.·

:~,

-i-:-+t--r-t-r----~

-~·~~~

' ' ' i " " ' I

~H<: r ~

~-:~'

~~ ';:~

I ' ' ' ' "

,_·::::~,,

-3~~

~~~·

' I : ....!~ [...,.._• I'

~:,,, '~

' ,, ,.,

'" -:-r:

' 1 • 1 ' , I I

' , , , , " l l

'::--r-;~·

'!-'--,:

:-++-.

.>

''-+-i

+t

,,.~,,

''+

-m.

-===

-1.

7. Prenaration of Mesityl-Semicarbazones.

a mixture 0.4 g. of mesi s carbazide

hydro-'

10 ml. and 10

'

1 '='" (J' s

ace \vas added a solution to a pH c. a. 4.5.

mixture was on a steam bath 1 all had diss slightly more one e (0.3-0.4 g.)

or ke This was n refluxed

an hour.

, acetaldehyde, propionaldehyde, a-crolein, and methyl e ketone, nre on occurred or within a

precipi slightly

one hour apparent r

glacial c acid were the

for a After had been

it v1as noticed some crystals had s

-v.ras continued !!. further t1>JO s. mixture \:Jas cooled and

Camphor~ for s only an

small cipitate at

one recrys on. There was i .

-'-cJ..en~_, for

recrys on or analysis ..

Cyclohexanone an extreme amount of

afte:r four s. was

Be!"'..z none no precipitate was isolated

semi s from or ketones

mo cular vJei t v1ere recrystalli alcohol-i'>Ta ter.

e of hi 1veight, alone vias

us

analyti obtained D. Campbell

Aldehyde Description or

ketone

Acetone vJhi te needles lVIethyl ethyl

ketone vfui te needles Acetophenone 11

Benzil Yellovv needles

Formaldehyde

Hhite needles Acetaldehyde u

Propionaldehyde

vlhi te needles Benzaldehyde it H

Cinnamic Yellow needles aldehyde

Ac':'olein ~vni te needles

Semicarbazones

1'-Lv. of deriv.

189° 139° 203-204° 182°

214-218°d 212°d 175°

214°d ;::J3,....,0 ~ (

192°

Analysis (Otago)

Re~~d

N% Calc. N%

17.6a 18.0

16.9 17

.o

14.0 14.2

10.9 10.9

20.4 20.5

18.6a 19.2

17.8 18.0

14.8 14.9

13.7 13.7

l7o8 18.1

a

=

analysed after repeated recrystallizations. d

=

melts vri th decomposition.

44.

8. Preparation of Nitrophenyl Ureas.

Three flasks fitted 1..vi th mechanical stirrers •trere placed in a ~tJater bath regulated at 50° c~;;. In each were placed 4& g. of ni trourea and 200 ml. of >iia ter. They "IN"ere then

stirred until all the nitrourea had dissolved. 5 g. of either orth- or meta- or para- nitro-aniline l'lfere added to each

flask and the stirring continued for seven days.

The flasks \vere then removed and the contents chilled and filtered. The respective precipitates were air-dried at the suction pu~p and the filtrates evaporated to one third of their volumes on a steam bath and allowed to cool.

The precipitates were washed with ether until the washings were colourless. From the flask which contained the

meta-nitro-aniline, a small quantity of precipitate was left "~AThich

was insoluble in ether. There was no ether-insoluble pre-cipitate from either the or~ho- or para- nitro-aniline flasks.

The precipitates from the partially evaporated filtrates vJere treated in the same manner as the original precipitates. A further quantity of meta-nitrophenyl urea was obtained and also a small quantity of para-nitrophenyl urea, but no orth-nitrophenyl urea.

Finally, the remainder of the original filtrates v1ere

evaporated to dryness and washed with ether. A fe~;v crystals of me!:a-ni trophenyl urea and a fe11/ crystals of par a-ni trophenyl urea were recovered. No orthonitrophenyl urea could be

isolated.

The crude meta-nitrophenyl urea weighed 1.2 g. and melted at 148°. On recrystallization from boiling water, light yellow plates \\Jere formed. Tv.ro further recrystalliza-tions gave a product melting indefinitely at 192° (literature

0

quotes 187-196 ). Yield 1.2 g. or 2q{b.

The crude para-nitrophenyl urea melted at 210°. Two further recrystallizations yielded 0.03 g. of a produce

melt-0

recrys on boi gave needles

228° ca. (

" quotes l I •

the ltrates were evaporated dryness

and :,Ji th eti1. e r • A om the me

~ Or c ( _{• ) ' p.}

2. Beri 18, p. 2229.

n, Organis Chemie, , p. 1164 (

.

)

.

4. I p. 1154 •.

5. A. S. ~'lheeler T. S.

vJ

alker • A.C.S.

£,

p.

(1925).

Organic Coll. . I (1932 • ) ' p. 442 •

7. I p. ¥A.

8. T. • Davis and C. Blanchard. J.A.C.S. 47, p.

9 .. , Organic Compounds ( • ) ' p. 234. 10. F. D. Chatta\r.ray, J. Soc., p. 170 (1926).

11. T. L. s F. ole.

J.A.c.s.

_,

56 p. 885 ( )

.

Organic ses, Call. (1943

13. . J. actions of c Compounds (

,.d.

.L ~. 's Organic try of Taylor

(1937 • ) t p. 284.

15. T. L. and l'J. JJo n J.

c.s.

58, p. 1800 ( )

.

16. R. cher and .. 4. (} +

_v'

_{Semimicro tative c}

s (1945

.

₎

_'

p .. 72. 17.

c.

A. 539 r i

'

' _" I •

18. J. and e, J. Chern. Soc.

'

p. 713 ( )

.

19.

c.

A. 7380 ( ).

20.

c.

589 r "\

.o.. \ )

.

21. I and Chemis

' '

p. 440 (1932).

22. 'T' _{L. and J.A.C.S. p • 2595 (}

... &

23.

c.

'

H' ~

.

i, .L. Conrad F. twan.

c.

'

(1939).

24. J. B. ,.ilG _{a~nd Po tt. J._LioC.S.} ,.../!