Reactions of flavonoid thiosemicarbazones under acetylating conditions

T&ah&on

Vol47.No44.p~93059316.1991

0040-4020/91 s3oLltoo PergamonRessplc

Rmtedm GreatBnu~n

Reactions

of Flavonoid Thiosemlcarbazones

under Acetylating

Conditions

L6SZ16 Research

Group

for Antibiotics,

somogy1

Hungarian

Debrecen,

P.O.Box

Academy

of Sciences,

H-4010

70, Hungary

(Recerved rn UK 18 January 1991)

Abstract: Upon acerylat1on, (Z-phenyl)drhydrobenzopyroneand 2'-hydroxychalcone thlosemlcarbazones (lc, Zc, 3~. and 7c) form 2,2-dlsubstltuted S-acetamldo-3-acetyl-2,3-dlhydro-1,3,4-th~ad~azoles (11, 21, 41, and 81) Instead of the dlacetylthlosemlSlmllarly, the carbazones (Ze, 8e) clalmed In the literature and reactlons of the aromatlc ketone thlosemlcarbazones 9c, 1UC lid result In the formation of thladlazollnes (91, 101, and Ilk, flavone thlosemlcarbazone respectively), however, (6c), flavone dlacetylhydrazone (6g) under the saiz degraded to The the condltlons synthesis of flavanone splro-1,3,4-oxadlazollne 2h 1s also described

INTRODUCTION

It

is

known

that

thiosemicarbazones

acetylation

affords

the

synthesis

values's 6). undergo

presence

lowers

influence acylating

carbon

of

an

C-2

hybridized

of

The

of

of various

transformation

aromatic

aldehyde

+acetamido-3-acetyl-2,3-

application

epimers

of

of formation

conditions.

atoms

sp2

direction

thiosemicarbazones

their

of the

the

or

with

aliphatic

of

choral

synthons

optical

rotation

alkyl-aryl

ketones

high and

reaction2* 7.

the rate

the

(and

thiosemicarbazones

an analogous

The group

The

also

aliphatic

2-substituted

-dihydro-1,3,4-thiadlazoles1~5 allows

of

transformation

present

oxidation

under

neighbouring

of the thiosemicarbazones,

the

diversely

carbon

paper

deals

substituted state,

acylating

with

the

flavonoid

and also

conditions.

9305

of

with

the

the

and may also latter

synthesis compounds the

carbonyl

under of

the

bearing

examination

of

L SoMoon

9306

X

X

X

R

R’

5

R=H

7

1

H

H

6

R=Ph

8 R=Ac

2

Ph

H

3

Ph

OH

4

Ph

OAc

X

X

a

Me

0

0

h

b

N NH;!

C

N-NH

N NH CS NHPh

e

N NH CS NAc2

f

N NHAc

9

N NAc2

)_-N, \

/

N-AC

AcHN

CS NH2

d

R=H

-N )_ S ‘N -Ac \ /

I

Ac2N >--N\ N-AC S \ 1

J AC

'N

k

Ph’ )_ -_N S \

‘N-Ac 1

Reactions of flavomd

RESULTB

The

reaction

anhydrlde

In

gave

-1,3,4-thiadlazole-2,4'-chroman]

thiosemicarbazone (lo) with acetic spiro[5-acetamido-3-acetyl-2,3-dihydro-

(li) as the mayor product, accompanied by

minor quantities of the corresponding splro-structure

9307

AND DISCUSElIOll

4-chromanone

of

pyrrdine

thmenmubamnes

5-diacetylamino derivative

lj. The

of these compounds was clearly proved by the S-CRR'-NAc 13C-NMR spectrum of Ii at 6 = 75.64 ppm, and by the

slgnal In the lndentrcal mass spectrometrrc fragmentation pattern of both compounds characterrstlc 179 and 178, respectively, and with lj) s/e

(li of

splro-thlazirlne fragments39 7. For comparatrve studies 4-chromone (5a) was not

under

srnce

suitable,

-formatron

reaction

cleavage,

into

-2-pyrazolrne

It

was

the

condltlons

reported'

to

of be

the

thlosemlcarbazone-

transformed,

wrth

ring

3-(2-hydroxyphenyl)-l-thlocarbamoyl-5-th~osem~carbaz~do-

In an atyprcal reactlon favoured by the known tendency for

chromylrum salt-formation. Treatment structurally acetlc

of

rsomerlc

anhydrlde

derrvatlves

the

(2i

flavanone

2'-hydroxychalcone

In pyrldlne and

thlosemrcarbazone

8i).

gave The

and

2a,

thiosemicarbazone

of

(7~)

the with

2,2-dlsubstltuted-1,3,4_thladlazollne

sprro[5-acetamldo-3-acetyl-2,3-dlhydro-

-1,3,4-thiadlazole-2,4 '-flavan] structure of 2i was assrgned by comparison wrth the above mass- and 13C-NMR spectral crrterra of the chroman analogue li [m/e

255 (thiazirlne + l), 6 = 76.99 (sprro carbon); see Tables 1 and

21. The considerably different chemical shift (A& = 0.88 ppm) of the H-3 and H-3' protons of the flavan rrng In Ii may be attributed to the selective steric shleldrng effect of the endocyclic acetamrdo group. The thiadrazolrne structure 8f of the product obtarned upon acetylatron of 7c was proved by the data: m/e and the spectrum.

6 = 79.36 ppm Thus,

the

280

(N-acetylthlazlrldine derrvatrve - OAc)

(S-CRR'-NAc) chemical shaft value

earlier

reports9

formation of dlacetyl-thlosemlcarbazones

In

the

literature,

In the

13C-NMR

clalmlng

the

2e and 8e upon acetylation of the

throsemrcarbazones 2c and 7c, must be consldered erroneous. Although

thloacylhydrazones

possess

greater

sure5,17, as compared to the correspondrng the hrgher nucleophllrc

tendency

oxygen

for

analogues,

rrng-clobecause of

character of the sulphur atom, we expected that

the acylhydrazones of flavonoids would transform into Spiro-oxadiazolrne derrvatrves (e.g. 2h) under acylatrng condltrons (in hot acetlc anhydride, or

more

Treatment

convenientlylo* 11,

wrth

Ac20/ZnClz

of flavanone acetylhydrazone

(2f)

or

near

room

temperature).

the dracetylhydrazone

2g

wrth Ac20/ZnC12 resulted, Indeed, m splro[3-acetyl-5-methyl-2,3-dlhydro-1,3,4-oxadlazole-2,4'-flavan] (2h). The Spiro-oxadiazoline structure of

9308

L SOMOOYI

2h was unequivocally proved by the 13C-NMN data (see Table 2), including the

6 = 95.95 ppm

ation12*13 according

(Spiro-carbon) chemical

from the to

the

shift. Moreover,

isomeric diacetylhydrazone 6

=

11.51

ppm

structure

[0-C(CIi3)=N-] signal

differenti-

could

be made

appearing

at

significantly higher field than the acetyl-methyl signal of the isomeric diacetylhydrazone

(6 = 22.33 ppm). In accordance with the Spiro-3-acetyl-

oxadiazoline structure 2h a significant difference lIi-NMR chemical

shift values

of the H-3

similarly to the thiadiazoline

(1.16 ppm) between the

and H-3' protons

derivative

2i

(see above).

was observed Based on the

elemental analysis data and m.p. the product proved to be identical with the

material

hydrazone

previously

(2b)

with

preparedI

acetic

(14OOC)" and mistakenly

by

anhydride

claimed

to be

the "under

acetylation more

of

drastic

"the diacetyl

flavanone conditions

derivative

of the

flavanone hydrazonel' (Zg). Acetylation

of trans-3-hydroxyflavanone thiosemicarbazone

(trans-SC),

containing asymmetric carbon neighbouring the prochiral reaction centre, gave two optically inactive products with identical elemental composition. Based on the 13C-NMH spectral data [6 = 78.98 and 81.36 ppm, respectively, (Spiro-carbon)]

both

have

products

the

spiro[5-acetamido-3-acetyl-2,3-

-dihydro-1,3,4-thiadiazole-2,4'-trans-3'-acetoxyflavan] and 4i 11)~ differing spirocarbon.

This

structure

from each other only in the configuration

was

clearly

supported

by

the

(4i

I

of the

'H-NMN spectra

(see

Table 2), showing different chemical shift for one of the three acetyl groups and for the H-2 and H-3 protons of the flavan rings. Flavone thiosemicarbazone from the previously -type

(6~) reacted in a way completely different

discussed transformations

(l-3) or chalcone

of the dihydrobenzopyran-

(711)thiosemicarbazones. Thus, treatment

of

6c

with acetic anhydride in pyrrdine afforded a product which did not contain sulphur,

1 e

flavone diacetylhydrazone

(6g). This was rather surprising

since, to our knowledge, the known degradation5*15-17 into On

of semicarbazones

(di)acetylhydrazones has not been observed with thiosemicarbazones.

the

bases

of

spectral

data

[vmax (KBr) 1707

and

1686

cm-'

(NAc2);

6 = 2.50 ppm (s, 6H, 2CH3-CO), and the single peak for the two CH3-CO at 8 = 25.82 ppm, as well as, m/e = 321 (M+ + 1); see Table 1 and 21, elemental analyses, m.p. and tic RF data, the product (6g) was found to be identical with an authentic samplel' of flavone diacetylhydrazone. Since under the given acetylating conditions each of the 2-benzylideneindanone and

9-fluorenone

thiosemicarbazone

thiosemicarbazones,

as well

as benzophenone

4-phenyl-

(9c, 1Oc and lld, respectively), carrying a similar sp2

carbon in the neighbourhood of the hydrazone function, transform into the corresponding 2,3-dihydro-1,3,4-thiadiazole

derivative

(9i, lOi and Ilk),

2cy

3c

41

2g2O

2i

2h

lc

13

2f9 120

1C

li

material

Compound Starting

Table

18)

(34,

20)

Ac2WPy

(16;

k20/Py

(100°)

5 hr

(100°)

5 hr

>

(r.t

2 3)

(33;

(r.t.1 40 hr

2)

23 hr

(100°)

Ac20/2nC12

(30,

Ac20/ZnC12

5.5)

5 hr

Ac2O/Py

(23;

clao”>

5.5)

(23;

5 hr

(tWQ.)

tmolja

Ac+V’y

time

agent

Reactlon

Preparetkon

Acylatlon

1.

rFGH”1

CFGIk

AI

I’FI

KE)gI

CEI

2h,

(m.w.1

Formula

15, 2x,

129-DO0

10

IJ CJY-

(56)”

100

(63)’

100

(67)’

97

(75)”

93

J

(EtOAc)

168O

(EtOAc)

229’

(EtOAc-hexanelk

166-168O

m

(EtOH-heptanef

179-180°

(EtOH-heptane)

17El-l-/Y0

J

(EtOH-heptane)

(EtOW

(651f

230’

(439 48)

C22H21N305S

(381.44)

C20H19N303S

(322.35)

C19H1ElN203

022.35)

C19H18N203

047.39)

C16W3O4S

(305.35)

C1a”1sN303S

(4 82) 4 94 (4.82)

60 23 (60 12)

4.93

(5.63)

5.80

(4.93)

5.19

(4.95)

(60 12)

59 82

(70.791

70.14

(55.32)

55.76

(55.06)

5.10

H

S

(7 30)

7 37

(7 30)

7.44

(8 41)

8.62

(9.23)

(thlazlrrne+l)

255

381(Mf)

179,178

3O%M-AC)

348(Mf+l)

179,178

(10.50) 9.46

306(Mf+l)

10.72

to be contlrcued

(9.56)

9 25

(Y-56)

9.25

(11.02)

10.85

(8.69)

8.92

(12.10)

11.81

(13.76)

13.77

N

MSe m/e

Analysxi

Ilk

found (calcd.

)

41, f;~, 81, 91, loi,

55.31

(8.81h

i

m.p.d (solvent)

11,

92

%

of

C

crude

‘field,

Data

(pure>’

Physical

Processingb

and

R;

UL:

lld

Pi

1Oi

Ilk

18)

164-165'

%eltzng

material.

(69.37)(5.10)(10.11)

10.03

278(M-CH2CO)

(0)

lxwor

of

crudeli

from ether

%t

toba continued

9 m p. (for compound& claimed) 196-198 OC.

RF (9 1 CHCl3_MelCO)0 52

%min the i&her

hydrazone") 179-180 'C kPrevlously crystalflsed

ff?F (9 1 CHCl3--Me#fJ)0.24.

PhH-EtOAc) 0 63 Jl.~t.14 RI+. (for the “diacetyl derivative of flavanone

technique).

blccit. %ass spectra (70eV)Wereobtslfwd by usinga W-7035

6oF254

121(PhC+S)

obtalnf?d after steps CE hRF (9 1 CHC13-Me+Xl)0 70. ‘RF (2 1

msertion

41500 (7.72) l%PhNHAc)

7.81

(9.50)

9.32

(8.50) 217

8.66 377fMf)

280

h23(M">'

321(Mf+l)

0

bSee General methods of preparation (Expermmantal). ‘Tic was performed on Alurolle-Kleselgel

poznts are uncorrected and were detsmuned on a Kofler

pro mole startwg

CC/MS/OS ws.trument (ion current, 0.1 mA, direct

&kck)

(87)' (EtDAc-hexane) (415.50)

C2hH21N3'ZS 69.85 5.64

(?OOO)

20)

164'

12.43

(64.07)(4 48) (12.46)

C18HlSN3D2S 64.02 4.49

m;

259-260'

99

99.7

11.00

(8.75)

8.24

(66.82)(5.07)(11.13)

C21HlYN3D25 65.61 5.06

(87)'(EtOAc-hexane)(377.45)

100

5 hr

CFGI

w 1hs-1h7°

C22n21N30hS (80)"(EtOH-heptane)(423.47)

92

U20.34)

'19"16N2'3

Ac20/PY

CEI

s 223-224o

(68)' (EtOhc)

loo@

5

(78f(CHC13-EtOAc) (337.39)

hr

224-225'

(slJr (EtOAc)

02

(loDo)

5

moo)

CFGIHYI

CIII

CFI

01

(13; 151

AC,O/PY _

(16;

4.5 hr

(lotlo)

(60, 50)

qwY

3 hr

(hh-h!jO)

20 hr

(loo01

5 hr

Ac2O/Py

%oles

7c9

18 Ac20/ZnC12 69 (50; 3.5)

8i

6s

(16, 19)

18,19 AG2DlPY fk

Table 1 continued

2h

13

li

Compound

as the eluent

KBr cm-l

lWX

‘RF

KHc13)

(C=N)

1603, 1578 (Ar)

1630'

1660 (amide)

2.

(9.1

RF

IR

‘!$

contwued

'H (200 MHz)

&

RF

clalmed)

Charschterlstics

“Ft,

l46-152

0

16

‘30

eV

“Wltbout

13 Hz,

~2~)

(s,

NAi)

3H,

3,

2.29

3 2 Hz, J2

2.28 (q,

(q,

.+

lH,22 ;, 13 Hz,3; 3s 14 Hz, H-3d) lH, _& 2 Hz, J,,3: 14 Hz, H-3d )

3.44

e 5.31 (dd, lH,

2.53 (5, 6H, 2Ac), 2 20 (s, 3H, AC>

(Qm, each lH, CH2CH2)

4.56-4.47, 4.23-4.10, 3.60-3.45, 2.64-2.55

e 7.50-6.80 (4m, 4H, H-Ar)

(C=O)

75 92

(C-2$

to

95.95(sp1ro C)

155.33WXe=N-)

e 166.00

be

23.79, 22.44 (CH3-CO)

153.05 (S-C(NHAc)=N-) 4H, H-Ar) 4.50-4.45 (ml, 4.10 (tr, 312.5 Hz), 3.25-3.17 (91, 75.64 (splro C) 64.36 (C-Zd) 2.30 (d, J12.5 Hz) (each lH, CH2CH2); 34.38 (Md> 2.15,2.05 (eachs, 3H, AC)

7.29-6.73 (m,

continued

6 ppma

Y~e~ng

b 169.45,167.24(CO)

131; (50.3 MHZ)

(CHC13) 0.51.

‘C (from EMH).

95 I EtOH).

system’.

Oc (from

qAn unseparated

solvent

m p. 218-221

second,

also when usmg another

ctiCi.pqo) 0 35.

6 ppm

Spectroscopxc

(9 1

&ted

PhH-EtJAc) 0 73. ‘l_lt.”

material69

(1.1

CHC13-Me2cO) 0.26.

1

(for mound

4ffF

m-p.

lHc,WAC)

and

(9.1

the startmg

% yield

with

35

first,

CHC13-Me2C0) 0 41

b 11.70 (s,

TabLe

1614, 1605, 1590, 1494 (Ar>

1745, 1713, 1697 WAC,)

and ldanti.cal

in

to the Table

r’htl-EtOAc) 0 42. wLlt.9

0 13,~~

(1.1

1710*,1704,1678(amide) 1649(C=N) 1626-1618 (Ar> 1590,1490(Ar>

3240, 3180, 3090 (NH)

+

‘9

UP UW mothet 1~uOr

CHC13 as the elwnt.

working

kuted

and ff_) wds recovered

%Q (9 1 CHC13-Me2CO) 0 74, hmogeneous.

ff

alxtuce

of the two lscmrs

"Using a 9.1 CW3-Et20

mlxtura

Legends

bi

21

1

a

e

1551

1583, 1570 (Ar)

1628
1707, 1606 (NAc2)

1457

2.50 (s, 6U, 2 AC)

e 6.43 (s, lH, H-3)

to be contmued

25.82 (2 CH,-CO)

95.61 (C-3)

e 170.46(2 C=O)

23.40,22.26,20.16ICHyCO)

78.03 (C-2d) 49.48 (C-3d1

2.20, 1.85, 1.71 (eachs, %I, kc)

1650 (C=N)

152.82(S-C@HAc)=N-1 Rl.36 (sprroC)

baa

5.00 (d, ltt,..710 Hz, O-CUR-Ph)

170.27,169.97,169.06tC=O)

1624, 1590 (Ar)

6.38 (d, lH, JlO Hz, CYf-OAc)

(s, ltf, WC)

1700", 1683 (arude)

e 10.30

1762 (OAc)

3235
1480 (am&da11)

24.09,22.79,20.24 (CH3-CO)

1618, 15x9 (Ar)

C)

79.37,70.29 (C-Zdand c-3d,

155.21fs-CmHAc)=N-1

170.20,168.96,168.15tc=a

76.99 k.prroCl 76.34 (O-CHR-l'h) 42.38 (C+$) 23.79,22.27 cCH,-a)

153.83(S-C(NHAc)=N-)

170.23,168.99(;=O>

78.98 (spm

2.26,2.09,1.80 (eachs, 3H, AC)

17ao*, 1690*, 1668 (amide)

e

e

11.51(O-&)=N-)

22.33 m,-ro)

38.16 (C-3d>

1645 (C=N)

5.6S (AF%q, Ztl,.?11 HZ, O-~~-~Ac-)

e 8.48 (s, lHc, NHAc)

1757 (OAc)

3250 (NH)

1401 (amideII or Ar)

1614, 1582 (AC)

2.53 (d, lH, J13 Hr, CH2) 2.34, 1.75 (aachs, 3H, AC)

3.41
1690*, 1670 hide)

1639 (C=N)

S.17 (d, lH, ~*,3 32 Hz, O-CfM'b)

e 11.03 (s, Ulc, NHAc)

3225 (NH)

3410

2.12 (s, M, 0-C(C/f$=N-)

Table2 cantinued

.r

I;

;s

Reactions of flavonoxl tbiosemc~nes

9313

L. SmYl

9314

the conversion hydrazone

of flavone thiosemicarbazone

(6~) may

be facilitated

by the

(60) into flavone diacetylformation

of

an

intermediate

flavylium salt. Such an effect of the flavone ring, resulting in different reactivity,

was

analogue

2g

indicated

also

diacetylhydrazone

(6s) -

by

in contrast

the to

- could not be converted

observation

the

that

corresponding

flavone

2,3-dihydro

into the respective

oxadiazoline

isomer 6h with the AczO/ZnClz reagent. Even under forcing conditions and after

prolonged

reaction

time,

the

unchanged

starting

6g

was

almost

quantitatively recovered (see Table 1). EXPERIMERTRL

Concerning

the

starting

materials,

acetylating

reagents,

reaction

conditions, and processing of the reaction mixtures, as well as yields and m.p. data (solvents for recrystallisation) see Table 1. General

methods

of

preparation

(A)

The reaction mixture was poured onto ice and water.

(B)

The reaction

mixture

was

cooled.

The crystals which

separated

were collected by suction, triturated with anhydrous ethanol-heptane 1:2, then with water, and dried. (C)

The

reaction

mixture

was

concentrated

under

reduced

pressure

(D)

The crystalline residue was triturated with 809 ethanol to give the

(< 48-C , bath ). crude product. (E)

The

crystalline

residue

was triturated with anhydrous ethanol and

heptane. The crude product was extracted with hot chloroform. The solution was concentrated. (F)

The residue was triturated with ice-water.

(C)

chloroform solution of the crude product A fuller's earth and charcoal, then concentrated.

(Ii) The (I)

product

purified

treated

with

by column chromatography on silica gel.

The product was crystallised from the solvent indicated.

4-Chromdnone

11.0

was

was

g,

74.0

thiosemlcarbazone

mmol,

(1c): A mixture

of 4-chromanone

(Se;

Aldrich),

thiosemicarbazide (13.2 g, 14-5 ~ol)~~ anhydrous ethanol (600 mL), and cont. HCl (3 mL) was boiled for 22 hr, then cooled to give crude (15.9 g, 97%, m.p. 208'C) or recrystallised Aa (15.28 g, RF

0.47,

2884,

93.3&), m.p. 215-216'C (from EtOH). Tic (8:2 CHCl3-EtOAc), (95:5 CHC13-MeOH) RF 0.74. IR (EBr): 3435, 3235, 3160, 2988,

1605,

1515,

1507

cm-l.

Anal.

Calcd

for

C10H11N30S:

C,

54.28;

9315

Reacuonsofflavonoidthxscnzcarbazones

Ii, 5.01; N, 18.99; S, 14.49. Found: C, 54.41; Ii, 5.18; N, 18.88; S, 14.50. thfosemicarbazone

trans-3-Hydroxyflavanone

(3823,

trans-3-hydroxyflavanone (1.641 g, 18 mmol),

anhydrous

3.604

ethanol

g,

(30):

15

mixture

A

of

lnmol), thiosemicarbazide

(140 mL), and cont. IiCl (0.6 mL,

7 mmol) was boiled for 6 hr, then concentrated. The residue was triturated with water 3c

(3.387

crude

(-100 mL) to give g,

72.1%),

m.p.

(4.156 g, 88.4%) or recrystallised (from

198-199'C

chloroform-ethanol).

Tic (3:l benzene-ethyl acetate) RF 0.45. IR (KBr):3225, 1560, 1478, 1472, 1456, 1440 cm-l. Anal. Calcd for C16H15N302S: C, 61.32; Ii, 4.82; N, 13.41; S, 10.23. Found: C, 61.57; Ii, 5.02; N, 13.29; S, 10.53. 2-Benzylrdene-l-lndanone

2-benzylldene-1-indanone

thlosemlcarbazone (9a21s22,

3.304 g,

(SC):

15 mmol),

mixture

A

of

thlosemicarbazide

(2.734 g, 30 HIIUO~), anhydrous ethanol (150 mL), and cont. HCl (0.6 mL) was bolled for 5 hr, then cooled to give crude (4.212 g, 95.7%, m.p. 213-C) or recrystallised (CHCls) RF

SC (3.618 g, 82.2%), m.p. 219'C (dec., from ethanol). Tic

0.22.

IR

1453 cm-l. MS m/e:

(KBr): 3340, 3232, 3144, 1635,

293

(Mt),

1570*, 1481,

275, 260, 233, 218 (100%). Anal.

C17HlsN3S: C, 69.59; H, 5.15; H, 5.35; N, 14.42; S, 10.98. Y-Fluorenone

1600,

N,

14.32;

S,

(10c): A

thlosemlcarbazone

10.93.

Found:

mixture

of

Calcd for C,

69.81;

9-fluorenone

(loa, 3.678 g, 98% purity, 20 mmol), thiosemicarbazide (2.111 g, 98% purity, 22.7 mmol), and acetic acid (96%, 10 mL) was boiled for 2 hr, then cooled. The product

separated was

filtered off and washed

successively

with 50% acetic acid, water, and hexane to give crude 10~ (4.860 g, 96%), lll.p.

217'C

(dec.). Recrystalllsatlon of the crude product

(1.755 g) from

2-methoxyethanol

(35 mL) upon addition of water (10 mL) afforded pure 1Oc

(1.537 g, yield

84%), m.p.

Anal.

214-C

(dec.). Tic

(2:l PhH-EtOAc)

RF

0.68.

Calcd for CH14HllN3S: C, 66.37; H, 4.38; N, 16.59; S, 12.66. Found:

C, 66.92; H, 4.60; N, 16.56; S, 12.80. Benzophenone

benzophenone

4-phenylthiosemlcarbasone

hydrazone

(llb, 7.850

g,

(lld): A 40 mmol), phenyl

mixture of isothiocyanate

(5.795 g, 42 mmol, purlty 98%), and ethyl acetate (12 mL) was boiled for 9 hr, then cooled and diluted gradually with hexane (60 mL) to give crude (13.261 g, 100%) or recrystalllsed isopropanol). Tic

(9.849 g, 74.3%) lid, m.p. 154-C

(from

(CHC13): RF 0.50. Anal. Calcd for C~OH~~N~S: C, 72.47;

H, 5.17; N, 12.68; S, 9.68. Found: C, 72.68; H, 5.24; N, 12.64; S, 9.74.

9316

L. soMcmYI

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