THE CURTEUS AND BECKMAMN REARRMQGEMERT
0? W45 ScEHiANAPI‘E-WL SYSTEM

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MICHIGAN STATE UNIVERSE”
Earl D. Mitchell, Er.
3.96.3

IHESIS-

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MICHIGi‘iN STATE UNIVERSITY

EAST LANSING, MlCnglg

1

THE CURTIUS AND EECKMANNLREARRANGEMENT

@F THE 2-THIANAPTHYL SYSTEM

Earl D. Mitchell, Jr.

A THESIS

Submitted to
uMiehigan State university
in partial fulfillment of the requirements
for the degree of

IMASTER 9F SCIENCE

Department of Chemistry

1965

 

' ACKNGWEEDGEMENT

The author wishes to express his earnest appreciation
to Professor Robert D..Schuetz for his counsel and friend-
,ship throughout the course of this work. .The author is
also grateful to his wife for her support and understanding
during the course of this investigation.

ii

INTRODUCTION. . .

HISTORICAL.

TABLE OF

RESULTS AND DISCUSSION. .

The Curtius Rearrangement.

The Beckmann Rearrangement .

EXPERIMENTAL. . .

Lithium Sand .

CONTENTS

Preparation of 2-Thianapthoic Acid .

Preparation of Diazomethane and Methyl

2-Thianapth Gate 0 o o o 0

Preparation
Preparation
Preparation
Preparation
Preparation
Preparation
Preparation

Preparation

SUMMARY.... .w. ------ . ........... ,,

REFERENCES. .

of

of

of

of

of

of

of

of

2-Thianapthoyl.Azide. .

Ethyl N-2 Thianapthyl Carbamate . . .

2~Acetyl Thianapthene .

syn-Methyl-2-Thianapthyl Ketoxime oi-

NaAcetyl 2-Thianapthylamine -

Phenyl 2-Thianapthyl Carbinol .

Phenyl 2-Thianapthyl Ketone . . . . .

Phenyl 2-‘11'11anapthyl Ketoxime . . . .

iii

Page

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16.

LIST OF FIGURES

. Infrared Spectrum of 2-Thianapthoic Acid.

Infrared Spectrum of 2-Thianapthy1amide . .

Infrared Spectrum of 2-Thianapthoyl Azide .
Infrared Spectrum of Hydrolyzed.Azide . . .

Infrared Spectrum.of Heated.Azide . . . . .

.Infrared Spectrum of Ethyl 2-Thianapthyl. .

- Infrared Spectrum of Methyl 2—Thianapthoate .

- Infrared Spectrum of 2-Thianapthoyl Hydrazide

N.m.r. Spectrum of Ethyl 2-Thianapthyl Carbamate.

Infrared Spectrum of 2-Thianapthyl Isocyanate .

Infrared Spectrum of 2-Keto Thianapthene. .

Infrared Spectrum of 22Acetyl Thianapthene. . . .

Infrared Spectrum of NAAcetyl 2-Thianapthylamine.

N.m.r. Spectrum of NAAcetyl 2-Thianapthylamine.

Infrared Spectrum of Phenyl 2-Thianapthyl Carbinol.

Infrared Spectrum of Phenyl 2-Thianapthyl Ketone.

iv

Page

15
16
18
19
2O
21
25
27
28
30
31

ABSTRACT

THE CURTIUS AND BECKMANN-REARRANGHENT

OF THE 2-THIANAPTHYL SYSTEM

by Earl D,‘ Mitchell

The purpose of this investigation was to develop new
synthetic methods to obtain derivatives of 2-amino thia-
napthene. _The procedures used were the Curtius and Beckmann
rearrangements.

..A new synthetic method was developed for the prepara-
tion of the intermediate ketones for the Beckmann rearrange-
ment on the 2-thianapthyl system. ,The reaction sequence

can be illustrated by the following equations.

 

O
.In

 

 

INTRGDUCTIGN
The present study was undertaken to develop synthetic

methods to obtain derivatives of 2-aminothianapthenes through.
nitrogen to carbon rearrangement reactions. .There have been

a few reports in the literature on 5-aminothianapthenel. 2-

» Aminothianapthene is unknown and B-aminothianapthene is
reported2 to be too unstable to be isolated. It is apparently
less stable than 2- and j—aminothiophene, since it has been

5

reported that 2- and j-aminothiophenes are undistillable.

The instability of the 2- and B-aminothianapthenes isivery

probably due to the existence of the amino form and the

d
F
. CMa

tautomeric imino form, in which the latter contributes greatly

 

to its instability.

.Stable aminothiophenes are obtainedll in the form of deb
rivatives. These derivatives are usually obtained via the
Gurtius, Beckmann, and Hoffmann rearrangements. eBaseduonfithis
Observation and the similarity in the chemistry of thiophene
and thianapthene, it was reasonable to anticipate that stable

aminothianapthenes could be obtained in the form of derivatives,

through the use of the Curtius, Beckmann, and Hoffman rearrange-
ment of appropriate nitrogen containing compounds of thianap-
thene. The Hoffmann rearrangement has been extensively studied
on the 2- and fi-thianapthyl systems. The Curtius rearrangement
has been partially examineds, but at present the Beckmann re-
arrangement has not been reported. The initial problem in
connection with a study of the Beckmann rearrangement in the
thianapthyl system is obtaining the intermediate ketones.

6 of 2-thianapthene

Previously reported methods for the preparation
ketones usually had limited applicability and did n0t,;in general
give satisfactory yields of these compounds. It was hoped that a
simpler and more easily applied method giving better yields

of pure product could be developed. .In the course of this in-

vestigation a satisfactory general procedure has been developed

to obtain acyl derivatives of thianapthene.

HISTGRICAL
While there has been rather extensive studies reported
on the 2- and j-aminothienyl system, relatively few 2- and 5-
aminothianapthene derivatives have been prepared up to the
present time.

‘7

In 1902, Curtius treated 2-thenoyl azide with absblute

ethanol at the reflux temperature of ethanol and obtained

' 0
[I ll ——> [I L n
CONs NFC-@CaHs

S S

ethyl 2-thienyl carbamate.
However, as early as 1899, Remini‘8 carried out the

Beckmann rearrangement on methyl 2-thienyl ketoxime to obtain
N”0H
[81:43:31, E SlN-CGCHa H01 3 l 2'HCl

2-acetyl 2-aminothiophene.

Recently Buzak and Teste9 have studied the same rearrange-

ment with the S-chloro-2-thienyl system.

I NIIOH l I
ll ’ ’ H .
Cl . S C-CHa Cl N-COCHs

27%
q 0H
\
ll Hi ——> [U H
Cl 8 C-CHa Cl .8 Co-N-CHa
52%

In the 5-thienyl system,~Campaignelo has investigated
the Hoffmann degradation of 3-thienamide and isolated the

substituted amide.

. H
CONH2 N393, N-coR
II I] ——* I l ‘
_ RCOCl a . ,
s ‘ s .

R=Me,¢

5

Weissgruber and Kruber reported that 2,5-thianapthene

dicarboxylic acid formed two isomeric monamides, when allowed

coan NH

5 CGQH

 

FI II

NaOBr

 

coaH

   

established by the Hoffmann degradation reaction in which

the known 2- and 5-hydroxy thianapthenes were Obtained. The
anticipated product in these Hoffmann degradation reactions.
would normally be the aminothianapthenes. The isolation of
the 2- and 5-hydroxy derivatives clearly demonstrate that the
amino group is unstable and is easily replaced by a hydroxyl ‘
group. The reaction is reversible since the acetamide deriva-

5

tive is obtained when 3-hydroxy thianapthene is treated with

 

acetamide in acetic'acid; the principle product being d1‘(5-

thianapthene )amine (II ).
In 1929, Kompall isolated B-amino thianapthene as its

stannic chloride double salt by the reduction of 5-nitro

N02

. Snflfl01> '_ SnClg

   

thianapthene with an acid solution of stannous chloride.

. The Beckmann rearrangement has not as yet been carried
out with the 2- and.3-thianapthyl system, an aim of this
study. HThe present investigation also examined the feasi-
bility of developing a good reaction sequence that, in A
general,-would give good yields of the desired ketones,
required for a study of the Beckmann arrangement in such a

system.‘

RESULTS.AND'DISCUSSISN
.In order to introduce substituent groups in the 2-
position on thianapthene, it is first necessary to metalate
thianapthene using an exchange reaction with n—butyl
lithiuml2. jMono metalation of thianapthene occurs almost
exclusively at the 2-position which can be explained by the

inductive effect of the hetero atomlj.

 

THE CURTIUS REARRANGEMENT
5

The Veissgerber method was used for the preparation

I

of thianapthoyl azide. To obtain quantitative yields of

methyl thianapthoate, diazomethane was used. .Diazotization

 

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13

of the hydrazide produced the azide. Crystalline thianapthoyl
azide is quite stable to light undergoing decomposition to the
isocyanate, only after a period of six months exposure.

Heating the azide in an inert solvent (toluene),.for four

hours produced a reddish-orange compound, the isocyanate,.which
melts at 96°-97° and unrearranged aride which melts at lO8°.
The attempt to interact sodium azide in absolute ethanol to

obtain the azide was unsuccessful.

 

o
fl| N=N=N 110° ’
r- l
.o
Nsc=o + Nét <"“" l u_N7fi=§
.s s i ..

 

The infra-red spectra of the heated azide showed strong
absorption at h. 39}; (isocyanate) and h. 68 u. (azide) indi-
cating that the rearrangement was not complete. Heating the
azide in acetyl chloride at the reflux temperature of the acid
chloride several products were detected through the use of .
thin strip chromatography; however, the principle product is
the one that melts at 96° -97° which is the isocyanate. The
infra-red spectra of this.crude product mixture showed strong

absorption peaks at h.39 p and h.7l u.

 

 

 

.1h

Hydrolysis of 2-thianapthoyl azide with hydrochloric
acid gave a product mixture which showed the same infra-red
spectra. However, one of the products isolated in very low
yield showed none of the characteristic azide and isocyanate
absorption peaks in the infraéred. This material showed
strong peaks at 2.9h (m) u (0-H) and 5.85 (s) H carbonyl.
.The melting point of this compound was 1935.. This dataonuld
suggest that this compound might be a mixture of the keto
and enol form of 2-hydroxy thianapthene; however, the melting

5

points do not coincide with the literature .

 

iNHg'HCl

 

H20

   

.Further identification of this material was not carried out,
though itbhassbeen clearly’demonstrated5 that the amino group
in aminothianapthenes can be easily replaced by a hydroxyl

group.

 

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16

l7

. ETHYL N—2-THIANAPIHYL GARBAMATE
The synthesis of ethyl N-2-thianapthyl carbamate was
accomplished by heating an ethanol-ether solution of thia-

napthoyl azide at its reflux temperature.

EtGH-Etao i I H fi
3 CONg reflux s . N-C—GCéHS

-A.crude yellow crystalline mixture was Obtained which
melted at lh8°C. The infra-red spectra showed absorpéion
bands at 5.10 (w)p,.(N-H)3 n.76 (w)u (azide); 5.75 (s)u,
(carbonyl) 6.h9 (s)u,.(N-H.def.) and 7.86 (m)u,.(N-C). The
area of the peak at h.76 u was very small indicating that
the amount of unrearranged azide was very small. Thin
layer chromatography showed that the product mixture con-
tained three major components. However, attempts to
separate the compounds on an aluminum oxide column resulted
in the isolation of a singular crystalline compound (m,p.
160°-161°c).

. The ultraviolet spectraof this compound showed @531 =
229 mu and (log e = 3.367). .The infra-red spectra was
identical to that described above except for the absence of
the azide absorption peak at h.70 u. The n.m.r. spectra

strongly supports the structure

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The aromatic rings gave an area ratio of h:l for the
aromatic protons. .In the aliphatic region there is a triplet
at 8.75 tau and a quartet.at,5,76 tau which shows the presence
of the ethyl group. Hydrolysis of the urethane gave a low

melting solid (m.p. 5h°C) which was the 2-keto thianapthenes...

 

 

m.p. h5°C

THE EECKMANNrREARRANGEMENT

The initial problem involved in a study of this rearrange-
ment with the 2-thianapthyl system was the synthesis of the
2-thianapthyl ketones. Thianapthene can be acylated in the
usual manner with acyl halides employing Friedel-Craft type
catalyst. .Ferrar andLevinelb')4 have found that thianapthene can
be acylated to give a mixture of very low yield of the 2- and

5-isomers; however, the 5-isomer is the predominant product.

23

+ ROCl 4193-)-
032
- , COR

 

10%

 

12%

The above results can be best explained by the resonance
structures I and Ill. The formation of I requires resonance

interaction involving the benzene ring which is not necessary

1‘ I) ___; ——

 

II IIa

 

 

 

II . 11a

for the formation of II. .Further there are two ionic struc-
tures II and 11a in which the negative charge is in the two
position while there is only one such structure in I. .Another
classical method used for the preparation of 2-thianapthyl
ketones involves a ring closure procedure. .The ring closure
of o-mercaptobenzaldehyde with Chloroacetone gives a very low

yield of 2—acetyl thianaptheneli. Since methods described in

2h

CH0 NaOH
+ ClCHgCOCHg W
' S OCHa

53H

the literature to obtain the necessary intermediate 2-thia-
napthyl ketonesegave very poor yields of the desired products,
an alternate was sought. The method of interacting an alkyl

lithium with a dimethylamide was usedus.
O

O

R-Li + (CH3)2N-C-R' -——e> R-C-R’
Interacting 2-thianapthyl lithium.with N,N—dimethylace-
tamide gave a yield of 56% of 2-acetyl thianapthene. This
compound was readily converted to its oxime.

o
H‘

+ (CH3)2-N-C-

   

56%

_As one might suggest, the anti 2-thianapthyl methyl
ketoxime was obtained. Since the thianapthyl group is bulky
and much larger than the methyl group, the most stable cone
firmation is that having the thianapthyl group anti to the
hydroxyl group.

The oxime was treated with phosphorus pentachloride to
cause it to undergo the Beckmann rearrangement. ,However, this
reagent was mudh too strong and a polymer-like material was
obtained. .Similar results were obtained with the use of 96%
sulfuric acid., The best'catalyst for this was the use of 85%

phosphoric acid. Under these mild.conditions, and at

655993.35. abmodum Ho agpoomm coughs” . .NH warm

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v p — F

 

 

 

 

 

 

 

 

 

 

 

 

 

 

25

26

N/,OH 85%
l H.120, 5
II
reflux
C-CHa

 

reflux temperature for only one hour was sufficient to obtain
rearrangement of the oxime. The compound obtained after puri-
,fication melted at 8u°-85°0. The infra-red spectra showed
amide absorption band I at 5.98 (s)u, (carbonyl); band II at
6.58 (s)u,.(N-H def.); and band III at 8.05 (s)u, (N-c).. The
n.m.r.spectra showed an area ratio of aromatic protons of‘
hzl and a singlet at 7.92 tau.due to the unsplit methyl group.
Methyl groups next to carbonyls vary from 7.80 tau to 8.05

17 16

tau . .Acetamide shows a singlet at 7.98 tau , indicating
that the singlet at 7.92 tau is the methyl group next to the
carbonyl. The structure of the oxime was concluded from the
structure of the rearranged product.
.PHENYL 2-THIANAPTHYL KETONE

Phenyl 2-thianapthyl ketone was prepared by the oxidation
of the corresponding alcohol. 8

.Phenyl 2-thianapthyl carbinol was prepared as described
17

by Shirley and Cameron , using the interaction'of 2-thia-

CHO .
+ "f€"
Li "

   

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28

29

napthyl lithium and benzaldehyde. The oxidation of the alcohol
initially presented some difficulties. .An Oppenauer oxidation
of this alcohol gave less than a 5% yield of the ketone. .Di-
chromate oxidation, using the procedure of Brownla, was
'attempted. That is, by slowly adding sodium dichromate and

asulfuric acid to a well stirred solution of the alcohol.

.OH

Na2Cr ' 2 H20
Hgso4 9

   

This procedure produced a 69% yield of the crude low melting
solid. ,Since the ketone was a low melting solid (m.p. 47°-
h8°C), it was necessary to use a low boiling solvent for re-
crystallization in order to keep it from coming out of solution
as an oil and carrying the impurities out of solution

with it. . (Previous attempts to vacuum distill the ketone led
to a tar-like product and no distillate.) Petroleum ether

was used as the solvent for recrystallization. .Shapely
monoclinic crystals were obtained. The infra-red spectra,
showed the characteristic aromatic protons 3.30 (m)u, carbonyl
6.10 (vs)u and phenyl 6.25 (m)u, 6.65 (s)p., 6.90 (m)u. The

oxime was prepared from the ketone. The beat procedure was to

U. °°°
KOH

 

NH

OH

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31

32

dissolve the ketone in 95% ethanol and add potassium hydroxide
along with the necessary amount of hydroxylamine hydrochloride.
A brownish solid was obtained. Recrystallization from a water-

acetone mixture produced a white crystaline compound, m.p.

1h5°-1h7°0.

EXPERIMENTAL

.All infra-red spectra were obtained on a PerkineElmer
Model 21 recording infra-red spectrophotometer, using a
sOdium chloride cell. ,The bands were determined in microns.
The ultraviolet spectra were determined in l-cm ground
stoppered quartz cells using a Beckmann DK-2 spectrophoto-
meter.

Proton magnetic resonance spectra were obtained on a
varian Model A-60 instrument. ,All Spectra.were obtained at
60 Megacycles using tetramethylsilane as an internal
standard. The band positions. were recorded in2T.(tau) units

as prescribed by Tierszo.

THIN'STRIP. CHROMATGGRAPHY

An 18.0 g. (0.017 moles) quantity or aluminum oxide and
12 g of plaster of paris were mixed in a petre dish with 32
ml.of 2% sodium hydroxide solution. Using a spatula,-two
levels of the mixture were placed and spread on a microscope
slide. The strips were dried in air for 3 hours and then
they were placed in an oven to dry at 100”C. for-h hours.
.The strips were removed from the oven and stored in a.desSi-

cator containing potassium hydroxide. 20 Strips.

33

3h

The chromatographic strips were used on reaction mix-
tures or impure solids. The impure compound was dissolved
in acetone using a small melting point capillary. _Approxi-
mately six drops were placed in a spot at the bottom of the
strip. The strip was then dried with air and placed into a
test tube containing enough eluent to touch the bottom part
of the strip. After.the solvent traveled the length of the
strip it was removed and dried with air. Isatin-sulfuric
acid was used as the dye to develop the spots on the strip.
The eluent was varied until there was a clear distinction of
products. This procedure can be used as a pre-check to find
the proper eluting solvent on a chromatographic column or to

determine the number of components in a reaction mixture.

LITHIUM SAND

To obtain a more reactive lithium for metalation
reactions, it is necessary to use lithium sand; that is, a
state of division of the metal giving a very large surface
area.

.Approximately 10.2 g. (1.60 moles) of lithium wire, cut
into 5 x 1 cm. strips, were placed in an iodine flask, con-
taining 100 ml. of mineral oil. The suspension of metal and
mineral oil were heated, with a bunsen burner, until the
temperature was approximately 200°C. Using asbestos gloves,

the flask was firmly stoppered and shaken vigorously for 5-

55

10 minutes and then was set aside to cool to room tempera-
ture. The finely divided lithium sand was recovered by
decantanation, washed with ether to remove the mineral oil

and stored under ether until used.

2-THIANAPTHOIC ACID

3 002H

Thianapthene was metalated as described by Shirley and
Cameron12

.A liter three neck round bottom flask fitted with a
stirrer, dropping funnel, nitrogen inlet tube and condenser
with an attached calcium chloride drying tube was charged
with 200 ml. of anhydrous ether and 7.1 g. (1.02 moles) of
lithium sand. The reaction flask was cooled below ~10° by
immersion in a dry ice 2épropanol bath and a solution con-
taining 1h1.0 g. (1.07 moles) of n-butyl bromide dissolved in
100 ml. of anhydrous ether was slowly added during two hours.
The reaction mixture was stirred for an hour following the
addition of the n-butyl bromide and then 81.0 g. (0.60
moles) of thianapthene dissolved in 150 ml. of anhydrous
ether was added to the cooled alkyl-lithium solution during
a half hour. .To obtain a maximum quantity of thianapthyl

lithium, the ether solution was subjected to a mild vacuum

36

with a water aspirator, forcing the equilibrium in the direction
favoring the production of the organometallic. The reaction
mixture became viscous and required the addition of ether
several times to permit good stirring. The thianapthyl lithium
solution was poured over a slurry of carbon dioxide and ether.
Following the evaporation of the carbon dioxide, the resulting
solution was acidified with a 5% hydrochloric acid solution to
obtain the crude acid. The crude product was recrystallized
from methanol to obtain 138.0 g. (0.77 moles) of pure acid

which had a melting point of 23h°-236°C. (lit.l2 23h°-236°C).

METHYL 2-THIANAPTHOATE

. s C02CH3

2-Thianapthoic acid was esterified with diazomethane. The
diazomethane was prepared as described by VOgellg.

To a four liter beaker containing 5h.0 g. (0.91 moles)
of acetamide, 88.0 g. (0.55 moles) of bromine was added very
slowly. The alkaline solution was heated until effervesence
occurred. The white crystalline acetyl methyl urea was re-
covered by filtration and washed with 100 m1. of cold water.
It was dissolved in 50 m1. of concentrated hydrochloric acid
and heated for 8-10 minutes. The solution was cooled to 0°C
and 38.0 g. (0.hh7 moles) of sodium nitrite was carefully added
to the acid solution. .The nitroso-methyl urea (m.p. 123°-12H°C.)

was recovered by filtration and stored for use.

37

A 60 ml. volume of 50%.potassium hydroxide diluted with
200 ml. of ether was added to a 500 ml. round bottom flask
fitted with a side arm condenser. The flask was cooled to
Q?C and 20.0 g. (0.19% moles) of nitroso-methyl urea was slowly
added with occasional shaking. The reaction flask was warmed
_ on a steam bath and the evolved diazomethane was bubbled
directly into 100 ml. of ether contained in a conical flask.
The diazomethane ether solution was then cautiously added to
a solution of 2-thianapthoic acid in ether. .Excess diazo-
methane was tested for by adding a drop of glacial acetic acid
and nitrogen evolution was observed.. The m.p. of the ester

was 72°—73°C. .Literature value: 72°-73°C.5’l2.

2—THIANAPTHOYL.AZIDE

 

WIN;

A 100 ml. round bottom flask was charged with 13.0 g.
(0.067 moles) of methyl thianapthoate dissolved in 25 ml.
of 95% ethanol. .An excess of hydrazine hydrate [10.0 g. (0.25
mole)] was added to the alcoholic [solution and -- thezreaction
mixture was heated on a steam bath for five hours to Obtain
21.0 g- (0.10h moles) of 2-thianapthoyl hydrazide (m.p. . 18M-
)“ w

185°C. .. .The hydrazide was dissolved in 100 ml. of ethanol

and added to 90 ml. of acetic acid saturated with sodium

38

nitrite. The long needle-like crystals of product, which
separated ,. were collected on a filter and recrystallized fran
an ethanol-water mixture. ,A 50% yield or 10.0 g. (0.019
moles) of 2-thianapth;oy1 azide was obtained which melted at
108° with decomposition.

'Ihe azide, when heated in a test tube ,produces an- oily
redissh-brown residue which on recrystallization from 8
ethanol yields a fine powdered.:solid (m.p.. 96°C, ).

Treatment of the azide with acetyl chloride yielded a
solid isocyanate (m.p. 96° -97°c. ). .Simple heating of the
azide in a toluene solution for four hours also produced the
isocyanate. Infra-red analysis of these materials gave the

characteristic isocyanate absorption peaks.

E‘I‘I-IYL N-2-‘I'HIANAPI‘HYL CARBAMATE

Into a. three necked round bottom flask. equipped with a
stirrer,,l.77 g. (0.008 moles) of 2-thianapthoyl hydrazide
dissolved in 100 ml. of water and 20 ml. . of 6 N hydrochloric
acid were added. The reaction flask was cooled to below 5°C
by immersion in an ice bath. ,A 100 ml. Volume of ether was

added, followed by a solution containing ll».0 g._ (0.058 moles)

39

of sodium nitrite dissolved in 50 ml. of water. The azide
produced was extracted into the ether layer. The two layers
were separated and the aqueous layer was washed with three

50 ml. portions of ether. .The combined ether layers were
dried, first over anhydrous sodium carbonate for five min-
utes and then over calcium chloride for ten minutes. The
dried ethered solution of 2-thianapthoyl azide was decanted
into a 300 ml. threeenecked round bottom flask equipped with
a stirrer and condenser. ”A ho ml. volume of absolute ethanol
was added to the reaction flask and the ether was removed by
distillation on a steam bath. .When the ether had been re-
moved the azide-alcohol reaction solution was heated at its
reflux temperature. .The solution was concentrated by dis-
tillation to about 25 ml. to Obtain the urethane. This was
recovered by filtration and recrystallized from.ethanol to
obtain a pure product in the form of yellow colored crystalline
needles. .This material melted at lh8°-l60°c. (Lit. 160°-
16130.)h indicating it was impure.

The yellow crystalline solid was dissolved in a minimum
vblume of acetone and applied as a spot on a chromatographic
strip. .0n elution with a 50:50 mixture of petroleum ether
and ethyl acetate, thrbe spots were observed when the isatinx
sulfuric acid test was applied. These spots were probably
the azide, the isocyanate and the urethane. The remainder of

the acetone solution was then applied to a chromatographic

to

column prepared from cotton, sand and alumina. The column was
eluted with a 50:50 mixture of petroleum ether and ethyl
acetate. -Six fractions of 10 ml. each were collected. 0n
evaporation, fraction v yielded a white solid (m.p. 160°-
161°C. ),/\Et®H 229 mu (log e = 3.367).

max
Anal.
Calc'd.: cllHllmoas: c, 59.75; H, h.97; N,6.§5;;s,,lhtu8£.

Found : c, 59.hl; H, 5.h1; N, 6.50, 5, 15.87.

22ACETYIQTEIANAPTHENE

D
In

C-CHs

V Thianapthene was metalated using 13.8 g. (2.0 moles) of
lithium, 136 g. (2.0 moles) of n-butyl bromide on 116.0 g.
.(O.870 moles) of thianapthene as described previously.

An 87.0 (1.0 mole) quantity of'N,N4dimethyl acetamide
was added slowly to the cold.(-10°C) stirred solution of 2-
thianapthyl lithium. The reaction mixture was stirred for
an additional hour and then extracted with water. ,The ether
was removed by evaporation and 85.0 g. (0.20 moles) of a
yellow crystalline solid was Obtained. This was purified by
sublimation to yield 76.0 g.~ (0.hh2 moles, 56%) of a pure I

product which melted at 87°-88°C. Literature6: 87°-88°C.

synrMETHYL 2—THIANAPTHYLIKETOXIME

A solution containing 25.0 g. (0.1hh moles) of 2 acetyl-
thianapthene, 15.0 g._(0.2l8 moles) of hydroxylamine hydro-
chloride, 28.0 g. (0.70 mole) of sodium hydroxide dissolved
in 50 m1. of 95% ethanol was heated at its reflux temperature
for five minutes. The basic solution was cooled and poured
into 75 ml. of cold 6 N hydrochloric acid solution. The solid
material which separated was collected on a filter. .Sub-
1imation of the crude material produced two products. .Qne
compound (less then 0.2 g.) melted at 33°-3h°C and the main
product (13.0 g.) melted at l81°-l82°. Literature value:

185°C.6.

NnACETYL 2-THIANAPTHXIAMINE

 

.A 2.0 g. (0.016 mole) quantity of a 2-thianapthyl ‘

ketoxime was dissolved in 25 ml. of 85% phosphoric acid and

(A1

h2

the acid solution was heated at its reflux temperature for an
hour. .An oily brown liquid which solidified on cooling was
obtained and purified by sublimation (m.p. 8h°-85°C.).

The infra-red spectrum of this material showed strong
absorption peaks at 2.99(w)u,3.26 (w)u, 5.95 (s)u, 6.61 (s)
p, 7.87 (s)u, 8.16 (m)u, and 13.78 (s)u. The n.m.r. spectra

showed a singlet at 7.92 tau.

PHENYL 2-THIANAPTHYL CARBINOL

NH
.5 I
H

Phenyl 2-thianapthyl carbinol was prepared as described
17

by Shirley and Cameron with some modification of their ex-
perimental procedure. A two liter three-neck flask was
fitted with a stirrer, dropping funnel, nitrogen inlet tube
and condenser with an attached calcium.drying tube was
charged with 200 ml. of anhydrous ether and 25.0 g. (3.6
moles) of lithium sand. The reaction flask.was cooled below
-10°C by immersion in a dry-ice 2-propona1 bath and a
solution of 260.0 g. (1.9 moles) of technical grade n-butyl
bromide dissolved in 200 m1. of anhydrous ether was added
slowly during a two hour period. Following addition of the
alkyl-halide solution, 179.0 g. (1.36 moles) of thianapthene

dissolved in 100 m1. of anhydrous ether was added to the

cooled alkyl lithium solution.

43

The thianapthyl lithium solution was subjected to a mild
vacuum with a water aspirator, forcing the equilibrium in the
direction favoring production of the organo metallic. .The
reaction mixture became rather viscous and required the addi-
tion of ether several times to permit effective stirring. A
solution containing 13h.0 g. (1.h moles) of benzaldehyde
dissolved in 200 ml. of anhydrous ether was added during a
15 minute period to the cooled (-lO°C) thianapthyl lithium
solution. .The reaction mixture was stirred for an additional
hour at a temperature between 0°-15°C., following the addition
of the benzaldehyde. The reaction mixture was then heated
at its reflux temperature for a half hour and poured over a
solution of ammonium chloride containing crushed ice. .The
water layer was extracted with ether and the combined ether
layers were evaporated to dryness to obtain 236.0 g. (0.98
moles, 82%) of crude alcohol, m.p. 83°-85°. Literature: 8h°-
85°C.

The yellow crystallizing material was recrystallized from
warm ligroin to Obtain a 210.0 g. (0.92 moles, 78%) quality
of pure product, melting in the temperature range of 8h°-

85°C.

PHENYL 2-THIANAPTHENYL KETONE

 

A 17.61 g._(0.075 mole) quantity of phenyl 2-thia-
napthyl carbinol dissolved in ether was added dropwise
to a stirred solution containing 15.1 g. (0.051 mole) of
sodium dichromate dihydrate, 6.78 ml. of concentrated
sulfur acid and 50 ml. of water. The stirred solution
was heated at its reflux temperature for four hours. The
ether layer was separated and washed successivley with a
10% sodium hydroxide solution, saturated sodium.bicarbonate
and finally with water. The washed ether layer was dried
over calcium chloride and then evaporated to dryness. An
oily residue which solidified after setting overnight
was obtained. .A 69% 12.2 g.(.051 moles) yield of crude
product, melting in the temperature range of h5°-51°C.,
was obtained. The crude material was recrystallized from
petroleum ether(b.p. 50°—60°) m.p. h8°-u9°c.
Anal.

.Calc’d.: C15H1906: .c, 75.60; H, 4.19, s, 13.h5.

Found : C, 75.81; H, h.hh3 S, 13.37.
EEEH = 306.5 mu (log e = h.218).

ht

PHENYL 2-THIANAPTHYL KETOXIME

OH
3
N
N

‘ l

A 5 g._(0.022 moles) quantity of phenyl thianapthyl ketone
was dissolved in 70 ml. of 95% ethanol and 5 g. (0.0uh moles)
of hydroxylamine hydrochloride along with 12 g- (0.21% moles)
of potassium hydroxide were added to a 300 m1. one-necked
round bottom flask equipped with a condenser. The reaction
mixture was refluxed for 2 hours and poured into 200 ml. of
water. The suspension was stirred and then acidified with a
6 N hydrochloric acid solution. The yellow solid which
separated was collected on a filter. .The crude mixture was'
then dissolved in warm acetone and water was added dropwise
until the solution became turbid. _After settling for a few
minutes a brown oil separated. The top layer was decanted and
allowed to set overnight. .White needle-like crystals were
obtained (m.p. 1h5°-1h7°c.).

..Anal.
Ca1c!d.: C15H11NOS: C, 71.15; H, n.55; N, 5.55; 5, 12.65.

.Fbund : c, 71.17; H, h.u8; N, 5.h6; 3, 12.67.

(#5 '

1.

SUMMARY

2-Thianapthy1 isocyanate was prepared and characterized.
This compound was previously unreported.

Ethyl N-2-thianapthyl carbamate was prepared and charac-
terized by n.m.r. spectroscopy.

2-Acety1 thianapthene was prepared by a new procedure.
syn-Methyl 2-thianapthyl ketoxime was prepared and
characterized.

anti-Methyl:2-thianapthyl ketoxime was prepared and
characterized.

The unreported N—acetyl 2-thianapthylamine was prepared
and characterized.

The unreported phenyl 2-thianapthyl ketone was prepared
and characterized.

The unreported phenyl 2-thianapthyl ketoxime was prepared.

 

l.

10.

ll.

12.
15.
1h.
l5.

16.

17.
18.
19.

20.

REFERENCES
H. D. Hartaugh, "Condensed 'Ihiophenes", Interscience,
New York (195%). l7
Chem._Abstracts _3_, l+92 (1909).
Konig and Hamprect, Ber. ,-%3 1596 (1930).

H. D. Hartaugh, "‘Ihiophene anLDerivatives", Interscience,
New York, 252 (1952).

 

weissgruber and Kruber, Ber., B53 1551 (1920).
Meyer et al,.Ann. , l+88,-259 (1931). .

H. D. Hartaugh, "Thiophene and Derivatives", Interscience,
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H. D. Hartaugh, "‘Ihiophene and Derivatives", Interscience,
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.A. Buzas and J. Teste, Index Chemicus, 1690

E. Campaigne, J. Am. Chem..Soc., 16, 2&45-50 (195A).

Kompa, J. Prakt. Chem., 122, 519 (1920); Chem. Abstracts,
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.Shirley and Cameron, J. Am. Chem. Soc., lg, 2788 (1950).

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L. . M. Jackman, "Nuclear Magnetic Resonance Spectroscopy",

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.Shirley and Cameron, J. .Am. Chem.. Soc. , 1’1, 6611—65 (1952).

H. c. Brown, J. Am. Chem..Soc., 82, 2952 (1961).

Vogel, "A Textbook of Practical Organic Chemistry",

.Spotteswoode,T'Ballantynecanwflo. ,p. 969 (1961).

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1+7

 

CHEWSTTTY UERAR’Y