July so, 1957 OF NITROCIIALCONES

AMINODERIVATI\'ISS 381!1

Using the above procedure, 35 g. of p-nitrohydrocinnamic lb./in.2 of hydrogen in the presence of 0.5 g. of W-2 Raney
acid produced 31.1 g. (69% yield) of 3-(p-nitrophenyl)-pro- nickel catalyst for 3 hr. a t room temperature. The oily
uioohenone.
- - m.D. 94-96'. product isolated from the reaction mixture was converted to
Anal. Calcd: for C16H1&O3: C, 70.58; H, 5.13. Found: its hydrochloride salt upon passing dry hydrogen chloride
C, 70.73; H, 5.24. gas into a dry ether solution of it; wt. 1.15 g. (40% yield),
Z-Brom0-3-(p-nitrophenyl)- ropiophenone (XU).-A 25.5- m.p. 220-225', recrystallized from abs. ethanol.
g. sample of 3-(p-nitrophenylT-propiophenone was dissolved Anal. Calcd. for ClsH18hTCl: C1, 14.67. F m n d : CI,
in 100 ml. of glacial acid and warmed to 50'. To this solu- 14.43.
tion was added 16 g. of bromine in 50 ml. of glacial acetic 2-Phenylquinoline.--A 2.0-9. sample of 2-nitrochalconc
acid. The temperature of the reaction mixture was main-
tained a t 50' for 1 hr., cooled and poured into 500 ml. of cold was dissolved in 60 ml. of ethyl acetate, and hydrogenated
water. The oily solid residue was crystallized from ethanol; in the presence of W-2 Raney nickel as outlined above t o
wt. 32.23 g. (96y0 yield), m.p. 100-101'. produce 1.3 g. (8270 yield) of 2-phenylquinoline, m.p. 81-
82". This product was identical with samples prepared b)
Anal. Calcd. for C16H12N03Br: C, 53.91; H, 3.62; (a) refluxing o-nitrochalcone for 16 hr. with 48y0 Vlydroiodir
Br,23.92. Found: C, 54.08; H, 3.62; Br,24.32. acid (31 70yield) or (b) by refluxing 3-(o-nitrophenyl)-pro-
2-Phenyl-l,2,3,4-tetrahydroquinoline Hydrochloride piophenone with the same reagent for 20 hr. (30'z yield).lO
(XIII).-A 3.O-g. sample of 3-(o-nitrophenyl)-propiophenone
was dissolved in 50 ml. of ethyl acetate and shaken with 45 LISCOLN,XEBRASKA

[CONTRIBUTION FROM -4VERY LABORATORY,

UNIVERSITP OF NEBRASKA]

Amino Derivatives of Nitrochalcones. I. Synthesis, Structure Studies and Absorption

Spectra
H. CROMWELL
BY NORMAN D. MERCER'
AND GERALD
RECEIVEDMARCH16, 1957

2,3-Dibromo-3-(o-nitrophenyl)-propiophenone and the corresponding a-bromo-2-nitrochalcone react with morpholine,

-propiophenones, while secondary amines
piperidine or dimethylamine t o produce the expected 2,3-diamino-3-(o-nitrophenyl)
with greater steric requirements, such as diethylamine and N-methylcyclohexylamine, react to produce p-amino-2-nitro-
chalcones. The corresponding bromine derivatives of 3-nitro and 4-nitrochalcone react with both classes of secondary
amines in the normal manner to produce 2,3-diamino-3-nitrophenylpropiophenones and/or a-aminonitrochalcones. The
structures of the amino chalcones were established by acid hydrolysis studies. A discussion of the ultraviolet and infrared
absorption spectra of these and related compounds is given.

The reactions of secondary amines with a,@- ucts were obtained in nearly the same yields from
dibromoketones and a-bromo-a,@-unsaturated ke- a-bromo-2-nitrochalcone.
tones have been the subject of numerous investiga- The unsaturated amino ketones IV and V were
tions reported from this Laboratory2 and from difficult to hydrolyze, but long heating with dilute
others. sulfuric acid produced the known o-nitrodibenzoyl-
The reaction of 2,3-dibromo-3-(o-nitrophenyl)- methane which readily gave a copper chelate.
pr~piophenone~ with morpholine, piperidine and This 1,3-diketone reacted with phenylhydrazine t o
dimethylamine produced the corresponding a,@- give the known 1,3-diphenyl-5-(o-nitrophenyl)-
diamino ketones I, I1 and 111. Only one of the p y r a ~ o l e . ~ , ~
two possible racemates was isolated in each case in I n contrast with the o-nitro compound, both 2,3-
a t least 75% yield, and it was not possible to isolate dibromo-3-(m-nitrophenyl)-propiophenone and
either a-amino- or @-amino-a,@-unsaturatedke- 2,3-dibromo-3-(p-nitrophenyl)-propiophenone re-
tones from the highly colored reaction mixtures. acted with diethylamine to produce the correspond-
These same products I, I1 and I11 also were ob- ing a-diethylamino-3-nitrochalcone (XI) and a-
tained in slightly lower yields from a-bromo-2- diethylamino - 4 - nitrochalcone (X), respectively.
nitro~halcone.~ The structures of these products X and X I were
When 2,3-dibromo-3-(o-nitrophenyl)-propiophe- established by analysis, absorption spectra studies
none was allowed t o react with secondary amines and their acid hydrolysis to the corresponding 1,2-
having higher steric requirements, yellow colored diketones. Compound X was hydrolyzed to p -
products were produced which analysis, absorp- nitrobenzylphenyl diketone (XII) which produced
tion spectra studies and acid hydrolysis showed 2- (p-nitrobenzyl)-3-phenylquinoxaline (XI 11) on
were P-amino-o-nitrochalcones. Thus P-diethyl- heating with o-phenylenediamine. The a-amino-a,
amino- (IV) and @-(N-methylcyclohexylamino)-2- @-unsaturated ketone X I produced the correspond-
nitrochalcone (V) were produced in good yields ing 1,2-diketone which was converted to the known
using the corresponding amines. These same prod- 2- (m-nitrobenzyl)-3-phenylquinoxalineon warming
(1) Standard Oil Co. (of Indiana) Fellow, 1955-1956.
with o-phenylenediamine,
(2) See N.H. Cromwell, Chrm. Revs., S8, 83 (19461,and ref. cited 2,3-Dibromo-3-(p-nitrophenyl) -propiop henone
therein. reacted with morpholine to give a mixture of 2,3-
(3) (a) R . Lutz, e2 al., J. Org. Ckcm., 14,982 (1949); (b) 16, 1442
(1951).
di- (N-morpholino) - 3 - ( p - nitrophenyl) - propiophe-
(4) R. Sorge, B e . , S6, 1065 (1902); W. Dilthey, L. Neuhaus and W. none (VI) and a-(N-morpholino)-4-nitrochalcone
Schommer. J . prakl. Chem., 133, 235 (1930); I. Tanasescu and A. (VIII), which were separated readily by fractional
Georgescu, ibid., 199, 189 (1934). recrystallization. Piperidine behaved in a similar
( 5 ) N. H. Cromwell and G . D. Mercer, THISJ O U R N A L , 79, 3815
(1957). (6) N. H. Cromwell and R . A. Setterquist. ibid.,76, 5752 (1954).
3820 H. CROMWBLL
NORMAN AND GERALD
D. MERCER Vol . 79

Ar-cH-cH-coC&
I
Br Br
1 - >NH
Ar-cH=C-coC~H~
I
B~ A
amine, morpholine and piperidine in the nor-
mal2manner t o produce the expected results,
via the intermediate quaternary ethylenim-
monium ion, since a-amino-a,@-unsaturated
ketones are included in the products.
The presence of an electron-attracting nitro
rr-C:;<CH-COC& group on the 3-aryl group in the 2,3-dibromo-
3-(nitropheny1)-propiophenones would be ex-
C pected t o activate the hydrogen atom in the
3-position and thus facilitate the loss of hy-
L J . \HN/ drogen bromide from the intermediate 2-bro-
mo - 3-amino- 3-(nitropheny1)-propiophenones
Ar-CH=C-COC616 +D .4r-C=CHCOC& (B) to produce 0-aminonitrochalcones. How-
I I ever, since only the 2,3-dibromo-3-(o-nitro-
-N- -N- phenyl)-propiophenone behaved in this man-
AI N< ner, it seems possible that a steric effect as well
XI, 3 - N o z C a 1 N(CzHJ9 "1 as the electrical effect of the o-nitro group is
VIII. 4-hTO&H4 NC4HsO " 9 ('ZH5)zN involved in determining the course of these
IX, 4-NOGH4 NCbHio I' Ar' 2-pLTo2csHp; reactions to produce the @-aminoa,p-uiisatu-
X, 'I-NOaCsH, N(C2Hs)s >N, CHsNCGHIi
rated ketones (IV) and (V). It is possible
manner to produce the corresponding a,P-di- (N- (but not certain) that the intermediate formation
piperidino) ketone VI1 and the a-(N-piperidin0)- of the usual ethylenimmonium bromides2 is not in-
a,p-unsaturated ketone I X . volved in the loss of hydrogen bromide from the
With anhydrous ammonia, 2,3-dibromo-3-@- intermediate 3-diethylamino- and 3-(N-niethylcy-
nitropheny1)-propiophenone produced trans-2-(p- clohexylamino)-2-bromo-3- (o - nitrophenyl) - propio-
nitrophenyl)-3-benzoylethylenimine (XIV), pre- phenones.
viously prepared by Wieland' but assigned a piper- Steric controlsll which are expected to operate in
izine structure without further investigation. A the formation of the 3-amino-2-bromo-3-arylpro-
molecular weight determination and the measure- piophenones suggest that the main products to be
ment of absorption spectra (infrared and ultra- expected from the reactions involving ammonia
violet) clearly established the structure of this are the trans-2-aryl-3-benzoylethylenimines(Le.,
ethylenimine ketone. XIV) .
Discussion of Reactions.-It has been shown2 B and/or C h'Ha 0
that a-bromochalcone or 2,3-dibromo-3-phenyl- -+ II
propiophenone reacts with secondary amines to
produce either mixtures of a-amino-a,p-unsatu-
>NH j H
\ /
CCsH,
c-c
rated ketones and a,&diaminoketones ( i e . , mor-
pholine and piperidine) or only the a-amino-a,@-
unsaturated ketone (i.e., diethylamine). An en-
docyclic a,P-unsaturated ketone, 8-bromoperi-
naphthenone-7, was found t o react with secondary Ar x< Ar N<
amines (Le., morpholine and piperidine) to produce I, o-NOzCsHc NCsHsO VI, p-NOzC&( NC4HaO
11, o-NOzCsH, NCsHio VII, ~-NOZC&I NCsHlo
either a-amino- or p-amino-a,p-unsaturated ke- 111, o-NO2CeHc N(CH3)z
tones, depending upon the conditions employed.8
Recently i t has been reported that 3-bromo-1,- It was of interest to find that o-nitrodibenzoyl-
l-dimethyl-2-keto-l,2-dihydronaphthalenereacts methane reacted with phenylhydrazine t o produce
with morpholine to give a @-amino-a,@-unsaturated the known 1,3-diphenyl-5-(o-nitrophenyl)-pyrazole.
ket~ne.~ This result implies that o-nitrodibenzoylmethane
reacts as the enol E.
It seems probable that the first step in the reac-
tion of amines with each of the 2,3-dibromo-3- o-NO~C&COCH,COC~H~ I_ o-NOzCeH4C=CHCOCeHe
arylpropiophenones (0-nitro, m-nitro and p-nitro) 1
OH E
involves the loss of hydrogen bromide to produce
the corresponding a-bromonitrochalcone (A). The
second step in the presence of excess reagent is the
addition of the amine t o produce the reactive 2-
bromo-3-amino-3-nitrophenylpropiophenones(B) .
With primary amines6,loor ammonia the last step I
CaHS
in the sequence of reactions in all three series in-
volves a ring closure to produce the ethylenimine Bodforss12 came to a similar conclusion with re-
ketone. Both the m-nitrophenyl and p-nitro- gard to the reaction of m-nitrodibenzoylmethane
phenyl series of bromo ketones react with diethyl- and phenylhydrazine. Although the course of
the reaction suggested by Bodforss has been dis-
(7) H. Wieland, Bcr., 97, 1150 (1904). puted by Barnes and D o d ~ o n , we ' ~ are inclined t o
(8) N. H. Cromwell. D . B. C a w s and S. E. Palmer, THISJOURNAL,
73, 1226 (1951). (11) N.H. Cromwell. W. Franklin and R . P. Cahoy, ibid., 79, 922
(9) N. 11. Cromwell and R. D Campbell, J . Org. Cliem., 22, 5 2 0 (1957).
(1957) ( 1 2 ' S. Bodforss, Ber., 49, 2796 (191G).
(10) N. H. Cromwell, THIS 69, 258
JOURNAL, (1947). L1.i) K. Barnes and L. Dodson, THIS JOURNAL,
65, 1.585 (1043).
July 20, 1057 AMINODERIVATIVES
OF NITROCHALCONES 382 1

believe that Bodforss' description of these reactions strong nitrocinnamoyl band a t 313 mp. The in-
is correct. The fact that 2,3-dibromo-3-phenyl- frared carbonyl stretching frequencies of all of
m'-nitropropiophenone reacts with a mixture of these a-aminochalcones were between 1677 and
potassium hydroxide and phenylhydrazine to pro- 1682 cm.-l. This shift to higher frequencies with
duce the same pyrazole13as does m-nitrodibenzoyl-
inethane12 cannot be taken as conclusive evidence
for the structure of the pyrazole. The dibromide
may have undergone an initial reaction with potas-
sium hydroxide to produce m-nitrodibenzoylmeth-
-
respect to the carbonyl values for nitrochalcones
(1671 cm.-l or less)6,Bindicates that the resonance
H J makes little or no contribution to the
ground state and that instead the inductive and
coulombic field efTects16 of the a-amino groups in-
ane. We believe that Bodforss' assignment of crease the double bond character of the carbonyl
the 1,3-diphenyl-5-(m-nitrophenyl)-pyrazole struc- group in the a-aminochalcones.lb This shift in
ture to this derivative is correct. carbonyl frequency also may be associated with a
Discussion of Absorption Spectra.-2-Nitro- steric inhibition of conjugation between the benzoyl
c h a l c ~ n ehas
~ - ~been shown to have only one maxi- and vinyl groups caused by the presence of the
mum in the ultraviolet a t 262 mp, which is to be a-amino group.6
associated with the vinyl-benzoyl chromophore. 3-(p-Nitrophenyl)-propiophenoneshows benzoyl
The p-amino-2-nitrochalcones (IV) and (V) both absorption in the ultraviolet a t 246 m p and a
showed benzoyl absorption in the range of 243-247 slightly less intense band a t 274 mp, possibly to be
inp and a new intense maximum a t 340 mp. Both associated with the nitrophenyl grouping. The
of these p-amino-a$-unsaturated ketones have ethylenimine derivative XIV showed similar ab-
carbonyl stretching frequencies near 1635 cm. -l sorption characteristics with an increase in wave

implied by (F) -
in the infrared. As has been suggested pre-
viously, l4.l5 such results indicate that the resonance
(G) makes an important con-
tribution to both the ground and excited states of
p-amino-a,@-unsaturatedketones.
length and intensity for the benzoyl and nitro-
phenyl bands. The infrared carbonyl stretching
frequency of the ethylenimine ketone XIV was
found a t 1680 cm.-' as compared with a value of
1686 cm.-' for 3-(p-nitrophenyl)-propiophenone.
I I These ultraviolet and infrared studies imply that
-C=C-C-- +j -c-c=c- hyperconjugation of the three-ring with the car-
I I/ /I I bonyl and p-nitrophenyl groups makes a small con-
N O N O tribution to both the ground and excited states of
/ \ /@\ e XIV, and that it has a trans configurationP
F G
The infrared spectrum for the copper chelate XV
The a-amino-a#-unsaturated ketones (VIII) of o-nitrodibenzoylmethane showed the charac-
and (IX) also showed vinyl-benzoyl absorption at teristics to be expected of such materials."
255 mp and moderately strong bands near the Acknowledgment.-This work was supported in
visible-ultraviolet boundary of the spectrum, part by a grant from the National Science Founda-
390-425 mp. These longer wave length bands
may be ascribed14 to chromophores involving the
whole molecule, and resonance implied by H
J is suggested as making a considerable contribu-
tion to the excited state.
- tion, N.S.F. G-1091.
Experimental
2,J-Di-sec-amino-J-(o-nitropheny1)-propiophenones.-The
2,3-di-N-morpholino- (I), the 2,3-di-N-piperidine (11) and
the 2,3-bis-dimethylamino-3-(o-nitrophenyl)-propiophenone
(111)were prepared by stirring a suspension of 10 g (0.0242
mole) of 2,3-dibromo-3-( o-nitropheny1)-propiophenone' in 50
N O ml. of abs. ethanol with 0.097 mole of the correZ3ponding
/ \ amine for 15 minutes with ice-bath cooling. These reaction
H mixtures were allowed to stand in the refrigerator for 24 hr.
The yellow-orange colored solids were removed by filtra-
00 H tion and the filtrates concentrated t o yield several more
\E=(-7>=c-c-c+)
I crops. These crude materials were combined in each run,
washed with water and recrystallized from benzene-alcohol
/ = - /I I mixtures using charcoal to decolorize the solutions; see
90 N+O Table I for yields, anal. and m.p. Attempts t o ieolate a-
/@\ amino or ,%amino a,@-unsaturated ketones from these three
J reaction mixtures were unsuccessful. These products, I , I1
and 111, also were obtained in slightly lower yields from a-
I t is important to observe that the presence of the brom0-2-nitrochalcone.~
nitro group in the p-position, which would be ex- Several attempts to prepare 2-bromo-3-morpholino-3-(o-
pected to support a negative charge through inter- nitropheny1)-propiophenone by mixing a-bromo-2-nitro-
action with the benzene ring, greatly enhances light chalcone with one molar equiv. of morpholine in dry ether
produced only small amounts of the diatnino ketone I.
absorption in this part of the spectrum. Although Treatment of 2-nitrochalcone with N-bromomorpholine us-
a-diethylamino-3-nitrochalcone(XI) also has an ing Southwick's18procedure failed t o give the a-halo-+amino
ultraviolet absorption band a t 400 m p , the inten- ketone in this case, and only small amounts of I could be
sity is much lower than for the a-amino-4-nitro- isolated.
&Diethylamino- (IV) and ~-(N-Methylcyclohexylamino)-2-
chalcones. Resonance interaction of the m-nitro nitrochalcone (V).-The dibromoketone (0.05 mole) was
group with the benzene ring is, of course, not
expected. Ketone XI also shows a moderately (16) R. D. Campbell and N.H. Cromwell, i b i d . , '79, 3456 (1957).
(17) L. J. Bellamy, "The Infrared Spectra of Complex Molecules,"
(14) PI'. H. Cromwell and W. R . Watson. J . Org. Chem., 14, 411 John Wiley and Sons, Inc., New York, N. Y., 1954, p. 126
(1949). (18) P . L. Southwick and W. L . Walsh, THIS JOURNAL,77, 405
(15) N. H. Cromwell, el ol., Tars JOURNAL,71, 3337 (1949). (1955).
 SORMAX AND GERALD
13. CROMWELL D. MERCER Vol. 79

TABLEI
PHYSICAL DATA
AND ANALYTICAL

Amino ketones SO.

Yield,
%
M.P.,
0 C. Farmula
---Calcd
C H
---- Analyses, To
S
---Found
C H
___-
x
3-(o-Nitropheny1)-propiophetione
2,3-Di-(N-morpholinoj- I 78 182-183 CzaH27X306 64.92 6.40 9 88 65.27 6 51 10 19
2,3-Di-( X-piperidin0)- I1 77 159-160 CzbHsiNaOj 71.23 7 . 4 1 9.97 71.31 7 40 9 89
2,3-Bis-(dimethylamino)- "-
I11 ICl 144-145 CisHzaN303 66.84 6.79 12.31 66.69 6.50 12 5S
2-Xtrochalcone
@-Diethylamino- It' 76 112-113 CisHiaSaOt 70.35 6.82 8 6-1 70.59 6.30 8.56
fl-( N-Methylcyclohexylamino I- \- 63 145-146 C22H21N203 72.50 6.64 7.69 72.86 6.92 7.55
3-(P-Sitrophenyl)-propiophenone
2,3-Di-(S-morpho1ino)- VI 43 183 C~sHnNa03 64.92 6.40 9.88 65.31 6.23 9.76
2,3-Di-(h'-piperidin0)- VI1 26 165-166 CzSH3tSa03 71.23 7.41 9.97 71.39 7.37 9.95
4-Sitrochalcone
CY-( K-Morpho1ino)- 1'111 30 159-160 CtgHiaN204 67.44 5.36 8.28 67.63 5.49 8.64
CY-( S-Piperidin0)- 1); 52 106-107 C21H21iX203 71.41 5.99 8.33 71.62 6.29 8.51
0-Diethylamino- s 99 102-103 CieHioNiOs 70.35 6 22 8 . 6 1 20.37 6 . 2 0 8.49
3-Sitrochalcone
a-Diethylamino- sI 90 92-93 CigHsaN20r 70.35 6 . 2 2 8.64 70.62 6.26 8.54
TABLE I1 solutions by evaporation followed by the addition of pe-
troleum ether, b.p. 30-60°, caused the crystallization of the
SUMMARY
OF ULTRAVIOLET SPECTRA
ASD INFRARED
crude products which were recrystallized from 95% etha-
Infrared bandsb nol; see Table I for m.p.'s, yields and analyses. These
Ultraviolet max.a Rel.
A, € x Wave yo yellow colored products were obtained in slightly lower yields
Compound S o . mp 10-8 Band no. abs. using a-bromo-2-nitrochalcone in place of the dibromoke-
2-Sitrochalcone IV 247 16.4 C=O 1635 83 tone.
8-Diethylamino- 340 23 6 C=C 1018 57 .--
2,3-Di-sec-amino-3-(p-nitrophenyl)-propiophenones
Ar 1600 30 The 2,3-di-N-morpholino- (VI) and the 2,3-di-N-piperidino-
5-(X-Methylcyclo- v 243 16 4 C=O 1636 88 3-(p-nitrophenyl)-propiophenone (VII) were prepared
hexy1amino)- 340 24 H C=C 1620 69 by stirring a t room temperature for 3 hr., suspensions of
Ar 1600 60 12.39 g. (0.030 mole) of 2,3-dibromo-3-(p-nitrophenyl)-pro-
4 -9itrochalcone 316 28.8'
piophenone in 250 ml. of abs. ethanol with 0.120 mole of the
C=O 1650 28''
(Irons) C=C 1605 25
co~respondingamine. T h e working up of these reaction
Ar 1593 ?i
mixtures in the usual manner produced both the diamino ke-
a-IN-hlorpholinol- 1'111 255 19.5 C=O 1682 13
tones VI and VI1 and the corresponding a-amino-a,p-un-
saturated ketones, a-morpholino-p-nitrochalcone (VIII) and
390 lL5 ArC=C 1593 2fi
a-IS-Piperidinu]. I X 25.5 19.5 C=O 1677
a-piperidino-p-nitrochalcone (IX); these products were re-
413 13.8 ArC=C
crystallized from 9570 ethanol, see Table I for yields, m.p.'s
1587 08
a-Diethylamino IC 258
and analytical data.
19.5 C=O 1677 33
425 15.7 ArC=C 1597 37
~t-Diethylamino-4-nitrochaIcone (X) and a-Diethylamino-
34trochalcone (XI).-These orange-red products were ob-
3-Nitrochalcone XI 256 22.3 C=O 1677 31 tained by mixing 2,3-dibromo-3-( p-nitropheny1)-propio-
a-Diethylamino- 313 17.2 ArCsC 1595 45 phenone and the m-nitrophenyl analog with three molar
400 2. 5 equivalents of diethylamine in abs. ethanol a t ice-bath tem-
2-(P-Nitrophenyl) - XI\' 255 20.5 N-H 3300 Ii"
perature. The reaction mixtures were allowed t o stand for
3-Benzoylethylen- 274 19.4 C=O 1680 26
two days a t room temperature and the products isolated in
imine ( ! r a m )
the usual manner and recrystallized from 95% ethanol; see
dr 1cI12 21
Table I for data.
3-(P-Nitrophenyl I - 216 12.3 C-0 16815 75 Hydrolysis of @-Amino and a-Amino-a,@-unsaturated Ke-
propiophenone 271 10.7 Ar 1597 36 tones.-(a) ~-Diethylamino-2-nitrochalcone(IV) (1.O g.)
was refluxed for 16 hr. in 20 ml. of 15yosulfuric acid. The
Bis- [ 1-(o-nitrophenyl). x1' Ar 1600 454
acid solution was extracted with ether and made basic with
3-phenyl-l,3-pro. C--U 1560 BO
panedionelcopper c=c I530 ti5
sodium hydroxide t o recover 0.49 g. of IV. Evaporation of
the ether extract and recrystallization from 957, ethanol
The ultraviolet spectra were determined with a Cary produced 0.092 g. (22% yield) of o-nitrodiben~oylmethane,'~
model 11 spectrophotometer in the range of 220-450 m p 111.p. 115-116 , This product gave n deep-red color with
in 95% ethanol using molar solutions. * The infrared alcoholic ferric chloride.
spectra were determined over the range of 4000-600 cm.-l A 0.05-g. sample of o-nitrodibenzoyltnethane was dis-
at 2.5' using 0.10-mm. matched cells with a Perkin-Elmer solved in 10 ml. of 50y0 acetone-water and treated with a
model 21 instrument and 12-20 mg./ml. CC14 solutions, uti- saturated solution of cupric acetate in 50% acetone-water.
less otherwise indicated. See K. Black and R. Lutz, The bis- [l-(o-nitrophenyl)-3-phenyl-l,3-propanedione]-cop-
THISJOURNAL, 77, 5134 (1955). Determined ab a Nujol per was filtered from the solution and recrystallized from di-
mull. e Determined with a satd. s o h . in CCL. oxane and benzene; m.p. 287-288', wt. 0.045 g. (80%
suspended in 100-ml. amounts of abs. ethanol and treated yield).
with 0.21 mole of diethylamine and 0.15 mole of N-methylcy- A n d . Calcd. for CuH2~N2O4C~i: Cu, 10.58. Found:
clohexylamine, respectively. These reaction mixtures were Cu, 10.69.
allowed t o stand in the dark a t room temperature for two A 0.025-g. sample of o-nitrodibenzoylmethane was dis-
days. The solvent was removed under reduced pressure and solved in 5 ml. of 1: 1 alcohol-chloroform and one molar
the oil-solid residues mixed with 400 ml. of ether. The equivalent of phenylhydrazine and a drop of gl. acetic acid
ether solutions were filtered t o remove the by-product added. The mixture was warmed and allowed to stand at
amine hydrobromides, washed with water and dried over
a n h l i i tnngticiiuni iulf i t e . Coticentrxtion of thew ether (10) S Gahriel a n d U'. G e r h a r d , B P ?, , 64B, 1613 : I O 2 1 !
July 20, 1957 ~eSO-I)IHYDROGUAIARETIC ACID AND ITS DERIVATIVES 3823

room temperature for a day. The yellow crystalline prod- (c) ~-Diethylamino-3-nitrochalcone (XI)(1.0 9.) was re-
uct was recrysotallized from 95% ethanol, 0.02 g. (63% yield), fluxed with 20 ml. of 15% sulfuric acid for 3 hr., cooled and
m.p. 178-180 . This product was identical with an authen- extracted with ether. Evaporation of the ether gave an oil
tic sample of 1,3-diphenyl-5-(o-nitropheny1)-pyrazole.e which was dissolved in 5 ml. of abs. ethanol and warmed with
( b ) p-( N-Methylcyclohexylamino)-2-nitrochalcone ( V ) 0.329 g. of o-phenylenediamine. Cooling produced 2-(m-
was hydrolyzed in a similar manner, as in (a), to produce a nitrobenzy1)-3-phenylquino~aline,1~ recrystallized from 95y0
47y0 yield of o-nitrodibenzoylmethane. Almost half of the ethanol, m.p. 120-121.5’, wt. 0.83 g. (78% yield).
starting material was recovered after 12 hr. of reflux with 2-(p-Nitrophenyl)-3-benzoylethylenimine(X1V:r .-A 4.13-
15% sulfuric acid. g. (0.010 mole) sample of 2,3-dibromo-3-(p-nitrophenyl)-
(c) a-Diethylamino-4-nitrochalcone (X) (1.0 g.) was re- propiophenone was suspended in 50 ml. of abs. ethanol and
fluxed for 6 hr. with 20 ml. of 15% sulfuric acid and the re- the mixture saturated with anhydrous ammonia and allowed
action mixture cooled and extracted with ether. Evapora- to stand in the dark a t room temperature for one week. The
tion of the ether extract produced an oily solid which was re- dibromide dissolved in about three days. The solvent was
crystallized from 95% ethanol after decolorizing with char- removed under reduced pressure and the residue mixed with
coal; m.p. 119-120”, wt. 0.70 g. (84.5y0 yield), p-nitro- water and extracted with ether. Evaporation of the ether
benzylphenyl diketone (XII). and recrystallization of the oily residue from 95% :than01
Anal. Calcd. for C1,Hl1NOd: C, 66.91; H, 4.12. produced 2.23 g. (78% yield) of XIV, m.p. 142-143 This .
Found: C, 67.09; H , 4.34. product appears to be identical with that reported by Wie-
A 0.027-g. (0.001 mole) sample of XI1 was heated fora few land’ as either the ethylenimine ketone or a dimer having a
minutes with 0.108 g. (0.001 mole) of a-phenylendiamine in piperazine structure, which he preferred. A mol. wt. de-
5 ml. of abs. ethanol. Cooling the mixture produced 2- termination by the cryoscopic method showed the structure
(p-nitrobenzyl)-3-phenylquinoxaline(XIII); recrystallized of this product actually t o be XIV.
from 95% ethanol, m.p. 124-125’, wt. 0.292 g. (86% yield). N o other identifiable products could be isolated from this
reaction mixture.
Anal. Calcd. for CZIHISN302: C, 73.89; H, 4.43; N ,
12.31. Found: C, 74.09; H,4.29; h-,12.78. SEBRASKA
LINCOLN,

[CONTRIBUTION FROM THE LABORATORY

OF CHEMICAL PHARMACOLOGY, NATIONAL CANCER INSTITUTE’]

meso-Dihydroguaiaretic Acid and its Derivatives2

W. SCHRECKER
BY ANTHONY
FEBRUARY
RECEIVED 28, 1957

The contaminant of crude guaiaretic acid (I, R = H ) has been identified as nzeso-dihydroguaiaretic acid (11, R = H).
I1 (R = Me) and its DL-isomer have been synthesized by a stereospecific method. The infrared spectra of diastereoisomers
in this series are discussed.

Guaiaretic acid (I, R = H), a key compound in configuration (11, R = Me) to the inactive ether,
the elucidation of the absolute configuration of m.p. 1OO-10lo, because of its mode of formation
lignans,a occurs in Guaiacum oficinale L.* together and because its diamino derivative could not be
with a number of related c o m p o ~ n d s . ~Its isola- resolved.6 Haworth,’ however, prepared the same
tion has, however, been complicated by the presence compound, m.p. 101-102°, by reduction of syn-
of a contaminant, which lowers the optical rotation thetic (DL)-I (R = Me) and named it “dl-dihydro-
of the crude product and from which it is not guaiaretic acid dimethyl ether.’’ He and Cart-
readily separated. Schroeter, who was the first Wright* later isolated I (R = Ac) and one of its di-
to obtain pure I (R = H) (m.p. 99-100.5’, [ a ] D hydro derivatives from Guaiac resin after acetyla-
-94“ in ethanol),6 informed Haworth7 that his tion, but reported no optical rotation^.^
crude material was contaminated with an optically Although it is generally assumed4that Schroeter’s
active (IIIa, R = H) and an inactive dihydro de- inactive dimethyl ether does possess the meso
rivative of I (R = H), both of which occurred rather than the DL-configuration, confirmatory
naturally in Guaiac resin; however, he never pub- proof was desired. This was accomplished by a
lished these findings. He had previously prepared stereospecific synthesis of both I1 and I I I b (R =
the dimethyl ethers of these dihydro compounds Ar CHzAr CH&
by reduction of I (R = Me) and assigned the meso I I I

(1) National Institutes of Health, Public Health Service, U. S.

H-C-CH~ CH~-C-H
Department of Health, Education and Welfare. H-kC-CH, I
H-C-CHI I
H-C-CHI
(2) Presented in part at the XIVth International Congress of Pure I
and Applied Chemistry in Zurich, Switzerland, July 22, 1955; cf.
H-C-CHs I I
Congress Handbook, p. 45. I CHzAr CH2Ar
(3) A. W. Schrecker and J. L. Hartwell, J . Or#. Ckcm., 31, 381 1 CHzAr 11 (meso)
. . IIIa. active
(1956); THISJOURNAL, 79, 3827 (1957).
(4) For leading references, see (a) H . Erdtman in Paech and Tracey, /OMe IIIb, DL
“Modern Methods of Plant Analysis,” Vol. 111. Springer-Verlag, Ar = ---OR_.
Berlin, 1955, p. 428; (b) W. M.Hearon and W. S. MacGrenor. - , Ckcm.
Reus., 66, 957 (1955).
( 5 ) F. E. King and J. G Wilson, Congress Handbook, XVIth In-
Me). I n addition, the contaminant that lowers the
ternational Congress of Pure and Applied Chemistry, paris,1957; J , rotation of crude I (R = H) was identified aS its
C h e w . Soc., to be published. ( 8 ) N. J. Cartwright and R. D.Haworth, ibid., 948 (1947).
(6) G. Schroeter, L. Lichtenstadt and D. Ireneu, Ber., 61, 1587 (9) Inactive dihydroguaiaretic acid dimethyl ether, m.p. 102-103°,
‘1918) was also obtained by methylation of nordihydroguaiaretic acid, isolated
( 7 ) I7 1) Haworth. C. K. Mavin and G. Sheldrick. J . Chcin. So:.. from Lovrea dioovirafa: c.f. C. W. Waller and 0 . Gisvold J .A i n . Pharnt
1423 (1934). ~ S S O C . Sci.
, E d . , 34, 78 (1815)