3874 J . Org. Chem., Vol. 40, No.

26, 1975 Cajipe, Landen, Semler, and Moore

Reaction of Aminoquinones and Related Vinylogous Amides with

Nitrous Acid. Synthesis and Chemistry of Cyclic Diazo Ketones

Gloria J. B. Cajipe, George Landen, Burt Semler, and Harold W. Moore*

Department of Chemistry, Uniuersity of California, Iruine, California 92664.
Receiued June 27. 1975

2-Amino-3-alkyl- (or aryl-) 1,4-quinones are shown to react with nitrous acid (sodium nitrite in glacial acetic
acid) to give 5-diazo-6-alkyl- (or aryl-) 6-hydroxycyclohex-2-ene-1,4-diones 2. Analogous reactions are observed
for the related vinylogous amides, 4-amino-2,5-di-tert-butyl-2-cyano-4-cyclopentene-l,3~dione (7) and 2,5H-3-
amino-4-methyl-6,7-benzoazepine-2,5-dione (9). The chemistry of the cyclic diazo compounds is discussed, and of
particular interest are the thermal rearrangements of 2a, 2b, and 4 to the corresponding ring-contracted 4-cyclo-
pentene-l,d-diones, 24, 25, and 27, respectively. Also discussed is the thermal rearrangement of 4-acetyl-3-diazo-
4-hydroxycarbostyril (12) to 3-acetyl-4-hydroxycarbostyril(261, the reductive cyclization of 12 to 3H,5H-l-meth-
ylpyrazolo[3,4-~]quinolin(4H)-one (19),and the acid-catalyzed conversion of 12 to 4H,GH(lH,5H)-diox0-3,4-diaz-
ino[3,4-c]quinoline(30).

A vast methodology exists in the iiterature for the syn- 0 0

thesis of aminoquinones. In fact, during the past 35 years
alone well over 150 substituted primary amino-1,4-qui-
nones have been reported. However, there is a paucity of
information regarding the chemistry of these compounds.
Our interest in the utility of quinones in organic synthesis'
along with the plethora of such readily available starting 1 2
materials2 and the rich chemistry of the amino group3 has R, R, Rj Yield %
stimulated a n investigation of aminoquinones as potential- a CH, -CH=CHCH=CH- 91
ly useful reagents. Reported here is a study of the reactions b CH, H CH, 81
of selected 2-amino-1,4-quinones and certain related cyclic
vinylogous amides with nitrous acid, a reaction resulting in c CH, h', CH, 92
the formation of cyclic a-diazo ketones. Also described is d CJ, H C,,H., 36
t h e pyrolytic ring contraction of such compounds. Of par- 0 0
ticular interest is the thermal rearrangement of the diazo
ketones 2 t o 2-acyl-4-cyclopentene-1,3-diones, a ring sys-
tem found in a number of natural product^.^
Synthetic Scope. Treatment of the aminoquinones l a 4
with sodium nitrite in glacial acetic acid results in a rapid, 0
exothermic reaction and gives fair to excellent yields of the 3
corresponding diazo ketones 2a-d. 2-Amino-3,6-di-tert-
butyl-1,4-benzoquinone (3), having a bulky substituent ad-
jacent t o the amino group, behaves anomalously in that the
acetoxy derivative 4 was obtained in 92% yield. T h e de-
tailed scope of this reaction of aminoquinones has not been
studied in detail. However, we have observed that 2-amino-
1,4-quinoneswhich are unsubstituted a t the 3 position give 0 0
complex reaction mixtures and that 2-amino-6-anilino-3- 5 6
carbomethoxy-1,4-benzoquinone,a compound having a
very nonnucleophilic amino group, fails to react. In addi- R Yield%
tion, Mosby and Silvas found that 2-amino-3-chloro-1,4- a CI 8"
naphthoquinone (5a) gave the diazo oxide 6 when treated b OCH, 85
with sodium nitrite in sulfuric acid. We have observed the N J 65
same product when 2-amino-3-chloro- (Sa), 2-amino-3- d SC,H, 61
methoxy- (5b), 2-amino-3-azido- (5c), and 2-amino-3-thio-
phenyl-1,4-naphthoquinone (5d) are diazotized as de- spectively, and the minor product was the quinoline 12.
scribed here. T h e major product is assumed t o be the azepine 10 which
T o further probe the utility of these diazotization reac- rearranges to 12 via the ring-opened intermediate 11. Such
tions, the scope was widened to include some nonquinoid a transformation was easily induced when the above di-
cyclic 2-aminoenediones. Treatment of 4-amino-2,5-di- chloromethane solution was treated with 3% methanolic
tert -butyl-2-cyano-4-cyclopentene-1,3-dione (7) with sodi- potassium hydroxide. This resulted in the disappearance of
um nitrite in glacial acetic acid gave a 62% yield of the ace- the 6 1.52 absorption and the 6 2.20 peak increased in in-
toxydiazo derivative 8. A more interesting transformation tensity. It was possible to interrupt the diazotization of 9 a t
was observed when 3-amino-2,5H-4-methyl-6,7-benzoaze- the azepine stage when the reaction was carried out in 1:l
pine-2,S-dione (9) was subjected to the above reaction con- acetic acid-methanol. Here, the methoxy adduct 13 was
ditions. Here, rather than the seven-membered cyclic diazo isolated in 90% yield. (See bcheme I).
compound 10, the ring-contracted quinoline 12 was isolat- Mechanism. T h e products observed from the diazotiza-
ed. However, a dichloromethane extract of the reaction tion reactions described here are consistent with a mecha-
mixture showed ( ' H NMR) two products in a ratio of 3:2 as nism (Scheme 11) in which the vinylogous amide is initially
evidenced by methyl absorptions a t d 1.52 and 6 2.20, re- converted to a diazonium salt 15 which then suffers nucleo-
Reaction of Aminoquinones with Nitrous Acid J . Org. Chem., Vol. 40, No. 26,1975 3875

Scheme I thoquinone (la) and 2-amino-3,6-di-tert- butyl-l,4-benzo-

0 quinone (3), respectively, when subjected to hydrogenation
II conditions. This reductive cleavage of the diazo nitrogen-
CHk. nitrogen bond appears t o be rare but not unprecedented;
Birkofer7 reported that a-diazoacetophenone gives a-ami-
noacetophenone when subjected t o hydrogenation under
slightly acidic condition in the presence of Pd/C. Hydroge-
nation of the diazoquinoline derivative 12 also resulted in
the reduction of the diazo nitrogen linkage. In this case, 19
was obtained in >90% yield and is envisaged as arising
7 0
from an intermediate hydrazine derivative which suffers
8
intramolecular condensation.
0 0

10

1-" 2a la
0 0

H
12
4 3
11

13

Wenkert and McPherson6 have shown that acyclic a-

Scheme I1 diazo-b-hydroxy ketones and esters thermally rearrange
with carbon or hydrogen migration as illustrated below. In

CCO,C,H, - CO,C,H,
14 15
20 21
0 0 0

II
N:, 23

22
philic attack by solvent (CHsC02H) t o give the acetoxy de- analogy to these rearrangements it was found that 2a and
rivative 16. For those compounds having a relatively small 2b thermally rearranged in refluxing chlorobenzene with
substituent adjacent t o the diazo linkage (2a-d, 9),hydrol- acyl migration t o give 2-acetyl-1,3-indandiones(24,97%)
ysis of the acetoxy group during the aqueous work-up a n d 2-acetyl-4-methyl-4-cyclopentene-1,3-dione
(25, 86%),
would result in the observed P-hydroxydiazo compounds. respectively. Also, 12 gave a 28% yield of 3-acetyl-4-hy-
Steric retardation of such hydrolysis by the bulky tert- droxycarbostyril (26)gand 4 gave a 90% yield of 27 when
butyl groups in 4 and 8 would account for the interception subjected to the thermolysis conditions.
of these esters. For those compounds having a potential The acid-catalyzed decomposition of two of the diazo
leaving group (It = c1, OCH3, N3, SC6H5) adjacent to the compounds described here was also studied. Decomposi-
diazo linkage, hydrolysis and subsequent elimination would tion of 2a in cold ( 5 O ) concentrated sulfuric acid gave the
give the diazo oxide 18. same product, Le., 24, that resulted from its thermolysis.
Chemistry. Wenkert and McPherson6 have shown t h a t An entirely different transformation was observed for the
catalytic hydrogenation (Pd/C) of acyclic a-diazo-@-hy- acid-catalyzed decomposition of 12. Here, a fascinating ring
droxycarbonyl compounds gives the corresponding 8-hy- closure t o 30 took place in nearly quantitative yield. This
droxycarbonyl compounds. Therefore, an analogous trans- product is viewed as arising from the diazonium salt 28
formation was anticipated for 2a and 4. However, these which electrophilically attacks the enol double bond. Such
compounds were converted to 2-amino-3-methyl-1,4-naph- a ring closure to a diazine is well documented in that one of
3876 J. Org. Chem., Vol. 40, No. 26, 1975 Cajipe, Landen, Semler, and Moore

0 0 was washed twice with 5% sodium bicarbonate and dried (MgSOd),

and the solvent was removed in vacuo (25') to give a yellow-orange
oil. Trituration of this oil with cold pentane-ether gave 0.48 g
(81%)of the yellow, crystalline diazo compound Zbernp 79-80' dec
(pentane-ether); ir (Nujol) 3450, 2100, 1675, 1640, 1610 cm-'; 'H
NMR (CDCl3) 1.62 s (31, 2.11 d (3) J = 2 Hz, 3.91 br (11, 6.60 q (1)
J=2Hz.
2a 24 Anal. Calcd for CaHsNsOs: C, 53.33; H, 4.44; N, 15.56. Found: C,
53.43; H, 4.41; N, 15.39.
0 0 3-Azido-6-diazo-5-hydroxy-2,5-dimethylcyclohex-Z-ene-
l,4-dione (2c). Treatment of 2-amino-5-azido-3,6-dimethyl-1,4-
benzoquinone (IC, 0.5 g, 2.6 mmol) with sodium nitrite (0.24 g, 3
mmol) was carried out as described above for l b to give 0.54 g
(92%) of the diazo compound 2c as a golden, crystalline solid: mp
107-109' dec (pentane-ether); ir (Nujol) 3200, 2120, 1690, 1585
cm-'; 'H NMR (CDC13) 1.68 s (3), 2.03 s (31, 3.52 br (1).
2b 25
Anal. Calcd for C8H7N503: C, 43.44; H, 3.17; N, 31.67. Found: C,
OH 43.55; H, 3.09; N, 31.57.
6-Diazo-5-hydroxy-2,5-diphenylcyclohex-2-ene- 1,a-dione
(Zd). To a solution of 1.0 g (3.6 mmol) of 2-amino-3,6-diphenyl-
1,4-benzoquinone ( I d ) in 50 ml of glacial acetic acid was added
0.48 g (7.2 mmol) of sodium nitrite. After stirring a t ambient tem-
perature for 15 min the initially purple solution turned yellow and
12 26 the solution was diluted with 200 ml of water and extracted three
times with diethyl ether. The combined organic extract was
0 0 washed twice with 5% sodium bicarbonate and dried (MgS04) and
the solvent was removed in vacuo (25'). The resulting orange oil
was chromatographed on silica gel using 1:l benzene-chloroform
as the eluent to give 0.40 g (36%) of the diazo compound Z d mp
108-109' dec; ir (Nujol) 3400, 2100, 1700, 1625, 1600 cm-'; 'H
NMR (CDC13) 6 4.65 br (l), 6.77 s (l),7.25-7.70 m (10).
4 Anal. Calcd for C18H12N203: C, 71.05; H , 3.95; N, 9.21. Found: C,
27 71.07; H, 3.93; N, 9.25.
H 5-Acetoxy-6-diazo-2,5-di( 1,l-dimethylethyl)cyclohex-Z-
,I ene-l,4-dione (4). A solution of 1.0 g (4.2 mmol) of 2-amino-3,6-
di-tert-butyl-1,4-benzoquinone(3) in 75 ml of glacial acetic acid
was treated with 0.44 g (6.3 mmol) of sodium nitrite a t ambient
temperature. After 15 min the reaction solution was diluted with
200 ml of water and extracted with three portions of dichlorometh-
ane. After drying (MgS04) the solvent was removed and the prod-
uct recrystallized from methanol to give 1.3 g (92%) of the yellow
n diazo compound 4: mp 83-84'; ir (Nujol) 2100, 1745, 1680, 1630,
12 1600 cm-'; 'H NMR (CDC13) d 1.03 s (9), 1.32 s (9), 2.14 s (3), 6.59
28
s (1).
Anal. Calcd for C16H22N204: C, 62.72; H, 7.24, N, 9.15. Found: C,
62.55; H, 7.28; N, 8.93.
2-Diazobenzocyclohexane-1,3,4-trione(6).Treatment of ace-
tic acid solutions of 2-amino-3-chloro- 2-amino-3-methoxy-
(5b),5 2-amino-3-azido- ( S C ) , ~and 2-amino-3-thiophenyl-1,4-
naphthoquinone (5d) with a twofold molar excess of sodium nitrite
29 30 gave the diazo oxide 6 in yields ranging from 61 to 85%. The prod-
uct showed spectral and physical properties that were identical
the standard synthetic routes to the cinnoline nucleus in- with those reported by Mosby and Silva.5
volves the intramolecular cyclization of an aryldiazonium 4-Diazo-5-acetoxy-Z-cyano-2,5-di( 1,l-dimethy1ethyl)cyclo-
pentene-l,j-dione (8). A solution of 1.0 g (4.4 mmol) of 4-amino-
salt which contains a reactive unsaturated ortho substitu- 2-cyano-2,5-di-tert-butyl-4-cyclopentene-1,3-dione (7) and 1.5 g of
ent.lOJ1 sodium nitrite in 70 ml of glacial acetic acid was stirred a t ambient
temfierature for 12 hr. The solution was then diluted with 200 ml
Experimental Section of water and extracted three times with dichloromethane. After
Z-Diazo-3-hydroxy-3-methylbenzocyclohexane-l,4-dione drying, the solvent was removed in vacuo (25') and the resulting
(2a). To a solution of 1.0 g (5 mmol) of 2-amino-3-methyl-1,4- yellow oil was crystallized from pentane-ether to give 0.87 g (62%)
naphthoquinone (la) in 50 ml of glacial acetic acid was added 0.5 g of the diazo compound 8: mp 99-101'; ir (Nujol) 2220, 2120, 1760,
(12 mmol) of sodium nitrite. After stirring for approximately 5 rnin 1725, 1675 cm-'; 'H NMR (CDCls) 6 1.18 s (9), 1.23 s (9), 2.15 s
a t ambient temperature the solution turned yellow and was then (3).
diluted with 200 ml of water and extracted three times with dichlo- Anal. Calcd for C16H21N304: C, 60.19; H, 6.58; N, 13.17. Found:
romethane. The combined organic extract was washed twice with C, 60.25; H, 6.60, N, 13.36.
5% sodium bicarbonate and dried (MgS04). The solvent was re- 2,5-Di( l,l-dimethylethyl)-Z-cyano-4-amino-4-cyclopen-
moved in vacuo (25') t o give 1.0 g (91%) of the yellow, crystalline tene-1,3-dione (7). A solution of 1 g (4.2 mmol) of 2,5-di-tert-
diazo compound 2a: mp 106-107' (from pentane-ether); ir (Nujol) butyl-3,6-diamino-l,4-benzoquinone and 3.72 g (8.4 mmol) of lead
3300, 2110, 1705, 1660, 1620 cm-'; 'H NMR (CDC13) 6 1.65 s (31, tetraacetate in 50 ml of chloroform was stirred a t ambient temper-
4.32 br ( l ) , 7.65-8.25 m (4). atures for 5 min and then 5 ml of ethylene glycol was added. The
Anal. Calcd for CllH8N203: C, 61.11; H, 3.70; N, 12.96. Found: reaction solution was then washed three times with water and
C, 60.99; H, 3.64; N, 12.89. dried (MgS04) and the solvent was removed in vacuo. The result-
6-Diazo-5-hydroxy-2,5-dimethylcyclohex-Z-ene- l,4-dione ing residue was recrystallized from hexane to give 0.7 g (71%) of 7:
(2b). T o a solution of 0.5 g (3.3 mmol) of 2-amino-3,6-dimethyl- mp 82-84'; ir (Nujol) 3450, 3330, 2250, 1760, 1680 cm-'; 'H NMR
1,4-benzoquinone ( l b ) in 20 ml of glacial acetic acid was added 0.3 (CDC13) 8 1.13s (9), 1.40 s (9),5.55 br (2).
g (4.3 mmol) of sodium nitrite. The initially purple solution turned Anal. Calcd for CldHzoN202: C, 67.74; H, 8.06; N, 11.29. Found:
~

yellow after approximately 5 min and was then diluted with 200 ml C, 67.84; H,8.12, N, 11.18.
of an aqueous saturated sodium chloride solution and extracted 2,583-Azid0-4-methyl-6,7-benzoazepine-2,5-dione. T o a SO-
four times with dichloromethane. The combined organic extract lution of 1.87 g (10 mmol) of 2,5H-4-methyl-6,7-benzoazepine-2,5-
Reaction of Aminoquinones with Nitrous Acid J. Org. Chem., Vol. 40, No. 26, 1975 3877

dione13 and 2.6 g (40 mmol) of sodium azide in 35 ml of dimethyl- 3H,5H-l-Methylpyrazolo[3,4-c]quinolin-(4H)-one (19). A
formamide was added 5.08 g (20 mmol) of iodine and the resulting suspension of 1.25 g (5.4 mmol) of 4-acetoxy-3-diazo-4-hydroxy-
reaction mixture was stirred a t ambient temperature. The course carbostyril (12)and approximately 10 mg of platinum oxide in 25
of the reaction was followed by ir spectroscopy and the mixture ml of 95% ethanol was treated with hydrogen a t 35 psi for 5 hr. Fil-
was worked up after all of the starting azepine had been consumed tration and removal of the solvent in vacuo gave 1.0 g (93%) of 19,
(-16 hr). Water was then added and the resulting white precipi- mp 330-340'. This product was recrystallized from 95% ethanol to
tate was collected and washed with methanol to give 1.67 g (73%) give the analytical sample: mp 356-358, sinter 345O; ir (Nujol)
of 2,5H-3-azido-4-methyl-6,7-benzoazepine-2,5-dione, mp 161' 3080, 1690, 1630 cm-'; 'H NMR (MezSO-ds) 2.68 s (3), 7.58-7.15
dec. The analytical sample was obtained by recrystallization (30') m (3), 8.10-7.80 m (l), 11.73 br (1) exchanges with DzO, 14.05 br
from dimethyl sulfoxide-methanol: ir (Nujol) 3125, 3005, 2130, (1) exchanges with DzO; mass spectrum (70 eV) m/e (re1 abun-
1650, 1585,1315 cm-l; IH NMR (MezSO-ds) 6 2.05 s (3), 7.00-7.70 dance) 200 (15.4). 199 (loo), 170 (14.6), 130 (12.8), 115 (12.2), 103
m (4), 11.32 br (1)exchanges with DzO; mass spectrum (70 eV) m/e (25.2), 76 (11.3).
(re1 abundance) 200 (40.9), 119 (loo), 117 (27.8), 92 (53.61, 64 __
Anal. Calcd for CJIHQNQO:
I ~
C., 66.33:, H., 4.52: N. 21.11. Found: C.
I ,

(39.0). 66.61; H, 4.72; N, 21.00.

Anal. Calcd for CllHsN402: C, 57.89; H, 3.51; N, 24.56. Found: 2-Acetyl-1,3-indandione (24). A solution of 0.50 g (3.5 mmol)
C, 57.86; H, 3.53; N, 24.56. of 2-diazo-3-hydroxy-3-methylbenzocyclohexane-l,4-dione (2a)in
2,5H-3-Amin(~-4-methyl-6,7-benzoazepine-2,5-dione (9). A 50 ml of dioxane was refluxed for 2 hr. Evaporation of the solvent
suspension of 2.28 g (10 mmol) of 2,5H-3-azido-4-methy1-6,7-ben- in vacuo and recrystallization of the residue from methanol gave
zoazepine-2,5-dione and 50 mg of platinum oxide in 100 ml of 95% 0.42 g (97%) of 24: mp 109-110 (lit! mp 110-112'); ir (Nujol) 1720,
ethanol was treated with hydrogen a t 50 psi for 9 hr. The catalyst 1700, 1660 cm-l; 'H NMR (CDC13) 6 2.52 s (3), 7.75 m (4), 10.92 br
and solvent were then removed to give 2.0 g (99%) of the amine 9 (1).
mp 241-243' (95% ethanol); ir (Nujol) 3380,3270,3060,1680,1595 2-Acetyl-4-methyl-4-cyclopentene-1,3-dione (25). The title
cm-'; l H NMR (MezSO-ds) 6 2.17 s (3), 6.67 br (2), 7.67-7.10 m compound was prepared as described above for 24 except benzene
(3), 8.23-7.98 m ( l ) , 11.50 br (1). was used as the solvent, Le., 0.270 g (1.54 mmol) of 2b give 0.20 g
Anal. Calcd for C11HloNzOZ: C, 65.34; H, 4.95, N, 13.86. Found: (86%) of 25: mp 53-55' (methanol); ir (Nujol) 1710, 1670, 1640
C, 65.49; H, 4.97; N, 13.89. cm-'; 'H NMR (CDC13) 6 2.05 d (3), J = 1.5 Hz, 2.35 s (31, 6.51 q
4-Acetyl-3-diazo-4-hydroxycarbostyril (12). T o a stirred so- ( l ) , J = 1.5 Hz, 11.51 br (1).
lution of 1.04 g (15 mmol) of sodium nitrite in 20 ml of water was Anal. Calcd for CsHs0.7: C, 63.16; H, 5.26. Found: C, 63.05; H,
added a suspension of 2.02 g (10 mmol) of 2,5H-3-amino-4-methyl- 5.32.
6,7-benzoazepine-2,5-dione (9) in 60 ml of acetic acid. After 15 min Acid-Catalyzed Rearrangement of 2-Diazo-3-hydroxy-3-
the reaction solution was diluted with 200 ml of water and extract- methylbenzocyclohexane-1,4-dione(2a). T o vigorously stirred,
ed with 200 mi of dichloromethane. The organic extract was cold (5') concentrated sulfuric acid was slowly added (20 min) 0.25
washed with water and saturated sodium bicarbonate and then g (1.2 mmol) of 2a. After gas evolution had ceased, the reaction
dried over anhydrous sodium sulfate. The dichloromethane extract mixture was diluted with ice water and the resulting precipitate
was analyzed by lH NMR, which showed two methyl absorptions was collected and dried to give 80 mg (38%) of 2-acetyl-1,3-indan-
in a ratio of 3:2 coming a t 6 1.52 and 2.20, respectively. The former dione which was shown to be identical with an authentic sample.8
absorption is assigned to the methyl group in the azepine 10 and 3-Acetyl-4-hydroxycarbostyril (26). A solution of 13.5 mg
the latter to the carbostyril 12. The dichloromethane solution was (0.05 mmol) of 12 in 5 ml of anhydrous benzene wa8 refluxed for 72
then treated with 20 drops of 3% methanolic potassium hydroxide. hr. Upon cooling 3.5 mg of 26, mp 254-257' (lit? mp 258-259'),
The solvent was then removed by rotoevaporation a t ambient tem- precipitated. This product was shown to be identical with an au-
perature. The resulting residue (2.3 g) was analyzed by 'H NMR thentic sample of 3-acetyl-4-hydroxycarbostyril which was kindly
(CHzC12) which showed only the 6 2.20 absorption in the methyl supplied by Calvin M. Foltz? This same compound was obtained
region of the spectrum. The crude product was recrystallized from in 74% yield when 50 mg of 2,3,4,5-tetrahydro-3-diazo-4-methyl-
benzene to give 1.02 g of pure 12: mp 171' dec; ir (Nujol) 3380, 4-methoxy-6,7-benzoazepine-2,5-dione (13) was decomposed in 5
3100, 2105, 1720, 1675, 1605 cm-'; lH NMR (CDC13) 6 2.22 s (3), ml of refluxing chlorobenzene. After 10 min a t the reflux tempera-
5.40 s ( l ) , 7.78-6.90 m (4), 9.93 br (1). ture the solution was cooled to 80-100' and a few drops of water
Anal. Calcd for CllHgN303: C, 57.14; H, 3.90; N, 18.18. Found: were added. The solvent was then removed and the residue was
C, 57.16; H, 4.02; N, 18.07. subjected to dry column chromatography over silica gel using
2,3,4,5H-3-Dirazo-4-methoxy-4-methyl-6,7-benzoazepine- methanol as the eluent to give 31 mg (74%) of 26.
2,5-dione (13). A solution of 0.57 g (2.5 mmol) of 2,5H-3-amino-4- 2-(1-Acetoxy-2,2-dimethylpropylidine)-4-(2,2-dimethyl,2-dimethyl-
methyl-6,7-benzazepine-2,5-dione (9) in 40 ml of anhydrous meth- ethyl)-4-cyclopentene-1,3-dione (27). A solut,ion of 1 g (3.75
anol and 40 ml of glacial acetic acid (35') was treated with 3.5 g of mmol) of 5-acetoxy-6-diazo-2,5-di(l,l-dimethylethyl)cyclohex-2~
sodium nitrite in 0.5-g portions over a period of 4 hr. The reaction ene-l,4-dione (4) in 25 ml of chlorobenzene was refluxed for 2 hr
mixture was then diluted with 100 ml of water and extracted four and the solvent was removed in vacuo. The resulting yellow solid
times with 15-ml portions of dichloromethane. The combined or- was recrystallized from heptane to give 0.83 g (90%) of 27: mp 61-
ganic extract was then washed twice with saturated aqueous sodi- 62'; ir (Nujol) 1815, 1750, 1710, 1625 cm-'; 'H NMR (CDCl.7) 6
um bicarbonate and dried (NaZS04) and the solvent was removed 1.25 s (18), 2.46 s (3), 5.16 s (1).
in vacuo (40'). The resulting residue (0.70 g) was shown by 'H Anal. Calcd for C16Hzz04: C, 69.04; H, 7.97. Found: C, 69.16; H,
NMR analysis to be composed of approximately 90% of 13, 3% of 8.09.
the starting amine, and several unidentified minor products. It was 4H,6H( 1H,5H)-Dioxo-3,4-diazino[3,4-c]quinoline (30). Con-
then subjected to column chromatography on silica gel using ethyl centrated sulfuric acid (5 ml, 0.5') was vigorously stirred while
acetate-petroleum ether (1:l) to give 13 as a yellow, crystalline 0.231 g (1.0 mmol) of 1,2,3,4-tetrahydro-4-acetyl-3-diazo-4-hy-
solid: mp 133' dec; ir (Nujol) 3250, 3150, 2990, 2090, 1690, 1640, droxy-2-oxoquinoline (12)was added over a period of 20 min. Dur-
1610, 1580 cm-l; 'H NMR (CDCls), 1.67 s (3), 3.17 s (3), 6.93-7.87 ing the course of this addition, the temperature of the reaction so-
m 4), 9.40 br (1) exchanges with D2O. lution raised to 30'. Thirty minutes after the addition was com-
Anal. Calcd for C1~HllN303:C, 58.78; H, 4.49; N, 17.14. Found: plete, the reaction solution was poured onto 20 ml of crushed ice.
C, 58.84; H, 4.55; N, 16.70. The resulting precipitate was collected to give 0.22 g of 29 as a
Catalytic Reduction of 2-Diazo-3-hydroxy-3-methylbenzo- light yellow solid, m p 430' dec, which was recrystallized from di-
cyclohexane-1,4-dione (2a). A suspension of 1.0 g (4.8 mmol) of methylformamide to give the pure product as white microcrystals:
2a and 0.5 g of 10% palladium on charcoal was subjected to 40 psi mp 430' dec; ir (Nujol) 3160, 1675, 1580, 1570, 1545 cm-I; 'H
of hydrogen for 1.5 hr. After removal of the catalyst and solvent NMR (MezSO-ds) 6 7.57-7.17 m (3), 8.00 s ( l ) , 9.60-9.37 m ( l ) ,
the residue was chromatographed on silica gel using chloroform as 12.77 br (l), 14.20 br (1); mass spectrum mle (re1 abundance) 213
the eluent to give 0.4 g (47%) of 2-amino-3-methyl-l,4-naphthoqui- (1001, 186 (14.6) 158 (12.5), 103 (15.6).
none (la) which was identical with an authentic sample. Anal. Calcd for CllH7N302: C, 61.97; H, 3.31; N, 19.71. Found:
Catalytic Reduction of 5-Acetoxy-6-diazo-2,5-di-tert- C, 61.91; H, 3.33; N, 19.63.
butylcyclohex-2-ene-1,4-dione(4). Catalytic reduction of 4 (0.5 2-Amino-3-thiophenyl-1,4-naphthoquinone (5d). T o a stirred
g, 1.6 mmol) using 10%palladium on charcoal (0.2 g) in 30 ml of solution of 1.0 g (5.0 mmol) of 2-azid0-1,4-naphthoquinone'~ in 70
methanol for 1 hr gave a quantitative yield of 2-amino-3,6-di-tert- ml of absolute ethanol was added 0.83 g (7.5 mmol) of thiophenol
butyl-1,4-henzoquinone (3) which was identical with an authentic in one portion; gas evolution was observed and the reaction solu-
sample. tion gradually turned from yellow-orange to red. After 12 hr the re-
3878 J . Org. Chem., Vol. 40, No. 26, 1975 Belzecki and Mostowicz

sulting precipitate was collected to give 1.15 g (82%) of the quinone Acknowledgment. The authors gratefully acknowledge
5d: mp 164-166' (lit.'6 mp 172'); ir (Nujol) 3475, 3275, 1685, 1590 the financial support of the National Science Foundation
cm-I; 'H NMR (CDCl:,) 6.05 br (2), 7.25 br (5), 7.62-8.33 m (4). (GP43712X) and the National Institutes of Health (CA
2-Amino-5-nzido-3,6-dirnethyl-l,4-benzoquinone (IC). A so-
lution of 1.1 g (5.0 mmol) of 2,5-diazido-3,6-dimethyl-1,4-benzo- 11890).
' ~ 200 ml of ether was treated with 100 ml of a saturated
q u i n ~ n e in
aqueous solution of sodium dithionite, and the mixture was vigor- Registry No.-la, 7427-09-0; lb, 31679-93-3; IC, 26351-46-2;
ously stirred for 60 min under an atmosphere of nitrogen. The or- Id, 56908-60-2; 2a, 56908-61-3; 2b, 56908-62-4; 212, 56908-63-5; 2d,
ganic layer was washed several times with water and dried and the 56908-64-6; 3, 35612-59-0; 4, 56908-65-7; 5d, 56908-66-8; 7, 56908-
solvent was then removed in vacuo (25'). The resulting 2,5-dia- 67-9; 8, 56908-68-0; 9, 56908-69-1; 12, 56908-70-4; 13, 56908-71-5;
zido-3,fi-dimethylhydroquinonewas dissolved in 75 ml of acetone 19, 56908-72-6; 24, 1133-72-8; 25, 4056-72-8; 26, 26138-64-7; 27,
and small amount of sodium azide was added. This caused the 56908-73-7; 30, 56908-74-8; 2,5-di-tert-butyl-3,6-diamino-l,4-ben-
rapid disproportionation'" of the hydroquinone and gave the crude zoquinone, 56908-75-9; 2,5H-3-azido-4-methyI-6,7-benzoazepine-
product, IC, after approximately 1 hr. Chromotography of this 2,5-dione, 56908-76-0; 2,5H-4-methyl-6,7-benzoazepine-2,5-dione,
crude product on 100 g of silica gel using chloroform as the eluent 10315-37-4; sodium azide, 26628-22-8; 2-azido-1,4-naphthoqui-
gave 0.72 g (74911) of IC, which turns from purple to white at 132- none, 15707-29-6; 2,5-diazido-3,6-dimethyl-1,4-benzoquinone,
134' with gas evolution and the white solid then melts at 150- 27977-29-3.
151': ir (Nujol) 3310, 3220, 2100, 1630, 1590 cm-I; 'H NMR
(CDCI:J 1.84 s ( 3 ) , 1.89 s (3),5.00 br (2).
Anal. Calcd for C"HsN402: C, 50.00; H, 4.17; N, 29.17. Found: C, References and Notes
49.83; H, 4.29; N, 28.93. (1) H. W. Moore, Chem. SOC.Rev., 2, 415 (1973).
2-Amino-3-methyl-1,4-naphthoquinone(2a), 2-Amino-3,6- (2) S. Patai, Ed.. "The Chemistry of the Quinonoid Compounds", Vol. 1,
dimethyl- (2b), 2-Amino-3,6-diphenyl- (2d), 2-Arnino-3,6- Wiley, New York, N.Y., 1974, p 2.
di( 1,l-dimethylethy1)- (3) and 2,5-Diamino-3,6-di(1,l-dimeth- (3) S. Patai. Ed., "The Chemistry of the Amino Group", Wiley. New York.
ylethyl)-1,4-benzoquinone.The above aminquinones were pre- N.Y.. 1974.
pared in good yields (>75%) by catalytic reduction (PtO2, 30-40 (4) For example, linderone. methyllinderone, lucidone, methyllucidone, ca-
lythrone. and a number of hop constituents are 2-acyl-4-cyclopentene-
psi) of ethanolic solutions of the respective a z i d o q ~ i n o n e s . ' ~ ~ ' ~ ~ ' ~ 1,3diones. In addition, variously 2-substituted indan-l,3diones show
2-Amino-3-methyl-1,4-naphthoquinone (la),mp 164-165' (lit.'* marked pharmacological activity as anticoagulants, and pyrethrins,
mp 162-163'). among the most important natural insecticides, are relatd structurally
2-Amino-3,6-dimethyl-1,4-benzoquinone (lb): mp 194-196'; ir to the cyclopentena1,3dione ring system. Indeed, even t h e prostaglan-
(Nujol) 3420,3300, 1640, 1600 cm-'; 'HNMR (CDCln) 6 1.82 s ( 3 ) , dins can be viewed as partially reduced cyclopentene-l,3diones.
(5) W. L. Mosby and M. L. Silva, J. Chem. Soc., 3990 (1964);W. L. Mosby
1.98 d (31, J = 2 Hz, 4.79 br (2), 6.42 q ( l ) , J = 2 Hz. and M. L. Silva, bid.. 1003, 2727 (1965).
Anal. Calcd for CaHgN02: C, 63.57; H, 5.96; N, 9.27. Found: C, (6) E. Wenkert and C. A. McPherson. J. Am. Chem. SOC., 94,8084 (1972).
63.71; H, 6.17; N, 9.12. (7) L. Birkofer, Ber.. 80, 83 (1947).
2-Amino-3,6-diphenyl-1,4-benzoquinone (Id): mp 244-246'; ir (8) A. Siegliz and 0. Horn, Ber., 84, 607 (1951).
(Nujol) 3410, 3250, 1630, 1560 cm-I; 'H NMR (MenSO-ds) d 6.14 (9) C. M. Foltz and Y. Kondo. TetrahedronLett., 3163 (1970).We thank Dr.
FoRz for supplying us with an authentic sample of this compound.
br (2),6.65 s ( l ) ,7.15-7.52 m (10). (10) J. C. E. Simpson. J. Chem. Soc., 673 (1946).
Anal. Calcd for ClsH1:~N02:C, 78.54; H, 4.72; N, 5.09. Found: C, (11) K. Schofield and T. Swain, J. Chem. Soc., 2393 (1949); F. Angelico.
78.39; H, 4.71; N, 4.92. Chem. Zentralbl., 1, 445 (1909); Atti R. Accad. Lincei, 17, 665
2-Ami1io-3,6-di(l,l-dimethylethyl)-l,4-benzoquinone (3): mp (1908).
111-113O; ir (Nujol) 3450, 3320, 1675, 1600 cm-l; 'H NMR (12) H. W. Moore and R. J. Wikholm, Chem. Commun.. 1073 (1971).
(13) D. Misiti, H. W. Moore, and K. Folkers, Tetrahedron,22, 1201 (1966);G.
(CDCI:j)6 1.22 s (9), 1.38 s (9),5.49 br (2), 6.44 s (1). R. Bedford, G. Jones, and B. R . Webster, Tetrahedron Lett.. 2367
Anal. Calcd for C14H21N02: C, 71.49; H, 8.94; N, 5.96. Found: C, (1966).
71.37; H, 9.10; N, 5.73. (14) H. W. Moore, H. R. Shelden, D. W. Deters, and R J. Wikholm, J. Am.
2,5-Diamino-3,6-di(l,l-dimethylethyl)-l,4-benzoquinone: mp Chem. Soc., 92, 1675 (1970).
192-193'; ir (Nujol) 3440, 3320, 1540 cm-'; 'H NMR (CDCI:,) d (15) N. Ikeda. J. Pharm. SOC.Jpn., 75, 649 (1955).
(16) H. W. Moore and H. R. Shelden, J. Org. Chem., 33, 4019 (1968).
1.34 . (17) H. W. Moore and W. Weyler, J. Am. Chem. Soc., 93, 2812 (1971).
Anal. Calcd for C14H22N202: C, 67.20; H, 8.80; N, 11.20. Found: (18) B. R. Baker. T. H. Davies, L. McElroy. and G. H. Carlson. J. Am. Chem.
C,67.15;H,8.94;N, 11.12. Soc.. 64, 1096 (1942).

Asymmetric Synthesis of Oxaziridines

Czesfaw Bebecki* and Danuta Mostowicz

Institute of Organic Chemistry, Polish Academy of Sciences, Warstawa 00961, Poland
Received May 14, 197ij

Oxidation of Schiff bases formed by the reaction of chiral (R)-(+)-a-phenylethylamineand carbonyl compound
using m-chloroperhenzoic acid gives rise to the formation of nonracemic diastereomeric 3,3-disubstituted oxaziri-
dines in a high optical yield. Oxidation of (E)-(R)-(-)-N-benzylidene-a-phenylethylamine yields a mixture of all
four possible nonracemic diastereomers with predominance of E products.

T h e relatively small group of oxaziridines, containing the physical methods; in the case of a mixture of enantiomers,
stable chiral N atom, is characterized by a high energy bar- multiple recrystallizations afforded compounds which did
rier for inversion, thus permitting the separation of enan- not show a marked change of optical rotation after further
tiomers.'-6 recry~tallizations.~*6
Until now, optically active oxaziridines have been ob- Two alternative mechanisms of imine oxidation have
tained by the oxidation of imines, using optically active pe- been postulated: (a) olefin type epoxidation (one step) in-
roxy Depending upon the substrate used, mixtures volving nucleophilic reaction of A electrons of the C=N
of compounds obtained represented nonracemic diastereo- b ~ n d ,(b)
~ , Baeyer-Villiger
~ (two step) type, through cleav-
mers or enantiomers with the presence of a small excess of age of A bonding followed by the elimination of one mole-
one of them.2.:3 Such mixtures were usually separated by cule of carboxylic acid used as peroxy acid.9