3426
J. Org. Chem. 1987,52, 3426-3434
The Vilsmeier-Haack Reaction of Isoxazolin-5-ones. Synthesis and Reactivity of 2-(Dialky1amino)-l,3-oxazin-6-ones1 Egle M. Beccalli and Alessandro Marchesini* Dipartinento di Chimica Organica e Industriale, Uniuersitd degli Studi di Milano, 20133 Milano, Italy
Received August 8, 1986
The Vilsmeier-Haack reaction on isoxazolin-5-onesgives 2-(dialkylamino)-l,3-oxazin-6-ones, and a reaction path is proposed depending on substitution pattern of the isoxazolin-5-onesstudied. A thermal equilibrium between the oxazinones, imino ketenes, and vinyl isocyanates is hypothesized to explain most of the chemical reactivity of the 2-(dialkylamino)-1,3-oxazin-6-ones.
The Vilsmeier-Haack reaction on heterocyclic compounds as well as the synthesis of heterocycles using this reaction has been widely studied.2 A report3 on the reaction between 3-arylisoxazolin-&ones and DMF-POC1, excess of POC1, indicated the formation of 4-(3-aryl-5isoxazolyl)3-aryl-5-isoxazolonesand 3-aryl-5-chloro-4-(dichloromethy1)isoxazoles. These results differ from the findings we described in our preliminary papers.’ More recently and at the time this work was nearly completed, D. J. Anderson reinvestigated the VilsmeierHaack reaction of 3-phenylisoxazolin-5-one4and was also not able to reproduce the earlier result. He found instead, 3-phenyl-4-[ (dimethylamino)methylene]isoxazolin-5-one and 2-(dimethylamino)-5-formyl-4-phenyl-1,3-oxazin-6-one. The proposed reaction path fits our proposed mechanism.’ To the best of our knowledge only two other reports covering the synthesis of 1,3-oxazin-6-onesfrom isoxazolin-Bones are available in the literature5 whereas 2H-1,3oxazines are known to be formed from isoxazolium Salk6 We now report the synthesis and reactivity of 2-(dialkylamino)-l,3-oxazin-6-ones (2),heterocycles which belong to a virtually unknown obtained by a VilsmeierHaack-type reaction from the readily available isoxazolin-5-ones 1. Vilsmeier-Haack Reaction of 3,4-Disubstituted and 3-Unsubstituted Isoxazolin-&ones. When the Vilsmeier-Haack reaction is carried out on 3,4-disubstituted and 3-unsubstituted isoxazolin-5-ones la-p, the heterocycles 2a-p are readily obtained in a pure state and in very good yields (Scheme I and Table I). Whereas with the 3,4-disubstituted isoxazolin-5-ones an excess of the Vilsmeier reagent may be used, with the 3-unsubstituted derivatives lm-p the rcaction must be carried out with a molar amount of the preformed reagent because the first formed 4-unsubstituted oxazines 2m-p react further with the Vilsmeier reagent (see later). We suggest that the reaction giving 2-(dialkylamino)1,3-oxazin-6-onesproceeds by the attack of the Vilsmeier reagent at position 2 of the isoxazolin-5-one, followed by ring opening and cyclization with hydrogen chloride elim~
(1) Preliminary papers: (a) Beccalli, E. M., Marchesini, A. Presented at the 1lth European Colloquium on Heterocyclic Chemistry, Ferrara, Italy, 1985. (b) Beccali, E. M.; Marchesini, A,; Molinari, H. Tetrahedron Lett. 1986, 627. (2) Jutz, C. Adu. in Org. Chem. 1976,9(1),225. Kantlehner, W. Ibid. 1976, 9(2), 5. Meth-Cohn, 0.;Tarnowski, B. Adv. Heterocycl. Chem. 1982, 31, 207. (3) Kallury, R. K. M. R.; Devi, P. S. U. Tetrahedron Lett. 1977, 3655. (4) Anderson, D. J. J. Org. Chem. 1986, 51, 945. (5) (a) Risitano, F.; Grassi, G.; Foti, F.; Caruso, F.; Lo Vecchio, G. J . Chem. Sac., Perkin Trans. 1 , 1979, 1522. (b) Beccalli, E. M.; La Rosa, C.; Marchesini, A. J. Org. Chem. 1984, 49, 4287. (6) King, J. F.; Durst, D. Can. J . Chem. 1962, 40, 882. (7) Some representatives have been described by: Chuche, J. Presented at the 11th European Colloquium on Heterocyclic Chemistry, Ferrara. Italy, 1985
J
2 a-p 2m
R L ~=-dimethylamino
: R Y
R , ~
2a-p k m m n
R
2 k’,m” R , ; ~
- .diethylomino
- = morpholino
R Y
ination as shown in Scheme I. Although we were unable to isolate any intermediate, this reaction path is strongly supported by its analogy with the easy cyclization of 1,4-diaryl-l-cyano-2-azabuta-1,3diene-4-carboxylicacids to give 2,5-diaryl-1,3-oxazinB-ones, as reported p r e v i o u ~ l y .The ~ ~ 2-(dialkylamino)-1,3-oxazin-6-ones are stable compounds and can be stored indefinitely at room temperature. The structure of the new compounds is based on analytical and spectroscopic data as well as chemical behavior. The structures of the oxazinones 2g, 2n, and 2n‘ were confirmed by X-ray diffraction analysis? Moreover good yields of oxazinones 2 were also obtained when formamides other than dimethylformamide (e.g., formylmorpholine or diethylformamide) were used (Table I, derivatives %k’,”,m’’,n’). The 2morpholino-5-phenyl-l,3-oxazin-6-one (2”) proved to be identical with the compound previously reported as 6morpholino-5-phenyl-2H-1,3-oxazin-2-one by G. V. Boyd.g On the basis of this we also synthesized, using our method, the oxazinone 2k’, which also proved to be identical with the compound described by Boyd as 4-(diethylamino)5,6,7,8-tetrahydro-2H-3,1-benzoxazin-2-one and synthesized from 2-(diethylcarbamoyl)-3,4,5,6-tetrahydrobenzoyl azide.g The structure of compound 2m’ also follows from the chemical behavior. Vilsmeier-Haack Reaction of 4-Unsubstituted Isoxazolin-5-ones. A more complex reaction pattern is shown by the 4-unsubstituted isoxazolin-5-ones lq-u when the Vilsmeier-Haack reaction is applied to these derivatives. Scheme I1 presents an overall picture of the products so formed. (8) Pilati, T., unpublished results (complete data were supplied to the editor for inspecting). (9) Baydar, A. E.; Boyd, G. V. J . Chem. SOC.,Perkin Trans. I 1981, 2871.
0022-326318711952-3426$01.50/0 0 1987 American Chemical Society
J. Org. Chem., Vol. 52, No. 15, 1987 3427
The Vilsmeier-Haack Reaction of Isoxazolin-5-ones
R
start matrl laz2 1 b23
Me Ph Me CO2Et Me Me Ph Ph Me Ph
124 id25
lez6
1f26 1gz7
1hZ8 1iz6 1j 2 9 1k'O lk
Ph H H H H H H H
1130 im31
lm lm in5b
In ip32
Table I. 2-(Dimethylamino)-ly3-oxazin-6-ones 2 from Isoxazolin-5-ones 1 R' product ( % yield) eluant mp, "C
Ph Me CHzPh Me CH2C02Me n-CXH33 C02Et n-Ct3H17 CH2CH2Ph Et (CH2)4 (CHZ)4 CHzPh CsH5
2a (73)
CH2C12-Et20 (20:l)
2b (87) 2c (80) 2d (70) 2e (62) 2f (77) 2g (74) 2h (90) 2i (87) 2j (72) 2k (85) 2k' (85) 21 (62) 2m (69) 2m' (60) 2m" (93) 2n (87) 2n' (45) 20 (62) 2~ (69)
C6H5 C6H5
C6H4Me-o C6H4Me-o c6HdCl-p C02Et
79-80" 115-1 16" 96-97" 60-61" 77-78' 63-64' 121-122' 41-42" 105-106' 126-127d 98-99" 43-44d 107-10ad 109-1 10c 149-1 50' 73-74' 104-105' 124-125" 154-155d 114-1 15'
CHzC12-Et20 (20:l) CH2C12-hexane (1:2) CHzCl2-hexane (1:l) CH2C12-Et20 (20:l) CH2C12-EtzO (20:1) Et20-hexane (3:l) Et20-hexane (4:l) CH2C12-Et20 (20:l) CHzClz-hexane (1:l) CH2C12-hexane(3:l) CH&-Et20 (20:l) CHZCl2 CHzClZ-EtzO (201)
reacn time, h 2.5 6 5 3 3 8 2 12 2 4 3 1.5 2 1.5 2 2 3 2 1 1.5
Et20-hexane. *Hexane. CH2ClZ-Et20. dEtzO. Scheme I1
rcH
R
Me
DMF-POCI,
'Me
DM F- POClj
Me
N :
\0/.5
4
3 s-u
1 q-u
1 3 : o
Me
s-u
1
DMF- POCI,
kv r!
Me>N Me
ob0
2
R
+
q-r
'&
Me\N,CO Me'
CON:
Me
Me 7 s-u
5 q-r
1
DMF- POCI,
R
R
R
q , R = M e ; r,-nC,H,;
s,Ph;t,
u . C(Me),
4 q-r
6r
We carried out the reaction with 1 and 2 mol of the Vilsmeier reagent, respectively. The results are reported in Table I1 and clearly show the effect of the steric hindrance of group R on the reaction path. For the alkylsubstituted isoxazolones lq,r, in which the steric hindrance at position 2 is low, the main products of the reaction with 1mol of the Vilsmeier reagent are the oxazinones 2qyr(see Table 11)arising from the attack of the reagent at position 2 of the isoxazolone nucleus; this is in agreement with the behavior of disubstituted isoxazolones. In the same reaction byproducts 5q,r were also formed, and a small amount of derivatives 4q,r were isolated: these products respectively arise from 2q,r and dimethylamine and from the attack of the Vilsmeier reagent a t position 5 of the main products 2q,r, as shown in a separate experiment. As shown in Table 11, and as expected, compounds 4q,r became the main products when an excess of the Vilsmeier reagent was used; when R = n-C3H7,6r was also formed
as a condensation product of 4r and the starting isoxazolone lr. In the case of isoxazolones 1s-u, where a more bulky substituent is present, the main products of the reaction with a molar amount of the Vilsmeier reagent are the [(dimethylamino)methylene]isoxazolones 3s-u, resulting from the attack of the reagent at position 4 of the isoxazolone ring. In the case of Is, also 4s and a minor amount of 7s were also isolated; starting from lu a minor amount of 7u was formed. With an excess of the reagent, compounds 4s-u and the chloroisoxazolaldehydes 7s-u became the favored products. The 2-(dimethylamino)-5-formyl-l,3-oxazin-6-ones 4s-u arise from the attack of the Vilsmeier reagent at position 2 of the [(dimethylamino)methylene]isoxazolones 3s-u (as also verified by Anderson for 4 ~ )whereas , ~ the chloroisoxazolaldehydes7s-u arise from the attack of the reagent on the carbonylic oxygen atom of compounds ~ s - u ,
3428 J. Org. Chem., Vol. 52, No. 15, 1987
start matrl 1q'O ir33
is34
it35
1u10
Beccalli and Marchesini
Table 11. Products from Vilsmeier-Haack Reaction of Isoxazolin-5-ones lq-u % yields products eluant mp, "C [bp, OC a b EtzO-hexane (2:l) 53 16 2q 103-104' 4q 5 42 177-178d 5q 9 6 88-8gd 2r EtzO-hexane (1:l) 62 0 [135-140 (0.2)] 4r 6 66 77-78e 5r 6 0 38-39' 6r 0 11 132d 4s CHzClZ-EtzO (201) 15 80 158-15gd 3s 50 0 143-144b 7s 4 15 44-49 4t CHzClz-Et20 (3:l) 0 54 208-210d 3t 67 22 195-196d 7t 0 11 116-1 17d 4u CHzClZ-EtzO (1O:l) 0 17 83-84f 3u 70 0 92-93' 7u 4 64 [105-110 (15)]
reacn time, h a
b
1
2
1.5
2
1.5
2
1.5
4
1
2
Reaction with 1 mol of Vilsmeier reagent. bReaction with 2 mol of Vilsmeier reagent. Hexane. dCHzClz-EtzO. eEtzO. fEtzO-hexane. Table I11 start matrl 2a
reacn time 24 h
2b
24 h
2c
10 h
2d
2h
2e
24 h
2f
6h
2g
0.5 h
2h
2h
2i 2j 2k 21 2m 2n 20
2P
6h 6h 3h 24 h 0.5 h 0.5 h
MeOH-TE A' products 8a 9a 8b 9b 8c 9c 8d 9d 8e 9e 8f
9f 8g 9g 8h 9h 8i 9i
% yields
38" 41 744 13 35b 21 80" 2 46" 20 68' 6 67" 34 60 85 53" 3
80
0.5 h
3 days 4 days
5 days 3 days 2h 4 days 4 days
0
9j 8k 9k 81 91 8m 9m 8n 9n 90 8P 9P
4 days
0
8j
0.5 h
reacn time 3 days
71
4 days
9j
4 days
0
50"
3 days
18
65
2 days
0
73 0 82
2 days
8k 9k 81 91 8m 9m 8n 9n
% yields
0 97 3 72 0 70 11 52 0 78 0 85 53 30 0 95 0 85 4
58 15O 40 0 90 0
72 0
80
2 days
80
0
42
2.5 h
90 8P 9P
0
75
MeOH products 8a 9a 8b 9b 8c 9c 8d 9d 8e 9e 8f 9f 8g 9g 8h 9h 8i 9i 8j
0
0 81
mp, "C 144-145d 114d 111-112d 134-135d 46-47d 123d 102-103d 96-97d 72-73d 86-87d 71-72' 64' 92-93d 68-6gd 47-48d 59-60' 53-54d 109-1 10d 93-94d 123-124d 69-70e 105-106d 106-107d 109-1 10d 112-113d 85-86d 82-83d 81-82d 115-116d 111-112d 81-82d 117-1 18d
Column chromatography eluant: CH2C12-Et20(30:l). Column chromatography eluant: EtzO-hexane (1:l). 'Column chromatography eluant: CH2Cl2 Crystallization solvent: EtzO-hexane. e Crystallization solvent: hexane. 'Similar results were obtained with acidic catalyst (p-toluenesulfonic acid).
as could also be shown in a separate experiment (Scheme 111). The ratio between derivatives 4 and 7 also reflects the steric hindrance of group R: when R = t-C4H, the chloroisoxazolaldehyde 7u is the main product. Compounds 3s, 75, and 4s are identical with those previously rep~rted.~ In principle, besides the steric effects, a change in the tautomeric composition of the 4-unsubstituted isoxazolin-5-one as a consequence of the kind of the substituent may also be considered in explaining the regiochemistry of the reaction of the Vilsmeier reagent with the isoxazolones lq-u. However this latter effect can be ruled out since Katritzky showed that the tautomeric equilibrium composition of isoxazolin-5-ones with a single substituent
in the 3-position changes according to the ionic strength of the medium independently of the nature of the substituent present.l0 Reactivity of 4,5-Disubstituted and 4-Unsubstituted 2-(Dialky1amino)-1,boxazin-6-ones(Scheme IV). (a) Reaction with MeOH. By refluxing in methanol with either acid (p-toluensulfonic acid) or base (triethylamine) as catalyst, the 4,5-disubstituted 2-(dimethylamino)-l,3oxazin-8ones 2a-1 gave a mixture of two derivatives 8 and 9, the 8 to (I ratio being variable and compounds 8 being generally more abundant. In the case of 2h,i,k only 8h,i,k (10)Katritzky, A. R.; Oksne, S.; Boulton, A. J. Tetrahedron 1962,18,
777.
J. Org. Chem., Vol. 52, No. 15, 1987 3429
The Vilsmeier-Haack Reaction of Isoxazolin-&ones Scheme I11
Table VI
start matrl
3
2a 14a 2b 2c 14c 2d 14d 2e 2f 2h 14h 2i 2j 2k 21 141
4
1) t
J
" CH2ClZ.
product (% yield) 14a (60) 15a (55) 14b (65) 14c (57) 15c (40) 14d (60) 15d (42) 14e (26) 14f (65) 14h (76) 15h (60) 14i (62) 14j (55) 14k (36) 141 (74) 151 (75)
mp, "C 226O 100-101d 192-193b 138-139' 93-94d 94-95d 80-82d 98-100b 106-107d 98-9gd 82-83d 174-176' 108-10gd 151-152d 152-153' 117-1 18d
reacn time, h 1 1 1 1 1 0.3
2.5 1
1.5 0.3 2.5
CHzClz-hexane. 'Et20. EtzO-hexane.
Table IV
start matrl
(% vield)
mD. "C
2a 9a 2b 9b 2c 9c
10a (36) 10a (45) 10b (62) 10b (41) 1Oc (67) 1Oc (71)
80-81a
a
product
Et,O-hexane.
86-87b oil
start matrl 2e 9e 2h 9h 21 91
product (% vield)
m n "C 10e (26) oil
Table VII. Products from Vilsmeier-Haack Reaction on Isoxazolin-5-ones lm-p with 2 mol of the Reagent
start matrl
10e (0) 10h (57) oil 10h (62) 101 (80) 105-106b 101 (76)
lm In lo
'CH2Cl2-Et20.
1P
Table V. Alkaline Hydrolysis of Oxazinones 2
start matrl 2a 2b 2c 2f 2h 2i 2j 2k 2k' 21 2m 2m' 2n 20 a
product ( % yield) l l a (90) l l b (46) l l c (50) l l f (60) l l h (71) l l i (79) l l j (80) I l k (90) 11 k' (60) 111 (50) l l m (57) l l m ' (86) l l n (71) 110 (68)
mp, O c a 107-110b 102-103' 86-8gd 72-76' 76-771 93-95e 99-100b 111-1 12' 102-105' 104-107' 163-165b 189-1908 183-185b 167-170'
reacn time, h 2.5 3 3 18 7 6 6 2 2 3 3 2 3 3
'
CH2Cl,-Et20. All derivatives melt with decomposition. CHzC1,-hexane. 'EtzO-hexane. f Hexane. THF.
'Et,O.
f
were formed (Table 111). On the other hand by refluxing in methanol with no added catalyst, the oxazinones 2a-1 gave, very slowly but in high yields, the corresponding amido esters 9. Only in the case of 2d,g,k was an appreciable amount of esters 8d,g,k also formed (Table 111). In the reaction with methanol the 4-unsubstituted oxazinones 2m-p gave only the esters 8m-p in the presence of a catalyst, whereas with no added catalyst only the amido esters 9m-p were formed. In this case both reactions are faster than the correspondingreactions of 4,5-disubstituted oxazinones (Table 111). Analytical and spectral data support structures 8 and 9. Acidic hydrolysis of the amido esters 9 afforded the corresponding @-ketoacids dimethyl amides 10 (Scheme IV and Table IV), and the amide 10a has already been reported.ll The structure of the amido ester 9m has been confirmed by X-ray diffraction analysis.8J2 (11)Butke, G.P.; Jimenez,F.; Michalik, J.; Gorski, R. A. J. Org. Chem. 954. (12) Previously we assigned the incorrect structure of 2-(dimethyl+ amino)-2-methoxy-2,3-dihydro-1,3-oxazin-6-ones1 to compounds 9. 1978. 43.
a
products ( % yield) 2m (73) 16m (11) 2n (28) 16n (57) 20 (48) 160 (49) 2~ (8) 1 6 (76) ~
mp, "C 98-99" 142-144' 107-108" 88-89'
Et2O. CH#&-EtZO.
(b) Alkaline Hydrolysis. Room temperature alkaline hydrolysis of the oxazinone 2 gave in good yields the ureido acids 11 (Scheme IV and Table V). The previously reported esters 8 may be obtained also by diazomethane esterification of these acids. An example of the reactivity of the acids 11 as well as of the esters 8 is shown in Scheme V for the acid llm' and the ester 8". The reported reactions have been used for a further confirmation by chemical methods of the structure of the oxazinone 2". Acidic hydrolysis of the acid 1 lm' afforded the aldehyde and carbamylmorpholine. The unsaturated aldehyde 12 arises from phenyl acetaldehyde, as proved in a separate experiment. From acidic hydrolysis of ester 8m' we were able to isolate, besides carbamylmorpholine, the methyl 2-formyl-2-phenylacetate(131, identical with an authentic ~amp1e.I~ (c) Acidic Hydrolysis (Scheme IV and Table VI). Acidic treatment of 4,5-disubstituted 1,3-oxazin-6-ones 2a-1 gave the corresponding 1,3-oxazin-2,6-diones14. This reaction greatly extends the range of the substitution pattern for these biologically interesting heterocycle^'^ which are obtained in a pure state and in good yields (Table VI). From 14 the 3-methyl derivatives 15 were easily obtained by reaction with sodium hydride and methyl iodide. The structures of 14 and 15 follow from analytical and spectroscopic data and are confirmed by the fact that compound 14d proved to be identical with an authentic sample synthesized by a reported method.I6 The acidic treatment of the 4-unsubstituted oxazinones 2m-o gave the same ureido acids 11 already obtained by room temperature alkaline hydrolysis of the same oxazinones. (13)Chelpanova, L. F.;Komer, V. A. Zh.Obshch. Khim. 1955, 25, 1513; Chem. Abstr. 1956,50, 4872f. (14) Wislicenus, W. Justus Liebigs Ann. Chem. 1916, 413, 206. (15) Washburne, S. S.;Park, K. K. Tetrahedron Lett. 1976, 243 and
references cited therein.
3430 J. Org. Chem., Vol. 52, No. 15, 1987
Beccalli and Marchesini Scheme IV
R I
R
0I"'CHR M e ~ N - C H C-N,
Me'
II
C-N,
Me
11
0
11 m - p
0 16 m-p Me Q Me>N=CHCI
,Me
I
,Me Me
10 Q
1
R
I
.>Nxb*O
R
Me
Me-N
11 a - I
J i o-ofio 15
14 a - I
8 m
11 m '
2m
n
Od-j-NH2
+
vC - P h
n
Ph - C -CHO I1 CHCH2Ph
UNTNH2 +
0
I
C 0 2 h
13
12
(d) Reaction with H20.The oxazinones 2 react with water only in a sealed tube at 110 "C for 16 h. Thus from the oxazinones Za-c,e,h,l the corresponding @-ketoamides 10 (Table IV) were obtained. (e) Reaction with the Vilsmeier Reagent. When the Vilsmeier-Haack reaction was carried out on 2-(dimethylamino)-5-carbethoxy-1,3-oxazin-6-one (2p) the corresponding 2-azabuta-173-diene16p was formed. Since 2 mol of the reagent are used to convert the primarily formed oxazinone to products 16, the Vilsmeier-Haack reaction on the isoxazolones lm-p must be carried out with 1 mol of the reagent to obtain good yields of the corresponding oxazinones. Accordingly, starting from lm-p and working with 2 mol of Vilsmeier reagent, the azadienes 16m-p were obtained as well as the oxazinones 2m-p (Table VII). The structure of compounds 16 is verified by analytical and spectroscopic data as well as by the fact that acidic hydrolysis of 160 gave the corresponding amido aldehyde 17, from which by reaction with NH20HxHC1,the starting isoxazolone l o was formed (Scheme VI). Reactivity of 2-(Dialkylamino)-l,3-oxazin-6-ones Bearing an Electron-Withdrawing Group in Position 5. The oxazinones bearing an electron-withdrawing group in position 5 (e.g., 2g,p and 4r-t) exhibit a peculiar reactivity (Scheme VII). These derivatives react with water
Scheme VI HOCH
, &
Me Me>N-CH
C 6-N:
NH20H.HCI
Me
C-N
.N-CO
3
1 8 g p r t
Me 1 9 g r t
CHO
at 100 "C in a maximum time of 2 h and give the dimethyl amides of substituted 3-aminopropenoic acids 18 (Table VIII) together with a small amount of compounds 19.
J. Org. Chem., Vol. 52, No. 15, 1987 3431
The Vilsmeier-Haack Reaction of Isoxazolin-5-ones Table VIII. Products from Reaction with Oxazinones ~ P . Dand 4r-t
Scheme IX
H20of
start matrl
(%
yields) eluant 18g (59) 19g (33) CHzCl2-Eh0 (1O:l) 1 8 (85) ~ 18r (64) 19r (7) CHzC12-EtzO (3:l) 18s (65) 19s (4) CHzCl2-MeOH (1001) 18t (60) 19t ( 3 ) CH2ClZ-MeOH (501)
2g 2~ 4r
4s 4t
Hexane. hexane.
'EtzO.
7'
Me.
~~
products
EtzO-hexane.
mp, "C 162-164" oil 124-125d 72-76' 36" 168-1 70d 6&6gC 178-182d 138-13ge
reacn time, h 2
N+Ph
Me,
C
MeHN'.' PO,CI*"
2l
LD
,N-CH, Me
N+Ph I CI,PO,-C
"'
A H O
II
0 J
L
21
0.5 2
0.3 0.3
r
-I
1 Me>N-Ccy+Ph Me
[
"28 0
-
J
PhCH=CH-N=CH-N
