Evaluación en invernadero del efecto de los prototipos de formulación sólidos

a. Pyrolysis of l,5-Diphenyl-3-iriphenylphosphoranylidenepentane-l,2A,5- tetraone

i. FVP of the ylide 144a (308 mg, 500 °C, 1.0-2.0 x 10-2 Torr) gave a red solid at the furnace exit which proved by iR and 3 Ip NMR to be Ph^PO,

and in the cold trap a mixture which was shown by IR NMR to contain mainly

benzoic anhydride (data as in E2a.), and benzaldehyde. The desired alkyne was

not present.

RgnzaMgAyüfg: 6n 10.2 (1 H, s. CHO), 7.96 (2 H, m, Ph), 7.62 (1 H, m, Ph) and 7.51 (2 R, m, Ph).

ii. Conventional pyrolysis of the ylide 144a (500 mg, 200 °C, 1.0 x 10-2 Torr) in a Kugelrohr gave a brown solid residue in the reaction flask which proved by IR and 3Ip NMR to be PhgPO, and in the receiver a mixture which

was shown by iR and 13C NMR to contain benzoic anhydride, data as in E2a.

The desired alkyne was not present.

b. Pyrolysis of Methyl 5-phenyl-2A,3~trioxo-3-triphenylphosphoranylidene pentanoate

i. FVP of the ylide methyl 144b (305 mg, 500 °C, 1.0-2.0 x 10-2 Torr) gave a red solid at the furnace exit which proved by iR and 3Ip NMR to be

PhgPO, and in the cold trap a mixture which was shown by iR and 13c NMR

to contain benzaldehyde (data as in ai.) and methanol (as the major products)

and some benzoic acid, and other, unidentified, material. The desired alkyne

was not present.

GczW.' ÔH 12.2 (1 H, s, CO2H), 8.15 (2 H, m), (1 H, m) and 7.48

ii. Conventional pyrolysis of the ylide 144b (488 mg, 200 °C, 1.0 x 10-2 Torr) in a Kugelrohr gave a solid residue in the reaction flask which proved

by iR and 3 Ip NMR to be PI13PO, and in the receiver a mixture which was

shown by IR and 13C NMR to contain benzaldehyde. 5h as in ai. The desired

alkyne was not present.

c. Pyrolysis of Ethyl 5-phenyl-2,4,5-trioxo-3-triphenylphosphoranylidene pentanoate

i. FVP of the ylide 144c (301 mg, 500 °C, 1.0-2.0 x 10-2 Torr) gave a red solid at the furnace exit which proved by IR and 3 Ip NMR to be PhgPO,

and in the cold trap a mixture which was shown by IR and 13C NMR to

contain benzaldehyde, 5h as in ai.; ethanol (as the major products) and benzoic

acid (ÔH as in F2b), and other, unidentified, compounds. The desired alkyne

was not present.

ii. Conventional pyrolysis of the ylide 144c (502 mg, 200 °C, 1.0 x 10-2 Torr) in a kugelrohr gave a brown solid residue in the reaction flask which proved by IR and 3Ip NMR to be mainly PhgPO, and in the receiver a

mixture which was shown by iR and 13c NMR to contain benzaldehyde. 5h as

in ai. The desired alkyne was not present.

d. Pyrolysis o f Dimethyl 2,4-dioxo-3-triphenyIphosphoranylidenepentane dioate

i. FVP of the ylide 144d (382 mg, 500 “C, 1.0-2.0 x 1 0 -2 Torr) gave a solid at the furnace exit which proved by iR and 3Ip NMR to be PhgPO, and

in the cold trap a yellow oil which was shown by IR and 13C NMR to contain

methanol. None of the desired alkyne 189 was present.

proved by iR and 31p NMR to be mainly PhgPO, and in the receiver a yellow oil which was shown by iR and l^C NMR to contain the desired alkyne 189. Chromatography on silica (ethyl acetate/hexane, 1:1) gave dimethyl 4- oxopent-2-ynedioate (77 mg, 39%) as a yellow oil (Found: M+R+, 171.0301. C7H6O5 requires M+R+, 171.0293);Vmax /cm-1 1765, 1745. 1725 and 1700; % 3.97 (3 H, s, OMe) and 3.89 (3 H, s, OMe); Jc 167.8 (COiCOC^C), 158.1 (C02C0 C=C), 151.9 (C=CC02Me), 83.4 (C=CC02Me), 79.1 (C=CC02Me), 54.1 (OMe) and 53.7 (OMe); /n/z (Cl) 171 (M+H+, 100%), 143 (28), 73 (67) and 59 (30).

Q, Pyrolysis of Ethyl methyl 2,4-dioxo-3-triphenylphosphoranylidenepentane dioate

i. FVP of the ylide 144e (299 mg, 500 °C, 1.0-2.0 x 10-2 Torr) gave a white solid at the furnace exit which proved by IR and 3 ip NMR to be PhgPO,

and in the cold trap a yellow oil which was shown by iR and 13C NMR to

contain a small amount of the desired alkynes, 190 and 191, data as in ii. below, as well as other unidentified products.

ii. Conventional pyrolysis of the ylide 144e (504 mg, 200 °C, 1.0 x 10-2 Torr) in a Kugelrohr gave a brown solid residue in the reaction flask which proved by iR and 3Ip NMR to be mainly Ph^PO, and in the receiver a yellow oil which was shown by iR and 13C NMR to contain a 1:1 mixture of the

alkynes 190 and 191. Chromatography on silica (ethyl acetate/hexane, 1:1)

gave a mixture of 1-ethyl 5-methyl- and 5-ethyl 1-methyl 4-oxopent-2-

ynedioate (94 mg, 47%) as a yellow oil. (Found: M+R+, 185.0248. CgRgOg

requires M+H+, 185.0450); v^ax /cm-1 1765, 1745, 1725 and 1700; m/z (Cl)

553 [(Mx3)+H+, 94%)], 369 [(Mx2)+R+, 100%)]; m/z (El) 185 (M+R+, 19%),

156 (20), 153 (27), 139 (38), 125 (62), 111 (100), 97 (33), 59 (73), 53 (82) and 45 (22).

1-Ethyl 5-methyl-4-oxopent-2-ynedioate 1 9 0 : 4 . 3 5 (2 H. q, J 7, OCH?),

3.90 (3 H, s, OMe) and 1.37 (3 H. t, 7 7, CHoMg); Jc 167.9 (MeC02C0C=C),

158.1 (M eC02C0C=C), 151.9 (C=CC02Et), 83.2 (C=CC02Et), 79.2

(C=CC0 2Et), 63.5 (OCH2), 53.7 (OMe) and 13.9 (CHiMe).

5-Ethyl l-methyl~4-oxopent-2-ynedioate 191:(5^; 4.42 (2 H. q, 7 7, OCH9),

3.99 (3 H, s, OMe) and 1.41 (3 H. t, 7 7, CH2Me); 168.3 (EtC02C0C=C),

157.7 (EtC02COCsC), 151.4 (C^CCOoMe), 83.8 (C=CC02Me), 78.8

(C=CC02Me), 64.0 (OCH2), 54.1 (OMe) and 13.9 (CHoMe).

f. Pyrolysis of Diethyl 2,4-dioxo-3-triphenylphosphoranylidenepentanedioate

i. FVP of the ylide 144f (311 mg, 500 °C, 1.0-2.0 x lOir Torr) gave a solid at the furnace exit which proved by iH and 3Ip NMR to be PhgPO, and

in the cold trap a yellow oil which was shown by iR and 13C NMR to contain

ethanol. None of the desired alkyne 192 was present.

ii. Conventional pyrolysis of the ylide 144f (504 mg, 200 °C, 1.0 x 10-2 Torr) in a Kugelrohr gave a brown solid residue in the reaction flask which proved by iR and 3Ip NMR to be mainly PhgPO, and in the receiver a yellow oil which was shown by iR and i3C NMR to contain the desired alkyne 192.

Chromatography on silica (ethyl acetate/hexane, 1:1) gave diethyl 4-oxopent- 2-ynedioate (88 mg, 42%) as a yellow oil (lit, 127 yellow oil) (Found: M+R+,

199.0600. C7H6O5 requires 199.0606);Vmax /cm-i 1765, 1745, 1725 and

1700; % 4.42 (3 H, q, 7 7, CH2), 4.35 (3 H, q, 7 7, CH2), 1.41 (3 H, t, 7 7,

CH2Mg) and 1.36 (3 H, t, 7 7, Me); 168.4 (C0 2C0 C=C), 157.7

(C02C0C=C), 151.4 (C=CC02Et), 83.7 (C=CC02Et), 78.9 (C=CC02Et),

64.0 (OCH2), 63.4 (OCH2) and 13.9 (2 x CH2Me); m/z (Cl) 199 (M+H+,

G Preparation and FVP of Qxalvl Bis-Ylides

1. Preparation of Precursor Phosphonium salts

a. (4-Chlorobenzyl)triphenylphosphonium chloride

A solution of 4-chlorobenzyl chloride (10.0 g, 62.1 mmol) and triphenylphosphine (16.3 g, 62.1 mmol) in dry toluene (150 cm^) was heated

under reflux for 3 d. The precipitate which formed was filtered off, washed

with ether and dried to afford the title salt (23.3 g, 89%) as a white powder,

m.p. 285-286 T (decomp.) (lit., 128 289 T ); <5p +23.1.

b. (4-Bromobenzyl)triphenylphosphonium bromide.

This was prepared as above using 4-bromobenzyl bromide (15.0 g, 60

mmol) and triphenylphosphine (16.0 g, 60.0 mmol) to afford the title salt

(27.5 g, 88%) as white powder, m.p. 276-278 T (lit., 129 278 T ): (5p +22.9.

2. Preparation of Oxalyl Bis-YIides from Non-stabilized Ylides

a. l,4-Bis(triphenylphosphoranylidene)-l,4-bis(4-chlorophenyl)biitane~2,3~ dione 201

To a suspension of (4-chlorobenzyl)triphenylphosphonium chloride

(10.0 g, 23.6 mmol) in dry THF (150 cm3) at RT and under a nitrogen

atmosphere, was added a solution of n-butyl lithium in hexane (9.3 cm3, 23.6

mmol). The mixture was stirred for 30 min and oxalyl chloride (0.75 g, 5.9

mmol) in dry THF (10 cm3) was added dropwise. The mixture was stirred at RT for 3 hours then poured into water and extracted with ethyl acetate (3 x 50

cm3). The combined organic phase was dried and evaporated give to the title

compound (2.2 g, 45%) as yellow crystals; m.p. 135 'C (Found: C, 75.1; H, 4.6; M+H+, 827.1819, C52H38CI2O2P2 requires C, 75.5; H, 4.6%; M+H+,

827.1802); v ^ a x /cm-1 1500, 1435, 1375, 1323, 1188. 1100.963, 835, 750. 722 and 693; % 1-2-1.1 (30 H, m. Ph) and 6.91 (8 H, s. Ph); 5q 187.9 (d d. J 5, 13, 2 X CO), 137.0 (d, 7 4, 4 C, C-2 ofp-Cl-Ph), 135.5 (d, J 12, 2 C,C-1 of p-Cl-Ph), 133.6 (d, / 10, 12 x C-2 of P-Ph), 131.4 (d, J <2. 6x C-4 of P-Ph), 130.6 (2 C, C-4 ofp-Cl-Ph), 128.4 (d, J 12, 12 x C-3 of P-Ph), 127.1 (4 C, C- 3 of p-Cl-Ph), 126.0 (d, 7 90, 6 x C-1 of P-Ph) and 67.8 (d. 7 104, 2 x P=C); (5p +14.5; m/z (FAB) 827 (35C12-M+H+, 10%), 415 (37C1-M+/2. 36), 413 (35C1-M+/2, 100), 279 (6), 262 (9), 201 (7) and 183 (15).

b. 1,4-Bis( tripheny Iphosphoranylidene )-l,4-bis(4-bromopheny l)butane-2,3- dione 202

Reaction as for the chloro analogue using (4-bromobenzyl)

triphenylphosphonium bromide (20.0 g, 39.0 mmol). and oxalyl chloride

(0.84 cm3, 1.23 g, 9.86 mmol) gave the title compound (0.96 g, 11%) as

yellow crystals; coiTect elemental analysis could not be obtained due to partial

hydrolysis and decomposition on attempted recrystallisation; v^ax /cm-1 1705,

1435, 1195, 1180, 1096, 1063, 961, 748, 711 and 688; % 7.5-7.2 (30 H, m),

and 7.05 and 6.83 (8 H, AB pattern, 7 9); 5q 185.5 (d d, 7 4, 12, 2 x CO),

137.2 (d, 7 4, 4C,p-Br-Ph), 133.6 (d, 7 10, 12 x C-2 of P-Ph), 131.8 (d, 7 <2,

6 X C-4 of P-Ph), 128.5 (d, 7 12, 12 x C-3 of P-Ph), 124.9 (d, 7 90, 6 x C-1 of P-Ph) and 70.7 (d, 7 102, 2 x P=C) (note: 3 signals from p-Br-Ph group could

not be assigned unambiguously); 5p +14.7; m/z 457 (M+/2, 0.2%), 379 (1),

350 (1), 278 (48), 277 (100), 271 (2), 269 (2), 262 (3), 201 (30), 199 (15), 185 (9), 183 (10) and 152 (6).