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Acylphosphonates: phosphorus-carbon bond cleavage

of dialkyl acylphosphonates by means of amines.
Substituent and solvent effects for acylation of amines
Mitsuo Sekine, Masaki Satoh, Hikaru Yamagata, and Tsujiaki Hata
J. Org. Chem., 1980, 45 (21), 4162-4167 • DOI: 10.1021/jo01309a019
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The Journal of Organic Chemistry is published by the American Chemical Society. 1155
Sixteenth Street N.W., Washington, DC 20036
4162 J . Org. Chem. 1980,45, 4162-4167
two 20-mL portions of HzS04(2 N) and four times with water. for 50 h with stirring. After removal of the insoluble solids and
After the solution was [dried over sodium sulfate and the solvent the solvent, the unreacted A2-isoxazoline2c was obtained quan-
was evaporated, the A"-isoxazoline (2c) was obtained quantita- titatively.
tively, identical with that previously prepared. Registry No. la, 74609-84-0; Ib, 74609-85-1; IC, 74609-86-2; 2a,
Attempted Interconversions of A2-Isoxazolines and A'- 50899-27-9; 2b, 4894-25-1; 212,5050-64-6; 2d, 74609-87-3; 2e, 74609-
Isoxazoline N-Oxides. A. Equimolecular amounts of N-oxide 88-4; 2f, 74609-89-5; 2g, 74609-90-8; 2i, 17669-31-7; 2j, 17669-33-9;
4b (0.024 g) and silver nitrite (0.012 g) in n-heptane (5 mL) were 3j, 17669-32-8; 4a, 74609-91-9; 4b, 19018-61-2; 412,74609-92-0; 4d,
heated under reflux for 50 h with stirring. After removal of the 74609-93-1; 4e, 74609-94-2; 4f, 74609-95-3; 4g, 74609-96-4; 4h,
insoluble solids and the solvent, the residue was chromatographed 74609-97-5; 512,74609-98-6; cyclohexene, 110-83-8; trans-stilbene,
(preparative TLC, silica gel, hexaneethyl acetate (1O:l)) to yield 103-30-0; 1,l-diphenylethylene, 530-48-3; 1-phenyl-1-@-tolyl)-
0.021 g of unreacted 4b. ethylene, 948-55-0; 1-@-bromophenyl)-1-phenylethylene, 4333-76-0;
B. Equimolecular amounts of A2-isoxazoline 2c (0.06 g) and 1,l-di-(p-tolyl)ethylene,2919-20-2; dimethyl fumarate, 624-49-7;
silver nitrate (0.03 g) in n-heptane (5 mL) were heated under reflux methyl cinnamate, 103-26-4.

Acylphosphonates: P-C Bond Cleavage of Dialkyl Acylphosphonates by

Means of Amines. Substituent and Solvent Effects for Acylation of Amines
Mitsuo Sekine, Masaki Satoh, Hikaru Yamagata, and Tsujiaki Hata*
D'epartment of Life Chemistry, Tokyo Institute of Technology, Nagatsuta, Midoriku, Yokohama 227, Japan
Received February 5, 1980

Studies 3n the benzoylation of amines of dialkyl benzoylphosphonates (1A-F) were described in detail.
Stoichiometric reactions of diethyl benzoylphosphonate (1B) with a variety of amines (2a-i) gave amides as the
main products along with diethyl phosphonate (4B) and a-(phosphory1oxy)benzyl phosphonate (5B). The yields
of amides increased with the ratio of lB/%a-i. The use of hindered dialkyl benzoylphosphonates resulted in
high yields of amides while the reaction rates decreased markedly. The benzoylations of n-propylamine (2d)
with 1B in various solvents having dielectric constants of 1.9-36.7 were conducted. The yields of N-n-
propylbenzamide (3d) and 5B were surprisingly almost constant. However, the reaction rates varied as follows.
In n o n p o h solvents such as n-hexane and cyclohexane benzoylation was remarkably rapid while the benzoylation
in methylene chloride was much slower than that in other solvents used. Compound 1B underwent smooth reaction
with aliphatic amines but did not react with aromatic amines under the same conditions. Selective N-benzoylation
of the bifunctional amine, ethanolamine, was achieved by means of diisopropyl benzoylphosphonate (1C) in
tetrahydroruran. The use of the hindered dialkyl benzoylphosphonate 1C resulted in poorer yields of amides
in the case of the reaction with a hindered amine such as diethylamine, but higher yields of amides in the case
of primary amines. Addition of triethylamine and 4-(dimethy1amino)pyridine(DMAP) slightly accelerated the
benzoylaticin, but yields of amides were similar to those in the absence of the catalysts. Optimum conditions
for high yields of amides were proposed for the practical use of dialkyl benzoylphosphonates as the acylating
agents in the present reaction.

Acylation of functional groups such as hydroxyl and A few studies on nucleophilic displacement reactions of
amino groups is one of the important and fundamental acylphosphonates have also been reported for reactions
reactions in organic synthesis. Various kinds of acylating with alcohols,*" t h i o l ~ , ' ~amines,"J4
J~ and carbanions.l"18
agents have been developed and employed, such as acyl In spite of the above features of acylphosphonates, no
halides, anhydrides, mixed anhydrides, active esters, azo- systematic study on acylphosphonates as acylating agents
lides, and ketones.' On the other hand, it is generally has appeared.
recognized that pho,aphorus-carbon (P-C) bonds of orga- In this paper, a systematic study on the benzoylation
nophosphorus compounds are quite stable and are not of various amines by use of dialkyl benzoylphosphonates
cleaved easily under the usual conditions.2 .Hence, studies is described in detail.
of the cleavage reaction of the P-C bond are lacking and
very little data are available for the utilization of orga- (7) R. Kluger, D. C. Pike, and J. Chin, Can. J . Chem., 56,1792 (1978).
nophosphorus compounds as synthetic agents. However, (8) K. S. Narayanan and K. D. Berlin, J. Am. Chem. SOC.,101, 109
the following character of dialkyl acylphosphonates might (1979).
provide some information in this direction. Dialkyl (9) M. I. Kabachnik and P. A. Rossiiskaya, Izu. Akad. Nauk SSSR,
Ser. Khim.,597 (1945); Chem. Abstr., 41, 88 (1945).
acylphosphonates possessing C(0)-P bonds are known to (10) K. Terauchi and H. Sakurai, Bull. Chem. SOC. Jpn., 43, 883
be labile, even toward moisture in air, and decompose into (1970).
carboxylic acids and dialkyl pho~phonates.~-* (11) A. P. Pashinkin, T. K. Gazizov, and A. N. Pudovik, Zh. Obshch.
Khim., 40, 28 (1970);Chem. Abstr., 72, 100827 (1970).
(12) A. Takamizawa and Y. Sato, Chem. Pharm. Bull. (Tokyo),12,398
(1964).
(13) A. Takamizawa, Y. Sato, and S. Tanaka, Yakugaku Zasshi, 85,
298 (1965).
(1)A. L. J. Beckwith in "The Chemistry of Functional Groups, The (14) M. Soroka and P. Mastalerz, Zh. Obshch. Khim., 44,463 (1974);
Chemistry of Amides", J. Zabicky, Ed., Wiley, London, 1970, pp 74-185. Chem. Abstr., 80, 121058 (1974).
(2) P. C. Crofts, Q. Rev., Chem. Soc., 12, 624 (1963);L. D. Freedman (15) I. Shahak and E. D. Bergmann, Isr. J . Chem., 4, 225 (1966).
and G. 0. Doak, Chem. lieu., 57, 479 (1957). (16) I. Shahak, Tetrahedron Lett., 2201 (1966).
(3) B. Ackerman, T. A. Jordan, C. R. Eddy, and D. Swern, J. Am. (17) G. M. Baranov, V. V. Perekalin, M. V. Ponamarenko, and I. A.
Chem. SOC.,78, 4444 (19.56). Orlovskii, Khim.Primen. Forsfororg. Soedin., Tr. Konf., 4th, 228 (1969);
(4) K. D. Berlin and H. A. Taylor, J . Am. Chem. SOC.,86,3862 (1964). Chem. Abstr., 78, 124686 (1969).
(5) W. Jugelt, S. Andreae, and G. Schubert,J. Prakt. Chem., 83 (1971). (18) 0. G. Plantema, H. de Konig, and H. 0. Huisman, Tetrahedron
(6) R. Kluger and J. Chin, J . Am. Chem. SOC.,100, 7382 (1978). Lett., 2945 (1975).

0022-3263/80/1945-4162$01.00/00 1980 American Chemical Society

P-C Bond Cleavage of Dialkyl Acylphosphonates J . Org. Chem., Vol. 45, No. 21, 1980 4163
Table I. Stoichiometric Reaction of Table 11. Reaction of Excess
Diethyl Benzoy1:phosphonate (1B) with Amines Diethyl Benzoylphosphonate (1B) with
_________ n-Propylamine ( 2 d ) in Dry Ether
product,
% yield product, % yield
amine pKb2' timea 3 4B 5B 1B/2d timea 3d 4B 5B
2a Et,NH 3.1 24 h 47 3 48 1.00 20min 76 46 22
b C,H,,NH, 3.3 50 min 58 2 38 1.20 80min 88 33 32
C ~I-BuNH, 3.4 20 min 79 42 18 1.40 5h 94 38 45
d n-PrNH, 3.5 20min 76 46 22 1.53 20 h 94 33 55
e i-BuNH, 3.6 1h 77 40 22
f PhCH,CH,NH, 4.2 1h I9 43 20 1.20 (1C/2d) 5 days 95 62 (4C) 1 0 (5C)
g HOCH,CH,NH, 4.5 2h 50b 46 13 a Time required for disappearance of 1 B or 1C.
h PhCH,NH, 4.6 3h 82 45 12
i 0-i k 5.6 6h 74 34 17 Table 111. Solvent Effects for Benzoylation of
,LJ n-Propylamine ( 2 d ) with
PhNH, 9.3 - no reactionC Diethyl Benzoylphosphonate (1B)
product, % yield
- - no reactionC dielectric
solvent constant timea 3d 4B 5B
a Time required for disappearance of 1B. 0,N- n-hexane 1.9 1 min 74 29 23
Dibenzoylated product (6) was obtained in 1 4 % yield, cyclohexane 2.0 1 min 75 48 23
There was no reaction in 24 h. benzene 2.3 30min 79 55 18
ether 4.2 20min 76 46 22
Results a n d Discussion tetrahydrofuran 7.4 40 min 78 39 20
Diethyl benzoylphosphonate (1B) was chosen to exam- CH,Cl, 8.9 2h 79 53 21
pyridine 12.3 30 min 76 34 22
ine the reactivity of 1, and its reaction with amines was HC(O)NMe, 36.7 20min 77 6b 20
tested. The reactions were carried out by use of stoi-
chiometric amounts (of amines (2a-k). For example, 1B a Time required for disappearance of 1B. Almost all
of 4B was removed in vacuo with the solvent.
was allowed to react with n-propylamine (2d) in dry ether
at room temperature. The reaction was monitored by silica slowly with 4B with conversion into 5B. Table I11 reveals
gel thin-layer chromatography. After 20 min 1B had the results of the solvent effect in the benzoylation of 2d
disappeared and the TLC showed three spots. The two with 1B and implies that there is no significant difference
major spots were N-propylbenzamide (3d) and diethyl among solvents possessing dielectric constants in the range
phosphonate (4B). The minor spot was found to be CY- of 1.9-36.7. However, a definite solvent effect on the re-
(phosphory1oxy)benzylphosphonate(5B). action rates was observed. The most remarkable difference
0 was observed between benzene and cyclohexane which
0 0-b: (OR' ) z
0 0
ph?-I(i)~'), . R'R'NH
0
-4 PhENR'R' H-b:(OR'), * Ph-FH
O=P (OR' ) t
have low dielectric constants of 2.0 and 2.3. In the former
solvent, benzoylation was complete within 1 min, but in
1 2 3 4
5 the latter required 30 min. The order of solvent effects
for the reaction rates was the following: n-hexane N cy-
5B may be formed by the successive reaction of 1B with clohexane > ether N DMF > benzene > pyridine > T H F
lowed by a C
group."Jg
-
4B, which accumulai,es during the formation of 3d, fol-
0 rearrangement of the phosphonyl
Similarly, several primary and secondary
> CH2C12.
As indicated by this order, there were no regular rela-
tionships between the polarity of the solvents and the
amines were treated with 1B. 1B reacted smoothly with reaction rate. The benzoylation proceeded quite rapidly
primary aliphatic aimines and slowly with secondary in nonpolar solvents such as n-hexane and cyclohexane.
amines. On the other hand, 1B did not react with aromatic The reaction rates were effectively constant in several
amines such as aniline and 2-aminopyridine under these solvents having higher dielectric constants than that of
conditions. The distinct difference in reactivity of 1B benzene. Contrary to our expectation, the reaction in
between aliphatic and aromatic amines is of interest. This dimethylformamide, having the highest dielectric constant
is one of the promising features of benzoylphosphonates among the solvents used, was essentially similar to those
as acylating agents and should be emphasized because in benzene, ether, tetrahydrofuran, and pyridine. On the
almost all of the previously known acylating agents react other hand, it was found that the benzoylation in methy-
easily with aromatic (amines.' These results are summa- lene chloride was remarkably slow.
rized in Table I. The reactivity of the amines for the The reaction of ethanolamine (2g) with 1B was con-
benzoylation was fourid to decrease in the following order: ducted in order to test the selectivity of 1B in the ben-
n-BuNH, N n-PrNH, > C6HllNH2> PhCH2CH2NH2N zoylation toward amino and hydroxyl groups. The ben-
(CHs),CHCH,NHz > HOCHzCHzNHz > PhCHZNH2 > zoylation of 2g with 1B in ether gave 3g in a relatively low
morpholine >> EtzNIl >> PhNH2 N 2-aminopyridine, yield (50%) and dibenzoylated product (6) was obtained
This order almost parallels the basicity of the amines. in 14% yield. Mono-0-benzoylated product (7) was not
With an increase of the molar ratio of 1B/2d, the yield of formed in this reaction.
3B increased gradually to 94%, the maximum isolated
R
yield, as indicated in 'Table 11. The use of a larger excess
of 1B than 1.4 equiv resulted in a longer period of time
1 + HOCH,CH,NH, >-
0
HOCHzCH,NHCPh .0
Ph!OCH+Y,NH?Ph + 4 B
29 39 6
for the consumption of 1B since the remaining 1B reacted
A similar benzoylation of 2g in dry T H F gave a little
(19) R. D. Moss, U.S. Patent 3012054 (1961); Chem. Abstr., 57,4698
better yield (59%) of 3g and the yield of 6 decreased to
(1962); A. N. Pudovik, I. V. Gur'yanova, Khim. Primen. Forsjororg. 7%. The mono-N-acylation was improved to a 78% yield
Soedin., Tr. Konj., 4th, 164 (1972); Chem. Abstr., 78, 136371 (1973). by using diisopropyl benzoylphosphonate (lD),described
4164 J. Org. Chem., Vol. 45, No. 21, 1980 Sekine et al.
Table IV. Benzoylation of Ethanolamine (29) with of triethylamine gave 5B in 86% yield after 1 h without
Dialkyl Benzoylphosphonates (1B and 1 C ) the solvent, but in the absence of triethylamine 5B was
product, not formed, even after 1 day. When 0.01 equiv of tri-
?6 yield ethylamine was employed in this reaction, only trace
benzo y lating
agent solvent timea 3g 6 4B amounts of 5B were formed. The use of enough tri-
ethylamine seemed necessary for the detectable accelera-
1B tetrahydrofuran 1h 59 7 13 tion of the side reaction. Therefore, acylation of 2d with
ether 2h 50 14 13 1 equiv of 1B in the presence of 1 equiv of triethylamine
1c tetrahydrofuran 3days 78 9 3
was conducted. Acylation was complete within 10 min, and
a Time required for disappearance of 1 B or 1C. 3d and 5B were obtained in 75% and 22% yields, re-
spectively. Unexpectedly this result showed no significant
Table V . Substituent Effects of Alkyl Groups of effect of the presence of triethylamine on the yields of the
Benzoyl Phosphonates in Benzoylation products. It was concluded that triethylamine catalyzed
_ _ ~ _ _ _ .

product, both the normal acylation and the side reaction.

% yield Recently, 4-(dimethylamino)pyridine(DMAP) has been
R’ Es c timeb 3d 4 5 utilized as a promising catalyst for the acetylation of
hindered alcohols.22 Therefore, acylation by 1B in the
1A Me O.C!O 3min 68 IC 27
B Et -0.07 20 min 76 46 22
presence of DMAP was studied. However, regardless of
C i-Pr -0.47 18 h 86 72 13 the addition of DMAP, the yields of 3d, 4B, and 5B were
D i-Bu -0.93 4 0 min 78 57 21 essentially unchanged. Even when a noncatalytic amount
E S-BU -1.13 40 h 89 76 9 of DMAP was employed, the yield of 3d did not increase
F Et,CH -1.98 4days 92 86 7 but the acylation was slightly (two times) accelerated.
a Steric factor reporlted by Taft e t al.zO,z’ Time The reaction of diethylbenzoylphosphine oxide (8) with
required for disappearance of 1. Almost all of dimethyl 2d in dry ether was conducted to examine the electrostatic
phosphonate was removed in vacuo with the solvent. effect of the substituent on the benzoylphosphonates.
However, 3d was obtained in a lower yield of 55%.
Table VI. Benzoylation Using 88 0
Diisopropyl Benzoylphosphonate (1C) PhC-PEt, H,NCH,CH,CH, >- PhfNHCH,CHLH,
- ~ - +

product, 7’ % yield 8 2d 3d

amine timea 3 4C 5C This result indicates that alkoxy substituents are su-
2a Et,NH 10days 44 2b 49 perior to the alkyl substituent in the present acylation.
d n-PrNH, 18 h 86 72 13 Next, the reaction of bis(trimethylsily1) benzoyl-
h PhCH,NH, 20 h 87 74 7 phosphonate (9)23with 2d in ether was examined. In this
a Time required for (disappearance of 1C. Almost all case, however, a complex reaction occurred and 3d was not
of 4C was removed in vacuo along with the solvent in detected among the products.
order to make the separation of the products easy. 8;
PhC-P(OSiMe,), * 2d >- 3d

in a later section (see Table IV). 9

The substituent effect of the alkyl groups of esters (1) In consideration of these facts, suitable conditions for
was also examined. ‘Table V reveals that an increase in the practical use of benzoylphosphonates as acylating
the bulkiness of an a1kyl group resulted in an increase in agents can be summarized as follows. It is expected that
the yield of 3d. When bis(1-ethylpropyl) benzoyl- the use of 2 equiv of the most reactive dialkyl benzoyl-
phosphonate (lF), containing two bulky1 1-ethylpropyl phosphonate in n-hexane or cyclohexane might give the
groups, was employed in the stoichiometric reaction with optimum yield of benzamides. However, the most reactive
2d, 3d was obtained in a higher yield (92%). However, the dimethyl benzoylphosphonate, 1A, was extremely insoluble
time taken to reach th,e complete reaction was 4 days. The in both n-hexane and cyclohexane. Therefore, satisfactory
order of the bulkiness of alkyl groups based on various results were not obtained under these conditions. On the
physical parameters has been proposed by Taft20,21 to be other hand, 1B can be used in n-hexane or cyclohexane
as follows: Et2CH > sec-Bu > i-Bu > i-Pr > Et > Me. because it is partially soluble in n-hexane and soluble in
Table V indicates that the efficiency of the acylation by cyclohexane. When 2 equiv of 1A or 1B was used in any
use of LA-F was consistent with the bulkiness of alkyl of the solvents studied, a considerable amount of 1A or
groups as given above, except for i-Bu. Comparison of the 1B remained after the benzoylation. Decomposition of the
results obtained for IiB with those for 1C indicates that remaining dialkyl benzoylphosphonates into benzoic acid
the use of more hindered phosphonates enhanced the se- and dialkyl phosphonates was necessary before separation
lectivity of the acylation between primary and secondary of the products by chromatography. Treatment of 1A or
amines. The acylation of 2d with 1.2 equiv of 1C gave 3d 1B with aqueous tetrahydrofuran showed that 1A was
in maximum yield (95%), where 5 days was taken in order much more easily hydrolyzed than 1B under these neutral
to complete the reaciion (see Table 11). conditions. Therefore, it is recommended that the acyla-
In the reaction of 2 with 1, the side reaction to give 5 tion of primary and secondary amines with less steric
seemed to be catalyzed by amines and to depend on their hindrance should be carried out by using 1A in solvents
basicities. This is supported by the fact that an inde- such as ether. The conditions for the practical use of 1A
pendent reaction of 1Ei with 4B in the presence of 0.1 equiv in this direction are listed in Table VII.
The acylation of amines with less than 1.4 equiv of 1B
(20) R. W. Taft. Jr., ‘Steric Effects in Organic Chemistry”, M. S. is also recommended since under these conditions 1B
Newmann, Ed., Wiley, 1950, p 556.
(21) E. Kutler, C. Hansch, J . Med. Chem., 12, 647 (1969); M. Charton,
J . A m . Chem. Soc., 91, 615 (1969); “Advances in Linear Free Energy ( 2 2 ) H. Vorbruggen, Angew. Chem., Int. Ed. Engl., 17, 569 (1978).
Relationships”, J. Shoeter, N. B. Chapmann and J. Shorter, Eds., Plenum, (23) M. I. Kabachnik and P. A. Rossiiskaya, Izu. Akad. Nauk SSSR,
1972, p 71; S. H. Unger, C. Ilansch, Prog. Phys. Org. Chem., 12,91 (1976). Sei-. Khim., 364 (1945); Chem. Abstr., 40, 4688 (1946).
P-C Bond Cleavage of Dialkyl Acylphosphonates J . Org. Chem., Vol. 45, No. 21, 1980 4165

Table VII. 13enzoylation of Amines with to an aspirator. The vessel was kept under slightly reduced
Two Equivalents of pressure (100 mmHg) by the aspirator and then trialkyl phosphite
Dimethyl Benzoylphosphonate (1A) in Dry Ethera (0.15 mol) was added dropwise, at 0 "C, over a period of 30 min.
The mixture was stirred at room temperature for 30 min under
product, the same pressure. Distillation of the resulting oil gave a dialkyl
5% product,
amine yield amine % yield
benzoylphosphonate as a slightly yellow oil. 1A: 83%; bp 13s133
_ _ _ _ _ ~ . "C (1.1mm) (lit.4 bp 146 "C (2.5 mm)). 1B: 74%; bp 141-147
2b C,H,,NH, 98 f PhCH,CH,NH, 94 "C (3 mm) (lit." bp 142 "C (1 mm)). 1C: 72%; bp 117-120 "C
c n-BuNH, 96 h PhCH,NH, 99 (0.3 mm) (lit.'O bp 127 "C (0.8 mm)). 1D: 63%; bp 130-137 "C
(0.15 mm); IR (NaCl) 1658 cm-' (C=O); NMR (CDCl,) 6 0.97 (d,
d n-PrNH, e18 i 2 s h 94 6 H, J = 8 Hz, CHJ, 2.00 (m, 2 H, CH), 4.00 (t, 4 H, JH-H = Jp-H
= 6.5 Hz, CHJ, 7.26-7.80 (m, 3 H, m- and p-ArH), 8.15-8.45 (m,
2 H, o-ArH). Anal. Calcd for Cl6Hz3O4P: C, 60.39; H, 7.77.
e i-BuNH, 97 Found: C, 60.54; H, 7.76.
a All of the reactions were carried out a t room tempera- 1E: 59%, bp 136-140 "C (0.2 mm); IR (NaC1) 1658 cm-'
ture for 1 day. (C=O); NMR (CC14)6 0.91 (t, 6 H, J = 7 Hz, CHzCH3),1.32 (d,
6 H, J = 6 Hz, CHCH,), 1.55 (m, 4 H, CH,CH,), 4.51 (m, 2 H,
Table VIII. Acetylation of Amines with CH), 7.16-7.73 (m, 3 H, m- and p-ArH), 8.06-8.40 (m, 2 H, o-ArH).
Diethyl Acetylphosphonate (10) Anal. Calcd for Cl5HZ3O4P:C, 60.39; H, 7.77. Found: C, 60.42;
_________ H, 7.86.
vroduct. 1F: 62%; bp 134-135 "C (0.02 mm); IR (NaCl) 1658 cm-'
'% yield' (C=O); NMR (CC1,) 6 0.87 (m, 12 H, CH3), 1.65 (m, 8 H, CH.J,
time,a
amine solvent h 11 4B 12 4.35 (m, 2 H, CH), 7.17-7.66 (m, 3 H, m- and p-ArH), 8.00-8.43
(m, 2 H, o-ArH). Anal. Calcd for C17H2:04P: C, 62.56; H, 8.34.
2f PhCH,CH,NH, ether 1 72 50 24 Found: C, 61.68, H, 8.15.
h PhCH,NH, ether 3 64 54 18 Distillation of I F must be done carefully at lower bath tem-
a Time required for disappearance of 10 perature than 160 "C, because distillation at higher temperature
caused the decomposition of 1F to form dealkylated products with
disappears after the reaction and the procedure for the evolution of 2-pentene gas. The elemental analysis was somewhat
hydrolysis of 1B c a n be omitted. For the acylation of poor, indicating decomposition. After careful distillation, the
relatively less reactive amines s u c h as diethylamine, the compound was homogeneous by thin-layer chromatography and
use of 2 equiv of 113 and cyclohexane as the solvent is was used for benzoylation without further purification.
T r i s ( 1-ethylpropyl) Phosphite. A solution of 45.3 g (0.33
recommended. Under these conditions, 1B disappears mol) of phosphorus trichloride in 200 mL of dry ether was added
almost completely after the reaction since the reaction rate to a mixture of 88.2 g (1 mol) of 3-pentanol and 121 g (1 mol) of
is q u i t e fast. Thus, the yield of 3a increased to 92%. In N,N-dimethylaniline in 200 mL of dry ether at -20 "C over a
the case of bifunctional amines such as ethanolamine, period of 3.5 h. After the addition was complete, 200 mL of dry
sterically hindered l~enzoylphosphonatessuch as bis(1- ether was added and the mixture stirred a t room temperature
ethylpropyl) benzoylphosphonate (1F) a r e recommended overnight. After filtration to remove N,N-dimethylaniline hy-
(see Table IV). drochloride, 75 g of crude product, which was contaminated with
For the comparison of benzoylation with acetylation, two a small amount of bis(1-ethylpropyl) phosphonate, was distilled.
reactions of 2f and 211 with diethyl acetylphosphonate (10) Treatment of the distilled compound with 3 g of sodium metal
a t 150 "C for 6 h gave 56.4 g (58%) of pure tris(1-ethylpropyl)
were studied. Table VI11 shows that the yields of the phosphite, bp 68-73 "C (0.1 mm) (lit.24bp 94 "C (0.25 mm)).
$8 0 OH General Procedure for Stoichiometric Reaction of Diethyl
CH,C-P(OEt), ?NH, -------? CH,!NHR 48 CH,t[P(O)(OEt),],
+ + +
Benzoylphosphonate ( I B ) w i t h Amines (2) i n D r y Ether.
10 11
12 To a solution of 1.21 g (5 mmol) of 1B in 25 mL of dry ether was
added 5 mmol of an appropriate amine. The mixture was stirred
corresponding acetamides ( l l f and llh) were a little lower at room temperature and the reaction was monitored by TLC.
than those of the benzamides. In these reactions, 1 , l - After 1B had disappeared by TLC, solvent was removed and the
bis(diethoxyphosphory1)ethanol (12) was obtained as a residue applied to a silica gel column. Elution was performed
byproduct. with benzene-ethyl acetate. The isolated amides were identified
by comparison of their NMR and IR spectra with those of au-
Experimental Section thentic samples. The byproducts of 4A-F were characterized by
NMR spectra were measured a t 60 MHz on a Hitachi R 24-B their NMR spectra which showed the characteristic long-range
spectrometer. Infrared 3pectra were recorded on a Hitachi Model couplings between the hydrogen and phosphorus atoms of H-P(0)
EPI-G3 spectrometer. groups (JH-p = 690-709 H z ) . ~The
~ byproducts of 5A-F were
All of the amines employed were purified by distillation and also characterized by their NMR spectra which showed the distinct
stored over calcium hydride except 2-aminopyridine which was double doublets of a-hydrogens (CH-P) at 5.33-5.54 ppm coupled
recrystallized from benzene. with the different phosphorus atoms ( J H - p = 10.5-10.7, J H - p =
Benzoylphosphonates 1A-F were prepared by the Arbuzov 13.5-14.0 H Z ) . ~Yields
~ of all products are listed in Table I.
reaction of benzoyl chloride with trialkyl phosphites by a mod- Reaction of Excess Diethyl Benzoylphosphonate (1B) o r
ification of the procedure of K a b a ~ h n i k . ~ ~ Diisopropyl Benzoylphosphonate (IC) with o-Propylamine
Ether, benzene, n-hexane, and cyclohexane were purified by (2d). To a solution of 1B (6 mmol, 7 mmol, or 7.7 mmol) or 1C
distillation and stored over sodium wire. Tetrahydrofuran was (6 mmol) in 25 mL of dry ether was added 296 mg (5 mmol) of
distilled from sodium wire after reflux for 6 h, redistilled over 2d. The mixture was kept a t room temperature until 1B had
potassium hydroxide after reflux for 6 h, and finally purified by reacted. After the disappearance of lB, the solvent was removed
distillation from benzophenone ketyl. Dimethylformamide was and residue applied to a silica gel column. Elution was performed
purified by distillation and stored over molecular sieves. Pyridine with benzene-ethyl acetate. Yields of the products and times
was purified by distillation from p-toluenesulfonyl chloride and required for the complete reaction are listed in Table 11.
stored over calcium hydride. Methylene chloride was distilled Solvent Effects for t h e Acylation Vising Diethyl Ben-
after drying over P4010for 1 day, purified by redistillation from zoylphosphonate (1B). To a solution of 1.21 g (5 mmol) of 1B
potassium carbonate, and stored over molecular sieves.
General Procedure f o r the Synthesis of Dialkyl Ben- (24) H. R. Hudson and D. Ragoonanan, J. Chem. SOC.B, 1755 (1970).
zoylphosphonates. Benzoyl chloride (0.15 mol) was put in a (25) N. F. Chamberlain, "The Practice of NMR Spectroscopy", Ple-
two-necked flask with a dropping funnel and an outlet connected num, 1974.
4166 J. Org. C'hem., Vol. 45, No 21, 1980 Sekine e t al.

in 25 mL of an appropriate dry solvent was added 296 mg (5 mmol) bp 97-98 "C (0.03 mm); IR (NaCl) 1650 cm-' (C==O). Anal. Calcd
of 2d. The mixture was kept at room temperature with stirring for CllH1502P: C, 62.85; H, 7.19. Found: C, 62.31; H, 7.32.
until 1B had disappeared. Products, isolated according to the Bis(trimethylsily1) Benzoylphosphonate (9). T o 21.3 g
procedure described above, are listed in Table 111. (87.8 mmol) of 1B was added 40 mL (311 mmol) of trimethylsilyl
Benzoylation of D iisopropyl Benzoylphosphonate (IC) bromide.29 After the mixture was stirred at room temperature
with Ethanolamine (2g). To a solution of 1.41 g (5.22 mmol) for 5 h, distillation gave 30 g (80%) of 9, bp 113-115 "C (0.5 mm)
of 1C in 26 mL of tetrahydrofuran was added 319 mg (5.22 mmol) (lit.30bp 140-145 "C (3 mm)).
of 2g. The mixture was, kept with stirring a t room temperature. Reaction of Bis(trimethylsily1) Benzoylphosphonate (9)
After 3 days IC disappeared and the solvent was then removed with n-Propylamine (2d). A. To a solution of 1.65 g (5 mmol)
in vacuo. The residue was chromatographed on silica gel and of 9 in 25 mL of dry ether was added 296 mg (5 mmol) of 2d. A
eluted with benzene-ethyl acetate to yield 672 mg (78%) of 3g, white precipitate appeared gradually. After the mixture was
127 mg (9%) of 6, and 68 mg (3%) of 4B. The effects of the use stirred for 4 h, the solvent was removed and the residue was
of 1B in place of 1C are described in Table IV. dissolved in dimethyl-d, sulfoxide. The NMR spectrum in the
Substituent Effects of Alkyl Groups of Dialkyl Ben- solvent indicated that 3d was not formed.
zoylphosphonates in Benzoylation. To a solution of 5 mmol B. To a solution of 1.63 g ( 5 mmol) of 9 in 25 mL of dry
of an appropriate dialkyl benzoylphosphonate in 25 mL of dry n-hexane was added 591 mg (10 mmol) of 2d. A white precipitate
ether was added 296 mg (5 mmol) of 2d. The mixture was kept appeared immediately on addition of 2d. After the heterogeneous
at room temperature with stirring until the benzoylphosphonate solution was stirred for 12 h, the precipitate was collected by
disappeared by TLC. Chmplete conversion of the starting material filtration, washed with dry ether, and dried over P4Ol0in vacuo.
was required for separation of the benzoylated products from the The white powder was extremely hygroscopic and quite unstable
reaction mixture. Products were isolated by column chroma- om exposure to air. Its NMR spectrum in dimethyl-d, sulfoxide
tography on silica gel 21s described above. These results are in showed that ratio of phenyl, n-propyl, and trimethylsilyl groups
Table V. was 2:1:0.3. When the powder was dissolved in aqueous pyridine
Benzoylation of Amines by Diisopropyl Benzoyl- and chromatographed on "Avicel" plates by development with
phosphonate (IC). To a solution of 1.35 g (5 mmol) of 1C in several solvent systems (for example, i-PrOH-concentrated
25 mL of dry ether was added 5 mmol of an appropriate amine. NHIOH-HZO, 7:1:2 (v/v); BuOH-HZO, 84:16 (v/v); EtOH-1 M
The mixture was kept at room temperature with stirring until NH,OAc, 7:3 (v/v)), it was found to be homogeneous. The
1C disappeared by TLC. The products obtained after workup Hanes-Isherwood test31 was positive, indicating that the com-
are listed in Table VI. pound contained phosphorus. The R, values of the phospho-
Diethyl a-((Diethylphosphory1)oxy)benzylphosphonate rus-containing spots were consistent with those of unesterified
(5B). To a mixture of 48.4 g (0.2 mol) of 1B and 27.7 g (0.2 mol) benzoylphosphonic acid. These results indicate the formation
of 4B was added 2.8 mL, (0.02 mol) of triethylamine. The mixture of the mono-n-propylammonium salt of a-(n-propy1imino)-
was kept a t room temperature with stirring. The NMR spectrum benzylphosphonic acid which seems to deposit with n-propyl-
of the mixture after 1 h showed that 5B was formed in 8670 yield. ammonium trimethylsilyl e-(n-propylimino) benzylphosphonate
After 16 h, triethylamine was removed in vacuo. Distillation of although these could not yet be characterized sufficiently.
the oily residue under reduced pressure gave 50 g (66%) of 5B Practical Methods for the Benzoylation of Amines by
as a pure material, bp 170-190 "C (0.3 mm) (litz6183-184 "C (3 Dimethyl Benzoylphosphonate (1A). A. To a solution of 2.14
mm)). g (10 mmol) of 1A in 25 mL of dry ether was added 5 mmol of
Benzoylation of Diethylamine (2a) by Diethyl Benzoyl- an appropriate amine. The mixture was kept, with stirring, a t
phosphonate (1B) in the Presence of 4-(Dimethylamino)- room temperature for 24 h. The solvent and 4A formed were
pyridine (DMAP). To a solution of 1.21 g (5 mmol) of 1B and removed in vacuo a t 40 "C; the residue was treated with 30 mL
60 mg (0.5 mmol) of DMAP in 25 mL of dry ether was added 366 of tetrahydrofuran-water (50:1, v/v) at room temperature until
mg (5 mmol) of 2a. After 12 h, solvent and 4B, formed as by- excess 1A was completely hydrolyzed (usually 2-3 h). The aqueous
product, were removed in vacuo a t 40-50 "C. The residue was tetrahydrofuran solution was evaporated to dryness. The residue
chromatographed on silica gel and eluted with benzene-ethyl was dissolved in methylene chloride. Benzoic acid was extracted
acetate to yield 297 mg (46%) of 3a and 931 mg (49%) of 5B. with 5% NaHC03 (3 x 20 mL) and the organic layer was dried
Benzoylation of n .Propylamine (2d) with Diethyl Ben- over Na2S04,filtered, and evaporated. The residue was dissolved
zoylphosphonate ( l B ) in the Presence of Triethylamine. To in benzene and applied to a silica gel column. Elution was
a solution of 312 mg (5 3 mmol) of 2d in 26 mL of dry ether was performed with benzene or toluene-ethyl acetate. The yields of
added 1.28 g (5.3 mmol) of 1B and 0.74 mL (5.3 mmol) of tri- amides are in Table VII.
ethylamine. TLC showed that the acylation was complete within B. To a solution of 2.42 g (10 mmol) of 1B in 25 mL of dry
10 min. After 20 min, solvent and 4B formed were removed in cyclohexane was added 366 mg (5 mmol) of 2a. The homogeneous
vacuo at 4C-50 "C. A workup similar to that described above gave solution obtained was kept at room temperature with stirring until
646 mg (75%) of 3d, 206 mg (28%) of 4B, and 444 mg (22%) of 1B disappeared (24 h).
5B. Acetylation of Amines (2) with Diethyl Acetyl-
Ethyl Diethylphosphinite. To a solution of 23.5 g (160 mmol) phosphonate (10). T o a solution of 1.2 g (6.67 mmol) of 10 in
of ethyl d i c h l o r ~ p h o s p h i t ein~ ~200 mL of dry ether was added, 33 mL of dry ether was added 809 mg (6.67 mmol) of 2f. After
dropwise a t 0 "C, 160 mmol of the Grignard reagent (Et,Mg) the mixture was stirred at room temperature for 1 h, the solvent
obtained from ethyl bromide in 160 mL of ether-dioxane. After was removed in vacuo and the residue applied to a silica gel
the mixture was stirred at room temperature for 8 h, distillation column. Elution with benzene-ethyl acetate (l:l,v/v) gave a
gave 11.3 g (53%) of the title compound, bp 61-64 "C (72 mm) mixture of l l f (72%) and 4B (50%). Further elution with
(lit.28bp 80-85 "C (15 mm)). methanol-ethyl acetate (1:9, v/v) gave 514 mg (24%) of crude
Benzoyldiethylphosphine Oxide (8). To 7.3 g (52 mmol) 12,11,32
of benzoyl chloride was added dropwise 11 g (82 mmol) of ethyl
diethylphosphinite a t 3 "C over a period of 10 min. When the Registry No. lA, 18106-71-3;lB, 3277-27-8;lC, 22950-57-8;ID,
addition was coimplete, the mixture had become red. After the 74449-26-6; lE, 74449-27-7; IF, 74449-28-8; 2a, 109-89-7;2b, 108-
mixture was stirred a t room temperature for 30 min, distillation 91-8; 2c, 109-73-9;2d, 107-10-8;2e, 78-81-9;2f, 64-04-0;2g, 141-43-5;
gave 7.9 g of crude 8 (bp 107-109 "C (0.154.2 mm)). Redistillation
of the crude praduct gave 4.6 g (42%) of pure 8 as a yellow oil:
~

(29) P. A. McCuskev and E. L. Reillv, J . Am. Chem. Soc., 75, 1583

(1953).
(30) M. Sekine and T. Hata, J . Chem. Soc , Chem. Commun., 285
(26) A. N. Pudovik, I. V. Gur'yanova, and M. G. Zimin, Zh. Obshch. (1978).
Khim., 37, 2088 (1967). (31) C. S.Hanes and F. A. Isherwood, Nature ( L o n d o n ) , 164, 1107
(27) J. E. Malowan, D. R. Martin, and P. J. Pizzolato, Inorg. Synth., (1949).
4, 63 (1953). (32) (a) A. N. Pudovik and I. V. Konovalova, Dokl. Akad. N a u k SSSR,
(28) A. Razuman and 0. Mukhocheva, Zh. Obshch. Khim., 26, 1436 143, 875 (1962); Chem. Abstr., 57, 3480 (1962); (b) St. J. Fitch and K.
(1956). Moedritzer, J . Am. Chem. Soc., 84, 1876 (1962).
 J. Org. Chem. 1980,45, 4167-4168 4167

2h, 100-46-9;2i, 110-91-8;3a, 1696-17-9;3b, 1759-68-8;3c, 2782-40-3; 61-2; tris(1-ethylpropyl) phosphite, 19322-55-5; benzoyl chloride,
3d, 10546-70-0; 3e, 570647-7; 3f, 3278-14-6; 3g, 18838-10-3; 3h, 98-88-4; phosphorus trichloride, 7719-12-2; 3-pentanol, 584-02-1;
1485-70-7;3i, 1468-28-6; 4A, 868-85-9; 4B, 762-04-9;4C, 1809-20-7; ethyl diethylphosphinite, 2303-77-7; ethyl dichlorophosphite, 1498-
4D, 1189-24-8; 4E, 2283-25-2; 4F, 1809-15-0; 5A, 16115-01-8; 5B, 42-6; ethyl bromide, 74-96-4; trimethylsilyl bromide, 2857-97-8; N -
18104-91-1; 5C, 74449-2!3-9; 5D, 74449-30-2; 5E, 74449-31-3; 5F, benzoyl-N-cyclohexylbenzamide, 74449-32-4; N-benzoyl-N-butyl-
74465-43-3; 6,16180-99-7;8,33327-40-1;9,33876-85-6; 10, 3266-66-8; benzamide, 73491-45-9;N-benzoyl-N-propylbenzamide, 74449-33-5;
l l f , 877-95-2; l l h , 588-46-5; 12, 20427-93-4; trimethyl phosphite, N-benzoyl-N-isobutylbenzamide, 73491-46-0; N-benzoyl-N-phen-
121-45-9; triethyl phosphite, 122-52-1;triisopropyl phosphite, 116- ethylbenzamide, 74449-34-6;N-benzoyl-N-benzylbenzamide, 19264-
17-6;triisobutyl phosphite, 1606-96-8;tri-sec-butyl phosphite, 7504- 38-1.

Ther:mal Rearrangement of 5,6-Benzotricycl0[3.2.0.0~~~]hept-5-ene

into
2-V'inylindene via an Intramolecular Retro-Diels-Alder Reaction

Waldemar Adam*' and Ottorino De Lucchi

Department of Chemistry, Uniuersity of Puerto Rico, Rio Piedras, Puerto Rico 00931

Received February 19, 1980

Flash vacuum pyrolysis of the 5,6-benzotricyclo[3.2.0.0z~7]hept-5-ene (2a) a t ca. 400 "C at 0.7 torr afforded
quantitatively 2-vinylindene (6). Catalytic hydrogenation of 6 gave 2-ethylindane, thereby unequivocally confirming
the proposed 2-vinylindene structure 6, resulting from intramolecular retrocyclic Diels-Alder reaction of 2a. Singlet
oxygen and F'TAD led to the expected cycloadducts, respectively, the endoperoxide 7 and the urazole 8. It was
not possible to trap the postulated isoindene with PTAD.

A recent communication2 reports the synthetically Presently we report our results of this study.
valuable and mechanistically interesting thermal isomer- Preliminary thermolysis attempts on the parent tri-
ization of 3-(2-styryl)-substituted cyclopropene 1 into cycloalkene 2a in solution at elevated temperatures (>200
heptene 2, the di-x-methane rear-
benzotricyc10[3.2.0.0~~~] "C)led to a complex mixture of products. For this reason
rangement product3 of benzonorbornadienes 3 (eq 1). In we examined the vacuum flash pyrolysis by volatilizing 2
at ca. 60 "C and 0.7 mmHg through a hot Pyrex tube and
condensing the effluent in a dry ice cold trap. Exceedingly
high temperatures (ca. 400 "C)were necessary under these
conditions to effect the thermal decomposition of the
tricycloalkene 2, affording 2-vinylindene (6) in quantitative
yield (eq 2).

2a 5

4
6
3
Confirmation of the indene structure 6 rests on satis-
connection with our mlechanistic work4 on the thermal and factory elemental composition for CllHloby combustion
photochemical denitro'genation of azoalkane 4 as an entry analysis and lH NMR, IR, and UV spectral data (cf. Ex-
di-x-methane rearrangement 3 -
into the diradical intermediates that are postulated in the
2, we examined the
thermal stability and behavior of the tricycloalkene 2.
perimental Section). However, since reasonable mecha-
nisms can be envisaged for the production of the isomeric
3-vinylindene, it was essential to conduct chemical
transformations for rigorous confirmation of the proposed
(1) NIH Career Developinent Awardee (1975-80). Present address: 2-vinylindene structure 6. For example, on catalytic hy-
Institute of Organic Chemistry, University of Wurzburg, D-8700 drogenation (Pd/C) 6 was transformed quantitatively into
Wiirzburg/Am Hubland, West Germany. 2-ethylindane, as confirmed by comparison of the physical
(2) Padwa, A.; Rieker, W . F. J . Org. Chem. 1979,44, 3273.
(3)(a) Paquette, L. A,; Yeh Ku, A,; Santiago, C.; Rozenboom, M. D.; constants with the authentic material.5 Unequivocal as-
Houk, K. N. J . Am. Chem. SOC.1979, 101, 5972. (b) Yeh Ku, A,; Pa- signment of the hydrogenation product as 2-ethyl- rather
quette, L. A.; Rozenboom, Ad. D.; Houk, K. N. J . Am. Chem. SOC.1979, than 3-ethylindane could be made by 13C NMR. As ex-
101, 5981. ( c ) Santiago, C.;McAlduff, E. J.; Houk, K. N.; Snow, R. A.;
Paquette, L. A. J . Am. Chena. Soc. 1978,100,6149. (d) Paquette, L.A,; pected, the more symmetrical 2-ethyl isomer exhibits four
Cottrell, D. M.; Snow,R. A. ,I. Am. Chem. Soc. 1977,99,3723.(e) Snow,
R. A.; Cottrell, D. M ; Paquette, L. A. J . Am. Chem. SOC.1977,99,3734.
(4)Adam, W.; De Lucchi, 0.;Erden, I. Angew. Chem. 1979,91,4735. (5) Mizta, R. B.; Kulkarni, G. H.; Kharma, P. N. Synthesis 1977,415.

0022-3263/80/1945-4167$01.00/0 0 1980 American Chemical Society