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New Reactions of Alkylidenephosphoranes and their Preparative Uses. Part I The Acid-Base Character of Phosphonium Salts and Alkylidenephosphoranes

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N e w M e t h o d s i n Preparative Organic Chemistry IV
New Reactions of Alkylidenephosphoranes and their Preparative Uses
Part I : The Acid-Base Character of Phosphonium Salts and Alkylidenephosphoranes [**]
Phosphoniuni salts may be regarded as Bronsted acids, and aikylidenrphosphoranrs as
the conjugate bases. Compounds of the two classes exist in equilibrium with each other,
Phosphonium salts and alkylidenephosphoranes can be obtained by this “transylidation”.
Other methods are also given for the preparation of members of both classes.
Contents :
Part I. The Acid-Base Character of Phosphonium Salts and
A. Introduction
B. Phosphonium Salts and Alkylidenephosphoranes as
Conjugate Acid-Base Pairs
C. Transylidation
D. The Preparation of Phosphonium Salts and
I. Phosphonium Salts
2. Alkylidenephosphoranes
Part 11. Alkylidenephosphoranes and Halogen Compounds
A. Introduction
B. Reactions Involving Transylidation
1. C-Acylation of Alkylidenephosphoranes
2. Reaction of Alkylidenephosphoranes with Esters of
Chloroformic Acid. Synthesis of Carboxylic Acids
3. Reaction with Organic Halides and Carbonium Salts
4. Reaction of Alkylidenephosphoranes with Halogens
C. Reactions Involving p-Elimination
1. The Mechanism of the Hofmann Degradation of
Quaternary Phosphonium Salts
2. Synthesis of Esters of P-Acylacrylic Acids
3. Synthesis of Esters of a,$Unsaturated Carboxylic
D. Reactions Involving -[-Elimination
1. Reaction of Allylidenetriphenylphosphoranes with
Esters of Chloroformic Acid. Preparation of Esters of
Polyenecarboxylic Acids
2. Synthesis of Esters of Allenecarboxylic Acid
E. Reactions of AlkyIidenephosphoranes and Halogen
Compounds at a Molar Ratio of 1 : I
1. Synthesis of Esters of a-Branched-8-Keto Acids
A. Introduction
The discovery by Wittig and co-workers [I] that alkylidenetriphenylphosphoranes react with aldehydes and
ketones to form olefins and triphenylphosphine oxide
[“I The contributions in the previous three series have been
published collectively in three volumes by Verlag Chemie, WeinheimiBergstr.; English edition : Academic Press, New YorkLondon.
I**] Parts I1 and Ill will appear shortly in this journal.
Angew. Chem. internat. Edit. 1 Yo]. 4 (I965) 1 No. 7
2. Reactions with Diazonium, Nitrilium, and Oxoniuni
F. Intramolecular Ring Closure
1. Monocyclic Compounds
2. Polycyclic Compounds
Part 111. Alkylidenephosphoranes and Reactants Containing
Multiple Bonds
A. Reaction with the Carbonyl Group (The Wittig Reaction)
B. Reaction with the C--C Double Bond
1. General
2. Formation of Cyclopropane Derivatives
3. Michael Addition
4. Synthesis of Pyran Derivatives
C. Reaction with the C-N Double Bond
1. Wittig-Type Olefin Syntheses
2. Synthesis of Allenes
3. Reaction of Alkylidenephosphoranes with Phenyl
D. Reaction with Esters of Acetylenedicarboxylic Acid
E. Autoxidation of Alkylidenephosphoranes
I . Olefins from Primary Alkyl Halides or Alcohols
2. Olefins and Ketones from Secondary Alkyl Halides 0 1
3. Cyclization by Autoxidation of Bis-Ylides. Synthesis
of Monocyclic and Polycyclic Compounds
F. Oxidation with Peracids
G . Cleavage with Ozone
H. Other Reactions of Alkylidenephosphoranes
1. Reaction with Aliphatic Diazo Compounds
2. Reaction with Phenyl Azide
3. Reaction with Carbenes
4. Reaction of Ethoxycarbonylmethylidenetriphenylphosphorane with Epoxides
has supplied the incentive to a large number of investigations. The Wittig reaction has already been discussed
by Schollkopf [2] and by Tripperf [3], as well as by Bergelson and Schemjakin [4].
[la] G. Wittigand G. Geissler, Liebigs Ann. Chem. 580,44 (1953).
[Ib] G. Wittig and U . SchoNkopf, Chem. Ber. 87, 1318 (1954).
[lc] G . Wittig and W . Haag, Chem. Ber. 88, 1654 (19SS).
[2] Li. Sclrollkopf; Angew. Chem. 7f,260 (1959).
[3] S. Trippett in: Advances in Organic Chemistry. Vol. I, Interscience, New York 1960; Quart. Rev. 17, 406 (1963).
The aim of the present series of articles is to show that
the recently discovered reactions of alkylidenephosphoranes with polar compounds are also of interest in
preparative chemistry.
group [11,12]. Compound (8) is stable towards cold water,
since the ester group lowers the basicity and so hinders the
attack of a proton on the lone electron pair of the open C-P
double bond. The alkylidenephosphorane (8) decomposes
with water into methyl acetate and triphenylphosphine oxide
only on boiling.
+ H3C02C-CH=PR:
33. Phosphonium Salts and Alkylidenephosphoranes
as Conjugate Acid-Base Pairs
Strong bases eliminate HX from phosphonium salts ( I )
to form alkylidenephosphoranes (2). Staudinger 151
found that the Iatter in turn can add HX, with re-formation of the phosphonium salts ( I ) .
Thus phosphonium salts can be regarded as Bronsted
acids, and alkylidenephosphoranes as the conjugate
( 7 ) , ( 8 ) : R3 = C6H5;
( 9 ) , (10): R3 = Cyclohexyl
The acid and base strengths of (1) and (2) are also determined by R3. The electron-attracting inductive effect of the
three phenyl groups in (7) loosens the H atoms of the CH2
group. If the triphenylphosphine residue in (7) is replaced
by a tricyclohexylphosphine residue, the (-I) effect of the
three cyclohexyl residues in the phosphonium bromide (9)
strengthens the CH bonds of the methylene group. The deprotonation of (9) can no longer be effected with sodium
carbonate solution, but requires the use of dilute sodium
hydroxide solution [12].
Methoxycarbonylmethylidenetricyclohexylphosphorane (10)
is more strongly basic than the triphenyl compound ( 8 ) . In
contrast t o (S), (10) decomposes simply on standing for a
short time in cold water.
The basicity of the ylides (2) is also apparent in their
reaction with water [lb, Ic, 2, 6,7], in which addition of
a proton to the free electron pair of the open C-P double
bond leads to formation of the phosphonium hydroxide
C . Transylidation
Since phosphonium salts and alkylidenephosphoranes
are related as an acid-base pair, and since the strength of
these acids and bases is governed by R1 and R2, an acidbase equilibrium is set up between alkylidenetriphenylphosphoranes (11) and triphenylphosphonium salts
(121 D31.
+ [R2-CH2-P(C6H5)31
The hydroxides (3) decompose via the compounds (4)
of pentavalent phosphorus into a hydrocarbon ( 5 ) and
a phosphine oxide (6) [8,9]. The ligand eliminated from
the phosphorus atom of (3) as a hydrocarbon is always
the most strongly electronegative or the most highly
resonance stabilized of the four [9,10].
The acid-base strength of the phosphonium salts ( I ) and the
alkylidenephosphoranes (2) depends mainly on R1 and R2.
Electron-attracting groups increase the acidity of the phosphonium salt ( I ) and lower the basicity of the corresponding
ylide (2). Thus dilute sodium carbonate solution is sufficient
to precipitate the ylide (8) from an aqueous solution of triphenylmethoxycarbonylmethylphosphonium bromide (7),
which is a very strong acid owing t o the presence of the ester
+ R~-CH=P(C~HS)~
The position of the equilibrium is governed by the residues R1 and R2. If the basicities of (11) and (14) or the
acid strengths of (12) and (13) are very different, the
equilibrium always favors the formation of the more
weakly basic alkylidenephosphorane and the more
weakly acidic phosphonium salt. Thus the reaction of
methylidenetriphenylphosphorane (15) with triphenylphenacylphosphonium bromide (16) yields triphenylmethylphosphonium bromide (17) and benzoylmethylidenetriphenylphosphorane (18) in almost 90 % yield.
This is an example of a reaction which we shall refer to
as transylidation.
H ~ C = P ( C ~ H S )[H5C6-CO-CH2-P(CsH5)3]
141 L . D. Bergelson and M. M . Schemjakin, Angew. Chem. 76.
113 (1964); Angew. Chem. internat. Edit. 3, 250 (1964).
[5] H . Staudinger and J. Meyer, Helv. chim. Acta 2, 635 (1919).
[6a] G. I.iischer, Doctorate Thesis, E.T.H. Zurich 1922.
[6b] H. Issler, Doctorate Thesis, E.T.H. Zurich 1924.
171 D. D. Coffmanand C . S. Marvel, J. Amer. chem. SOC. 51,3496
( 1 929).
[8] J. Meisenheimer, J . Casper, M . Horing, W. Lauter, L . Lirhtensfadt, and W. Samuel, Liebigs Ann. Chem. 449,213 (1926).
191 G. W. Fenton and C . A.' Ingold, J. chem. SOC.(London) 1929,
[lo] L . Hey and C. K. Ingold, J. chem. SOC.(London) 1933, 531 ;
L. Horner, H . Hoffmann, H. G. Wippel, and G. Hassel, Chem. Rer.
91, 52 (1958).
( 15)
' [ H ~ C - P ( C S H ~BrQ
) ~ ] + H5C6-CO-CH=P(C6H5)3
Transylidation provides a method of comparing the
strengths of the mesomeric or inductive effects of the
substituents on the acidity of the methylene group 0: to
[ I 11 0 .Isler, H. Gutmann, M . Montavon, R. Riiegg, G . Rwer, and
P . Zeller, Helv. chirn. Acta 40, 1242 (1957).
[ I21 H. J. Besrmann and 0 . Kratzer, Chem. Ber. 95, I894 (1962).
[I31 H. J. Bestmann, Chem. Ber. 95, 58 (1962).
Angew. Chem. internat. Edit. / Vol. 4(1965)
No. 7
the P atom in the phosphonium salt or on the basicity of
the alkylidenephosphorane. Such a comparison gives
the sequence :
> COzCH3 > C6Hs > alkyl
The reaction of phosphoniurn salts
A phosphonium salt (21) is obtained from an alcohol by
reaction with triphenylphosphonium halides (22) (preferably the bromide). Triphenylphosphonium bromide
(22), X = Br, adds onto the ends of many polyene
chains by w,w'-addition. Thus 1,6-addition of the
bromide (22), X = Br, to the triene (23) leads to the
phosphonium salt (24) [16].
with alkylidenephosphoranes R ~ - C H = P ( C ~ H Sin
which R2 lies to the right of R1 in the above series
leads to transylidation.
Experiments with phosphonium salts labelled with tritium have shown that transylidation also takes place if
R1 and R2 in (11) and (12) are identical, or if the inductive or mesomeric effects of R1 and R2 differ only
slightly [13].
Procedure :
Preparation of Benzoylmethylidenetriphenylphosphorane
by Transylidation [131
Finely powdered triphenylphenacylphosphonium bromide
(16) (9.24 g), which has been dried in vacuum over P205,
is added to a salt-free solution (see Section D 2 for preparation) of 0.02 mole of methylidenetriphenylphosphorane (15)
in 100 ml of anhydrous toluene 1141, and the mixture is
refluxed for 24 h in the absence of moisture and oxygen. The
benzoylmethylidenetriphenylphosphorane (18) is filtered off,
the precipitate is washed with toluene, and the solution
is evaporated in vacuum. The crystalline residue is mixed
with 15 to 20 ml of ethyl acetate and filtered. A small second
fraction is obtained by slow evaporation of the filtrate. Total
yield 6.65 g (87.5 %); m.p. and mixed m.p. with benzoylmethylidenetriphenylphosphorane 180 O C .
The salt filtered o f ffrom the solution in ethyl acetate weighs
7.8 g. It is dissolved in 60 ml of water by warming, and the
pH of the solution is adjusted to 13-14 with dilute sodium
hydroxide solution, whereupon 0.65 g of (18), formed from
unchanged triphenylphenacylphosphonium bromide ( I 6 ) ,
precipitates. This is filtered off, and the aqueous solution is
acidified with acetic acid, heated to boiling, and a solution
of 3 g of NaI in 10 ml of water is added. Triphenylmethylphosphonium iodide crystallizes o n cooling; yield 4.9 g
(60.8 %), m.p. and mixed m.p. 182'C (from isopropanol).
Phosphonium salts can also be obtained from compounds containing polarized C-C double bonds (e.g.
cr,P-unsaturated nitriles, esters of carboxylic acids (25),
and nitro compounds) by reaction with the bromide (22),
X = Br [17].
The reaction of quaternary ammonium salts of Mannich
bases (26) with triphenylphosphine also allows the preparation of phosphonium salts (27) which are difficult
or impossible to obtain by other methods [18].
+ P(C~HS)~
New possibilities in the preparative field are opened up
by additions to vinylphosphonium salts (28) 1191 and to
phenylethynylphosphonium salts (29) [20].
3 [(C4H&P-CH=CHz]Br@ + H3C-CO-C6H5 --c
D. Preparation of Phosphonium Salts and
3 Bra
1. Phosphonium Salts
Phosphonium salts (21) are generally prepared from
alkyl halides (19) and triphenylphosphine (20) [2].
+ P(C&5)3
The following method is of great preparative interest
+ [H-P(C6Hs)3IXs
+ [R-P(c6H5)3]xa
+ H20
(141 F.Ramirez and S.Dershowitz, 22, 41 (1957).
[I51 German Patent 1046046 (Dec. llth, 1958), BASF, inventors: W . Sarnecki and H. Pommer.
1161 H. Pommer, Angew. Chern. 72, 81 1 (1960).
Angew. Chem. internut. Edit. 1 VoI. 4 (1965) 1 No. 7
The possibility of synthesizing phosphonium salts from
alkylidenephosphoranes and halogen compounds is discussed in Part 11.
[I71 H. Hoffmann, Chem. Ber. 94, 1331 (1961).
[181 H . Hellmann and 0. Schumacher, Liebigs Ann. Chem. 640,
79 (1961).
I191 P.T . Keorrgh and M.Gruyson, 29,631 (1964).
[201 H.Hoflmnnn and H.Forsrer,Tetrahedron Letters 1964,983.
F-MethoxyethyltriphenylphosphoniumBromide [151
A mixture of 34 g of triphenylphosphonium bromide (22),
= Br, and 8 g of glycol monomethyl ether is refluxed for
7 h with 50 g of anhydrous tetrahydrofuran. When the
reaction mixture is cooled, 17 g of B-methoxyethyltriphenylphosphonium bromide (ZI), R = H ~ C - O - C H ~ C H Zm.
, p.
216OC, separates out. A further 7 g is obtained by concentration of the mother liquor.
phosphorus atom can lead to decomposition of the initially
formed ylide into an olefin and triphenylphosphine by intermolecular proton migration [221 (cf. also Part 11, Section C 1,
o n the Hofmann degradation of quaternary phosphonium
salts). In such cases, sodium alkoxides should not be used as
bases, since these compounds strongly favor the Hofmann
degradation [22].
Ylides are also formed from triphenylphosphine and
carbenes (30). Alkylidenephosphoranes with halogen
atoms on the C-atom a to the C-P double bond have
become available by this method [23,24].
Phosphonium Salts from Compounds Containing
Activated Double Bonds and Triphenylphosphonium
Bromide [17]
Method a : 2.62 g (10 mmok) of triphenylphosphine (20)
and 10 mmole of the component containing a n activated
double bond are heated with stirring at 100 "C with 5 ml of
4 8 % aqueous HBr for 5-15 min. The mixture is then
diluted with about 10 ml of water, extracted with ether to
removeany unchangedstarting materia1,and the phosphonium
salt is allowed to crystallize or is extracted with chloroform,
depending on its solubility. Iodides can be precipitated by
addition of excess Nal.
Method b: 3.4 g (10 mmole) of triphenylphosphonium
bromide (22), X = Br, and 10 mmole of the component
containing an activated double bond are heated in 5 ml of
acetonitrile for 5-15 min on a boiling water bath. The
phosphonium salt is then precipitated with ethyl acetate or
ether, and purified as described under a.
Aliphatic diazo compounds can also be used as sources
of carbenes for the preparation of ylides. However, they
must be decomposed in the presence of copper salts [251,
since the reaction Of diazo compounds with triphenylphosphine generally leads to phosphazines (31) 1261.
+ INEN-CR~ - -
-+ ( C ~ H ~ ) ~ P = C+RN2
The diha~ogenomethylidenephosphoranes(32) are also
readily obtainable by the reaction of triphenylphosphine
with carbon tetrachloride or carbon tetrabromide [27].
Skatyltriphenylphosphonium Methylsurfate [ 181
Three grams of gramine methylsulfate is boiled with 15 mmole
of triphenylphosphine (20) in 30 ml of methanol for 90 min
under nitrogen (trimethylamine is liberated). The precipitatc
formed on cooling is washed with methanol, and can be
recrystallized from water to give a pale pink salt, m.p. =
185- 186 OC.
The reaction of acrylic acid derivatives (33) with triphenylphosphine leads to ylides (34) which can be
intercepted with carbonyl compounds by a Wittig reaction [28], and which are difficult to obtain by other
methods owing to the ease with which the Hofmann
degradation takes place.
2 . Alkylidenephosphoranes
The best method of preparing alkylidenephosphoranes
is the action of bases on phosphonium salts [(1)+(2)]
(see Section B). The strength of the base necessary for deprotonation depends on the acidity of the phosphonium
salt. A base recently found to be particularIy useful is the
methylsulky1 carbanion obtained from dimethyl sulfoxide and sodium hydride and used in dimethyl sulfoxide as solvent [21a].
In many of the reactions described below, it is important
that the ylide solutions used should be free from lithium
salts, since these react with the ylide to form complexes
which strongly interfere with the reaction. The most
suitable method for the preparation of such solutions
is the sodamide method [21b] described below.
Schollkopf [2] has made reference t o elimination reactions
which can hinder ylide formation. The action of bases o n
phosphonium salts containing activated hydrogen p t o the
[2la] R. Greenwald, M . Chaykovsky, and E. J. Corey, J. orp.
Chemistry 28, 1128 (1963).
[21b] G . Wittig, H . Eggers, and P . Duflner, Liebigs Ann. Chem.
619, 10 (1958).
R = -COzR';
-CONH2; -C_N
[22] H . J. Bestmann, H . Haberlein, and I. Pils, Tetrahedron 20,
2079 (1964).
[23a] A. J. Speziale, G . J . Marco, and K. W. Ratts, J. Amer. chem.
SOC.82, 1260 (1960); A. J . Speziale and K . W . Ratts, ibid. 84,
854 (1962).
[23b] D.Seyferrh, S. 0. Grim, and T.0.Read, J. Amer. chem. SOC.
82,1510 (1960); D.Seyferth and S.O.Grim, ibid. 83, 1610 (1961).
[24] G . Wittig and M . Schlosser, Angew. Chem. 72, 324 (1960);
Chem. Ber. 94, 1373 (1961).
1251 G. Wittig and M . Schlosser, Tetrahedron 18, 1023 (1962).
[26a] H . Staudinger and J. M e p r , Helv. chim. Acta 2, 619 (1919).
[26b] H . Staudinger and G. Luscher, Helv. chim. Acta 5,75 (1922,.
[26c] G. Wittig and W. Haag, Chem. Ber. 88, 1654 (1955).
[26d] H . J. Bestmann, H. Bucksch'wski, and H. teube, Chem. Ber.
92, 1345 (1 959).
[27] R. Rabinowitz and R. Marcus, J. Amer. chem. SOC.84, 1312
(1962); F. Ramirer, N . B. Desai, and N . McKelvie, ibid. 84, 1745
( 1962).
[28] R. Oda, T. Kawabata, and S. Tanimoto, Tetrahedron Letters
1964, 1653. Cf. also the analogous formation of ylide from triphenylphosphine and maleic anhydride: R. F. Hudson and P. A .
Cliopard, Helv. chim. Acta 46, 2178 (1963).
Angew. Chem. internat. Edit.
Vol. 4(1965)
I NO. 7
Alkylidenephosphoranes are also formed on thermal
decomposition of triphenyl-cr-methoxycarbonylalkylphosphonium salts (35) [29].
with mercury. The solid residue is then filtered off using rl
G-3 frit. The filtration can be dispensed with if the subsequent
reactions are not affected by excess sodamide and undissolved
sodium halide.
Preparation of' Ylide Solutions by the
DimethylsulJinate Method
The ylides formed can be isolated if they are stable. They
can also be intercepted by various reagents, or undergo
intramolecular reactions.
Procedures :
Salt-free Alkylidenephosphorane Solutions
All operations are carried out under nitrogen or argon.
Ammonia is condensed in a trap cooled with liquid air and
containing sodium. The resulting dry ammonia is distilled
into a second tube (75- 100 ml), and the required quantity of
excess) and a few grains
finely chopped sodium (up to 25
of ferric nitrate are added. When the blue sodium solution
has turned grey, the absolutely dry and finely powdered
phosphonium salt is added, stirred for a short time with a
glass rod, and the ammonia is then evaporated off through
a mercury valve. The evaporation is accelerated by heating
the tube with hot air. To the residue is added 100 ml of an
inert, anhydrous solvent, e.g. benzene, toluene, ether, or
tetrahydrofuran, and the solution is boiled for about 10 min
to remove residual gas, the reflux condenser being sealed
_ - - ~ .. .
I291 H . J . Bestmonn, H. Hortimg, and I. Pils, unpublished work.
The preparation must be carried out under nitrogen and i n
the strict absence of moisture. The stoichiometric quantity of
sodium hydride (as a 50 % suspension in mineral oil) is freed
from mineral oil by repeated washing on a sintered glass
filter with anhydrous petroleum ether, and placed in the reaction vessel. Dimethyl sulfoxide (dried over calcium hydride) is
added (50 ml of dimethyl sulfoxide per 100 mmole of NaH),
a reflux condenser with a mercury valve is fitted to the vessel,
and the mixture is slowly heated to 70-80 ' C , with stirring
(magnetic stirrer). The evolution of hydrogen stops after
about 45 min. The resulting solution of the dimethyl sulfoxide
anion is cooled in ice and the solution or suspension of the
phosphonium salt in dimethyl sulfoxide (50 mmole of salt
in about 100 ml of dimethyl sulfoxide) is added. The mixture
is stirred for a further 10-20 min at room temperature before
being used for further reactions.
Chloromethylidenetr@henylphosphorane Solution [24b]
A solution of 40 mmole of butyl-lithium in about 25 ml of
anhydrous ether is added dropwise, over a period of 40 min,
to a well-stirred solution of 35 mmole of triphenylphosphine
in 45 ml of absolute methylene chloride at -60 ' C . The resulting solution of the chloromethylidenetriphenylphosphorane
is then used for further reactions.
Received: November Znd, 1964 [A 443a/231 I€]
German version: Angew. Chem. 77, 609 (1965)
Translated by Express Translation Service, London
Melting and Crystal Structure - Some Current Problems
The "classical" definition of liquid and solid phases acording to mechanical criteria is
unsatisfactory. It is now known that ''premeltinp'' efects occur in crystals, and in many
liquids the formation of clusters is observed near the melting point, with structures which
can correspond to the short-range order of the crystals from which the melt is derived. -In particular, the implications of the theories of Lennard-Jones and Devonshire and of
Mizushima and Ookawa are discussed.
As is now well known, many melts have structures which
resemble the crystals from which they are formed more
or less closely. This is shown, for example, by the similarity of density. X-ray diffraction shows, too, that the
interatomic or intermolecular distance in many melts is
quite close to that in the crystals. However, the conventional radial distribution function of melts gives data
which are far too condensed to be really informative.
Methods are required which give a three-dimensional
representation of regions or domains in the liquid, as a
Angew. Chem. internnt. Edit. 1 Vol. 4(1965)
No. 7
counterpart to the elaborate three-dimensional information usually available about the crystals.
This gap i n o u r direct structural knowledge about the molecular arrangements in melts is a serious obstacle to systematic
development of theories of the liquid state. It has tended
to direct mathematical theories to the discussion of
liquids whose units of structure are extremely simple, such
as atoms or diatomic molecules [I]. Actually, such melts form
only a minute fraction of the range of known liquids; their
[ I ] K . Fiirukawo, Rep. Progr. Physics 25, 396 (1950).
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