Note: Descriptions are shown in the official language in which they were submitted.
~L2Z7~
This invention relates -to a new preparative
process for obtaining 3,4-dihydro-~-pyrones of the
formula:
< 3
H (I)
owe
lo wherein Al, R2 and R are the same or different and each
stands for hydrogen or an alkyd group with l to lo C-
atoms, as well as the new compounds serving as starting
materials which are of the formula:
Al H (IIa,b)
H I
R
wherein Al, R2 and R3 have the foregoing meaning and R4
denotes the group
O O O
I 5
-O-C-H, OKAY --C-c2H5 or -O-R ,
wherein R5 stands for a lower alkyd group.
Compounds of formula (I) are known from German
Offenlegungsschrift 29 52 068, although there the prepare-
lion from substituted dihydro-5-hydroxymethyl-furanones is
indicated for the one denoted preparative process.
The present invention in particular provides a
process for the preparation of 3,4-dihydro-~-pyrones of
the formula (I): '
. .
71~)S
Al R2
O
wherein Al, R2 and R3 are the same ox different and each
stands for hydrogen or alkyd groups with 1 to 10 C-atoms,
which is characterized in that a compound of the formula
2 3
lo 7
Al l H
Ho (II)
R4
- wherein Al, R2 and R3 have the foregoing meaning and R4
denotes the groups O O O or
, " - 5
-OKAY OKAY OKAY -O-R
wherein R stands for lower alkyd groups, is heated.
According to the process, the residue is prefer-
ably -O-C-H, next in importance being the residue -C-CH3.
O O
The lower alkyd group of R5 can contain 1 to 4 preferably
1 to 3 C-atoms. Preferably one or two of the residues Al,
R and R3 are alkyd residues.
An advantage of the process is the easy access
sublet of the new substances of formula (II), or otherwise
the reduction by one step of the preparation, as well as
high yields and good purity.
The reaction is possible in the temperature region
of 150 to about 650C, and is however preferably carried out
in the temperature region of 200 to 500C. Should one
choose a lower temperature, then the reaction is slow.
Conveniently, the starting material is dripped
-- 2 --
~L.22~78~
through a heated tube filled with temperature resistant
material. The reaction is preferably carried out in an
inert gas atmosphere at normal pressure or reduced pressure,
generally between 10 3 and 1 bar The temperature resistant
filler material can be an inert substance such as glass,
ceramic or the like. Preferably, silicates and alumina-
silicates such as montmorilloni.te or zealot are used as
filler materials; these act as catalysts so that good con-
versions are already achieved at temperatures of 200 to
300C.
The starting materials can be employed in admixture
with one another or also in admixture with dodder hydroxy-
methyl-furanones of the formula
R2 R3
Al H
WHOOSH o (Tic)
20 wherein the substituents Al to R3 are identical with those
of formula (II).
The starting materials can be employed as such or
in solution. Temperature stable compounds such as for
example Bunsen, Tulane, zillion are preferably to be con-
ridered as solvents. The working up and purification of the compounds of formula (I) preferably takes place by
distillation.
The starting compounds of the formula (II):
2 R3
1 H
H 2 ISSUE I
R4
. ,
- 3 -
~2~7~3~1S
wherein Al, R2 and R3 are the same or different and each
stands for hydrogen or an alkyd group with 1 to 10 C-atoms~are
new. In the case of the esters of formula (Ire at least
one of the residues Al, R2 or R3 is such an alkyd group and
R4 the residue 0 0 0 or
.. ..
-0-C-H, 0-C-CH3~ -0-C-C2H5 -0-R5
wherein R stands for lower alkyd groups. The residue R
preferably has 1 to 4 carbon atoms.
Of particular interest as starting compounds, are
the substituted lactones of the formula (Ida):
R2 R3
H
R
H21C (Ida)
R4
1 2 3
wherein R , R and R are the same or different and each
stands for hydrogen or an alkyd group with 1 to 10 C-atoms,
wherein at least one of the residues R1, R2 or R3 is such
an alkyd group and R denotes the residue
O O O
l l if 11
-0-C-H, -0-C-CH3 or -0-C-C2H5.
Also of interest as starting compounds, are the
lactones of the formula (IIb~2 R3
Al ) ( H
Jib
R50
wherein Al, R2 and R3 are the same or different and each
stands for hydrogen or an alkyd group with 1 to 10 C-atoms
and R5 denotes an alkyd group with 1 to 4 C-atoms.
isles
The formic acid, acetic acid and proplonic cold
esters of -the formula Ida, as well as the corresponding
esters wherein R1, R2 and R3 denote hydrogen, can be pro-
duped from penten-4-carboxylic acid esters of the formula
(III)
R OR OR
H2C=CH - C - OH - COO (III)
wherein Al, R2 and R3 have the same meaning as in formula
(Ida) and R6 is an alkyd residue of 1 to 10, preferably 1
to 4 carbon atoms or an alkenyl residue with 2 to 10 C-atoms,
by reaction with hydrogen peroxide and an acid, said acid
being formic, acetic or prop ionic acid; subsequently referred
to as process A.
The carboxylic acids can be employed in amounts of
2 to 20 mow per mow of pontoon carboxylic acid ester.
Hydrogen peroxide can be employed as aqueous solution. 0.9
to 1.1 mow of H202 per mow of pontoon carbolic acid ester
should be employed. The temperatures can lie between 20~C
and the boiling point of the reaction mixture.
The compounds of formula Jib i.e. with Wrier,
can be obtained by reaction of dihydro-5-halomethyl furanones
of the formula
R2 R3
25 Al H
/ \ (IV)
X-CH2 O X = Of, By
in which Al, R2 and R3 are the same or different and each
denotes an alkyd group with 1 -to 10 C-atoms or H, with a
suitable base and an alcohol of the formula R50H. Suitable
bases are of the alkali or alkaline earth metal hydroxides,
oxides, carbonates and alkali or alkaline earth metal
alcoholates of the alcohols R50H in at least equivalent
-- 5 --
I
amounts. Preferred are the alcoholates.
An excess of 0.1 to 1 equivalents of base is con-
lenient. The -temperatures lie between 20C and the boiling
point of the reaction mixture.
Within the framework of the invention, methyl and
ethyl are preferred among the alkyd residues. Furthermore
one or two of the groups Al, R2 and R are preferably
hydrogen.
The substituted penten-4-carboxylic acid esters
are obtainable by reaction of correspondingly substituted
azalea alcohols with correspondingly substituted orthoacetic
- acid esters (Tetrahedron Letters ~1977), page 2543).
The substituted dihydro-5-halomethyl furanones can
be obtained in the manner set out in German Offenlegungsschrift
29 52 068.
The substituted pureness and furanones are important
intermediate products for, inter alias insecticides.
A process for the preparation of lactones, that
is substituted or unsubstituted dihydro-5-hydroxymethyl-
furanones of the formula (Tic)
R2 R3
H
Ho O (Tic)
Hi .
wherein Al, R2, R3 are the same or different and each denotes
hydrogen or an alkyd group with 1 to 10 C-atoms from the
penten-4-carboxylic acid esters of the formula (III) or the
carbolic acid esters of the lactones of formula (Ida), will new be described.
As already indicated, the thus prepared 5-hydroxy-
methyl-lactones of formula (Tic) can serve for the preparation
of the 3,4-dihydro-~-pyrones.
Al
6 -
Lowe
The substances of formula icky) are already known
from German Offenlegungsschrift 29 52 068, but they are
prepared in a completed manner. The preparation of the
basic substrate, that is the unsubstituted 5-hydroxymethyl
forenoon is known from Chum. Abstr.Vol.87 (1977) 151575 w,
(Research Bulletin of Miss University No. 13 (1977) pages
31 to 38), by reaction of penten-4-carboxylic acid bottle
ester in a very large amount of carboxylic acids, with HOWE,
wherein however the hydrolysis of the 5-carboxy-4-pentanolide
with aqueous alkali required an at least equivalent amount of
alkali metal hydroxide. The product can only be obtained by
an involved extraction and in low yield.
There existed therefore the object of producing
unsubstituted and alkyd group-substituted dihydro-5-hydroxy-
methyl furanones simply with low amounts of starting materials
and auxiliary materials as well as high space-time yields and
moreover with use of HOWE, although preferably with avoidance
of the dangers encountered with HOWE.
The process for the preparation of lactones of
the formula:
I R3
Rl~H
1 (Tic)
SUE ~~~
HO
wherein Al, R2 and R3 are the same or different and each
denotes hydrogen or an alkyd group with 1 to 10 C-atoms, in
characterized in that a compound of the formula
~2R3
I H (III)
CRY
-- 7 --
, .~.
7~0~
wherein R1, R2 and R3 have the above indicated meanings and
R6 stands for an alkyd group with 1 to 10 C-atoms or an
alkaline group with 2 to 10 Caroms is reacted with an
acid, said acid being formic acid, acetic acid or prop ionic
acid and an aqueous HOWE solution and after removal of the
water and excess amounts of carboxylic acid, the ester
obtained (i.e. of formula (Ida)) is, then, without further
isolation thereof,
I) heated after addition of an aliphatic saturated alcohol
with 1 to 10 C-atoms in the presence of an acidic or
basically acting catalyst, or
I) in the case of an obtained formic acid ester is decarbon-
slated without addition of an alcohol, with the exception
of the alcohol optionally used as solvent for the alcohol,
by heating with a catalytic amount of an alkali metal or
alkaline earth metal alcohol ate
to form the desired dihydro-5-hydroxymethyl forenoon;
revered to subsequently as process B.
Another process for the preparation of lactones
of formula (Tic):
R3
1 ) H
Ho (Tic)
wherein Al, R2 and R3arethe same or different and each
denotes hydrogen or an alkyd group with 1 to 10 C-atoms,
characterized in that a compound of the formula (Ida)
H
Ho (Ida)
-- 8 --
~L~2~7~3C35i
wherein Al to I have the above meaning and R4 denotes the
group O O O is
"
-Okra OKAY or OKAY
- I) heated after an addition of an aliphatic saturated alcohol
with 1 to 10 C-atoms in the presence of an acidic or
basically acting catalyst, or
I) in the case of the formic acid ester of formula (Ida)
wherein R4 denotes a Al is decarbonylated without
addition of an alcohol, with the exception of the alcohol
lo optionally as solvent for the alcohol ate, by heating with
a catalytic amount of an alkali metal or alkaline earth
metal alcohol ate
to form the desired dihydro-5-hydroxymethyl forenoon; revered
to subsequently as process C.
In the preparation of the dihydro-5-hydroxymethyl furanones
from the penten-4-carboxylic acid esters or the acid esters of dodder-
hydroxymethyl furanones, according to procedure I) of process
B or C, only catalytic amounts of basic or acid substances
are used. Procedure I) according to process B or C, wherein
only catalytic amounts of alcoholates are employed is strongly
preferred. For both procedures according to process B or also
process C, the formic acid esters according to procedure I)
are necessary, and according to procedure I) very much
preferred.
The process according to process B may be explained
with reference to the reaction with formic, acetic or prop-
onto acid like the process A, so that what is said there is
also valid here.
Accordingly, according to process B, 1.3 to 20 mow
of carboxylic acid and 0.9 to 1.2 mow of HOWE as aqueous
solution can be used per mow of pontoon carboxylic acid ester.
Preferably less than 2.5 molt related to the starting compound
of formula IT of said acid is employed, said acid being
9 _
3!L;~Z~7~3~1r;
formic acid, acetic acid or prop ionic acid. According to
process B, as for process A, 1.01 to 1.05 Molly of HzO2 are
preferred per mow of strutting substance. Preferably the
aqueous HOWE solution possesses an HOWE content of less than
35% by weight. Insofar as a starting substance with an
alkaline residue as residue R6 is used, the amount of HOWE
is approximately to be doubled in the general range and the
preferred range. The temperature according to process B
and process A is between 20C and the boiling point of the
reaction mixture, preferably I and 80C.
The manner in which pontoon carboxylic acid ester
of unsaturated alcohols may be used, which has been found,
is advantageous since these otherwise deposited substances
were hitherto not usable.
Lo Formic acid, among the carboxylic acids for use as
starting substance according to process A and process B as
well as the formic acid esters of dihydro-5-hydroxymethyl
forenoon as starting material according to process C is
very much preferred.
According to process A and process B, the water
and the excess of carboxylic acid is to be removed as come
pletely as possible, if appropriate by distillation. Should
the removal not be completely achieved, the amount of
catalysts in the reaction for the hydroxymethyl compound
must be increased in disadvantageous manner. According -to
process B there is no need to achieve any isolation of the
ester formed from the carboxylic acid of formula (Ida), the
dihydro-5-hydroxymethyl furanones being already able to be
formed generally in yields of about 95~ which is very
advantageous and much simplifies the process. Moreover,
these can be reacted directly as residue of the distillation.
Before the distillation, it is appropriate for reasons of
safety to decompose residual TAO or peroxides possibly pro-
sent. This can occur for example by addition of iron-II
-- 10 --
~2~t~0~
salts such as Phase in solution in the water. The amollnt
of Phase is to be determined according to the measured
amount of peroxides.
According to process A and B, the dicarboxylic
acids are very much preferably employed only in an amount
of 2.1 to 2.5 mow per mow pontoon carboxylic acid ester,
which, together with the likewise small amount of HOWE,
represents an essential simplification and saving of
material with respect to the state of the art. Advent-
juicily, also, only a small excess of carboxylic acid is then to be removed after the reaction.
As is very much preferred, it is furthermore
possible to employ HOWE only as 30 to 35: by weight aqueous
solution, so that there does not exist any danger of an
explosion.
With the further reaction according to process B
or process C for substituted or unsubstituted dodder-
hydroxymethylene furanones according to procedure I) of I).
Likewise according to the invention, only a small
amount of auxiliary substances used and especially according
to I), but also according to I) an essential simplification
with respect to the hydrolysis according to the state of the
art is achieved.
With procedure I), there takes place a transes-terif-
cation with the added alcohol which is employed in amounts of 1 to 20 molt preferably 1 to 5 mol. For complete reaction,
the ester formed from the added alcohol and the carboxylic
acid split off is removed by distillation from the equilib-
rum. Methanol, followed by ethanol, is preferred as alcohol.
For this purpose, advantageously only an amount of 0.1 to 10
mow percent, preferably 0.5 to 6.0 mow percent of an acidic
or basically acting catalyst is employed. Acid catalysts
are Lewis or Bronstedt acids, for example H2SO4, H3PO4
borontrifluoride, acetic or prop ionic acid. Basic catalysts
-- 11 --
:.'. .
are, in particular alcoholates of alkali or alkaline earth
metals with alcohol residues of 1 to 10 C-atoms, in which
the alcohol residue corresponds preferably to the alcohol
added. Preferred alcoholates are the methylates, ethylates
and left. bu-tylates of No or K. The formation of the
dihydro-5-hydroxymethyl furanones is surprising since
butyrolactone undergoes self condensation in the presence
of alcoholates to form high molecular substances (see
Aniline don Chemise, Vol. 597 (1955), page 163 -to 178).
Procedure I) accord:irlg to process B to process C
involving decarbonylation of the formic acid ester with
alcohola-tes, which likewise are required in catalytic amounts
of 0.1 to 10 mow percent, preferably 0.5 to 6.0 mow percent
related to the formic acid, is especially preferred and
advantageous.
Alcohols do not need to be added in procedure I).
As a matter of convenient operation, alcohols can
be employed there as solvents for the alcoholates which are
then added as for example 10 to 20~ by weight solution in
an alcohol. The generally and preferably employed alcohol-
ales are the same as those for procedure I.
The small amount of base employed in this reaction
is advantageous. It is known from the literature that this
splitting reaction takes place in good yields, indeed with
the bouncily formats likewise with employment of catalytic
amounts of the base (German Offenlegungsschrift 2B 25 362),
but, with aliphatic formats such as for example bottle
formats, stoichiometric amounts of base are necessary (J.
Org. Chum. (1966), page 2623). It is very surprising with
the present invention that also an oxygen-function a-t the
a-C atom of the aliphatic format makes possible a reduction
of the required amounts of base to the catalytic region.
The yields amount to above 90~.
The 3,4-dihydro-furanones with substltuen-ts in the
8(15i
5-position and optionally substltuents in further positions,
can also be designated as dihydro-3(3H)-furanones.
Example 1
-
3,4-dihydro-4,4-dimethyl pry _
60 g of -the formic acid ester of dodder-
dimethyl-5-hydroxymethyl-(3~)-furanone are dropped through
an upright glass tube (length 30 cm, diameter 2.2 cm) which
is filled with montmorillonite spheres and possesses an
internal temperature of 300C as a result of external
heating. The dropping time amounts to two hours. The
thermolysed material is taken up in a cooled container.
After fractional distillation, 31 g of dodder-
dimethyl-~-pyrone are obtained.
Example 2
3,4-dihydro-4,4-dimethyl-~-pyrone
20 g of the acetic acid ester of dodder-
dimethyl-5-hydroxymethyl-(3H)-furanone are thermolysed in
the manner described in Example 1. After fractional disk
tillation and separation off of the upper fraction which
passes over at 65 to 70C (12 mm) in order to remove with
water residual acetic acid, 9.7 g of dodder-
dimethyl-~-pyrone are obtained.
Example 3
3,4-dihydro-4,4-dimethyl-~-pyrone
13 g of dihydro-4,4-dimethyl-5-methoxymethyl-
(OH) forenoon are thermolysed as in Example 1. After
fractional distillation of the crude thermolysate, 6.6 g
of 3,4-dihydro-4,4-dimethyl-~-pyrone are obtained.
Example 4
3,4-dihydro-~-py~rone
In the same way as in Example 3, 10 g of the
methyl ether of hydro-5-hydroxymethyl-(3H)-furanone are
thermolysed. The crude thermolysate contains, after gas
chromatographic examinations and NO analyses, 5.1 g of
~2Z~
3,4-dihydro-~-pyrone.
Example 5
crone of formula Ida
109 g of 3,3-dimethylpen-ten-4-carboxylic acid
methyl ester are added by dropping to a solution of 95.5 g
HOWE (30% aqueous solution) and 150 g of formic acid. This
results in the temperature of the reaction mixture increasing
to 60C. After completion of the reaction (6 hours) the
excess HOWE is decomposed with ferrous sulfite. After
distillation ox the crude mixture, 119.8 g of the formic
acid ester of dihydro-4,4-dimethyl-5-hydroxymethyl-(3H)-
forenoon (boiling point 127C/0.1 mm) are obtained.
NOR spectrum (80 MHZ, C6D6): Pam = 0.55 (OH);
0.68 (OH) 1.94 (OH); 3.35-4.13 (OH), 7.65 (lo)
Example 6
Lactose of formula Ida
In the same way as in Example 5, 109 g of 3,3-
dimethylpenten-4-carboxylic cold methyl ester are reacted
with HOWE in 170 g of acetic acid. After working up in
the same way, 128 g of the acetic acid ester of dodder-
4,4-dimethyl-5-hydroxymethyl-(3H)-furanone (boiling point
126C/0.9 mm) are obtained.
NMR-spectrum (30 MHZ, CDC13): Pam = 1.1 (OH);
1.3 (OH); 2.1 (OH); 2.5 t2H); 4.4 (OH)
Example 7
Lactose of formula Jib
169 g of dodder 7 4-dimethyl-5-bromomethyl-(3H)-
forenoon are mixed with 680 m] of methanol and 47 g of
sodium ethyl ate and this mixture is heated for 7 hours at
68C. Afterwards the methanol is distilled off, the
residue is taken up in water and the aqueous solution is
extracted with ether. After drying of the ethereal phase
with sodium sulfite, and after removal of the solvent and
fractional distillation of the residue, 28 g of dodder-
- 14 -
~X~7~
dimethyl-5-methoxymethyl-(3H)-furanone (boiling punt 156C/
33 mm) are obtained.
NM~-spect.rum (30 MHZ, CC14): y Pam: lo (OH);
1.2 (OH); 2.3 (OH); 3.4 (OH); 3.5-4.4 (OH).
Example 8
-
Lactose of formula Tic according to process B
375 g of a 30% by weight aqueous HOWE solution is
added drops at a temperature of 60 to 70C to a mixture
of 426 g of 3,3-dimethyl penten-4-carboxylic acid methyl
ester and 281 g of formic acid (90~ by weight) with stirring.
Then the water and the formic acid which has not been
combined is distilled off and the residue is mixed with 10 g
of prop ionic acid as acid catalyst and 183 g of methanol.
Heating to boiling is effected and the formic acid methyl
ester being formed is removed continuously through a column.
After completion of the reaction, the methanol is distilled
off and -the residue is distillatively purified in vacua.
There are obtained 406 g of dihydro-4,4-dimethyl-5-hydroxy-
methyl-(3H)-furanone which equals 94% of theoretical.
Examples pa to 9c
Lactose for formula Tic according to process B
In an analogous procedure as that in Example 8, in
three further experiments, different catalyst are employed
instead of prop ionic acid:
Kettle Amount Yield of dodder-
dimehtyl-5-hydroxy-
methyl-(3H)-furanone
a) Nash 17 g 411 g
20% solution
in methanol
b) H3PO4 10 g 406 g
80-~ in water
c) H2SO4 5 g 402 g *)
*) -the acid solution is neutralized before the final
distillation.
.
I
Example 10
Lactose of formula Tic according to process B
Corresponding to the procedure of Exalnple 8,
however with the employment of 460 CJ of prop ionic acid,
instead of 281 g of a 98~ by weight formic acid, as well
as with transesterification to the product with use of
20 g of KOCH in 1000 g of methanol. The prop ionic acid
methyl ester being formed is removed distillatively.
400 g of dihydro-4,4-dimethyl-5-hydroxymethyl-
(forenoon, that is 92~ of theoretic]., are obtained.
Example 11
Lactose of formula Tic according to process C
20 g of the formic acid ester of dihydro-5-hydroxy-
methyl-(3H)~furanone are treated with 6 g of K-tert. -
butylate and this mixture is heated at 100C to 110C. Then
a further 90 g of the indicated formic acid ester are added
drops to this mixture with stirring, as a result of which
the temperature is slowly increased so that 150C is achieved
towards the end of the drops addition. After the residue
is distilled in vacua, I g of dihydro-5-hydroxymethyl-(3H)-
forenoon are obtained.
Example 12
Lactose of formula Tic according to process C
Corresponding to Example 10, 140 g of the formic
acid ester of dihydro-4,4-dimethyl-5-hydroxymethyl-2(3H)-
forenoon are reacted. 112 g of dihydro-4,4-dimethyl-S-
hydroxymethyl-(3H)-furanone are obtained.
Example 13
Proceeding in the same manner in Example 8, 25.4 g
of 3-methyl-3-n-octyl-penten-4-carboxylic acid ethyl ester
and 10 g of formic acid are treated while undergoing stirring
with 12 g of a 13% by weight HOWE solution over the course
of 4 hours.
After distilling of the water and excess formic
- 16 -
~Z7~
acid and after decarbonyla-tion with 0.5 g of Nash, 20.6 y
ofdihydro~4-me-thyl-4-n~oc-tyl-5-hydroxymethyl-2(3H)forenoon
Yield 85%) are obtained.
Example 14
Lactose of formula Tic according to process C
23 g of 3,3-Dimethyl penten-4-carboxylic acid
phenol ester, that is the ester of 3-methyl-buten-2-ol, are
mixed with 11 g of formic acid 198% by weight) and, while
undergoing stirring at 50 to 70C, 29 g of aqueous 30~ by
weight HOWE are added clropwise to this mixture. After the
water and the used formic acid are distilled off and -the
remaining residue is dissolved in 74 g of methanol, 1 g of
Nash (20% by weight in methanol) are supplied to this
mixture and the mixture is heated to boiling. The formic
acid methyl ester being formed is removed by distillation
from the reaction mixture. After the methanol is distilled
off and the residue distilled, 14.6 g of dodder-
dimethyl-5-hydroxymethyl-(3H)- forenoon = 86% of theoretical
are obtained.
Example 15
Lactose of formula Tic according to process C
Example 8 is repeated with the amounts and condo-
lions there set out, but with -the decarbonylisation with
6 g of K-tert. butylate to the product taking place after
the distillation of the water and the excess formic acid.
401 g of Dihydro-4,4-dimethy]-5-hydroxymethyl-
(forenoon, that is 93% of theoretical, are obtained.
- 17 -
