PREPARATION OF 7-METHYL-4-OXO-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID DERIVATIVES

PREPARATION DES DERIVES DE L'ACIDE 7-METHYL-4-OXO-1,4-DIHYDRO-1,8-NAPHTYRIDINE-3-CARBOXYLIQUE

English Abstract

A B S T R A C T
Process for the preparation or 1-alkyl-7-methyl-4-oxo-1,4-dihydro-
1,8-naphthyridine-3-carboxylic acids useful as antibacterial agent.
A compound of the general formula II
<IMG>
where R1, R2, Y, Z and n are defined in the disclosure is hydrolysed.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Process for the preparation of 1-alky1-7-methyl-
4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acids of
the general formula I,
<IMG>
which comprises subjecting to hydrolysis a compound of the
general formula II
<IMG>
wherein
R1 stands for hydrogen, -/CH2/m-CH3, a /CH2/n-aryl, or
-/CH2/p-cycloalkyl groups,
R2 is -/CH2/m-CH3, -/CH2/n-aryl, or -/CH2/p-cycloalkl;
Y stands for a tertiary nitrogen-containing aromatic,
heterocyclic ring attached through the nitrogen atom
or a trialkylamino group:
Z is an anion;
n, m and p stand for an integer number of 0 to 5, and
wherein alkyl represents a lower alkyl group.
14

2. Process according to claim 1, which comprises to
carry out hydrolysis in the presence of hydroxides or car-
bonates, or organic amines.
3. Process according to claim 27 which comprises
carrying out hydrolysis in the presence of ammonium-, alkali-,
or alkaline earth metal hydroxides or -carbonates, or tri-
ethylamine.
4. Process according to claims 1-3, which comprises
carrying out the reaction at 20-150 °C.
5. Process according to claims 1-3, which comprises
using as starting materials of general formula II quaternary
iodide salts.
6. Process according to any of claims 1-3, which com-
prises using as starting material 1-ethyl-7-methyl-4-oxo-1,4-
dihydro-1,8-naphthyridine-3-carbonyl-/methyl-methyl-pyridinium/-
iodide,
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/
ethyl-methyl-pyridinium/-iodide,
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/
propyl-methyl-pyridinium/-iodide,
1-ethyl-7-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/
phenyl-methyl-pyridinium/-iodide,
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/
benzyl-methyl-pyridinium/-iodide,

1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/
cyclohexyl-methyl-pyridinium/-iodide, 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-
naphthyridine-3-carbonyl-[/cyclohexyl-methyl/-methyl-pyridinium]-iodide,
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/dimethyl-
methyl-pyridinium/-iodide, 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-
naphthyridine-3-carbonyl-[/dimethyl-methyl/-triethyl-ammonium]-bromide.
7. Process according to claim 2 in which the organic amine is a
trialkylamine.
8. Process according to claims 1-3, which comprises carrying out
the reaction at 80-120°C.
16

9. Process according to claim 1 in which Y is a tertiary nitrogen-
containing aromatic, heterocyclic ring.
10. Process according to claim 1 in which Y is a trialkylamino group.
11. Process according to claim 2 in which the hydrolysis is carried out
in the presence of an alkali.
12. Process according to claim 11 in which the alkali is sodium
hydroxide.
13. Process according to claim 1 in which 1-ethyl-7-methyl-4-oxo-1,4-
dihydro-1,8 naphthyridine-3-carboxylic acid is prepared by hydrolysing 1-ethyl-
7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/methyl-methyl-
pyridinium/-iodide, 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-
carbonyl-/ethyl-methyl-isoquinolinium/-iodide or 1-ethyl-7-methyl-4-oxo-1,4
dihydro-1,8-naphthyridine-3-carbonyl-(propyl-methyl-pycolinium)-iodide,
acidifying the reaction mixture and collecting the solid which separates.
14. Process according to claim 1 in which 1-ethyl-7-methyl-4-oxo-1,4-
dihydro-1,8-naphthyridine-3-carboxylic acid is prepared by hydrolysing
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-(phenyl-methyl-
pyridinium)-iodide, 1-ethyl-7-methyl-4-oxo-1,4-dihydro-3-carbonyl-(benzyl-
methyl-quinolinium)-iodide, 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthy-
ridine-3-carbonyl-(cyclohexyl-methyl-pyridinium)-iodide, 1-ethyl-7-methyl-4-
oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-[(cyclohexyl-methyl)-methyl-
pyridinium]-iodide, 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-
carbonyl-/dimethyl-methyl-pyridinium-/iodide, 1-ethyl-7-methyl-4-oxo-1,4-
dihydro-1,8-naphthyridine-3-carbonyl-/dimethyl-methyl-pyridinium/-bromide or
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-[/dimethyl-
methyl-/triethyl-ammonium]-bromide, acidifying the reaction mixture and
collecting the solid which separates.
15, Process according to claim 13 or 14 in which the hydrolysis is
effected by reaction with aqueous sodium hydroxide.
17

16. 1-Ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic
acid whenever prepared by the process of claim 13 or 14 or by an obvious
chemical equivalent thereof.
18

Description

~3~ 2 -
This invention relates to the preparation of 1-ethyl-
7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic
acid, and other 1-all<yl-7-methyl-4-oxo-1,4-dihydro-1 J8-
naphthyridine-3-carboxylic acids.
; 1-Alkyl-7-methyl-4-oxo-1~4-dihydro-1l8-naphthyridine-
3-carboxylic acids are well-l<nown valuable antibacterial
agents, being used in therapy. These compounds were prepared
by alkylation and subsequent hydrolysis of 7-methyl-4-oxo-
3-alkoxycarboilyl-1,4 dihydro-1l8-naphthyridine (British
patent No. 1,000l892)r
It has bean found according to the present invention
. that 1-all<yl-7-methyl-4-oxo-1,4-dihydro-'l~8-naphthyridine-
.: 3-carboxylic acids of the general formula I
H C / ~ ~
. all<yl
~ 20 may be prepared in a pure state with good yields by sub;ecting
~ compounds of the general formula II 1;:
~CO - C ~ Y~Z ~ ~
: H3C
all<yl
;
to hydrolysis J
11511-77 /Fné
''' '
'':~
: . . . .. ... :.
.. .. .
.. :......... . ..... . . .. ...
.:...... . ~ .. :.- .. ~ . ,

~(~3g:Z85
/wherein -
R stands for hydrogen, -/CH2/m-CH3~ a /OH2/n,aryl~ or -
-/C~l2/p-cycloalkyl groups;
/ H2/m-CH3, -/CH2/n-aryl, or /CH2/ -cycloalkyl;
Y stands for a tertiary nitrogen-containing aromatic,
heterocyclic ring attached through the nitrogen atom
or a trialkylamino group;
Z is an anion; `~
n, m and p stand for an integer number of 0 to 5, and ~ ;;
wherein alkyl represents a lower alkyl group.
This process has the advantage to use starting
materials which can be purified easily.
Hydrolysis is carried out preferably in the
presence of alkaline agents. Thus alkali hydroxide~/e.g~
potassium hydroxide or sodium hydroxide/ or alkaline
earth metal hydroxides /e.g. calcium hydroxide/ or ammonium
hydroxide or carbonates may also be used as alkaline hydro-
lysing agents. Hydrolysis may be accomplished also in
; neutral or acidic medium.
Hydrolysis may also be carried out in aqueous
medium in the presence of a trialkylamine. For this purpose
lower trialkylamines such as trimethylamine or advantage-
ously triethylamine may be used.
According to a preferred embodiment of the
present inventionj a compound o-f the general formula II is -
.'. '
~,
: , . :
. .: . . :
. : : .

~a3s~
treated with an aqueous alcoholic, preferably ethanolic
sodium hydroxide or potassium hydroxide solution~ Hydrolysis
may be carried out at a temperature of 2~-150C, preferably 80-120C
The compound of the formula I may be precipitated by
acidifying the reaction mixture preferably by adding an
acid. Mineral acids, such as hydrochloric acid, or organic
acids, such as acetic acid, formic acidJ etc~l may be used
for this purpose~
In the starting materials of the Formula II Y stands
preferably For a pyridinel quinoline, or all<yl-sub-
stituted pyridines~ such as pieoline ring, but it may
also stand for a quinaldine~ lepidine or other lower-
allcyl-substituted pyridine ring. Y may also stand for
a trialkylamino ~e.g. trimethyl-, triethyl-J tri-
propyl-, triisopropylamino-group, etc.) group~ The ;~
anion ot the starting material may be a halogenide,
such as iodide, bromide or chlorideJ or sulphate,
phosphatel perchlorate, etc.
The N-alkyl-group represents a straight or branched
chained allcyl group, having 1-6 carbon atoms (e.g.
methyl, ethylJ n-propylJ isopropyl~l isobutyl, etc.).
In the specification the term "alkyl~ means -(CH2)m-
-CH3 ~e,.g. methyl~ ethyl3 n-propyl)~ the term incycloallcyl"
means -(CH2)p~cycloalkyl (eag. cyclopentyl, cyclohexyl,
cyclohexylmethyl3 etc.)~ In these formulae m, n, and p are
integers in the range of from 0 to 5~ The cycloallcyl
; group may have 3-6 carbon atoms. The aryl groups may
optionally bear one or more substituents (e~g. halogen, allcyl
or alkoxy~ The term "arallcyl" means -~CH2~n-aryl ~e~g~benzyl
phenylethyl).
,.. . i .

~l~3~Z~35
. - 5 -
,~
As starting material of the formula II preferably the
. following compounds may be used:
: 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1~8-naphthyridine-3-
. -carbonyl-(methyl-methyl-pyridinium)-iodide;
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3- :
-carbonyl-(ethyl-methyl-pyridinium~-iodide;
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1~8-naphthyridine-3-
.- -carbonyl-(propyl-methyl-pyridinium)-iodide~ ;
1-ethyl-7-methyl-~-oxo-1,4-dihydro-1,8-naphthyridine-3-
-carbonyl-(phenyl-methyl-pyridinium)-iodide~
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3~
-carbonyl-(benzyl-methyl-pyridinium~-iodide~
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3
-carbonyl-~cyclohexyl-methyl-pyridinium)-iodide;
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-
:: -carbonyl C(cyclohexyl-methyl)-methyl-pyridinium~-iodide;
-- 1-ethyl-7-methyl-4~oxo-1,4-dihydro-1,8-naphthyridine-3-
-carbonyl-(dimethyl-methyl~pyridinium)-iodide,
1~ethyl-7-methyl-4-oxo-1,~-dihydro-1,8-naphthyridine-3-
~ 20 -carbonyl-C~dimethyl-methyl)-triethyl-ammonium~-bromide.
`. The starting materials of the general formula II are
,..i.
new compounds and may be prepared as follows!: :
2-Amino-6-methyl-pyridine or an acid addition salt
thereof is condensed with a compound of the formula III
- CH
O ~ C (III)
alkylO - CH - C
--: 30 COOall<yl
; .
... .. .
. ~, .
; . .
.
~.... . . . .

~39A~5 :
- 6 -
The compounds o~ the formula IV
R - CH (IV)
H3C ~NH CH C
COOall<yl
thus obtained are subjected to ring closurel whereupon the ~-
1,8-naphthyridine-derivatives of the formula V
R~

~d~ co CH (V) ~;
H3C
H
thus obtained are N-all<ylated~ The compounds of the
formula VI . .
0 R
~ C0 -CH2 (VI)
H3C~r
all<yl
thus formed are reacted with a tertiary nitrogen-containing
heterocyclic base or a trialkylamina in the presence of a
halogen to yield the starting materials of the formula II.
The anion can be exchanged for an other anionO
Further details of our invention are disclosed in the
following Examples~ serving merely the purpose o~ illustra-
: 30 tion, but not of limitation.

~392~3S
Example 1:
A mixture of 1,22 g of 1-ethyl-7-methyl-3-propionyl~
4~oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of pyridine and
1,27 g of iodine is s~i~red at 100 C~ whereupon the reaction
mixture is evaporated in vacuo. The l-ethyl-7-methyl-4-oxo-
1~4-dihydro-1~8-naphthyridine-3-carbonyl-/methyl-methyl-
pyridinium/-iodide thus obtained is admixed with 25 ml of
a 10 % sodium hydroxide solution and heated to boiling~ The
resulting clear solution is cooled, extracted with chloro-
form, clarified with activated charcoal and filtered off.
the filtrate is acidified with hydrochloric acid, The
precipitated crystals are filtered off and washed with
water. The melting point oE the 1-ethyl-7-methyl-4-oxo-
1,4-dihydro-1,8-naphthyridine-3-carboxylic acid amounts to
224-226 C.
Example 2:
A mixture of 1,29 g of 1-ethyl-7-methyl-3-butyryl-
; 4-oxo-1~4-dihydro-1~8-naphthyridine~ 10 ml of isoquinoline
and 1,27 g of iodine is stirred at 100 C, whereupon the
reaction mixture is evaporated in vacuo. The l-ethyl-7-
methyl-4-oxo-1~4-dihydro-1,8-naphthyridine-3-carbonyl-/ethyl-
methyl-isoquinolinium/-iodide thus obtained is admixed ~ith
25 ml of a 10 % sodium hydroxide solution and heated to boil-
ing. The resulting clear solution is cooled, extracted with
chloroform, clarified with activated charcoal and filtered
off. The filtrake is acidified
,
.:. - - :
:: ~,: : ..

1(~39Z~95 - a -
with hydrochloric acid. The precipitated crystals are
- filtered off and washed with water. The melting point
of the 1-ethyl-7-methyl-4-oxo-1,4-d~hydro-1,8-napht-
hyridine~3-carboxylic acid amounts to 225~227 C~
Example 3
A mixture of 1t36 g of 1-ethyl-7-methyl-3-valeroyl-
4-oxo-1,4-dihydro-1,8-naphthyridine, 10 ml of pycoline
and 1~27 9 of io~ine is stirred at 100 C, whereupon
the reaction mixture is evaporated in vacuo. The 1-
ethyl-7-methyl-4-oxo-114-dihydro-1j,8-naphthyridine-3-
carbonyl-~propyl-methyl-pycolinium)-iodide thus obtain-
ed is admixed with 25 ml o~ a 10 % sodium hydroxide
solution and heated to boiling. The resulting clear
solution is cooled, extracted with chloroform, clarified
with activated charcoal and fil~red off. The filtrate
is acidified with hydro~hloric acid~ The precipitated
crystals are filtered otf and washed with water~ The
melting point of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-
1,8-naphthyridine-3-carboxylic acid amounts to 223-
-225 C.
Example 4
A mixture of 1,53 9 of 1-ethyl-7-methyl-3-phena-
cetyl-4-oxo-1~4-dihydro-1~8-naphthyridinel 10 ml of
pyridine and 1,27 g of iodine is stirred at 100 C,
whereupon the reaction mixture is evaporated in ~Jacuo.
The 1-ethyl~7-methyl-4-oxo-1J4-dihydro-118-naphthyri-
dine-3-carbonyl-~phenyl-methyl-pyridinium)-iodide thus
:
~ .: - .. . . .............................. . . .
.

2~5
g
obtained is admixed with 25 ml of 10 % sodium hydroxide
solution and heated to boiling. The resulting clear
solution is cooled, extracted with chloroform, clarified
with activated charcoal and filtered off, The filtrate
is acidified with hydrochloric acid~ The precipitated
crystals are filtered off and washed wit~l water. The
melting point of the 1-ethyl-7-methyl~4-oxo~1 ,4-dihydro-
1 ,8-naphthyridine-3-carboxylic acid amounts to 224-
226 C.
Example 5
A mixture of 1160 g oF 1-ethyl-7-methyl-3-(3-phenyl-
proplonyl)-4-oxo-1,4-dihydro-1J8-naphthyridine, 10 ml of
quinoline and 1~27 g of iodine is stirred at 100 C,
whereupon the reaction mixture is evapor-ated in vacuo.
The 1-ethyl-7-methyl-4-oxo-1~4-dihydro-3-carbonyl-
~benzyl-methyl-quinolinium)-iodide thus obtained is
admixed with 25 ml oF a 10 % sodium hydroxide solution
and heated to boiling. The resulting clear solution
is cooled, extracted with chloroform, clariFied with
20 activated charcoal and filtered off. The filtrate is
acidified with hydrochloric acid. The precipitated
crystals are filtered oFf and washed with water~ The
melting point of the 1-ethyl-7-methyl-4~oxo-1,~-
dihydro-1 ,8-naphthyridine-3-carboxylic acid amounts
to 227-228 C.
Example 6
A mixture of 1956 9 of 1-ethyl-7-methyl-3-cyclohexyl-

1(~3~8~
acetyl-4 oxo~ -dihydro-1,8-naphthyridine, 10 ml of
pyridine and 1,27 9 of iodine is stirred at 100 CJ
whereupon the reaction mixture is evaporated in vacuo.
The 1-ethyl-7-methyl-4-oxo-1~4~dihydro-1,8-naphthy-
ridine-3-carbonyl-(cyclohexyl-methyl-pyridinium)-
iodide thus obtained is admixed with 25 ml of a 10 %
sodium hydroxide solution and heated to boiling, The
resulting clear solution is cooled~ extracted with
chloroform, clarified with activated charcoal and
filtered off. The Filtrate is acidified with hydro--
chloric acid. The precipitated crystals are filtered
oFf and washsd with water. The melting point of the
1-ethyl-7-methyl-4-oxo-1~4-dihydro-1~8-naphthyridine-
3-carboxylic acid amounts to 226-228 C.
: ` .
Example 7
A mixture of 1f63 9 of 1-ethyl-7-methyl-3-(3-cyclo-
hexyl-propionyl)-4-oxo-1~4-dihydro-1~8-naphthyridine
10 ml of pyridine and 1?27 9 of iodine is stirred at
100 C, whereupon the reaction mixture is evaporated
in vacuo. The 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-
naphthyridine-3-carbonyl-[lcyclohexyl-methyl)-methyl-
pyridinium]-iodide thus obtained is admixed with
25 ml of a 10 % sodium hydroxide solution and heated
to boiling. The resulting clear solution is cooled,
extracted with chloroform, clarified with activatecl
charcoal and filtered off. The filtrate is acidified
.
-., . - ~
,
.

~L~3~3Z85
with hydrochloric acid. The precipitated crystals are
filtered off and washed with water. The melting point
of the l-ethyl-?-methyl-4-oxo-1,4-dihydro-1,8-Mapht-
hyridine-3-carboxylic acid amounts to 221-223 C.
Example 8:
A mixture of 1,29 g of 1-ethyl-7-methyl-3-/2-
methyl-propionyl/-4-oxo-dihydro-1~8-naphthyricline~ 10 ml
of pyridine and 1,27 g of iodine is stirred at 100 C,
whereupon the reaction mixture is evaporated in vacuo.
The l-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-
3-carbonyl-/dimethyl-methyl-pyridinium-/iodide thus
obtained is admixed with 25 ml of a 10 % sodium hydroxide
solution is heated to boiling, then it i9 cooled~ extract-
ed with chloroform~ clariEied with activated charcoal and
filtered off. The filtrate is acidified with hydrochloric
acid~ The precipitated crystals are filtered off and
washed with water. The melting point of the l-ethyl-7-
methyl-4_oxo-1,4_dihydro-1,8-naphthyridine-3_carboxylic
acid amounts to 226-228 C.
Example 9:
A mixture of 1,69 g of 1-ethyl-7-methyl-3-/2-
bromo-2-methyl-propionyl-/-4-oxo-1,4-dihydro-1,8-naphth~ridine
and 50 ml of pyridine is heated to boiling, whereupon the
reaction mixture is evaporated in vacuo~ The l-ethyl-7-
methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbonyl-/
dimethyl-methyl-pyridinium/-bromide is admixed with 25 ~1
of a 10 % sodium hydroxide solution, whereupon the mixture
_ 11 --
.
.
' '. ' ~ , ~ . .', ' ' ' '
.: . , ~. . .

~()39;~
is heated to boiling~ The residual solution is cooled,
extracted with chloroform~ the extract is clarified and
acidified with diluted hydrochloric acid. The precipi~
tated l-ethyl-7 methyl-4-oxo-1~4-dihydro-1~8-naphthyri-
ne-3-carboxylic acid melts at 225-226 C.
Example 10:
A mixture of 1,69 g of 1-ethyl-7-methyl-3-/2-
bromo-2-methyl-propionyl/-4-oxo-1,4-dihydro-1,8-naphthy-
ridine is heated to boiling in 100 ml of triethylamine,
whereupon the reaction mixture is evaporated in vacuo.
The l-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphkhyridine-
3-carbonyl-C/dimethyl-methy'l-/triethyl-ammonium]-'bromide
thus obtained is admixed with 25 ml of a 10 % sodium
hydroxide solution, whereupon the reaction mixture is
,.;
heated to boiling. The residual solution is cooled, ex-
tracted with chloroform~clarified with activated charcoal
and acidified with diluted hydrochloric acid. The precip-
itated l-ethyl-7-methyl-4-oxo-1~4-dihydro-1~8-naphthyridine-
3-carboxylic acid is filtered off, washed with water and
d~ied. Mp~: 226-227 C.
Example 11:
A mixture of 2,11 g of 7-methyl-4-oxo-1~4-dihydro-
1,8-naphthyridine-3-carbonyl-/methyl-methyl-pyridinium/-
iodide, 4,55 g of triethylphosphate, 0,7 g of potassium
carbonate is heated to boiling. The reaction mixture is
cooled, poured into a 10 % sodium hydroxide solution and the
.,
.: :
~ 12 -
,
,,, ~ , : . ,.,, . : :
~, , .. . . . . , , . ., , . . ~

~03~Z8S - 13 -
aqueous reaction mixture is heated to boiling~ The
` solution is cooled~ extracted with activated charcoal
and filtered off. The filtrate is acidified with 20 %
hydrochloric acid. The precipitated crystals are filter-
- ed off, washed with water and dried. The 1-ethyl-7-methyl-
4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
: melts at 225-227 C.
','
~'"'
;'.,''
:
.
;
,,
~ ,