Butyrolactone 1

Butyrolactone
Wolfgang Schwarz, BASF AG, Ludwigshafen, Federal Republic of Germany (Chaps. 1 – 7)

Jürgen Schossig, BASF AG, Ludwigshafen, Federal Republic of Germany (Chaps. 1 – 7)

Roland Rossbacher, BASF AG, Ludwigshafen, Federal Republic of Germany (Chap. 8)

Hartmut Höke, Weinheim, Federal Republic of Germany (Chap. 8)

1. Introduction . . . . . . . . . . . . . . . . . . 1 6. Storage and Transportation . . . . . . . . 4

2. Physical Properties . . . . . . . . . . . . . . 1 7. Uses . . . . . . . . . . . . . . . . . . . . . . . . 4
3. Chemical Properties . . . . . . . . . . . . . 2
8. Toxicology and Occupational Health . . 4
4. Production . . . . . . . . . . . . . . . . . . . 2
5. Quality Specifications and Analysis . . . 4 9. References . . . . . . . . . . . . . . . . . . . 5

1. Introduction solvent for lower hydrocarbons. Some physical

properties of γ-butyrolactone are listed below.
γ-Butyrolactone or γ-hydroxybutyric acid lac-
Density
tone [96-48-0], C4 H6 O2 , M r 86.09, became in- at 0 ◦ C 1.15 g/cm3
dustrially available in the 1940s as a result of the at 20 ◦ C 1.13 g/cm3
work of W. Reppe and his colleagues at BASF. at 40 ◦ C 1.11 g/cm3
Critical temperature T crit. 436.5 ◦ C
Critical pressure pcrit. 3.35 MPa
Vapor pressure
at 20 ◦ C 0.04 kPa
at 50 ◦ C 0.3 kPa
at 100 ◦ C 3.6 kPa
To date, the Reppe process (see Chap. 4) has at 150 ◦ C 22.5 kPa
at 205 ◦ C 101.3 kPa
remained the most important process for the Heat of vaporization at 206 ◦ C 535 kJ/kg
production of butyrolactone. Butyrolactone is Heat of solution in water 2500 J/mol
Specific heat capacity cp (l)
important as an intermediate in the manufacture at 25 ◦ C 1680 J kg−1 K−1
of pyrrolidone derivatives and as a solvent for at 100 ◦ C 1850 J kg−1 K−1
polymers and agrochemicals. at 200 ◦ C 2200 J kg−1 K−1
Specific heat capacity cp (g)
Methods of synthesis of historical and prepar- at 100 ◦ C 1275 J kg−1 K−1
ative interest are summarized in Beilstein [1] and at 200 ◦ C 1575 J kg−1 K−1
in Houben-Weyl [2]. In the mid-1960s butyro- at 300 ◦ C 1820 J kg−1 K−1
Evaporation number
lactone was discovered in nature, as a normal (DIN 53170) 216
metabolic product in animals [3]. Flash point (DIN 51758) 100 – 101 ◦ C
Ignition temperature
(DIN 51794) 455 ◦ C
Heat of combustion at constant 234 kJ/g
2. Physical Properties volume or constant pressure
Explosion limits
lower 2.7 vol %
Butyrolactone, mp − 43.5 ◦ C, bp 204 – 206 ◦ C upper 15.6 vol %
Refractive index n20
D 1.4352
(at 101.3 kPa), is a colorless, slightly hygro- Viscosity
◦
scopic liquid having a faint odor. Butyrolactone at 20 C 1.90 mPa · s
is miscible in all proportions with water, alco- at 50 ◦ C 1.25 mPa · s
at 80 ◦ C 0.86 mPa · s
hols, esters, ethers, ketones, and aromatic hydro- at 110 ◦ C 0.63 mPa · s
carbons. It has limited miscibility with linear and at 140 ◦ C 0.49 mPa · s
at 170 ◦ C 0.40 mPa · s
cyclic aliphatic hydrocarbons. It is an excellent
solvent for numerous polymers and a selective

c 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

10.1002/14356007.a04 495
2 Butyrolactone
Surface tension (20 ◦ C) 44.6 × 10−5 N/cm
Dielectric constant (20 ◦ C) 39.1
Thermal conductivity
(25 – 65 ◦ C) 0.276 J m−1 s−1 K−1
Conductivity 0.7 µS/cm
3. Chemical Properties
In aqueous solution there is an equilibrium bet-
ween the lactone and free hydroxybutyric acid,
which lies 100 % on the lactone side at 0 ◦ C,
and about 80 % at 100 ◦ C. In the presence of
one molar equivalent of alkali, the equilibrium
is displaced 100 % to the hydroxybutyric acid
side; therefore, butyrolactone can be determined
by titration with a base. At pH 7 the compound
is extremely stable. Butyrolactone reacts with
bases, hydrogen halides, and alcohols (in the
presence of acids), undergoing ring cleavage and
giving derivatives of γ-hydroxybutyric acid. It
reacts with ammonia, amines, carbonyl com-
pounds, and halogens in the α-position without
ring cleavage. For example, butyrolactone con-
denses with ethyl acetate [141-78-6] to give α-
acetobutyrolactone, an intermediate in the pro-
duction of vitamin B1 :
Cleavage of the lactone ring gives derivatives
of γ-substituted butyric acid. For example, buty-
rolactone reacts with sodium sulfide to give the
rubber additive thiodibutyric acid [5152-99-8]:
Reaction with phenols gives phenoxybutyric
acids [6303-58-8]:
Replacement of the ring oxygen atom by ni-
trogen yields pyrrolidone derivatives, a reaction
often used in industry. For example, butyrolac-
tone reacts with methylamine [74-89-5] to give
N-methylpyrrolidone [872-50-4]:
The chemistry of butyrolactone, and its use in
a variety of syntheses, was investigated, above
all, by W. Reppe [4] and others [5]. Reactions,
generally typical of lactones, are described in
Houben-Weyl [2].
Homopolymerization of butyrolactone can
be effected only under very high pressure
(2000 MPa) [6].
4. Production
Dehydrogenation of 1,4-Butanediol
[110-63-4] (→ Butanediols, Butenediol, and
Butynediol). The Reppe process for manufac-
turing butyrolactone involves theendothermic
dehydrogenation of 1,4-butanediol in the gas
phase. This process is used by BASF, ISP, and
Lyondell.
Preheated 1,4-butanediol vapor is introduced
into a hot stream of circulating hydrogen and
passed at atmospheric pressure through a bed of
copper catalyst at temperatures between 180 and
240 ◦ C (Figure 1). The yield of butyrolactone is
approximately 95 %. The reaction takes place
via γ-hydroxybutyraldehyde [25714-71-0] [7].
The byproduct hydrogen off-gas requires
only simple purification before reuse (e.g., cat-
alytic methanization of carbon monoxide impu-
rities). The crude butyrolactone separated from
the recycle gas stream contains small amounts
of byproducts, including 1,4-butanediol, butyric
acid, and high boilers, from which butyrolactone
is separated by distillation.
Butyrolactone itself is noncorrosive and can
be handled in carbon steel apparatus. However,
where parts of the synthesis or distillation ves-
sels and pipes come into contact with hot crude
product containing butyric acid, they must be
made of stainless steel.
 Butyrolactone 3

Figure 1. Production of γ-butyrolactone by dehydrogenation of 1,4-butanediol

Hydrogenation of Maleic Anhydride In a process developed by Kvaerner Pro-

[108-31-6]. In the preparation of butyrolac-
tone by hydrogenatingmaleic anhydride, molten
maleic anhydride is fed into a preheated circu-
latingstream of hydrogen and passed under a
pressure of 6 – 12 MPa at 160 – 280 ◦ C over a
nickel-containing catalyst [8].
cess Technology (KPT, London) [10] dimethyl
maleate [624-48-6] is producedin a first step
from maleic anhydride and methanol with a
strongly acidicion exchanger as catalyst. The re-
sulting dimethyl maleate is hydrogenated in the
gas phase on a Cu-containing catalyst at a pres-
sure of 2 – 8 MPa at 150 – 250 ◦ C and gives a
mixture of 1,4-butanediol, tetrahydrofuran, bu-
tyrolactone, and a small amount of the interme-
diate dimethyl succinate [106-65-0].

The reaction takes place via succinic anhy-

dride [108-30-5] and can, by choice of the con-
ditions, be continued to produce tetrahydrofuran
[109-99-9]. The excess hydrogen is washed with
water and recycled tothe synthesis. Byproducts
contained in the butyrolactone are separated out
of the circulating gas: propanol [71-23-8], buta-
nol [71-36-3], propionic acid [79-09-4], and bu-
tyric acid [107-92-6]. The butyrolactone is sep-
arated from these by distillation.
Because of the acids present, both the synthe-
sis apparatus and the distillation apparatus must
be made of stainless steel. The Japanese man-
ufacturer Mitsubishi Chemical Corporation [9]
Butyrolactone and dimethyl succinate can be
uses this process.
recovered as an azeotrope and recycled to the
hydrogenation stage to obtain complete con-
Hydrogenation of Maleic Esters. New version to 1,4-butanediol and tetrahydrofuran.
processes for the production of 1,4-butanediol Alternatively the azeotrope can be refined by
and tetrahydrofuran starting from maleic anhy- distillation to recover pure butyrolactone. The
dride via dimethyl maleate have been developed amount of butyrolactone depends on the pres-
in the past few years (→ Tetrahydofuran). They sure and temperature in the hydrogenation step,
offer the possibility of extracting butyrolactone, which influence the equilibrium between 1,4-
which is an intermediate in these processes.
4 Butyrolactone
butanediol and butyrolactone. Under the condi-
tions described above it may vary from 5 to 50 %.
The new process has been licensed by KPT
several times. The first commercial plants using
this process are expected to come on stream in
2000.
A proprietary process practised by Eurodiol,
a Belgian company of the SISAS group also
starts from dimethyl maleate, which is hydro-
genated in the gas phase at 1 – 2 MPa to give
a mixture of butyrolactone and tetrahydrofu-
ran in variable proportions. Butyrolactone and
tetrahydrofuran are recovered as pure products
by distillation, while the byproduct azeotrope
butyrolactone/dimethyl succinate can be recy-
cled for full conversion to butyrolactone and
tetrahydrofuran or hydrogenated in a subsequent
hydrogenation step in the liquid phase to give
1,4-butanediol and additional tetrahydrofuran.
Other Processes. Processes via tetra-
hydrofuran [11], dihydrofuran [12], acetylene
[13], [14], butynediol [15], olefins [16–18], bu-
tadiene [8], or by carbonylation [19–21] are not
industrially important.
Producers. Butyrolactone is manufactured
by BASF (Ludwigshafen, Germany and Geis-
mar, USA), ISP (Calvert City and Texas City,
USA), Lyondell (Channelview, USA), MCC
(Mizushima, Japan) and Eurodiol (Feluy, Bel-
gium).
5. Quality Specifications and
Analysis
Standard-grade butyrolactone is about 99.7 %
pure. The main impurities in the Reppe-based
process are 1,4-butanediol, butyric acid, and
water; in the maleic ester based processes, di-
methyl succinate, 4-hydroxybutyl butyl ether,
and water. Electronic-grade butyrolactone is
about 99.9 % pure and is subject to stringent re-
strictions regarding the content of specific ions
such as Fe ions, Na+ , Cl− , NO−3.
Butyrolactone is usually analyzed by gas
chromatography. The butyric acid content can
be determined by titration with alkali. The water
content is determined by coulometric titration.
Cations and anions are analyzed by atomic spec-
troscopy and ion chromatography, respectively.
6. Storage and Transportation
Butyrolactone can be stored indefinitely. The
pure product is noncorrosive and therefore can
be stored and transported in carbon steel contain-
ers. Butyrolactone becomes slightly yellow on
prolonged storage in carbon steel vessels with-
out nitrogen padding. In this case stainless steel
containers are recommended. The hygroscopic-
ity of the product requires some precautions. Bu-
tyrolactone attacks concrete vigorously.
For detailed transport information (classifi-
cation, regulatory data etc.), see the safety data
sheet [22].
7. Uses
The main use of butyrolactone is as an interme-
diate in the synthesis of N-methylpyrrolidone
(NMP) [23], pyrrolidone [24], herbicides
(e.g., MCPB = γ-2-methyl-4-chlorophen-
oxybutyric acid) [25], growth regulators (e.g.,
α-(4-methylbenzylidene)-γ-butyrolactone
[5418-24-6] [26]), α-acetobutyrolactone (a vi-
tamin B1 intermediate) [27], and the rubber ad-
ditive thiodibutyric acid [28]. Butyrolactone is
used as a solvent for polymers [29], [30] and as a
polymerization catalyst [31]; in hairwave com-
positions [32] and sun lotions [33]; and in phar-
maceuticals [34]. It is also used in printing inks,
e.g., for ink-jet printing [35], as an extractant in
the petroleum industry [36], as a stabilizer for
chlorohydrocarbons [37] and phosphorus-based
pesticides [38], and as a nematocide [39]. More
recent applications are in the electronics field as
a cosolvent for capacitor electrolytes [40] and
as a cosolvent for photoresists [41].
8. Toxicology and Occupational
Health
γ-Butyrolactone is readily absorbed from the
intestine and through the skin [42], [43]; the
half-life was about 20 min in the blood of
rats after oral administration [43]. Metabolism
and excretion is rapid; γ-hydroxybutyric acid
is the primary metabolite. Following i.v. in-
jection in rats, ca. 60 % of radiolabeled lac-
tone was detected in the expired air as CO2

within 2.5 h with the peak level about 20 min
after application [44]. In human volunteers
who received 1 g of γ-butyrolactone in wa-
ter, (S)-3,4-dihydroxybutyrate, glycolic acid, γ-
hydroxybutyrate, and an isomer of 4-hydroxy-3-
oxobutyrate were analyzed in the urine 4 h after
application [45].
γ-Butyrolactone has a low acute toxicity:
LD50 data in the literature vary between 800
and 1800 mg/kg (rat, mouse) and 500 and
1700 mg/kg (guinea pig). The dermal LD50 in
guinea pigs is 5600 mg/kg [46], [47], [48]. The
inhalative LC50 (rat, 4-h) lies above the highest
tested concentration which did not cause mor-
tality (>5.1 mg/L) [49]. Inhalation (8-h) of air
saturated with γ-butyrolactone at room temper-
ature produced no symptoms in rats [50].
γ-Butyrolactone causes depression of
the CNS by means of its metabolite γ-
hydroxybutyric acid and, in addition, anesthetic
effects on the peripheral nervous system [51],
[52].
In adult human volunteers, a dose of 2500 mg
per person (estimated dose: 35 – 45 mg/kg) in-
duced a 1-h sleep [53]. When used as an anes-
thetic in children, 66 mg/kg of γ-butyrolactone
resulted in deep sleep with rare cases of respira-
tory depression [54]. Higher specific oral doses,
accidentally ingested by adults or infants, are re-
ported to have caused unconsciousness within
minutes due to CNS depression, occasionally
coma, as well as brachycardia and respiratory
depression. The patients had to be provided sup-
portive medical treatment, but apparently recov-
ered completely within ca. 24 h [55], [56].
In rabbits, γ-butyrolactone does not cause
primary skin irritation but is irritating to the
eye [50]. It does not cause skin sensitization in
guinea pigs [57]. In humans, no skin reactions
were seen after patch-testing of γ-butyrolactone
for skin-contact allergy in 200 volunteers [47].
Lotions containing γ-butyrolactone are well tol-
erated when applied to the skin [51]. The sub-
stance served as successful topical analgesic
for the relief of pain arising from local in-
juries of the musculoskeletal system, including
rheumatic complaints, or from headache (e.g.,
migraine) [51].
Prolonged administration of γ-butyrolactone
in drinking water for four weeks at a daily dosage
of 3 g/kg led to depression of the CNS in rats.
Apart from a slight reduction in body weight
Butyrolactone 5
gain, the animals showed no further health ef-
fects [58]. The low toxicity can be explained by
the fast metabolism and elimination. In animal
studies with repeated oral administration by gav-
age to rats and mice, somewhat higher toxicity
was observed than with application via drinking
water (bolus effect) [59].
The majority of the large number of muta-
genicity and genotoxicity studies provides ev-
idence that γ-butyrolactone is devoid of geno-
toxic potential [47]. Several repeated dose [58],
[60] and lifelong carcinogenicity studies [47],
[59] failed to reveal any signs of chronic organo-
toxic effects by any route of application. Two
valid two-year (lifetime) carcinogenicity stud-
ies in rats and mice receiving up to 450 or
525 mg kg−1 d−1 ) of γ-butyrolactone by gavage
(5 d per week in corn oil) showed no evidence
of tumorigenic potential. The slight increase of
pheochromocytomas in low-dosed male mice
was interpreted by the authors as an equivocal
response [59]. These findings principally con-
firmed the consistently negative results found
in early dermal and oral studies [61], [62], [47]
and therefore allow the conclusion that no sig-
nificant carcinogenic potential is attributable to
γ-butyrolactone.
Prenatal exposure to γ-butyrolactone gave
no evidence of substance-related developmen-
tal toxic effects either by the oral route (rats,
10 – 500 mg kg−1 d−1 ) [63] or by inhalation
(rabbits, 0.5 – 5 mg/L air) [64].
In Europe and the United States, no spe-
cific occupational exposure limits for γ-
butyrolactone have been established.
Experimental acute toxicity data and its ready
degradability suggest that γ-butyrolactone is un-
likely to pose any risk to the environment [65],
[66].
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