Process for nitrosation of C-H-acidic compounds

A process for nitrosating C-H-acidic compounds. The process substantially avoids producing polluted wastewater.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to a process for nitrosating compounds 
containing an active hydrogen bonded to a carbon atom. 
2. Description of the Background 
Nitrosation products of C-H-acidic compounds are used as intermediates in 
the preparation of the corresponding amines, which are, in turn, useful in 
synthesizing a variety of pharmaceuticals and active agents for plant 
protection products. Hydroxyimino and nitroso compounds of malonic acid 
derivatives are examples of these nitrosation products. Many processes for 
nitrosation of malonic acid derivatives, such as esters, amides, 
imidoesters and malononitrile, are known. For example, J. B. Paine III et 
al., in J Org. Chem., 50 (1985), 5598-5604, describe a process for 
preparing diethyl hydroxyiminomalonate by slowly adding an aqueous 
solution of sodium nitrite to a solution of diethyl malonate in glacial 
acetic acid, adding sodium hydroxide solution to the homogeneous reaction 
mixture, followed by separating the reaction product from the aqueous 
phase by extraction with diethyl ether. This process produces an aqueous 
solution containing sodium acetate in approximately 4 times the molar 
amount of the diethyl malonate. 
In German Offenlegungsschrift 23 52 706, ethyl cyanoacetate is first 
converted to diethyl monoimidomalonate hydrochloride with hydrogen 
chloride in absolute alcohol, and then the hydrochloride is dissolved in 
acetic acid. To this solution is added, gradually, an aqueous solution of 
sodium nitrite, and, at the end of the nitrosation reaction, water is 
added to the reaction mixture. The reaction product is separated by 
solvent extraction of the aqueous phase, which contains the sodium acetate 
by-product of the formation of nitrous acid. 
EP-A1-0 517 041 discloses preparing dimethyl hydroxyiminomalonate by adding 
sodium nitrite and acetic acid to a mixture of dimethyl malonate and 
water. The reaction mixture is extracted twice using dichloroethane in 
order to separate the diethyl hydroxyiminomalonate from the sodium 
acetate, which remains in the aqueous phase. Although sodium nitrite is 
used only in amounts of 1.2 mol per mole of malonate, the reaction time of 
21 hours makes this reaction virtually unusable as an industrial process. 
Furthermore, the process is unsuitable for reacting malonates of low water 
solubility. 
All of the processes discussed above produce sodium acetate in the form of 
impure aqueous solutions, which are difficult to dispose of. These 
processes are, therefore, ecologically unsuitable on an industrial scale. 
DE 954 873 describes a process for the preparation of diethyl 
hydroxyiminomalonate by dissolving diethyl malonate in a solvent, such as 
toluene, which is not discernibly miscible with water and can be separated 
from the end product by distillation. To this solution, at least molar 
amounts of sodium nitrite and from 1 to 10 percent by weight, based on the 
malonate, of water are added, followed by gradual addition of acetic acid 
to the suspension at 30.degree. to 70.degree. C. When the nitrosation is 
finished, the undissolved sodium acetate is separated from the reaction 
solution and crystallized diethyl hydroxyiminomalonate is obtained from 
the filtered solution. This process requires no solvent extraction, and 
indeed about 2/3 of the sodium acetate is obtained in solid form. The 
process claims to give "smooth and fast reactions and good yields". The 
latter, at least, is not correct, because the resulting crystalline 
product having a melting point of 86.5.degree.-88.degree. C. was not 
diethyl hydroxyiminomalonate, but instead, a complex with sodium acetate. 
This nitrosation product is so impure that hydrogenation to diethyl 
acetaminomalonate on platinum catalysts in acetic anhydride, a preferred 
solvent, is not possible. 
Accordingly, there remains a need for a method of nitrosating C-H-acidic 
compounds that avoids these disadvantages and provides reaction products 
that can be converted to the corresponding amines. 
OBJECTS OF THE INVENTION 
It is an object of the present invention to provide a process for 
converting C-H-acidic compounds to the corresponding hydroxyimino or 
nitroso derivatives which provides highly pure products in high yield with 
short reaction times and substantially or even completely avoids producing 
polluted wastewater. 
SUMMARY OF THE INVENTION 
The above objects and others are accomplished with a process tor 
nitrosating a compound containing an active hydrogen by contacting a 
cation-containing niitrite salt with a protic acid in the presence of 
water to produce nitrous acid and a salt of the cation from the nitrite 
salt and the conjugate base of the protic acid, followed by nitrosating a 
compound of formula (I): 
EQU X.sup.1 --CHR--X.sup.2 (I), 
where X.sup.1 and X.sup.2 are each electron-withdrawing groups. and R is 
hydrogen or an organic radical. 
where the nitrosation reaction occurs in a homogenous liquid phase 
containing the compound of formula (I), the nitrosation product of the 
compound of formula (I), water, at least a portion of the nitrite salt and 
at least a portion of the protic acid, and 
not less than 50% by weight of the cation-conjugate base salt precipitates 
from the reaction mixture. 
A more complete appreciation of the invention and many of the attendant 
advantages thereof will be readily obtained as the same becomes better 
understood by reference to the following detailed description. 
DETAILED DESCRIPTION OF THE INVENTION 
In the preferred C-H-acidic compounds, i.e., compounds that contain at 
least one active hydrogen bonded to a carbon atom, of the general formula 
(I), R is hydrogen. In this case, the nitrosation products are formed not 
as nitroso compounds but as the tautomeric hydroxyimino compounds, see J. 
March, Advanced Organic Chemistry, Reactions, Mechanisms, and Structure, 
Fourth Edition, John Wiley and Sons, 1992, pp. 592-593, incorporated 
herein by reference. If the protic acid, which liberates nitrous acid from 
the nitrite salt, is a carboxylic acid, the corresponding O-acylated 
hydroxyimino compounds may also form in variable amounts. The nitrosation 
products, therefore, may comprise the group C.cuberoot.NOR' in which R' is 
hydrogen or an acyl radical derived from the carboxylic acid. 
R may also be a organic radical. The organic radical is preferably inert to 
reaction with any of the components of the present process, such as 
nitrite salts, protic acids, nitrous acid and water. Preferably, R is a 
hydrocarbon group containing 1 to 20 carbon atoms. The hydrocarbon group 
may have any structure. such as linear, branched or cyclic. More 
preferably, R is an aliphatic or aromatic radical. Most preferably, R is 
an alkyl radical having 1 to 4 carbon atoms or an aromatic radical having 
6 to 10 carbon atoms. 
The electron-withdrawing groups X.sup.1 and X.sup.2 may be the same or 
different. X.sup.1 and X.sup.2 are preferably --COOR, --C(NR)OR, 
--CON(R).sub.2, --COR, --CN, --NO.sub.2 or an aromatic radical which may 
optionally be substituted with inert groups or atoms. In these 
electron-withdrawing groups, R is as defined above. Preferred aromatic 
radicals have 6 to 10 carbon atoms which may be substituted by inert 
groups or atoms. Non-limiting examples of the C-H-acidic compounds of 
formula (I) include malonic acid and its esters and imidoesters (such as 
dimethyl malonate, dimethyl 2-methylmalonate, diethyl malonate, diethyl 
2-phenylmalonate, diisobutyl malonate, di-2-ethylhexyl malonate and 
diethyl monoimidomalonate); malonic acid amides and amide esters (such as 
malonamide, N,N'-dimethylmalonamide, N,N,N',N'-tetra-methylmalonamide and 
ethyl N,N-dimethylamidomalonate); malononitrile; cyanoacetic acid and its 
esters (such as ethyl cyanoacetate); 2-cyano-propionic acid and its esters 
(such as ethyl 2-cyanopropionate); .beta.-keto acids and their derivatives 
(such as acetoacetic acid and benzoylacetic acid and their esters and 
amides, for example ethyl acetoacetate, N,N-dimethylacetoacetamide and 
ethyl benzoylacetate); 1,3-diketones (such as acetylacetone, 
benzoylacetone and dibenzoylmethane); nitro compounds (such as 
dinitromethane, ethyl nitroacetate and nitroacetonitrile); aromatic 
compounds having a further electron-withdrawing group adjoining the 
--CHR-- group (such as phenylacetic acid esters, phenylacetonitrile 
(benzyl cyanide) and p-nitrophenylacetonitrile). 
The nitrosating agent in the present process is presumably nitrous acid, 
which is liberated in situ from the nitrite salt by the protic acid in the 
presence of water. The nitrite include alkali metal nitrites, such as 
sodium and potassium nitrite. The nitrite salt is preferably used in 
amounts up to 3 mole per mole of C-H-acidic compound (I), more preferably 
from 1 to 1.5 mol, and most preferably from 1.05 to 1.2 mol per mole of 
compound (I). 
Any inorganic or organic protic acid which is able to at least partially 
protonate the nitrite salt to form the nitrous acid is suitable in the 
present process. Preferable inorganic acids include hydrochloric, 
sulfuric, nitric and phosphoric acids. Carboxylic acids are the preferred 
organic acids. Non-limiting examples of organic acids include formic acid, 
acetic acid and propionic acid. Sulfuric acid and acetic acid are 
particularly preferred. It is advantageous to use the acid in at least the 
stoichiometric amount corresponding to the nitrite salt. Larger amounts of 
acid are not harmful, and larger amounts of carboxylic acid are 
particularly recommended when the nitrosation product is subsequently 
hydrogenated to the corresponding amine without separation or 
purification. The acid may also be completely or partially replaced by an 
acid anhydride. This is particularly advantageous when the C-H-acidic 
compound and/or its nitrosation product is not highly soluble in water, or 
in reaction mixtures comprising high proportions of water. The acid 
anhydride scavenges the water which is formed in the nitrosation reaction, 
so that the reaction mixture does not accumulate water to an undesirable 
extent. Naturally, the acid anhydride should not be present in such large 
amounts that it consumes the added water as well because the solubility of 
the nitrite salt in the reaction medium would be too low to provide a 
useful reaction rate. 
Formation of nitrous acid from the nitrite salt and the protic acid 
produces a salt by-product comprising the cation from the nitrite salt and 
the conjugate base of the protic acid. For, example, sodium acetate is 
produced when sodium nitrite and acetic acid are used. Sodium sulfate is 
produced from sodium nitrite and sulfuric acid. The major portion of this 
salt by-product precipitates from the nitrosation reaction mixture, as 
discussed below. 
Water is an important component of the reaction mixture, since it enables 
and promotes the liberation of nitrous acid from the nitrite salt. A 
certain minimum amount of water should be present in order that conversion 
is as complete and as fast as possible at temperatures which are not 
excessively high. If less water is used, then a part of the nitrite salt 
may remain unconverted and make the disposal or re-use of the salt 
by-product which is formed in the reaction more difficult. On the other 
hand, the water should be present in the smallest possible amount, 
particularly when the C-H-acidic compound and/or its nitrosation product 
have low water solubility. In general, these requirements may be met by 
using from 0.01 to 50, preferably 0.03 to 20 percent by weight of water, 
based on the inert organic solvent or solvent mixture which is at least 
partially miscible with water. The use of a solvent or solvent mixture of 
this type is an important characteristic of the novel process. It allows 
nitrosation of C-H-acidic compounds which have low water solubility, such 
as esters of malonic acid, esters of .beta.-ketoacids and 
.beta.-diketones. The solvent or solvent mixture contributes to the 
formation of a homogeneous liquid phase, in which all constituents of the 
reaction mixture are represented, in which the nitrosation reaction takes 
place and out of which the salt formed in the nitrosation reaction to a 
large extent precipitates. It is not necessary for all of the nitrite salt 
to be present in solution in the homogeneous phase. It is sufficient if a 
part of it is dissolved, so that an amount of nitrous acid which is 
sufficient for a fast reaction can be liberated, while the remaining part 
remains suspended and gradually goes into solution at the rate at which 
the dissolved nitrite salt is consumed in the nitrosation reaction. This 
condition is fulfilled by using the amounts of water disclosed above. The 
amount of the protic acid dissolved in the reaction medium, i.e., in the 
homogeneous liquid phase, which liberates the nitrous acid from the 
nitrite salt must naturally correspond at least to the amount of dissolved 
nitrite salt. Since, however, the protic acid is in generally more soluble 
in the reaction mixture than is the nitrite salt, this presents no 
difficulties. In fact, the protic acid is preferably completely dissolved 
in the aqueous phase. This naturally applies, in particular, for the 
embodiments described below in which the acid is metered in, but also when 
the protic acid is part of the initial charge. 
For the purposes of the present process, the organic solvents at least 
partially miscible with water are preferably those which at ambient 
temperature can dissolve at least 1 percent by weight, more preferably at 
least 3 percent by weight and, most preferably, more than 5 percent by 
weight of water. In a particularly preferred embodiment, the organic 
solvent is miscible in all proportions with water and forms a homogeneous 
solution. Solvent mixtures are also suitable as long as the mixture 
dissolves the minimum amount of water discussed above. It is possible, 
therefore, to work with a solvent mixture containing one solvent which 
does not dissolve any discernible amount of water and another solvent in 
which water is highly soluble or which is highly miscible in water, as 
long as this mixture dissolves water in the stated minimum amounts. The 
inert organic solvent or solvent mixture is preferably employed in amounts 
of from 0.05 to 2.5 parts by weight, more preferably from 0.35 to 2.0 
parts by weight per part by weight of C-H-acidic compound. Of course, 
larger amounts of inert organic solvent or solvent mixture can also be 
used, but this may reduce the space-time yield. 
Suitable inert organic solvents include, for example, aliphatic or cyclic 
ethers (such as dibutyl ether, methyl tert-butyl ether, tetrahydrofuran, 
1,4-dioxane, dialkoxyalkanes (for example 1,2-dimethoxyethane) and 
polyethylene glycol ethers); carboxylic acid esters (particularly those 
derived from carboxylic acids and alcohols each having from 1 to 4 carbon 
atoms, such as methyl acetate and ethyl acetate); and N,N-disubstituted 
carboxylic acid amides (particularly those derived from carboxylic acids 
having from 1 to 4 carbon atoms, such as N,N-dimehylformamide and 
N,N-dimethylacetamide); and nitriles (such as acetonitrile and 
propionitrile). A particularly preferred solvent is 1,4-dioxane. If an 
organic acid, such as formic acid, acetic acid or propionic acid, is used 
to liberate the nitrous acid, this acid can serve simultaneously as the 
inert solvent and the protic acid. This is possible provided that the 
amounts of the organic acid and the other constituents of the reaction 
mixture are selected so that, on the one hand, the nitrosation reaction 
proceeds in a homogeneous phase and, on the other hand, at least the 
largest part of the salt formed during liberation of the nitrous acid 
precipitates. 
The relative amounts of the inert organic solvent or solvent mixture at 
least partially miscible with water and water are adjusted such that a 
homogeneous liquid phase forms as a reaction medium, which completely 
dissolves the C-H-acidic compound and its nitrosation product and 
partially dissolves and the nitrite salt and the protic acid. In addition, 
at least the greatest part, i.e, not less than 50% by weight, preferably 
at least 60 percent by weight and in particular at least 80 percent by 
weight, of the salt by-product of the nitrosation reaction is precipitated 
in solid form. Determining the relative amounts of water and inert solvent 
is well within the ability of one of ordinary skill in the art. In any 
case, the major portion of the salt by-product should precipitate, and not 
be produced as aqueous solution. 
The novel process is preferably conducted in the temperature range of 
0.degree. to 100.degree. C. It is particularly advantageous to work in the 
range from 20.degree. to 60.degree. C., more particularly from 30.degree. 
to 40.degree. C. Below 0.degree. C., the reaction proceeds very slowly. 
Above 100.degree. C., decomposition occurs and/or byproducts form. It is 
preferable to increase the temperature toward the end of the reaction, 
within the stated ranges, in order to complete the conversion. Operation 
at atomospheric pressure is preferred. Higher pressures may be preferred 
at higher reaction temperatures or when using low-boiling inert organic 
solvents, such as methyl acetate, so that these solvents does not escape 
from the reaction vessel. 
To carry out the novel process, the inert organic solvent (if present), the 
water, the nitrite salt and the C-H-acidic compound may be charged to a 
stirred reactor and the protic acid which liberates the nitrous acid 
gradually added. Alternatively, the C-H-acidic compound, the inert organic 
solvent (if present), water and the protic acid can be charged and the 
nitrite salt gradually added. This method of operation is preferred when a 
carboxylic acid simultaneously functions as the protic acid and the inert 
organic solvent. In both variations it is possible to omit the water from 
the initial charge and, instead, feed it gradually and separately or 
together with the acid and/or the nitrite salt. Finally, it is also 
possible to precharge all of the reaction components except the water, and 
then add the water gradually. As discussed above, the protic acid can be 
at least partially substituted by an anhydride so that the water content 
of the reaction phase does not rise undesirably. This is particularly true 
when the acid is not precharged but rather is added gradually. 
In all the embodiments described above, cooling is applied if desired, in 
order to maintain the desired reaction temperature. The reaction time 
depends, in part, on the type of C-H-acidic compound, the reaction 
temperature and the cooling capacity. It is expedient to increase the 
temperature by from 10.degree. to 20.degree. C. toward the end of the 
addition of the acid and to continue the reaction at this temperature. By 
this means, the last residues of nitrite salt are decomposed, so that the 
precipitated salt by-product is free from the nitrite salt, and any 
remaining nitrous gases are driven out of the reaction mixture. This can 
be achieved, inter alia, by passing an inert gas (such as nitrogen) 
through the reaction mixture. At the preferred temperatures of from 
20.degree. to 60.degree. C., the reaction requires, in general, up to 
approximately 2 hours. 
The lower the water content in the reaction mixture, the smaller the amount 
of salt by-product that remains dissolved in the reaction mixture. It is 
possible to reduce the water content of the reaction mixture after 
nitrosation, for example, by adding an anhydrous salt which takes on water 
of crystallization. Generally, this also improves the filterability of the 
precipitated salt. Anhydrous sodium acetate or sodium sulfate are 
preferred. It is particularly preferred to isolate the sodium acetate or 
sodium sulfate which forms as the by-product of the present process, 
dehydrate it by heating at 100.degree. to 200.degree. C. and use this 
dehydrated salt to remove water from the reaction mixture after 
nitrosation. In so doing, the salt by-product of the invention process is 
recycled and reused. Water may, of course, also be removed from the 
reaction mixture by distilling or stripping it off at the end of the 
reaction. 
In many cases, it may be advantageous to dilute the reaction mixture before 
separating the precipitated salt by-product with a solvent that is as 
non-polar and inert as possible. Preferred solvents are ethers or 
hydrocarbons. Particularly preferred solvents include, for example, such 
as methyl tert-butyl ether, cyclooctane or isooctane. The reaction mixture 
can then be more easily manipulated and the salt is more easily filtered 
off. Furthermore, it has been found that this gives the nitrosation 
product in a purer form, so that the catalyst requirement in the 
subsequent catalytic hydrogenation which frequently follows is reduced. 
Reaction conditions for catalytic hydrogenation are well-known, see, for 
example, H. O. House, Modern Synthetic Reactions, Second Edition, 
Benjamin/Cummings Publishing Co., 1972, pp. 1-34 and F. A. Carey and R. J. 
Sundberg, Advanced Organic Chemistry, Part B: Reactions and Synthesis, 
Third Edition, Plenum Press, 1990, pp. 219-232, both incorporated herein 
by reference. Platinum catalysts are preferred. 
Even without dilution of the reaction mixture, the salt by-product can be 
isolated with remarkable purity and, after washing with a suitable solvent 
(such as methyl tert-butyl ether, cyclohexane or ethyl acetate), and after 
drying, can be employed in other processes. In the novel process, salt 
solutions which are difficult to dispose of are produced in, at most, 
minor amounts. 
Having generally described this invention, a further understanding can be 
obtained by reference to certain specific examples which are provided 
herein for purposes of illustration only and are not intended to be 
limiting unless otherwise specified.

EXAMPLES 
Example 1 
112.2 g of acetic acid (96%; 1.8 mol) were added dropwise over 2 hours to a 
stirred mixture of 120.0 g (1.0 mol) of dimethyl malonate, 250.0 g of 
1,4-dioxane, 35.6 g of water and 80.0 g (1.15 mol) of sodium nitrite 
(technical grade), maintained at from 35.degree. to 40.degree. C. The 
reaction was allowed to continue for 2 hours at 50.degree. C., then 35 g 
of anhydrous sodium acetate and 400 g of methyl tert-butyl ether were 
added. After cooling to ambient temperature, the precipitated coarsely 
crystalline solid was filtered off using suction and was washed twice 
using 150 ml of methyl tert-butvl ether each time. The filtrate and the 
wash liquid were freed from low-boilers at 60.degree. C. under water pump 
vacuum. This gave 186.4 g of a solid residue melting in the range from 
47.degree. to 56.degree. C. Analysis by gas chromatography/mass 
spectroscopy (GC/MS) showed a mixture of dimethyl hydroxyiminomalonate and 
dimethyl acetoxyiminomalonate. By GC analysis the product contained &lt;0.5 
FID area percent of unconverted dimethyl malonate. 
Example 2 
224.3 g (3.6 mol) of acetic acid were added dropwise over 2 hours to a 
mixture of 320.4 g (2.0 mol) of diethyl malonate, 500 g of 1,4-dioxane, 
71.2 g of deionized water and 160 g (2.3 mol) of sodium nitrite (technical 
grade), maintained at 40.degree. C. The reaction mixture was allowed to 
continue reacting for 1 hour at 50.degree. C., was cooled to ambient 
temperature and the homogeneous mixture was seeded with sufficient sodium 
acetate trihydrate to cover the tip of a spatula, upon which the sodium 
acetate formed during the reaction precipitated in coarsely crystalline 
form comprising from 0 to 3 molecules of water of crystallization. The 
mixture was filtered, the filter cake washed using 1,4-dioxane, and the 
low boilers were distilled off from the filtrate and from the wash liquid. 
There remained 423.0 g of a clear, light yellow oil, containing &lt;0.6 FID 
area percent of unconverted diethyl malonate. Catalytic hydrogenation and 
recrystallization of the crude product gave diethyl acetaminomalonate in a 
yield of 85% of theory, based on diethyl malonate employed, with a purity 
of &gt;99.8 FID area percent. 
Example 3 
The procedure of Example 2 was followed, however after the end of the 
reaction 70 g of anhydrous sodium acetate (obtained from a previous 
reaction mixture by filtration and drying at 130.degree. C. under 
water-pump vacuum) were added. By this method, the sodium acetate formed 
could be filtered off more easily than in Example 2, the yield was 417.2 g 
of light yellow oil comprising &lt;0.6 FID area percent of unconverted 
diethyl malonate. Catalytic hydrogenation and recrystallization of the 
crude product gave diethyl acetamidomalonate at a yield of 85% of theory, 
based on the diethyl malonate employed, and a purity of &gt;99.8 FID area 
percent. 
Example 4 
The procedure of Example 3 was followed, but after addition of the 
anhydrous sodium acetate 400 g of methyl tert-butyl ether was also added. 
426 g of light yellow oil remained, which gave, on catalytic hydrogenation 
and recrystallization of the crude product, diethylacetamidomalonate at a 
yield of 88% of theory, based on the diethyl malonate employed, and with a 
purity of &gt;99.8 FID area percent. 
Example 5 
A mixture of 1,4-dioxane, acetic acid and water, obtained from a previous 
reaction mixture by taking a low-boiling cut, was metered into a stirred 
mixture of 320.4 g (2.0 mol) of diethyl malonate and 160 g (2.3 mol) of 
sodium nitrite (technical grade), maintained at 35.degree. C. 12.0 g of 
water were then metered in and 166 g (207. mol) of acetic acid (96%) were 
added dropwise over 2 hours. The mixture was allowed to continue reacting 
for 2 hours at 40.degree. C. and was worked up as described in Example 4. 
There remained 425 g of light yellow oil, which, after catalytic 
hydrogenation and recrystallization of the crude product, gave diethyl 
acetaminomalonate at a yield of 86% of theory, based on the diethyl 
malonate employed, and with a purity of &gt;99.8 FID area percent. 
Example 6 
The procedure of Example 2 was followed, but the 1,4-dioxane was replaced 
by tetrahydrofuran. There remained 427 g of light yellow oil, which 
comprised &lt;1 FID area percent of unconverted diethyl malonate. 
Example 7 
The procedure of Example 3 was followed, however the 1,4-dioxane was 
replaced by 600 g of ethyl acetate, the amount of water added was reduced 
to 20 g and the acetic acid was replaced by 166.6 g of acetic anhydride. 
There remained 425 g of light yellow oil, which, after catalytic 
hydrogenation and recrystallization of the crude product, gave diethyl 
acetaminomalonate in a yield of 85% of theory, based on the diethyl 
malonate employed, and with a purity of &gt;99 FID area percent. 
Example 8 
The procedure of Example 3 was followed, but the 1,4-dioxane was replaced 
by the same amount of polyethylene glycol ether (molecular weight about 
500). This gave 921 g of a solution comprising the nitrosation products. 
It comprised &lt;1 FID area percent of unconverted diethyl malonate. 
Example 9 
112.2 of acetic acid (96%) were added dropwise over 2 hours to a stirred 
mixture of 216.0 g (1 mol) of diisobutyl malonate, 250 g of 1,4-dioxane, 
25.6 g of deionized water ad 80 g (1.15 mol) of sodium nitrite (technical 
grade), maintained at from 35.degree. to 40.degree. C. The mixture was 
allowed to continue reacting for 2 hours at 50.degree. C., then 35.0 g of 
anhydrous sodium acetate and 200 g of methyl tert-butyl ether were added. 
After cooling of the mixture, the precipitated coarsely-crystalline sodium 
acetate trihydrate was filtered off and washed using methyl tert-butyl 
ether. Removal of the low-boilers by distillation at 60.degree. C. under 
water-pump vacuum gave 258.7 g (88.6% of theory) of residue comprising 
primarily diisobutyl hydroxyiminomalonate. The content of unconverted 
diisobutyl malonate was 0.4 FID aea percent. 
Example 10 
570.0 g of concentrated sulfuric acid was added dropwise over 2 hours to a 
stirred mixture of 113.1 g (1.0 mol) of ethyl cyanoacetate, 250.0 g of 
1,4-dioxane, 35.6 g of deionized water and 80.0 g (1.15 mol) of sodium 
nitrite (technical grade), maintained at 25.degree. C. The mixture was 
allowed to continue reacting for 2 hours at 25.degree. C., then 400 g of 
methyl tert-butyl ether were added, the mixture was cooled to ambient 
temperature, and the suspension obtained was filtered. The filter cake was 
washed twice using 100 ml of methyl tert-butyl ether each time. 
Low-boilers were removed from the filtrate and the wash liquid at 
60.degree. C./16 mm Hg. There remained 136.7 g of oily crystalline residue 
comprising &lt;0.4 FID area percent of unconverted ethyl cyanoacetate. 
Example 11 
112.2 g of acetic acid (96%; 1.8 mol) were added dropwise over 2 hours to a 
stirred mixture of 130.2 g of ethyl acetoacetate, 250 g of 1,4-dioxane, 
35.6 g of deionized water and 80 g of sodium nitrite, maintained at 
35.degree. C. The mixture was allowed to continue reacting for 2 hours at 
50.degree. C., 200 g of methyl tert-butyl ether were added to the clear 
solution obtained and the mixture was cooled to ambient temperature. After 
filtering off and washing the precipitated solid, the filtrate and the 
wash liquid were concentrated at 60.degree. C. under water-pump vacuum. 
There remained 170.4 g (99% of theory) of ethyl acetoxyiminoacetoacetate 
comprising 0.5 FID area percent of unconverted ethyl acetoacetate. 
Example 12 
112.2 g of acetic acid (96%; 1.8 mol) were metered in over 2 hours to a 
stirred mixture of 224.0 g of dibenzoylmethane, 250 g of 1,4-dioxane, 35.6 
g of deionized water and 80.0 g of sodium nitrite (technical grade), 
maintained at 35.degree. C. The mixture was allowed to continue reacting 
for 2 hours at or below 40.degree. C., 600 g of methyl tert-butyl ether 
was added and the mixture cooled to ambient temperature. After filtering 
off and washing the precipitated sodium acetate, the filtrate and the wash 
liquid was freed from low-boilers at 60.degree. C. under water-pump 
vacuum. There remained 216.6 g of crystalline residue comprising 4 FID 
area percent of unconverted dibenzoylmethane. 
Example 13 
28.2 g sulfuric acid was added dropwise over 3 hours to a stirred mixture 
of 51.0 g of malonamide, 41.8 g of deionized water, 250 g of 1,4-dioxane 
and 19.9 g of sodium nitrite (technical), maintained at 20.degree. C. The 
reaction was allowed to continue for 2 hours at 30.degree. C., 300 ml of 
ethvl acetate, followed by 20.0 g of anhydrous sodium sulfate, were added 
to the mixture, and it was cooled to ambient temperature. The precipitated 
solid was filtered off and washed several times using ethyl acetate. The 
low-boilers were removed from the filtrate and from the wash liquid under 
reduced pressure. The residue was a nitrosation product having a melting 
range of from 158.degree. C. to 167.degree. C. and comprising &lt;2 FID area 
percent of unconverted malonamide. 
Example 14 
225.0 g of glacial acetic acid were added dropwise over 2 hours to a 
stirred mixture of 320 g (2 mol) of diethyl malonate, 15 g of deionized 
water and 160 g (2.3 mol) of sodium nitrite, maintained at 35.degree. C. 
The reaction was allowed to continue for 2 hours at 50.degree. C., then 
the mixture was filtered and the filter cake washed with glacial acetic 
acid. The filtrate and the wash liquid were freed from low-boilers at 
60.degree. C. under water-pump vacuum. The residue was 410.1 g of a clear, 
light yellow oil, which gas-chromatographic analysis showed to contain, in 
addition to diethyl hydroxyiminomalonate and diethyl 
O-acetoxyiminomalonate, 5 FID area percent of unconverted diethyl 
malonate. The separated sodium acetate was dried at 60.degree. C. under 
water-pump vacuum (final weight 160.0 g). It was fully soluble in 
deionized water. 
Example 15 
The procedure of Example 14 was followed, however after the end of the 
reaction 800 g of methyl tert-butyl ether were added, and the mixture was 
filtered at ambient temperature. There remained 420.0 g of clear, light 
yellow oil, which gas-chromatographic analysis showed to comprise, in 
addition to diethyl hydroxyiminomalonate and diethyl 
O-acetoxyiminomalonate, 5 FID area percent of unconverted diethyl 
malonate. 
Obviously, numerous modifications and variations of the present invention 
are possible in light of the above teachings. It is therefore to be 
understood that within the scope of the appended claims, the invention may 
be practiced otherwise than as specifically described herein. 
The present application is based on German Patent Application No. 196 22 
467.5, filed Jun. 5, 1996, and incorporated herein by reference in its 
entirety.