Classifications

• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
  • C12P7/00—Preparation of oxygen-containing organic compounds
  • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
  • C12P7/42—Hydroxy-carboxylic acids
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C253/00—Preparation of carboxylic acid nitriles

Definitions

• This invention relates to a chemical process to synthesize glycolonitrile from formaldehyde and hydrogen cyanide. More specifically, a method to produce substantially pure glycolonitrile is provided by reacting pre-heated formaldehyde with hydrogen cyanide. BACKGROUND OF THE INVENTION
• Glycolonitrile (HOCH 2 CN; CAS Registry Number 107-16-4) is an ⁇ - hydroxynitrile that can be enzymatically converted to glycolic acid using a catalyst having nitrilase activity or a combination of nitrile hydratase and amidase activities.
• Glycolic acid (HOCH 2 CO 2 H; CAS Registry Number is 79-14-1 ) is the simplest member of the ⁇ -hydroxy acid family of carboxylic acids. Its properties make it ideal for a broad spectrum of consumer and industrial applications, including use in water well rehabilitation, the leather industry, the oil and gas industry, the laundry and textile industry, and as a component in personal care products like skin creams.
• Glycolic acid also is a principle ingredient for cleaners in a variety of industries (dairy and food processing equipment cleaners, household and institutional cleaners, industrial cleaners [for transportation equipment, masonry, printed circuit boards, stainless steel boiler and process equipment, cooling tower/heat exchangers], and metals processing [for metal pickling, copper brightening, etching, electroplating, electropolishing]).
• Glycolonitrile is also a versatile intermediate in the preparation of aminonitriles, which are, in turn, useful in preparing aminocarboxylic acid compounds.
• US 5,208,363 discloses the use of glycolonitrile in the preparation of aminonitrile precursors for the production of ethylenediaminetetraacetic acid (EDTA), and US 5,817,613 describes the use of glycolonitrile in the synthesis of 2-hydroxyethyl iminodiacetic acid (HEIDA). EDTA and HEIDA are useful as chelating agents as components of detergent compositions.
• FR1575475 describes the use of glycolonitrile in the synthesis of alkali metal salts of nitrilotriacetic acid.
• glycolonitrile can be used as a precursor to glycinonitrile, which can be converted to glycine as disclosed in US2003/0040085.
• Glycine is widely used as an additive in processed meats and beverages, and as a raw material for the commercially important herbicide, N- (phosphonomethyl)glycine, also known by its common name glyphosate, as described in US 6,759,549.
• Microbial catalysts can hydrolyze a nitrile (e.g., glycolonitrile) directly to the corresponding carboxylic acids (e.g., glycolic acid) using a nitrilase (EC 3.5.5.7), where there is no intermediate production of the corresponding amide (Equation 1 ), or by a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) enzymes, where a nitrile hydratase (NHase) initially converts a nitrile to an amide, and then the amide is subsequently converted by the amidase to the corresponding carboxylic acid (Equation 2):
• Concentrated aqueous solutions of formaldehyde typically are comprised of free formaldehyde and various oligomers of formaldehyde (for example, paraformaldehyde and trixoxymethylene).
• formaldehyde e.g., 37 wt% solutions commercially known as formalin
• oligomers of formaldehyde for example, paraformaldehyde and trixoxymethylene.
• the presence of formaldehyde oligomers can influence overall conversion to glycolonitrile.
• a method to pre-treat the formaldehyde that transforms formaldehyde oligomers to more free formaldehyde in the feed stream prior to reacting with hydrogen cyanide should increase the yield of glycolonitrile and should decrease the conversion of unwanted secondary products produced from the oligomers.
• Jacobson discloses a method of obtaining pure glycolonitrile by the reaction of hydrogen cyanide and formaldehyde in the presence of an acidic compound followed by distillation at subatmospheric pressure (vacuum distillation step conducted at about 125 0 C).
• the reactants are preferably mixed "in the cold" (i.e., below 26 °C to maintain the hydrogen cyanide in liquid form).
• Also described in US 2,175,805 is the observation that 1 ) glycolonitrile decomposes at ambient temperature, and 2) glycolonitrile contacted with bases decomposes violently within hours at ambient temperature. Jacobson does not disclose pre-treatment of the concentrated aqueous formaldehyde feed prior to reacting with hydrogen cyanide.
• Sexton discloses a method of preparing glycolonitrile in which formaldehyde is fed into an aqueous solution of HCN. The reaction is run "with efficient reflux or a closed pressure system, with the reaction allowed to go as high as 100 0 C.” However, as described in Jacobson, glycolonitrile decomposes at room temperature. A reaction run at temperatures as high as 100 0 C would be expected to result in an increase in the decomposition of the glycolonitrile. Similar to
• Jacobson, Sexton does not describe a method to pre-treat the formaldehyde prior to reacting with hydrogen cyanide.
• Cullen et al. discloses a method for making iminodiacetonitrile from glycolonitrile. This reference describes how glycolonitrile can be formed in a process (either batch or continuous) by maintaining the pH of the formaldehyde above about 3, preferably in the range of about 5-7, most preferably about 5.5, with suitable acids and bases. The formaldehyde is then reacted with hydrogen cyanide in a temperature range of about 20 to 80 °C, preferably about 30 °C, to form glycolonitrile.
• a reaction run within the conditions specified in Cullen et al. results in a significant amount of unreacted free formaldehyde after 2 hours of reaction time.
• the problem to be solved is the lack of a method to produce glycolonitrile by reacting formaldehyde and hydrogen cyanide under conditions that produce a substantially pure reaction product. Specifically, a method is lacking that reduces the amount of unreacted formaldehyde (one of the impurities associated with enzyme inactivation when convertii ⁇ glycolonitrile to glycolic acid), and minimizes the number of post-reaction purification steps.
• a method for preparing glycolonitrile comprising: (a) providing an aqueous formaldehyde feed stream that is heated to a temperature of about 90 °C to about 150 ° for a determinable period of time; and
• the glycolonitrile produced by the present process is recovered.
• the amount of time the aqueous formaldehyde feed stream is heated may vary as long as the polymeric formaldehyde impurities are substantially decomposed into monomeric formaldehyde prior to reacting the heated aqueous stream with hydrogen cyanide.
• the aqueous formaldehyde feed stream is heated to a temperature of about 90 °C to about 150 0 C for a period of time from about 10 seconds to about 24 hours. In another embodiment, the period of heating may range from about 30 seconds to about 6 hours.
• the method further comprises the addition of catalytic amounts of base, such as NaOH or KOH, to accelerate the conversion of higher molecular weight polymeric formaldehyde into lower molecular weight and monomeric formaldehyde.
• the heated formaldehyde is promptly fed to the reactor and reacted with hydrogen cyanide.
• the heated aqueous formaldehyde feed stream is promptly fed to a reaction chamber pre-charged with hydrogen cyanide at a temperature suitable for glycolonitrile synthesis.
• the reaction temperature is typically about 70 0 C or less in order to minimize glycolonitrile decomposition.
• the reaction temperature is between about -20 °C to about 70 °C, preferably about 0 °C to about 70 0 C, more preferably about 0 °C to about 55 °C, even more preferably about 10 °C to about 30 0 C, and most preferably about 20 °C to about 25 °C.
• Additional embodiments of the invention include the aqueous formaldehyde feed stream further comprising about 0.1 wt% to about 15 wt% methanol, or about 3 wt% to about 8 wt% methanol.
• the method further comprises adding glycolic acid to the aqueous glycolonitrile to maintain the pH of the glycolonitrile below 7.
• the resulting product may be recovered, isolated, and/or purified.
• Figure 1 shows 13 C NMR spectrum of the resulting glycolonitrile solution from Comparative Example A, qualitatively indicating the purity of the glycolonitrile product.
• the 13 C NMR spectrum shows the major glycolonitrile 13 C resonances at about ⁇ 48 and 119 ppm. There are also substantial resonances around ⁇ 80 - 90 ppm for unreacted formaldehyde and around ⁇ 60 ppm for other by-product species derived from unreacted formaldehyde.
• Figure 2 shows 13 C NMR spectrum of the resulting glycolonitrile solution from Example 1 , qualitatively indicating the purity of the glycolonitrile product.
• the major resonances for glycolonitrile at about ⁇ 48 and 119 ppm are observed.
• the resonances around ⁇ 80 - 90 ppm evident in Figure 1 for unreacted formaldehyde are noticeably reduced in Figure 2.
• the resonances around ⁇ 60 ppm for by-products derived from unreacted formaldehyde remain, most likely due to the initial formaldehyde reactor charge.
• Figure 3 shows 13 C NMR spectrum of the resulting glycolonitrile solution from Example 2, qualitatively indicating the purity of the glycolonitrile product.
• the major resonances for glycolonitrile at about ⁇ 48 and 119 ppm are evident in Figure 3, while the levels of impurities are substantially reduced from the levels observed in Figure 1 and Figure 2.
• Figure 4 shows 13 C NMR spectrum of the resulting glycolonitrile solution from Example 3, qualitatively indicating the purity of the glycolonitrile product.
• the major resonances for glycolonitrile at about ⁇ 48 and 119 ppm are evident in Figure 4, while the levels of impurities are substantially reduced from the levels observed in Figure 1 and Figure 2.
• Figure 4 also clearly shows the resonance at ⁇ 49 ppm for the methanol from the formalin feed used in Example 3.
• Figure 5 shows the 13 C NMR spectrum of the composite sample produced by mixing the 5 concentrated glycolonitrile samples prepared in Examples 4-8, quantitatively indicating the purity of the glycolonitrile product.
• the quantitative 13 C NMR analysis was performed on the composite sample to determine the purity of the glycolonitrile produced.
• Figure 6 shows 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product produced in Example 9.
• Figure 7 shows 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product produced in Example 10.
• the stated problem has been solved by providing a method that produces an aqueous solution comprising glycolonitrile with significantly fewer impurities, especially unreacted free formaldehyde, than can be obtained by other methods.
• the aqueous formaldehyde feed stream is heat-treated prior to the reaction with hydrogen cyanide. The reaction yields very high formaldehyde conversion and few accompanying impurities.
• Concentrated aqueous formaldehyde solutions are typically comprised of monomeric formaldehyde ("free formaldehyde", the desired substrate for the reaction) and oligomers of formaldehyde. Pre-heating the formaldehyde feed stream improves the purity of the resulting glycolonitrile product.
• the reaction of formaldehyde with hydrogen cyanide is temperature-controlled to minimize glycolonitrile decomposition.
• the reaction product formed is an aqueous solution comprising glycolonitrile and significantly less unreacted formaldehyde when compared to a reaction product obtained without pre-heating the aqueous formaldehyde feed stream.
• the resulting aqueous glycolonitrile solution requires fewer post reaction purification steps (such as distillative purification), thus reducing the cost of producing glycolonitrile that is suitable for uses requiring a certain level of purity, such as, enzymatic synthesis of glycolic acid. Additionally, reducing the amount of unreacted formaldehyde in the aqueous glycolonitrile solution used for enzymatic synthesis of glycolic acid should extend the enzymatic catalyst's lifespan (i.e., the number of recycle reactions). This improves the catalyst's productivity and reduces the cost for preparing glycolic acid.
• the invention yields a glycolonitrile product that may be used directly for enzymatic conversion without purification, significantly reducing the cost of producing glycolic acid.
• Aqueous formaldehyde (ranging in concentration from about 5 wt% to about 70 wt%; preferably about 20 wt% to about 55 wt%) is heated to a temperature ranging from about 35 °C to about 200 0 C; preferably about 90 °C to about 150 0 C.
• the heated aqueous formaldehyde feed stream is promptly fed to a reaction chamber pre-charged with hydrogen cyanide at a temperature suitable for glycolonitrile synthesis.
• a temperature suitable for glycolonitrile synthesis is used to describe a reaction temperature range suitable for reacting hydrogen cyanide and the heat-treated formaldehyde.
• the reaction temperature is typically about 70 °C or less in order to minimize glycolonitrile decomposition. In another embodiment, the reaction temperature is between about -20 °C to about 70 °C, preferably about 0 0 C to about 70 °C, more preferably about 0 0 C to about 55 °C, even more preferably about 10 0 C to about 30 °C, and most preferably about 20 0 C to about 25 0 C.
• the heated aqueous formaldehyde and the hydrogen cyanide are added to the reaction mixture at a rate to ensure 1 ) the hydrogen cyanide is in slight excess (at least 1 % molar excess compared to the amount of formaldehyde added; preferably at least 10% excess), and 2) the overall reaction temperature is maintained at a temperature suitable for glycolonitrile synthesis.
• the resulting aqueous solution of glycolonitrile is significantly purer (i.e., has less unreacted formaldehyde), requiring less post-reaction purification.
• the aqueous glycolonitrile reaction product formed does not require any post-reaction purification prior to enzymatic conversion to glycolic acid. Definitions:
• the term “comprising” means the presence of the stated features, integers, steps, or components as referred to in the claims, but that it does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.
• the term “about” modifying the quantity of an ingredient or reactant of the invention employed refers to variation in the numerical quantity that can occur, for example, through typical measuring and liquid handling procedures used for making concentrates or use solutions in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of the ingredients employed to make the compositions or carry out the methods; and the like.
• the term “about” also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term “about”, the claims include equivalents to the quantities. In one aspect, the term “about” means within 20% of the recited numerical value, preferably within 10%, and most preferably within 5%.
• Glycolonitrile is abbreviated as "GLN” and is synonymous with hydroxyacetonitrile, 2-hydroxyacetonitrile, hydroxymethylnitrile, and all other synonyms of CAS Registry Number 107-16-4.
• GLA glycol acid
• formaldehyde is abbreviated as "FA” and is synonymous with formic aldehyde, methyl aldehyde, oxomethane, and all other synonyms of CAS Registry Number 50-00-0.
• Commercially available formaldehyde is typically comprised of a mixture of monomeric formaldehyde ("free formaldehyde”) and various oligomers of formaldehyde.
• free formaldehyde refers to monomeric formaldehyde.
• hydrogen cyanide is synonymous with prussic acid, hydrocyanic acid, and all other synonyms of CAS Registry Number 200-821-6.
• heat treatment As used herein, the terms "heat treatment”, “heat-treated”, “heating the formaldehyde feed stream”, “pre-heated formaldehyde”, and “an aqueous formaldehyde feed stream that is heated” are used to describe the process of subjecting an aqueous formaldehyde solution to a prescribed temperature for a period of time prior to reacting with hydrogen cyanide. The temperature and duration of the heat treatment is chosen to optimize the amount of monomeric formaldehyde in the heated formaldehyde feed stream.
• the aqueous formaldehyde solution is heat-treated at a temperature from about 35 °C to about 200 °C, preferably from about 75 0 C to about 150 0 C, more preferably from about 90 °C to about 150 °C, and most preferably from about 100 0 C to about 125°C for a determinable period of time, ranging from about 10 seconds to about 24 hours, preferably from about 10 seconds. to about 6 hours, and more preferably about 10 seconds to about 20 minutes, and most preferably about 2 minutes to about 10 minutes.
• the heat treatment time is about 2 minutes to about 10 minutes in the presence of a base catalyst. The heated formaldehyde is promptly fed to the reactor and reacted with hydrogen cyanide.
• the terms "promptly fed to the reactor” and “promptly adding the heated formaldehyde” are used to described the time period between the end of the heat treatment period and the initiation of the reaction with hydrogen cyanide, typically less than about 24 hours, preferably less than about 1 hour, more preferably less than about 15 minutes, most preferably less than about 5 minutes.
• the time between the end of heat treatment period and the initiation of the hydrogen cyanide reaction may be more than about 24 hours.
• the present method describes a process to produce aqueous glycolonitrile by reacting formaldehyde and hydrogen cyanide.
• the formaldehyde is heated prior to reacting with the hydrogen cyanide to make glycolonitrile.
• the starting concentration of the formaldehyde is typically an aqueous solution of about 5 wt% to about 70 wt%.
• the formaldehyde feed stream is comprised of about 20 wt% to about 55 wt% formaldehyde.
• the formaldehyde feed stream is comprised of about 37 wt% formaldehyde.
• the formaldehyde feed stream may optionally be comprised of about 0.1 wt% to about 15 wt% (typically 6-8 wt%) methanol (an additive typically found in some 37 wt% solutions [/.e.,formalin]).
• a base catalyst (KOH, NaOH, etc.) may be added to the aqueous formaldehyde solution prior to heating the aqueous formaldehyde feed stream.
• sodium hydroxide may be added to the aqueous formaldehyde feed stream prior to heating the formaldehyde feed stream.
• the molar ratio of NaOH:formaldehyde in the heated aqueous formaldehyde feed stream is about 1 :50 to about 1 :2000.
• the molar ratio of NaOH:HCHO in the heated aqueous formaldehyde feed stream is about 1 :100 to about 1 :2000.
• the formaldehyde feed stream is heated to a temperature of about 35 0 C to about 200 °C for a determinable period of time.
• the formaldehyde feed stream is heated to a temperature of about 75 °C to about 150 °C.
• the formaldehyde feed stream is heated to a temperature of about 90 °C to about 150 0 C.
• the formaldehyde feed stream is heated to a temperature of about 100 °C to about 125 0 C.
• the term "determinable period of time" is used to describe the amount of time the formaldehyde feed stream is heated to the specified temperature.
• the optimal length of time the formaldehyde is heat-treated can be easily determined and may be adjusted depending upon the selected temperature in combination with the specific design of the heat treatment system and the reactor.
• the length of the heat treatment is chosen to maximize the amount of monomeric formaldehyde in the heated feed stream.
• the monomeric formaldehyde reacts with the hydrogen cyanide to produce a glycolonitrile solution with substantially fewer impurities (i.e. unreacted formaldehyde and impurities associated with polymeric forms of formaldehyde).
• the heat treatment period can last from about 10 seconds to about 24 hours, preferably about 10 seconds to about 6 hours, more preferably about 10 seconds to about 20 minutes, and most preferably about 2 minutes to about 10 minutes.
• the heat treatment time is about 2 minutes to about 10 minutes in the presence of a base catalyst. The heated formaldehyde is then promptly fed to the reaction chamber.
• the hydrogen cyanide feed stream is typically added at a rate sufficient to maintain a slight molar excess of hydrogen cyanide relative to the amount of formaldehyde added to the reaction chamber.
• the molar ratio of hydrogen cyanide to formaldehyde is at least about 1.01 :1 , preferably no greater than about 10:1.
• the molar ratio of HCN to formaldehyde is about 1.01 :1 , more preferably no greater than about 2:1.
• the molar ratio of HCN to formaldehyde is about 1.05:1 to about 1.15:1.
• the reaction chamber may optionally be pre-charged with hydrogen cyanide so that the formaldehyde is immediately in contact with the hydrogen cyanide upon addition to the reaction chamber. Pre-charging the reaction chamber with hydrogen cyanide aids in maintaining the slight excess of hydrogen cyanide during the reaction.
• HCN pre-charge the mole ratio of the HCN to formaldehyde rapidly transitions from infinity to the more sustainable ration of 10:1 or less, preferably 2:1 or less, more preferably about 1.01 :1 to about 1.15:1 , and most preferably about 1.01 :1 to about 1.05:1.
• the temperature of the reaction chamber is typically about 70 °C or less in order to minimize glycolonitrile decomposition.
• the reaction temperature is between about -20 °C to about 70 °C, preferably about 0 0 C to about 70 °C, more preferably about 0 °C to about 55 0 C, even more preferably about 10 °C to about 30 °C, and most preferably about 20 °C to about 25 °C.
• Atmospheric pressure is satisfactory for carrying out the reaction of formaldehyde and hydrogen cyanide, and hence pressures of from about 0.5 to about 10 atmospheres (50.7 kPa to 1013 kPa) are preferred. Higher pressures, up to 20,000 kPa or more may be used, if desired, but any benefit that may be obtained thereby would probably not justify the increased cost of such operations.
• the pH in the glycolonitrile synthesis reaction chamber is about 3 to about 10, preferably about 5 to about 8.
• the present glycolonitrile synthesis reaction can be run in continuous, batch, or fed batch mode.
• the fed batch reaction typically is run for about 10 seconds to about 24 hours, preferably about 30 minutes to about 8 hours, more preferably about 0.5 hours to about 4 hours.
• a variety of analytical methods can be used in the present methods to analyze the reactants and products including, but not limited to titration, high performance liquid chromatography (HPLC), gas chromatography (GC), mass spectroscopy (MS), quantitative 13 C nuclear magnetic resonance (NMR), and capillary electrophoresis (CE), to name a few.
• HPLC high performance liquid chromatography
• GC gas chromatography
• MS mass spectroscopy
• NMR quantitative 13 C nuclear magnetic resonance
• CE capillary electrophoresis
• the present method produces glycolonitrile with significantly less free (monomeric) formaldehyde.
• the glycolonitrile does not require additional purification/isolation/recovery steps prior to being enzymatically converted into glycolic acid (typically in the form ammonium glycolate).
• the glycolonitrile produced by the present method can be purified, isolated, and/or recovered using a variety of techniques including, but not limited to distillation, crystallization, and solvent extraction. Stabilization of Glvcolonitrile Under Acidic Conditions
• a mineral acid e.g., HCI, H 2 SO 4 , or H 3 PO 4
• a mineral acid e.g., HCI, H 2 SO 4 , or H 3 PO 4
• glycolic acid is added to the glycolonitrile mixture obtained by the present method to maintain the pH of the glycolonitrile below 7.
• the amount of glycolic acid added is sufficient to maintain the pH of the glycolonitrile below about 6, preferably below about 5, more preferably below about 4, and most preferably below about 3.5.
• Stabilization with glycolic acid is a preferred embodiment in the instance where the glycolonitrile is subsequently converted to glycolic acid using an enzyme catalyst.
• the use of glycolic acid to adjust the pH in this instance avoids the addition of a mineral acid, where, upon conversion of glycolonitrile to glycolic acid, the presence of a mineral acid and/or the production of the corresponding mineral acid salt may require a purification step to remove the mineral acid and/or the corresponding salt from the glycolic acid product.
• the pH of the acid-stabilized glycolonitrile solution is adjusted with a base to a more neutral pH range (i.e. pH of about 6 to about 8) prior to enzymatic conversion of glycolonitrile to glycolic acid (typically in the form of the ammonium salt of glycolic acid).
• the reaction product mixtures were analyzed by the following HPLC method. Aliquots (0.01 mL) of the reaction mixture were added to 1.50 mL of water, and analyzed by HPLC (HPX 87H column, 30 cm x 7.8 mm; 0.01 N H 2 SO 4 mobile phase; 1.0 mL/min flow at 50 °C; 10 ⁇ L injection volume; Rl detector, 20 min analysis time). The method was calibrated for glycolonitrile at a series of concentrations using commercially available glycolonitrile purchased from Aldrich.
• Figure 1 shows the 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product.
• the 13 C NMR spectrum shows the major glycolonitrile 13 C resonances at about ⁇ 48 and 119 ppm. There are also substantial resonances around ⁇ 80 - 90 ppm for unreacted formaldehyde and around ⁇ 60 ppm for other by-product species derived from unreacted formaldehyde.
• the reaction vessel equipped with stirring, was placed within an oil bath maintained at 55 0 C.
• the approximately 12-inch section of the formaldehyde feed line (1/16 " OD (about 1.6 mm) x 0.040 " ID (about 1.02 mm)) directly preceding the inlet to the reaction flask was heated to 120 °C, and the reactants were then each continuously pumped into the reaction vessel over a period of about 2.0 hr, as follows:
• Figure 2 shows the 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product.
• the major resonances for glycolonitrile at about ⁇ 48 and 119 ppm are observed.
• the resonances around ⁇ 80 - 90 ppm evident in Figure 1 for unreacted formaldehyde are noticeably reduced in Figure 2.
• the resonances around ⁇ 60 ppm for by-products derived from unreacted formaldehyde remain, most likely due to the initial formaldehyde reactor charge.
• Figure 3 shows the 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product.
• the major resonances for glycolonitrile at about ⁇ 48 and 119 ppm are evident in Figure 3, while the levels of impurities are substantially reduced from the levels observed in Figure 1 and
• the reaction vessel equipped with stirring, was charged with a mixture of 0.18 g of HCN in 3.4 g of water and then placed within an oil bath maintained at 55 0 C.
• the approximately 12-inch section of the formaldehyde feed line (1/16" OD x 0.040" ID) directly preceding the inlet to the reaction flask was heated to 120 °C, and the reactants were then each continuously pumped into the reaction vessel over a period of about 2.0 hr, as follows:
• Figure 4 shows the 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product. Again, the major resonances for glycolonitrile at about ⁇ 48 and 119 ppm are evident in Figure 4, while the levels of impurities are substantially reduced from the levels observed in Figure 1 and Figure 2. Figure 4 also clearly shows the resonance at ⁇ 49 ppm for the methanol from the formalin feed used in Example 3.
• the approximately 36-inch section of the formaldehyde feed line (1/8" OD (about 3.18 mm) x 0.085" ID (about 2.16 mm)) directly preceding the inlet to the reaction flask was heated to 120 °C after filling the formaldehyde feed line, and the flow of heated formaldehyde feed was first established by observing two-phase flow from the outlet of the formaldehyde feed line. After establishing two-phase flow out of the formaldehyde feed line, the reaction vessel was raised to introduce the formaldehyde feed directly into the liquid reaction mixture.
• the stirplate, water bath, and lab jack assembly was then raised accordingly to provide reactor mixing and to maintain the reaction temperature around 20 - 25 0 C, which was accomplished by periodically adding ice and/or dry ice to the external water bath.
• the reactants were each continuously pumped into the reaction vessel over a period of about 2.0 hr, as follows:
• Each of the glycolonitrile reaction product solutions was individually concentrated to remove the excess unreacted HCN and the methanol from the commercial source of formaldehyde.
• the concentration step was performed under vacuum with mild heating using an external oil bath at 60 - 70 0 C.
• the weight of each concentrated glycolonitrile product solution was recorded, and the glycolonitrile concentration was determined by HPLC.
• the reaction vessel equipped with a magnetic stirbar, was initially charged with a mixture of 0.29 g HCN in 10.3 g water and placed within a water bath maintained at around 25 °C, on top of a stirplate.
• the approximately 12-inch section of the formaldehyde feed line (1/8" OD x 0.085" ID) directly preceding the inlet to the reaction flask was heated to 150 °C after filling the formaldehyde feed line, and the flow of heated formaldehyde feed was first established outside the reaction vessel by observing two-phase flow from the outlet of the formaldehyde feed line. After establishing heated formaldehyde feed, the end of the formaldehyde feed line was placed directly into the liquid reaction mixture.
• the reaction temperature was maintained around 20 - 25 0 C, which was accomplished by periodically adding ice and/or dry ice to the external water bath.
• the reactants were each continuously pumped into the reaction vessel over a period of about 2.0 hr, as follows:
• Example 10 Pre-Heatinq 100% of Formaldehyde Approximately 0.40 ml_ of 16.7 wt% aqueous NaOH solution was added to
• the reaction vessel equipped with a magnetic stirbar, was initially charged with a mixture of 0.29 g HCN in 10.3 g water and placed within a water bath maintained at around 25 0 C, on top of a stirplate.
• the approximately 24-inch section of the formaldehyde feed line (1/8" OD x 0.085" ID) directly preceding the inlet to the reaction flask was heated to 90 °C after filling the formaldehyde feed line.
• After establishing heated formaldehyde feed outside of the reaction vessel the end of the formaldehyde feed line was placed directly into the liquid reaction mixture.
• the reaction temperature was maintained around 20 - 25 °C, which was accomplished by periodically adding ice and/or dry ice to the external water bath.
• the reactants were each continuously pumped into the reaction vessel over a period of about 2.0 hr, as follows:
• Figure 7 shows the 13 C NMR spectrum of the resulting glycolonitrile solution, qualitatively indicating the purity of the glycolonitrile product.

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