CA1190938A - PROCESS FOR THE SYNTHESIS OF .alpha.-CHLOROMETHYL CHLOROFORMATE - Google Patents
PROCESS FOR THE SYNTHESIS OF .alpha.-CHLOROMETHYL CHLOROFORMATEInfo
- Publication number
- CA1190938A CA1190938A CA000415267A CA415267A CA1190938A CA 1190938 A CA1190938 A CA 1190938A CA 000415267 A CA000415267 A CA 000415267A CA 415267 A CA415267 A CA 415267A CA 1190938 A CA1190938 A CA 1190938A
- Authority
- CA
- Canada
- Prior art keywords
- formaldehyde
- process according
- phosgene
- reaction
- catalyst
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0239—Quaternary ammonium compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0215—Sulfur-containing compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
- B01J31/0247—Imides, amides or imidates (R-C=NR(OR))
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
- B01J31/0249—Ureas (R2N-C(=O)-NR2)
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0255—Phosphorus containing compounds
- B01J31/0264—Phosphorus acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C68/00—Preparation of esters of carbonic or haloformic acids
- C07C68/02—Preparation of esters of carbonic or haloformic acids from phosgene or haloformates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
- B01J2231/341—1,2-additions, e.g. aldol or Knoevenagel condensations
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
Process for the Synthesis of ?-Chloromethyl Chloroformate Abstract of the Disclosure A process for the preparation of chloromethyl chloro-formate is described which consists of introducing dry gaseous formaldehyde in monomeric form into a reactor containing phos-gene and a catalyst, which is a substituted amide, tetrasub-stituted urea, thiourea, a nitrogen completely substituted phosphoramide, a quaternary ammonium halide, the substituents of which include a total of at least 16 carbon atoms, an alkali or alkaline earth halide associated with a sequestering agent of its cation or the reaction product of this catalysts with phos-gene, in the total absence of water and hydrochloric acid. The temperature is between -10°C and +60°C.
Description
This invention relates to the manufacture of chloromethyl chloroformate, which is a rraterial useful in numerous oxganic syntheses but not easily available on an inclustrial scale.
The synthesis of ~-chlorinated chloroformates, of general formula: P~-CHCl-O-C-Cl, in which R is an aliphatic or aroma-tic substltuent, is very difficult if L0 it is desired to avoid -the introduction of additional chlorine atoms in the radical ~ during the synthesis.
~luller, in Liebiy's Annalen der Chemie, 1890, volume 257l pages 50 and following, has suggested a process which is still the only one known and in use to date.
This process consists of photoly-tically chlorinating the corresponding chloroforma-te, which is not substituted in the f.~ posi-tion. Unfor-tunately, in addition to the desired product, one obtains numerous by-produc-ts which are more chlorinated -than it was intended.
20 ~uller has counted not less than five of these by-produc-ts in the case of the ethyl chloroformate which he studied. The presence of these by-produc-ts is very disturbing due to the main subsequent application oE
the chloroformates, -that is their transformation into carbonates, notably used in the synthesis of fine pharma-ceutica:Ls such as penicillin acids acylals. A distil-lation of the reac-tion product is -thus indispensable, although delicate to carry out due to the presence of numerous by-products.
Another old publication, German Paten-t 121/223, hich issued in 1901, describes the synthesis of 1,2/2,2-tetrachloroethyl chloroformate and f~-chiorobenzyl chloroformate, by phosgenation of chloral and benzalde-hyde respectively, in the presence of a stoichiometric amount of a tertiary amine, which does not belong to -the pyridine series.
However, if i-t is attemp-ted to phosgenate, ~0 under the same conditions, other aldehydes, in addition to xpecific chloral and benzaldehyde, such as acetalde-hyde, there is noted the forrnation of nurnerous cornplexes and by-prodllcts in addition , ~
rnab/ ' ~909313 to the ~ -~hloroethyl chloroformate, the latter being obtained with poor yield, which renders -this process not suit~ble on an industrial scale. Moreover, if one -tries to carry ou-t this phosgenation with an alipha-tic -tertiary amine such as trietnyl-amine, one mainly notes the destruc-tion of this amine, with formation of a very small amoun-t o:E the derived chl.oroformate.
`Thus, there is a need of a manufacturing process of pure .~-chlorinated chloroformates in yields.which will permit a complete application of these .f)~chlorinated chloroformates, compounds of simple chemical structure and substantial value as intermediates.
A process for manufac-turing -',-chlorinated chloro formates :Eree of the by-prod~cts resulting from substi-tution of chlorine for hydro~Jen has recen-tly been proposed from inex-pensive raw materials and in e.xcellen-t yield. This process, described in Irish Paten-t Application ~ , consists of phosgenating an aldehyde of formula RCHO in the presence of catalysts, so as to obtain /~-chlorinated RCHClOCOCl chloro-formate. However, this process cannot be applied to formalde-hyde itself, HCHQ and does not permit to prepare ~ -chloromethyl chloroformate C~2Clococl.
In the case of chloromethyl chloroformate, it is known that it may be obtained by chlorination of methyl chloro-~ormate or methyl formate. M~TZNER et al, in Chemical Re~iew 64, page 6~6 (196~), yive several references of known methods bu-t these methods are always delicate syntheses leading to numerous by-products, difficult to separate from the desired product.
An object of the present invention is to provide a process for the manufacture of .~ chloromethyl chloroformate in a high yield.
The crux of the present invention resides in intro-ducing previously-dried gaseous monomeric formaldehyde into a reactor containing phosgene and a catalyst, selected from the group consisting of substituted amines, tetrasubstituted ureas and thioureas, nitrogen completely substituted phosphoramides, quaternary ammonium halides, having a total of at least 16 carbon atoms and preferably those in which every substituent includes at least ~ carbon atoms, alkali or alkaline-earth halides associated to a seques-tering agent of their cation 3~ ( as well as the reac-tion products of -these catalys-ts with phos-gene. The reaction takes place in the total absence of water and hydrochloric acid, at a temperature between -10C and +60C.
According to a specific embodimen-t of the invention, the react--ion oF formalclehyde and phosgene, in the presence of a catalys-t, is carried out in a solvent, which is toluene, methylene chlor-ide, chloroform or carbon tetrachloride.
~ ccording to a preferred embodiment of the invention, the catalyst is benzyl-tributyl ammonium chloride, potassium chloride associated to a crown ether or to a cryptate capable of complexing its cation or phosgenated tetrabutyl urea.
The process according to the invention consists of carrying out the reac~ion of dry gaseous formaldehyde in lts monomeric form with phosgene in a reactor at a temperature hetween -10C and 60C in the presence of a catalyst and in total absence of water and hydrochloric acid.
According to the invention, the formaldehyde must be perfectly dry and completely monomeric. It is thus necessary, before starting the reaction, to dry the formaldehyde and, in general, to depolymerize it since formaldehyde cannot be stored in the monomeric form, but forms either the trimer trioxane or a linear polymer of general formula ~CH2otn; which is known as paraformaldehyde, in which "n" is an integer,usually between 6 and 100.
The forma]dehyde is dried in a dryer, in the presence of a good drylng agent such as phosphorus pentoxide. The oper-ation of drying the formaldehyde may be performed before or during the depolymerization but, in any e~-ent, before its introduction into the phosgenation reactor. The drying oper-ation is essential for the process according to the invention, and it must be complete. Indeed, any trace of moisture causes repolymerization of the monomeric formaldehyde and lowers the yield of -the phosgenation since only monomeric formaldehyde reacts with phosgene. Monomeric formaldehyde is obtained in a known manner, such as by thermal depolymerization in the case of paraformaldehyde, or by depolymerization in the presence of catalysts in the case of trioxane. Depolymerization can tak~
place either during the drying of formaldehyde or after drying of the polymeric formaldehyde. Dry formaldehyde/ in monomeric form, is then introduce~ into a perfect]y dry reactor, containing the catalyst and the phosgene. Wlthin the scope of the present invention, the term "catalyst" must be unders-tood restric-tively.
The compound added as catalyst is esSential to tlle react-ion but does not directly participate to the reaction and is used in relatively small amounts with respect to the formaldehyde. It is indeed a catalyst, but contrary to what is the general view of catalysts, it cannot always be reused for another reaction once the introduction oE phosgene has been stopped. No theoretical explanation may be suggested for this phenomenon.
It hss been possible to find a definition cornmon to a certain number o catalysts suitable for the invention. These catalysts are organic or inorganic substances which can generate, in a medium containing formalclehyde, phosgene and a solvent if applicable, a pair of ions, one of which is a halide anion and t~e other one a cation sufficiently separated from the halide anion so that it possesses a nucleophilic acti~ity allowing it to re-act with the aldehyde function of the formaldehyde. Catalysts according to the invention and Ealling within this definition include among others, the following as such or as their reaction products with phosgene: substituted amides, tetrasubstituted ureas and thioureas, nitrogen completely substituted phosphor-amides, quaternary ammonium halides, the substituents of which include a total of at least 16 carbon atoms and preferably those whose every constituent includes at least 4 car~on atoms and alkali and alk~line-earth halides associated to a sequester-ing agen-t of their cation. ~he preferred halide is chloride.
As mentioned hereinabove, certain catalysts generate a halide ion either directly, or after reaction with phosgene.
In this case, the general mechanism of the catalyst is probably as follows:
M Cl - ~ ~C ~ O -> ~9 ~ C1 - C - 01 t ~1 Cl Cl- ~/
Cl - C -- O - C ~ Cl ~) M
H O ~HCOH o 3~ ( in which M is an organic or inorganic cation, complexed or not, present as such in the catalyst from the start or formed at the beginning of the reaction by the action oE phosgene on the cat-alyst. Thus, M may be a complexed metalli.c cation or a fully-organic cation o:E onium type, $uc~ as, for instance:
~ O K O N Cl 0~ 0 ~ /
or M+ may be formed from the more or less advanced reaction oE
phosgene and the substance responsible for the catalytic action, such as in the following sequence, for ins-tance:
- Bu~ ~ ~Bu Cl~
IN ~ C ~ N ~ _~ C = O
Bu/ `,? ~ Cl~
Bu~ ~j N~ -~ Cl ~ CO2 ~u~ ~ Cl . HCOH
in which M is a large chlorimonium ca-tion.
It has been noted that the most interesting results have been obtained with the following catalysts: substi-tu-ted amides, particularly dimethylformamide; tetrasubstituted ureas and thioureas, particularly tetraalkyl ~ ~ s' such as tetra-butylurea and tetramethylurea; completely nitrogen substi-tuted phosphoramides, particularly hexamethylphosphotriamide, quater-nary ammonium halides which include a total of at least 16 carbon atoms and preferably each substituent has at least 4 carbon atoms, such as tri.butylbenzyl ammonium chloride; alkali or alkaline-earth halides associated to a sequestering agent of their cation, particularly potassium chloride associated to a crown ether such as 18-crown-6 or a cryptate such as (222) or diaza-1,10 hexaoxa - 4,7,13,16,21,24 - bicyclo(8~8,8)hexacosane.
Naturally, in this latter case, it is preferable to associate a sequestering agent which forms with the metal chlor-ide cation a complex with a high stability constant, which is very easy to achieve due to the numerous studies per~ormed in this field, such as the study of Kappenstein published in the ~ulletin de la ~ocie-te Chimique de France, 197~, N l-2, pages ~9-109 and the work of J.M. LEHN published in Structure and Bon-ding, volume 16, pages 2-6~, Sp.r:inger Verlag (197~). The term "halide" essentially indicates a chloride, bromide, or iodide, it being understood that a chloride is preferred, so that even the first molecule of formaldehyde transformed t.hrough the ac-tion of the halide coming from the catalyst is transformed into chloromet.hyl chloroformate.
The ratio of catalyst used is important but is not essential to the process according to the inven-tion. Indeed, when -the catalys-t is very efective, a xatio of catalys-t of 0.5 to 10 percent in moles (preferably 2 to 7 percent) with respect to the molar ~uantity of phosgene used is satisfactory. On the other hand, some catalys-ts according to the invention are less effective and a highex ratio, about l -to 50 percent (preferably 5 to 40 percent) must be used.
I'he order o~ introduction of the reagents into the reactor is impor-tant. It is indeed essential to introduce the monomeric gaseous Eormaldehyde into the reactor already containing the catalys-t and phosgene, so tha-t the formaldehyde reacts imme~
diately with the phosgene wi-thou-t having the time to repolymerize, because the ra-te of reaction of formaldehyde with phosgene i.s hiyher -than its rate of polymerization under the operatiny con-ditions used. The reactor must thus contain at ].east the cata-lyst with all the phosgene being introduced into the reactor before the start of the reaction or being introduced at the same time the formaldehyde is introduced at the bottom of the vessel containing phosgene and catalyst. On the other hand, within the present invention, it is not possible to place in a vessel the formaldehyde and the catalyst to introduce the phosyene into this vessel since, in this case, the formaldehyde would polymerize and the phosgenation reaction would become virtually impossible~
The phosgenation reaction advantageously takes place under stirriny. The temperature of the reaction medium is pre-ferahly kept be-tween -10C and -~30C duriny the introduction of forrnaldehyde. It is still better to keep the temperature of the reaction medium at abou-t 0C at the beyinning of the introduction of the formaldehyde and by the end of -the introduction of the formaldehyde, -the temperature is allowed to reach about 20C.
It may be advantageous to end the reaction by heating the re-action mixture up to a temperature between ~0 and 60C.
The reac-tion mix-ture must be totally free of any trace of water or hydrochloric acid so as to avoid all risks of formal-dehyde repolymerization. For this purpose, the reactor must be flushed with dry air or with a dry inert gas before the reaction.
Althou~h this is not a preferred embodiment of the invention, it is possible to carry out the reaction in the pre-sence of a sol~ent. One.must, however, avoid using solvents which react with phosgene to form hydrochlori.c acid, s~lch as alcohols and amlnes or solvents which break down to form hydro-chloric acid, such as ketones and t.etrahydrofuran and finally,.
solvents which are difficult to dry, such as ethers. If desired, it is possible to use solvents such as toluene or chlorinated aliphatic solvents such as methylene chloride, chloroform and carbon tetrachloride. However, the use of a solvent may some-times prove useful since, when the reaction takes place in the presence of a solvent, the temperature may be kept between 30 and 60C even during the introduction of formaldehyde.
The following examples illustrate the utilization of the process according to the in~ention.
Exam~le 1 The apparatus used is a 100-ml capacity glass reactor, fitted with a dry ice cooler, a thermometer, a stirrer and an inlet for the introduction of a gas. The reactor is flushed with dry nitrogen. Phosgene 0.3X mole (38 grams), which ~.n.tains 3-3 grams (0.0106 mole of perfectly dry benzyl tributylammonium chloride, is introduced into the reactor.
While the temperature of the mi~ture is kept at around 0C, there is introduced through the yas inlet tube, dip-ping in the phosgene, the formaldehyde which is taken from a bottle containing 18 grams (0.6 mole) paraformaldehyde and 10 grams phosphorus pentoxide P2O5, this bottle being flushed with dry nitrogen and being heated at 150~. The addition of formal-dehyde is carried on for 30 minutes, until full disappearance of the paraformaldehyde and the reaction mixture is allowed to - 9 -- ~
reach 20C and is kept stirred for one hour at this temperature.
The residual phosgene is removed by deaeration and the chloro-methyl chloroformate obtained is purified first by evaporation under vacuum and then by distillation at atmospheric pressure.
The boiling point is 106C. There is obtained 20.7 grams of perfectly dry product, which is e~uivalent to a yield of 42 percent with respect to the phosgene used. In ~MN spectrography, chloromethyl chloroformate is characteri~ed by a singlet at 5.5 ppm.
Example 2 One operates as described in example 1 above, with 10 grams phosgene, 10 grams paraformalAehyde and 5 grams P2O5, using phosgenated tetra n-butyl urea as catalyst. This catalyst is prepared by phosgenating 1.5 grams tetra n-butyl urea at 50C
according to the following reaction scheme:
n butyl n butyl n butyl C1Cl - C f n butyl --~
~N n butyl COC12~ ~ n butyl ~ butyl `n butyl The reaction temperature is brought up to 50C for one hour after the end of the introduction of the formaldehyde.
There is ob-tained chloromethyl chloroformate with a yield of 91.5 percent with respect to the phosgene used. This yield is determined by RMN dosing, using toluene as internal standard.
Example 3 The process is carried out as described in example 2 above, with 20 grams phosgene, 15 grams paraformaldehyde and 10 grams P2O5, using as catalyst 1.3 grams potassium chloride as-sociated -to 0.4 grams cryptate (2,2,2). Chloromethyl chloro-formate with a yield of 63 percent with respect to the phosgene used, is obtained.
Example 4 The apparatus used is identical to the apparatus de-scribed in example 1 above. The reac-tor is fl~lshed wi-th ary nitrosen. Phos~ene, 20 grams is introduced in-to this reactor, which already contains 1.3 ~rams potass:ium chloride associated to 0.4 gram cryptate (2,2,2).
While -the temperature of the mixture is kept at about 0C, there is introduced through the bubblin~ tube which dips in~o the phosgene, the formaldehyde coming from a bottle contain-ing 15 grams paraformaldehyde, heated at 150C. This bottle has previously been flushed dry with nitrogen and the paraformalde-hyde dried over P2O5 under a vacuum of 0.1 mm Hg in a drier be-fore being inserted into the depolymerizing bottle. The intro-duction of formaldehyde is carried out ~or 30 minutes, then the reaction mixture is heated at 50C for one hour to allow the reaction to proceed to completion. There is obtained chloro-methyl chloroformate with a yield of 73 percent with respect to the phosgene used.
Example 5 The same apparatus as described under Example 1 is used. The reactor is flushed with dry nitrogen. There is intro-duced, 40 ml anhydrous carbon tetrachloride as a solvent, 12 grams of phosgene and, as catalyst, phosgenated tetra n-butyl urea, prepared as described in example 2 from 1.5 grams tetra n~butyl urea.
After the temperature of the reaction mixture has been raised to ~0C, t.here is introduced formaldehyde, prepared as described in example 4 from 3O8 grams paraformaldehyde. The reaction mixture is kept at 40C for 2 hours after introduction o~ the formaldehyde.
There is obtained chloromethyl chloroformate with a yield of 65 percent with respect to the formaldehyde used.
The synthesis of ~-chlorinated chloroformates, of general formula: P~-CHCl-O-C-Cl, in which R is an aliphatic or aroma-tic substltuent, is very difficult if L0 it is desired to avoid -the introduction of additional chlorine atoms in the radical ~ during the synthesis.
~luller, in Liebiy's Annalen der Chemie, 1890, volume 257l pages 50 and following, has suggested a process which is still the only one known and in use to date.
This process consists of photoly-tically chlorinating the corresponding chloroforma-te, which is not substituted in the f.~ posi-tion. Unfor-tunately, in addition to the desired product, one obtains numerous by-produc-ts which are more chlorinated -than it was intended.
20 ~uller has counted not less than five of these by-produc-ts in the case of the ethyl chloroformate which he studied. The presence of these by-produc-ts is very disturbing due to the main subsequent application oE
the chloroformates, -that is their transformation into carbonates, notably used in the synthesis of fine pharma-ceutica:Ls such as penicillin acids acylals. A distil-lation of the reac-tion product is -thus indispensable, although delicate to carry out due to the presence of numerous by-products.
Another old publication, German Paten-t 121/223, hich issued in 1901, describes the synthesis of 1,2/2,2-tetrachloroethyl chloroformate and f~-chiorobenzyl chloroformate, by phosgenation of chloral and benzalde-hyde respectively, in the presence of a stoichiometric amount of a tertiary amine, which does not belong to -the pyridine series.
However, if i-t is attemp-ted to phosgenate, ~0 under the same conditions, other aldehydes, in addition to xpecific chloral and benzaldehyde, such as acetalde-hyde, there is noted the forrnation of nurnerous cornplexes and by-prodllcts in addition , ~
rnab/ ' ~909313 to the ~ -~hloroethyl chloroformate, the latter being obtained with poor yield, which renders -this process not suit~ble on an industrial scale. Moreover, if one -tries to carry ou-t this phosgenation with an alipha-tic -tertiary amine such as trietnyl-amine, one mainly notes the destruc-tion of this amine, with formation of a very small amoun-t o:E the derived chl.oroformate.
`Thus, there is a need of a manufacturing process of pure .~-chlorinated chloroformates in yields.which will permit a complete application of these .f)~chlorinated chloroformates, compounds of simple chemical structure and substantial value as intermediates.
A process for manufac-turing -',-chlorinated chloro formates :Eree of the by-prod~cts resulting from substi-tution of chlorine for hydro~Jen has recen-tly been proposed from inex-pensive raw materials and in e.xcellen-t yield. This process, described in Irish Paten-t Application ~ , consists of phosgenating an aldehyde of formula RCHO in the presence of catalysts, so as to obtain /~-chlorinated RCHClOCOCl chloro-formate. However, this process cannot be applied to formalde-hyde itself, HCHQ and does not permit to prepare ~ -chloromethyl chloroformate C~2Clococl.
In the case of chloromethyl chloroformate, it is known that it may be obtained by chlorination of methyl chloro-~ormate or methyl formate. M~TZNER et al, in Chemical Re~iew 64, page 6~6 (196~), yive several references of known methods bu-t these methods are always delicate syntheses leading to numerous by-products, difficult to separate from the desired product.
An object of the present invention is to provide a process for the manufacture of .~ chloromethyl chloroformate in a high yield.
The crux of the present invention resides in intro-ducing previously-dried gaseous monomeric formaldehyde into a reactor containing phosgene and a catalyst, selected from the group consisting of substituted amines, tetrasubstituted ureas and thioureas, nitrogen completely substituted phosphoramides, quaternary ammonium halides, having a total of at least 16 carbon atoms and preferably those in which every substituent includes at least ~ carbon atoms, alkali or alkaline-earth halides associated to a seques-tering agent of their cation 3~ ( as well as the reac-tion products of -these catalys-ts with phos-gene. The reaction takes place in the total absence of water and hydrochloric acid, at a temperature between -10C and +60C.
According to a specific embodimen-t of the invention, the react--ion oF formalclehyde and phosgene, in the presence of a catalys-t, is carried out in a solvent, which is toluene, methylene chlor-ide, chloroform or carbon tetrachloride.
~ ccording to a preferred embodiment of the invention, the catalyst is benzyl-tributyl ammonium chloride, potassium chloride associated to a crown ether or to a cryptate capable of complexing its cation or phosgenated tetrabutyl urea.
The process according to the invention consists of carrying out the reac~ion of dry gaseous formaldehyde in lts monomeric form with phosgene in a reactor at a temperature hetween -10C and 60C in the presence of a catalyst and in total absence of water and hydrochloric acid.
According to the invention, the formaldehyde must be perfectly dry and completely monomeric. It is thus necessary, before starting the reaction, to dry the formaldehyde and, in general, to depolymerize it since formaldehyde cannot be stored in the monomeric form, but forms either the trimer trioxane or a linear polymer of general formula ~CH2otn; which is known as paraformaldehyde, in which "n" is an integer,usually between 6 and 100.
The forma]dehyde is dried in a dryer, in the presence of a good drylng agent such as phosphorus pentoxide. The oper-ation of drying the formaldehyde may be performed before or during the depolymerization but, in any e~-ent, before its introduction into the phosgenation reactor. The drying oper-ation is essential for the process according to the invention, and it must be complete. Indeed, any trace of moisture causes repolymerization of the monomeric formaldehyde and lowers the yield of -the phosgenation since only monomeric formaldehyde reacts with phosgene. Monomeric formaldehyde is obtained in a known manner, such as by thermal depolymerization in the case of paraformaldehyde, or by depolymerization in the presence of catalysts in the case of trioxane. Depolymerization can tak~
place either during the drying of formaldehyde or after drying of the polymeric formaldehyde. Dry formaldehyde/ in monomeric form, is then introduce~ into a perfect]y dry reactor, containing the catalyst and the phosgene. Wlthin the scope of the present invention, the term "catalyst" must be unders-tood restric-tively.
The compound added as catalyst is esSential to tlle react-ion but does not directly participate to the reaction and is used in relatively small amounts with respect to the formaldehyde. It is indeed a catalyst, but contrary to what is the general view of catalysts, it cannot always be reused for another reaction once the introduction oE phosgene has been stopped. No theoretical explanation may be suggested for this phenomenon.
It hss been possible to find a definition cornmon to a certain number o catalysts suitable for the invention. These catalysts are organic or inorganic substances which can generate, in a medium containing formalclehyde, phosgene and a solvent if applicable, a pair of ions, one of which is a halide anion and t~e other one a cation sufficiently separated from the halide anion so that it possesses a nucleophilic acti~ity allowing it to re-act with the aldehyde function of the formaldehyde. Catalysts according to the invention and Ealling within this definition include among others, the following as such or as their reaction products with phosgene: substituted amides, tetrasubstituted ureas and thioureas, nitrogen completely substituted phosphor-amides, quaternary ammonium halides, the substituents of which include a total of at least 16 carbon atoms and preferably those whose every constituent includes at least 4 car~on atoms and alkali and alk~line-earth halides associated to a sequester-ing agen-t of their cation. ~he preferred halide is chloride.
As mentioned hereinabove, certain catalysts generate a halide ion either directly, or after reaction with phosgene.
In this case, the general mechanism of the catalyst is probably as follows:
M Cl - ~ ~C ~ O -> ~9 ~ C1 - C - 01 t ~1 Cl Cl- ~/
Cl - C -- O - C ~ Cl ~) M
H O ~HCOH o 3~ ( in which M is an organic or inorganic cation, complexed or not, present as such in the catalyst from the start or formed at the beginning of the reaction by the action oE phosgene on the cat-alyst. Thus, M may be a complexed metalli.c cation or a fully-organic cation o:E onium type, $uc~ as, for instance:
~ O K O N Cl 0~ 0 ~ /
or M+ may be formed from the more or less advanced reaction oE
phosgene and the substance responsible for the catalytic action, such as in the following sequence, for ins-tance:
- Bu~ ~ ~Bu Cl~
IN ~ C ~ N ~ _~ C = O
Bu/ `,? ~ Cl~
Bu~ ~j N~ -~ Cl ~ CO2 ~u~ ~ Cl . HCOH
in which M is a large chlorimonium ca-tion.
It has been noted that the most interesting results have been obtained with the following catalysts: substi-tu-ted amides, particularly dimethylformamide; tetrasubstituted ureas and thioureas, particularly tetraalkyl ~ ~ s' such as tetra-butylurea and tetramethylurea; completely nitrogen substi-tuted phosphoramides, particularly hexamethylphosphotriamide, quater-nary ammonium halides which include a total of at least 16 carbon atoms and preferably each substituent has at least 4 carbon atoms, such as tri.butylbenzyl ammonium chloride; alkali or alkaline-earth halides associated to a sequestering agent of their cation, particularly potassium chloride associated to a crown ether such as 18-crown-6 or a cryptate such as (222) or diaza-1,10 hexaoxa - 4,7,13,16,21,24 - bicyclo(8~8,8)hexacosane.
Naturally, in this latter case, it is preferable to associate a sequestering agent which forms with the metal chlor-ide cation a complex with a high stability constant, which is very easy to achieve due to the numerous studies per~ormed in this field, such as the study of Kappenstein published in the ~ulletin de la ~ocie-te Chimique de France, 197~, N l-2, pages ~9-109 and the work of J.M. LEHN published in Structure and Bon-ding, volume 16, pages 2-6~, Sp.r:inger Verlag (197~). The term "halide" essentially indicates a chloride, bromide, or iodide, it being understood that a chloride is preferred, so that even the first molecule of formaldehyde transformed t.hrough the ac-tion of the halide coming from the catalyst is transformed into chloromet.hyl chloroformate.
The ratio of catalyst used is important but is not essential to the process according to the inven-tion. Indeed, when -the catalys-t is very efective, a xatio of catalys-t of 0.5 to 10 percent in moles (preferably 2 to 7 percent) with respect to the molar ~uantity of phosgene used is satisfactory. On the other hand, some catalys-ts according to the invention are less effective and a highex ratio, about l -to 50 percent (preferably 5 to 40 percent) must be used.
I'he order o~ introduction of the reagents into the reactor is impor-tant. It is indeed essential to introduce the monomeric gaseous Eormaldehyde into the reactor already containing the catalys-t and phosgene, so tha-t the formaldehyde reacts imme~
diately with the phosgene wi-thou-t having the time to repolymerize, because the ra-te of reaction of formaldehyde with phosgene i.s hiyher -than its rate of polymerization under the operatiny con-ditions used. The reactor must thus contain at ].east the cata-lyst with all the phosgene being introduced into the reactor before the start of the reaction or being introduced at the same time the formaldehyde is introduced at the bottom of the vessel containing phosgene and catalyst. On the other hand, within the present invention, it is not possible to place in a vessel the formaldehyde and the catalyst to introduce the phosyene into this vessel since, in this case, the formaldehyde would polymerize and the phosgenation reaction would become virtually impossible~
The phosgenation reaction advantageously takes place under stirriny. The temperature of the reaction medium is pre-ferahly kept be-tween -10C and -~30C duriny the introduction of forrnaldehyde. It is still better to keep the temperature of the reaction medium at abou-t 0C at the beyinning of the introduction of the formaldehyde and by the end of -the introduction of the formaldehyde, -the temperature is allowed to reach about 20C.
It may be advantageous to end the reaction by heating the re-action mixture up to a temperature between ~0 and 60C.
The reac-tion mix-ture must be totally free of any trace of water or hydrochloric acid so as to avoid all risks of formal-dehyde repolymerization. For this purpose, the reactor must be flushed with dry air or with a dry inert gas before the reaction.
Althou~h this is not a preferred embodiment of the invention, it is possible to carry out the reaction in the pre-sence of a sol~ent. One.must, however, avoid using solvents which react with phosgene to form hydrochlori.c acid, s~lch as alcohols and amlnes or solvents which break down to form hydro-chloric acid, such as ketones and t.etrahydrofuran and finally,.
solvents which are difficult to dry, such as ethers. If desired, it is possible to use solvents such as toluene or chlorinated aliphatic solvents such as methylene chloride, chloroform and carbon tetrachloride. However, the use of a solvent may some-times prove useful since, when the reaction takes place in the presence of a solvent, the temperature may be kept between 30 and 60C even during the introduction of formaldehyde.
The following examples illustrate the utilization of the process according to the in~ention.
Exam~le 1 The apparatus used is a 100-ml capacity glass reactor, fitted with a dry ice cooler, a thermometer, a stirrer and an inlet for the introduction of a gas. The reactor is flushed with dry nitrogen. Phosgene 0.3X mole (38 grams), which ~.n.tains 3-3 grams (0.0106 mole of perfectly dry benzyl tributylammonium chloride, is introduced into the reactor.
While the temperature of the mi~ture is kept at around 0C, there is introduced through the yas inlet tube, dip-ping in the phosgene, the formaldehyde which is taken from a bottle containing 18 grams (0.6 mole) paraformaldehyde and 10 grams phosphorus pentoxide P2O5, this bottle being flushed with dry nitrogen and being heated at 150~. The addition of formal-dehyde is carried on for 30 minutes, until full disappearance of the paraformaldehyde and the reaction mixture is allowed to - 9 -- ~
reach 20C and is kept stirred for one hour at this temperature.
The residual phosgene is removed by deaeration and the chloro-methyl chloroformate obtained is purified first by evaporation under vacuum and then by distillation at atmospheric pressure.
The boiling point is 106C. There is obtained 20.7 grams of perfectly dry product, which is e~uivalent to a yield of 42 percent with respect to the phosgene used. In ~MN spectrography, chloromethyl chloroformate is characteri~ed by a singlet at 5.5 ppm.
Example 2 One operates as described in example 1 above, with 10 grams phosgene, 10 grams paraformalAehyde and 5 grams P2O5, using phosgenated tetra n-butyl urea as catalyst. This catalyst is prepared by phosgenating 1.5 grams tetra n-butyl urea at 50C
according to the following reaction scheme:
n butyl n butyl n butyl C1Cl - C f n butyl --~
~N n butyl COC12~ ~ n butyl ~ butyl `n butyl The reaction temperature is brought up to 50C for one hour after the end of the introduction of the formaldehyde.
There is ob-tained chloromethyl chloroformate with a yield of 91.5 percent with respect to the phosgene used. This yield is determined by RMN dosing, using toluene as internal standard.
Example 3 The process is carried out as described in example 2 above, with 20 grams phosgene, 15 grams paraformaldehyde and 10 grams P2O5, using as catalyst 1.3 grams potassium chloride as-sociated -to 0.4 grams cryptate (2,2,2). Chloromethyl chloro-formate with a yield of 63 percent with respect to the phosgene used, is obtained.
Example 4 The apparatus used is identical to the apparatus de-scribed in example 1 above. The reac-tor is fl~lshed wi-th ary nitrosen. Phos~ene, 20 grams is introduced in-to this reactor, which already contains 1.3 ~rams potass:ium chloride associated to 0.4 gram cryptate (2,2,2).
While -the temperature of the mixture is kept at about 0C, there is introduced through the bubblin~ tube which dips in~o the phosgene, the formaldehyde coming from a bottle contain-ing 15 grams paraformaldehyde, heated at 150C. This bottle has previously been flushed dry with nitrogen and the paraformalde-hyde dried over P2O5 under a vacuum of 0.1 mm Hg in a drier be-fore being inserted into the depolymerizing bottle. The intro-duction of formaldehyde is carried out ~or 30 minutes, then the reaction mixture is heated at 50C for one hour to allow the reaction to proceed to completion. There is obtained chloro-methyl chloroformate with a yield of 73 percent with respect to the phosgene used.
Example 5 The same apparatus as described under Example 1 is used. The reactor is flushed with dry nitrogen. There is intro-duced, 40 ml anhydrous carbon tetrachloride as a solvent, 12 grams of phosgene and, as catalyst, phosgenated tetra n-butyl urea, prepared as described in example 2 from 1.5 grams tetra n~butyl urea.
After the temperature of the reaction mixture has been raised to ~0C, t.here is introduced formaldehyde, prepared as described in example 4 from 3O8 grams paraformaldehyde. The reaction mixture is kept at 40C for 2 hours after introduction o~ the formaldehyde.
There is obtained chloromethyl chloroformate with a yield of 65 percent with respect to the formaldehyde used.
Claims (10)
1. A process for the preparation of chloromethyl chloroformate which consists of introducing gaseous formaldehyde, previously dried in monomeric form into a reactor containing phosgene and a catalyst which is a member selected from the group consisting of substituted amides, tetrasubstituted ureas and thioureas, nitro-gen completely substituted phosphoramides, quaternary ammonium halides the substituents of which include a total of at least 16 carbon atoms, alkali and alkaline earth halides associated with a sequestering agent of their cations and the reaction products of these catalysts with phosgene, in the total absence of water and hydrochloric acid at a temperature between -10°C and +60°C.
2. The process according to claim 1, wherein said catalyst is a member selected from the group consisting of substituted amides, tetrasubstituted ureas and thioureas, nitrogen completely sub-stituted phosphoramides, quaternary ammonium halides each sub-stituent of which includes at least four carbon atoms, alkali and alkaline-earth halides associated with a sequestering agent of their cations and the reaction products of these catalysts with phosgene.
3. The process according to claim 2, wherein said catalyst is a member selected from the group consisting of dimethylformamide, tetrabutylurea, tetramethylurea, hexamethylphosphotriamide, tri-butyl benzyl ammonium chloride, potassium chloride associated to ether 18-crown-6 and potassium chloride associated to cryptate (2,2,2).
4. The process according to claim 1, 2 or 3, wherein the drying agent used to dry the formaldehyde is phosphorus pentoxide.
5. The process according to claim 1, wherein the tempera-ture of the reaction mixture is kept between -10°C and +30°C
during the introduction of formaldehyde.
during the introduction of formaldehyde.
6. The process according to claim 5 wherein the temperature of the reaction mixture is kept at about 0°C at the beginning of the introduction of formaldehyde and is kept at about 20°C at the end of the introduction of formaldehyde.
7. The process according to claim 6 wherein the temperature of the reaction mixture is brought up to between 40 and 60°C after the formaldehyde has been introduced into said reactor.
8. The process according to claim 1 wherein the reaction is carried out in a solvent.
9. The process according to claim 8 wherein said solvent is a member selected from the group consisting of toluene, methylene chloride, chloroform and carbon tetrachloride.
10. The process according to claim 8 or 9, wherein the reaction is carried out at a temperature between 30 and 60°C.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32000681A | 1981-11-10 | 1981-11-10 | |
| US320,006 | 1981-11-10 | ||
| US36047182A | 1982-03-22 | 1982-03-22 | |
| US360,471 | 1982-03-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1190938A true CA1190938A (en) | 1985-07-23 |
Family
ID=26982248
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000415267A Expired CA1190938A (en) | 1981-11-10 | 1982-11-10 | PROCESS FOR THE SYNTHESIS OF .alpha.-CHLOROMETHYL CHLOROFORMATE |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0080913B1 (en) |
| CA (1) | CA1190938A (en) |
| DE (2) | DE3262568D1 (en) |
| DK (1) | DK161886C (en) |
| ES (1) | ES517220A0 (en) |
| FR (1) | FR2516075A1 (en) |
| GB (1) | GB2108961B (en) |
| HU (1) | HU198671B (en) |
| IL (1) | IL67077A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4686017A (en) * | 1981-11-05 | 1987-08-11 | Union Oil Co. Of California | Electrolytic bath and methods of use |
| DE19518473A1 (en) * | 1995-05-19 | 1996-11-21 | Basf Ag | Process for the preparation of aryl chloroformates |
| US6911558B2 (en) | 2003-02-05 | 2005-06-28 | Ppg Industries Ohio, Inc. | Method for purifying chloromethyl chloroformate |
| CN1298695C (en) * | 2004-01-19 | 2007-02-07 | 上海康鸣高科技有限公司 | Gas phase chlorination method and device for preparing chloro-formic acid-1-chloro-formic ester |
| DE102008004559B4 (en) * | 2007-01-23 | 2017-03-16 | General Electric Technology Gmbh | Method for processing a thermally loaded component |
| CN109096111A (en) * | 2018-09-11 | 2018-12-28 | 安徽东至广信农化有限公司 | A kind of synthetic method of chloro-methyl-chloroformate |
| CN115779882A (en) * | 2022-12-08 | 2023-03-14 | 万华化学集团股份有限公司 | Preparation method and application of activated carbon catalyst for phosgene synthesis |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2131555C3 (en) * | 1971-06-25 | 1983-01-13 | Hoechst Ag, 6000 Frankfurt | Process for the preparation of phenyl chloroformate |
| FR2296615A1 (en) * | 1974-12-31 | 1976-07-30 | Poudres & Explosifs Ste Nale | PERFECTED PROCESS FOR MANUFACTURING TRICHLOROETHYL CHLOROFORMIATE |
| FR2381739A1 (en) * | 1977-02-25 | 1978-09-22 | Poudres & Explosifs Ste Nale | PROCESS FOR THE INDUSTRIAL SYNTHESIS OF VINYL CHLOROFORMIATE |
| DE3000524A1 (en) * | 1980-01-09 | 1981-07-16 | Basf Ag, 6700 Ludwigshafen | METHOD FOR PRODUCING AROMATIC CHLORINE FORMATS |
| FR2482587A1 (en) * | 1980-05-14 | 1981-11-20 | Poudres & Explosifs Ste Nale | PROCESS FOR THE SYNTHESIS OF A-CHLORINATED CHLOROFORMIATES AND NEW A-CHLORINATED CHLOROFORMIATES |
-
1982
- 1982-10-26 IL IL67077A patent/IL67077A/en not_active IP Right Cessation
- 1982-10-28 FR FR8218057A patent/FR2516075A1/en active Granted
- 1982-10-28 DE DE8282401994T patent/DE3262568D1/en not_active Expired
- 1982-10-28 EP EP82401994A patent/EP0080913B1/en not_active Expired
- 1982-10-29 DK DK480482A patent/DK161886C/en active
- 1982-11-01 GB GB08231132A patent/GB2108961B/en not_active Expired
- 1982-11-08 ES ES517220A patent/ES517220A0/en active Granted
- 1982-11-09 HU HU823600A patent/HU198671B/en not_active IP Right Cessation
- 1982-11-10 DE DE19823241568 patent/DE3241568A1/en not_active Withdrawn
- 1982-11-10 CA CA000415267A patent/CA1190938A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ES8400728A1 (en) | 1983-12-01 |
| DE3262568D1 (en) | 1985-04-18 |
| DK161886B (en) | 1991-08-26 |
| HU198671B (en) | 1989-11-28 |
| IL67077A (en) | 1986-04-29 |
| EP0080913A1 (en) | 1983-06-08 |
| ES517220A0 (en) | 1983-12-01 |
| EP0080913B1 (en) | 1985-03-13 |
| GB2108961B (en) | 1985-09-18 |
| GB2108961A (en) | 1983-05-25 |
| FR2516075B1 (en) | 1984-12-21 |
| DK480482A (en) | 1983-05-11 |
| DE3241568A1 (en) | 1983-05-19 |
| FR2516075A1 (en) | 1983-05-13 |
| IL67077A0 (en) | 1983-02-23 |
| DK161886C (en) | 1992-02-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4533729A (en) | Process for the preparation of polycarbonate polyols | |
| CA1190938A (en) | PROCESS FOR THE SYNTHESIS OF .alpha.-CHLOROMETHYL CHLOROFORMATE | |
| Clark et al. | Calcium fluoride-supported alkali metal fluorides. New reagents for nucleophilic fluorine transfer reactions | |
| US3904701A (en) | Process for the catalytic hydrofluorination of halogenated hydrocarbons | |
| JPS5849363A (en) | Production of 2,2,6,6-tetramethyl-4-oxopiperidine | |
| CA1259321A (en) | Process for producing 1,3-dimethyl-2-imidazolidinone | |
| Aresta et al. | Reaction of alkali-metal tetraphenylborates with amines in the presence of CO2: a new easy way to aliphatic and aromatic alkali-metal carbamates | |
| US6353126B1 (en) | Process for the production of malononitrile | |
| US6020514A (en) | Process for producing di-tert-butyl dicarbonate | |
| KR870000956B1 (en) | Porcess for the preparation of -chlorinated chloroformates | |
| US3839387A (en) | Process for preparing n-trimethyl-silylacetamide | |
| JPH0350741B2 (en) | ||
| US5449842A (en) | Gas phase process for the production of 1,1-dichloro-1-fluoroethane and/or 1-chloro-1,1-difluoroethane from vinylidene chloride | |
| White et al. | Chemistry of N-haloamines. XXIV. Behavior of N, N-dichloroamides and N, N-dichlorocarbamates toward nucleophiles | |
| US4401639A (en) | Preparation of carbonyl cyanide | |
| CA1064508A (en) | Chlorination of butadiene sulfone to 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide | |
| JPH09502179A (en) | Method for producing difluoromethane | |
| JP3164284B2 (en) | Method for producing 2-chloro-4-trifluoromethylbenzal chloride | |
| JPH05125017A (en) | Production of chloromethyl pivalate | |
| US4435582A (en) | Manufacture of macrocyclic polyethers | |
| US5476959A (en) | Process for the preparation of dialkyl carbonates | |
| EP0032733B1 (en) | Process for preparing polymethylene polyphenyl polycarbamates | |
| US3399119A (en) | Reaction and distillation process for nu-containing solvents from mixtures thereof with hydrogen halides | |
| CA1261351A (en) | Method for the production of hydroxylamine derivatives | |
| JPH0564142B2 (en) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEC | Expiry (correction) | ||
| MKEX | Expiry |