GB2352239A - Preparation of Glycerol Dinitrates - Google Patents
Preparation of Glycerol Dinitrates Download PDFInfo
- Publication number
- GB2352239A GB2352239A GB9915558A GB9915558A GB2352239A GB 2352239 A GB2352239 A GB 2352239A GB 9915558 A GB9915558 A GB 9915558A GB 9915558 A GB9915558 A GB 9915558A GB 2352239 A GB2352239 A GB 2352239A
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- GB
- United Kingdom
- Prior art keywords
- glycidol
- dinitrate
- glycerol
- product
- reacting
- 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.)
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- 238000002360 preparation method Methods 0.000 title claims description 16
- GFVHBTOOPNJKLV-UHFFFAOYSA-N 1,2-dinitroglycerol Chemical class [O-][N+](=O)OC(CO)CO[N+]([O-])=O GFVHBTOOPNJKLV-UHFFFAOYSA-N 0.000 title claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 22
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 claims abstract description 15
- ZWWCURLKEXEFQT-UHFFFAOYSA-N dinitrogen pentaoxide Chemical compound [O-][N+](=O)O[N+]([O-])=O ZWWCURLKEXEFQT-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000006239 protecting group Chemical group 0.000 claims abstract description 3
- 125000004665 trialkylsilyl group Chemical group 0.000 claims abstract 3
- 125000001033 ether group Chemical group 0.000 claims abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- -1 trialkylsilyl ether derivative Chemical class 0.000 claims description 12
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 10
- ASIGVDLTBLZXNC-UHFFFAOYSA-N 1,3-dinitroglycerol Chemical compound [O-][N+](=O)OCC(O)CO[N+]([O-])=O ASIGVDLTBLZXNC-UHFFFAOYSA-N 0.000 claims description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims 1
- 230000000802 nitrating effect Effects 0.000 abstract description 5
- 238000000926 separation method Methods 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 1
- 238000007796 conventional method Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000000047 product Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 238000006396 nitration reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- JKXONPYJVWEAEL-UHFFFAOYSA-N oxiran-2-ylmethyl acetate Chemical compound CC(=O)OCC1CO1 JKXONPYJVWEAEL-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- OMBRFUXPXNIUCZ-UHFFFAOYSA-N dioxidonitrogen(1+) Chemical compound O=[N+]=O OMBRFUXPXNIUCZ-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical group [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- UTANVRJWTDLNNZ-UHFFFAOYSA-N nitric acid thionyl dichloride Chemical compound O[N+]([O-])=O.ClS(Cl)=O UTANVRJWTDLNNZ-UHFFFAOYSA-N 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/16—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by esterified hydroxyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/02—Preparation of esters of nitric acid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A method for preparing either the 1,2-dinitrate or the 1,3-dinitrate of glycerol involves protecting glycidol respectively with either a trialkylsilyl ether group or an acetate group then nitrating with dinitrogen pentoxide under anhydrous conditions, after which the protecting group is removed. High yields of exclusively the desired isomer are obtained avoiding the difficulties of isomer separation which arise with conventional methods.
Description
1 2352239 PROCESS FOR THE PRODUCTION OF GLYCEROL DINITRATES The present
invention relates to methods for the production, independently, of glycerol-1,2- and 1,3-dinitrates (1,2- or 1,3-dinitrato- 2-hydroxypropane or 1,2- or 1,3dinitroglycerine).
Both the 1,2- and 1,3-dinitrates of glycerol have potential application in the synthesis of new energetic materials and as pharmaceuticals, for the alleviation of heart complaints.
Synthesis of dinitroglycerine (either 1,2- or 1,3-dinitrato-2hydroxypropane) has heretofore been achieved generally by mixed acid nitration of glycerol but this inevitably leads to a mixture of the isomers which are extremely difficult to then separate. Moreover the yield of the dinitrated product by this route is not very good as the reaction mixture further includes both mono- and tri-nitrated species, and these also have to be separated off in order to obtain the desired nitro-compounds.
Hakimelahi et al (Helv. Chim. Acta 67, 906 (1984)) have described the use of either thionyl chloride nitrate or thionyl nitrate as the nitrating agent in the preparation specifically of the 1,3-dinitrate in 70% yield. The use of silver nitrate to produce the nitrating agent makes the process relatively expensive and the non-quantitative yield means that extensive separation efforts are required in order to arrive at the desired product in pure form.
The applicant has now found that by use of the unconventional nitrating agent dinitrogen pentoxide in conjunction with other relatively straightforward process steps it is not only possible to achieve synthesis of specifically either the 1,2- or the 1,3dinitrate under mild conditions but also in high (virtually quantitative) yield. In the case of the 1,3-dinitrate preparation route this result is particularly surprising as on the basis of all previous knowledge the expected product would be the 1,2-dinitrate. However, by the present method none of the latter isomer is produced. Instead that 2 material may be obtained in high yield by use of a variation on the preparative method for the 1,3-dinitrate.
Accordingly the present invention provides a process for the preparation of glycerol 1,2- or glycerol I,')-dinitrate from glycidol which comprises the steps of- a) preparing either the acetate derivative of glycidol where the desired product is the 1,3-dinitrate or a trialkylsilyl ether derivative (as hereinafter defined) where the desired product is the 1,2-dinitrate; b) reacting the glycidol derivative from step (a) with dinitrogen pentoxide under anhydrous conditions in order to form the corresponding dinitrato compound; and c) removing the protective group from the product of step (b) to obtain the glycerol 1,2-dinitrate or glycerol 1,3-dinitrate product as the case may be.
For the preparation of the 1,3-dinitrate, step (a) is conveniently accomplished using acetyl chloride or acetyl bromide in the presence of triethylamine at a temperature of below 50C, preferably around OOC, in dichloromethane. The product is purified by aqueous workup followed by distillation. Other methods for accomplishing step (a) would include use of acetic anhydride in the presence of a catalyst such as trimethylsilyl trifluoromethanesulphonate.
Step (c) of this process is conveniently carried out by the use of potassium carbonate in methanol. Alternatively, other deprotection procedures such as treatment with iodine/methanol, p-toluenesulphonic acid/methanol and hydrochloric acid/methanol could be used.
In the nitration step (b) for either process, the protected derivative of glycidol is added to an eqimolar amount of N201in dry dichloromethane at sub-ambient 3 temperature (preferably below I OOC, most preferably at about -5 to 5'C) and left to stir at this temperature for about 2 hours before being allowed to warm up to ambient temperature and left for a further hour. A simple aqueous workup followed by removal of the organic solvent gives the pure glycerol dinitrate product.
For the preparation of the 1,2-dinitrate, step (a) is conveniently carried out by reaction of the glycerol with t-butyldimethylsilyl chloride in dry dichloromethane followed by slow addition to the reaction mixture of triethylamine. A temperature of below 5'C is again suitable for this step, as with the preparation of the 1,3 isomer. After stirring for 8 to 10 hours, pentane is added to the mixture and the mixture filtered to provide, after concentration, a residue from which the product may be distilled. As an alternative to the use of the t- butyldimethylsilyl chloride, other analagous reagents with at least one higher alkyl substituent may be used. The corresponding trimethylsilyl compound is not suitable as it is subject to reaction with the N,O, nitrating agent and likewise silyl species which contain aromatic substituents such as benzyl or phenyl groups are unsuitable for use because of the competing reaction of N20, to nitrate the aromatic ring of the substituent.
Accordingly the term "trialkylsilyl ether derivative" is used herein in relation to the process of the present invention to mean a trialkylsilyl ether derivative in which at least one of the alkyl groups is a propyl group or preferably a butyl or higher alkyl group.
In the case of the 1,2-dinitrate preparation, step (c) involves the use of wellknown reagents for removing the silyl ether protecting group such as 2,3-dichloro-5,6dicyano-1,4-benzoquinone (DDQ), lithium chloride in dimethylformamide, ceric ammonium nitrate, iodine or tetrabutylammonium fluoride/boron trifluoride complex for example.
4 Other variations of the reaction conditions detailed above for the protection and deprotection steps, as may be readily apparent to the skilled reader, shall be encompassed within the scope of the invention.
In the case of the process for the 1,3-dinitrate, it is hypothesised that the nitration reaction involves addition of a nitronium ion at the epoxide oxygen, followed by an intramolecular rearrangement producing a stable intermediate dioxaleniurn salt. This is then attacked by the nitrate anion to give (unexpectedly) the 1,3-dinitrato compound.
The invention is now further described with reference to the accompanying examples.
Preparation of Glycerol- I 2-Dinitrate Example I - Preparation of Glycidol t-Butyldimethylsilyl Ethe A three-necked round-bottom flask (100 cm') was equipped with a stirrer bar, alcohol thermometer and a pressure equalised dropping funnel. The flask was charged with glycidol (0.74 g, 10 mmol) in dry dichloromethane (DCM)(30 cm') followed by the addition of t-butyldimethylsilyl chloride (1.65 g, I I mmol) in dichloromethane (30 em') at O'C via the pressure equalised dropping ftmel. The reaction was allowed to stir for 30 minutes before slow addition of triethylamine (L I I g, I I mmol in 10 cm 3 of DCM). The reaction was then allowed to stir at ambient temperature overnight, after which pentane (30 cm') was added and the mixture filtered. The filtrate was concentrated and the residue distilled on a kugelrohr to give the product in almost quantitative yield (98%).
Example_2 - Nitration of Glycidol t-Butyldimethylsilyl Ethe A three-necked round-bottom flask (100 cm') was equipped with a stirrer bar, alcohol thermometer and a pressure equalised dropping funnel. The flask was charged with glycidol t-butyidimethylsilyl ether (0.36 g, 2 mmol) in dry dichloromethane (20 cm') followed by N205 (0.33 g, 3 mmol) in dichloromethane (20 cm') at O'C. The reaction was allowed to stir for 2 h at O'C and then at ambient for a further I h. The reaction was quenched with saturated sodium bicarbonate solution (30 cm') and stirred for a further 15 minutes, separated, dried and the solvent removed to give the glycerol- 1,2-dinitrate-3-t-butyldimethylsilyI ether derivative in 89% yield as a yellow oil. 'H nmr (CDC13): 8 4.83 (1 H, dd '2j = 12.79, 3j = 4.20 Hz, CH20NO2),4.64 (I H, dd, 2j = 12.83 and 3j = 6.82 Hz, CH20NO2)18 3.89 (1 H, dd, 2j = 5.09, 3j = 1.72 Hz, CH20Si), 3.88 (IH, dd, 2j = 5.09 and 'J = 2.09 Hz, CH20Si), 3.32 (IH, m, CHON02), 0.89 (9H, CMe3) and 0.09 (6H, S'Me2)' "C nmr 69.08 (C 1), 78.71 (C2), 59.65 (0), 25. 42 (CMe3) and 17.94 (SiMe2).
Example 3 - Deprotection of Glycerol- 1,2-Dinitrate-3-1ButyldimethylsilyI Ether A single-neck round-bottom flask (10 CM3) was charged with glycerol-1, 2dinitrate-3-t-butyldimethylsilyI ether [2 CM3 of IM solution in acetonitrile (0.59 g, 2 mmol)]. 2,3-Dichloro-5,6-dicyano-I 4-benzoquinone, DDQ [2 cm' of I M solution in acetonitrile:water (9:1), 2 mmol)] was added and the mixture stirred overnight. The mixture was then passed through a silica column (I g) and the remaining residue washed with fresh ethyl acetate (5 cm') and also passed through the column. The mixture was concentrated under vacuum to give glycerol-1,2-dinitrate in 92% yield.
H nmr (CDC'3)8 4.86 (IH, dd, 2j = 12. 0, 'J = 4.3 0 Hz, CH20NO2), 4.43 (IH, dd, 2j 12. 0 and 'J = 5.80 Hz, CH20NO2), 8 3.96, (2H, m, CH20H), 5.3 8 (1 H, m, CHON02). 13 C nmr 69.12 (C 1), 79.3 9 (U), 59.91 (0).
6 Preparation of Glycerol- 1,3-D initrate Example 4 - Preparation of Glycidyl Acetate A three-necked round-bottom flask (100 cm') was equipped with a stirrer bar, alcohol thermometer and a pressure equalised dropping ftinnel. The flask was charged with glycidol (1.16 g, 10 mmol) in dry dichloromethane (30 cm') followed by acetyl chloride (0.86 g, I I mmol) in dichloromethane (30 cm') at O'C via the pressure equalised dropping funnel. The reaction was allowed to stir for 30 minutes before slow addition of triethylamine (I. I I g, I I mmol in 10 cm' of DCM). The reaction was then allowed to stir at ambient temperature overnight, after which pentane (30 cm 3) was added and the mixture filtered. The filtrate was concentrated and the residue distilled on a kugelrohr to give the product in almost quantitative yield (98%).
Example 5 - Nitration of Glycidyl Acetate A three-necked round-bottom flask (100 cm') was equipped with a stirrer bar, alcohol thermometer and a pressure equalised dropping funnel. The flask was charged with glycidyl acetate (0.23 g, 2 mmol) in dry dichloromethane (20 cm') followed by N205 (0.33 g, 3 mmol) in dichloromethane (20 cm') at O'C. The reaction was allowed to stir for 2 h at O'C and then at ambient for a further I h.
The reaction was quenched with saturated sodium bicarbonate solution (30 cm') and stirred for a further 15 minutes, separated, dried and the solvent removed to give the product in almost quantitative yield (95%) as a yellow oil.
H nmr (CDC'3)8 4.71, (2H, dd 2j = 12.50, 'J = 4.01 Hz, CH20NO2),4.59 (214, dd, 2j = 12.48 and'J = 5.83 Hz, CH20NO2),5.37 (IH, m, CHOCOCHO and 2.12, (3H, s, OCOCH3). "C nmr 69.65 (C I and 3), 66.24 (C2), 20.44 (Me) and 169. 81 (CO).
7 Mass spectrum (Cl-NH3), 242 (10, M + NE4'), 22 5 (15, M + H-), 162 (75,H - ON02), 116 (38, M+ - ON02-NO2) and 46 (100, N02').
Example 6 - Deprotection of Glycerol-2-Acetoxy-1,3-Dinitrate A single-necked round-bottom flask (10 cm') was charged with glycerol2acetoxy-1,3-dinitrate (0.42 g, 2 mmol)] and methanol (10 cm'). Potassium carbonate (0.055 g, 0.4 mmol in I cm' of water was added and the mixture stirred for 4 h. The mixture was then extracted with DCM (2 x 10 cm'), separated and the organic layers combined, dried and the solvent removed in vacuo to give a 93% yield of the glycerol- 1,3-dinitrate.
114 nmr (CDC'3)8 4.62, (2H, dd'J = 11.70, 'J = 4.26 Hz, CH20NO2),4.55 (2H, dd, 2j = 11.70 and'J = 6.25 Hz, CH20NO2),4.41 (IH, m, CHON) and 3.22, (OH, br). "C nmr 72.42 (C I and 3), 65.40 (C2).
8
Claims (1)
- ClaimsI A process for the preparation of glycerol 1,2- or glycerol 1,3dinitrate from glycidol which comprises the steps of:a) preparing either the acetate derivative of glycidol where the desired product is the 1,3-dinitrate or a trialkylsilyl ether derivative (as herein defined) where the desired product is the 1,2-dinitrate; b) reacting the glycidol derivative from step (a) with dinitrogen pentoxide under anhydrous conditions in order to form the corresponding dinitrato compound; and c) removing the protective group from the product of step (b) to obtain the glycerol 1,2-dinitrate or glycerol 1,3-dinitrate product as the case may be.2. A process for the preparation of glycerol 1,3-dinitrate from glycidol which comprises the steps of:a) preparing the acetate derivative of glycidol; b) reacting the glycidol acetate from step (a) with dinitrogen pentoxide under anhydrous conditions in order to form the corresponding 1,3- dinitrato compound; and c) removing the acetate protective group from the product of step (b) to obtain the glycerol 1,3-dinitrate product.9 3. A process as claimed in claim I or claim 2 wherein the acetate derivative of glycidol is prepared by reacting glycidol with acetyl chloride or acetyl bromide in the presence of triethylamine at about O'C or by reacting with acetic anhydride in the presence of trimethylsilyl trifluoromethanesulphonate.4. A process as claimed in any of claims I to 3 wherein the acetate protective group is removed by reacting the product of step (b) with potassium carbonate in methanol, iodine in methanol, p-toluenesulphonic acid in methanol or hydrochloric acid in methanol.5. A process for the preparation of glycerol 1,2-dinitrate from glycidol which comprises the steps of- a) preparing a trialkylsilyl ether derivative (as herein defined) of glycidol; b) reacting the trialkylsilyl ether derivative from step (a) with dinitrogen pentoxide under anhydrous conditions in order to form the corresponding dinitrato compound; and c) removing the trialkylsilyl ether protecting group from the product of step (b) to obtain the glycerol 1,2-dinitrate product.6. A process according to claim I or claim 5 wherein the trialkylsilyl ether derivative is prepared by reacting glycidol with the corresponding trialkylsilyl chloride in the presence of triethylamine at a temperature of about OOC.7. A process according to claim 1, 5 or 6 wherein the trialkylsilyl ether protective group is removed by reacting the product of step (b) with 2,3-dichloro-5, 6dicyano-1,4-benzoquinone (DDQ), lithium chloride in dimethylformamide, ceric ammonium nitrate, iodine or tetrabutylammoniurn fluoride/boron trifluoride complex.8. A process as claimed in any of claims 1, 5, 6 or 7 wherein the trialkylsilyl in the trialkylsilyl ether derivative is butyldimethylsilyl.9. A process substantially as described herein and with reference to the examples.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9915558A GB2352239A (en) | 1999-07-03 | 1999-07-03 | Preparation of Glycerol Dinitrates |
| PCT/GB2000/002515 WO2001002336A1 (en) | 1999-07-03 | 2000-06-26 | Process for the production of glycerol dinitrates |
| AU55576/00A AU5557600A (en) | 1999-07-03 | 2000-06-26 | Process for the production of glycerol dinitrates |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9915558A GB2352239A (en) | 1999-07-03 | 1999-07-03 | Preparation of Glycerol Dinitrates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB9915558D0 GB9915558D0 (en) | 1999-09-01 |
| GB2352239A true GB2352239A (en) | 2001-01-24 |
Family
ID=10856557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9915558A Withdrawn GB2352239A (en) | 1999-07-03 | 1999-07-03 | Preparation of Glycerol Dinitrates |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU5557600A (en) |
| GB (1) | GB2352239A (en) |
| WO (1) | WO2001002336A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101665434B (en) * | 2009-09-15 | 2012-09-05 | 天津大学 | Safe separation and purification method of nitrate ester |
| SK288302B6 (en) * | 2013-05-31 | 2015-09-03 | Stu Fakulta Chemickej A Potravinárskej Technológie | An additive to increase the cetane number of diesel fuel or biodiesel fuel and use of it |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2181124B (en) * | 1982-07-15 | 1987-10-14 | Secr Defence | Process for producing high energy materials |
| NO167087C (en) * | 1985-10-25 | 1991-10-02 | Secr Defence Brit | PROCEDURE FOR PREPARING A NITRATE TESTER. |
| GB2317172A (en) * | 1996-09-05 | 1998-03-18 | Secr Defence | Dinitrate esters |
-
1999
- 1999-07-03 GB GB9915558A patent/GB2352239A/en not_active Withdrawn
-
2000
- 2000-06-26 AU AU55576/00A patent/AU5557600A/en not_active Abandoned
- 2000-06-26 WO PCT/GB2000/002515 patent/WO2001002336A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU5557600A (en) | 2001-01-22 |
| WO2001002336A1 (en) | 2001-01-11 |
| GB9915558D0 (en) | 1999-09-01 |
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| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |