US814496A - Process of making barbituric acids. - Google Patents
Process of making barbituric acids. Download PDFInfo
- Publication number
- US814496A US814496A US23187304A US1904231873A US814496A US 814496 A US814496 A US 814496A US 23187304 A US23187304 A US 23187304A US 1904231873 A US1904231873 A US 1904231873A US 814496 A US814496 A US 814496A
- Authority
- US
- United States
- Prior art keywords
- acid
- alcohol
- kilograms
- making
- barbituric
- 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 - Lifetime
Links
- 238000000034 method Methods 0.000 title description 8
- 150000007656 barbituric acids Chemical class 0.000 title description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229960004198 guanidine Drugs 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 229960002319 barbital Drugs 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- DPHBCBNBDNTWKL-UHFFFAOYSA-N 2,2-diethyl-3-hydroxybutanedinitrile Chemical compound C(C)C(C(C#N)O)(C#N)CC DPHBCBNBDNTWKL-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 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
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- ZQXCMFRWRHARIB-UHFFFAOYSA-N 2-ethyl-2-hydroxybutanedinitrile Chemical compound CCC(O)(C#N)CC#N ZQXCMFRWRHARIB-UHFFFAOYSA-N 0.000 description 1
- FMTLDVACNZDTQL-UHFFFAOYSA-N 5-ethyl-1,3-diazinane-2,4,6-trione Chemical compound CCC1C(=O)NC(=O)NC1=O FMTLDVACNZDTQL-UHFFFAOYSA-N 0.000 description 1
- JSVFGUVEXOEQEC-UHFFFAOYSA-N 5-imino-1,3-diazinane-2,4,6-trione Chemical compound N=C1C(=O)NC(=O)NC1=O JSVFGUVEXOEQEC-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 101150032584 oxy-4 gene Proteins 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Definitions
- My invention relates to the manufacture of 1o barbituric acids; and it consists of certain novel processes particularly pointed out in the concluding claims.
- R and R indicate hydrogen atoms or simple alkyl radicals
- X indicates a bivalent body, such 'as oxygen and irnino, (NH radical.)
- the bodies obtained in this way may be easily converted into the corresponding barbituric acids by an agent separating ammonia.
- agent may be sulfuric acid, hydrochloric acid, or nitric acid or even alkalis, (the latter, however, be ing less suitable.)
- Second example 12.2 kilograms dieth lmalonicacidnitrlle are heated with six kil rams urea and 2.3 kilograms sodium in fifty Titers of absolute alcohol for four hours in an autoclave to centigrade. After adding six liters of glacial acetic-acid the alcohol is The residue is heated for an hour with about one hundred liters of water and is then left standing over night. After bein dissolved in two molecules of warm dilute hydrochloric acid and being precipitated with ammonia the base crystallizes in tufted aggregates of crystal. It is a 5-diethyl-2 oxy-4, 6-diiminopyrimidin.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
UNITED sTATEs PATENT oEEioE;
OTTO WOLFES,
OF DARMSTADT, GERMANY. ASSIGNOR TO THE FIRM OF E. MEROK, OF DARMSTADT. GERMANY.
PROCESS OF MAKING- BARBITURIC ACIDS- I Specification of Letters Patent.
Patented March 6, 1906.
. Application filed November 8, 1904. Serial No. 231,873
My invention relates to the manufacture of 1o barbituric acids; and it consists of certain novel processes particularly pointed out in the concluding claims.
From experiments made by Traube, Conrad, and myself it is known that cyanacetic I5 ester and its substitution products may be condensed with urea, guanidin, and similar bodies to derivates of pyrimidin, one amid of the urea, &c., combining with the cyano en group of the ester, while the carboxethy in separating alcohol participates with the second amid of the ring formation. The process is represented by the following equation:
w on NH m co COOR NH/ NH :10 OL NH\ /CO+ROH. y comm It has been discovered by me that compounds with two cyanogen groi1ps-as, for instance, the malonitrilemay be condensed with urea and with compounds constituted in an analogous Wayas, for example, guanidin and the derivatives and homologues of urea and guanidinif condensing means (viz., alkali metals, their amids, or alcoholates) are employed; but even without the em- 0 ployment of such condensing means the combination is successful if the bodies are permitted to act on each other for a prolonged time at a high temperature or under pressure.
My process as outlined above and em.-
bodied in various forms in the following exalcohol.
amples may be expressed by the following formula:
In the above formula R and R indicate hydrogen atoms or simple alkyl radicals, and X indicates a bivalent body, such 'as oxygen and irnino, (NH radical.) The bodies obtained in this way may be easily converted into the corresponding barbituric acids by an agent separating ammonia. Such agent may be sulfuric acid, hydrochloric acid, or nitric acid or even alkalis, (the latter, however, be ing less suitable.)
I will now describe the manner in which I at present prefer to practice my invention, giving, by way of illustration, a number of examples thereof; but it willbe understood that various modifications and changes, both as to materials and treatment, may be made without departing from the spirit of my in- 7 5 vention and Without exceeding the scope of my claims.
First example: A solution of 9.6 kilograms guanidinhydrochlorate (one molecule) in alcohol is mixed with a solution of 2.3 kilograms sodium (one molecule) in fifty liters of alcohol, the separated chlorid of sodium drawn ofi,-and the solution of the free guanidin then heated with 12.2 kilograms (one molecule) diethylmalonitrile for five hours to centigrade. After being cooled off the reactionary mass, fine colorless needles, is drawn OE and carefully Washed with The new product contains alcohol of crystalli'zation and melts at 240centigrade o sulfate or nitrate.-
v wit evaporated.
while foaming up. It is dissolved easily in water and in diluted acids even in the cold. In cold alcohol it can be dissolved only with difficulty. This triiminodiethylbarbituric acid (diiminodiethylmalonyl-guanidin) is converted smoothl into diethylbarbituric acid by being heate for three hours to 120 centigrade with diluted hydrochloric. acid in a closed receptacle. When cooled ofi, the product congeals to a crystalline mass. Separate from the mother-liquor, 'wash with water, and again crystallize from hot water. The thus-purified substance melts at 191 centigrade and has all the properties of the known diethylbarbituric acid.
Second example: 12.2 kilograms dieth lmalonicacidnitrlle are heated with six kil rams urea and 2.3 kilograms sodium in fifty Titers of absolute alcohol for four hours in an autoclave to centigrade. After adding six liters of glacial acetic-acid the alcohol is The residue is heated for an hour with about one hundred liters of water and is then left standing over night. After bein dissolved in two molecules of warm dilute hydrochloric acid and being precipitated with ammonia the base crystallizes in tufted aggregates of crystal. It is a 5-diethyl-2 oxy-4, 6-diiminopyrimidin. melts, while developing basic vapors, at about 272, (277 corr.) The chlorid is dissolved with more difficulty in water than the In alkalis the base issoluble, but not in ammonia. From hot water it ma be ,crystallized over a ain. If boiled five times the amount of thirty per cent. sulfuric acid, it is converted also into diethylbarbituric acid. The purifying and isolating is'done as in the first example.
Third example: 9.4 kilograms monoethylmalonitrile are heated for five hours with an e uivalent amount of guanidin in alcoholic so ution in an autoclave to 100 centigrade. Lustrous small leaves are separated containing alcohol of crystallization. After being crystallized over again from alcohol and being dried at 100 centigrade they melt at 189, (190 corr.) They can be easily dissolved in cold water and hot alcohol. If this compound is heated for several hours in a closed vessel with diluted hydrochloric acid (1 3)'to it is converted into the monoethylbarbituric acid. This acid melts at 194 corr., (Conrad and Guthzeit giving corr.) It reacts and tastes rather strongly acid just as the barbituric acid itself. It dlffers thereb distinctly from the diethylbarbituric aci which tastes bitter and possesses a reaction which is acid only. to a very small degree.
Fourth example: 6.6 kilograms malonitrile are heated to 100 centigrade for one hour in an autoclave with an equivalent amount of guanidin prepared from 9.6 kilograms hydrochlorate and 2.3 kilograms sodium in eighty liters of alcohol. When cooled off, colorless small needles are separated, the amount of which needles is about 6.5 kilograms when dried. The melting-point of this triiminobarbituric acid is 248, (corr. 252.) The base forms with diluted cold mineral acid salts, which are dissolved only with difficulty. With nitrate of sodium and glacial acetic acid a light violet nitroso body is formed at once. It has a remarkable resistance a ainst warm strong sulfuric acid or boiling so ium hydroxid. By prolonged and highly heating it with acids barbituric acid is obtained therefrom.
Having thus fully described my invention, what I claim, and desire to secure by Letters Patent, is-
1. The process of manufacturing a barbituric acid consisting in the condensation of a malonitrile of the general formula R/ \cN with a substance having the general formula Nl'lz NHZ whereby a 4.6 diimino-pyrimidin of the gen eral formula.
' R cNH-NH c c=x R. (JNHNH is produced, the latter being subsequently converted by saponification into a 4-6-dioxypyrimidin.
2. The process of manufacturing a barbituric acid consisting in condensing a malonitrile with a substance of the general formula NH2 xo NHz the iminobarbituric acid and converting barbituric acid by saponifithus formed into cation. 1
The process consisting in-condensing diethylmalonitrile with guanidin with the aid of sodium alcoholate, and subsequently saponifying to produce barbituric acid.
In testimony whereof I have signed my name to this specification in the presence of two subscribing witnesses.
- OTTO WOLFES. Witnesses:
MAX CON-RAD, WALTER HOUSING.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23187304A US814496A (en) | 1904-11-08 | 1904-11-08 | Process of making barbituric acids. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23187304A US814496A (en) | 1904-11-08 | 1904-11-08 | Process of making barbituric acids. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US814496A true US814496A (en) | 1906-03-06 |
Family
ID=2882977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US23187304A Expired - Lifetime US814496A (en) | 1904-11-08 | 1904-11-08 | Process of making barbituric acids. |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US814496A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5262402A (en) * | 1990-02-08 | 1993-11-16 | Sapos S.A. | Process for preparing pyrimidinetrione derivatives |
| US5274093A (en) * | 1989-08-03 | 1993-12-28 | Huels Aktiengesellschaft | Process for the preparation of sodium thiobarbiturate |
-
1904
- 1904-11-08 US US23187304A patent/US814496A/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5274093A (en) * | 1989-08-03 | 1993-12-28 | Huels Aktiengesellschaft | Process for the preparation of sodium thiobarbiturate |
| US5262402A (en) * | 1990-02-08 | 1993-11-16 | Sapos S.A. | Process for preparing pyrimidinetrione derivatives |
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