Oct., 1929
~ - N J R P U R Y L CHLORIDE AND ITS
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DERIVATIVES. 11
[CONTRIBUTION FROM THE CHEMISTRY LABORATORY O F THE
RICEINSTITUTE]
ALPHA-FURFURYL CHLORIDE AND ITS DERIVATIVES.
I1
BY W. R. KIRNERAND G. HOLMES RICHTER RECEIVEDJ U N E 7, 1929
PUBLISHED OCTOBER 5 , 1929
The recent preparation and isolation of a-furfuryl chloride' has greatly simplified the synthesis of a-furfuryl compounds and it is now possible, by using this reagent, to prepare compounds which were in many cases previously obtainable only by more or less indirect methods which usually started with furfural and involved several steps in the procedure. By the use of a-furfuryl chloride, which contains a highly reactive chlorine atom, we have prepared the following new compounds, which are listed in Table I, together with their physical constants. TABLE I NEWFURYL DERIVATIVES 1 2 3 4 5 6 7
B. p., O C .
Name
NO.
Ethyl a-furfurylmalonic ester Ethyl a-furfurylbarbituric acid a-Furfuryl-acetoacetic ester a-Furfuryl nitrile a-Furylacetic acid a-Furfuryl thiocyanate a-Furfuryl ethyl sulfide Yield,
......... 144.5-145
......... ......... 108.5-109.5
......... .........
5
........
..
111-111.5" 74-75
51
.....
61 90 43 70 80
1.10366 I.04627
4 27
........
..
111.5-112.5° 90.5-9 1O
27 28
(AbbC)
R 67
Press., mm.
135.F&136.5"
Molecular refraction Calcd. Obs.
....
.... ....
.... ....
1.4718 1.4833
53.172 30.571
53.290 29.236
....
.....
....
....
....
1.18709 1.04958
1.5614 1.5140
36.083 41.005
37.971 40.773
We have also prepared the following known substances (Table 11) by simple replacement reactions, whereas their previous preparation started with furfural,and was accomplished by more or less roundabout methods, TABLE I1 SUBSTANCES PREPARED NO.
1 2 3 4 5
6
Name
a-Furfurylmalonic ester a-Furfurylbarbituric acid 2-a-Furfurylacetic acid a-Furfuryl acetone a-Furfuryl acetone semicarbazone a-Furfuryl mercaptan
Kirner, THISJOURNAL, 50, 1955 (1928).
B. p . . OC.
125.5-127
Press., mm.
4
....... .......
..
.......
..
84
ti5
.......
.. *.
3132
W . R . KIRNSR AND G. HOLMES RICHTER
Vol. 51
TABLE I1 (Concluded) NO.
1 2 3 4 5
D
M P., OC.
....... 186-187.5 56.5-58
....... 140-141
.......
Yield,
7%
d;
76 37 75 12
1.10999
.. 33
Molecular refraction
n;
1.4591
Calcd.
Obs.
59.433
59.152
.....
....
.....
.... ....
.... .... .... ....
1.13186
1.5329
31.489
..... .....
....
....
.... .... ....
31.302
I n most of these reactions i t was not considered necessary t o use the pure distilled furfuryl chloride so the ethereal solution obtained directly from the reaction mixture was treated with the desired reagent. The main objection to this procedure is that i t does not permit of an accurate method of determining the yield of product theoretically obtained in the various reactions. However, by assuming that the crude reaction product was formed in 70% yield (since a 63% yield of distilled product can be obtained)] an approximate idea is obtained of the percentage yields in the various reactions. The furfuryl-ethyl-barbituric acid is of special interest because of the possibility of its possessing a physiological activity analogous to that of Veronal. We are indebted to Professor A. M. Hjort of the Dartmouth Medical School for his investigation of the action of this substance in producing hypnosis. A more detailed report of the physiological action will ,be published elsewhere.
Experimental a-Furfurylmalonic Ester.-This substance was first prepared by Sandelin* by condensing furfural with malonic acid, yielding furfuralmalonic acid which was then reduced to furfurylmalonic acid and esterified; b. p. 171-173' a t 33 mm.; 265-267" a t atmospheric pressure. It was described as a light yellow oil with a weak fruity odor. This ester was also prepared by Ojiyama, Hasegawa and Matsumura.3 Only the abstract of their article was available in which no details were given but their method is obviously complicated. We obtained this ester by the usual malonic ester condensation using thoroughly anhydrous alcohol prepared according to the method of Smith In this one case distilled furfuryl chloride was used and was added in a solution of Grignard ether. The yield of distilled product was 76%; b. p. 125 5-127' a t 4 mm. The product was a colorless oil with an odor resembling that of malonic ester; di: 1.11196; d:' 1,10999; n': 1.4591; Mn (calcd.) 59.433; MD (obs.) 59.152. Apzal. Subs., 0.2033: C02, 0.4457; H10, 0.1283. Calcd. for CllH1606: C, 59.98; H, 6.72. Found: C, 59.79; H, 7.06. Ethyl-a-furfurylmalonic Ester.-This is a new compound. It was made by ethylating the above furfurylmalonic ester in the usual manner using ethyl iodide. The
* Sandelin, Ber.,
33, 490 (1900). Ojiyama, Hasegawa and Matsumura, J . Pharm. SOC.Japan, 533, 597 (1926); C. A . , 21, 2251 (1927). 4 Smith, J . Chew. SOC., 1288 (1927). 3
Oct., 1929
(r-FURFURYL CHLORIDE AND
ITS DERIVATIVES.
I1
3133
purification of the compound was found difficult due to the continued appearance of iodine during the vacuum distillation. This was finally all removed by several extractions with scdium thiosulfate solution The hoiling point was 135.5-136.5' a t 5 mm.; yield, 67%. This substance was not analyzed but was used directly for the preparation of the furfuryl-ethylbarbituric acid. a-Furfurylbarbituric Acid:-This substance was first prepared by Ojiyama, Hasegawa and M a t ~ u m u r a . ~ They gave the melting point as 193'. We prepared it according to the directions given by Dox and Ycider,6using furfurylmalonicester, urea and srdium ethylate made from special anhydrous alcohol. In the isolation of the compound it was found that it was quite sensitive to the action of mineral acids and therefore should be left in contact with them over as short a pericd as possible and a t a low temperature. The yield was 37%; m . p. 186-18i.5'. Anal. Subs., 0.2511: N2, 30.00 cc. a t 2G0 and 762.3 mm. Calcd. for CgHs04Nn: N, 13.46. Found: N, 13.53. Ethyl-a-furfurylbarbituricAcid.-This is a new compound and was made in precisely the same manner as the substance just described above; yield, 51%; m. p. 144.5145'. Anal. Subs, 0.1168: NI, 13.15 cc. a t 23.6' and 760.1 mm. Calcd. for Cl1Hl2O4NI: N, 11.86. Found: N, 12.41. a-Furfurylacetoacetic Ester.-This new substance was prepared by the usual acetoacetic ester cnndensation using specially dehydrated alcohol, the crude furfuryl chloride being addt.d in a solution of dry ether. The product was' purified hy distillation in a vacuuin; b. p. 111.0-11 1.5' a t 4 mm ; yield, 61%; d i t 1.10562; d:' 1.10366; n2: 1.4718; MD (calcd.) 53.172; M D (obs.) 53.290. Anal. Subs., 0.1993: COX.0.4556; H,O, 0.1193. Calcd. for CllH1404:C, 62.83; H, 6.71. Found: C, 62.34; H, 6.70. 2-a-Furfurylacetic Acid (3-a-Furylpropanoic Acid) .-Baeyere and also Marckwald7 made this acid by first carrying out a Perkin's synthesis on furfural, yielding furfurvlacrylic acid, which was then reduced. They give the melting point as 50-51'. Marckwald* also obtained it by preparing furfurylmalonic acid, which was heated and thus made to lose carbon die xide. Sandclingprepared furfuralmalonic ester, which was converted to furvlsuccinic acid; this on loss of carbon dioxide yielded the furfurylacetic acid. He gave the melting pr,int as 58.5". We obtained tl is arid by the usual acid splitting cf the acetcacetic ester using very conccntratcd alkali fcr the h!-drl lysis accl d i n g to the ccmditic ns given by v. Euler and Clander.Io We obtained in this nay a i595 yield of crcde prcdilct which was twice recrystallized from Mater; rn. p. 56
