HEXAHYDROPYRIMIDINES FROM NITROPARAFFINS
Aug., 1946
1611
[COSTRIBIJTIOX FROM RESEARCH AND DEVELOPMENT DEPARTMENT, COMMERCIAL SOLVENTS CORPORATION]
The Preparation of Some Hexahydropyrimidines from Nitroparaffins1 B Y M U R R A Y SENKUS
Method B. (a) 5-Nitro-l,3-dibenzyl-5-methylhexahydropyrimidine from 2-Nitro-2-methyl-l,3-propanediol, Benzylamine and Formaldehyde.-A mixture which consisted of 57 ml. (0.76 mole) of 36% (by wt.) aqueous formaldehyde, 102 g. (0.76 mole) of 2-nitro-2-1ncthyl-l,3-propanediol, ltil g. (1.51 mole) of beiizylamiiie arid 300 ml. of methanol was reflused for six hours. The homogeneous solution was poured into a 1-liter beaker and the product commenced to Crystallize. The mixture was allowed to stand overnight and then it was filtered. Thc product was mashed on the funnel with 200 n i l . of cold ( l o o ) methanol and dried in air; yield was 196 g. (b) 5-Nitro-l,3-diisopropyl-5-hydroxymethylhexahydropyrimidine from Tris-( hydroxymethyl) -nitromethane, Isopropylamine and Formaldehyde.-To 15 g. (0.1 mole) of tris-(hydroxymethyl)-nitromethane were added in the cold 12 g. (0.2 mole) of isopropylamine and 7 ml. (0.1 mole) of 36y0 (by weight) aqueous formaldehyde. The mixture was stirred at room temperature for thirty minutes and then was allowed to stand a t 5 " overnight. The mixture was filtered and the solid product was dried in the air for four hours; yield was 22 g: Method C. (a) 5-Nitro-1,3-bis-( l-methyl-3,5-dioxacyclohexyl)-5-propylhexahydropyrimidine from 5-Amino5-methyl-l,3-dioxane, Formaldehyde and 1-Nitrobutane. -To 210 g. (1.8 moles) of 5-amino-5-methyl-l,3-dioxane were added 202 ml. (2.7 moles) of 3670 (by weight) aqueous formaldehyde, 95 g. (0.9 mole) of 1-nitrobutane and 200 n i l . of methanol. The mixture was stirred for a short time iii order to make it homogeneous. The product began t o crystallize from the solution after two hours a t room temperature. The niixturr was filtered after twenty hours. The solid was washed with cold mcthanol and then was dried in air; yield was 130 g. Experimental (b) 5-Nitro-l,3-diisopropylhexahydropyrimidine from I. 5-Nitrohexahydropyrimidines Nitromethane, Isopropylamine and Formaldehyde.--To 120 g. (2.02 moles) of isopropylamine was added 225 ml. Examples of each of the three procedures which were (3 moles) of 36y0(by weight) aqueous formaldehyde in the developed for the preparation of 5-nitrohexahydropyrimicold. While the mixture was stirred and held a t 10" by a dines are given below. Method A. (a) 5-Nitro-l,3-diisopropyl-5-methylhexa- bath, 61 g. (1 mole) of nitrotriethane was added dropwise. hydropyrimidine from 2-Nitro-2-methyl-l,3-propanebis- Stirring was continued for one and one-half hours and then (isopropylamine) and Formaldehyde.-To a 2-liter, round- the mixture was estracted with 1 liter of ethyl ether. The bottom flask equipped with a stirrer and a Dean and ether extract was stored over anhydrous sodium sulfate Stark3 moisture trap which was connected to a condenser a t 0 " overnight. The ethcr solution was concentrated on the steam-bath to 400 ml. To the residue JTas added 1 were added 217 g. (1 mole) of 2-nitro-2-methyl-1,3-propanebis-(isopropylamine), 500 ml. of cyclohexane and liter of petroleum ether and the solution was again con7 5 ml. (1mole) of 36% (by weight) aqueous formaldehyde. centrated on thesteam-bath, this time to300ml. A brown product separated from the residue a t room temperature; The mixture was agitated and refluxed until water had ceased separating in the trap. The volume of the mixture yield was 147 g. Two recrystallizations from petrowas reduced t o 400 ml. by evaporation on the steam-bath. leum ether yielded a white product. The 5-nitrohexahydropyrimidines derived from aliThe residue was cooled to 15" and the product was allowed phatic amines are either white crystalline solids or colorto crystallize; yield was 195 g. (b) 5-Nitro-l,3-diphenyl-5-methylhexahydropyrimidine less liquids; those derived from aromatic amines possess a light-yellow color. The 5-nitrohexahydropyrimidines from 2-Nitro-2-methyl-l,3-propanebis-(aniline)and Formare soluble in acetone, benzene and ether. The low molecaldehyde.-A mixture which consisted of 570 g. (2 mole,,) of 2-nitro-2-methyl-l,3-propanebis-(aniline),150 ml. (2 ular weight compounds are appreciably soluble in water but those with long non-polar groups on the nitrogens in moles) of 36% aqueous formaldehyde and 1500 ml. of the ring are insoluble in water. 5-Nitro-1,3-diisopropylethyl alcohol was stirred and refluxed for eight hours. Stirring was continued and the mixture was cooled slowly hexahydropyrimidine decomposes to a tar a t room temt o 25" during which time the product crystallized. The perature after several days; the other nitro compounds mixture was filtered and the solid was washed with 400 ml. have shown no signs of decomposition on storage in the of ethyl alcohol. The yield of a light yellow crystalline room for two years. They are decomposed slowly by hot mineral acids. The 5-nitrohexahydropyriniidines toproduct was 525 g. gether with some properties and analyses are listed in Table I. (1) Prepared for t h e 1946 Spring meeting of the Organic Divlsion A. C. S . The subject matter of this paper is covered b y L . S. 11. 5-Aminohexahydropyrimidines Patents 2,391,847a n d 2,387,043. All 5-aminohexahydropyriidines which are reported ( l a ) Senkus, THIS JOURNAL, 68, 10 (1946) herein were prepared by the same procedure. One mole ( 2 ) Johnson, % b a d ,14 (1946) of a 5-nitrohexahydropyrimidine was hydrogenated in (3) Dean a n d Stark, Ind. Eng. Chem., 12, 486 (1920),
Recent studies'" of the reaction of nitroparaffins with formaldehyde and amines had made available some new nitro amines. Some reactions of the 1,3-propanediamines were investigated and i t was found that they will react with formaldehyde to give 5-nitrohexahydropyrimidines. For example '2-nitro-2-methyl-l,3-propanebis(isopropylamine) and formaldehyde gave S-nitro- lJ-diisopropyl-5-methylhexahydropyrimidinein good yield. Further work showed that 5nitrohexahydropyrimidines could be prepared by other methods. Thus the above compound was also prepared by allowing one mole of 2-nitro-2-methyl1,3-propanediol to react with 2 moles of isopropylamine and one mole of formaldehyde; i t was also prepared by allowing one mole of nitroethane to react with 2 moles of isopropylamine and 3 moles of formaldehyde. A number of &nitrohexahydropyrimidines were prepared by the above methods and are reported herein. It was also found that the Z-nitrohexahytiropyrimidines can be hydrogenated readily in the presence of Raney nickel to the corresponding 5aminohexahydropyrimidines. The new amines that were prepared are also described in the present paper. t2
MIJRRAY SENKUS
1612
Vol. 68
TABLE I CI-1, S O M E ~ ~ E X A H Y D R O P Y R I M I D I N EOF S THE T Y P E
I1-N' I
1
Analyses.
c
R
R"
R'
CaHaCHt CsH5CH2 C~I-I~CHZ CbHsCHz CaHaCH2 CeHaCI-12
hi. p. C.
CHI CH3 CHI CzHs C3H7 C11?7
NO2 NHr N=CI1z
113.5
NO2 NO2
93.7 113.0
CII,
h*02
CHI
NU2
CiHi
NO2
NHa
B. p. OC.
Mm.
d%o
n%
178 196
0.6 0.8
1.51359 1,0184 1.5628 1 0 0 1 0
178
0 3
l..;T,T,.l
Carbon Calcd Found
-53.I 5
0.3
1.1891
7*
Hydrogen
Calcd.
Found
1.0304
1.71.8 173
R
E ''
52.03
7.84
0.3
1.4968
-
12.90
Found 12.48 14.15 13.46 12.11 11.80 12.91
13 32
13.26
11.25
11 18
12.24
12.25
7.cifi
1.1028
94.4 169
-- ---
Nitrogen
Calcd. 12.01 1&.33 13.67 12.38 11.89
1.1050
C3H7
NHi
(CHzOH) (CHdzC (CHzOH) (CHdzC (C4H9)2NCHzCHnCHz CHI
CHI CH3 CHa
NO2 2"
2"
162 230
0.4 0.7
1.4923 1.0514 1.4724 0.8892
16.20 1.5.44
16.01 15.40
(CHs)zN--CHd-
CHI
NHz
162
0.4
1.4767 0.9261
20.50
19.72
C2Hr CzHs CHa CzHs
NHi NHz NHI
6.45 6.39 12.44 11.70
CHI
NHz
CHz
124.0
d3,95
53.68
9.41
9.06
CHi CiiHn CnHn (CoHid (CHz)CH (CsHir) ( C H d C H
NO2
45.8 33.2 167 160
0.5 0.2
1.4622 1.4669
0.8648 0.8801
6.33 6.63 12.37 11.88
160
0.4
1.4668 0.8889
12.37
12.49
CxHs
2"
140
0.3
1.4686
0.8832
11.88
11.57
CHI
NA2
120
1 . 0 . 1.4556
0.8610
14.82
14.53
122
0.4
14.12
13.73
1!1.51
19.22
21.08
21.02
22.68
22.71
29.34
29.37
15.72 13.91 14.22
15.69 12.50 14.20
CHI CH3>CH-CH~ )CH CHB (CHdnCH (CHn)zCH (CHdzCH (CHdzCH (CHs)zCH fCH1)zCH CH3 CHn CHI CHI CHI CaHs C6H5 P-CHI-C~HI p-CHl-CsH4
C2Ho
hTHa
CH20H CHzOH CkIs CH3 H H CHIOH CHn CHa CzHs CsHs CHa CHa CHs CHI
NO2
137.0
NH? NO2 N HZ
40.9
SOa
77.0
111
100 108
2"
NO2 "a.
10 LO
1.484.5 1.4577
38.5 97.4 68.2
NO¶
113.2
69
LO
53.83
54.29
9.45
9.10
57.61
58.09
10.11
9.79
55.78
56.34
9.83
9.65
44.43 48.53
44.57 48.97
7.99 8.73
7.94 8.33
51.31 61.25 68.66
51.21 61.18 68.51
9.15 7.28 6.44
8.88 7.16 6.28
1.0136 0.8828
1.45G9 0.8794
121.0 48.6
NHa NO: NO, NO2 NH2 NHr
0.4
1.4626 0.8785
1.4704
0.9039
180
0.1
1.4005
1.0998
190
0.2
1.5968
1.0707
approximately !jOO ml. of methanol in the presence of Kaney nickel catalyst a t 75 to 100" and a pressure of 1000 lb. per sq. in. The mixture was filtered and the filtrate was distilled a t atmospheric pressure through a one-foot Vigreux column to remove the methanol. The product was isolated by rectification of the residue a t reduced pressure. The c5-amit~ohexahydropyrimidines which were prepared are colorl.ess liquids. The lower members in this series and those which contain hydrophilic groups o n the ring nitrogens are soluble in water. The higher members are insoluble in water. All of the compounds which were prepared are soluble in petroleum ether, methanol and benzene. The lower members possess a pyridine-like odor
which becomes less pronounced with increase in molecular 'weight. Their thermal stability is good since there was no observable decomposition of any of these compounds during their distillation in uacuo. The 5aminohexahydropyrimidines which were prepared together with some properties and analyses are listed in Table I . No debenzylation occurred during the hydrogenation of any of the 5-nitro-1,3-dibenzylhexahydropyrimidines. Further attempts were made t o debenzylate 5-amino-l,3dibenzyl-5-methylhexahydropyrimidineby hydrogenating it in methanol in presence of palladized charcoal a t a pressure of 1500 lb. per sq. inch and temperatures of 75, 100 and 150", but with no success. The stability of the nitrogen to beiizyl group linkage during these hydrogenations
PREPARATION OF DDT USINGHYDROGEN FLUORIDE
Aug., 1946
is noteworthy in view of reported debenzylations of compounds like 2-benzylamino-2-methyl-1-propanol*and benzylethylmethylamine.6 5-Amino- 1,3 -dibenzyl- .5 -methylhe9ahydropvrimidine was allowed to rcact with aqueous formaldehyde in an attempt t o prepare a derivative of this compound. Distillation of this reaction 'mixture gave 5-methyl-5-methyleneimino-1,3-cliberizylhexahydropyrimidine. Sonic properties of this cornpound are liited in Tablc I.
Summary The preparation of a number of 5-nitrohexahydropyrimidines by one or more of the three following procedures is described : SO? (1) RSH--CH2--C--CEI1--IZ;H-R
I
+ HCHO +
T IJ O U~R N A L , 67, 151.5 (1946).
THE STAMFORD 'II&SEAR(!R
I
R'
N
/R
I
CHZ,
,CH*
IC\
+ Hz0
SO2
I R'
I
(2) HOCH-C-CHLOII
I NO2
(3)
R'CHzXO2
T F K K HAL T rr , 1
(5) Baltzly a n d Buck, ibid., 63, 1064 (1941).
[CONTRIBUTION FROM
CHZ\
+ HCHO + 2RNI-12 + I -I- 3H20
+ 2RNH2 + 3HCHO +I + 3Hz0
The hydrogenation of some of the 5-nitrohexaliydropyri~iiidinesto the corresponding 5-aminohesahydropyriiiiidines is also reported.
R' (4) Senkus,
R-N'
1613
IdARORATORIESO P
~ 1 )
RECEIVED MAY10, 1 9 i b
TIIE ~ ' A Y C R I C A SCYAYAMID
COMPAliY]
The Preparation of DDT Using Hydrogen Fluoride as the Condensing Agent AND PAUL TARRANT BY J. H. SIMOPJS,' J. C. B ICON, C. W. BR \DLEY,* J T. Ca%SS.\D~IY,E. I. HOEGBERG
Hydrogen fluoride has been found to be a good condensing agent for a number of different reactions catalyzed by reagents such as sulfuric acid or aluminum c h l o r ~ d e . ~I t was hoped that one of the particular advantages of the USP of hydrogen fluoride in the preparation of DD'T would be the elimination of side reactions usually encountered in the use of the other catalqsts. For example, in a recent article Haller* states that thirteen impurities are present in technical DDT made by condensing chloral a n t i chlorobenzene in the presence of sulfunc acid. Iiour of these conipounds are formed directly in ~;lCiCt reactions inrwlviiig the wlfuric acid. As soon as sufficient information was available from the early experiments to show the possibilities of the condensation, the scale of the experiments was increased and the conditions of the reaction and the nature of the product were examined more accwratrly. Table I shows the various conditions under which the reaction i m s run and the results obtained. Discussion 'I he result4 (,how that a large exceb:, of chlorobetuene did not altw thc reaction appreciably. A very great eYcess of hydrogen fluoride is ne(-essary to complete the condensation, and lower temperatures with slower reaction sates are desirable. Preliminary work in the laboratory and pilot plant 011 tlie 1)roductioti of chloral from alcohol ( I ) Peunsyltani~.St it r C o l l e p ',tate College, P e n n s ~ l v ~ . n i a (2) Deceased ( ' 5 ) Sirnuns and Archer THISJ O U R N A I 60, 2953 (1838) ( I ) Hd11
