Characterization of Alkyl Halides Ethylenethiourea R.
by
Use of
N. BOYD and MORTON MEADOW
Deparfmenf o f Chemistry, New York University, New York 3, N. Y.
b Ethylenethiourea (2-imidazolidinethione) was studied as an agent for identification of alkyl halides by preparing and characterizing a variety of S alkyl 2 ,-mercapto 43 dihydroglyoxalinium salts, the corresponding free bases, and the picrates of these free bases. An alkyl halide can be identified through the melting points of these derivatives, the picrates generally being the most suitable. Volumetric determination of equivalent weights of the bases and picrates is a simple matter and offers a further aid in identification of alkyl halides.
-
I
-
-
-
organic analysis the final test for the identification of any compound is the preparation of some solid derivative of definite melting point. For routine work it is essential that the derivative be easily prepared and purified. No general type of derivative is available for alkyl halides in spite of their importance, and there are few satisfactory reagents for their identification. S o n e of the many reagents suggested ( 5 , IS) for the identification of alkyl halides are entirely satisfactory, either because of experimental difficulties or because their application is not general. Brown and Campbell ( 4 ) found that thiourea was a fairly suitable reagent for the identification of alkyl bromides and iodides. Later the method mas extended to chlorides (8). S-Alkylisothioureas are formed which yield well-defined picrates.
derivatives and a resultant improvement in identification procedures. There have been several isolated reports on the preparation of S-alkyl derivatives of ethy1enethiourea-Salkyl-2-mercapto - 4,5 - dihydroglyoxalinium salts-but up to the present these compounds have not been extensively investigated. A series of S-alkyl-2-mercapto-4,5dihydroglyoxalinium salts was prepared from ethylenethiourea and a wide range of alkyl halides (Tables I and 11). Treatment of the salts with aqueous ammonia gave the free bases, listed with their equivalent weights and picrates in Tables I11 and IV.
N QUALITATIVE
+
H*NC(=S)NH2 RX -+ H2NC(=NH)SR,HX --+ HtXC(=:NH)SR.picric acid The use of ethylenethiourea (2imidazolidinethione), a larger molecule of slightly different structure than the often-used thiourea, CHz-NH
+
\C=S R X -+ LHz--NH/ E thylenethiourea CHpNH /)C-S-R.HX CHr-N
I
offered the possibi1it.y of obtaining a greater spread in melting points of
EXPERIMENTAL
Ethylenethiourea.
Ethylenethiourea was prepared by the method of Allen, Edens, and Van Allan (1); it is commercially available from Distillation Products Industries, Rochester 3, N. Y.
4,5-Dihydroglyoxalinium
Salts.
The salts were prepared by refluxing 0.06+ mole of a halide with 0.06 mole (6.12 grams) of ethylenethiourea
Table 1.
in 60 ml. of n-propyl alcohol for 6 hours. For dihalides, 2 equivalents of ethylenethiourea were employed. The salts of the more reactive halides such as the allyl and benzyl halides began to precipitate almost immediately and caused bumping of the reaction mixture. Refluxing was terminated when bumping became severe. If the salt failed to precipitate on cooling, one half to two thirds of the solvent was removed by distillation and the residue cooled. If the salt failed to precipitate at this point, 10 to 25 ml. of ether was added and the salt allowed to crystallize. The salt was then collected on a Biichner funnel, sucked as dry as possible, and then washed with three 15-ml. portions of ether. After drying, the salt was recrystallized from ethyl alcohol, and dried in vacuo, and its melting point determined. Halides that failed to react with ethylenethiourea in n-propyl alcohol were refluxed with the characterizing agent in formic acid. If the halide failed to react in formic acid, it was refluxed with the characterizing agent in n-propyl alcohol with 0.5 to 1.0 gram of potassium iodide.
4,5-Dihydroglyoxalinium Salts from Monohalides
CHI-NH
I
45 72 129 160 179
182 108/17 mm. 130/11 mm. 150/14 mm. M.p., C.
\C--S-R.
HX
Allyl Methallyl 8-Hydroxyethyl n-Heptyl Benzyl n-Octyl n-Decyl n-Dodecyl 1-Xaphthylmethyl
86-7 121-2 265-6 d. 92-4 171-3* 98-100 54-6 102-3 232-4
15.7 14.6 14.0. 11.8
15.4 14.4 14.0" 12.0
11.2 10.1 9.1 10.1
11.1 10.4 9.1 9.9
n-Hexadecyl n-Octadecyl m-Nitrobenzyl p-Nitrobenzyl
153-5 83-5 254-6 d. 190-10
7.7 7.2 15.4 ...
7 7 7.0
157-8 89-91 13Md 95-5.5'
14.2 13.3 ...
85-7 133.5-5 108.5-9.5
11.7 11.7 11.1
...
...
O
14 20 45 73
B.p.,
O
5
40 59 71 71 91 93 123
C.
Bromides Methyl Ethyl Isopropyl n-Propyl Allyl sec-Butyl Isobutyl Isoamyl
Liquid
15.3 .
.
I
14.2 13.3
... ...
...
...
...
11.9 11.8 10.8 ( Continued)
VOL. 32, NO. 4, APRIL 1960
551
Table 1.
4,5-Dihydroglyoxalinium Salts from Monohalides (Confinued)
CH2-NH&+R.HT; I bHZ--N// B.p., ' C. 130 139 145 156 179 198 201 91/9 mm. 109/8 mm. 103/20 mm. 180/45 mm. M.p.,
Alkyl Halide Chlorides n-.4myl Cyclopentyl p-Hydroxyethyl n-Hexyl n-Heptyl Benzyl n-Octyl n-Nonvl n-Decil p-Phenethyl n-Dodecyl
h1.p.. ' C. Liquid >310 Liquid Liquid Liquidf 175-6 67-8.5 Liquid 75-6 136-7
Nitrogen Analysis Calcd. Found
...
11.2
...
...
...
...
11.o
...
...
...
10.3 9.5
10.1 9.7
8.7 9.8
81-29
...
9.0 9.9
95-6 95-6 175-6h
6.9 6.4
6.8 6.4
...
...
...
' c. n-Hexadecyl n-Octadecyl p-Nitrobenzyl
18
27 98
...
...
' C.
Iodides 142-4i Methyl 43 112-14i ... Ethyl 72 10.1 72-4 10.4 Allvl 103 105 n-Propyl 120 sec-Butyl 121 Isobutyl 130 n-Butyl 148 Isoamyl 156 n-Amyl Liquid ... ... 180 n-Hexyl 61-2 8.5 8.3 204 n-Heptyl 86-8k ... *.. 20 (m.p.) n-Hexadecyl a Nitrogen analysis corresponds to-a monohydrate. b Two melting points have been reported for this compound: 147-7.5' ( 2 ) ; 173.4' (6). When prepared in this laboratory, a melting point of 171-3' wm obtained. c Lit.: m.p. 191' (8, 14). Lit.: m.p. 135-5.5' ( 2 ) . 8 Lit.: m.p. 95-5.5' (2). f Lit.: reported aa a liquid (14). Lit.: m.p. 82' (11). h Lit.: m.p. 150-1' (14). When prepared in this laboratory compound melted at 1756'. Anal.: Calcd. for CloH&,02SBr: N, 13.2. Found: N, 13.2. Lit.: m.p. 145' (18). j Lit.: m.p. 113-14.5' ( 2 ) . k Lit.: m.p. 83.54' (14). B.p.,
...
Q
Table 11.
95 122 155 178
Bis(4,5-dihydroglyoxalinium)Salts from Dihalides
2,3-Dic!doropropene 1,3-Dichloropropane 1.4-Dichlorobutane 1;5-Dichloropentane
153-4 205-7 1265 Liquid
131 141 167 196 224 26 (m.p.) 93 (m.p.) 145 (m.p.)
Bromides 1,2-Dibromoethane 1,2-Dibromopropane 1,3-Dibromopropane 1,4Dibromobutane l,5-Dibromopentane 1,lO-Dibromodecane a,a'-Dibromo-o-xylene a,a'-Dibromo-p-xylene
278-80 d.b 273-4 d. 224-5d 233-4O 158-9 175-7f 209-108 253-4
9.2c
9.50
13.3 12.9
13.2 13.1
12.0 12.0
12.0 11.8
111/23 mm. 10 (m.p.)
Iodides 1,3-Diiodopropane 1,FGDiiodopentane
235-7 d. 143-5
11.2 10.6
11.1
'
13.2" 17.7 16.9 .
I
.
13.4 17.9 17.1
...
@
552
0
ANALYTICAL CHEMISTRY
4,5-Dihydroglyoxalines (Imidazolines). To obtain the free base, 2 to 3 grams of finely divided dihydroglyoxaliniuni salt were dissolved or suspended in 25 ml. of water and 1 t o 1 aqueous ammonia mas added t o this until t h e reaction t o litmus was basic. I n most cases, the free base precipitated either immediately or after a very short time. The free base was collected on a Buchner funnel and washed in succession with 10 ml. of 1 to 1 aqueous ammonia to ensure completeness of reaction and then with two 10-ml. portions of water to remove any excess ammonia. The base was then recrystallized from ethyl alcohol and water, or, after drying, from a benzene-ligroine mixture. Free bases which came out of ethanolic solution as liquids were crystallized from the benzene-ligroine solvent pair. After the product had been collected and dried, its melting point and equivalent weight were determined. Any free base r h i c h still remained liquid m-as extracted with ether. After the ether extract had been dried over anhydrous magnesium sulfate, the solvent was removed. If the liquid still failed to crystallize. the base was characterized as the picrate. Picrates. Picrates were prepared from ethyl alcohol solutions of t h e free bases in the usual manner. After recrystallization from ethyl alcohol and drying, their melting points and equivalent weights were determined. Determination of Equivalent Weights. The equivalent weights of the bases a n d their picrates were determined by a volumetric method described by Berger (S), using standardized perchloric acid in glacial acetic acid in the presence of crystal violet indicator (10).
...
...
...
...
...
Determination of Nitrogen. The nitrogen content of all samples was determined by the modified microKjeldahl method developed by Rla (9).
...
10.4
Nitrogen value calculated was on basis that only allylic chlorine atom reacted. Lit.: m.0. 275-6' (14). Analytical data indicate that only one bromine atom took part in the reaction. d Lit.: m.p. 224' (7). 6 Lit.: m.p. 205' (14). f Lit.: m.p. 174-6' (14). Lit.: m.p. 200-1' ( 1 4 ) . @
b
Yields of 4,j-dihj-droglSosalinium salts ranged from 60 to 90% of theoretical, I n cases where the halide failed to react, the starting materials were recovered unchanged. Most salts which formed were also characterized as free base and picrate, including those listed in Tables I and I1 as liquids. 1,2-Dihalides, with the exception of 132-dibromopropane, failed to react with ethylenethiourea.
DISCUSSION
Chlorides generally did not exhibit the same degree of reactivity as the corresponding bromides and iodides. Aside from reactive chlorides of allyl and benzyl types, the only reactive chlorides were the normal heptyl. octyl, decyl, dodecyl, hexadecyl, and octadecyl chlorides. n-Hexyl, n-propyl. isopropyl, n-butyl, sec-butyl, terl-butyl, wamyl, isoamyl. cyclohesyl. and trityl chlorides
were unreactive in either n-propyl alcohol or forniic acid. Failure t o obtain derivatives from tertiary halides or trityl chloride was not surprising, because such halides are known to solvolyze rapidly in alcohols or formic acid. A suitable solvent for characterization of tertiary halides has yet to be found, but further work in this direction by the present authors is not possible. 1,2-Dichloroethanek 1,2-dichloropropane, and 1,2,3-tricliloropropane were also completely unreactive. Reactivity of an 0.w-dichloride was first noticed with the trimethylene compound. a.w-Dibromides and diiodides reacted very readily with ethylenethiourea. a,@-Dibromides,with the exception of 1,2-dibromopropaiie, were unreactive. Iiicluded in this latter category are 2,3 - dibromobutane, 1,2 - dibromo - 2methylpropane, and a,? - dibromoethylene. (The iioiireactivity of the vinyl halide was not unexpected.) Bromocyclohesane failed to yield a derivative. The so-called activated aromatic halides, such as 2,4-dinitrobroniobenzene, IT hich usually iiiidergo displacement of halide ion, failed to react with eth ylenetliiourca. Formic acitl \\-as used in place of npropyl alcohol in a nuniber of cases in hope of promoting displacement of halide ion in a mor(' ionizing solvent; it was beneficial in the cases of only t x o halides, bromocyclopentane and 1,2-dibroiiiopropaiie. T h a t n-amyl and n-hexyl chlorides r e r e unreactive toward ethylenethiourra, yet n-heptyl and n-octyl chlorides did react, was unexpected, for reactivity generally falls off as one goes to higher homologs. Ethylene chlorohydrin was reactive but ethylene chloride was inactive; a,@-dibromides were generally inactive; aiid I ,3dichloropropane aiid homologous a , w tlichlorides were active hut ethylene chloride n as inactive. Because some of the free bases and the halide salts from monohalides are uncrystallizahle liquids, the picrates are the preferred derivatives. The picrates are spread over a range of melting points of 210" C. as compared to a range of only 110" for the corresponding S-alkylisothiouronium picrates. This in itself is a considerable advantage in identifiration procedures, as is the fact that the cyclic sulfur derivatircs are less easily cleaved than the isothiouronium compouiids (14). Characterization by ethylmethiourea thus is satisfactory for the identification of alkyl halides. Use can be made of the melting points of the S-alkyl-2mercapto-4,5-dihydroglyosalinium salts, the free bases, or the picrates of the latter. Volumetric determination of equivalent weights of the bases and
picrates, which is a very simple matter,
ACKNOWLEDGMENT
come available from what is essentially one identification procedure.
and Barbara Hensle, Microchemical Laboratory, Kew York University, for
Table 111.
S-Alkyl-2-mercapto-4,5-dihydroglyoxalines and Their Picrates from Monohalides
CHz-NH /)C-S-R H2-K
177-gb 101-25 Methyl 359 355 153-5 ... ... Ethyl 57-6OC 143-5 375 378 Liquid ... ... P-Hydroxyet hyl 283-5 d. 371 370 . Liquid ... Allyl ... 283-5 d. 400 2-C hlorallyl Liquid ... 224d 457 223d 218-19 d. Bromopropyl 165-6 370 130-2 71-3a n-Propyl ... 371 150-2 106-8, ... Isopropyl 382 127-9 Liquid ... Methallyl ... 389 115-16 387 52-4P n-Butyl ... 380 387 159 158 104-06 sec-Butyl 52-4 h h 142-3 158 160 Isobutyl 68.5-9.5 401 278-80 404 176 172 n-Amyl 62-3 140-1 40 1 172 394 174 72.5-3 Isoamyl 1746 400 112-14 392 171 167 Cyclopentyl 420 415 85-6 54.5-6' ... n-Hexyl 94-5 429 431 69-71 2OQ 199 n-Heptyl 161-3k 68-91 Benzyl 466 464 182.5-4 236 103-5 237 m-Nitrobenzyl 466 155-6.5 464 158-8, j 2 ... ... p-Sit robenzyl 443 438 80-1 213 70-2 214 n-Octyl m m 130-1 Liquid 8-Phenethvl 101-3 458 229 450 i6-8 n-Xonyl 228 n 78-80 283-4 d. 238 n-Decyl 242 471 150-2 475 Liquid ... 1-Xaphthylmethyl 110-1 1 264 508 270 86-7 n-Dodec yl 112-13 546 318 n-Hexadecvl 90-1 326 353 118-19 584 575 97-8 n-Octadecyl 354 Lit.: m.p. 100-2' (14). b Lit.: n1.p. 177.5-8" ( 1 4 ) . c Lit.: m.p. 55-60' ( 6 ) . d Compound obtained in reaction between 1,2-dibromopropane and ethylenethiourea in formic acid. Analytical data indicate that only one bromine atom reacted. Lit.: m.o. 73-4" ( 2 ) . Lit.: m:p. 106-80 (2). g Lit.: m.p. 55-7.5" ( 2 ) . h Calcd. for C13HliNsOiS: K, 18.1. Found: N, 17.8. Lit.: m.p. 54-5' (14). 1 Lit.: m.p. 69" (14). Lit.: m.p. 162' ( 1 4 ) . Lit.: m.p. 158' (14). Calcd. for CI7H17N6OiS: N, 16.1. Found: N, 16.1. Calcd. for C19HzgSsOiS: X, 14.9. Found: N,15.0. ~~
.
.
~
I
0
6
Table IV.
Bis(S-alkyl-2-mercapto-4,5-dihydroglyoxalines) and Their Picrates from Dihalides
CHI-KH CHz-N I /
/
XH-CH2
1
'C-S-R-S-C/
%-CH*
Free Base Equiv. Wt. M.p., ' C. Calcd. Found 202-40 ... ... 140-1 122 124 130 183-5 129 131-2 136 136 171 172 161-2 153 152 150-1 187-8 5 153 153
Dipicrate Equiv. Wt. h1.p , O C. Calcd. Found 223-5 344 338 172-3 b b
R -(CHz)z-(CHz),-fCHqL-(CHiji-( CHz)ioo-Xylvlene p-Xylylene a Lit.: m.p. 203" ( 7 ) . Calcd. for C21H2J-J10014Sz:N, 19.9. Found: N , 19.9. Calcd. for C22H24N10014S?:N, 18.1. Found: N, 18.3.
214-1.5
c
c
128-30 150-2 188-9 210-12
365 400 382 382
360 393 381 374
VOL. 32, NO. 4, APRIL 1960
553
making its facilities available and rendering assistance when needed. LITERATURE CITED
(1) Allen. C. F. H., Edens, C. O., Van Allan, J. A., Org. Syntheses 26, 34 (1946). (2) Baer, J. E., Lockwood, R. G., J . Am. Chem. SOC.76, 1162 (1954). (3) Berger, J., Acta Chem. S a n d . 8, 427 (1954). (4) Brown, E. L., Campbell, N., J . Chem. SOC.1937, 1699. (5) Cheronis, N. D., Entrikin, J. B., “Semimicro Qualitative Organic An-
alysis,” 2nd ed., p. 455, Interscience, Xew York, 1957. (6) Easton, N. R., Hlynsky, A., Foster, H., J. Am. Chem. SOC.73,3507 (1951). (7) Knott, E. B., Morgan, J., U. S. Patent 2,514,650 (July 11, 1950). ( 8 ) Levy, W. J., Campbell, N., J. Chem. SOC.1939, 1442. (9) Ma, T. S., New York University (present address, Brooklyn College, Brooklyn, N. Y.), personal communication. (10) Markunas, P. C.. Riddick, J. A., ANAL.CHEM.23,337 (1951). (11) Puetzer, B., U. S. Patent 2,156,193 (April 25, 1939).
(12) Schacht, W., Arch. Pharm. 235, 441 (1897) [Chem.Zentr. 1897 11,1941. (13) Shriner, R. L., Fuson, R. C., Curtin, D. Y., “Systematic Identification of Organic Compounds,” 4th ed., pp. 243-4, Wiley, New York, 1956. (14) Wilson, W.,J. Chem. SOC. 1955, 1389. RECEIVEDfor review August 24, 1959. Accepted December 7, 1959. Taken from a dissertation presented by Morton Meadow in 1956 to the Graduate Facult of New York University in partial fulfiz ment of the requirements for the degree of doctor of philosophy.
Characterization of Alkyl Halides P. M. G. BAVIN Chemistry Department, The University, Hull, East Yorkshire, England
b Methyl fluorene-9-carboxylate anion reacts rapidly with a wide range of alkyl halides to give good yields of the methyl 9-alkylfluorene-9-carboxylates, many of which are easily obtained in crystalline form. Saponification to the 9-alkylfluorene-9-carboxylic acid and determination of the equivalent weight enable the size of the alkyl group to b e determined. The alkylation succeeds with some tertiary halides and polymethylene diha lides; some hyd roxya I ky I halides also yield characteristic products. Table
1
2 3 4 5 6 7 8
9 10 11 12 13 14 15 16 17
I.
T
HE alkyl halides have been commonly characterized by their physical properties and by the formation of derivatives, particularly S-alkylisothiourea picrates, alkyl 2-naphthyl ethers and their picrates, N-alkylphthalimides, N-alkylsaccharins, and N-alkyl-p-bromobenzenesulfon - p - anisidides. I n addition, derived Grignard reagents have been allowed to react with isocyanates or mercuric halides t o give, respectively, anilides or alkyl mercuric halides (’7). These methods are not universally applicable, are not always
Melting Points of Methyl 9-Alkylfluorene-9-carboxylates and 9-Alkylfluorene-9-carboxylic Acids
(X, preparation in a crystalline condition not attempted.) Melting Points, O C. Methyl Alkyl Group Halide Used ester Acid CH, 170-1 Br, I 108-9 Methyl Br, I 81.5-2 0 Ethyl Br 85.0-5,5 Propyl 79-80 Br Isopropyl 745 132.0-2.5 Br Allyl Br 34.0-4.5 115-16 Butvl 70-1 Br sec-Butyl 68-9 Br Isobutyl 112-13 233-5 tert-Butyl c1, Br 125-6 x Br Pentyl 200-1 56-7 c1 tert-Pentyl 117-18 x Br Hexyl c1 53-4 3-Methyl-3-pentyl c1 66.5-7 .O 3-Ethyl-3-pentyl X 120-2 Br Crotyl 182-1 117-19 Br Propargyl 20 1-2 c1 74-5 Benzyl
18 2-Phenylethyl
Br
(yCClzCH2
G7-8
113 5-4.0
‘Q
c1
19 Cinnamyl
s
162-3
*CH=CHCHz
L.5J 554
ANALYTICAL CHEMISTRY
(Continued)
well suited t o characterizing small quantities of compounds, and generally fail with weakly reactive halides. The formation of Grignard reagents and subsequent reaction with isocyanate8 have been reported to yield rearranged products in some instances (6).
q coocr, I
Methyl fluorene-9-carboxylate anion (I), easily generated from the ester with methanolic sodium methoxide, reacts rapidly with a wide range of alkyl halides t o give good yields of the corresponding 9-alkyl derivatives (11) (1,
R COOCH3
I1
3). [Wislicenus prepared several derivatives of the ethyl ester (8), but these have lower melting points than the methyl homologs.] Many of the products are easily obtained in crystalline form and have sharp melting points. Although isomeric derivatives may have similar melting points, this is a defect common to many methods of characterization; suitable mixed melting point determinations show large depressions. EXPERIMENTAL
Fluorene-9-carboxylic acid may be prepared from benzilic acid (6). The following has proved to be more convenient on a large scale. Fluorene (166 gram, 1 mole) in dry ether (500 ml.) was added with stirring
