Guanidine ring compounds of 3,4-dihydro-2-amino pyrimidine derivatives 7a, 7b, 7d, and 7e were successfully synthesized by cyclization of free guanidine derivatives with α,β-unsaturated ketones such as mesityl oxide, benzalacetophenone and dypnone in tertiary butanol at 25℃.
These products are the first examples to be isolated as pure compounds which have been known to be unstable. These products are stable in solid state or in aprotic solvents such as dimethyl sulfoxide, dimethyl formamide, pyridine and chloroform. However they are unstable in a protic solvents such as water, methanol and ethanol, though they are quite stable in tertiary butanol.
Isomeric transformation of 2-amino-3,4-dihydro-4,4,6-trimethyl pyrimidine, 2-amino-3,4-dihydro-3,4,4,6-tetramethyl pyrimidine, and 2-amino-3-ethyl-3,4-dihydro-4,4,6-trimethyl pyrimidine by $^1H$ nmr and uv spectral studies were found to occur in water and methanol. In $D_2O$, 2-amino-3,4-dihydro-4,4,6-trimethyl pyrimidine (7a) undergoes ring fission to give acyclic intermediate, which was actually isolated and cyclized again to 7a by treatment with $DMSOd_6$.
This isomerization of 7a to the intermediate was found to be like the "Dimroth Rearrangement" type reaction in polar solvents such as water, methanol, ethanol and isopropyl alcohol.
Thus, best way to synthesize the 3,4-dihydro-2-amino-pyrimidine derivatives is to keep low reaction temperature (lower than 25℃) and to avoid using protic solvents for crystallization.
구아니딘 부분을 가진 3,4 디히드로-피리미딘 화합물은 테트로도톡신이나 섹시톡신과 유사한 생화학적 활성을 갖는다는 것이 알려지고 있는데 순수한 생성물로써 분리된 적이 없었다.
구아니딘 유도체와 α,β 불포화 케톤과의 반응을 온화한 조건에서 행함으로써 5,6 위지가 2중결합으로 되어있는 2-amino-3,4-dihydro-4,4,6-trialkyl pyramidine을 분리했다. 화학구조는 $^1H$ nmr, uv, 그리고 mass 스펙트럼을 사용하여 확인했다. 구아니딘 유도체들과 αβ 불포화 케톤과의 반응기구는 1,4 첨가 반응 기구로서 진행함을 확인했다.
이들 미리미딘 유도체들은 물, 알코올 등의 protic 용매에서는 매우 불안정하며 DMSO, $CH_3CN$, $CHCl_3$등의 aprotic 용매에서는 비교적 안정함을 알았다.
